American Journal of Kidney Diseases - Articles in Press

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

2012-01-30

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

Association of Factor V Gene Polymorphism With Arteriovenous Graft Failure - Corrected Proof

2012-01-27

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

Longitudinal Progression Trajectory of GFR Among Patients With CKD - Corrected Proof

2012-01-27

Background: The traditional paradigm of glomerular filtration rate (GFR) progression in patients with chronic kidney disease (CKD) is a steady nearly linear decline over time. We describe individual GFR progression trajectories over 12 years of follow-up in participants in the African American Study of Kidney Disease and Hypertension (AASK). Study Design: Longitudinal observational study. Setting & Participants: 846 AASK patients with at least 3 years of follow-up and 8 GFR estimates. Measurements: Longitudinal GFR estimates from creatinine-based equations. Predictors: Patient demographic and clinical features. Outcomes: Probability of a nonlinear trajectory and probability of a period of nonprogression calculated for each patient from a Bayesian model of individual estimated GFR (eGFR) trajectories. Results: 352 (41.6%) patients showed a >0.9 probability of having either a nonlinear trajectory or a prolonged nonprogression period; in 559 (66.1%), the probability was >0.5. Baseline eGFR >40 mL/min/1.73 m2 and urine protein-creatinine ratio <0.22 g/g were associated with a higher likelihood of a nonprogression period. 74 patients (8.7%) had both a substantial period of stable or increasing eGFR and a substantial period of rapid eGFR decrease. Limitations: Clinical trial population; absence of direct GFR measurements. Conclusions: In contrast to the traditional paradigm of steady GFR progression over time, many patients with CKD have a nonlinear GFR trajectory or a prolonged period of nonprogression. These findings highlight the possibility that stable kidney disease progression can accelerate and, conversely, provide hope that CKD need not be relentlessly progressive. These results should encourage researchers to identify time-dependent factors associated with periods of nonprogression and other desirable trajectories.

TINU (Tubulointerstitial Nephritis and Uveitis) Syndrome Is Not Usually Associated With IgG4 Sclerosing Disease - Corrected Proof

Donald Houghton, Megan Troxell, Eric Fox, James Rosenbaum — 2012-01-27

Immunoglobulin G4 (IgG4) systemic disease has been implicated in a spectrum of sclerosing inflammatory lesions, including forms of interstitial nephritis, pancreatitis, sialadenitis, cholangitis, dacryoadenitis, mediastinitis, mesenteritis, and retroperitoneal fibrosis. Sugimoto et al described a patient with interstitial nephritis and subsequent anterior uveitis whose renal infiltrate was rich in IgG4-positive plasma cells, leading them to suggest that TINU (tubulointerstitial nephritis and uveitis) syndrome may be another condition of IgG4 systemic disease. Recently, we addressed this possibility by re-examining the renal interstitial infiltrates of 4 patients with TINU.

Erratum Regarding “Cystatin C in Prediction of Acute Kidney Injury: A Systematic Review and Meta-analysis” (Am J Kidney Dis 2011; 58:356-365) - Corrected Proof

2012-01-27

The article entitled “Cystatin C in Prediction of Acute Kidney Injury: A Systematic Review and Meta-analysis” (Zhang et al, American Journal of Kidney Diseases 2011;58(3):356-365) contained important errors in analysis and presentation of data.

Uromodulin in Kidney Injury: An Instigator, Bystander, or Protector? - Corrected Proof

Tarek M. El-Achkar, Xue-Ru Wu — 2012-01-25

Uromodulin, also known as Tamm-Horsfall protein, is a glycoprotein expressed exclusively by renal tubular cells lining the thick ascending limb of the loop of Henle. Although the physiologic functions of this protein remain elusive, significant progress has been made during the last decade that highlights the importance of uromodulin in the pathophysiology of various diseases, such as medullary cystic kidney disease, urinary tract infections, and nephrolithiasis. Meanwhile, there is renewed interest in the role of uromodulin in kidney injury, both acute and chronic. In this article, we review the existing evidence that supports a role for uromodulin in acute kidney injury, chronic kidney disease, and renal inflammation. Contrary to the conventional view of uromodulin as an instigator in kidney injury, new data from uromodulin knockout mice show a protective role for this protein in acute kidney injury, possibly through downregulating interstitial inflammation. In chronic kidney disease, uromodulin excretion, when adjusted for kidney function, is increased; the significance of this is unclear. Although it has been suggested that uromodulin exacerbates progressive kidney injury, we propose that the elevation in uromodulin secretion is instead reactive to injury and reflects an increase of uromodulin in the renal parenchyma, where it slows the injury process.

Metabolic Alkalosis From Unsuspected Ingestion: Use of Urine pH and Anion Gap - Corrected Proof

Joo-Hark Yi, Sang-Woong Han, June-Seok Song, Ho-Jung Kim — 2012-01-24

Underlying causes of metabolic alkalosis may be evident from history, evaluation of effective circulatory volume, and measurement of urine chloride concentration. However, identification of causes may be difficult for certain conditions associated with clandestine behaviors, such as surreptitious vomiting, use of drugs or herbal supplements with mineralocorticoid activity, abuse of laxatives or diuretics, and long-term use of alkalis. In these circumstances, clinicians often are bewildered by unexplained metabolic alkalosis from an incomplete history or persistent deception by the patient, leading to misdiagnosis and poor outcome. We present a case of severe metabolic alkalosis and hypokalemia with a borderline urine chloride concentration in an alcoholic patient treated with a thiazide. The cause of the patient's metabolic alkalosis eventually was linked to surreptitious ingestion of baking soda. This case highlights the necessity of a high index of suspicion for the diverse clandestine behaviors that can cause metabolic alkalosis and the usefulness of urine pH and anion gap in its differential diagnosis.

