Journal of the American Society of Nephrology : JASN
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Obesity is linked to the development and progression of CKD, but whether bariatric surgery protects against CKD is poorly understood. We, therefore, examined whether bariatric surgery influences CKD risk. The study included 2144 adults who underwent bariatric surgery from March of 2006 to April of 2009 and participated in the Longitudinal Assessment of Bariatric Surgery-2 Study cohort. ⋯ Sensitivity analyses using year 1 as baseline to minimize the effect of weight loss on serum creatinine and differing eGFR equations offered qualitatively similar results. Treatment with bariatric surgery associated with an improvement in CKD risk categories in a large proportion of patients for up to 7 years, especially in those with moderate and high baseline risk. These findings support consideration of CKD risk in evaluation for bariatric surgery and further study of bariatric surgery as a treatment for high-risk obese patients with CKD.
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J. Am. Soc. Nephrol. · Mar 2018
Randomized Controlled TrialLong-Term Clinical Outcomes after Early Initiation of RRT in Critically Ill Patients with AKI.
Whether earlier initiation of RRT in critically ill patients with AKI can improve outcomes remains debated. We examined follow-up data from a large clinical trial to prospectively investigate the long-term outcomes associated with the timing of RRT initiation in such patients. We extended the follow-up of patients in the Early Versus Delayed Initiation of RRT in Critically Ill Patients with AKI (ELAIN) Trial from 90 days to 1 year after randomization for 230 (99.6%) patients. ⋯ The early initiation group had a 1-year all-cause mortality rate (56 of 111 [50.2%]) significantly lower than that of the delayed initiation group (83 of 119 [69.8%]; absolute difference, -19.6%; 95% CI, -32.0% to -7.2%; P<0.01). After 1 year, 16 of 55 (29.1%) and 23 of 36 (63.9%) surviving patients in the early and delayed groups, respectively, failed to recover renal function (absolute difference, -34.8%; 95% CI, -54.6% to -15.0%; P=0.001). In conclusion, early initiation of RRT in these critically ill patients with AKI significantly reduced the occurrence of major adverse kidney events, reduced mortality, and enhanced renal recovery at 1 year.
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J. Am. Soc. Nephrol. · Mar 2018
Exosomal CCL2 from Tubular Epithelial Cells Is Critical for Albumin-Induced Tubulointerstitial Inflammation.
Albuminuria is a key instigator of tubulointerstitial inflammation associated with CKD, but the mechanism through which filtered albumin propagates renal injury remains unclear. In this study, we explored the role in this process of exosome mRNA released from tubular epithelial cells (TECs). Compared with control mice, acute and chronic kidney injury models had more exosomes containing inflammatory cytokine mRNA, particularly the chemokine CCL2, in kidneys and urine. ⋯ Finally, in patients with IgA nephropathy, the increase of proteinuria correlated with augmented urinary excretion of exosomes with exaggerated expression of CCL2 mRNA. Moreover, the level of CCL2 mRNA in urinary exosomes correlated closely with levels of renal interstitial macrophage infiltration in these patients. Our studies demonstrate that the increasing release of exosomes that transfer CCL2 mRNA from TECs to macrophages constitutes a critical mechanism of albumin-induced tubulointerstitial inflammation.
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J. Am. Soc. Nephrol. · Feb 2018
Randomized Controlled Trial Multicenter StudyPhospholipase A2 Receptor 1 Epitope Spreading at Baseline Predicts Reduced Likelihood of Remission of Membranous Nephropathy.
The phospholipase A2 receptor (PLA2R1) is the major autoantigen in primary membranous nephropathy. Several PLA2R1 epitopes have been characterized, and a retrospective study identified PLA2R1 epitope spreading as a potential indicator of poor prognosis. Here, we analyzed the predictive value of anti-PLA2R1 antibody (PLA2R1-Ab) titers and epitope spreading in a prospective cohort of 58 patients positive for PLA2R1-Ab randomly allocated to rituximab (n=29) or antiproteinuric therapy alone (n=29). ⋯ Ten (58.8%) of the 17 patients who had epitope spreading at baseline and were treated with rituximab showed reversal of epitope spreading at month 6. In adjusted analysis, epitope spreading at baseline was associated with a decreased remission rate at month 6 (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.72; P=0.02) and last follow-up (median, 23 months; odds ratio, 0.14; 95% confidence interval, 0.03 to 0.64; P=0.01), independently from age, sex, baseline PLA2R1-Ab level, and treatment group. We propose that epitope spreading at baseline be considered in the decision for early therapeutic intervention in patients with primary membranous nephropathy.
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J. Am. Soc. Nephrol. · Dec 2017
Relationship of Kidney Injury Biomarkers with Long-Term Cardiovascular Outcomes after Cardiac Surgery.
Clinical AKI, measured by serum creatinine elevation, is associated with long-term risks of adverse cardiovascular (CV) events and mortality in patients after cardiac surgery. To evaluate the relative contributions of urine kidney injury biomarkers and plasma cardiac injury biomarkers in adverse events, we conducted a multicenter prospective cohort study of 968 adults undergoing cardiac surgery. On postoperative days 1-3, we measured five urine biomarkers of kidney injury (IL-18, NGAL, KIM-1, L-FABP, and albumin) and five plasma biomarkers of cardiac injury (NT-proBNP, H-FABP, hs-cTnT, cTnI, and CK-MB). ⋯ In contrast, four out of five postoperative cardiac injury biomarkers (NT-proBNP, H-FABP, hs-cTnT, and cTnI) strongly associated with the primary outcome. Mediation analyses demonstrated that cardiac biomarkers explained 49% (95% confidence interval, 1% to 97%) of the association between AKI and the primary outcome. These results suggest that clinical AKI at the time of cardiac surgery is indicative of concurrent CV stress rather than an independent renal pathway for long-term adverse CV outcomes.