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Am J Kidney Dis [journal]
- Urine Neutrophil Gelatinase-Associated Lipocalin and Risk of Cardiovascular Disease and Death in CKD: Results From the Chronic Renal Insufficiency Cohort (CRIC) Study. [JOURNAL ARTICLE]
- Am J Kidney Dis 2014 Oct 10.
Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria).Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study.3,386 participants with estimated glomerular filtration rate of 20 to 70mL/min/1.73m(2) enrolled from June 2003 through August 2008.Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration.Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011.Urine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories).There were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5ng/mL] vs lowest [≤6.9ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths.Urine NGAL was measured only once.Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths.
- Proliferative Glomerulonephritis Due to Monoclonal Deposition With Organized Substructures. [JOURNAL ARTICLE]
- Am J Kidney Dis 2014 Oct 10.
A growing number of monoclonal gammopathy-associated kidney diseases recently have been recognized. We present the case of a 54-year-old man who presented with acute kidney injury and hypocomplementemia. Kidney biopsy confirmed the presence of immunoglobulin G κ pseudothrombi with intracytoplasmic crystals in glomeruli and tubules. Levels of κ free light chains were elevated without a detectable monoclonal gammopathy, and bone marrow biopsy results were normal. After the first course of rituximab, cyclophosphamide, and dexamethasone in addition to daily plasmapheresis, kidney function recovered within 2 weeks and dialysis therapy was discontinued. Treatment for monoclonal protein-induced kidney disease should be considered in the setting of progressive decreased kidney function, even in the absence of a circulating monoclonal protein or cellular clone of origin.
- Membranous Nephropathy as a Manifestation of Graft-Versus-Host Disease: Association With HLA Antigen Typing, Phospholipase A2 Receptor, and C4d. [JOURNAL ARTICLE]
- Am J Kidney Dis 2014 Oct 7.
Glomerulopathy is an uncommon but increasingly recognized complication of hematopoietic cell transplantation. It typically manifests as membranous nephropathy, less commonly as minimal change disease, and rarely as proliferative glomerulonephritis. There is evidence to suggest that these glomerulopathies might represent manifestations of chronic graft-versus-host disease. In this report, we focus on membranous nephropathy as the most common form of glomerulopathy after hematopoietic cell transplantation. We present a case of membranous nephropathy that developed 483 days post-allogeneic hematopoietic stem cell transplantation in a patient with a history of acute graft-versus-host disease. We also share our experience with 4 other cases of membranous nephropathy occurring after allogeneic hematopoietic stem cell transplantation. Clinicopathologic correlates, including the association with graft-versus-host-disease, HLA antigen typing, glomerular deposition of immunoglobulin G (IgG) subclasses, subepithelial colocalization of IgG deposits with phospholipase A2 receptor staining, C4d deposition along the peritubular capillaries, and treatment, are discussed with references to the literature.
- Understanding by Older Patients of Dialysis and Conservative Management for Chronic Kidney Failure. [JOURNAL ARTICLE]
- Am J Kidney Dis 2014 Oct 7.
Older adults with chronic kidney disease stage 5 may be offered a choice between dialysis and conservative management. Few studies have explored patients' reasons for choosing conservative management and none have compared the views of those who have chosen different treatments across renal units.Qualitative study with semistructured interviews.Patients 75 years or older recruited from 9 renal units. Units were chosen to reflect variation in the scale of delivery of conservative management.Semistructured interviews audiorecorded and transcribed verbatim.Data were analyzed using thematic analysis.42 interviews were completed, 4 to 6 per renal unit. Patients were sampled from those receiving dialysis, those preparing for dialysis, and those choosing conservative management. 14 patients in each group were interviewed. Patients who had chosen different treatments held varying beliefs about what dialysis could offer. The information that patients reported receiving from clinical staff differed between units. Patients from units with a more established conservative management pathway were more aware of conservative management, less often believed that dialysis would guarantee longevity, and more often had discussed the future with staff. Some patients receiving conservative management reported that they would have dialysis if they became unwell in the future, indicating the conditional nature of their decision.Recruitment of older adults with frailty and comorbid conditions was difficult and therefore transferability of findings to this population is limited.Older adults with chronic kidney disease stage 5 who have chosen different treatment options have contrasting beliefs about the likely outcomes of dialysis for those who are influenced by information provided by renal units. Supporting renal staff in discussing conservative management as a valid alternative to dialysis for a subset of patients will aid informed decision making. There is a need for better evidence about conservative management to support shared decision making for older people with chronic kidney failure.