Myoglobin-Associated Acute Kidney Injury in the Setting of Ciprofloxacin Administration - Corrected Proof

Qi Qian, Samih H. Nasr, Clement O. Akogyeram, Sanjeev Sethi — 2012-01-20

Myoglobin-associated kidney injury typically is seen in severe rhabdomyolysis. Nontraumatic rhabdomyolysis may be triggered by direct drug toxicity, drug-drug interactions, and individual patient myopathic risk factors. We present a case of myoglobin-associated kidney failure in the setting of repeated ciprofloxacin administration in a lung transplant patient. Kidney biopsy was critical to establishing the diagnosis and avoiding future exposure.

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

2012-01-16

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

Dosing of Renal Replacement Therapy in Acute Kidney Injury - Corrected Proof

Anitha Vijayan, Paul M. Palevsky — 2012-01-13

The impact of the intensity of renal replacement therapy on outcomes in patients with acute kidney injury has been studied intensively during the past decade. In this review, we consider the concept of dose of renal replacement therapy in acute kidney injury and summarize the recent clinical trials addressing this topic. Although several single-center trials suggest that more intensive therapy is associated with improved outcomes, 2 large multicenter randomized trials do not find a benefit with higher doses of therapy. Based on these studies, we provide recommendations for the delivered intensity of renal replacement therapy in acute kidney injury.

Regional Citrate Versus Heparin Anticoagulation for Continuous Renal Replacement Therapy: A Meta-Analysis of Randomized Controlled Trials - Corrected Proof

Mei-Yi Wu, Yung-Ho Hsu, Chyi-Huey Bai, Yuh-Feng Lin, Chih-Hsiung Wu, Ka-Wai Tam — 2012-01-09

Background: Anticoagulation of the extracorporeal circuit is required in continuous renal replacement therapy (CRRT). Heparin is the classic choice for anticoagulation, although it may increase the risk of bleeding. Regional citrate anticoagulation reduces the risk of bleeding, but may cause hypocalcemia and metabolic disturbances. Study Design: Systematic review and meta-analysis of randomized controlled trials (RCTs). Setting & Population: Patients admitted to the intensive care unit with acute kidney injury that required CRRT. Selection Criteria for Studies: RCTs regardless of publication status or language. Intervention: Regional citrate versus heparin anticoagulation in CRRT. Outcomes: The primary outcomes were circuit survival time, the occurrence of major bleeding defined as a site of gross bleeding with a decrease in blood pressure or requiring transfusion of 2 or more units of red blood cells, metabolic alkalosis, hypocalcemia, and thrombocytopenia. The secondary outcome was cost. Results: 6 RCTs with 488 patients were identified. Citrate anticoagulation was associated with a significant decrease in bleeding (RR, 0.34; 95% CI, 0.17-0.65). Circuit survival time, the incidence of metabolic alkalosis, and thrombocytopenia showed no significant difference between groups. Hypocalcemia was more common in patients receiving citrate, although no clinical adverse event was reported in the included studies. Limitations: Significant heterogeneity in the primary outcome. Conclusion: The efficacy of citrate and heparin anticoagulation for CRRT was similar. However, citrate anticoagulation decreased the risk of bleeding with no significant increase in the incidence of metabolic alkalosis. We recommend citrate as an anticoagulation agent in patients who require CRRT but are at high risk of bleeding.

Incidence and Consequences of Acute Kidney Injury in Kidney Transplant Recipients - Corrected Proof

2012-01-09

Background: In the nontransplant setting, acute kidney injury (AKI) may lead to chronic kidney disease (CKD) and end-stage renal disease, but the epidemiology of AKI in transplant recipients has not been characterized. The purpose of this study was to determine the incidence and consequences of AKI in kidney transplant recipients outside the peritransplant period and unrelated to acute rejection. Study Design: Retrospective longitudinal cohort study. Setting & Participants: 27,232 adult Medicare-insured transplant recipients with transplant survival of 6 months or longer in the US Renal Data System in 1995-2000. Predictors: International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) hospital discharge diagnostic codes were used to identify AKI during the first 3 posttransplant years. Outcomes: Transplant loss from any cause, mortality (death with a functioning transplant), and death-censored transplant loss. Measurements: Estimated glomerular filtration rate calculated by the MDRD (Modification of Diet in Renal Disease) Study equation 6 months posttransplant. Results: 3,066 (11.3%) patients had 4,181 hospitalizations with AKI, of which 14.8% required dialysis therapy. The incidence of AKI more than doubled during the study, and AKI was more frequent in patients with lower levels of transplant function. AKI was associated independently with increased risk of transplant loss from any cause (HR, 2.74; 95% CI, 2.56-2.92), death with a functioning transplant (HR, 2.36; 95% CI, 2.14-2.60), and death-censored transplant loss (HR, 3.17; 95% CI, 2.91-3.46). However, AKI-associated risks paradoxically were higher in patients with earlier CKD stage. Limitations: Because of the limited sensitivity of ICD-9-CM codes for non–dialysis-requiring AKI events, the overall incidence of AKI likely is underestimated in this study. Conclusions: We conclude that AKI is increasingly common and associated with transplant failure and death. Later CKD stage increases the risk of AKI, but AKI-associated risks of transplant failure were greater in those with higher levels of kidney function (earlier CKD stage).

Discussions of the Kidney Disease Trajectory by Elderly Patients and Nephrologists: A Qualitative Study - Corrected Proof

2012-01-06

Background: Elderly patients with advanced kidney disease experience considerable disability, morbidity, and mortality. Little is known about the impact of physician-patient interactions on patient preparation for the illness trajectory. We sought to describe how nephrologists and older patients discuss and understand the prognosis and course of kidney disease leading to renal replacement therapy. Methods: We conducted focus groups and interviews with 11 nephrologists and 29 patients older than 65 years with advanced chronic kidney disease or receiving hemodialysis. Interviews were audiorecorded and transcribed. We used qualitative analytic methods to identify common and recurrent themes related to the primary research question. Results: We identified 6 themes that describe how the kidney disease trajectory is discussed and understood: (1) patients are shocked by their diagnosis, (2) patients are uncertain how their disease will progress, (3) patients lack preparation for living with dialysis, (4) nephrologists struggle to explain illness complexity, (5) nephrologists manage a disease over which they have little control, and (6) nephrologists tend to avoid discussions of the future. Patients and nephrologists acknowledged that prognosis discussions are rare. Patients tended to cope with thoughts of the future through avoidance by focusing on their present clinical status. Nephrologists reported uncertainty and concern for evoking negative reactions as barriers to these conversations. Conclusions: Patients and nephrologists face challenges in understanding and preparing for the kidney disease trajectory. Communication interventions that acknowledge the role of patient emotion and address uncertainty may improve how nephrologists discuss disease trajectory with patients and thereby enhance their understanding and preparation for the future.

