American Journal of Kidney Diseases - Articles in Press

Early Urinary Markers of Diabetic Kidney Disease: A Nested Case-Control Study From the Diabetes Control and Complications Trial (DCCT) - Corrected Proof

Elizabeth F.O. Kern, Penny Erhard, Wanjie Sun, Saul Genuth, Miriam F. Weiss — 2010-02-08

Background: Urinary markers were tested as predictors of macroalbuminuria or microalbuminuria in patients with type 1 diabetes.Study Design: Nested case-control of participants in the Diabetes Control and Complications Trial (DCCT).Setting & Participants: 87 cases of microalbuminuria were matched to 174 controls in a 1:2 ratio, while 4 cases were matched to 4 controls in a 1:1 ratio, resulting in 91 cases and 178 controls for microalbuminuria. 55 cases of macroalbuminuria were matched to 110 controls in a 1:2 ratio. Controls were free of micro-/macroalbuminuria when their matching case first developed micro-/macroalbuminuria.Predictors: Urinary N-acetyl-β-d-glucosaminidase (NAG), pentosidine, advanced glycation end product (AGE) fluorescence, and albumin excretion rate (AER).Outcomes: Incident microalbuminuria (2 consecutive annual AERs > 40 but ≤ 300 mg/d) or macroalbuminuria (AER > 300 mg/d).Measurements: Stored urine samples from DCCT entry and 1-9 years later when macro- or microalbuminuria occurred were measured for the lysosomal enzyme NAG and the AGE pentosidine and AGE fluorescence. AER and adjustor variables were obtained from the DCCT.Results: Submicroalbuminuric AER levels at baseline independently predicted microalbuminuria (adjusted OR, 1.83; P < 0.001) and macroalbuminuria (adjusted OR, 1.82; P < 0.001). Baseline NAG excretion independently predicted macroalbuminuria (adjusted OR, 2.26; P < 0.001) and microalbuminuria (adjusted OR, 1.86; P < 0.001). Baseline pentosidine excretion predicted macroalbuminuria (adjusted OR, 6.89; P = 0.002). Baseline AGE fluorescence predicted microalbuminuria (adjusted OR, 1.68; P = 0.02). However, adjusted for NAG excretion, pentosidine excretion and AGE fluorescence lost the predictive association with macroalbuminuria and microalbuminuria, respectively.Limitations: Use of angiotensin-converting enzyme inhibitors was not directly ascertained, although their use was proscribed during the DCCT.Conclusions: Early in type 1 diabetes, repeated measurements of AER and urinary NAG excretion may identify individuals susceptible to future diabetic nephropathy. Combining the 2 markers may yield a better predictive model than either one alone. Renal tubule stress may be more severe, reflecting abnormal renal tubule processing of AGE-modified proteins, in individuals susceptible to diabetic nephropathy.

Dialysis Research and N-of-1 Trials: Made for Each Other? - Corrected Proof

Deborah R. Zucker, Aneet Deo, Christopher H. Schmid — 2010-02-08

The American Journal of Kidney Diseases Acid-Base and Electrolyte Teaching Case from Saito et al, which appeared in a recent issue of the journal, presents a teaching opportunity about research designs and in particular the use of single-subject (N-of-1 or N=1) trials. Saito et al observed instability in a patient with congenital methylmalonic acidemia during hemodialysis (HD) using an acetate-containing dialysate. Based on biochemistry, they assumed that this response likely was caused by the acetate. They tested an acetate-free citrate HD dialysate in the same patient and did not find this response. Their study looked to more rigorously compare the effectiveness of these 2 buffers and also to verify the connection between the observed adverse reactions (hypotension) and the acetate-based dialysate in this individual.

Comparison of the Prevalence and Mortality Risk of CKD in Australia Using the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) Study GFR Estimating Equations: The AusDiab (Australian Diabetes, Obesity and Lifestyle) Study - Corrected Proof

Sarah L. White, Kevan R. Polkinghorne, Robert C. Atkins, Steven J. Chadban — 2010-02-08

Background: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) is more accurate than the Modification of Diet in Renal Disease (MDRD) Study equation. We applied both equations in a cohort representative of the Australian adult population.Study Design: Population-based cohort study.Setting & Participants: 11,247 randomly selected noninstitutionalized Australians aged ≥ 25 years who attended a physical examination during the baseline AusDiab (Australian Diabetes, Obesity and Lifestyle) Study survey.Predictors & Outcomes: Glomerular filtration rate (GFR) was estimated using the MDRD Study and CKD-EPI equations. Kidney damage was defined as urine albumin-creatinine ratio ≥ 2.5 mg/mmol in men and ≥ 3.5 mg/mmol in women or urine protein-creatinine ratio ≥ 0.20 mg/mg. Chronic kidney disease (CKD) was defined as estimated GFR (eGFR) ≥ 60 mL/min/1.73 m2 or kidney damage. Participants were classified into 3 mutually exclusive subgroups: CKD according to both equations; CKD according to the MDRD Study equation, but no CKD according to the CKD-EPI equation; and no CKD according to both equations. All-cause mortality was examined in subgroups with and without CKD.Measurements: Serum creatinine and urinary albumin, protein, and creatinine measured on a random spot morning urine sample.Results: 266 participants identified as having CKD according to the MDRD Study equation were reclassified to no CKD according to the CKD-EPI equation (estimated prevalence, 1.9%; 95% CI, 1.4-2.6). All had an eGFR ≥ 45 mL/min/1.73 m2 using the MDRD Study equation. Reclassified individuals were predominantly women with a favorable cardiovascular risk profile. The proportion of reclassified individuals with a Framingham-predicted 10-year cardiovascular risk ≥ 30% was 7.2% compared with 7.9% of the group with no CKD according to both equations and 45.3% of individuals retained in stage 3a using both equations. There was no evidence of increased all-cause mortality in the reclassified group (age- and sex-adjusted hazard ratio vs no CKD, 1.01; 95% CI, 0.62-1.97). Using the MDRD Study equation, the prevalence of CKD in the Australian population aged ≥ 25 years was 13.4% (95% CI, 11.1-16.1). Using the CKD-EPI equation, the prevalence was 11.5% (95% CI, 9.42-14.1).Limitations: Single measurements of serum creatinine and urinary markers.Conclusions: The lower estimated prevalence of CKD using the CKD-EPI equation is caused by reclassification of low-risk individuals. Am J Kidney Dis 00:00-00

Light Microscopic Features of Membranous Nephropathy With Unusual Changes of the Podocytes and Glomerular Basement Membrane in a Patient With Sudden Onset of Nephrotic Syndrome - Corrected Proof

Yoshikuni Nagayama, Hiroyuki Morita, Eri Kawashima, Ashio Yoshimura — 2010-02-08

Membranous nephropathy (MN) is a pathologic entity characterized by a spectrum of changes in the glomerular basement membrane (GBM). Diagnostic features include subepithelial immune deposits and thickening of the GBM. In 1968, Ehrenreich and Churg proposed a morphologic classification of MN using electron microscopic findings. This classification was based on immune deposits in the GBM, GBM reaction to the deposits, and resolution of glomerular injury with resorption of the deposits. However, some biopsy specimens with features of MN also show spherical microparticles and podocyte microvillous entrapment in thickened GBM on electron microscopy. The presence of such features has been the source of considerable confusion. In this report, we describe an adult patient with the membranous pattern of injury using light microscopy and atypical electron microscopy findings. It is likely that this represents a distinct pathologic entity unrelated to classic membranous nephropathy.

Reappraisal of the Impact of Race on Survival in Patients on Dialysis - Corrected Proof

Vardaman M. Buckalew, Barry I. Freedman — 2010-02-08

Racial differences in the cause, natural history, and effects of chronic kidney disease have long been the subject of investigation. Dialysis-dependent kidney failure occurs nearly 4 times more often in African Americans than European Americans. Despite this observation, studies repeatedly show that African Americans have a significant survival advantage after initiating dialysis therapy. Although this phenomenon has been attributed to environmental and socioeconomic factors, recent studies show that inherited factors strongly influence racial differences in the development of diverse kidney diseases and may affect the risk of nephropathy-associated cardiovascular disease. We review relevant studies and propose the hypothesis that inherited factors leading to organ-limited kidney diseases and a lower burden of systemic atherosclerosis contribute in part to the improved survival rates in African American patients on dialysis therapy.

