American Journal of Kidney Diseases

Masthead

2012-05-01

Editorial Board

2012-05-01

June Highlights

2012-05-01

Information for Contributors

2012-05-01

This Month in AJKD

2012-05-01

See Rule et al, pages 611-618; and Grantham pages 593-594. Simple renal cysts are usually considered to have little clinical significance. In this month's AJKD, Rule et al turn their attention to these largely ignored structures. The authors retrospectively examined 1,957 contrast enhanced CT scans of potential kidney donors undergoing standardized evaluation. Higher numbers and larger sizes of cysts were associated with male sex and older age. Moreover, the authors found an association between renal cysts in the cortex or medulla that were larger than 5 mm and albuminuria, hyperfiltration, and hypertension in relatively healthy adults, implying that these cysts may be markers of kidney damage. In the accompanying editorial, Grantham applauds Rule and colleagues for remaining undeterred by the widespread lack of interest in solitary cysts and calls for other clinicians and researchers to follow their lead in investigating renal cysts more closely.

Quiz Page May 2012: Severe Hypocalcemia in a Hemodialysis Patient

Samir Nangia, Scott Mullaney — 2012-05-01

A 46-year-old man with end-stage renal disease secondary to focal segmental glomerulosclerosis treated with hemodialysis presents with perioral numbness and tingling and a new seizure. He also notes the recent development of left-sided neck pain with a tender 2×2-cm mass. Before admission, the patient had elevated parathyroid hormone (PTH) and serum calcium levels (1,770 pg/mL [1,770 ng/L] and 11.5 mg/dL [2.87 mmol/L], respectively, with an ionized calcium level of 2.58 mEq/L [1.29 mmol/L]). His elevated calcium-phosphorus product level prevented the use of intravenous vitamin D while on dialysis therapy. As an outpatient, lanthanum carbonate, 1,000 mg, 3 times daily was prescribed as a phosphorus binder.

Solitary Renal Cysts: Worth a Second Look?

Jared J. Grantham — 2012-05-01

Condition-Specific Disease Treatment in Dialysis Patients: Utilization, Costs, and Guideline and Policy Imperatives

Barry M. Straube — 2012-05-01

Dialysis and Kidney Transplantation: Why Have Our Rehabilitation Hopes Not Been Achieved Fully?

Maristela Böhlke — 2012-05-01

Delivering Accountable Care to Patients With Complicated Chronic Illness: How Does It Fit Into Care Models and Do Nephrologists Have a Role?

Amy W. Williams, Robert E. Nesse, Douglas L. Wood — 2012-05-01

In an article appearing in the American Journal of Kidney Diseases World Kidney Forum, Nissenson et al outline the need for improved coordination of care for individuals with chronic kidney failure treated by dialysis (end-stage renal disease) and transplant and earlier stages of chronic kidney disease (CKD) and review the accountable care organization (ACO) rules that were released in 2011 by the Centers for Medicare & Medicaid Services. Nissenson et al state that the value of ACOs is the potential elimination of fragmented care, which should lead to decreased costs and improved outcomes. The ACO rules declare that patients' care within ACOs will be coordinated by a multidisciplinary team of providers centered around primary care and that financial rewards will be based on outcomes designed for the general population. The implementation of preventive and acute-care models for the general population with up to 1 or 2 uncomplicated chronic illnesses, such as hypertension and diabetes, seems straightforward because in these populations, the cost of the care model is easily defined and evidence-based guidelines are in place. Furthermore, the interaction between 2 stable comorbid conditions generally is well understood, with the functional performance of patients remaining high in the early stages of illness. However, how the ACO model of care will apply to those who require multispecialty collaboration for their care, those with advanced chronic disease, or those with significant comorbid chronic illnesses is less clear. As outlined by Nissenson et al, many of the evidence-based quality measures intended to promote health upon which the ACO's incentives are based cannot be extrapolated to those with complex advanced chronic disease, such as late stages of CKD, and as a result could potentially lead to malalignment of incentives, harm to patients, and increased cost. Furthermore, there is little evidence to suggest that significant cost savings might occur for patients with late stages of CKD under an ACO system.

The US Food and Drug Administration's Risk Evaluation and Mitigation Strategy (REMS) Program in Practice: Does It Really Inform Patients and Limit Risk?

Robert A. Cohen, Robert S. Brown — 2012-02-24

What is the most important information I should know about Epogen? Using Epogen can lead to death or other serious side effects. US Food and Drug Administration (FDA) This is the opening question (in bold print) and its answer in a Medication Guide produced by the FDA as part of the Risk Evaluation and Mitigation Strategy (REMS) for erythropoietic stimulating agents (ESAs). The REMS program was authorized in 2007 by the FDA to ensure that the benefits of a drug outweigh its risks. There are now 190 REMS guides approved by the FDA to promote the safe use of various drugs. In the case of ESAs, since February 2010, the FDA has required that a Medication Guide be distributed by prescribers and dispensers of epoetin alfa (Epogen or Procrit) and darbepoetin alfa (Aranesp) to every dialysis patient and patient with chronic kidney disease (CKD) upon initiation of treatment. However, many physicians remain unaware of or are perplexed by this program, raising a question of whether the goal of safe medication use is being achieved.

