American Journal of Kidney Diseases - Articles in Press

Important Outcomes for Kidney Transplant Recipients: A Nominal Group and Qualitative Study - Corrected Proof

Martin Howell, Allison Tong, Germaine Wong, Jonathan C. Craig, Kirsten Howard — 2012-05-11

Background: Immunosuppression is associated with a number of adverse outcomes, but typically it is the physician, not the patient, who decides on the drug regimen. The perspective of the patient in clinical decision making is increasingly recognized in other settings, but the perspectives of kidney transplant recipients are largely unknown. The aim of this study was to elicit patient perspectives and priorities for outcomes after transplant and the reasons underpinning these priorities. Methods: Outcome identification and ranking were undertaken using a focus/nominal group technique. Adult kidney transplant recipients, purposively sampled from 3 transplant centers, participated in 1 of 8 nominal groups. Each group (6-10 participants) listed and ranked outcomes relevant to immunosuppressant medications. Results: 57 participants identified 47 outcomes relevant to immunosuppression after transplant surgery. Transplant survival consistently was ranked more highly than any other outcome, followed by damage to other organs, survival, and cancer. Only 12% of participants ranked their own survival as more important than transplant survival. In contrast, the relative importance of side effects differed among participants. Themes underpinning priorities were concern for fatal and serious events; relevance to life circumstance; acceptance, trivialization, and tolerance; and future outlook. Participants described a willingness to tolerate side effects, dependent on personal relevance and ability to manage the side effect. Conclusions: Transplant survival appears to be more important than life itself to kidney transplant recipients, suggesting that they may be willing to tolerate a higher level of immunosuppression than is assumed by clinicians and researchers.

Risk of Herpes Zoster in CKD: A Matched-Cohort Study Based on Administrative Data - Corrected Proof

Mei-Yi Wu, Yung-Ho Hsu, Chien-Ling Su, Yuh-Feng Lin, Hui-Wen Lin — 2012-05-10

Background: Immune system dysregulation is associated with end-stage renal disease. Although decreased cellular immunity increases susceptibility to herpes zoster, the risk of herpes zoster in patients with earlier stages of chronic kidney disease (CKD) is unclear. Study Design: A matched-cohort study. Setting & Participants: Data from the Taiwan Longitudinal Health Insurance Database (LHID) for 2004-2006 were analyzed. The study cohort included patients 18 years or older given a diagnosis of CKD (excluding patients treated by dialysis or transplant) in 2004-2005 (n = 13,321). The comparison cohort (n = 66,605) included 5 randomly selected age- and sex-matched controls for each patient in the study cohort. Predictor: CKD. Incident cases of CKD were identified using the Taiwan LHID. CKD was ascertained from International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Outcomes: Herpes zoster, ascertained from ICD-9-CM codes. All participants were followed up from the date of cohort entry until they developed herpes zoster or the end of 2006. Cox proportional hazard regressions were performed to compare the hazard rates of herpes zoster in the CKD cohort and the age- and sex-matched comparison cohort. Results: We identified 13,321 patients with a diagnosis of CKD who matched the inclusion criteria. 1,602 patients developed herpes zoster during the study period, of whom 353 were from the CKD cohort and 1,249 were from the comparison cohort. After adjusting for potential confounding factors, CKD was associated independently with greater risk of herpes zoster (HR, 1.60; 95% CI, 1.41-1.81). Limitations: Some patients with CKD or herpes zoster may have chosen not to seek medical care. Misclassification of CKD due to use of diagnostic codes also is a limitation. Conclusions: This population-based cohort study indicated that patients with CKD are at increased risk of herpes zoster compared with the general population.

A One-Day Centralized Work-up for Kidney Transplant Recipient Candidates: A Quality Improvement Report - Corrected Proof

2012-05-10

Background: Waiting time for a kidney transplant is calculated from the date the patient is placed on the UNOS (United Network for Organ Sharing) waitlist to the date the patient undergoes transplant. Time from transplant evaluation to listing represents unaccounted waiting time, potentially resulting in longer dialysis exposure for some patients with prolonged evaluation times. There are established disparities demonstrating that groups of patients take longer to be placed on the waitlist and thus have less access to kidney transplant. Study Design: Quality improvement report. Setting & Participants: 905 patients from a university-based hospital were evaluated for kidney transplant candidacy, and analysis was performed from July 1, 2004, to January 31, 2010. Quality Improvement Plan: A 1-day centralized work-up was implemented on July 1, 2007, whereby the transplant center coordinated the necessary tests needed to fulfill minimal listing criteria. Outcome: Time from evaluation to UNOS listing was compared between the 2 cohorts. Multivariable Cox proportional hazards models were created to assess the relative hazards of waitlist placement comparing 1-day versus conventional work-up and were adjusted for age, sex, race, and education. Results: Of 905 patients analyzed, 378 underwent conventional evaluation and 527 underwent a 1-day center-coordinated evaluation. Median time to listing in the 1-day center-coordinated evaluation compared with conventional was significantly less (46 vs 226 days, P < 0.001). On multivariable analysis controlling for age, sex, and education level, the 1-day in-center group was 3 times more likely to place patients on the wait list (adjusted HR, 3.08; 95% CI, 2.64-3.59). Listing time was significantly decreased across race, sex, education, and ethnicity. Limitations: Single center, retrospective. Variables that may influence transplant practitioners, such as comorbid conditions or functional status, were not assessed. Conclusions: A 1-day center-coordinated pretransplant work-up model significantly decreased time to listing for kidney transplant.

Inflammation and Coagulation Markers and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis (MESA) - Corrected Proof

2012-05-07

Background: The strength and direction of the associations between inflammation and coagulation biomarkers with kidney disease onset and progression remain unclear, especially in a population-based setting. Study Design: Prospective observational study. Setting & Participants: 4,966 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with a cystatin C–based estimate of glomerular filtration rate (eGFRcys) >60 mL/min/1.73 m2 and at least one follow-up measurement of kidney function. All participants were free of cardiovascular disease at entry. Predictor: We evaluated the associations of C-reactive protein (CRP), interleukin 6 (IL-6), fibrinogen, factor VIII, and d-dimer levels with kidney function decrease. Outcomes & Measurements: Kidney function decrease was assessed primarily by repeated measurements of eGFRcys over 5 years. Rapid decrease in kidney function was defined as eGFR decrease >3 mL/min/1.73 m2 per year. Incident low eGFR was defined as the onset of eGFRcys <60 mL/min/1.73 m2 at any follow-up examination and eGFRcys decrease ≥1 mL/min/1.73 m2 per year. Results: Mean age was 60 years, 39% were white, 52% were women, and 11% had diabetes. Mean eGFRcys was 96 mL/min/1.73 m2 and 7% had albuminuria. Median follow-up was 4.77 years. Higher factor VIII levels (per 1 standard deviation [SD] of biomarker) had the strongest association with kidney function decrease (β = −0.25; 95% CI, −0.38 to −0.12; P < 0.001), followed by IL-6 (β = −0.16; 95% CI, −0.29 to −0.03; P = 0.01), CRP (β = −0.09; 95% CI, −0.22 to 0.03; P = 0.1), and fibrinogen levels (β = −0.09; 95% CI, −0.22 to 0.04; P = 0.2). Each 1-SD higher concentration of IL-6 (OR, 1.15; 95% CI, 1.07-1.23), factor VIII (OR, 1.11; 95% CI, 1.03-1.18), and CRP (OR, 1.09; 95% CI, 1.02-1.16) at baseline was associated significantly with rapid kidney function decrease. Only IL-6 level was associated significantly with incident low eGFR (OR, 1.09; 95% CI, 1.00-1.19). Limitations: Observational study design and absence of measured GFR. Conclusions: Inflammation and coagulation biomarkers are associated with decreasing kidney function in ambulatory adults without established cardiovascular disease or chronic kidney disease.

Financial Implications of Choice of Dialysis Type of the Revised Medicare Payment System: An Economic Analysis - Corrected Proof

John Hornberger, Richard A. Hirth — 2012-05-07

Background: In 2011, the Medicare Improvements for Patients and Providers Act replaced the case-mix–adjusted composite payment system for Medicare outpatient dialysis facilities with a bundled end-stage renal disease prospective payment system (PPS). We assessed the economic implications for modality choice of the revised Medicare payment system. Study Design: Microeconomic analyses. Setting & Population: Patients eligible for dialysis in the United States. Model, Perspective, & Timeframe: The perspective of this analysis is that of a financial administrator of a representative dialysis center in the United States. Data were obtained from the Medicare Payment Advisory Commission, the US Renal Data System, the DOPPS (Dialysis Outcomes and Practice Patterns Study) Practice Monitor, the US Bureau of Labor Statistics, and Medicare fee schedules. Interventions: Recently implemented end-stage renal disease PPS versus the prior case-mix composite payment system. Outcomes: Medicare payment per month, center fixed and variable costs per month, net difference in revenue and variable costs (direct contribution), and net difference in revenue and total costs (operating margin). Results: The direct contribution and operating margin for in-center hemodialysis and peritoneal dialysis are expected to be positive under the new bundled PPS. For Medicare fiscal intermediaries/administrators, paid treatments for home hemodialysis vary from 3.2 to more than 4.8 per week. The direct contribution and operating margin are expected to be negative for home hemodialysis if the number of paid treatments is similar between in-center and home hemodialysis; they are almost identical when the number of paid treatments increases for home hemodialysis by approximately 1 per week. Limitations: Experience across centers and intermediaries/administrators may vary. Sensitivity analyses were conducted to assess the robustness of findings and determine which variables most influenced results. Conclusions: The new bundled PPS created a financial incentive for increased use of peritoneal dialysis. Use of home hemodialysis may be influenced by number of paid treatments per week.