Serum Cystatin C May Diagnose Rather Than Predict Acute Kidney Injury - Corrected Proof

Michael Haase, Rinaldo Bellomo, Anja Haase-Fielitz — 2012-01-06

We read the recent meta-analysis by Zhang et al with concern. Recalculation of the main result (an area under the curve [AUC] of 0.96 with a narrow confidence interval [0.95-0.97]) using the data provided shows an (un)weighted AUC of 0.8 regardless of whether the Liang et al study is included or not. The diagnostic odds ratio of 23.5 cannot be related to the reported AUC of 0.96.

Predictive Models for Acute Kidney Injury Following Cardiac Surgery - Corrected Proof

2011-12-30

Background: Accurate prediction of cardiac surgery–associated acute kidney injury (AKI) would improve clinical decision making and facilitate timely diagnosis and treatment. The aim of the study was to develop predictive models for cardiac surgery–associated AKI using presurgical and combined pre- and intrasurgical variables. Study Design: Prospective observational cohort. Settings & Participants: 25,898 patients who underwent cardiac surgery at Cleveland Clinic in 2000-2008. Predictor: Presurgical and combined pre- and intrasurgical variables were used to develop predictive models. Outcomes: Dialysis therapy and a composite of doubling of serum creatinine level or dialysis therapy within 2 weeks (or discharge if sooner) after cardiac surgery. Results: Incidences of dialysis therapy and the composite of doubling of serum creatinine level or dialysis therapy were 1.7% and 4.3%, respectively. Kidney function parameters were strong independent predictors in all 4 models. Surgical complexity reflected by type and history of previous cardiac surgery were robust predictors in models based on presurgical variables. However, the inclusion of intrasurgical variables accounted for all explained variance by procedure-related information. Models predictive of dialysis therapy showed good calibration and superb discrimination; a combined (pre- and intrasurgical) model performed better than the presurgical model alone (C statistics, 0.910 and 0.875, respectively). Models predictive of the composite end point also had excellent discrimination with both presurgical and combined (pre- and intrasurgical) variables (C statistics, 0.797 and 0.825, respectively). However, the presurgical model predictive of the composite end point showed suboptimal calibration (P < 0.001). Limitations: External validation of these predictive models in other cohorts is required before wide-scale application. Conclusions: We developed and internally validated 4 new models that accurately predict cardiac surgery–associated AKI. These models are based on readily available clinical information and can be used for patient counseling, clinical management, risk adjustment, and enrichment of clinical trials with high-risk participants.

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

2011-12-30

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

Effect of Frozen Storage on Urinary Concentration of Kidney Damage Markers - Corrected Proof

2011-12-30

Measurement of urinary concentrations of tubular damage markers has the potential to predict the outcome of acute kidney damage and the course of chronic kidney disease. Urine samples for such studies are often stored frozen for prolonged periods before analysis. Previously, we have shown that frozen storage for 1 year is associated with a decrease in urinary albumin concentration, with wide intersample variation in the extent of the decrease. We have also shown that this effect is more marked after storage at −20°C versus −80°C and that alkalinization of urine before freezing at −20°C partially prevents the decrease in albumin concentration and increase in variability. As yet, little is known about the effect of frozen storage on the concentration and variability of other urinary kidney damage markers. We therefore investigated the effect of storage at −20°C and −80°C on the concentration and variability of various urinary kidney damage markers and the effect of different storage protocols.

Long-term Risk of CKD in Children Surviving Episodes of Acute Kidney Injury in the Intensive Care Unit: A Prospective Cohort Study - Corrected Proof

2011-12-30

Background: The development of standardized acute kidney injury (AKI) definitions has allowed for a better understanding of AKI epidemiology, but the long-term renal outcomes of AKI in the pediatric critical care setting have not been well established. This study was designed to: (1) determine the incidence of chronic kidney disease (CKD) in children 1-3 years after an episode of AKI at a tertiary-care pediatric intensive care unit (ICU), (2) identify the proportion of patients at risk of CKD, and (3) compare ICU admission characteristics in those with and without CKD. Design: Prospective cohort study. Setting & Participants: Patients admitted to the British Columbia Children's Hospital pediatric ICU from 2006-2008 with AKI, as defined by AKI Network (AKIN) criteria. Surviving patients, most with short-term recovery from their AKI, were assessed at 1, 2, or 3 years after AKI. Predictors: Severity of AKI as defined by AKIN and several ICU admission characteristics, including demographics, diagnosis, severity of illness, and ventilation data. Outcomes & Measurements: CKD was defined as the presence of albuminuria and/or glomerular filtration rate (GFR) <60 mL/min/1.73 m2. Being at risk of CKD was defined as having a mildly decreased GFR (60-90 mL/min/1.73 m2), hypertension, and/or hyperfiltration (GFR ≥150 mL/min/1.73 m2). Results: The proportion of patients with AKI stages 1, 2, and 3 were 44 of 126 (35%), 47 of 126 (37%), and 35 of 126 (28%), respectively. The number of patients with CKD 1-3 years after AKI was 13 of 126 (10.3% overall; 2 of 44 [4.5%] with stage 1, 5 of 47 [10.6%] with stage 2, and 6 of 35 [17.1%] with stage 3; P = 0.2). In addition, 59 of 126 (46.8%) patients were identified as being at risk of CKD. Limitations: Several patients identified with AKI were lost to follow-up, with the potential of underestimating the incidence of CKD. Conclusions: In tertiary-care pediatric ICU patients, ∼10% develop CKD 1-3 years after AKI. The burden of CKD in this population may be higher with further follow-up because several patients were identified as being at risk of CKD. Regardless of the severity of AKI, all pediatric ICU patients should be monitored regularly for long-term kidney damage.