Fibroblast Growth Factor 23 and CKD Prognosis

Navdeep Tangri, Andrew S. Levey — 2011-12-09

Commentary on Isakova T, Xie H, Yang W, et al; for the Chronic Renal Insufficiency Cohort (CRIC) Study Group. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA. 2011;305(23):2432-2439.

Characteristics of Renal Cystic and Solid Lesions Based on Contrast-Enhanced Computed Tomography of Potential Kidney Donors

2012-03-09

Background: The presence of a few renal cysts is considered of little relevance in healthy adults, although acquired renal cystic disease occurs in advanced kidney failure. The objective of this study was to detail renal cystic and solid lesions and identify any association with clinical characteristics. Study Design: Clinical-pathologic correlation. Setting & Participants: Potential kidney donors undergoing a standardized evaluation at the Mayo Clinic in 2000-2008. Predictors: Age, kidney function, and chronic kidney disease risk factors. Measurements: Renal cystic and solid lesions by contrast-enhanced computed tomographic images. Outcomes: Cyst number, diameter, and location. Results: After excluding 8 with cystic disease, 7 of whom had autosomal dominant polycystic kidney disease, there were 1,948 potential kidney donors (42% men; mean age, 43 years). A cortical, medullary, or parapelvic cyst ≥5 mm was present in 12%, 14%, or 2.8%. For ages 19-49 years, 39%, 22%, 7.9%, and 1.6% had a cortical or medullary cyst ≥2, ≥5, ≥10, and ≥20 mm in diameter. For ages 50-75 years, 63%, 43%, 22%, and 7.8% had a cortical or medullary cyst ≥2, ≥5, ≥10, and ≥20 mm in diameter. The 97.5th percentile for number of cortical and medullary cysts ≥5 mm increased with age (10 for men and 4 for women in the 60- to 69-year group). After age and sex adjustment, cortical and medullary cysts ≥5 mm were associated with higher 24-hour urine albumin excretion, as well as increased body surface area, hypertension, and higher glomerular filtration rate in some analyses. Angiomyolipomas, hyperdense cysts, and enhancing masses or cysts with concerning features for malignancy occurred in 2.2%, 1.2%, and 0.6% and were associated with older age (P ≤ 0.05 for each). Limitations: Persons with known chronic kidney disease were excluded. Conclusions: Renal cysts are common, particularly in older men, and may be a marker of early kidney injury because they associate with albuminuria, hypertension, and hyperfiltration.

Effect of GFR on Plasma N-Terminal Connective Tissue Growth Factor (CTGF) Concentrations

2012-02-20

Background: Connective tissue growth factor (CTGF) has a key role in the pathogenesis of renal and cardiac fibrosis. Its amino-terminal fragment (N-CTGF), the predominant form of CTGF detected in plasma, has a molecular weight in the middle molecular range (18 kDa). However, it is unknown whether N-CTGF is a uremic retention solute that accumulates in chronic kidney disease (CKD) due to decreased renal clearance and whether it can be removed by hemodiafiltration. Study Design: 4 observational studies in patients and 2 pharmacokinetic studies in rodents. Setting & Participants: 4 single-center studies. First study (cross-sectional): 88 patients with CKD not receiving kidney replacement therapy. Second study (cross-sectional): 23 patients with end-stage kidney disease undergoing low-flux hemodialysis. Third study: 9 kidney transplant recipients before and 6 months after transplant. Fourth study: 11 low-flux hemodialysis patients and 12 hemodiafiltration patients before and after one dialysis session. Predictor: First, second, and third study: (residual) glomerular filtration rate (GFR). Fourth study: dialysis modality. Outcomes & Measurements: Plasma (N-)CTGF concentrations, measured by enzyme-linked immunosorbent assay. Results: In patients with CKD, we observed an independent association between plasma CTGF level and estimated GFR (β = −0.72; P < 0.001). In patients with end-stage kidney disease, plasma CTGF level correlated independently with residual kidney function (β = −0.55; P = 0.046). Successful kidney transplant resulted in a decrease in plasma CTGF level (P = 0.008) proportional to the increase in estimated GFR. Plasma CTGF was not removed by low-flux hemodialysis, whereas it was decreased by 68% by a single hemodiafiltration session (P < 0.001). Pharmacokinetic studies in nonuremic rodents confirmed that renal clearance is the major elimination route of N-CTGF. Limitations: Observational studies with limited number of patients. Fourth study: nonrandomized, evaluation of the effect of one session; randomized longitudinal study is warranted. Conclusion: Plasma (N-)CTGF is eliminated predominantly by the kidney, accumulates in CKD, and is decreased substantially by a single hemodiafiltration session.