Potential New Therapeutic Agents for Diabetic Kidney Disease - Corrected Proof

Faruk Turgut, Warren Kline Bolton — 2010-02-08

Diabetic nephropathy is the leading cause of end-stage renal disease, and both the incidence and prevalence of diabetic nephropathy continue to increase. Currently, various treatment regimens and combinations of therapies provide only partial renoprotection. It is obvious that new approaches are desperately needed to retard the progression of diabetic nephropathy. Recently, a number of new agents have been described that have the potential to delay the progression of diabetic kidney disease and minimize the growing burden of end-stage renal disease. These include inhibitors and breakers of advanced glycation end products, receptor antagonists for advanced glycation end products, protein kinase C inhibitors, NADPH (reduced nicotinamide adenine dinucleotide phosphate) oxidase inhibitors, glycosaminoglycans, endothelin receptor antagonists, antifibrotic agents, and growth factor inhibitors. This review addresses these promising new therapeutic agents for delaying the progression of diabetic kidney disease.

Systematic Review and Meta-analysis of Exercise Tolerance and Physical Functioning in Dialysis Patients Treated With Erythropoiesis-Stimulating Agents - Corrected Proof

2010-02-04

Background: The role of erythropoiesis-stimulating agents (ESAs) in treating the anemia of chronic kidney disease has been reevaluated in view of recent studies suggesting that the use of these agents may be associated with increased morbidity and mortality. This potential increased risk needs to be weighed against the potential benefit of ESAs in improving various aspects of health-related quality of life, in particular, exercise tolerance and physical functioning.Study Design: A systematic review and meta-analysis of exercise tolerance and physical functioning.Setting & Participants: Adults on maintenance dialysis therapy.Selection Criteria for Studies: Outcomes measured before and after ESA treatment were required. Studies of physical function were required to include at least 25 participants.Intervention: Treatment with any ESA.Outcomes: Exercise tolerance measured using VO2peak (oxygen consumption per minute at the peak workload during the test), duration of exercise, or 6-minute walk distance or physical functioning assessed using ≥ 1 patient- or clinician-reported outcome measure that included a physical function domain.Results: 28 articles met criteria for inclusion for evaluation of exercise tolerance, and 14 articles, for physical function. Meta-analysis showed a 23.8% increase in VO2peak from before to after erythropoietin therapy initiation (15 studies) and a nonsignificant 8.2% increase comparing a higher with a lower hemoglobin target (3 studies). For physical functioning, 4 studies met criteria for inclusion in the meta-analysis: there was a 10.5% increase in Karnofsky score from before to after erythropoietin therapy initiation.Limitations: Many studies of exercise tolerance did not include control groups. A wide variety of instruments was used to assess physical function.Conclusions: Partial correction of anemia through ESA treatment has a consistent and positive impact on VO2peak. ESA treatment improves patient- and clinician-assessed physical functioning.

Risks of Kidney Failure Associated With Consumption of Herbal Products Containing Mu Tong or Fangchi: A Population-Based Case-Control Study - Corrected Proof

2010-02-01

Background: Taiwan has a remarkably high incidence of end-stage renal disease (ESRD). The objective of this study is to determine the association between prescribed herbal products containing aristolochic acid and ESRD.Study Design: Population-based case-control study.Setting & Participants: All new ESRD cases in Taiwan and a simple random sample (200,000 people) drawn from the national health insurance reimbursement database in 1997-2002.Predictor: Age; sex; hypertension; diabetes; cumulative doses of nonsteroidal anti-inflammatory drugs, acetaminophen, and adulterated herbal supplements potentially containing aristolochic acid before the development of chronic kidney disease; and indications for prescribing such herbs, including chronic hepatitis, chronic urinary tract infection, chronic neuralgia, or chronic musculoskeletal diseases.Outcomes & Measurements: Occurrence of ESRD through construction of multiple logistic regression models.Results: There were 36,620 new ESRD cases from 1998 through 2002. After exclusion of cases with chronic kidney disease diagnosed before July 1, 1997, there were 25,843 new cases of ESRD and 184,851 controls in the final analysis. Women, older age, hypertension, and diabetes were significantly associated with increased risks of the development of ESRD. After adjustment for known risk factors, cumulative doses >60 g of Mu Tong (OR, 1.47 [95% CI, 1.01-2.14] for 61-100 g; OR, 5.82 [95% CI, 3.89-8.71] for >200 g) or Fangchi (OR, 1.60 [95% CI, 1.20-2.14] for 61-100 g; OR, 1.94 [95% CI, 1.29-2.92] for >200 g) were associated with increased risk of the development of ESRD with a dose-response relationship. This relationship persisted when analyses were limited to participants who consumed <500 pills of nonsteroidal anti-inflammatory drugs and those without diabetes.Limitations: No measurement of renal function, no contact with patients, over-the-counter sales were not recorded, and potential underestimation of exposure dose for cases and ORs.Conclusions: Consumption of >60 g of Mu Tong or Fangchi from herbal supplements was associated with an increased risk of developing kidney failure.

Dosing of Renal Replacement Therapy in Acute Kidney Injury: Lessons Learned From Clinical Trials - Corrected Proof

Josée Bouchard, Etienne Macedo, Ravindra L. Mehta — 2010-02-01

Prescribing dialysis to manage acute kidney injury (AKI) is common and recently has become a controversial area for physicians. The concept of dialysis “dose” initially was developed for end-stage renal disease and has been extended to AKI in the last decade. Urea kinetic modeling has been the mainstay of dose quantification in end-stage renal disease. Extrapolation of these techniques to critically ill patients with AKI is difficult because of a non–steady state leading to a variable increase in urea generation rate, alterations in total-body water and its compartmental distribution, and changing renal excretory capacity. Additional challenges are imposed when dose is considered for different modalities of dialysis that vary in operational characteristics (diffusion, convection, and adsorption), duration (intermittent and continuous), and frequency. The purpose of this article is to review the concept of dialysis dose, perform a critical assessment of the most important clinical trials of dialysis dose in AKI, summarize clinical evidence from these trials, and define key research issues that should be addressed in the future.

Patient Views About Treatment of Stage 5 CKD: A Qualitative Analysis of Semistructured Interviews - Corrected Proof

2010-02-01

Background: How patients choose between alternative treatments for kidney failure is poorly understood. Recent studies of chronic kidney disease report that clinical outcomes, such as life expectancy, are rarely reflected in a patient's decision for type of treatment compared with nonclinical outcomes, such as time on dialysis therapy, convenience, or impact on the family.Methods: A qualitative analysis using thematic synthesis of patient views about renal replacement therapy (RRT) was undertaken. As part of a national study of patients and renal health care providers, we interviewed 95 Australian dialysis and transplant patients to explore how they perceive these alternative treatments.Results: 52 patients were on satellite hemodialysis therapy, 8 patients were on incenter hemodialysis therapy, 8 patients were on continuous ambulatory peritoneal dialysis therapy, 5 patients were on automated peritoneal dialysis therapy, 4 patients were on home hemodialysis therapy, and 18 patients had a functioning transplant at the time of interview. Freedom, convenience, self-care, effectiveness, and simplicity were commonly cited positive characteristics, whereas confinement, risk, family burden, pain, and time commitment were negative characteristics associated with RRTs. Characteristics were not specific to dialysis modalities, and some (eg, self-care) were seen as both positive and negative. A limitation of the study was that only 17 of 77 (22%) dialysis patients interviewed were on a home-based therapy.Conclusions: Patients preferred RRTs that enhanced their freedom and autonomy and were convenient, effective, and simple. Treatments that minimized confinement and risk also were viewed positively. Our analysis suggests that patients might choose between therapies based on their perception regarding which therapy most embodies particular characteristics that minimize impact on their lifestyle. Presentation of information regarding RRTs should focus on these characteristics and the potential impact of alternative treatments on the patients and how they wish to lead their lives.