Laxative Abuse, Eating Disorders, and Kidney Stones: A Case Report and Review of the Literature - Corrected Proof

David E. Leaf, Phillip R. Bukberg, David S. Goldfarb — 2012-05-07

Kidney stones are listed among the complications of eating disorders; however, very few cases have been reported. We present an additional case of nephrolithiasis associated with laxative abuse, including detailed results of the patient's urine metabolic profiles, in a patient with idiopathic hypercalciuria. We review the literature and provide an explanation for the paucity of cases of nephrolithiasis associated with these disorders. Despite low urine volumes resulting from extracellular fluid volume depletion and hypocitraturia resulting from hypokalemia, both of which would tend to favor the formation of kidney stones, most patients with eating disorders are likely to be protected from stone formation by the hypocalciuric effect of extracellular fluid volume depletion and increased proximal tubular sodium reabsorption. However, patients with underlying idiopathic hypercalciuria who develop eating disorders may be at increased risk of stone formation in the setting of low urine volume and therefore high supersaturation of calcium oxalate and phosphate.

Ergocalciferol and Cholecalciferol in CKD - Corrected Proof

Sagar U. Nigwekar, Ishir Bhan, Ravi Thadhani — 2012-05-07

The development of chronic kidney disease (CKD) is accompanied by a progressive decrease in the ability to produce 1,25-dihydroxyvitamin D. Pharmacological replacement with active vitamin D therefore has been a cornerstone of secondary hyperparathyroidism therapy in the end-stage renal disease population treated by long-term dialysis. Recent evidence suggests that extrarenal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D may have significant biological roles beyond those traditionally ascribed to vitamin D. Furthermore, low 25-hydroxyvitamin D levels are common in patients with all stages of CKD. This article focuses on the role of nutritional vitamin D replacement in CKD and aims to review vitamin D biology and summarize the existing literature regarding nutritional vitamin D replacement in these populations. Based on the current state of the evidence, we provide suggestions for clinical practice and address areas of uncertainty that need further research.

Impact of Donor Hepatitis C Virus Infection Status on Death and Need for Liver Transplant in Hepatitis C Virus–Positive Kidney Transplant Recipients - Corrected Proof

Lauren M. Kucirka, Thomas G. Peters, Dorry L. Segev — 2012-05-07

Background: Only 29% of deceased donor kidney recipients with hepatitis C virus (HCV) receive HCV-positive (HCV+) kidneys. These kidneys are discarded 2.5 times more often than their HCV-negative (HCV−) counterparts, possibly due to the sense that an HCV+ kidney may adversely affect recipient liver function. The goals of this study were to characterize liver disease in HCV+ kidney recipients and compare rates of liver-related outcomes by kidney donor HCV status. Study Design: Observational cohort study. Setting & Participants: 6,250 patients with HCV who had a kidney transplant in 1995-2008 as captured in the United Network for Organ Sharing (UNOS) database. Liver-related outcomes were assessed by cross-linking with the liver waitlist and transplant data sets. Predictor: HCV status of transplanted kidney. Outcomes: Joining the liver waitlist, receiving a liver transplant, death. Measurements: Time to event. Results: Only 63 (1%) of HCV+ kidney recipients eventually joined the liver waitlist during the 13-year study period. Those who received HCV+ kidneys had a 2.6-fold higher hazard of joining the liver list (P < 0.001); however, the absolute difference in rate of listing between recipients of HCV− and HCV+ kidneys was <2%. This is consistent with findings of only 2% lower patient survival at 3 years in HCV+ patients receiving HCV+ versus HCV− kidneys. Limitations: We lacked data for HCV viral load and genotype of both HCV+ recipients and transplanted HCV+ kidneys. Conclusions: Because transplant with an HCV+ kidney may reduce waiting-time by more than a year for an HCV+ patient and there is a high risk of kidney waitlist mortality, a 2% increased rate of adverse liver outcomes and 2% increased rate of death at 3 years should not universally preclude the use of HCV+ kidneys when the intended recipient is also HCV+.

Commentary on ‘The DOPPS Practice Monitor for US Dialysis Care: Trends Through August 2011': An ESA Confluence - Corrected Proof

Daniel E. Weiner, Wolfgang C. Winkelmayer — 2012-05-07

The end-stage renal disease (ESRD) prospective payment system (PPS), also referred to as the expanded bundle, and the accompanying Quality Incentive Program (QIP), were implemented by the US Centers for Medicare and Medicaid Services (CMS) on January 1, 2011. These conjoined rules expanded the bundled payment to include many previously separately billable dialysis-related services and added penalties for failing to meet anemia and dialysis adequacy metrics. Many of the most expensive components of dialysis care (eg, erythropoiesis-stimulating agents [ESAs], intravenous iron supplements, and intravenous vitamin D analogues and their oral equivalents) were rolled into this single payment.

Clinical Risk Implications of the CKD Epidemiology Collaboration (CKD-EPI) Equation Compared With the Modification of Diet in Renal Disease (MDRD) Study Equation for Estimated GFR - Corrected Proof

2012-05-07

Background: The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine-based equation for estimated glomerular filtration rate (eGFR) is more accurate than the MDRD (Modification of Diet in Renal Disease) Study equation. However, it has not been determined whether the improvement in risk categorization applies to all segments of the population. Study Design: Population-based cohort study. Setting & Participants: Adults (aged ≥18 years) who did not have kidney failure at baseline and had at least one serum creatinine measurement and dipstick proteinuria evaluation in a province-wide laboratory registry from Alberta, Canada, in 2002-2007 (N = 1,010,988). Predictor: eGFR categories of ≥90, 60-89, 45-59, 30-44, and 15-29 mL/min/1.73 m2. Outcomes: All-cause mortality, acute myocardial infarction, end-stage renal disease, and doubling of serum creatinine level. Measurements: GFR was estimated by the CKD-EPI and MDRD Study equations. Results: The CKD-EPI equation reclassified 22.6% and 1.2% of participants to a higher and lower eGFR category, respectively, and decreased the prevalence of CKD stages 3 and 4 from 9.2% to 7.3%. Of 70,071 participants with eGFRMDRD of 45-59 mL/min/1.73 m2, 30.8% were reclassified to eGFRCKD-EPI of 60-89 mL/min/1.73 m2, and after adjusting for potential confounders, participants reclassified had a lower risk of all-cause mortality (incidence rate ratio [IRR], 0.77; 95% CI, 0.69-0.86), acute myocardial infarction (IRR, 0.73; 95% CI, 0.60-0.88), end-stage renal disease (IRR, 0.55; 95% CI, 0.32-0.94), and doubling of creatinine level (IRR, 0.78; 95% CI, 0.59-1.04) compared with those not reclassified. Similar findings were observed for those reclassified to a higher eGFR category from other eGFRMDRD categories. Net reclassification improvements based on eGFR categories were positive for all outcomes (range, 0.146-0.256; all P < 0.001). Limitations: Relatively short follow-up (median, 2.8 years), lack of data for some potential confounders (eg, smoking), and mainly white participants. Conclusions: These results suggest that the CKD-EPI equation more accurately categorizes individuals regarding clinical risk than the MDRD Study equation.

Use and Safety of Unfractionated Heparin for Anticoagulation During Maintenance Hemodialysis - Corrected Proof

Jenny I. Shen, Wolfgang C. Winkelmayer — 2012-05-07

Anticoagulation is essential to hemodialysis, and unfractionated heparin (UFH) is the most commonly used anticoagulant in the United States. However, there is no universally accepted standard for its administration in long-term hemodialysis. Dosage schedules vary and include weight-based protocols and low-dose protocols for those at high risk of bleeding, as well as regional anticoagulation with heparin and heparin-coated dialyzers. Adjustments are based largely on clinical signs of under- and overanticoagulation. Risks of UFH use include bleeding, heparin-induced thrombocytopenia, hypertriglyceridemia, anaphylaxis, and possibly bone mineral disease, hyperkalemia, and catheter-associated sepsis. Alternative anticoagulants include low-molecular-weight heparin, direct thrombin inhibitors, heparinoids, and citrate. Anticoagulant-free hemodialysis and peritoneal dialysis also are potential substitutes. However, some of these alternative treatments are not as available as or are more costly than UFH, are dependent on country and health care system, and present dosing challenges. When properly monitored, UFH is a relatively safe and economical choice for anticoagulation in long-term hemodialysis for most patients.

Peripheral Artery Disease and CKD: A Focus on Peripheral Artery Disease as a Critical Component of CKD Care - Corrected Proof

2012-05-07

The incidence of peripheral artery disease (PAD) is higher in patients with chronic kidney disease (CKD) than in the general population. PAD is a strong independent risk factor for increased cardiovascular disease mortality and morbidity, including limb amputation, in persons with CKD. Diagnosis of PAD in patients with CKD may be challenging in the absence of classic intermittent claudication or the presence of atypical leg symptoms. In addition, pedal artery incompressibility may decrease the accuracy of ankle-brachial index measurement, the most common PAD diagnostic tool. Alternative methods such as toe-brachial index should be used if clinical suspicion persists despite a normal ankle-brachial index value. Aggressive risk-factor modification, including treatment of diabetes, hyperlipidemia, and hypertension and smoking cessation, should be mandatory in all patients. Treatment of all individuals with PAD should include antiplatelet medications and prescribed supervised exercise programs and/or cilostazol for individuals with claudication symptoms. Preventive foot care measures and a multidisciplinary approach involving podiatrists and vascular and wound care specialists should be used to reduce amputations. Revascularization for critical limb ischemia is associated with poor outcomes in patients with CKD with PAD. Future investigation is recommended to evaluate the benefit of earlier treatment strategies in this high cardiovascular disease risk population with CKD.