Risk Factors for ESRD in HIV-Infected Individuals: Traditional and HIV-Related Factors

Vasantha Jotwani, Yongmei Li, Carl Grunfeld, Andy I. Choi, Michael G. Shlipak — 2011-12-30

Background: Despite improvements in survival with human immunodeficiency virus (HIV) infection, kidney disease remains an important complication. Few studies have evaluated risk factors associated with the development of end-stage renal disease (ESRD) in HIV-infected individuals. We sought to identify traditional and HIV-related risk factors for ESRD in HIV-infected individuals and compare ESRD risk by estimated glomerular filtration rate (eGFR) and proteinuria levels. Study Design: Retrospective cohort study. Setting & Participants: 22,156 HIV-infected veterans without pre-existing ESRD receiving health care in the Veterans' Affairs medical system between 1996 and 2004. Predictors: Hypertension, diabetes, cardiovascular disease, hypoalbuminemia (serum albumin <3.5 mg/dL), CD4 lymphocyte count, HIV viral load, hepatitis C virus coinfection, proteinuria, and eGFR were identified using the Veterans' Affairs electronic record system. Outcomes: ESRD was ascertained by the US Renal Data System. Results: 366 cases of ESRD occurred, corresponding to 3 cases/1,000 person-years. Hypertension (HR, 1.9; 95% CI, 1.5-2.4), diabetes (HR, 1.7; 95% CI, 1.3-2.2), and cardiovascular disease (HR, 2.2; 95% CI, 1.7-2.7) were associated independently with ESRD risk in multivariate-adjusted models, as were CD4 lymphocyte count <200 cells/μL (HR, 1.5; 95% CI, 1.2-2.0), HIV viral load ≥30,000 copies/mL (HR, 2.0; 95% CI, 1.5-2.8), hepatitis C virus coinfection (HR, 1.9; 95% CI, 1.5-2.4), and hypoalbuminemia (HR, 2.1; 95% CI, 1.8-2.5). Compared with persons without chronic kidney disease, defined as eGFR >60 mL/min/1.73 m2 and no proteinuria, lower eGFR and higher proteinuria categories were associated jointly with exponentially higher ESRD rates, ranging from 6.6 events/1,000 person-years for persons with urine protein excretion of 30-100 mg/dL and eGFR >60 mL/min/1.73 m2 to 193 events/1,000 person-years for persons with urine protein excretion ≥300 mg/dL and eGFR <30 mL/min/1.73 m2. Limitations: Results may not be generalizable to female and nonveteran populations. Conclusions: In HIV-infected persons, ESRD risk appears attributable to a combination of traditional and HIV-related risk factors for kidney disease. Combining eGFR and proteinuria for chronic kidney disease staging is most effective for stratifying the risk of ESRD.

Bisphosphonate Therapy, Death, and Cardiovascular Events Among Female Patients With CKD: A Retrospective Cohort Study

2012-01-16

Background: Accelerated vascular calcification contributes to cardiovascular disease burden in patients with chronic kidney disease (CKD). We hypothesized that bisphosphonate therapy would reduce the risk of mortality and cardiovascular events in this population. Study Design: Retrospective cohort study. Setting & Participants: Adult women with stage 3 or 4 CKD receiving primary care in a large rural integrated health care system in 2004-2010. Exposure: Time-dependent exposure status based on outpatient prescription for any medication within the bisphosphonate class, obtained from electronic health records. Outcomes: Time to death and first cardiovascular event (composite of myocardial infarction, heart failure, or stroke). Results: Data from 9,604 eligible female patients with CKD were analyzed; 3,234 were treated with bisphosphonate therapy. During a median follow-up of 3.9 (25th-75th percentile, 2.3-5.4) years, there were 286 versus 881 deaths and 206 versus 571 cardiovascular events (treated vs not-treated groups, respectively). In a multivariate Cox proportional hazard model, the adjusted HR for death (treated vs not treated) was 0.78 (95% CI, 0.67-0.91; P = 0.003). In Cox modeling adjusted for similar baseline covariates, treatment with bisphosphonates was not associated with a lower risk of the composite cardiovascular outcome (adjusted HR, 1.14; 95% CI, 0.94-1.39; P = 0.2). Limitations: Residual confounding by unidentified factors, exclusion of male patients, and lack of information about longitudinal drug adherence. Conclusions: For female patients with CKD, treatment with bisphosphonates is associated with a lower risk of death, but not cardiovascular events. Confirmatory studies and investigations of potential causal mechanisms are warranted.

Variation in Oral Calcitriol Response in Patients With Stages 3-4 CKD

2012-01-30

Background: Oral calcitriol decreases parathyroid hormone (PTH) concentrations in patients who have chronic kidney disease (CKD); however, treatment response is highly variable. We evaluated whether patient characteristics affect the PTH response to oral calcitriol in nondialysis patients with CKD in a clinic-based setting. Study Design: Cohort study. Setting & Participants: This study included 379 new oral calcitriol users in the Veterans' Affairs Northwest Health Network. All had stages 3-4 CKD, hyperparathyroidism, and a serum PTH measurement before and 1-6 months after initiating oral calcitriol therapy. Predictors: Patient-level characteristics hypothesized to affect calcitriol response: race, body size, concurrent medications, and kidney function. Outcomes: Relative decrease in serum PTH concentration after starting oral calcitriol therapy. Measurements: Data were abstracted from the Veterans' Affairs Northwest Health Network (VISN 20) Data Warehouse, which includes electronic pharmacy and laboratory records. Results: Mean estimated glomerular filtration rate was 30 mL/min/1.73 m2 and mean initial PTH concentration was 199 pg/mL. Regular- (0.25 μg/d) and low-dose (<0.25 μg/d) oral calcitriol were associated with on average 23% and 13% relative decreases in serum PTH concentrations, respectively. After adjustment for calcitriol dosage, initial PTH concentration, and time to follow-up measurement, African American race was associated with a blunted calcitriol response (geometric mean final PTH value, 26% higher; 95% CI, 8%-47%). Serum albumin concentration <3.5 g/dL also was associated with a diminished calcitriol response (geometric mean final PTH, 19% higher; 95% CI, 6%-35%). Although numbers were small, concurrent use of benzodiazepines and nonactivated vitamin D supplements was associated with a significantly greater PTH response. Limitations: Clinic-based study is limited by the availability of PTH measurements after starting calcitriol therapy. Study of a predominantly older male population. Conclusions: In patients with stages 3-4 CKD, African American race and low serum albumin level are associated with a diminished PTH response to oral calcitriol.