Occupational Lead Exposure and Severe CKD: A Population-Based Case-Control and Prospective Observational Cohort Study in Sweden - Corrected Proof

2010-02-01

Background: The role of low-level lead exposure in the cause of chronic kidney disease (CKD) is unsettled.Study Design: Case-control study and prospective observational cohort study.Setting & Participants: 926 cases with incident severe CKD (serum creatinine > 3.4 mg/dL for men and > 2.8 mg/dL for women for the first time) and 998 population controls were included. Cases represented nearly all patients with incident severe CKD in Sweden during 2 years. Cases also were followed up prospectively for 7-9 years. Exposed and nonexposed cases were compared with regard to rate of change in estimated glomerular filtration rate (eGFR) and renal survival.Predictor: Lead exposure was assessed using the expert rating method.Outcomes & Measurements: Associations between lead exposure and risk of CKD, adjusted for factors associated with this outcome, were analyzed using multivariable logistic regression modeling, whereas links to the rate of change in eGFR were analyzed in mixed-effects multivariable models based on up to 6 measurements. Renal survival in relation to lead exposure was analyzed in a Cox proportional hazards model.Results: The adjusted OR for incident severe CKD was 0.97 (95% CI, 0.68-1.38) in lead-exposed compared with nonexposed participants. The OR for individuals with the highest average exposure (>0.0075 mg/m3) was 1.09 (95% CI, 0.64-1.85). ORs for CKD caused by glomerulonephritis, nephrosclerosis, and diabetic nephropathy did not differ importantly. In patients with CKD ever exposed and most exposed to lead, eGFRs changed by −4.27 and −3.39 mL/min/1.73 m2/y compared with −4.55 mL/min/1.73 m2/y in nonexposed patients, respectively.Limitations: Only native Swedes were included, which may limit generalizability. Blood lead was not measured to confirm the validity of the expert rating method.Conclusion: Our data provide no evidence of an important role of low-level occupational lead exposure in the cause or progression of severe CKD.

Trends in Patient Characteristics and First-Year Medical Costs of Older Incident Hemodialysis Patients, 1995-2005 - Corrected Proof

2010-02-01

Background: Characteristics of patients with chronic kidney disease who survive to end-stage renal disease may change over time, affecting subsequent outcomes and costs. We examined trends in older incident hemodialysis patient characteristics and analyzed first-year post–dialysis therapy initiation medical costs.Study Design: Retrospective cohort study.Setting & Participants: All US incident hemodialysis patients aged ≥67 years at dialysis therapy initiation from January 1, 1995, to December 31, 2005, with Medicare Part A and Part B in the prior 2 years.Predictor: Year of dialysis therapy initiation.Outcomes: Changes in patient characteristics and first-year costs.Measurements: Mean and median values for continuous variables and percentages of categorical variables; first-year total medical costs measured per person per year. Observed costs were adjusted using Medicare Price Indices and patient case-mix.Results: Median age at dialysis therapy initiation increased from 74.9 to 77.0 years from 1995 (n = 19,044) to 2005 (n = 31,796; P < 0.001). Diabetes prevalence increased from 54.2% to 64.1% (P < 0.001). Median estimated glomerular filtration rate increased from 8.0 to 11.2 mL/min/1.73 m2, and median hemoglobin level increased from 9.4 to 10.2 g/dL. Obesity increased from 8.9% to 22.9% (P < 0.001). First-year observed costs increased by 37.9%; however, inflation-adjusted and case-mix-inflation–adjusted costs were stable. Important adjusters for costs are inability to ambulate/transfer, baseline serum albumin level, primary end-stage renal disease cause, comorbid peripheral vascular disease, and baseline hospital days.Limitations: Population aged ≥67 years at dialysis therapy initiation and results may not generalize to the overall hemodialysis population.Conclusions: From 1995 to 2005, incident hemodialysis patients aged ≥67 years became older, sicker, and more obese with significantly increased estimated glomerular filtration rates and hemoglobin levels at dialysis therapy initiation. Increased first-year post–dialysis therapy initiation costs became stable over time after adjustment for price inflation; case-mix-inflation–adjusted costs remained constant, possibly because of mixed changes in patient characteristics.

Decreased Kidney Function of Unknown Cause in Nicaragua: A Community-Based Survey - Corrected Proof

2010-02-01

Background: End-stage kidney disease overwhelms health services in Central America. We determined prevalences of decreased kidney function in distinct populations in the most affected region of Nicaragua.Study Design: Cross-sectional survey.Setting & Participants: Total populations aged 20-60 years of 5 villages in Northwest Nicaragua: mining/subsistence farming (elevation, 100-300 m above sea level), banana/sugarcane (100-300 m), fishing (0-100 m), services (0-100 m), and coffee (200-675 m); 479 men and 617 women (83% response).Predictor or Factor: Village; participant sex, age, and occupation; conventional chronic kidney disease risk factors.Outcomes: Serum creatinine (SCr) values greater than laboratory reference range for sex, estimated glomerular filtration rate <60 mL/min/1.73 m2, proteinuria stratified in the low (dipstick protein excretion, 30-300 mg/dL) and high (>300 mg/dL) range.Results: Prevalences of abnormal SCr levels: 18% (of all men) and 5% (of all women); in the mining/subsistence farming village, 26% and 7%; banana/sugarcane, 22% and 6%; fishing, 13% and 4%; services, 0% and 1%; and coffee, 7% and 0%. Prevalences of estimated glomerular filtration rate <60 mL/min/1.73 m2: 14% (of all men) and 3% (of all women); in the listed villages, 19% and 5%, 17% and 4%, 10% and 2%, 0% and 0%, and 7% and 0%, respectively. Proteinuria, predominantly in the low range, affected 14% and 11% of all men and women without marked differences between villages. By occupation, abnormal SCr levels occurred in 31% and 24% of male and female agricultural workers at 100-300 m above sea level, but not at higher altitudes, and also was high in male artisans (43%), construction workers (15%), and miners (14%). In logistic regression models, for the banana/sugarcane and mining/subsistence farming villages, high blood pressure and age were significant predictors of abnormal SCr levels in men, and for mining/subsistence farming, age in women.Limitations: Causality is not addressed.Conclusions: In some Nicaraguan villages and population segments, men in particular show a high prevalence of decreased kidney function of unknown origin, possibly environmental or occupational.

A Health Policy Model of CKD: 1. Model Construction, Assumptions, and Validation of Health Consequences - Corrected Proof

2010-02-01

Background: A cost-effectiveness model that accurately represents disease progression, outcomes, and associated costs is necessary to evaluate the cost-effectiveness of interventions for chronic kidney disease (CKD).Study Design: We developed a microsimulation model of the incidence, progression, and treatment of CKD. The model was validated by comparing its predictions with survey and epidemiologic data sources.Setting & Population: US patients.Model, Perspective, & Timeframe: The model follows up disease progression in a cohort of simulated patients aged 30 until age 90 years or death. The model consists of 7 mutually exclusive states representing no CKD, 5 stages of CKD, and death. Progression through the stages is governed by a person's glomerular filtration rate and albuminuria status. Diabetes, hypertension, and other risk factors influence CKD and the development of CKD complications in the model. Costs are evaluated from the health care system perspective.Intervention: Usual care, including incidental screening for persons with diabetes or hypertension.Outcomes: Progression to CKD stages, complications, and mortality.Results: The model provides reasonably accurate estimates of CKD prevalence by stage. The model predicts that 47.1% of 30-year-olds will develop CKD during their lifetime, with 1.7%, 6.9%, 27.3%, 6.9%, and 4.4% ending at stages 1-5, respectively. Approximately 11% of persons who reach stage 3 will eventually progress to stage 5. The model also predicts that 3.7% of persons will develop end-stage renal disease compared with an estimate of 3.0% based on current end-stage renal disease lifetime incidence.Limitations: The model synthesizes data from multiple sources rather than a single source and relies on explicit assumptions about progression. The model does not include acute kidney failure.Conclusion: The model is well validated and can be used to evaluate the cost-effectiveness of CKD interventions. The model also can be updated as better data for CKD progression become available.

A Health Policy Model of CKD: 2. The Cost-Effectiveness of Microalbuminuria Screening - Corrected Proof

2010-02-01

Background: Microalbuminuria screening may detect chronic kidney disease in its early stages, allowing for treatment that delays or prevents disease progression. The cost-effectiveness of microalbuminuria screening has not been determined.Study Design: A cost-effectiveness model simulating disease progression and costs.Setting & Population: US patients.Model, Perspective, and Timeframe: The microsimulation model follows up disease progression and costs in a cohort of simulated patients from age 50 to 90 years or death. Costs are evaluated from the health care system perspective.Intervention: Microalbuminuria screening at 1-, 2-, 5-, or 10-year intervals followed by treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. We considered universal screening, as well as screening targeted at persons with diabetes, persons with hypertension but no diabetes, and persons with neither diabetes nor hypertension.Outcomes: Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios.Results: For the full model population, universal screening increases costs and increases QALYs. Universal annual screening starting at age 50 years has a cost-effectiveness ratio of $73,000/QALY relative to no screening and $145,000/QALY relative to usual care. Cost-effectiveness ratios improved with longer screening intervals. Relative to no screening, targeted annual screening has cost-effectiveness ratios of $21,000/QALY, $55,000/QALY, and $155,000/QALY for persons with diabetes, those with hypertension, and those with neither current diabetes nor current hypertension, respectively.Limitations: Results necessarily are based on a microsimulation model because of the long time horizon appropriate for chronic kidney disease. The model includes only health care costs.Conclusions: Microalbuminuria screening is cost-effective for patients with diabetes or hypertension, but is not cost-effective for patients with neither diabetes nor hypertension unless screening is conducted at longer intervals or as part of existing physician visits.