The DOPPS Practice Monitor for US Dialysis Care: Trends Through August 2011 - Corrected Proof

2012-05-04

The Dialysis Outcomes and Practice Patterns Study (DOPPS) Practice Monitor (DPM) was developed to report trends in dialysis care in the context of the implementation of the end-stage renal disease prospective payment system (PPS) by the US Centers for Medicare & Medicaid Services (CMS). The DPM comprises a national sample of dialysis facilities and is updated every 4 months, with a data lag of 2 to 4 months. The rationale and strategy of the DPM have been previously described, and detailed findings including graphics, data tables, and study methods are publicly available at the DPM website (www.dopps.org/DPM). In a previous issue of the American Journal of Kidney Diseases, we summarized the key trends and associations we observed in data covering August 2010 through April 2011. Here, we provide an update based on trends through August 2011.

Association of Hepatitis C Virus Infection With Risk of ESRD: A Population-Based Study - Corrected Proof

2012-05-04

Background: The association between chronic hepatitis C virus (HCV) infection and end-stage renal disease (ESRD) has been widely debated. Study Design: National population-based cohort study. Setting & Participants: Insurance claims data from the Taiwan National Health Insurance Research Database in 2000-2005. Predictor: Chronic HCV infection as defined by the International Classification of Diseases, Ninth Revision, Clinical Modification. Outcomes: ESRD as defined by the International Classification of Diseases, Ninth Revision, Clinical Modification. Results: We identified 6,291 adults with chronic HCV infection. The control group included 31,455 sex- and age-matched individuals without evidence of chronic hepatitis. The incidence of ESRD was 2.14-fold higher in patients with chronic HCV infection (HR, 1.53; 95% CI, 1.17-2.01; P = 0.002) than in patients without HCV infection. Age stratification analysis showed that patients aged 50-59 years with chronic HCV infection (HR, 7.77; 95% CI, 4.23-14.3; P < 0.001) had the highest risk of developing ESRD relative to patients aged 20-49 years without chronic HCV infection (interaction P < 0.001). Limitations: Lack of clinical data. Conclusions: Patients with chronic HCV infection are at greater risk of developing ESRD than individuals without chronic HCV infection. In addition, the risk of developing ESRD is highest in younger patients with HCV infection. Early renal screening programs should be initiated for this high-risk group of young individuals with chronic HCV infection.

Effects of Mediterranean Diets on Kidney Function: A Report From the PREDIMED Trial - Corrected Proof

2012-04-30

Background: Epidemiologic observations have linked healthy dietary patterns to improved kidney function. Study Design: We assessed the effects of the Mediterranean diet (MedDiet) on kidney function in both a cross-sectional assessment and after a 1-year intervention in a cohort of the PREDIMED (Prevención con Dieta Mediterránea) Study, a multicenter 3-arm randomized clinical trial to determine the efficacy of the MedDiet on primary cardiovascular prevention. Setting & Participants: Community-dwelling men aged 55-80 years and women aged 60-80 years at high risk of cardiovascular disease from Reus, Spain. Intervention: Participants were randomly assigned to 3 ad libitum diets: a MedDiet supplemented with virgin olive oil (MedDiet + olive oil), a MedDiet supplemented with mixed nuts (MedDiet + nuts), or a control low-fat diet. Outcomes: Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (ACR). Measurements: Nutrient intake, adherence to the MedDiet, lifestyle variables, cardiovascular risk factors, serum urea and creatinine concentrations, eGFR, and urinary ACR were evaluated at baseline and after intervention for 1 year. Results: Baseline kidney function markers were similar across quartiles of adherence to the MedDiet in 785 participants (55% women; mean age, 67 years). After a 1-year intervention in 665 participants, the 3 dietary approaches were associated with improved kidney function, with similar average increases in eGFR (4.7 [95% CI, 3.2-6.2], 3.5 [95% CI, 1.9-5.0], and 4.1 [95% CI, 2.8-5.5] mL/min/1.73 m2 for the MedDiet + olive oil, MedDiet + nuts, and control groups, respectively [P < 0.001 vs baseline for each; P = 0.9 for differences among groups]), but no changes in ACRs after adjustment for various confounders. Limitations: Generalization of results to other age groups or ethnicities. GFR was not directly measured. Conclusions: The results do not support the notion that the MedDiet has a beneficial effect on kidney function over and above that of advice for a low-fat diet in elderly individuals at high cardiovascular risk.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Injury Molecule 1 (KIM-1) as Predictors of Incident CKD Stage 3: The Atherosclerosis Risk in Communities (ARIC) Study - Corrected Proof

Nrupen A. Bhavsar, Anna Köttgen, Josef Coresh, Brad C. Astor — 2012-04-30

Background: Identifying individuals at risk of chronic kidney disease (CKD) is critical for timely treatment initiation to slow progression of the disease. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) are known biomarkers of acute kidney injury, but it is unknown whether these markers are associated with incident CKD stage 3 in the general population. Study Design: Matched case-control study. Setting & Participants: African American and white participants from the Atherosclerosis Risk in Communities (ARIC) Study who at baseline had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and urinary albumin-creatinine ratio ≤30 mg/g. 143 controls were matched for age, sex, and race to 143 cases of incident CKD stage 3 after 8.6 years of follow-up. Predictors: Quartile of NGAL and KIM-1. Outcomes & Measurements: Incident CKD stage 3 (eGFR <60 mL/min/1.73 m2 at follow-up and a decrease in eGFR from baseline to follow-up ≥25%). Results: Both NGAL (P = 0.05) and KIM-1 levels (P < 0.001) were correlated positively with baseline urinary albumin-creatinine ratio; neither was associated with baseline eGFR. Participants with NGAL concentrations in the fourth quartile had more than 2-fold higher odds (adjusted OR, 2.11; 95% CI, 0.96-4.64) of incident CKD stage 3 compared with participants in the first quartile after multivariable adjustment (P-trend = 0.03). Adjustment for urinary creatinine and albumin levels resulted in a nonsignificant association (highest quartile adjusted OR, 1.52; 95% CI, 0.64-3.58; P = 0.2). No significant association between KIM-1 level and incident CKD was observed in crude or adjusted models. Limitations: The relatively small sample size of the study limits precision and power to detect weak associations. Conclusions: Higher NGAL, but not KIM-1, levels were associated with incident CKD stage 3. Adjustment for urinary creatinine and albumin concentration attenuated this association. Additional studies are needed to confirm these findings and assess the utility of urinary NGAL as a marker of CKD risk.

Association of Complete Recovery From Acute Kidney Injury With Incident CKD Stage 3 and All-Cause Mortality - Corrected Proof

2012-04-30

Background: There is a gap of knowledge in the long-term outcomes of patients who have complete recovery of kidney function after an episode of acute kidney injury (AKI). We sought to determine whether complete recovery of kidney function after an episode of AKI is associated with the development of incident stage 3 chronic kidney disease (CKD) and mortality in patients with normal baseline kidney function. Design: Retrospective cohort study. Setting & Participants: 3,809 patients from an integrated health care delivery system who had a hospitalization between January 1, 1999, and December 31, 2009, with follow-up through March 31, 2010. Predictor: AKI defined by International Classification of Diseases, Ninth Revision (ICD-9) codes and using the AKI Network (AKIN) definition, with complete recovery defined as a decrease in serum creatinine level to less than 1.10 times the baseline value. Outcomes and Measurements: Incident stage 3 CKD persistent for 3 months and all-cause mortality. Results: After a median follow-up of 2.5 years, incident stage 3 CKD occurred in 15% and 3% of those with and without AKI, respectively, with an unadjusted HR of 5.93 (95% CI, 4.49-7.84) and HR of 3.82 (95% CI, 2.81-5.19) in propensity score–stratified analyses. Deaths occurred in 35% and 24% of those with and without AKI, respectively, with an unadjusted HR of 1.46 (95% CI, 1.27-1.68). In propensity score–stratified analyses, HR decreased to 1.08 (95% CI, 0.93-1.27). Limitations: Measurements of albuminuria were not available. Conclusions: Complete recovery of kidney function after an episode of AKI in patients with normal baseline kidney function is associated with increased risk of the development of incident stage 3 CKD, but not all-cause mortality.

Association of a Novel Complement Factor H Mutation With Severe Crescentic and Necrotizing Glomerulonephritis - Corrected Proof

Fernando C. Fervenza, Richard J.H. Smith, Sanjeev Sethi — 2012-04-27

Severe crescentic and necrotizing glomerulonephritis typically is associated with anti–glomerular basement membrane or antineutrophil cytoplasmic antibodies. In this report, we describe a 23-year-old man with severe crescentic and necrotizing glomerulonephritis. Both anti–glomerular basement membrane and antineutrophil cytoplasmic antibody titers were negative. Kidney biopsy showed bright C3 staining in the mesangium and along capillary walls and no staining for immunoglobulins. Electron microscopy showed waxy deposits (many mesangial; few intramembranous or subendothelial), prompting evaluation of the alternative pathway of complement. Alternative pathway evaluation showed a novel mutation in short consensus repeat (SCR) 19 of complement factor H. In addition, the patient carried complement factor H and C3 risk alleles. Prompt treatment with intravenous steroids followed by oral steroids resulted in symptom alleviation and improved kidney function. This case shows what is to our knowledge a unique and previously unpublished cause of severe crescentic and necrotizing glomerulonephritis. Furthermore, the case demonstrates an expanding spectrum of complement-mediated glomerulonephritis and shows that crescentic and necrotizing glomerulonephritis with solely complement deposits should be evaluated for abnormalities in the alternative pathway of complement.

Immune Monitoring of Kidney Allografts - Corrected Proof

Julie Ho, Chris Wiebe, Ian W. Gibson, David N. Rush, Peter W. Nickerson — 2012-04-27

Current strategies for posttransplant monitoring of kidney transplants consist of measuring serial serum creatinine levels, clinical follow-up, and in some programs, protocol biopsies. These strategies may be insufficient to predict acute rejection in kidney transplants, which remains the major factor affecting long-term transplant outcomes. Immune monitoring may conceptually be divided into strategies for detecting humoral rejection (eg, donor-specific antibody) or cellular rejection. Cellular rejection markers may be separated further into those related to cytotoxic T lymphocytes (granzyme A/B, perforin, Fas ligand, and serpin B9), regulatory T cells (FOXP3), and CD4 T cells (the chemokines CXCL9, CXCL10, CXCL11, CCL2, and fractalkine, as well as TIM-3). Finally, transcriptomic changes and renal tubular injury markers also may be useful for detecting early inflammatory changes post–kidney transplant. Ultimately, novel strategies for monitoring the immune status of the kidney transplant may lead to early therapeutic intervention and improved kidney transplant outcomes.