Novel Markers of Kidney Function as Predictors of ESRD, Cardiovascular Disease, and Mortality in the General Population

2012-02-10

Background: Cystatin C level predicts mortality more strongly than serum creatinine level. It is unknown whether this advantage extends to other outcomes, such as kidney failure, or whether other novel renal filtration markers share this advantage in predicting outcomes. Study Design: Observational cohort study. Setting & Participants: 9,988 participants in the Atherosclerosis Risk in Communities (ARIC) Study, a population-based study in 4 US communities, followed for approximately 10 years. Predictors: Serum creatinine–based estimated glomerular filtration rate calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (eGFRCKD-EPI) and cystatin C, β-trace protein (BTP), and β2-microglobulin (B2M) levels. Outcomes: Mortality, coronary heart disease, heart failure, and kidney failure. Results: Higher cystatin C and B2M concentrations were associated more strongly with mortality (n = 1,425) than BTP level and all were associated more strongly than eGFRCKD-EPI (adjusted HR for the upper 6.7 percentile compared with the lowest quintile: 1.6 [95% CI, 1.3-1.9] for eGFRCKD-EPI, 2.9 [95% CI, 2.3-3.6] for cystatin C level, 1.9 [95% CI, 1.5-2.4] for BTP level, and 3.0 [95% CI, 2.4-3.8] for B2M level). Similar patterns were observed for coronary heart disease (n = 1,279), heart failure (n = 803), and kidney failure (n = 130). The addition of cystatin C, BTP, and B2M levels to models including eGFRCKD-EPI and all covariates, including urinary albumin-creatinine ratio, significantly improved risk prediction for all outcomes (P < 0.001). Limitations: No direct measurement of GFR. Conclusions: B2M and, to a lesser extent, BTP levels share cystatin C's advantage over eGFRCKD-EPI in predicting outcomes, including kidney failure. These additional markers may be helpful in improving estimation of risk associated with decreased kidney function beyond current estimates based on eGFRCKD-EPI.

Addition of Plasma Exchange to Glucocorticosteroids for the Treatment of Severe Henoch-Schönlein Purpura in Adults: A Case Series

2012-02-10

Background: Adult Henoch-Schönlein purpura (HSP) has been associated with poor outcome and end-stage renal disease in >20% of cases. Although the benefit of adding another immunosuppressant to steroids in severe adult HSP has not been shown, the benefit of plasma exchange (PE) therapy has been poorly evaluated. Study Design: Case series. Setting & Participants: 11 consecutive patients with severe and newly diagnosed HSP since 1988 who were treated with steroids and PE. Outcome & Measurement: Patients' characteristics and outcome were analyzed. Birmingham Vasculitis Activity Score (BVAS), estimated glomerular filtration rate (eGFR), and proteinuria were measured at baseline, at the end of PE treatment, at months 6 and 12, and at the last visit. Side effects of corticoid treatment and PE were recorded. Results: 11 patients were identified in 1988-2010. Patients received intravenous corticoid pulses in 64% of cases, followed by oral prednisone for a median of 6.6 months. They received a median of 12 PE sessions. BVAS, eGFR, and proteinuria improved significantly between baseline and the last PE at a median of 2 months. PE sessions were well tolerated, except in one patient who developed central catheter–associated septicemia. One patient required dialysis therapy 15 days after HSP diagnosis and did not recover kidney function. At the last medical evaluation at a mean follow-up of 6 years, median eGFR and proteinuria were 83 ± 22 mL/min/1.73 m2 and protein excretion of 140 ± 10 mg/d, respectively. 3 women had pregnancy without complications. Limitations: This case series did not have a control group. Conclusions: The combination of PE and corticoid therapy in severe forms of HSP was associated with fast improvement and good long-term outcome.

Utilization and Costs of Cardiovascular Disease Medications in Dialysis Patients in Medicare Part D

2011-12-30

Background: Cardiovascular disease (CVD) is a major source of mortality and morbidity in dialysis patients. Population-level descriptions of CVD medication use are lacking in this population. Study Design: Retrospective cohort study. Setting & Participants: Adult dialysis patients in the United States, alive on December 31, 2006, with Medicare Parts A and B and enrollment in Medicare Part D continuously in 2007. Predictor: CVDs and demographic characteristics. Outcome: ≥1 prescription fill during follow-up (2007). Measurements: Average out-of-pocket costs per user per month and average total drug costs per member per month were calculated. Results: Of 225,635 dialysis patients who met inclusion criteria during the entry period, 70% (n = 158,702) had continuous Part D coverage during follow-up. Of these, 76% received the low-income subsidy. β-Blockers were the most commonly used CVD medication (64%), followed by renin-angiotensin system inhibitors (52%), calcium channel blockers (51%), lipid-lowering agents (44%), and α-agonists (23%). Use varied by demographics, geographic region, and low-income subsidy status. For CVD medications, mean out-of-pocket costs per user per month were $3.44 and $49.59 and mean total costs per member per month were $124.02 and $110.32 for patients with and without the low-income subsidy, respectively. Limitations: Information was available for only filled prescriptions under the Part D benefit; information for clinical contraindications was lacking, information for over-the-counter medications was unavailable, and medication adherence and persistence were not examined. Conclusions: Most Medicare dialysis patients in 2007 were enrolled in Part D, and most enrollees received the low-income subsidy. β-Blockers were the most used CVD medication. Total costs of CVD medications were modestly higher for low-income subsidy patients, but out-of-pocket costs were much higher for patients not receiving the subsidy. Further study is warranted to delineate sources of variation in the use and costs of CVD medications across subgroups.