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

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

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

Factors Associated With Intradialytic Systolic Blood Pressure Variability - Corrected Proof

2011-12-30

Background: Although blood pressure lability during hemodialysis has long been recognized, little is known about factors that promote nonsystematic intradialytic blood pressure variability. Study Design: Prospective observational cohort. Setting & Participants: Random cluster sample of 218 prevalent hemodialysis patients treated at 5 participating DaVita Dialysis units. Predictors: Clinical variables that may plausibly influence intradialytic systolic blood pressure (SBP) variability. Outcomes: SBP variability as described by: (1) the deviation of SBP from its anticipated course (primary metric) and (2) the absolute value of the difference between successive SBP measurements (secondary metric). Measurements: SBPs measured and recorded (n = 19,170) per clinical protocol during hemodialysis treatments (n = 2,422; median 11 per patient) occurring in the first 30 days of study. Predictors were assessed through standardized interview, examination, and medical record abstraction. Results: Results were similar when SBP variability was considered in terms of the primary and secondary metrics. Older age and longer dialysis vintage were associated with increased SBP variability, whereas other patient characteristics were not. Greater fluid removal during hemodialysis (whether considered as volume or rate either absolute or relative to total-body water) was associated with greater SBP variability independently of its effects on net pre- to posttreatment SBP reduction. Neither number nor dialyzability of antihypertensive medications nor individual classes of agents showed an association with SBP variability. Limitations: Over-representation of African Americans and patients with congestive heart failure; observational design; use of clinically measured blood pressures; absence of medication adherence confirmation. Conclusions: Increased intradialytic SBP variability is associated with greater dialytic fluid removal and rate, as well as demographic characteristics, such as older age and dialysis vintage. Further work is needed to confirm these findings and measure associations between SBP variability and clinical outcomes.

Eculizumab in the Treatment of Atypical Hemolytic Uremic Syndrome in Infants - Corrected Proof

2011-12-26

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

Erratum Regarding “Factors Associated With Kidney Disease Progression and Mortality in a Referred CKD Population” (Am J Kidney Dis 2011; 56:1072-1081) - Corrected Proof

2011-12-26

In the article entitled “Factors Associated With Kidney Disease Progression and Mortality in a Referred CKD Population” (Hoefield et al, American Journal of Kidney Diseases 56(6):1072-1081, 2011), the data given for current smokers inadvertently listed the values for nonsmokers instead. Specifically, in Table 1, the values listed for percent current smokers should have been 13.7 for all patients, and 15.5, 13.5, 12.1, and 16.2 for the >45, 30-44, 15-29, and <15 mL/min/1.73 m2 categories, respectively, of estimated glomerular filtration rate. Likewise, in the first sentence of the second paragraph of the Results section, the statement that “417 (31.5%) were current smokers” should have been given as “181 (13.7%) were current smokers”.

New Anemia Therapies: Translating Novel Strategies From Bench to Bedside - Corrected Proof

Iain C. Macdougall — 2011-12-23

Recombinant human erythropoietin (epoetin) has been available for the treatment of renal anemia for more than 20 years, and within the last decade two molecularly engineered analogues darbepoetin alfa and pegylated epoetin beta were introduced as longer-acting erythropoiesis-stimulating agents. Recently, newer strategies for correcting anemia have been explored, some of which remain in the laboratory while others are translating across into clinical trials. Peginesatide has completed phase 3 clinical trials for the treatment of anemia associated with chronic kidney disease; this molecule is immunologically distinct from the erythropoietic proteins, with no cross-reactivity with anti-erythropoietin antibodies. HIF (hypoxia inducible factor) stabilization involves the pharmacologic inhibition of prolyl hydroxylation of HIF-α (the major transcription factor controlling erythropoietin gene expression), thereby preventing its degradation in the proteasome. Hepcidin is the master regulator of iron metabolism, and this peptide is upregulated in inflammatory conditions, including uremia; its antagonism has been shown to cause amelioration of inflammatory anemia in animal models. For the time being, erythropoiesis-stimulating agent therapy remains the mainstay of anemia management in chronic kidney disease, but it is possible that one or more of the strategies discussed in this review may have a future role in the treatment of this condition.

Noncontrolled Trial of Monovalent AS03A-Adjuvanted Vaccine for 2009 Pandemic Influenza A(H1N1) in Long-term Dialysis Patients and Transplant Recipients - Corrected Proof

2011-12-23

Vaccination is an important means to reduce the risk of influenza infection. Vaccination strategies against 2009 pandemic influenza A(H1N1) include widely used adjuvanted monovalent influenza vaccines. This report summarizes the efficacy and safety of an AS03A-adjuvanted H1N1 vaccine in patients with end-stage renal disease with and without kidney transplant.

ANCA-Associated Glomerulonephritis in Systemic-Onset Juvenile Idiopathic Arthritis - Corrected Proof

2011-12-22

Systemic-onset juvenile idiopathic arthritis is an inflammatory disease of unknown cause and is not commonly associated with kidney involvement. We describe 3 patients with systemic-onset juvenile idiopathic arthritis with high disease activity who developed antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis 1-6 years after the onset of systemic-onset juvenile idiopathic arthritis. Renal and systemic-onset juvenile idiopathic arthritis remission occurred in one patient under anti–interleukin 1 (anti–IL-1) treatment associated with immunosuppressive drugs. The other 2 patients developed end-stage renal disease, and one of those patients died. This report suggests that the diagnosis of ANCA-associated glomerulonephritis must be considered in patients with systemic-onset juvenile idiopathic arthritis with persistently active systemic disease who present with proteinuria. Furthermore, use of an anti–IL-1 agent might be an effective therapeutic option.

