American Journal of Kidney Diseases

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

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.

Blood Pressure Control in CKD Patients: Why Do We Fail to Implement the Guidelines?

Gavin J. Becker, David C. Wheeler — 2010-03-01

The Map Is Not the Territory—Mapping Out the Course and Cost of CKD

Kevin C. Abbott, Cristina M. Yuan — 2010-03-01

Quality of Life in CKD Patients Treated With Erythropoiesis-Stimulating Agents

Patrick S. Parfrey, Tyler Wish — 2010-03-01

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

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.

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

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.

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

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.

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

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

Intradialytic Hypertension: A Less-Recognized Cardiovascular Complication of Hemodialysis

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.

Hypertension in the Developing World: Challenges and Opportunities

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.

Pathophysiology and Management of Preeclampsia-Associated Severe Hyponatremia

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.

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

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.

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

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.

Charge States of Deferasirox–Ferric Iron Complexes

Robert C. Hider — 2010-03-01

The study of Rafat et al reports a case of deferasirox-induced Fanconi syndrome in an elderly patient receiving multiple transfusions. In the discussion of this article, the authors refer to the properties of the deferasirox–ferric iron complex. Some of these comments are incorrect. A similar error has been made previously, when Neufeld reported that the iron complex of deferasirox is uncharged. As this error may well have a bearing on chelator-associated kidney toxicity, we thought it appropriate to describe the nature of the iron complexes of the 3 chelators in current clinical practice. We summarize the marked differences in the properties of these chelators in .

Rhabdomyolysis and Acute Kidney Injury Associated With 2009 Pandemic Influenza A(H1N1)

Chih-Cheng Lai, Cheng-Yi Wang, Hen-I. Lin — 2010-03-01

Pandemic 2009 influenza A(H1N1) is an emerging disease first reported in April, 2009. Previous studies have pointed out that patients with pneumonia and respiratory failure arising from pandemic H1N1 may have abnormal laboratory examination results, including elevated creatine kinase (CK) levels. We report a patient with pandemic H1N1 infection who developed mild rhabdomyolysis and acute kidney injury (AKI).

Errata

2010-03-01

In the article entitled “Effect of a Carbonaceous Oral Adsorbent on the Progression of CKD: A Multicenter, Randomized, Controlled Trial” (Akizawa et al, American Journal of Kidney Diseases 54:459-467, 2009), errors appeared in the abstract, the methods section of the article, and in Tables 1 and .

Errata

2010-03-01

In the article entitled “Association of the Q121 Variant of ENPP1 Gene With Decreased Kidney Function Among Patients With Type 2 Diabetes” (De Cosmo et al, American Journal of Kidney Diseases, 53(2):273-280, 2009), the name and degree of the fourth author were listed incorrectly (as “Robert Thompson, MD”). The correct listing is Ryan Thompson, BS.

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

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.

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

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.

TREAT Versus Treatment: A Patient's View of a Scientific Interpretation

Alexander Prisant — 2010-03-01

In recent months articles and editorials have presented varied physician views on an issue with broad ramifications, ever more relevant, in our transitional medical age: treat the patient as an individual, or treat in line with the latest empirical study.

Quiz Page March 2010: Pruritus in Advanced CKD

2010-03-01

A 55-year-old man with a history of hypertension, type 2 diabetes, and advanced chronic kidney disease (CKD) presented with generalized pruritus for > 6 months. The patient had no history of allergic or atopic disease. Physical examination showed generalized xerosis and hyperpigmentation of the trunk (). No papules, pustules, or vesicles were noted, but hyperkeratosis and heavy crusting were present on both palms (). Routine blood tests showed the following values: urea nitrogen, 49 mg/dL (17.4 mmol/L); serum creatinine, 5.3 mg/dL (468.5 μmol/L, estimated glomerular filtration rate, 12.5 mL/min/1.73 m2 [0.21 mL/s/1.73 m2]); calcium, 9.2 mg/dL (2.3 mmol/L); phosphate, 5.2 mg/dL (1.6 mmol/L); and hemoglobin, 6.4 g/dL (64 g/L). Despite treatment with topical emollients, oral antihistamine, and UV-B light therapy, there was no improvement in pruritus. Additional blood tests showed a white blood cell count of 16.1 × 103/μL (16.1 × 109/L), eosinophil count of 5,876/μL (36.5%; normal, <5%), and an extremely high immunoglobulin E (IgE) level of 11,500 IU/mL (normal range, 0-100 IU/mL). C-reactive protein returned at 10.9 mg/L (normal range, <5 mg/L).

Masthead

2010-03-01

Editorial correspondence should be addressed to Andrew S. Levey, MD, Editor-in-Chief, AJKD, Tufts Medical Center, Box #391, 800 Washington Street, Boston, MA 02111. Telephone (617) 636-0599.

Editorial Board

2010-03-01

Feature Editors & Advisory Boards

2010-03-01

Scott J. Gilbert, MD Boston, MA

2010-03-01

April Highlights

2010-03-01

Bone Marrow Iron in CKD: Correlation With Functional Iron Deficiency Szu-Chun Hung and Der-Cherng Tarng

Abbreviated Information for Authors

2010-03-01

The American Journal of Kidney Diseases (AJKD) serves clinicians and scientists who treat and investigate kidney disease and associated conditions. AJKD is dedicated to providing high-quality, clinically relevant information in the form of original investigations, case reports, narrative reviews, editorials, and features.

Announcement

2010-03-01

The National Kidney Foundation 2010 Spring Clinical Meetings (SCM10) presents a unique opportunity for front line kidney health care providers to learn new developments related to the care of patients covering the entire spectrum of kidney disease. The meeting is specially designed for nephrologists in the private sector and academia as well as fellows and residents with a special interest in kidney disease, general internists, pharmacists, and advanced practitioners.

This Month in AJKD

2010-03-01

See Muntner et al, pages 441-451; and Becker and Wheeler, pages 415-418. In many CKD patients, blood pressure is not controlled to the target of < 130/80 mm Hg as recommended in most clinical practice guidelines. It is believed that a higher level of patient and doctor awareness of the presence of hypertension may lead to better control. In this issue, Muntner et al analyze blood pressure control data among 3,612 patients with CKD in the Chronic Renal Insufficiency Cohort (CRIC) study. 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. An editorial by Becker and Wheeler points out that these results are a strong example of why the upcoming KDIGO blood pressure guidelines relevant to stages 1-5 CKD patients worldwide are sorely needed, and that the guidelines must have rigorous implementation strategies if patients are to benefit fully.

American Journal of Kidney Diseases

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

Blood Pressure Control in CKD Patients: Why Do We Fail to Implement the Guidelines?

The Map Is Not the Territory—Mapping Out the Course and Cost of CKD

Quality of Life in CKD Patients Treated With Erythropoiesis-Stimulating Agents

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Intradialytic Hypertension: A Less-Recognized Cardiovascular Complication of Hemodialysis

Hypertension in the Developing World: Challenges and Opportunities

Pathophysiology and Management of Preeclampsia-Associated Severe Hyponatremia

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

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

Charge States of Deferasirox–Ferric Iron Complexes

Rhabdomyolysis and Acute Kidney Injury Associated With 2009 Pandemic Influenza A(H1N1)

Errata

Errata

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

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

TREAT Versus Treatment: A Patient's View of a Scientific Interpretation

Quiz Page March 2010: Pruritus in Advanced CKD

Masthead

Editorial Board

Feature Editors & Advisory Boards

Contents

April Highlights

Abbreviated Information for Authors

Announcement

This Month in AJKD