- Predicting Kidney Transplantation Outcomes Using Proteinuria Ascertained From Spot Urine Samples Versus Timed Urine Collections. [JOURNAL ARTICLE]
- Am J Kidney Dis 2014 Oct 7.
Proteinuria has been associated with transplant loss and mortality in kidney transplant recipients. Both spot samples (albumin-creatinine ratio [ACR] and protein-creatinine ratio [PCR]) and 24-hour collections (albumin excretion rate [AER] and protein excretion rate [PER]) have been used to quantify protein excretion, but which measurement is a better predictor of outcomes in kidney transplantation remains uncertain.Observational cohort study.Tertiary care center, 207 kidney transplant recipients who were enrolled in a prospective study to measure glomerular filtration rate. Consecutive patients who met inclusion criteria were approached.ACR and PCR in spot urine samples, AER and PER in 24-hour urine collections.Primary outcome included transplant loss, doubling of serum creatinine level, or death.Urine and serum creatinine were measured using a modified Jaffé reaction that had not been standardized by isotope-dilution mass spectrometry. Urine albumin was measured by immunoturbidimetry. Urine protein was measured by pyrogallol red molybdate complex formation using a timed end point method.Mean follow-up was 6.4 years and 22% developed the primary end point. Multivariable-adjusted areas under the receiver operating characteristic curves were similar for the different protein measurements: ACR (0.85; 95% CI, 0.79-0.89), PCR (0.84; 95% CI, 0.79-0.89), PER (0.86; 95% CI, 0.80-0.90), and AER (0.83; 95% CI, 0.78-0.88). C Index values also were similar for the different proteinuria measurements: 0.87 (95% CI, 0.79-0.95), 0.86 (95% CI, 0.79-0.94), 0.88 (95% CI, 0.82-0.94), and 0.86 (95% CI, 0.77-0.95) for log(ACR), log(PCR), log(PER), and log(AER), respectively.Single-center study. Measurement of proteinuria was at variable times posttransplantation.Spot and 24-hour measurements of albumin and protein excretion are similar predictors of doubling of serum creatinine level, transplant loss, and death. Thus, spot urine samples are a suitable alternative to 24-hour urine collection for measuring protein excretion in this population.
- Viable Podocyturia in Healthy Individuals: Implications for Podocytopathies. [LETTER]
- Am J Kidney Dis 2014 Oct 7.
- A Genetic Marker of Uric Acid Level, Carotid Atherosclerosis, and Arterial Stiffness: A Family-Based Study. [JOURNAL ARTICLE]
- Am J Kidney Dis 2014 Oct 6.
Hyperuricemia associates with atherosclerosis complications, but it is uncertain whether this relationship is causal in nature. The urate transporter GLUT9 (encoded by the SLC2A9 gene) is a major genetic determinant of serum uric acid level in humans. Because polymorphisms are distributed randomly at mating (Mendelian randomization), studies based on GLUT9 polymorphisms may provide unconfounded assessment of the nature of the link between uric acid and atherosclerosis.Cross-sectional study.Family-based study including 449 individuals in 107 families in a genetically homogeneous population in Southern Italy.Serum uric acid level, rs734553 allele, and age.Ultrasound biomarkers of atherosclerosis (intima-media thickness [IMT] and internal diameter) and pulse wave velocity (PWV).Serum uric acid level was dose-dependently associated with the T allele of rs734553, a polymorphism in SLC2A9 (P=8×10(-6)). Serum uric acid level was a strong modifier of the relationship between age and IMT in fully adjusted analyses (β=0.33; P=0.01), whereas no such relationship was found for internal diameter (β=-0.15; P=0.3) or PWV (β=0.10; P=0.6). The T allele coherently associated with carotid IMT, internal diameter, and PWV and emerged as an even stronger modifier of the age-IMT and age-internal diameter relationships in both crude and fully adjusted (β=0.40 [P<0.001] and β=0.48 [P=0.003], respectively) analyses.This is a hypothesis-generating study.Results in this family-based study implicate uric acid as an important modifier of the age-dependent risk for atherosclerosis. Trials testing uric acid-lowering interventions are needed to prove this hypothesis.