Effect of Thiazolidinediones on Albuminuria and Proteinuria in Diabetes: A Meta-analysis - Corrected Proof

2010-01-29

Background: Because of the major clinical and economic burden of diabetic nephropathy, new therapeutic tools to delay its progression are needed. Recent studies suggest that thiazolidinediones have renal benefits. We aimed to evaluate the effect of thiazolidinediones on urinary albumin and protein excretion in patients with diabetes mellitus.Study Design: Systematic review and meta-analysis by searching MEDLINE/PubMed, EMBASE, and Cochrane CENTRAL databases (1991 to September 2009).Setting & Population: Patients with diabetes mellitus.Selection Criteria for Studies: Randomized controlled trials.Intervention: Thiazolidinediones (rosiglitazone and pioglitazone) compared with placebo or other antidiabetic agents.Outcomes: Weighted (WMDs) and standardized mean differences (SMDs) for changes in urine albumin or protein excretion between the thiazolidinedione and control groups.Results: Of 171 originally identified articles, 15 studies (5 with rosiglitazone and 10 with pioglitazone) involving 2,860 patients were included in the analysis. In participants with baseline normo- or microalbuminuria, the WMD of proportional changes between the thiazolidinedione and control groups in urinary albumin excretion measured using time-specified collections was −64.8% (95% CI, −75.6 to −53.9) and the WMD of changes in albumin-creatinine ratio was −24.8% (95% CI, −39.6 to −10.0). Overall, in participants with normo- and microalbuminuria, thiazolidinedione treatment was associated with a significant decrease in urinary albumin excretion (SMD, −0.6 units of standard deviation [SD]; 95% CI, −0.8 to −0.4). Similarly, thiazolidinediones were associated with a significant decrease in urinary protein excretion in patients with proteinuria (SMD, −1.1 units of SD; 95% CI, −1.8 to −0.4).Limitations: Significant heterogeneity across included studies in several subgroup analyses; patient-level data not available.Conclusions: Treatment with thiazolidinediones significantly decreases urinary albumin and protein excretion in patients with diabetes. This finding calls for clinical trials with hard renal outcomes to elucidate the potential benefits of thiazolidinediones on diabetic nephropathy.

Culture-Negative Peritonitis in Peritoneal Dialysis Patients in Australia: Predictors, Treatment, and Outcomes in 435 Cases - Corrected Proof

2010-01-29

Background: Reports of culture-negative peritoneal dialysis (PD)-associated peritonitis have been sparse, conflicting, and limited to small single-center studies. The aim of this investigation is to examine the frequency, predictors, treatment, and outcomes of culture-negative PD-associated peritonitis.Study Design: Observational cohort study using Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data.Setting & Participants: All Australian PD patients between October 1, 2003, and December 31, 2006.Predictors: Demographic, clinical, and facility variables.Outcomes & Measurements: Culture-negative PD-associated peritonitis occurrence, relapse, hospitalization, catheter removal, hemodialysis transfer, and death.Results: Of 4,675 patients who received PD in Australia during the study period, 435 episodes of culture-negative peritonitis occurred in 361 individuals. Culture-negative peritonitis was not associated with demographic or clinical variables. A history of previous antibiotic treatment for peritonitis was more common with culture-negative than culture-positive peritonitis (42% vs 35%; P = 0.01). Compared with culture-positive peritonitis, culture-negative peritonitis was significantly more likely to be cured using antibiotics alone (77% vs 66%; P < 0.001) and less likely to be complicated by hospitalization (60% vs 71%; P < 0.001), catheter removal (12% vs 23%; P < 0.001), permanent hemodialysis therapy transfer (10% vs 19%; P < 0.001), or death (1% vs 2.5%; P = 0.04). Relapse rates were similar between the 2 groups. Patients with relapsed culture-negative peritonitis were more likely to have their catheters removed (29% vs 10% [P < 0.001]; OR, 3.83; 95% CI, 2.00-7.32). Administration of vancomycin or cephalosporin in the initial empiric antibiotic regimen and the timing of catheter removal were not significantly associated with clinical outcomes.Limitations: Limited covariate adjustment. Residual confounding and coding bias could not be excluded.Conclusions: Culture-negative peritonitis is a common complication with a relatively benign outcome. A history of previous antibiotic treatment is a significant risk factor for this condition.

Thrombocytopenia Associated With Use of a Biocompatible Hemodialysis Membrane: A Case Report - Corrected Proof

James B. Post — 2010-01-29

Biocompatibility of a dialyzer membrane has been defined largely by the degree to which it activates complement. Modifications of the cellulose membrane and the development of synthetic membranes have minimized the activation of complement and its associated complications. However, less is known about the blood–dialyzer membrane interactions that may occur in membranes made of the same synthetic polymer. A patient is described who developed dialysis-associated thrombocytopenia using a Fresenius Medical Care Optiflux polysulfone membrane (F-160) that significantly improved when switched to the polysulfone Asahi REXEED 25S membrane (AR-25S). A comparison of postdialysis d-dimer level suggests that the F-160 membrane activated the coagulation pathway to a greater extent than the AR-25S. Subtle differences between the internal surfaces of the membranes that are manufacturer specific may be responsible for exposing this patient's unique predisposition to thrombosis and thrombocytopenia. Despite the advances in membrane biocompatibility, differences may exist among membranes made of the same synthetic polymer.

Is Collapsing C1q Nephropathy Another MYH9-Associated Kidney Disease? A Case Report - Corrected Proof

2010-01-29

C1q nephropathy is a rare kidney disease that can present with nephrotic syndrome and typically has the histologic phenotype of either minimal change disease or focal segmental glomerulosclerosis (FSGS). Disagreement exists about whether it is a distinct immune complex–mediated glomerulopathy or it resides in the spectrum of FSGS-minimal change disease. Two African American patients with C1q nephropathy histologically presenting as the collapsing variant of FSGS (collapsing C1q nephropathy) and rapid loss of kidney function were genotyped for polymorphisms in the non–muscle myosin heavy chain 9 gene (MYH9). Both cases were homozygous for the MYH9 E1 risk haplotype, the variant strongly associated with idiopathic FSGS, collapsing FSGS in human immunodeficiency virus–associated nephropathy, and focal global glomerulosclerosis (historically attributed to hypertensive nephrosclerosis). Collapsing C1q nephropathy with rapid progression to end-stage renal disease appears to reside in the MYH9-associated disease spectrum.

Cyclophosphamide Therapy for Corticoresistant Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome in a Patient With Severe Kidney and Eye Involvement and Epstein-Barr Virus Reactivation - Corrected Proof

2010-01-28

DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome is a severe adverse drug reaction with significant mortality, characterized by erythroderma, fever, lymphadenopathy, and visceral involvement. We report a case of multivisceral DRESS syndrome with posterior multifocal placoid pigment epitheliopathy and acute tubulointerstitial nephritis responsible for dialysis-dependent acute kidney failure in the context of reactivation of Epstein-Barr virus infection. Because of resistance of the skin and kidney manifestations to prolonged corticosteroid therapy, a 6-month course of oral cyclophosphamide resulted in complete recovery of all symptoms. To our knowledge, this is the first case showing the efficacy of cyclophosphamide in severe DRESS syndrome.