Bleeding Complications of Native Kidney Biopsy: A Systematic Review and Meta-analysis - Corrected Proof

Kristin M. Corapi, Joline L.T. Chen, Ethan M. Balk, Craig E. Gordon — 2012-04-26

Background: Kidney biopsy provides important information for nephrologists, but the risk of complications has not been systematically described. Study Design: Meta-analysis of randomized controlled trials and prospective or retrospective observational studies. Setting & Population: Adults undergoing native kidney biopsy in an inpatient or outpatient setting. Selection Criteria for Studies: MEDLINE indexed studies from January 1980 through June 2011; sample size of 50 or more. Intervention: Native kidney biopsy with automated biopsy device and real-time ultrasonographic guidance. Outcomes: Macroscopic hematuria and erythrocyte transfusion rates and factors associated with these outcomes. Results: 34 studies of 9,474 biopsies met inclusion criteria. The rate of macroscopic hematuria was 3.5% (95% CI, 2.2%-5.1%), and erythrocyte transfusion was 0.9% (95% CI, 0.4%-1.5%). Significantly higher rates of transfusion were seen with the following: 14-gauge compared with smaller needles (2.1% vs 0.5%; P = 0.009), studies with mean serum creatinine level ≥2.0 mg/dL (2.1% vs 0.4%; P = 0.02), ≥50% women (1.9% vs 0.6%; P = 0.03), and ≥10% of biopsies for acute kidney injury (1.1% vs 0.04%; P < 0.001). Higher transfusion rates also were observed in studies with a mean age of 40 years or older (1.0% vs 0.2%; P = 0.2) and mean systolic blood pressure ≥130 mm Hg (1.4% vs 0.1%; P = 0.09). Similar relationships were noted for the macroscopic hematuria rate with the same predictors, but none was statistically significant. Limitations: Publication bias, few randomized controlled trials, and missing data. Conclusions: Native kidney biopsy using automated biopsy devices and real-time ultrasonography is associated with a relatively small risk of macroscopic hematuria and erythrocyte transfusion requirement. Using smaller gauge needles may lower complication rates. Patient selection may affect outcome because studies with higher serum creatinine levels, more women, and higher rates of acute kidney injury had higher complication rates. Future studies should further evaluate risk factors for complications.

Effect of Hemoglobin Target on Progression of Kidney Disease: A Secondary Analysis of the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) Trial - Corrected Proof

2012-04-26

Background: Conflicting relationships have been described between anemia correction using erythropoiesis-stimulating agents and progression of chronic kidney disease (CKD). This study was undertaken to examine the impact of target hemoglobin level on progression of kidney disease in the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial. Study Design: Secondary analysis of a randomized controlled trial. Setting & Participants: 1,432 participants with CKD and anemia. Intervention: Participants were randomly assigned to target hemoglobin levels of 13.5 versus 11.3 g/dL with the use of epoetin alfa. Outcomes & Measurements: Cox regression was used to estimate HRs for progression of CKD (a composite of doubling of creatinine level, initiation of renal replacement therapy, or death). Interactions between hemoglobin target and select baseline variables (estimated glomerular filtration rate, proteinuria, diabetes, heart failure, and smoking history) also were examined. Results: Participants randomly assigned to higher hemoglobin targets experienced shorter time to progression of kidney disease in both univariate (HR, 1.25; 95% CI, 1.03-1.52; P = 0.02) and multivariable models (HR, 1.22; 95% CI, 1.00-1.48; P = 0.05). These differences were attributable to higher rates of renal replacement therapy and death for participants in the high hemoglobin arm. Hemoglobin target did not interact with estimated glomerular filtration rate, proteinuria, diabetes, or heart failure (P > 0.05 for all). In the multivariable model, hemoglobin target interacted with tobacco use (P = 0.04) such that the higher target had a greater risk of CKD progression for participants who currently smoked (HR, 2.50; 95% CI, 1.23-5.09; P = 0.01), which was not present for those who did not currently smoke (HR, 1.15; 95% CI, 0.93-1.41; P = 0.2). Limitations: A post hoc analysis; thus, cause and effect cannot be determined. Conclusions: These results suggest that a high hemoglobin target is associated with a greater risk of progression of CKD. This risk may be augmented by concurrent smoking. Further defining the mechanism of injury may provide insight into methods to optimize outcomes in anemia management.

Combined Association of Albuminuria and Cystatin C–Based Estimated GFR With Mortality, Coronary Heart Disease, and Heart Failure Outcomes: The Atherosclerosis Risk in Communities (ARIC) Study - Corrected Proof

2012-04-26

Background: Serum cystatin C level has been shown to have a stronger association with clinical outcomes than serum creatinine level. However, little is known about the combined association of cystatin C–based estimated glomerular filtration rate (eGFRcys) and albuminuria with clinical outcomes, particularly at levels lower than current chronic kidney disease (CKD) cutoffs. Study Design: Prospective cohort. Setting & Participants: 10,403 ARIC (Atherosclerosis Risk in Communities) Study participants followed up for a median of 10.2 years. Predictor: eGFRcys, albuminuria. Outcomes: Mortality, coronary heart disease (CHD), and heart failure, as well as a composite of any of these separate outcomes. Results: Both decreased eGFRcys and albuminuria were associated independently with the composite outcome, as well as mortality, CHD, and heart failure. Although eGFRcys of 75-89 mL/min/1.73 m2 in the absence of albuminuria (albumin-creatinine ratio [ACR] <10 mg/g) or albuminuria with ACR of 10-29 mg/g with normal eGFRcys (90-104 mL/min/1.73 m2) was not associated significantly with any outcome compared with eGFRcys of 90-104 mL/min/1.73 m2 and ACR <10 mg/g, the risk of each outcome was significantly higher in those with both eGFRcys of 75-89 mL/min/1.73 m2 and ACR of 10-29 mg/g (for mortality, HR of 1.4 [95% CI, 1.1-2.0]; for CHD, HR of 1.9 [95% CI, 1.4-2.6]; for heart failure, HR of 1.8 [95% CI, 1.2-2.7]). Combining the 2 markers improved risk classification for all outcomes (P < 0.001), even in those without overt CKD. Limitations: Only one measurement of cystatin C. Conclusions: Mildly decreased eGFRcys and mild albuminuria independently contributed to the risk of mortality, CHD, and heart failure. Even minimally decreased eGFRcys (75-89 mL/min/1.73 m2) is associated with increased risk in the presence of mild albuminuria. Combining the 2 markers is useful for improved risk stratification even in those without clinical CKD.

Blood Pressure Measurement: Clinic, Home, Ambulatory, and Beyond - Corrected Proof

Paul E. Drawz, Mohamed Abdalla, Mahboob Rahman — 2012-04-23

Blood pressure traditionally has been measured in the clinic setting using the auscultatory method and a mercury sphygmomanometer. Technologic advances have led to improvements in measuring clinic blood pressure and allowed for measuring blood pressures outside the clinic. This review outlines various methods for evaluating blood pressure and the clinical utility of each type of measurement. Home blood pressures and 24-hour ambulatory blood pressures have improved our ability to evaluate the risk of target-organ damage and hypertension-related morbidity and mortality. Measuring home blood pressures may lead to more active participation in health care by patients and has the potential to improve blood pressure control. Ambulatory blood pressure monitoring enables measuring nighttime blood pressures and diurnal changes, which may be the most accurate predictors of risk associated with elevated blood pressure. Additionally, reducing nighttime blood pressure is feasible and may be an important component of effective antihypertensive therapy. Finally, estimating central aortic pressures and pulse wave velocity are 2 of the newer methods for assessing blood pressure and hypertension-related target-organ damage.

Long-term Management of CKD–Mineral and Bone Disorder - Corrected Proof

Kevin J. Martin, Esther A. González — 2012-04-23

Chronic kidney disease–mineral and bone disorder (CKD-MBD) is the term used to describe the abnormalities of bone and mineral metabolism that occur in the setting of kidney disease. The spectrum of these abnormalities is wide, ranging from severe high-turnover bone disease on one end to marked low bone turnover bone disease on the other. Similarly, some patients have severe vascular calcifications while others do not, and the values for biochemistry determinations, including calcium, phosphorus, and parathyroid hormone, also may vary widely among patients. This variability may be influenced by such things as the chronicity of the particular kidney disease, effects of therapies such as corticosteroids on modifying the course of kidney disease, and comorbid conditions, such as diabetes, heart disease, age, and osteoporosis. The heterogeneity of CKD-MBD makes strict protocol-driven therapeutic approaches difficult; accordingly, considerable individualized therapy is required. Using a case history, we explore several of the variables and difficulties involved in patient management.