Antibodies to M-Type Phospholipase A2 Receptor (PLA2R) and Membranous Lupus Nephritis - Corrected Proof

Iva Gunnarsson, Wolfgang Schlumberger, Johan Rönnelid — 2011-12-19

The diagnosis of glomerulonephritis generally is based on kidney biopsy; to date, only a few diagnostic serologic markers have been described. To discriminate between different forms of nephritis without having to perform a kidney biopsy, new serologic biomarkers are needed. In systemic lupus erythematosus (SLE), the most common and severe forms of lupus nephritis are classified as either proliferative (ISN/RPS [International Society of Nephrology/Renal Pathology Society] class III/IV) or membranous (ISN/RPS class V) forms.

Predicting the Number of US Medical Graduates Entering Adult Nephrology Fellowships Using Search Term Analysis - Corrected Proof

Tejas Desai, Maria Ferris, Cynthia Christiano, Xiangming Fang — 2011-12-19

There has been a worrisome decrease in the number of applicants to nephrology fellowship training programs. First identified in 2008, the number of nephrology applications has been decreasing annually since 2002. Given the annual increase in kidney disease and projected shortage of nephrologists, this downward trend is concerning. Various studies have suggested that a lack of interest in nephrology is a key factor in this decrease. Parker et al have used the percentage of adult nephrology positions filled by US medical graduates as a surrogate marker of nephrology interest, but this measurement is a late indicator. Investigations have suggested that the frequency of internet search term use can serve as a leading and accurate indicator of future events. We hypothesize that the frequency of nephrology-specific search term queries can predict the percentage of US medical graduates entering nephrology fellowships.

Cardiovascular Disease Mortality in Kidney Transplant Recipients: No Light at the End of the Tunnel? - Corrected Proof

Gere Sunder-Plassmann, Manuela Födinger, Marcus D. Säemann — 2011-12-19

Commentary on Bostom AG, Carpenter MA, Kusek JW, et al. Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial. Circulation. 2011;123(16):1763-1770.

Risk of Herpes Zoster in Patients Treated With Long-term Hemodialysis: A Matched Cohort Study - Corrected Proof

Chien-Chun Kuo, Chien-Te Lee, I-Ming Lee, Shu-Chen Ho, Chun-Yuh Yang — 2011-12-19

Background: The risk of herpes zoster in the dialysis population relative to the general population is not known. The aim of this study was to perform a population-based cohort study to investigate the risk of herpes zoster after the initiation of hemodialysis therapy in patients with end-stage renal disease (ESRD) in Taiwan, a country with the highest incidence of ESRD in the world. Study Design: Matched cohort study. Setting & Participants: Data were obtained from the Taiwan National Health Insurance Research Database. 843 patients who were beginning hemodialysis therapy in 1999-2003 were included as the study cohort and 3,372 patients without ESRD matched for age and sex were included as a comparison cohort. A multivariate frailty Cox proportional hazard regression model was used to adjust for confounding and compare the 6-year herpes zoster–free survival rate between these 2 cohorts. Predictors: Hemodialysis. Outcomes: Herpes zoster. Results: Mean years of follow-up were 4.73 and 5.49 for the hemodialysis and comparison cohorts, respectively. 868 patients developed herpes zoster throughout the study period, 294 from the hemodialysis cohort and 574 from the comparison cohort. The incidence rate of herpes zoster (73.34 events/1,000 person-year) was significantly higher in the hemodialysis cohort than in the control cohort (31.03 events/1,000 person-years). After adjusting for potential confounders, the adjusted HR of herpes zoster was 1.98 (95% CI, 1.72-2.27). Limitations: We expect that some patients with mild zoster chose not to seek medical help. Conclusions: We conclude that patients treated with long-term hemodialysis are at an increased risk of herpes zoster compared with the general population.

Hypertension and Symptomatic Hypokalemia in a Patient With Simultaneous Unilateral Stenoses of Intrarenal Arteries and Mesangioproliferative Glomerulonephritis - Corrected Proof

2011-12-12

We present the case of a young patient with hypertension and unprovoked symptomatic hypokalemia. His workup uncovered secondary aldosteronism, moderate proteinuria, and, quite unusually, concurrent chronic hepatitis B. Detailed investigations, including renal angiography, renal vein sampling, and kidney biopsy, showed unilateral renin hypersecretion due to intrarenal arterial stenoses and mesangioproliferative glomerulonephritis, presumed to be secondary to hepatitis B infection. Targeted pharmacotherapy reversed all clinical manifestations, normalizing blood pressure and serum potassium level and achieving full remission of proteinuria and loss of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg), and a dramatic decrease in viral load.

A Family With Hyponatremia and the Nephrogenic Syndrome of Inappropriate Antidiuresis - Corrected Proof

2011-12-12

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is an X-linked disorder caused by activating mutations in arginine vasopressin receptor 2 (AVPR2), resulting in persistently concentrated urine. We report on a family affected by NSIAD with the known mutation R137C, an arginine to cysteine substitution at amino acid 137. The spectrum of symptoms varied markedly and ranged from infrequent voiding to incidentally noted hyponatremia to recurrent admissions with hyponatremic seizures. There was evidence for physiologic compensatory mechanisms: most affected members intuitively compensated for the concentrated urine by curtailing their fluid intake. Before the genetic diagnosis, these members had recognized each other by their infrequent voiding, which especially suited one patient, a London cab driver. Interestingly, after water deprivation, urine osmolality was significantly lower in patients compared with unaffected members, suggesting desensitization of the downstream signaling pathway with persistent AVPR2 activation. Urine osmolality was as low as 241 mOsm/kg (241 mmol/kg) in patients, which could obfuscate the diagnosis. The development of symptoms of hyponatremia was strikingly different in the 2 male patients: one patient was asymptomatic with a plasma sodium level of 120 mEq/L (120 mmol/L), whereas another experienced seizures with similar values. Investigations of such genetically defined patients show clues for the understanding of human physiology and inform diagnosis and clinical management.