Association of Factor V Gene Polymorphism With Arteriovenous Graft Failure

2012-01-27

Background: Dialysis grafts fail due to recurrent stenosis and thrombosis. Vasoactive and prothrombotic substances affecting intimal hyperplasia or thrombosis may modify graft outcomes. Study Design: Genetic polymorphisms association study of patients enrolled in a multicenter randomized clinical trial. Setting & Participants: 354 Dialysis Access Consortium (DAC) Study patients receiving a new graft with DNA samples obtained. Participants were randomly assigned to treatment with aspirin plus dipyridamole versus placebo. Predictor: DNA sequence polymorphisms for the following candidate genes and their interaction with the study intervention: methylenetetrahydrofolate reductase (MTHFR), heme oxygenase 1 (HO-1), factor V (F5), transforming growth factor β1 (TGFβ1), klotho, nitric oxide synthase (NOS), and angiotensin-converting enzyme (ACE). Outcome: Graft failure (>50% stenosis, angioplasty, thrombosis, surgical intervention, or permanent loss of function). Results: During a median patient follow-up of 34.3 months, 304 grafts failed. After adjusting for clinical factors (patient age, sex, access location, diabetes, cardiovascular disease, baseline aspirin use, body mass index, timing of graft placement, and study treatment) and genetic ancestral background, single-nucleotide polymorphism rs6019 of the factor V gene was associated significantly with graft failure in a dominant model (HR of 1.70 [95% CI, 1.32-2.19; P < 0.001] for G/C and G/G genotypes vs C/C genotypes). There was no significant association between graft failure and polymorphisms of MTHFR, HO-1, TGFβ1, klotho, NOS, or ACE. Limitations: Small sample size. Conclusion: The rs6019 genotype of Factor V is associated with increased risk of graft failure. Anticoagulation may reduce graft failure in patients with the G/C or G/G genotypes.

Effect of Frequent or Extended Hemodialysis on Cardiovascular Parameters: A Meta-analysis

2012-02-27

Background: Increased left ventricular (LV) mass is a risk factor for cardiovascular mortality in patients with chronic kidney failure. More frequent or extended hemodialysis (HD) has been hypothesized to have a beneficial effect on LV mass. Study Design: Meta-analysis. Setting & Population: MEDLINE literature search (inception to April 2011), Cochrane Central Register of Controlled Trials and ClinicalTrials.gov using the search terms “short daily HD,” “daily HD,” “quotidian HD,” “frequent HD,” “intensive HD,” “nocturnal HD,” and “home HD.” Selection Criteria for Studies: Single-arm cohort studies (with pre- and post-study evaluations) and trials examining the effect of frequent or extended HD on cardiac morphology and function and blood pressure parameters. Studies of hemofiltration, hemodiafiltration, and peritoneal dialysis were excluded. Intervention: Frequent (2-8 hours, >3 times weekly) or extended (>4 hours, 3 times weekly) HD compared with conventional (≤4 hours, 3 times weekly) HD. Outcomes: Absolute changes in cardiac morphology and function, including LV mass index (LVMI; primary) and blood pressure parameters (secondary). Results: We identified 38 single-arm studies, 5 crossover trials, and 3 randomized controlled trials. By meta-analysis of 23 study arms, frequent or extended HD significantly reduced LVMI from baseline (−31.2 g/m2, 95% CI, −39.8 to −22.5; P < 0.001). The 3 randomized trials found a less pronounced net reduction in LVMI (−7.0 g/m2; 95% CI, −10.2 to −3.7; P < 0.001). LV ejection fraction improved by 6.7% (95% CI, 1.6% to 11.9%; P = 0.01). Other cardiac morphologic parameters showed similar improvements. There also were significant decreases in systolic, diastolic, and mean blood pressure and mean number of antihypertensive medications. Limitations: Paucity of randomized controlled trials. Conclusions: Conversion from conventional to frequent or extended HD is associated with improvements in cardiac morphology and function, including LVMI and LV ejection fraction, respectively, and several blood pressure parameters, which collectively might confer long-term cardiovascular benefit. Trials with long-term clinical outcomes are needed.