Intensive Versus Conventional Therapy to Slow the Progression of Idiopathic Glomerular Diseases - Corrected Proof

Stefano Bianchi, Roberto Bigazzi, Vito M. Campese — 2010-01-25

Background: Chronic kidney disease (CKD) caused by idiopathic glomerular diseases usually is progressive. Inhibition of the renin-angiotensin system (RAS) retards, but does not abrogate, CKD progression. Statins and spironolactone may decrease the rate of CKD progression independently or in addition to RAS inhibition.Study Design: Randomized open-label study.Setting & Participants: We recruited 128 patients (82 men and 46 women) with a clinical diagnosis of idiopathic chronic glomerulonephritis and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 (range, 36-102 mL/min/1.73 m2), and urine protein-creatinine ratio ranging from 1.1-5.2 g/g.Intervention: Intensive therapy (a combination of RAS inhibitors [angiotensin-converting enzyme [ACE] inhibitors plus angiotensin receptor blockers [ARBs] plus a high-dose statin and spironolactone) versus conventional therapy (a regimen based on ACE inhibitors with a low-dose statin).Outcomes: Changes in eGFR, proteinuria, and adverse events after 3 years of therapy.Results: With intensive therapy, urine protein-creatinine ratio decreased from 2.65 (range, 1.1-5.2) to 0.45 (0.14-1.51) g/g (P < 0.001) and eGFR did not significantly change over time (64.6 ± 2.1 vs 62.9 ± 2.9 mL/min/1.73 m2). With conventional therapy, urine protein-creatinine ratio decreased from 2.60 (range, 1.32-5.4) to 1.23 (0.36-3.42) g/g (P < 0.001) and eGFR decreased from 62.5 ± 1.7 to 55.8 ± 1.9 mL/min/1.73 m2 (P < 0.001). Comparison of the decreases in proteinuria and GFR between intensive versus conventional therapy was significantly different starting in the 1st and 12th months, respectively. Systolic blood pressure was lower with intensive than conventional therapy (113.5 ± 1.4 vs 122.7 ± 1.2 mm Hg; P < 0.01). We found an inverse relationship between percentage of decrease in proteinuria and change in eGFR (P < 0.001). Patients on intensive therapy were more likely to develop adverse events, such as hyperkalemia (9 vs 3 patients in the conventional therapy group) and discontinue therapy (15 vs 8 patients in the conventional therapy group).Limitations: Open-label design.Conclusions: A more intensive therapy that includes a combination of ACE inhibitors and ARBs plus high-dose statins and spironolactone may retard CKD progression more effectively than conventional therapy based on ACE inhibitors plus low-dose statin, but may lead to more adverse effects and discontinuation of therapy.

Incidence and Outcomes of Contrast-Induced Nephropathy After Computed Tomography in Patients With CKD: A Quality Improvement Report - Corrected Proof

2010-01-25

Background: Although there has been considerable investigation of the general characteristics of contrast-induced nephropathy (CIN), it has not been studied adequately in a computed tomography (CT) population. We assessed the incidence and outcomes of CIN after contrast-enhanced CT in patients with chronic kidney disease pretreated with saline and N-acetylcysteine (NAC).Design: Quality improvement report.Setting & Participants: 520 patients registered in a CIN prevention program.Quality Improvement Plan: We initiated the CIN prevention program in January 2007. In this program, patients with chronic kidney disease undergoing contrast-enhanced CT in an outpatient setting were automatically referred to nephrologists, and patients received saline and NAC before and after CT. The development of CIN was assessed 48-96 hours after CT.Outcomes: Incidence of CIN and time to renal replacement therapy.Measurements: Baseline serum creatinine, hemoglobin, and serum albumin levels; type and volume of contrast agents; and post-CT serum creatinine level.Results: Overall, CIN occurred in 13 (2.5%) patients. Incidences of CIN were 0.0%, 2.9%, and 12.1% in patients with an estimated glomerular filtration rate of 45-59, 30-44, and <30 mL/min/1.73 m2, respectively. The risk of CIN was increased in patients with severely decreased kidney function and diabetes. The development of CIN consequently increased the risk of renal replacement therapy (P < 0.001 by log-rank), and the risk was significantly accentuated in patients with estimated glomerular filtration rate <30 mL/min/1.73 m2.Limitations: A single-center study and comparison with previous studies.Conclusions: The incidence of CIN was relatively low in patients treated with saline and NAC. The development of CIN predisposed to poor kidney survival in the long term.

Long-term Effects of Arteriovenous Fistula Closure on Echocardiographic Functional and Structural Findings in Hemodialysis Patients: A Prospective Study - Corrected Proof

2010-01-20

Background: The arteriovenous fistula (AVF) provides an effective vascular access for hemodialysis; however, the associated hemodynamic effects may alter cardiac structure and function. The objective of this study is to evaluate the effect of AVF closure on functional and structural echocardiographic findings.Study Design: Prospective observational study.Setting & Participants: In a single center between 2003 and 2006, we enrolled 25 consecutive hemodialysis patients with AVF malfunction who underwent AVF closure and conversion to a tunneled central venous catheter because of exhaustion of alternative vascular sites and 36 matched controls with a well-functioning AVF.Predictor: AVF closure.Outcomes & Measurements: Outcomes were changes in findings on echocardiograms obtained before and 6 months after AVF closure for patients in the AVF-closure group and at baseline and 6 months later for controls. Echocardiographic measurements included left ventricular (LV) internal diastolic diameter, interventricular septum thickness, diastolic posterior wall thickness, LV mass (LVM), LVM index (LVMi), and LV ejection fraction (LVEF). Dialysis modality and scheme were unchanged.Results: In the AVF-closure group, LVM decreased from 225 ± 55 to 206 ± 51 g (P < 0.001) and LVMi decreased from 135 ± 40 to 123 ± 35 g/m2 (P < 0.001). LV internal diastolic diameter, interventricular septum thickness, and diastolic posterior wall thickness decreased significantly, whereas LVEF increased from 56% ± 7% to 59% ± 6% (P < 0.001). No significant changes were observed in controls. In patients with AVF closure, LV morphologic characteristics showed a decrease in both eccentric and concentric hypertrophy in favor of normalization or a pattern of concentric remodeling. No significant changes were observed in controls.Limitations: Use of matched rather than randomized controls.Conclusions: Closure of an AVF determines a significant decrease in LV internal diastolic diameter, interventricular septum thickness, and diastolic posterior wall thickness. This is associated with significant improvement in LVEF, a significant decrease in LVM and LVMi, and a more favorable shift of cardiac geometry toward normality.

Bone Marrow Iron, Iron Indices, and the Response to Intravenous Iron in Patients With Non–Dialysis-Dependent CKD - Corrected Proof

2010-01-18

Background: Information about iron stores and their relationship with transferrin saturation (TSAT), serum ferritin, and the erythropoietic response to iron therapy is scarce in anemic non–dialysis-dependent patients with chronic kidney disease (CKD). We examined the diagnostic utility of peripheral-iron indices and the erythropoietic response to intravenous iron as indices of iron store depletion using bone marrow iron as a reference test in anemic non–dialysis-dependent patients with CKD.Study Design: Diagnostic test study.Setting & Participants: 100 anemic (hemoglobin <11 g/dL) patients with CKD stages 3-5, not receiving epoetin and iron.Index Tests: TSAT index and serum ferritin level at baseline and increase in hemoglobin level 1 month after 200 mg of iron sucrose daily for 5 days.Reference Test: Bone marrow iron (assessed using aspiration and Perls' stain), depleted versus replete, at baseline.Measurements: Area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of peripheral-iron indices and erythropoietic response to describe bone marrow iron stores.Results: Bone marrow iron stores were depleted in 48% of patients at baseline. In iron-depleted versus -replete subjects, mean hemoglobin level, median TSAT index, median serum ferritin level, and hemoglobin level increase after iron sucrose administration were 8.74 ± 1.1 (SD) versus 9.22 ± 0.9 g/dL (P = 0.02), 19% (interquartile range [IQR], 15%) versus 28% (IQR, 12%; P < 0.001), 100 (IQR, 131) versus 220 ng/mL (IQR, 213; P < 0.001), and 1.2 ± 0.4 versus 0.8 ± 0.3 g/dL (P < 0.001), respectively. TSAT, ferritin level, and increase in hemoglobin level AUROCs were similar: 0.75 (95% CI, 0.66-0.85), 0.76 (95% CI, 0.66-0.85), and 0.74 (95% CI, 0.65-0.84), respectively.Limitations: Bone marrow iron as the index of iron stores.Conclusions: Half the anemic patients with CKD stages 3-5 had depleted iron stores. Peripheral-iron indices and erythropoietic response had equivalent, but limited, utility in identifying depletion of bone marrow iron stores. Use of these indices to indicate depletion of iron stores should be reconsidered.