Baseline Kidney Function as Predictor of Mortality and Kidney Disease Progression in HIV-Positive Patients - Corrected Proof

2012-04-23

Background: Chronic kidney disease (CKD) is associated with increased all-cause mortality and kidney disease progression. Decreased kidney function at baseline may identify human immunodeficiency virus (HIV)-positive patients at increased risk of death and kidney disease progression. Study Design: Observational cohort study. Setting & Participants: 7 large HIV cohorts in the United Kingdom with kidney function data available for 20,132 patients. Predictor: Baseline estimated glomerular filtration rate (eGFR). Outcomes: Death and progression to stages 4-5 CKD (eGFR <30 mL/min/1.73 m2 for >3 months) in Cox proportional hazards and competing-risk regression models. Results: Median age at baseline was 34 (25th-75th percentile, 30-40) years, median CD4 cell count was 350 (25th-75th percentile, 208-520) cells/μL, and median eGFR was 100 (25th-75th percentile, 87-112) mL/min/1.73 m2. Patients were followed up for a median of 5.3 (25th-75th percentile, 2.0-8.9) years, during which 1,820 died and 56 progressed to stages 4-5 CKD. A U-shaped relationship between baseline eGFR and mortality was observed. After adjustment for potential confounders, eGFRs <45 and >105 mL/min/1.73 m2 remained associated significantly with increased risk of death. Baseline eGFR <90 mL/min/1.73 m2 was associated with increased risk of kidney disease progression, with the highest incidence rates of stages 4-5 CKD (>3 events/100 person-years) observed in black patients with eGFR of 30-59 mL/min/1.73 m2 and those of white/other ethnicity with eGFR of 30-44 mL/min/1.73 m2. Limitations: The relatively small numbers of patients with decreased eGFR at baseline and low rates of progression to stages 4-5 CKD and lack of data for diabetes, hypertension, and proteinuria. Conclusions: Although stages 4-5 CKD were uncommon in this cohort, baseline eGFR allowed the identification of patients at increased risk of death and at greatest risk of kidney disease progression.

Membranous Nephropathy With Renal Salt Wasting: Role of Neurohumoral Factors in Sodium Retention - Corrected Proof

Musab Hommos, Christine Sinkey, William G. Haynes, Bradley S. Dixon — 2012-04-20

The role of neurohumoral factors in the sodium retention of nephrotic syndrome is controversial. We report a case with abrupt onset of severe nephrotic-range proteinuria and hypoalbuminemia due to membranous glomerulonephritis that was associated with renal salt wasting and hypovolemia without edema. Further evaluation showed hypoaldosteronism, hyporeninemia, and primary autonomic failure principally affecting the sympathetic nervous system, determined by the Valsalva maneuver. Administration of exogenous mineralocorticoid and oral salt caused edema and accelerated hypertension. The severe hypoaldosteronism likely was due to use of the angiotensin-converting enzyme inhibitor lisinopril, and it improved after this drug treatment was discontinued. The nephrotic proteinuria resolved after treatment with cyclosporine and prednisone, but the primary autonomic failure with hyporeninemic hypoaldosteronism persisted. The case shows that intratubular factors activated by nephrotic proteinuria are not sufficient to produce sodium retention in the absence of aldosterone and an intact sympathetic nervous system.

Effect of Theophylline on Prevention of Contrast-Induced Acute Kidney Injury: A Meta-analysis of Randomized Controlled Trials - Corrected Proof

Bing Dai, Yawei Liu, Lili Fu, Yongchuan Li, Jiayou Zhang, Changlin Mei — 2012-04-19

Background: Whether treatment with adenosine receptor antagonists such as theophylline can prevent contrast-induced acute kidney injury (AKI) remains controversial. Study Design: We conducted a meta-analysis of randomized controlled trials using MEDLINE (1966 to July 2011), EMBASE (1980 to July 2011), Web of Science (1986 to July 2011), and the Cochrane Central Register of Controlled Trials (1996 to July 2011), without language restriction. Setting & Population: Patients undergoing contrast procedures. Selection Criteria for Studies: Randomized controlled trials assessing adenosine antagonists versus control for prevention of contrast-induced AKI. Intervention: Adenosine antagonists with or without N-acetylcysteine versus control with or without N-acetylcysteine. Outcomes: Contrast-induced AKI, change in serum creatinine level, requirement of dialysis, and in-hospital mortality. Results: 16 trials (1,412 participants) were included. Theophylline significantly decreased the risk of contrast-induced AKI (13 trials, 1,222 patients; risk ratio, 0.48; 95% CI, 0.26-0.89; P = 0.02; I2 = 45%) and had a protective effect on the absolute change in serum creatinine concentration (13 trials, 1,170 patients; standardized mean difference, −0.31 mg/dL; 95% CI, −0.50 to −0.11; P = 0.002; I2 = 60%). Meta-regression showed a significant relation between the relative risk of contrast nephropathy and baseline serum creatinine level or Jadad score. No clear effects of treatment on risk of dialysis and in-hospital mortality were identified. Limitations: Power to assess clinical end points was limited. Conclusions: Theophylline treatment significantly reduced the incidence of contrast-induced AKI and had a modest improvement on kidney function after contrast exposure in the general population. However, beneficial effects of theophylline were not observed in patients with high baseline creatinine values (serum creatinine ≥1.5 mg/dL). In addition, the long-term effect of this agent on more clinically important outcomes was not established. Future large-scale high-quality multicenter trials in participants with different underlying risks of contrast-induced AKI and that incorporate the evaluation of clinically relevant outcomes are required.

Exposure to Potentially Toxic Hydrocarbons and Halocarbons Released From the Dialyzer and Tubing Set During Hemodialysis - Corrected Proof

2012-04-16

Background: Although much is known about the effect of chronic kidney failure and dialysis on the composition of solutes in plasma, little is known about their impact on the composition of gaseous compounds in exhaled breath. This study was designed to explore the effect of uremia and the hemodialysis (HD) procedure on the composition of exhaled breath. Breath samples were collected from 10 dialysis patients immediately before, during, and after a dialysis session. To determine the potential introduction of gaseous compounds from dialysis components, gasses emitted from dialyzers, tubing set, dialysate, and water supplies were collected. Study Design: Prospective cohort study. Participants: 10 HD patients and 10 age-matched healthy individuals. Predictor: Predictors include the dialyzers, tubing set, dialysate, and water supplies before, during, and after dialysis. Outcomes: Changes in the composition of exhaled breath. Measurements: A 5-column/detector gas chromatography system was used to measure hydrocarbon, halocarbon, oxygenate, and alkyl nitrate compounds. Results: Concentrations of 14 hydrocarbons and halocarbons in patients' breath rapidly increased after the onset of the HD treatment. All 14 compounds and 5 others not found in patients' breath were emitted from the dialyzers and tubing sets. Contrary to earlier reports, exhaled breath ethane concentrations in our dialysis patients were virtually unchanged during the HD treatment. Limitations: Single-center study with a small sample size may limit the generalizability of the findings. Conclusions: The study documented the release of several potentially toxic hydrocarbons and halocarbons to patients from the dialyzer and tubing sets during the HD procedure. Because long-term exposure to these compounds may contribute to the morbidity and mortality in dialysis population, this issue should be considered in the manufacturing of the new generation of dialyzers and dialysis tubing sets.

Dispensed Selective and Nonselective Nonsteroidal Anti-inflammatory Drugs and the Risk of Moderate to Severe Hyperkalemia: A Nested Case-Control Study - Corrected Proof

Jean-Philippe Lafrance, Donald R. Miller — 2012-04-16

Background: It is not known whether nonselective and cyclooxygenase 2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs) differ in terms of hyperkalemia risk. The aim of this study was to compare the differential risk of hyperkalemia associated with various NSAIDs. Study Design: Nested case-control study. Setting & Participants: New NSAID users receiving care in the US Department of Veterans Affairs (VA) health care system from October 2000 to September 2006. Predictor of Factor: Different NSAIDs ordered by COX-2 selectivity. Outcomes & Measurements: Risk of hyperkalemia (defined as first serum potassium value ≥6.0 mEq/L) was estimated with a multivariate conditional logistic model adjusting for age, race, morbidities, medications, and contrast media. Results: We identified 18,326 cases of hyperkalemia and 355,106 matched controls. Risk of hyperkalemia did not differ in patients using a single NSAID (adjusted OR, 1.03; 95% CI, 0.98-1.08) or 2 or more NSAIDs (OR, 1.16; 95% CI, 0.96-1.41) compared with patients no longer using an NSAID. However, risk varied by specific NSAID and elevated risks were found for use of rofecoxib, celecoxib, diclofenac, and indomethacin, but not meloxicam, etodolac, piroxicam, sulindac, ibuprofen, naproxen, and ketorolac. Interactions were found between NSAID use and exposure to renin-angiotensin blockers and contrast media. Limitations: Some NSAIDs are available over the counter and women are under-represented in the VA population. Conclusions: NSAIDs may not by themselves carry a higher risk of moderate to severe hyperkalemia. Certain NSAIDs may increase the risk of hyperkalemia, but it is not related to COX-2 selectivity of the NSAID and may depend on concurrent exposure to other agents.

Acute Presentation and Persistent Glomerulonephritis Following Streptococcal Infection in a Patient With Heterozygous Complement Factor H–Related Protein 5 Deficiency - Corrected Proof

2012-04-16

Acute poststreptococcal glomerulonephritis is a common cause of acute nephritis in children. Transient hypocomplementemia and complete recovery are typical, with only a minority developing chronic disease. We describe a young girl who developed persistent kidney disease and hypocomplementemia after a streptococcal throat infection. Kidney biopsy 1 year after presentation showed isolated glomerular complement C3 deposition, membranoproliferative changes, and subendothelial, intramembranous and occasional subepithelial electron-dense deposits consistent with C3 glomerulopathy. Complement gene screening revealed a heterozygous single nucleotide insertion in exon 4 of the complement factor H–related protein 5 gene (CFHR5), resulting in a premature stop codon. This variant was not detected in 198 controls. Serum CFHR5 levels were reduced. The mother and sister of the index patient were heterozygous for the sequence variant, with no overt evidence of kidney disease. We speculate that this heterozygous CFHR5 sequence variant is a risk factor for the development of chronic kidney disease after streptococcal infection.