Employment of Patients Receiving Maintenance Dialysis and After Kidney Transplant: A Cross-sectional Study From Finland

2011-09-29

Background: Associations between mode of renal replacement therapy and employment rate have not been well characterized. Study Design: Cross-sectional registry analysis. Setting & Participants: The employment status of all prevalent 15- to 64-year-old dialysis and kidney transplant patients in Finland at the end of 2007 (N = 2,637) was analyzed by combining data from the Finnish Registry for Kidney Diseases with individual-level employment statistics of the Finnish government. Predictor: Prevalence rate ratios (PRRs) of employment according to treatment modality with adjustment for age, sex, cause of end-stage renal disease (ESRD), duration of ESRD, and comorbid conditions were estimated using Cox regression with a constant time at risk. Outcome: Employment status of patients on dialysis therapy or after transplant. Measurements: Clinical data were collected from the Finnish Registry for Kidney Diseases, and employment data were acquired from Statistics Finland. Results: 19% of hemodialysis patients, 31% of peritoneal dialysis patients, and 40% of patients with a functioning transplant were employed; the overall employment rate for the Finnish population aged 15-64 years is 67%. Home hemodialysis patients and those treated with automated peritoneal dialysis had employment rates of 39% and 44%, respectively. In adjusted analysis, patients on home hemodialysis therapy (PRR, 1.87), on automated peritoneal dialysis therapy (PRR, 2.14), or with a kidney transplant (PRR, 2.30) had higher probabilities of employment than in-center hemodialysis patients. Patients with type 1 or 2 diabetes as the cause of ESRD had the lowest probability of employment (PRR, 0.48-0.60 compared with glomerulonephritis). Patients aged 25-54 years more frequently were employed than those younger than 25 or older than 54 years. Sex did not predict employment. For transplant recipients, longer time since transplant was associated with higher employment in addition to the mentioned factors. Limitations: Cross-sectional design. Conclusions: Employment rate of home dialysis patients was similar to that of transplant recipients and higher than that of in-center hemodialysis patients. Patients with diabetes were less likely to be employed.

Eculizumab in the Treatment of Atypical Hemolytic Uremic Syndrome in Infants

2011-12-26

A 28-day-old male newborn weighing 3.6 kg was given a diagnosis of atypical hemolytic-uremic syndrome, new-onset thrombotic microangiopathy (TMA; hemoglobin, 7.7 g/dL; schistocytes, 9%), thrombocytopenia (platelets, 49 × 103/μL [49 × 109/L]), and acute kidney failure (serum creatinine, 1.13 mg/dL [99.8 μmol/L], corresponding to estimated glomerular filtration rate [eGFR] of 15 mL/min/1.73 m2 [0.25 mL/s/1.73 m2]). Repeated high-volume plasma infusions were ineffective. Plasma exchange was attempted, but not tolerated. The patient required mechanical ventilation and continuous renal replacement therapy. He developed multiple intestinal perforations and leg skin necrosis due to systemic TMA. A low C3 level (36 mg/dL) suggested complement activation. Eculizumab, 300 mg, was administered, and within 48 hours the patient recovered from acute kidney failure, with complete hematologic remission 2 weeks later. The infant, 14 months old at the time of writing, continues to receive eculizumab, 300 mg, every 3 weeks; he is free of disease activity and has a normal creatinine level of 0.2 mg/dL (17.68 μmol/L; corresponding to eGFR of 110 mL/min/1.73 m2 [1.83 mL/s/1.73 m2]), but mild proteinuria (urinary protein-creatine ratio, 1 mg/g). Results of additional studies, including probing for cobalamin anomalies and measuring levels of ADAMTS13, complement factor H (CFH), factor I (CFI), and membrane cofactor protein (MCP), were unremarkable. Antibodies to CFH were undetectable, and mutation testing of the genes for CFH, CFI, and MCP gave negative results. Treatment with eculizumab was life saving, and with continued treatment, the patient showed sustained freedom from clinical TMA complications.

Acute Interstitial Nephritis With Predominant Plasmacytic Infiltration in Patients With HIV-1 Infection

2012-02-20

We describe a new form of acute interstitial nephritis with predominant plasmacytic infiltration in 2 patients with active human immunodeficiency virus 1 (HIV-1) infection. Clinical features included acute kidney injury and proteinuria, but no sicca syndrome. Acute kidney injury was characterized by a high serum creatinine level and nephrotic syndrome with no hematuria or leukocyturia. Kidney biopsy specimens from both patients showed interstitial infiltration by mononuclear cells composed mainly of CD138+ plasmacytes and diffuse effacement of podocyte foot processes with no deposits. In one patient with Guillain-Barré syndrome, a sural nerve biopsy showed plasmacyte infiltration and immunohistochemistry was strongly positive for HIV-1 p24 protein. In both patients, minor salivary glands and bone marrow were infiltrated by lymphocytes, consistent with B-cell activation induced by HIV-1 infection. Other common causes of acute interstitial nephritis, including B-cell lymphoma and diffuse infiltrative lymphocytosis syndrome, were actively looked for and excluded. Treatment with highly active antiretroviral therapy was effective; symptoms rapidly improved, serum creatinine level decreased, and proteinuria resolved. Exclusion of other common known causes of acute interstitial nephritis and the dramatic response with highly active antiretroviral therapy suggests HIV-1 as a likely cause. The acute interstitial nephritis probably was induced by HIV-1–driven nonspecific B-cell activation. Further investigations are needed to confirm the direct pathogenic role of HIV-1.