Binder Blinders—Niacin of Omission? - Corrected Proof

Andrew G. Bostom — 2010-01-18

It is common knowledge to every schoolboy and even every Bachelor of Arts,That all sin is divided into two parts.One kind of sin is called a sin of commission, and that is very important,And it is what you are doing when you are doing something you ortant,And the other kind of sin is just the opposite and is called a sin of omissionand is equally bad in the eyes of all right-thinking people, fromBilly Sunday to Buddha,And it consists of not having done something you shuddha….From Ogden Nash, “Portrait of the Artist as Prematurely Old Man”

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) Grant Initiative: Moving Clinical Practice Forward - Corrected Proof

Holly Kramer — 2010-01-11

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines have made a substantial impact on the overall care of adults and children with chronic kidney disease (CKD) and have increased awareness of the importance of diagnosing and treating kidney disease for health care providers in all specialties, but especially primary care. Despite ongoing research, many key issues in clinical care remain controversial, with little evidence to support existing management practices. The evidence review process for developing the KDOQI guidelines not only summarizes existing research to create guidelines, but also identifies gaps in knowledge, which then are included as research recommendations.

Subcapsular Fluid Collection: An Unusual Manifestation of Nephrotic Syndrome - Corrected Proof

Nisar A. Wani, Farooq Mir, Tariq Gojwari, Umar A. Qureshi, Rayees Ahmad — 2010-01-11

Nephrotic syndrome is characterized by heavy proteinuria (protein excretion >3.5 g/24 h in adults or 40 mg/m2/h in children), hypoalbuminemia (albumin <2.5 g/dL), edema, and hyperlipidemia. Edema results from fluid accumulation in the subcutaneous tissue. Fluid also commonly accumulates in the peritoneal and pleural cavities. Rarely, fluid may accumulate in the subcapsular space around the kidneys. Such subcapsular fluid accumulation has been reported as a complication of nephrotic syndrome or in association with severe pulmonary hypertension. We describe a patient with nephrotic syndrome who presented with hypertension and pain in the left lumbar region. Ultrasonography and magnetic resonance imaging (MRI) showed a massive subcapsular collection around the left kidney. The patient was treated successfully with ultrasonography-guided drainage of the collection and medical treatment. The kidney biopsy specimen showed changes of focal segmental glomerulosclerosis.

Effect of Short-term High-Dose Creatine Supplementation on Measured GFR in a Young Man With a Single Kidney - Corrected Proof

2010-01-11

It currently is unknown whether creatine supplementation is safe for people with or at risk of kidney disease. We report on the short-term effects of creatine supplementation on kidney function in a young man with a single kidney and mildly decreased glomerular filtration rate (GFR). A 20-year-old man who had undergone unilateral nephrectomy and presented with mildly decreased GFR without kidney damage underwent a trial with 35 days of creatine supplementation (20 g/d for 5 days followed by 5 g/d for the next 30 days) and had his kidney function monitored. After the intervention, 51Cr-EDTA clearance (pre, 81.6 mL/min/1.73 m2; post, 82.0 mL/min/1.73 m2), proteinuria (protein excretion: pre, 130 mg/d; post, 120 mg/d), and electrolyte levels were unchanged. Albuminuria, serum urea level, and estimated creatinine clearance were decreased (pre, 4.6 mg/d; post, 2.9 mg/d; pre, 37 mg/d; post, 28 mg/dL; and pre, 88 mL/min/1.73 m2; post, 71 mL/min/1.73 m2, respectively), whereas serum creatinine level was slightly increased (pre, 1.03 mg/dL; post, 1.27 mg/dL), falsely suggesting kidney function impairment. This prospective report suggests that short-term creatine supplementation may not affect kidney function in an individual with a single kidney, mild decreased GFR, and ingesting a high-protein diet (ie, 2.8 g/kg/d). This finding has great relevance considering that creatine-induced kidney disease has been a growing concern, even for healthy people.

Impact of Erythropoiesis-Stimulating Agents on Energy and Physical Function in Nondialysis CKD Patients With Anemia: A Systematic Review - Corrected Proof

2009-12-23

Background: Previous analyses report the impact of erythropoiesis-stimulating agents (ESAs) on health-related quality of life across various populations. In this analysis, we review published studies and quantify the effect of ESA therapy on energy/fatigue and physical function in nondialysis patients with chronic kidney disease (CKD) related anemia.Study Design: Systematic literature search to identify articles (1980-2008) that evaluated effects of ESAs on patient-reported energy and physical function.Setting & Population: Nondialysis CKD patients with anemia enrolled in prospective trials.Selection Criteria for Studies: Prospective studies measuring energy or physical function with both baseline and follow-up measurement.Intervention: ESA treatment.Outcomes: Improvements in energy and physical function assessed using effect size, a measure of treatment responsiveness.Results: 14 studies were identified: 11 measured energy and 14 measured physical function. The 36-Item Short-Form Health Survey (SF-36) was the most common instrument used to report energy and physical function. Of 11 studies measuring energy, 2 were double-blind randomized placebo-controlled trials (RCTs), 5 were open-label RCTs, and 4 were single-arm open-label studies. Eight of 11 studies reported statistically significant improvements in energy. Effect size for energy ranged from small (0.24) to large (1.90) in ESA-treated groups and was moderate in each arm of the low- versus high-hemoglobin target RCTs. Of 14 studies measuring physical function, 2 were double-blind RCTs, 6 were open-label RCTs, and 6 were single-arm open-label studies. Ten of 14 studies reported statistically significant improvements in physical function. Effect size for physical function ranged from small (0.37) to large (2.38) in ESA-treated groups and was negligible to moderate in each arm of low- versus high-hemoglobin target studies.Limitations: Findings and conclusions were limited by the available evidence.Conclusion: RCTs and single-arm studies indicate that treatment of anemia with ESAs improves energy and physical function in nondialysis CKD patients.

Nutcracker Syndrome and Radiographic Evaluation of Loin Pain and Hematuria - Corrected Proof

Amir Bhanji, Paul Malcolm, Mahzuz Karim — 2009-12-21

Loin pain and hematuria are common symptoms, presenting in patients of all ages. There are various underlying pathologic causes, including renal or ureteric calculi or tumors, intrinsic kidney disease (including glomerulonephritis), and loin pain hematuria syndrome. Since some of these causes are potentially serious and may be treatable if identified early, it is important to establish a diagnosis. Patients therefore often undergo multiple investigations and procedures. However, in some cases, no cause is identified unless rarer pathologic states are considered. We describe a patient with loin pain and hematuria who proved to be a diagnostic dilemma for several years before the diagnosis of nutcracker syndrome was established.

Prevention of Diabetic Kidney Disease: Negative Clinical Trials With Renin-Angiotensin System Inhibitors - Corrected Proof

Robert G. Nelson, Katherine R. Tuttle — 2009-12-11

Commentary on Bilous R, Chaturvedi N, Sjølie AK, et al. Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials. Ann Intern Med. 2009;151(1):11-20; and Mauer M, Zinman B, Gardiner R, et al. Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med. 2009;361(1):40-51.

Pathophysiology and Management of Preeclampsia-Associated Severe Hyponatremia - Corrected Proof

Gagangeet Sandhu, Senthil Ramaiyah, Germaine Chan, Ira Meisels — 2009-12-11

Severe hyponatremia is a rare complication of preeclampsia. Of 8 cases reported in the literature, the postulated mechanism was hypervolemic hyponatremia in 5 and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in the remaining 3. Irrespective of the type, early diagnosis and treatment are of the utmost importance. Hyponatremia in patients with preeclampsia may be associated with increased risk of maternal seizures, and fetal sodium level < 130 mEq/L (<130 mmol/L) can cause fetal jaundice, tachypnea, seizures, and polyhydramnios. Treatment of hyponatremia presents unique challenges in the setting of preeclampsia. Demeclocycline and conivaptan are contraindicated in pregnancy, and furosemide, a US Food and Drug Administration (FDA) class C drug, is best avoided. Fluid restriction alone may not always be effective, and worsening hyponatremia should be an indication for induction of labor. We report the fourth case of SIADH in patients with preeclampsia and discuss the pathophysiologic characteristics and management of severe hyponatremia in preeclampsia.