A Randomized Trial of Catheters of Different Lengths to Achieve Right Atrium Versus Superior Vena Cava Placement for Continuous Renal Replacement Therapy - Corrected Proof

David Morgan, Kwok Ho, Conor Murray, Hugh Davies, Jeanne Louw — 2012-04-13

Background: The aim was to assess whether inserting a longer soft silicone short-term dialysis catheter targeting tip placement in the right atrium could improve dialyzer circuit life span compared with inserting a shorter dialysis catheter targeting tip placement in the superior vena cava. Study Design: Randomized unblinded controlled study. Setting & Participants: A tertiary multidisciplinary intensive care unit enrolling 100 critically ill patients requiring continuous renal replacement therapy (CRRT). Intervention: Placement of longer (20-24 cm) versus shorter dialysis catheters (15-20 cm) within one of the major thoracic veins for initiation of CRRT. Outcomes: The primary study outcome was duration of dialysis circuit life span. Secondary outcomes included delivered daily dialysis dose, incidence and cause of CRRT circuit failure, complications potentially related to the position of the short-term dialysis catheter, mortality, and patient length of stay. Results: Placing the longer dialysis catheters was associated with an increased average dialyzer life span of 6.5 hours (24 hours [25th-75th percentile, 11-32] vs 17.5 hours [25th-75th percentile, 8-23]; P = 0.001), improved delivered daily dialysis dose (91% [25th-75th percentile, 85%-100%] vs 81% [25th-75th percentile, 72%-97%]; P < 0.001), and reduced number of dialyzers clotted (2.3 vs 3.6; P = 0.04) or circuits taken down due to vascular access problem (0.19 vs 0.53; P = 0.04) per patient compared with placing shorter dialysis catheters. The incidence of atrial arrhythmias was similar between groups (28% vs 21%; P = 0.6) and the only mechanical complication was the malposition of one dialysis catheter tip in the longer dialysis catheter group. Limitations: Single-center study design. Conclusions: The use of longer soft silicone short-term dialysis catheters targeting right atrial placement appeared to be safe and could improve dialyzer life span and daily dialysis dose of CRRT delivered compared with the use of shorter catheters targeting superior vena cava placement.

Effect of Electronic Alert on Risk of Contrast-Induced Acute Kidney Injury in Hospitalized Patients Undergoing Computed Tomography - Corrected Proof

2012-04-13

Background: Prophylaxis against contrast-induced acute kidney injury (AKI) in hospitalized patients is underused. We evaluated the impact of a computerized alert program for contrast-induced AKI for hospitalized patients undergoing contrast-enhanced computed tomography (CT). Study Design: Quality improvement report. Setting & Participants: 463 adult inpatients in a single center with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Quality Improvement Plan: We developed a computer alert program in which the responsible physician was alerted to a patient's risk of contrast-induced AKI in the form of a warning message box and was recommended to consider prophylactic measures for contrast-induced AKI when he or she ordered contrast-enhanced CT for patients with eGFR <60 mL/min/1.73 m2. The intervention was applied simultaneously to all hospitalized patients from March 18, 2010. The hospital's contrast-induced AKI preventive guidelines included prehydration, posthydration, and oral N-acetylcysteine. Outcome & Measurements: Use of prophylactic interventions, development of contrast-induced AKI. Contrast-induced AKI was defined as an increase in serum creatinine level (≥0.3 mg/dL or ≥50%) 24-72 hours after contrast medium exposure. Results: 258 adult inpatients with eGFR <60 mL/min/1.73 m2 were identified as undergoing contrast-enhanced CT before application of the computer alert program (from October 28, 2009, to March 17, 2010), and 205, after its application (from March 18, 2010, to August 5, 2010). Individuals in the postalert group received contrast-induced AKI prophylaxis more often than those in the prealert group (55% vs 25% for total prophylaxis; P < 0.001). The incidence of contrast-induced AKI was lower in the postalert group than in the prealert group (3% vs 10%; P = 0.02). Limitations: Observation bias; only 61.5% of participants were evaluated for contrast-induced AKI. Conclusions: Implementation of a computerized alert program in hospitalized patients was followed by increased use of prophylaxis and decreased risk of contrast-induced AKI.

Erratum Regarding Charytan et al, “Trends in the Use and Outcomes of Implantable Cardioverter-Defibrillators in Patients Undergoing Dialysis in the United States” [Am J Kidney Dis 2011; 58:409-417] - Corrected Proof

2012-04-13

In the article entitled “Trends in the Use and Outcomes of Implantable Cardioverter-Defibrillators in Patients Undergoing Dialysis in the United States” (Charytan et al, American Journal of Kidney Diseases, 58(3):409-417, 2011), the wrong article was listed for reference 26. The correct reference follows:

Factors Associated With Depressive Symptoms and Use of Antidepressant Medications Among Participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies - Corrected Proof

2012-04-12

Background: Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied. Study Design: Cross-sectional analysis. Settings & Participants: Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at 7 centers in 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois in 2005-2008. Measurement: Depressive symptoms measured by Beck Depression Inventory (BDI). Predictors: Demographic and clinical factors. Outcomes: Elevated depressive symptoms (BDI score ≥11) and antidepressant medication use. Results: Of 3,853 participants, 27.4% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 31.0% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 23.6% for participants with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and 33.8% of those with eGFR <30 mL/min/1.73 m2. Lower eGFR (OR per 10-mL/min/1.73 m2 decrease, 1.10; 95% CI, 1.04-1.17), and non-Hispanic black race (OR, 1.42; 95% CI, 1.16-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, whereas female sex was associated with greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher urine albumin levels were associated with decreased odds of antidepressant use (P < 0.05 for each). Limitations: Absence of clinical diagnosis of depression and use of nonpharmacologic treatments. Conclusions: Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. Individuals of racial and ethnic minority background and with more advanced CKD had a greater burden of elevated depressive symptoms and lower use of antidepressant medications.

Racial Survival Paradox of Dialysis Patients: Robust and Resilient - Corrected Proof

Kamyar Kalantar-Zadeh, Csaba P. Kovesdy, Keith C. Norris — 2012-04-12

Commentary on: Kucirka LM, Grams ME, Lessler J, et al. Association of race and age with survival among patients undergoing dialysis. JAMA. 2011;306(6):620-626.

Effect of Renal Artery Stenting on Left Ventricular Mass: A Randomized Clinical Trial - Corrected Proof

2012-04-12

Background: Whether renal revascularization reduces left ventricular hypertrophy in patients with coronary artery disease is uncertain. Study Design: Randomized clinical trial testing the effect of renal artery stenting versus medical therapy on left ventricular hypertrophy progression in patients affected by ischemic heart disease and renal artery stenosis. Setting & Participants: Incident patients with ischemic heart disease undergoing cardiac catheterization with renal artery stenosis >50%-≤80%. Intervention: Revascularization plus standard medical therapy versus medical therapy alone. Outcomes: Primary end point was change in echocardiographic left ventricular mass index (LVMI). Measurements: Clinical and echocardiographic studies were performed at baseline and after 1 year. Results: 84 patients were randomly assigned: 43 to revascularization plus standard medical therapy and 41 to medical therapy alone. At baseline, clinical characteristics were similar in the 2 study groups. After 1 year, there was no statistically significant difference between longitudinal change in the medical therapy group versus that in the medical therapy plus revascularization group for LVMI (2.1; 95% CI, −6.1 to 10.3 g/m2), blood pressure (systolic, −0.2 [95% CI, −9.1 to 8.8 mm Hg]; diastolic, −3.3 [95% CI, −8.4 to 1.8 mm Hg]), or estimated glomerular filtration rate (1.5; 95% CI, −5.8 to 8.9 mL/min/1.73 m2). The number of major cardiovascular events was similar in the 2 groups (revascularization plus standard medical therapy [fatal, n = 2; nonfatal, n = 11] and medical therapy alone [fatal, n = 2; nonfatal, n = 11]). Limitations: Patients with very severe renal artery stenosis were excluded from the study. Conclusions: Our study was unable to detect a clinically significant benefit of renal revascularization on LVMI in patients with coronary artery disease and renal artery stenosis of 50%-80%.

Accuracy of a GFR Estimating Equation Over Time in People With a Wide Range of Kidney Function - Corrected Proof

2012-04-12

Background: Change in glomerular filtration rate (GFR) is important for clinical decision making. GFR estimates from serum creatinine level provide an unbiased but imprecise estimate of GFR at single time points. However, the accuracy of estimated GFR over time is not well known. Study Design: Longitudinal study of diagnostic test accuracy. Settings & Participants: 4 clinical trials with longitudinal measurements of GFR and serum creatinine on the same day, including individuals with and without kidney disease with a wide range of kidney function, diverse racial backgrounds, and varied clinical characteristics. Index Test: GFR estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Reference Test: GFR measured using urinary clearance of 125I-iothalamate. Results: Data included 19,735 GFR measurements in 3,531 participants during a mean follow-up of 2.6 years. Mean values at baseline for measured and estimated GFR and error (measured GFR – estimated GFR) were 73.1 (95% CI, 71.6 to 74.5), 72.7 (95% CI, 71.5 to 74.0), and 0.14 (95% CI, −0.35 to 0.63) mL/min/1.73 m2, respectively. Mean rates of change in measured and estimated GFR and error were −2.3 (95% CI, −2.4 to −2.1), −2.2 (95% CI, −2.4 to −2.1), and −0.09 (95% CI, −0.24 to 0.05) mL/min/1.73 m2 per year (P < 0.001, P < 0.001, and P = 0.2, respectively). Variability (ie, standard deviation) among participants in rate of change in measured GFR, estimated GFR, and error was 4.3, 3.4, and 3.3 mL/min/1.73 m2 per year, respectively. Only 15% of participants had a rate of change in error >3 mL/min/1.73 m2 per year, and only 2% had a rate of change in error >5% per year. Limitations: Participants' characteristics were not available over time. Conclusion: The accuracy of GFR estimates did not change over time. Clinicians should interpret changes in estimated GFR over time as reflecting changes in measured GFR rather than changes in errors in the GFR estimates in most individuals.