Hemodynamic Monitoring in the Critically Ill: Spanning the Range of Kidney Function

Danielle L. Davison, Kanak Patel, Lakhmir S. Chawla — 2012-03-05

Critically ill patients often have deranged hemodynamics. Physical examination, central venous pressure, and pulmonary artery occlusion pressure (“wedge”) have been shown to be unreliable at assessing volume status, volume responsiveness, and adequacy of cardiac output in critically ill patients. Thus, invasive and noninvasive cardiac output monitoring is a core feature of evaluating and managing a hemodynamically unstable patient. In this review, we discuss the various techniques and options of cardiac output assessment available to clinicians for hemodynamic monitoring in the intensive care unit. Issues related to patients with kidney disease, such as timing and location of arterial and central venous catheters and the approach to hemodynamics in patients treated by long-term dialysis also are discussed.

Accountable Care Organizations and ESRD: The Time Has Come

2012-03-29

Accountable care organizations (ACOs) are a newly proposed vehicle for improving or maintaining high-quality patient care while controlling costs. They are meant to achieve the goals of the Medicare Shared Savings Program mandated by the Patient Protection and Affordable Care Act (PPACA) of 2010. ACOs are voluntary groups of hospitals, physicians, and health care teams that provide care for a defined group of Medicare beneficiaries and assume responsibility for providing high-quality care through defined quality measures at a cost below what would have been expected. If an ACO succeeds in achieving both the quality measures and reduced costs, the ACO will share in Medicare's cost savings. Health care for patients with end-stage renal disease is complex due to multiple patient comorbid conditions, expensive, and often poorly coordinated. Due to the unique needs of patients with end-stage renal disease receiving dialysis, ACOs may be unable to provide the highly specialized quality care these patients require. We discuss the benefits and risks of a renal-focused ACO for dialysis patients, as well as the kidney community's prior experience with an ACO-like demonstration project.

An Unusual Case of Nephrotic Syndrome and Glucosuria

Sophie Kwok, Vivette D'Agati, Kisra Anis, Belinda Jim — 2012-02-16

We report a case of a 57-year-old man with hypertension and smoking history who presented with decreased glomerular filtration rate, nephrotic-range proteinuria, and persistent glucosuria. He underwent a kidney biopsy that showed nodular glomerulosclerosis. We discuss the clinicopathologic entities of idiopathic nodular glomerulosclerosis and primary renal glucosuria.

Oral Vitamin D Effects on PTH Levels

Paul G. Jenkins, Debesh C. Mazumdar — 2012-05-01

Kovesdy et al compared the effect of paricalcitol and ergocalciferol on parathyroid hormone (PTH) levels in 80 patients with chronic kidney disease (CKD) stage 3 or 4 and found that PTH levels decreased only in patients receiving paricalcitol. However, mean 25-hydroxyvitamin D level increased to just 29 ng/mL in the ergocalciferol group. Conversely, we observed a decrease in PTH levels in 13 of 26 patients with CKD stages 2-5 treated with ergocalciferol, 50,000 units, 1-2 times per week for 6-23 months. Mean 25-hydroxyvitamin D level in the 13 responders increased from 15 to 82.5 ng/mL, with mean serum PTH level decreasing 46%, from 392 to 213 pg/mL. In the 13 nonresponders, mean PTH level increased from 239 to 396 pg/mL, with 25-hydroxyvitamin D level increasing from 16 to 56 ng/mL.

In Reply to ‘Oral Vitamin D Effects on PTH Levels’

Csaba P. Kovesdy — 2012-05-01

Jenkins and Mazumdar report their personal experience with using high-dose vitamin D supplementation to treat secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) stages 2-5. In contrast with the results of our study, in which administration of ergocalciferol according to the Kidney Disease Outcomes Quality Initiative (KDOQI) regimen had no significant effect on parathyroid hormone (PTH) levels, they report a significant reduction proportional to the achieved serum 25-hydroxyvitamin D levels. We noted in the Discussion section of our report that the possible reason for nonresponse in patients randomly assigned to ergocalciferol in our study was a suboptimal response to the treatment regimen that was being advocated based on expert opinion at the time we conceived our study. Additional evidence has accumulated in the meantime suggesting that the opinion-based KDOQI regimen of vitamin D supplementation in CKD is ineffective when applied toward treatment of SHPT. Unfortunately, it is unclear what alternative regimen one should apply to this patient population. Reports such as the one by Jenkins and Mazumdar are useful to point out the potential benefit of high-dose vitamin D, but offer insufficient evidence regarding several key elements without which their application to the wider CKD population cannot be implemented. Knowledge of patients' baseline clinical characteristics, their indications and contraindications to vitamin D therapy, variables associated with response and nonresponse to therapy, the impact on relevant non-PTH end points such as alkaline phosphatase level, and the incidence of adverse events in response to therapy are just a few that need to be analyzed before deriving conclusions about the efficacy and safety of such regimens. Furthermore, neither the report by Jenkins and Mazumdar nor the other studies that have examined the effects of vitamin D supplementation in CKD can offer insight into the comparative effectiveness of high-dose vitamin D (ergocalciferol or cholecalciferol) versus active vitamin D in this patient population, which is paramount in light of the potential mortality benefits associated with the latter.

A Large Dialysis Provider Committed to Home Modalities

Allen R. Nissenson, John Moran — 2012-05-01

We are grateful for the article by Golper et al regarding the barriers to home dialysis in the United States. As representatives of a large dialysis provider, we are committed to identifying and overcoming all barriers to home therapy and would respectfully differ with some of the authors' statements.