Hypertension in the Developing World: Challenges and Opportunities - Corrected Proof

Bharati V. Mittal, Ajay K. Singh — 2009-12-07

Hypertension is a major public health problem and a leading cause of death and disability in developing countries. One-quarter of the world's adult population has hypertension, and this is likely to increase to 29% by 2025. Modeled projections indicate an increase to 1.15 billion hypertensive patients by 2025 in developing countries. There is variability in the global prevalence of hypertension: hypertension is present in ∼35% of the Latin American population, 20%-30% of the Chinese and Indian population, and ∼14% in Sub-Saharan African countries. This heterogeneity has been attributed to several factors, including urbanization with its associated changes in lifestyle, racial ethnic differences, nutritional status, and birth weight. Compounding this high burden of hypertension is a lack of awareness and insufficient treatment in those with hypertension. The public health response to this challenge should drive greater promotion of awareness efforts, studies of risk factors for hypertension, and understanding of the impact of lifestyle changes. Also important are efforts to develop multipronged strategies for hypertension management in developing nations.

Hypertension Awareness, Treatment, and Control in Adults With CKD: Results From the Chronic Renal Insufficiency Cohort (CRIC) Study - Corrected Proof

2009-12-07

Background: A low rate of blood pressure control has been reported in patients with chronic kidney disease (CKD). These data were derived from population-based samples with a low rate of CKD awareness.Study Design: Cross-sectional.Setting & Participants: Data from the baseline visit of the Chronic Renal Insufficiency Cohort (CRIC) Study (n = 3,612) were analyzed. Participants with an estimated glomerular filtration rate of 20-70 mL/min/1.73 m2 were identified from physician offices and review of laboratory databases.Outcomes: Prevalence and awareness of hypertension, treatment patterns, control rates, and factors associated with hypertension control.Measurements: Following a standardized protocol, blood pressure was measured 3 times by trained staff, and hypertension was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg and/or self-reported antihypertensive medication use. Patients' awareness and treatment of hypertension were defined using self-report, and 2 levels of hypertension control were evaluated: systolic/diastolic blood pressure <140/90 and <130/80 mm Hg.Results: The prevalence of hypertension was 85.7%, and 98.9% of CRIC participants were aware of this diagnosis and 98.3% were treated with medications, whereas 67.1% and 46.1% had hypertension controlled to <140/90 and <130/80 mm Hg, respectively. Of CRIC participants with hypertension, 15%, 25%, 26%, and 32% were using 1, 2, 3, and ≥4 antihypertensive medications, respectively. After multivariable adjustment, older patients, blacks, and those with higher urinary albumin excretion were less likely, whereas participants using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were more likely to have controlled their hypertension to <140/90 and <130/80 mm Hg.Limitations: Data were derived from a single study visit.Conclusions: Despite almost universal hypertension awareness and treatment in this cohort of patients with CKD, rates of hypertension control were suboptimal. Am J Kidney Dis 00:00-00 © 2009 by the National Kidney Foundation, Inc

Localized Cystic Disease of the Kidney: An Unusual Entity That Can Mimic a Cystic Neoplasm - Corrected Proof

Erik E. Dowden, Adeboye O. Osunkoya, Deborah A. Baumgarten — 2009-12-07

The differential diagnosis for cystic kidney masses is extensive and includes both benign and malignant processes. In most cases, a combination of clinical history, laboratory data, and imaging can aid in limiting this differential. In the case that a specific diagnosis cannot be made, a lesion usually can be characterized as benign or malignant based on this information. Knowledge of the spectrum of cystic kidney masses and their clinical and radiologic presentations often can help avoid unnecessary kidney biopsy or surgery. We report a case of a benign cystic kidney entity with diagnostic imaging characteristics that aid in its differentiation from other malignant processes.

Extensive Infiltrating Renal Cell Carcinoma With Minimal Distortion of the Renal Anatomy Mimicking Benign Renal Vein Thrombosis - Corrected Proof

2009-12-07

Malignancies of the kidney can present with an infiltrative appearance and may include lymphoma; metastatic disease; epithelial tumors, such as invasive transitional cell carcinoma; medullary carcinoma; renal sarcoma; and occasionally, aggressive renal cell carcinoma (RCC). Although an infiltrative appearance is not common for RCC, it can occur in up to 6% of cases. These tumors do not present as discrete expansile masses, but instead show an infiltrative pattern of growth preserving the overall size and contour of the kidney. The normal internal architecture of the kidney is replaced and obliterated by tumor. This infiltrative appearance can even mimic benign infectious and inflammatory processes, such as bacterial and xanthogranulomatous pyelonephritis or benign renal vein thrombosis.

First Identification of an Antigen in Autoimmune Idiopathic Membranous Nephropathy: Toward Targeted Therapy? - Corrected Proof

Pierre Ronco, Hanna Debiec — 2009-11-18

Commentary on Beck LH Jr, Bonegio RG, Lambeau G, et al. M-Type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 2009;361(1):11-21.

Incidental Discovery of a Renal Cell Carcinoma on Native Kidney Biopsy - Corrected Proof

C. John Sperati, Nada Alachkar, Ronald Rodriguez, Mark Haas, Michael J. Choi — 2009-11-02

Although definitive management of kidney cysts and tumors typically is performed by urologists, the initial diagnosis and longitudinal follow-up often are the responsibility of nephrologists. As such, understanding the natural history and spectrum of disease associated with kidney cysts is important to practicing nephrologists. We present the case of an incidentally detected renal cell carcinoma (RCC) on a biopsy of a native kidney and discuss therapeutic considerations in the management of cystic kidney lesions.

Maintenance of Kidney Function Following Treatment With Eculizumab and Discontinuation of Plasma Exchange After a Third Kidney Transplant for Atypical Hemolytic Uremic Syndrome Associated With a CFH Mutation - Corrected Proof

2009-10-26

Kidney transplant in patients with atypical hemolytic uremic syndrome (aHUS) is associated with a poor outcome because of recurrent disease, especially in patients known to have a factor H mutation. Long-term prophylactic plasma exchange and combined liver-kidney transplant have prevented graft loss caused by recurrence. However, the mortality associated with liver transplant is not negligible, and prophylactic plasma exchange requires permanent vascular access and regular hospitalization and exposes the patient to potential allergic reactions to plasma. Eculizumab is a high-affinity humanized monoclonal antibody that binds to C5 and thus prevents generation of C5a and the membrane attack complex. We report the case of a 17-year-old girl with aHUS associated with a mutation in the gene for complement factor H (CFH; c.3572C>T, Ser1191Leu) who was highly dependent on plasma exchange. Because of severe allergic reactions to plasma after the third renal graft, eculizumab was introduced in place of plasma exchange without problems. This and other reports suggest that the promise of complement inhibitors in the management of aHUS is going to be fulfilled.

Intradialytic Hypertension: A Less-Recognized Cardiovascular Complication of Hemodialysis - Corrected Proof

Jula K. Inrig — 2009-10-23

Intradialytic hypertension, defined as an increase in blood pressure during or immediately after hemodialysis that results in postdialysis hypertension, has long been recognized to complicate the hemodialysis procedure, yet often is largely ignored. In light of recent investigations suggesting that intradialytic hypertension is associated with adverse outcomes, this review broadly covers the epidemiologic characteristics, prognostic significance, potential pathogenic mechanisms, prevention, and possible treatment of intradialytic hypertension. Intradialytic hypertension affects up to 15% of hemodialysis patients and occurs more frequently in patients who are older, have lower dry weights, are prescribed more antihypertensive medications, and have lower serum creatinine levels. Recent studies associated intradialytic hypertension independently with higher hospitalization rates and decreased survival. Although the pathophysiologic mechanisms of intradialytic hypertension are uncertain, it likely is multifactorial and includes subclinical volume overload, sympathetic overactivity, activation of the renin-angiotensin system, endothelial cell dysfunction, and specific dialytic techniques. Prevention and treatment of intradialytic hypertension may include careful attention to dry weight, avoidance of dialyzable antihypertensive medications, limiting the use of high-calcium dialysate, achieving adequate sodium solute removal during hemodialysis, and using medications that inhibit the renin-angiotensin-aldosterone system or decrease endothelin 1 levels. In summary, although intradialytic hypertension often is underappreciated, recent studies suggest that it should not be ignored. However, further work is necessary to elucidate the pathophysiologic mechanisms of intradialytic hypertension and its appropriate management and determine whether treatment of intradialytic hypertension can improve clinical outcomes.