Kidney Disease in People With Diabetes: The Expanding Epidemic - Corrected Proof

Elizabeth Selvin, Stephen P. Juraschek, Josef Coresh — 2011-12-12

Commentary on de Boer IH, Rue TC, Hall YN, Heagerty PJ, Weiss NS, Himmelfarb J. Temporal trends in the prevalence of diabetic kidney disease in the United States. JAMA. 2011;305(24):2532-2539.

Prevalence of Inadequate Platelet Inhibition by Clopidogrel in Patients Receiving Hemodialysis - Corrected Proof

2011-12-12

A variable antiplatelet response to clopidogrel is a well-recognized phenomenon studied mostly in patients with percutaneous coronary intervention (PCI), for whom high on-treatment platelet reactivity is associated with an elevated risk of adverse events, including stent thrombosis. Patients undergoing maintenance hemodialysis (HD) therapy present enhanced platelet reactivity, and clopidogrel often is prescribed to prevent atherothrombotic or, specifically, vascular access thrombotic complications. However, few and contradictory data for clopidogrel's platelet inhibitory effect in HD patients are available. In a randomized comparison of prasugrel versus high clopidogrel in HD patients, we identified 21 of 25 (84%) with high on-treatment platelet reactivity. In the present prospective multicenter study, we extend this observation by defining the prevalence of high on-treatment platelet reactivity in a larger number of HD patients.

Fibroblast Growth Factor 23 and CKD Prognosis - Corrected Proof

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

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

Comparison of Concurrent Complications of CKD by 2 Risk Categorization Systems - Corrected Proof

2011-11-24

Background: Using both estimated glomerular filtration rate (eGFR) and proteinuria to classify the severity of chronic kidney disease (CKD) has been proposed. The utility of a staging system incorporating both eGFR and proteinuria for guiding the evaluation of concurrent CKD complications is not known.Study Design: Cross-sectional analysis.Setting & Participants: 30,528 participants in the US National Health and Nutrition Examination Survey conducted in 1988-1994 and 1999-2006 (n = 8,242 for hyperparathyroidism).Predictors: Classification system that uses both eGFR and proteinuria (alternative) and a system that primarily uses eGFR (NKF-KDOQI [National Kidney Foundation's Kidney Disease Outcomes Quality Initiative]).Outcomes: Prevalence of anemia, acidosis, hyperphosphatemia, hypoalbuminemia, hyperparathyroidism, and hypertension.Measurements: GFR estimated from the CKD Epidemiology Collaboration (CKD-EPI) equation and proteinuria assessed using urine albumin-creatinine ratio.Results: Prevalences of hypoalbuminemia, hypertension, and hyperparathyroidism increased with more severe CKD using the NKF-KDOQI system. For example, the prevalence of hyperparathyroidism was 9.1%, 11.1%, 28.2%, and 72.5% for stages 1, 2, 3 and 4, respectively. Similarly, prevalences of anemia, acidosis, and hyperphosphatemia increased progressively from stage 2 through 4. With the alternative system, prevalences of anemia, hyperphosphatemia, hypertension, and hyperparathyroidism were lower in stage 3 than in stage 2. For example, the prevalence of hyperparathyroidism was 13.5%, 40.3%, 22.2%, and 63.4% for stages 1, 2, 3 and 4, respectively. Applying the alternative system, participants without each complication were more likely to be reclassified appropriately to lower stages (eg, overall net reclassification index of −6.5% for hyperparathyroidism). However, participants with complications (except for hypoalbuminemia) were more likely to be reclassified inappropriately to lower stages.Limitations: Use of a single creatinine measurement to estimate GFR and single measurement to assess albumin-creatinine ratio. Small number of participants with CKD stage 4.Conclusions: The NKF-KDOQI system may better identify patients with certain concurrent CKD complications compared with systems using eGFR and proteinuria.

Association Between GFR, Proteinuria, and Adverse Outcomes Among White, Chinese, and South Asian Individuals in Canada - Corrected Proof

2011-11-24

Background: We investigated the association between proteinuria, estimated glomerular filtration rate (eGFR), and risk of mortality and kidney failure in white, Chinese, and South Asian populations.Study Design: Population-based cohort study.Setting & Participants: Participants from Alberta, Canada, with a serum creatinine and urine protein dipstick measurement from January 1, 2005, to December 31, 2005.Predictor: White, Chinese, or South Asian ethnicity.Outcomes: Prevalence of proteinuria by level of eGFR (estimated using the MDRD [Modification of Diet in Renal Disease] Study equation) and the association between eGFR, proteinuria, and all-cause mortality and kidney failure.Measurements: Rates of all-cause mortality and kidney failure per 1,000 person-years were calculated using Poisson regression by ethnicity, eGFR level, and proteinuria level while adjusting for sociodemographic variables and comorbid conditions.Results: Of 491,729 participants, 5.3% were Chinese and 4.7% were South Asian. For participants with eGFR <60 mL/min/1.73 m2, the prevalence of heavy proteinuria was higher in Chinese and South Asians compared with whites. Compared with whites, adjusted rates of death were significantly lower for Chinese and South Asian populations (rate ratios, 0.67 [95% CI, 0.56-0.80] and 0.73 [95% CI, 0.59-0.88], respectively); these rate ratios did not vary by eGFR and proteinuria levels.Limitations: Using surname to identify ethnicity has the potential for misclassification due to name changes and identical last names from different ethnic groups. Also, to be eligible for inclusion, participants had to have a measurement of serum creatinine and urine dipstick proteinuria.Conclusions: Although increasing proteinuria and lower eGFR predicted mortality and progression to kidney failure in all 3 ethnic groups, both Chinese and South Asian populations experienced a lower risk of death and similar risk of kidney failure compared with whites at all eGFR and proteinuria levels. Studies exploring this association further are required.