Association of Symptoms of Depression With Progression of CKD - Corrected Proof

2012-04-12

Background: Depression is related to morbidity and mortality in patients with kidney failure treated by dialysis, but its influence on patients with earlier stages of chronic kidney disease (CKD) is uncertain. This study investigates the association of depressive symptoms with clinical outcomes in patients with CKD not requiring dialysis. Study Design: Prospective observational cohort study. Setting & Participants: 568 participants with CKD not requiring maintenance dialysis were recruited consecutively at a tertiary hospital in Southern Taiwan and followed up for 4 years. Predictors: Baseline status of depressive symptoms. Outcomes: The primary outcome is a composite of progression to end-stage renal disease (ESRD), defined as requiring maintenance dialysis treatment, or all-cause mortality; and secondary outcome was first hospitalization. Measurements: Depressive symptoms were assessed by Beck Depression Inventory. Estimated glomerular filtration rate (eGFR) was computed using the 4-variable MDRD (Modification of Diet in Renal Disease) Study equation. Results: 428 participants completed the questionnaires and 160 (37%) had depressive symptoms. During a mean follow-up of 25.2 ± 11.9 months, 136 participants (32%) reached the primary outcome (119 reached ESRD and 17 died) and 110 participants (26%) were hospitalized. High depressive symptoms increased the risk of progression to ESRD or death (HR, 1.66; 95% CI, 1.14-2.44) and first hospitalization (HR, 1.59; 95% CI, 1.03-2.47). Participants with high depressive symptoms had more rapid GFR decrease (eGFR slopes of −2.3 [25th-75th percentile, −5.3 to −0.4] vs −1.2 [25th-75th percentile, −3.5 to 0.3] mL/min/1.73 m2 per year; P = 0.001) and initial dialysis treatment at a higher eGFR (OR for initiation of dialysis at eGFR >5 mL/min/1.73 m2, 4.45; 95% CI, 1.44-13.78). Limitations: A single-center study of Taiwanese, Beck Depression Inventory evaluates only depressive symptom burden. Conclusions: Depressive symptoms in CKD are independent predictors of adverse clinical outcomes, including faster eGFR decrease, dialysis therapy initiation, death, or hospitalization. Depression should be evaluated early and treated in patients with CKD.

Risk Stratification of Patients With IgA Nephropathy - Corrected Proof

Sean J. Barbour, Heather N. Reich — 2012-04-12

In this review, we summarize recent advances in the risk stratification of patients with immunoglobulin A (IgA) nephropathy. Several clinical variables have consistent and independent associations with worse kidney prognosis, including blood pressure, proteinuria, and baseline kidney function. Although one-time cross-sectional assessments of blood pressure and proteinuria are important, a more thorough understanding of risk can be achieved when these variables are considered over a follow-up period. IgA nephropathy is unique compared with other glomerular diseases in that a much lower threshold of proteinuria (protein excretion, 1 g/d) is associated with glomerular filtration rate (GFR) loss. Controlling proteinuria and blood pressure over time is important to reduce the risk of future loss of kidney function. The recently described Oxford classification has helped standardize the pathologic characterization of IgA nephropathy using a scoring system that is readily reproducible and associated with increased risk of GFR loss independent of clinical variables. We suggest an approach to risk stratification in IgA nephropathy when considering potential treatment with immunosuppression. Despite our current understanding of risk stratification in IgA nephropathy, the ability to accurately predict individual patient-level risk currently is limited, and further research into additional biomarkers or risk prediction tools is needed to improve the care of patients with IgA nephropathy.

A Varying Patient Safety Profile Between Black and Nonblack Adults With Decreased Estimated GFR - Corrected Proof

2012-04-09

Background: Chronic kidney disease is a high-risk condition for a variety of adverse safety events, yet little is known about differential rates of safety events across racial groups with decreased kidney function. We sought to examine the incidence of an array of disease-specific adverse safety events in black versus nonblack patients with decreased estimated glomerular filtration rate (eGFR). Study Design: Retrospective observational study of a national US Veterans Affairs cohort. Settings & Participants: Veterans with eGFR <60 mL/min/1.73 m2 and one or more hospitalization during federal fiscal year 2005 (n = 70,154). Predictor: Self-reported race/ethnicity dichotomized as black or nonblack. Outcomes: Hospital discharge coding for Agency for Healthcare Research and Quality (AHRQ) patient safety indicators (PSIs), laboratory records for detection of hyperkalemia and hypoglycemia, and pharmacy records to determine dosing of 4 selected medications. Measurements: Relationship between race and disease-specific patient safety events. Results: Black veterans were more likely than nonblack veterans to experience one type of safety event (33% vs 32%, respectively) and multiple types of safety events (32% vs 23%, respectively; both P < 0.001). After adjustment, black veterans were 11% and 36% more likely to have at least one episode of hyperkalemia and hypoglycemia, respectively, than nonblack veterans, but were 14% less likely to experience a medication error (all P < 0.001). There was no association between the occurrence of AHRQ PSIs and race after adjustment. Limitations: Use of administrative data has a risk of imprecision in coding; Veterans Affairs cohort may limit generalizability. Conclusions: Black veterans with decreased eGFR are more likely to experience a broad array of safety events than nonblacks with decreased eGFR, with a preponderance of metabolic disturbances rather than medication errors or AHRQ PSIs. The differential safety phenotype in blacks versus nonblacks may have implications for preventive strategies to improve patient safety in an integrated health care system.

Hepatorenal Syndrome: A Severe, but Treatable, Cause of Kidney Failure in Cirrhosis - Corrected Proof

Cláudia Fagundes, Pere Ginès — 2012-04-06

Hepatorenal syndrome (HRS) is a unique type of kidney failure that occurs in advanced cirrhosis. It is characterized by functional impairment of the kidneys due to vasoconstriction of the renal arteries in the setting of preserved tubular function and absence of significant histologic abnormalities. Renal vasoconstriction in HRS is due to severe vasodilation of the splanchnic arteries associated with portal hypertension, leading to a decrease in effective arterial blood volume and arterial pressure. HRS commonly develops after a trigger, usually a bacterial infection, that disrupts the arterial circulation, but it also may occur spontaneously. There are 2 forms of HRS: type 1 is characterized by an acute progressive decrease in kidney function and very short survival without treatment, whereas type 2 features stable less severe kidney failure and longer survival compared with type 1. A liver transplant is the preferred treatment for HRS. Pharmacologic treatment with vasoconstrictors to reverse splanchnic vasodilation, together with albumin, is effective in 40%-50% of patients with type 1 HRS and improves survival. The drug of choice is the vasopressin analogue terlipressin. Renal replacement therapy should not be used as first-line therapy.

Tinzaparin Versus Dalteparin for Periprocedure Prophylaxis of Thromboembolic Events in Hemodialysis Patients: A Randomized Trial - Corrected Proof

2012-04-06

Background: Low-molecular-weight heparin (LMWH) is cleared predominantly by the kidneys and hence there is uncertainty about the safety of its use in hemodialysis (HD) patients. Our primary objective was to compare whether tinzaparin and dalteparin differentially accumulate in HD patients. Study Design: Open-label randomized controlled trial. Setting & Participants: HD patients undergoing periprocedure bridging anticoagulation. Intervention: After warfarin therapy was discontinued, participants were randomly assigned to either 3 daily doses of tinzaparin (175 IU/kg) or dalteparin (200 IU/kg), with 2 intervening HD treatments between the first dose of study drug and their procedure. Outcomes: The primary outcome was predialysis anti-Xa levels 20 to 24 hours after the third LMWH dose (therapeutic target, <0.2 IU/mL). Secondary outcomes included thromboembolic events and major bleeding. Results: Of 29 eligible and consenting patients, 17 patients received tinzaparin and 12 patients received dalteparin. Mean predialysis anti-Xa level 20-24 hours after the third LMWH dose was 0.37 ± 0.23 (SD) IU/mL for tinzaparin and 0.62 ± 0.41 IU/mL for dalteparin (P = 0.1), indicating clinically important accumulation for both drugs. No invasive procedures were canceled due to study drug accumulation. 4 patients experienced serious adverse events (1 major bleed after traumatic arteriovenous fistula puncture in the tinzaparin arm, 2 non–ST-elevation myocardial infarctions [1 in each group], and 1 upper-extremity deep venous thrombosis [dalteparin group]). Limitations: Small sample size. Conclusions: Dalteparin and tinzaparin significantly accumulate in HD patients at therapeutic doses. “Bridging therapy” with LMWHs at therapeutic doses in HD patients who require temporary interruption of warfarin therapy has the potential for complications and is of uncertain benefit. Other anticoagulation strategies, including no bridging therapy or intravenous heparin, need comparative evaluation in this unique patient population.

Optimizing Care for Patients With CKD - Corrected Proof

Paul E. Ronksley, Brenda R. Hemmelgarn — 2012-04-06

Care of patients with chronic kidney disease (CKD) is complex and requires a standardized and multidisciplinary approach. A number of strategies have been suggested to improve care for patients with CKD, including the development of clinical practice guidelines and introduction of chronic disease management (CDM) programs. CDM programs represent a proactive approach to care by supporting the physician and patient, with an emphasis on prevention of exacerbations and complications achieved through a coordinated multidisciplinary team. In addition to targeting patients at highest risk, CDM programs also emphasize intensive monitoring and proactive follow-up. The expansion of professional roles may be an important component in ensuring the success of this approach. Although observational studies suggest that specific components of CDM programs may improve care for patients with CKD, further research is needed to evaluate the program component effectiveness in CKD prevention and management. This includes well-conducted randomized trials and long-term follow-up of patients with CKD to assess changes in adverse health outcomes.