Screening for CKD and Cardiovascular Disease Risk Factors Using Mobile Clinics in Jalisco, Mexico - Corrected Proof

2009-10-22

Background: Chronic kidney disease (CKD) is a major cause of morbidity and mortality in Mexico. However, many residents of underserved areas may be unaware that they potentially are affected.Study Design: In an observational cross-sectional study, we examined the diagnostic yield of screening for CKD and cardiovascular disease risk factors using mobile units that traveled to poor communities in Jalisco, Mexico.Setting & Participants: We excluded individuals who were aware that they had CKD and those < 18 years of age.Outcomes: Glomerular filtration rate, cardiovascular risk.Measurements: Demographic data, socioeconomic status, blood pressure, fasting glucose, and dipstick urinalysis.Results: 3,734 participants; 29.3% men and mean age of 57.4 ± 13.0 years. Most (99.7%) had no history of cardiovascular disease; however, 43.5% had a history of diabetes, 11.4% had dipstick-positive proteinuria, 62.0% had blood pressure in the hypertensive range, and 15.8% had an estimated glomerular filtration rate compatible with stages 3-5 CKD. In patients with no history of cardiovascular disease, proportions with predicted 5-year risks of new cardiovascular events <5%, 5%-10%, 10.1%-20%, 20.1%-30%, and >30% were 10.0%, 11.7%, 26.6%, 20.7%, and 30.9%, respectively. Screening 18 participants aged < 40 years would be expected to detect 6 new cases of hypertension or 2 new cases of diabetes.Limitations: Data may not be generalizable to all low-income settings or other regions of Mexico.Conclusions: Impaired kidney function, proteinuria, and cardiovascular risk factors were detected frequently when mobile units were used to perform screening in poor areas of Jalisco, Mexico. This suggests that trials of targeted screening and intervention are feasible and warranted.

Plasma Cell Dyscrasia Causing Light Chain Tubulopathy Without Fanconi Syndrome - Corrected Proof

Matthew R. Elliott, Cherise Cortese, Alvaro Moreno-Aspitia, Jamie P. Dwyer — 2009-10-22

Light chain tubulopathy is a rare complication associated with plasma cell dyscrasias. There are no more than 80 cases reported in the English literature; the defining series was 17 patients described by Maldonado et al in 1975. That original work showed in patients with acquired Fanconi syndrome an association with monoclonal immunoglobulin light chain proteinuria, slow progression of the plasma cell dyscrasia, and crystal formation in proximal tubule cells. Since that time, a variety of clinical and pathologic findings have been reported with respect to light chain tubulopathy. Messiaen et al reported a series of 11 cases, 3 of which had no crystal formation, 2 had only partial Fanconi syndrome, and the degree of plasma cell dyscrasia ranged from monoclonal gammopathy of undetermined significance (MGUS) to full-blown multiple myeloma. The timing of kidney manifestations in relation to the diagnosis of plasma cell dyscrasia also varies. Most reports show that the investigation of proteinuria, kidney failure, Fanconi syndrome, or osteomalacia leads to the discovery of plasma cell dyscrasia; however, there are instances in which light chain tubulopathy proceeded the diagnosis of plasma cell dyscrasia. Additionally, light chain tubulopathy rarely occurs without Fanconi syndrome, as was described recently in 1 case report. We report a case of light chain tubulopathy without Fanconi syndrome found to have significant crystalline inclusions in tubular epithelial cells and podocytes discovered many years after the diagnosis of MGUS.

Permanent Hearing Loss With Iopamidol Following Aortic Angiography in a Hemodialysis Patient: A Case Report and Review of the Literature - Corrected Proof

Mohammed R. Karim, Leah Balsam, Sofia Rubinstein — 2009-10-22

Nonionic low-osmolar contrast agents are considered safe for intravenous or intra-arterial administration and are used widely in the general population, as well as in patients on hemodialysis therapy. There are data limited to case reports for contrast-induced hearing loss; however, the ototoxicity induced by contrast agents in patients with chronic kidney disease has never been described. We report a case of permanent sensorineural deafness after abdominal aortic angiography with iopamidol in a woman with end-stage renal disease on hemodialysis therapy and review the literature relating to contrast use with the development of hearing impairment.

Glomerular Collapse Associated With Subtotal Renal Infarction in Kidney Transplant Recipients With Multiple Renal Arteries - Corrected Proof

2009-10-05

Collapsing glomerulopathy is an aggressive kidney disease with rapid progression toward end-stage renal disease. Rare cases of de novo collapsing glomerulopathy have been reported during the post-transplant course and, in some instances, have been associated with renal graft vascular lesions. This finding raises the important question of whether ischemia could induce podocyte transdifferentiation, a hypothesis supported by evidence of hypoxia-inducible factor–dependent podocyte proliferation in HIV-associated nephropathy. We describe here 3 HIV-negative kidney transplant recipients in whom early graft biopsy performed in the vicinity of segmental graft infarction disclosed the typical features of glomerular collapse. Podocyte transdifferentiation was characterized by hallmark lesions, such as loss of mature podocyte phenotype, podocyte proliferation, and acquisition of a macrophage-like phenotype. Together, these data suggest that acute glomerular ischemia may lead to glomerular collapse in kidney transplants.

Recurrent Pauci-immune Necrotizing Crescentic Glomerulonephritis in a Kidney Transplant Patient - Corrected Proof

Heidi M. Schaefer, Anthony Langone, J. Harold Helderman, Agnes B. Fogo — 2009-09-27

Glomerulonephritis is the primary cause of end-stage renal disease (ESRD) in a substantial proportion of patients and includes antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis. Although recognition and treatment of ANCA-associated vasculitis (AAV) has improved, the diagnosis can be difficult to make. In 1 study, the diagnosis was missed (before ANCA testing was performed) in 43% of patients. It is estimated that 20%-40% of patients with AAV will progress to kidney failure requiring replacement therapy. It is important to be aware of the diagnosis before transplant to provide patient counseling and monitor allograft function closely in the postoperative period because the relapse rate can be significant. In a pooled analysis by Nachman et al, the overall recurrence rate was 17%. We present a case of a patient with reported “focal sclerosing nephropathy” and an acute increase in serum creatinine level shortly after transplant who was noted to have crescentic glomerulonephritis with the absence of immune complexes on allograft biopsy. This case shows the importance of confirming the cause of ESRD before transplant and the role of allograft biopsy in identifying the causes of decreased kidney function.

Development of Anti–Glomerular Basement Membrane Disease After Remission From Perinuclear ANCA-Associated Glomerulonephritis in a Patient With HLA Susceptibility - Corrected Proof

Kate O'Connor, David Fulcher, Richard K.S. Phoon — 2009-09-07

A 62-year-old woman presented with acute renal failure, hematuria, proteinuria, and increased C-reactive protein level. She was positive for antineutrophil cytoplasmic antibodies (ANCAs) directed against myeloperoxidase (MPO) and negative for anti–glomerular basement membrane antibody. Kidney biopsy confirmed a diagnosis of pauci-immune crescentic glomerulonephritis with no immunoglobulin G staining. Remission was induced with prednisolone and intravenous cyclophosphamide, followed by maintenance therapy with azathioprine, during which MPO-ANCA results became negative. Nine months after the initial presentation, kidney function rapidly deteriorated again in association with hematuria, proteinuria, and increased C-reactive protein level. A second kidney biopsy again showed crescentic glomerulonephritis; however, on this occasion, direct immunofluorescence showed prominent linear staining of the glomerular basement membrane with immunoglobulin G. Test results were strongly positive for glomerular basement membrane antibody, but remained negative for MPO-ANCA. HLA-DR typing showed HLA-DRB1*15011, an allele strongly associated with anti–glomerular basement membrane disease. To our knowledge, this is the only reported case of 2 distinct forms of crescentic glomerulonephritis characterized by separate autoantibody profiles developing sequentially in a patient with proved HLA susceptibility. We speculate that glomerular damage caused by the initial renal insult resulted in a subsequent autoimmune response to autoantigen presented on the HLA-DR susceptibility allele.

New-Onset Proteinuria With Massive Amorphous Glomerular Deposits - Corrected Proof

Dylan V. Miller, Ahmet Dogan, Sanjeev Sethi — 2009-07-21

We present 2 patients with long-standing mild hypertension who presented with new-onset proteinuria and decreased kidney function. We describe interesting and unusual kidney biopsy findings in these 2 patients.