- Intravascular Foscarnet Crystal Precipitation Causing Multiorgan Failure. [JOURNAL ARTICLE]
- Am J Kidney Dis 2014 Oct 6.
We report a case of multiorgan failure resulting from treatment with the antiviral foscarnet in a kidney transplant recipient. Precipitation of foscarnet crystals was confirmed histologically from a biopsy of the transplant using optical and infrared microscopy. In addition to kidney damage resulting from foscarnet crystal precipitation in the tubular lumen and glomerular capillaries, the patient presented with pancreatitis, pancolitis, and myocarditis with shock. Interruption of the treatment led to rapid improvement in her general condition, but did not prevent permanent loss of the kidney transplant. When faced with unexplained multiorgan failure in a patient treated with foscarnet, one should assume this substance to be toxic. A kidney biopsy can confirm this diagnosis.
- The Kinetics of Cystatin C Removal by Hemodialysis. [LETTER]
- Am J Kidney Dis 2014 Oct 1.
- Fibroblast Growth Factor 23 and the Antiproteinuric Response to Dietary Sodium Restriction During Renin-Angiotensin-Aldosterone System Blockade. [JOURNAL ARTICLE]
- Am J Kidney Dis 2014 Sep 30.
Residual proteinuria during renin-angiotensin-aldosterone system (RAAS) blockade is a major renal and cardiovascular risk factor in chronic kidney disease. Dietary sodium restriction potentiates the antiproteinuric effect of RAAS blockade, but residual proteinuria remains in many patients. Previous studies linked high fibroblast growth factor 23 (FGF-23) levels with volume overload; others linked higher serum phosphate levels with impaired RAAS-blockade efficacy. We hypothesized that FGF-23 reduces the capacity of dietary sodium restriction to potentiate RAAS blockade, impairing the antiproteinuric effect.Post hoc analysis of cohort data from a randomized crossover trial with two 6-week study periods comparing proteinuria after a regular-sodium diet with proteinuria after a low-sodium diet, both during background angiotensin-converting enzyme inhibition.47 nondiabetic patients with CKD with residual proteinuria (median protein excretion, 1.9 [IQR, 0.8-3.1] g/d; mean age, 50±13 [SD] years; creatinine clearance, 69 [IQR, 50-110] mL/min).Plasma carboxy-terminal FGF-23 levels.Difference in residual proteinuria at the end of the regular-sodium versus low-sodium study period. Residual proteinuria during the low-sodium diet period adjusted for proteinuria during the regular-sodium diet period.Higher baseline FGF-23 level was associated with reduced antiproteinuric response to dietary sodium restriction (standardized β=-0.46; P=0.001; model R(2)=0.71). For every 100-RU/mL increase in FGF-23 level, the antiproteinuric response to dietary sodium restriction was reduced by 10.6%. Higher baseline FGF-23 level was a determinant of more residual proteinuria during the low-sodium diet (standardized β=0.27; P=0.003) in linear regression analysis adjusted for baseline proteinuria (model R(2)=0.71). There was no interaction with creatinine clearance (P interaction=0.5). Baseline FGF-23 level did not predict changes in systolic or diastolic blood pressure upon intensified antiproteinuric treatment.Observational study, limited sample size.FGF-23 levels are associated independently with impaired antiproteinuric response to sodium restriction in addition to RAAS blockade. Future studies should address whether FGF-23-lowering strategies may further optimize proteinuria reduction by RAAS blockade combined with dietary sodium restriction.