Bone and Mineral Metabolism and Fibroblast Growth Factor 23 Levels After Kidney Donation - Corrected Proof

2011-11-17

Background: Living kidney donation offers a unique setting to study changes in phosphate and vitamin D homeostasis attributable to mild isolated decreases in estimated glomerular filtration rate (eGFR).Study Design: Cross-sectional study.Setting & Participants: 198 living kidney donors and 98 nondonor controls from 9 transplant centers across 3 countries. For donors, median time after donation was 5.3 years. At assessment, donors had a lower eGFR than controls (73 vs 98 mL/min/1.73 m2).Predictor: Living kidney donation (mildly decreased eGFR).Outcomes: Biochemical markers of chronic kidney disease–mineral and bone disorder.Measurements: Serum creatinine, total serum calcium, serum and urine inorganic phosphate, plasma intact parathyroid hormone, serum calcidiol and calcitriol, renal fractional excretion of inorganic phosphate, and intact serum fibroblast growth factor 23 (FGF-23).Results: Serum FGF-23 levels were significantly higher in donors (38.1 vs 29.7 pg/mL; P < 0.001). For every 10-mL/min/1.73 m2 decrease in eGFR, FGF-23 level was higher by 3.2 (95% CI, 2.0-4.4) pg/mL. Compared with controls, donors showed higher renal tubular fractional excretion of inorganic phosphate (17.8% vs 12.3%; P < 0.001), lower serum phosphate (0.97 vs 1.02 mmol/L; P = 0.03), and lower serum calcitriol values (63 vs 77 pmol/L; P < 0.001). Serum calcium levels were not significantly different between the 2 groups. Plasma intact parathyroid hormone levels were significantly higher in donors (5.7 vs 5.0 pmol/L; P = 0.03), but were not correlated with FGF-23 or calcitriol levels.Limitations: Enrollment of a small proportion of past donors at participating centers; assessment of only postdonation values; unable to assess seasonal variation or other temporal patterns in biochemical markers; assessment of kidney function was based on eGFR, not measured GFR.Conclusions: The FGF-23 pathway may be activated in living kidney donors who show early biochemical changes compatible with chronic kidney disease–mineral and bone disorder. Whether these changes influence bone mineral density and fracture rates warrants consideration.

Multiple Versus Single and Other Estimates of Baseline Proteinuria Status as Predictors of Adverse Outcomes in the General Population - Corrected Proof

2011-11-07

Background: The association of proteinuria and adverse clinical outcomes is well established. The optimal method of classifying proteinuria status for study participants in whom it is measured multiple times is unknown, especially when the frequency of measurement varies between participants.Study Design: Population-based longitudinal study.Setting & Participants: All adults with at least one outpatient serum creatinine measurement in the province of Alberta, Canada.Factor: Proteinuria (dipstick, albumin-creatinine ratio [ACR]).Outcomes: All-cause mortality, end-stage renal disease, or doubling of serum creatinine level.Measures: All outpatient urine dipstick and ACR measurements in the 6-month period before and after the first (index) estimated glomerular filtration rate were used to establish baseline proteinuria. Dipstick measures were analyzed as ceiling (median value up to the next integer), floor (median value down to the next integer), high (single highest dipstick value), low (single lowest dipstick value), and first (first available dipstick value only). Measurements of ACR were evaluated similarly and a median (median of all ACR measurements) value was added.Results: Of 920,985 participants, 17% (n = 160,548) had multiple dipstick urinalysis measurements and 22% (n = 22,814) had multiple ACR measurements. With single measurements, absolute rates of mortality and renal outcomes were lower in every proteinuria category compared with multiple measurements. In contrast, the relative increase in rate ratio was greater with increasing proteinuria in patients with single measurements compared with those with multiple measurements. In all classification systems evaluated, more severe proteinuria was associated with significantly higher rates of both outcomes (all P for trend <0.001).Limitations: Lack of a gold standard for choosing between methods.Conclusions: Rates of adverse outcomes related to multiple baseline proteinuria/albuminuria measurements were similar, independent of the measure of baseline proteinuria that was used to combine results. In contrast, discarding follow-up measurements and relying on only the first measurement led to lower estimates of absolute and relative risk for each proteinuria category.

Evidence and Outcomes in CKD - Corrected Proof

Bertram L. Kasiske, Kai-Uwe Eckardt — 2011-11-07

Commentary on recent studies from the Chronic Kidney Disease Prognosis Consortium published in The Lancet1 and Kidney International.

Circulating Mediators of Focal Segmental Glomerulosclerosis: Soluble Urokinase Plasminogen Activator Receptor in Context - Corrected Proof

Samir M. Parikh — 2011-10-28

Commentary on Wei C, El Hindi S, Li J, et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med. 2011;17(8):952-960.

Self-reported Sleep Duration and Prediction of Proteinuria: A Retrospective Cohort Study - Corrected Proof

2011-10-24

Background: Although multiple studies have shown that sleep duration is a predictor of cardiovascular diseases and mortality, few studies have reported an association between sleep duration and chronic kidney disease.Study Design: Retrospective cohort study.Setting & Participants: 6,834 employees of Osaka University aged 20-65 years who visited Osaka University Healthcare Center for their mandatory annual health examinations between April 2006 and March 2010 and did not have estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, proteinuria, or treatment for self-reported kidney disease.Predictor: Self-reported questionnaires about life style, including sleep duration, and blood and urine testing at the first examinations during the study period. An association between sleep duration and outcome was assessed using multivariate Poisson regression models adjusting for clinically relevant factors.Outcome: Time to the development of proteinuria defined as 1+ or higher by dipstick test.Results: Self-reported baseline sleep duration was 6.0 ± 0.9 hours, which reflected the mean sleep duration during a median of 2.5 (25th-75th percentile, 1.4-3.9) years of the observational period. Development of proteinuria was observed in 550 employees (8.0%). A multivariate Poisson regression model clarified that shorter sleep duration, especially 5 or fewer hours, was associated with the development of proteinuria in a stepwise fashion (vs 7 hours; incidence rate ratios of 1.07 [95% CI, 0.87-1.33; P = 0.5], 1.28 [95% CI, 1.00-1.62; P = 0.05], and 1.72 [95% CI, 1.16-2.53; P = 0.007] for 6, 5, and ≤4 hours, respectively), along with younger age, heavier current smoking, trace urinary protein by dipstick test, higher eGFR, higher serum hemoglobin A1c level, and current treatment for heart disease. A stepwise association between shorter sleep duration and the development of proteinuria also was verified in 4,061 employees who did not work the night shift.Limitations: Self-reported sleep duration might be biased. Results in a single center should be confirmed in the larger cohort including different occupations.Conclusion: Short sleep duration, especially 5 or fewer hours, was a predictor of proteinuria.