In Reply to ‘A Large Dialysis Provider Committed to Home Modalities’

Thomas A. Golper, Anjali B. Saxena, Beth Piraino — 2012-05-01

We thank Drs Nissenson and Moran for their interest. With respect to modality awareness, the majority of patients starting dialysis therapy in the United States do not receive adequate modality education. The first citation in our article should have been to Wave 2 of the US Renal Data System Dialysis Morbidity and Mortality Study. Mehrotra et al found that 66%, 84%, and 74% of patients in Network 18 were not offered peritoneal dialysis, home hemodialysis, and transplant, respectively, data supported further by Finkelstein et al. We applaud the fact that some dialysis providers support pre–end-stage renal disease education and wish that this would become more widespread. Data from Fresenius' treatment options program strongly support our point that patients do not chose a modality they know nothing about, and the vast majority of patients do not receive the necessary education.

Cefepime for Gram-Negative Bacteremia in Long-term Hemodialysis: A Single-Center Experience

2012-03-22

Catheter-related bloodstream infections have dramatically increased in 1993-2006 in patients receiving long-term hemodialysis. Gram-negative organisms cause a significant portion (21%-30%) of these infections. Intravenous (IV) cefepime, a broad-spectrum cephalosporin efficacious for Gram-negative bacteremia, currently is dosed at 1 g daily in long-term hemodialysis patients. Pharmacokinetic data suggest that administering cefepime at 2 g thrice weekly exclusively after hemodialysis sessions maintains serum concentrations above the minimum inhibitory concentration for susceptible Gram-negative organisms (8 μg/mL, per the Clinical and Laboratory Standards Institute) during the entire dosing interval. We report our clinical experience with this novel regimen.

Erratum Regarding “Phosphate Removal With Several Thrice-Weekly Dialysis Methods in Overweight Hemodialysis Patients” [Am J Kidney Dis 2009; 54:1108-1115]

2012-05-01

The article entitled “Phosphate Removal With Several Thrice-Weekly Dialysis Methods in Overweight Hemodialysis Patients” (Tonelli et al, American Journal of Kidney Diseases 2009;54(6):1108-1115) underreported the calculated dialyzer phosphorus clearance due to an error in the adjustment of the average intradialysis serum phosphorus level to plasma water concentration.

American Journal of Kidney Diseases

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This Month in AJKD

Quiz Page May 2012: Severe Hypocalcemia in a Hemodialysis Patient

Solitary Renal Cysts: Worth a Second Look?

Condition-Specific Disease Treatment in Dialysis Patients: Utilization, Costs, and Guideline and Policy Imperatives

Dialysis and Kidney Transplantation: Why Have Our Rehabilitation Hopes Not Been Achieved Fully?

Delivering Accountable Care to Patients With Complicated Chronic Illness: How Does It Fit Into Care Models and Do Nephrologists Have a Role?

The US Food and Drug Administration's Risk Evaluation and Mitigation Strategy (REMS) Program in Practice: Does It Really Inform Patients and Limit Risk?

Fibroblast Growth Factor 23 and CKD Prognosis

Characteristics of Renal Cystic and Solid Lesions Based on Contrast-Enhanced Computed Tomography of Potential Kidney Donors

Effect of GFR on Plasma N-Terminal Connective Tissue Growth Factor (CTGF) Concentrations

Risk Factors for ESRD in HIV-Infected Individuals: Traditional and HIV-Related Factors

Bisphosphonate Therapy, Death, and Cardiovascular Events Among Female Patients With CKD: A Retrospective Cohort Study

Variation in Oral Calcitriol Response in Patients With Stages 3-4 CKD

Novel Markers of Kidney Function as Predictors of ESRD, Cardiovascular Disease, and Mortality in the General Population

Addition of Plasma Exchange to Glucocorticosteroids for the Treatment of Severe Henoch-Schönlein Purpura in Adults: A Case Series

Utilization and Costs of Cardiovascular Disease Medications in Dialysis Patients in Medicare Part D

Association of Factor V Gene Polymorphism With Arteriovenous Graft Failure

Effect of Frequent or Extended Hemodialysis on Cardiovascular Parameters: A Meta-analysis

Employment of Patients Receiving Maintenance Dialysis and After Kidney Transplant: A Cross-sectional Study From Finland

Eculizumab in the Treatment of Atypical Hemolytic Uremic Syndrome in Infants

Acute Interstitial Nephritis With Predominant Plasmacytic Infiltration in Patients With HIV-1 Infection

Hemodynamic Monitoring in the Critically Ill: Spanning the Range of Kidney Function

Accountable Care Organizations and ESRD: The Time Has Come

An Unusual Case of Nephrotic Syndrome and Glucosuria

Oral Vitamin D Effects on PTH Levels

In Reply to ‘Oral Vitamin D Effects on PTH Levels’

A Large Dialysis Provider Committed to Home Modalities

In Reply to ‘A Large Dialysis Provider Committed to Home Modalities’

Cefepime for Gram-Negative Bacteremia in Long-term Hemodialysis: A Single-Center Experience

Erratum Regarding “Phosphate Removal With Several Thrice-Weekly Dialysis Methods in Overweight Hemodialysis Patients” [Am J Kidney Dis 2009; 54:1108-1115]