Fracture Risk in Living Kidney Donors: A Matched Cohort Study - Corrected Proof

2012-04-03

Background: Chronic kidney disease increases the risk of bone fragility fractures (osteoporotic fractures). Living kidney donors lose 50% of their renal mass and show changes in calcium homeostasis. We studied whether living kidney donation increases the risk of fragility fracture. Design: Retrospective matched-cohort study. Setting & Participants: We reviewed the medical charts of all 2,015 adults in Ontario, Canada, who donated a kidney between 1992 and 2009 (surgeries performed across 5 transplant programs). We linked this information to health care databases and randomly selected 20,150 matched nondonors from the healthiest portion of the general population. Median age was 43 (95% CI, 24-50) years at study enrollment. Donors and nondonors were then followed up for a median of 6.6 years and a maximum of 17.7 years. Predictor: Living donor nephrectomy. Outcomes: The primary outcome was lower- and upper-extremity fragility fractures. Individuals who reached 66 years or older in follow-up had bisphosphonate prescriptions recorded. Results: The rate of fragility fracture was no higher in donors compared with nondonors (16.4 vs 18.7 events/10,000 person-years; rate ratio, 0.88; 95% CI, 0.58-1.32). Results were similar in multiple additional analyses. There was little difference in the proportion of older adults in follow-up who received a bisphosphonate prescription (17.1% vs 15.2%; P = 0.4). Limitations: These are interim results. Ongoing surveillance of this and other donor cohorts is warranted to be sure an association does not manifest with longer follow-up. Conclusions: To date, there is no evidence of increased fragility fracture risk in living kidney donors. Our results meet an information need and are reassuring for the safety of the practice.

GFR at Initiation of Dialysis and Mortality in CKD: A Meta-analysis - Corrected Proof

2012-04-02

Background: The proportion of patients with advanced chronic kidney disease (CKD) initiating dialysis therapy at a higher glomerular filtration rate (GFR) has increased during the past decade. Recent data suggest that higher GFR may be associated with increased mortality. Study Design: A meta-analysis of cohort studies and trials. Setting & Population: Patients with advanced CKD. Selection Criteria for Studies: We performed a systematic literature search in MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, American Society of Nephrology abstracts, and bibliographies of retrieved articles to identify studies reporting on GFR at dialysis therapy initiation and mortality. Predictor: Estimated or calculated GFR at dialysis therapy initiation. Outcome: Pooled adjusted hazard ratio (HR) of continuous GFR for all-cause mortality. Results: 16 cohort studies and 1 randomized controlled trial were identified (n = 1,081,116). By meta-analysis restricted to 15 cohorts (n = 1,079,917), higher GFR at dialysis therapy initiation was associated with a higher pooled adjusted HR for all-cause mortality (1.04; 95% CI, 1.03-1.05; P < 0.001). However, there was significant heterogeneity (I2 = 97%; P < 0.001). The association persisted among the 9 cohorts that adjusted analytically for nutritional covariates (HR, 1.03; 95% CI, 1.02-1.04; P < 0.001; residual I2 = 97%). The highest mortality risk was observed in hemodialysis cohorts (HR, 1.05; 95% CI, 1.02-1.08; P < 0.001), whereas there was no association between GFR and mortality in peritoneal dialysis cohorts (HR, 1.04; 95% CI, 0.99-1.08, P = 0.1; residual I2 = 98%). Finally, higher GFR was associated with a lower mortality risk in cohorts that calculated GFR (HR, 0.80; 95% CI, 0.71-0.91; P = 0.003), contrasting with a higher mortality risk in cohorts that estimated GFR (HR, 1.04; 95% CI, 1.03-1.05; P < 0.001; residual I2 = 97%). Limitations: Paucity of randomized controlled trials, different methods for determining GFR, and substantial heterogeneity. Conclusions: Higher estimated rather than calculated GFR at dialysis therapy initiation is associated with a higher mortality risk in patients with advanced CKD, independent of nutritional status. Although there was substantial heterogeneity of effect size estimates across studies, this observation requires further study.

Serum Metabolite Concentrations and Decreased GFR in the General Population - Corrected Proof

2012-04-01

Background: Metabolites such as creatinine and urea are established kidney function markers. High-throughput metabolomic studies have not been reported in large general population samples spanning normal kidney function and chronic kidney disease (CKD). Study Design: Cross-sectional observational studies of the general population. Setting & Participants: 2 independent samples: KORA F4 (discovery sample, n = 3,011) and TwinsUK (validation sample, n = 984). Exposure Factors: 151 serum metabolites, quantified by targeted mass spectrometry. Outcomes & Measurements: Metabolites and their 22,650 ratios were analyzed by multivariable-adjusted linear regression for their association with glomerular filtration rate (eGFR), estimated separately from creatinine and cystatin C levels by CKD-EPI (CKD Epidemiology Collaboration) equations. After correction for multiple testing, significant metabolites (P < 3.3 × 10−4 for single metabolites; P < 2.2 × 10−6 for ratios) were meta-analyzed with independent data from the TwinsUK Study. Results: Replicated associations with eGFR were observed for 22 metabolites and 516 metabolite ratios. Pooled P values ranged from 7.1 × 10−7 to 1.8 × 10−69 for the replicated single metabolites. Acylcarnitines such as glutarylcarnitine were associated inversely with eGFR (−3.73 mL/min/1.73 m2 per standard deviation [SD] increase, pooled P = 1.8 × 10−69). The replicated ratio with the strongest association was the ratio of serine to glutarylcarnitine (P = 3.6 × 10−81). Almost all replicated phenotypes associated with decreased eGFR (<60 mL/min/1.73 m2; n = 172 cases) in KORA F4: per 1-SD increment, ORs ranged from 0.29-2.06. Across categories of a metabolic score consisting of 3 uncorrelated metabolites, the prevalence of decreased eGFR increased from 3% to 53%. Limitations: Cross-sectional study design, GFR was estimated, limited number of metabolites. Conclusions: Distinct metabolic phenotypes were reproducibly associated with eGFR in 2 separate population studies. They may provide novel insights into renal metabolite handling, improve understanding of pathophysiology, or aid in the diagnosis of kidney disease. Longitudinal studies are needed to clarify whether changes in metabolic phenotypes precede or result from kidney function impairment.

Desensitization Offers Hope to Highly HLA-Sensitized Patients for a Longer Life Expectancy After Incompatible Kidney Transplant - Corrected Proof

Stanley C. Jordan, Ashley A. Vo — 2012-04-01

Commentary on Montgomery RA, Lonze BE, King KE, et al. Desensitization in HLA-incompatible kidney recipients and survival. N Engl J Med. 2011;365(4):318-326.

Kidney Disease Education One Year After the Medicare Improvement of Patients and Providers Act: A Survey of US Nephrology Practices - Corrected Proof

Kim Zuber, Jane Davis, Dana V. Rizk — 2012-04-01

The past 20 years witnessed a 67% increase in the prevalence of chronic kidney disease (CKD) stage 4 (glomerular filtration rate of 15-30 mL/min/1.73 m2). Patient knowledge of CKD increases the incidence of permanent arteriovenous access placement before dialysis therapy initiation and can extend time to and improve outcomes after renal replacement therapy (RRT) initiation. Knowledge also facilitates early transplant referral. Recognizing this, Congress passed the Medicare Improvement of Patients and Providers Act (MIPPA) in 2010, authorizing 6 hours of kidney disease education for patients with CKD stage 4 who are Medicare beneficiaries. Classes should include management of comorbid conditions, prevention of uremic complications, review of currently available RRTs, and engagement of the patient in decisions related to treatment. A “qualified practitioner” (physician or advanced practitioner [physician assistant, nurse practitioner, or clinical nurse specialist]) is authorized to teach these classes in a neutral location, using an individual or group format. Only rural practices are exempt from these restrictions. Outcome measurements to assess effectiveness are to be performed during the class.

Community-Based Strategies for Blood Pressure Control in Low-Income Countries - Corrected Proof

Dorothea Nitsch, David C. Wheeler — 2012-03-26

Commentary on Jafar TH, Islam M, Bux R, et al. Cost-effectiveness of community-based strategies for blood pressure control in a low-income developing country: findings from a cluster-randomized, factorial-controlled trial. Circulation. 2011;124(15):1615-1625.

Cost-Effectiveness of Cinacalcet Hydrochloride for Hemodialysis Patients With Severe Secondary Hyperparathyroidism in Japan - Corrected Proof

2012-03-26

Background: Cinacalcet effectively reduces elevated levels of parathyroid hormone (PTH) in patients with secondary hyperparathyroidism (SHPT), even those with severe disease for whom parathyroidectomy can be the treatment of choice. The objective of this study was to estimate the cost-effectiveness of cinacalcet treatment in hemodialysis patients with severe SHPT in Japan. Study Design: Cost-effectiveness analysis. Setting & Population: Patients with severe SHPT (intact PTH >500 pg/mL) who were receiving hemodialysis in Japan. Model, Perspective, & Timeframe: A Markov model was constructed from the health care system perspective in Japan. Patients were followed up over their lifetime. Dialysis costs were not included in the base case. Intervention: Cinacalcet as an addition to conventional treatment compared to conventional treatment alone. In both arms, patients underwent parathyroidectomy if intact PTH level was >500 pg/mL for 6 months and they were eligible for surgery. Outcomes: Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results: ICERs for cinacalcet for those who were eligible for surgery and those who were not were $352,631/QALY gained and $21,613/QALY gained, respectively. Sensitivity and scenario analyses showed that results were fairly robust to variations in model parameters and assumptions. In the probabilistic sensitivity analysis, cinacalcet was cost-effective in only 0.9% of simulations for those eligible for surgery, but in more than 99.9% of simulations for those ineligible for surgery, if society would be willing to pay $50,000 per additional QALY. Limitations: Data for the long-term effect of cinacalcet on patient-level outcomes are limited. The model predicted rates for clinical events using data for the surrogate biochemical end points. Conclusions: The use of cinacalcet to treat severe SHPT is likely to be cost-effective for only those who cannot undergo parathyroid surgery for medical or personal reasons.