Urgent-Start Peritoneal Dialysis: A Quality Improvement Report - Corrected Proof

Arshia Ghaffari — 2011-10-24

Background: Compared with hemodialysis, peritoneal dialysis (PD) is a cost-effective and patient-centered option with an early survival advantage, yet only 7% of patients with end-stage renal disease in the United States receive PD. PD underutilization is due in part to nephrologists' unfamiliarity with directly starting PD in patients who present with kidney failure requiring urgent initiation of dialysis.Design: Quality improvement report.Setting & Participants: Single-center study whereby 18 patients who presented urgently with chronic kidney disease stage 5 without a plan for dialysis modality were offered PD as the initial modality of dialysis. Concurrently, 9 patients started on PD therapy nonurgently were included as the comparative group.Quality Improvement Plan: An urgent-start PD program was developed to support and standardize the process by which patients without a plan for dialysis modality were started on PD. This included rapid PD access placement, PD nursing education, and administrative support. Standardized protocols were created for modality selection, initial prescription, and prevention and management of complications.Measures: Short-term (90-day) clinical outcomes (Kt/V, hemoglobin, iron saturation, parathyroid hormone, phosphorus, calcium, and albumin) and complications (peritonitis, exit-site infections, leaks, and catheter malfunction) were compared between the urgent-start and non–urgent-start PD groups.Results: Short-term clinical outcomes were similar between the 2 groups for all parameters except uncorrected serum calcium level, which was lower in the urgent-start group (P = 0.02). Peritonitis, exit-site infection, catheter-related complications, and other complications were similar between the 2 groups, although the number of minor leaks was higher in the urgent-start group.Limitations: This is a single-center nonrandomized study with a small sample size.Conclusions: Our structured program shows safety and feasibility in starting PD in patients with kidney failure who present without a plan for dialysis modality. The steps laid out in this report can provide the framework for creating local urgent-start PD programs.

Patients Who Plan for Conservative Care Rather Than Dialysis: A National Observational Study in Australia - Corrected Proof

2011-10-21

Background: It is unclear how many incident patients with stage 5 chronic kidney disease (CKD) referred to nephrologists are presented with information about conservative care as a treatment option and how many plan not to dialyze.Study Design: National observational survey study with random-effects logistic regression.Setting & Participants: Incident adult and pediatric pre-emptive transplant, dialysis, and conservative-care patients from public and private renal units in Australia, July to September 2009.Predictors: Age, sex, health insurance status, language, time known to nephrologist, timing of information, presence of caregiver, unit conservative care pathway, and size of unit.Outcomes & Measurements: The 2 main outcome measures were information provision to incident patients about conservative care and initial treatment regardless of planned conservative care.Results: 66 of 73 renal units (90%) participated. 10 (15%) had a formal conservative-care pathway. Of 721 incident patients with stage 5 CKD, 470 (65%) were presented with conservative care as a treatment option and 102 (14%) planned not to dialyze; median age was 80 years. Multivariate analysis for information provision showed that patients older than 65 years (OR, 3.40; 95% CI, 1.97-5.87) and those known to a nephrologist for more than 3 months (OR, 6.50; 95% CI, 3.18-13.30) were more likely to receive information about conservative care. Patients with conservative care as planned initial treatment were more likely to be older than 65 years (OR, 4.71; 95% CI, 1.77-12.49) and women (OR, 2.23; 95% CI, 1.23-4.02) than those who started dialysis therapy. Those with private health insurance were less likely to forgo dialysis therapy (OR, 0.40; 95% CI, 0.17-0.98).Limitations: Cross-sectional design prohibited longer term outcome measurement. Excluded patients with stage 5 CKD managed in the community.Conclusions: 1 in 7 patients with stage 5 CKD referred to nephrologists plans not to dialyze. Comprehensive service provision with integrated palliative care needs to be improved to meet the demands of the aging population.

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

2011-09-29

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

The Risk of Infection-Related Hospitalization With Decreased Kidney Function - Corrected Proof

2011-09-12

Background: Moderate kidney disease may predispose to infection. We sought to determine whether decreased kidney function, estimated by serum cystatin C level, was associated with the risk of infection-related hospitalization in older individuals.Study Design: Cohort study.Setting & Participants: 5,142 Cardiovascular Health Study (CHS) participants with measured serum creatinine and cystatin C and without estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 at enrollment.Predictor: The primary exposure of interest was eGFR using serum cystatin C level (eGFRSCysC).Outcome: Infection-related hospitalizations during a median follow-up of 11.5 years.Results: In adjusted analyses, eGFRSCysC categories of 60-89, 45-59, and 15-44 mL/min/1.73 m2 were associated with 16%, 37%, and 64% greater risk of all-cause infection-related hospitalization, respectively, compared with eGFRSCysC ≥90 mL/min/1.73 m2. When cause-specific infection was examined, eGFRSCysC of 15-44 mL/min/1.73 m2 was associated with an 80% greater risk of pulmonary and 160% greater risk of genitourinary infection compared with eGFRSCysC ≥90 mL/min/1.73 m2.Limitations: No measures of urinary protein, study limited to principal discharge diagnosis.Conclusions: Lower kidney function, estimated using cystatin C level, was associated with a linear and graded risk of infection-related hospitalization. These findings highlight that even moderate degrees of decreased kidney function are associated with clinically significant higher risks of serious infection in older individuals.