SummaryBackground and objectives At least four definitions of AKI have recently been proposed. This study sought to characterize the epidemiology of AKI according to the most recent consensus definition proposed by the Kidney Disease Improving Global Outcomes (KDIGO) Work Group, and to compare it with three other definitions.Design, setting, participants, & measurements This was a retrospective cohort study of 31,970 hospitalizations at an academic medical center in 2010. AKI was defined and staged according to KDIGO criteria, the Acute Dialysis Quality Initiative's RIFLE criteria, the Acute Kidney Injury Network (AKIN) criteria, and a definition based on a model of creatinine kinetics (CK). Outcomes of interest were incidence, in-hospital mortality, length of stay, costs, readmission rates, and posthospitalization disposition.Results AKI incidence was highest according to the KDIGO definition (18.3%) followed by the AKIN (16.6%), RIFLE (16.1%), and CK (7.0%) definitions. AKI incidence appeared markedly higher in those with low baseline serum creatinine according to the KDIGO, AKIN, and RIFLE definitions, in which AKI may be defined by a 50% increase over baseline. AKI according to all definitions was associated with a significantly higher risk of death and higher resource utilization. The adjusted odds ratios for in-hospital mortality in those with AKI were highest with the CK definition (5.2; 95% confidence interval [95% CI], 4.1 to 6.6), followed by the RIFLE (2.9; 95% CI, 2.2 to 3.6), KDIGO (2.8; 95% CI, 2.2 to 3.6), and AKIN (2.6; 95% CI, 2.0 to 3.3) definitions. Concordance in diagnosis and staging was high among the KDIGO, AKIN, and RIFLE definitions. ConclusionsThe incidence of AKI in hospitalized individuals varies depending on the definition used. AKI according to all definitions is associated with higher in-hospital mortality and resource utilization. AKI may be inappropriately diagnosed in those with low baseline serum creatinine using definitions that incorporate percentage increases over baseline.

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Few studies have evaluated whether histopathologic lesions on kidney biopsy provide prognostic information beyond clinical and laboratory data. We enrolled 676 individuals undergoing native kidney biopsy at three tertiary care hospitals into a prospective, observational cohort study. Biopsy specimens were adjudicated for semiquantitative scores in 13 categories of histopathology by two experienced renal pathologists. Proportional hazards models tested the association between histopathologic lesions and risk of kidney disease progression (≥40% eGFR decline or RRT). Mean baseline eGFR was 57.5±36.0 ml/min per 1.73 m During follow-up (median, 34.3 months), 199 individuals suffered kidney disease progression. After adjustment for demographics, clinicopathologic diagnosis, and laboratory values, the following lesions (hazard ratio; 95% confidence interval) were independently associated with progression: inflammation in nonfibrosed interstitium (0.52; 0.32 to 0.83), moderate and severe versus minimal interstitial fibrosis/tubular atrophy (2.14; 1.24 to 3.69 and 3.42; 1.99 to 5.87, respectively), moderate and severe versus minimal global glomerulosclerosis (2.17; 1.36 to 3.45 and 3.31; 2.04 to 5.38, respectively), moderate and severe versus minimal arterial sclerosis (1.78; 1.15 to 2.74 and 1.64; 1.04 to 2.60, respectively), and moderate and severe versus minimal arteriolar sclerosis (1.63; 1.08 to 2.46 and 2.33; 1.42 to 3.83, respectively). An 11-point chronicity score derived from semiquantitative assessments of chronic lesions independently associated with higher risk of kidney disease progression (hazard ratio per one-point increase, 1.19; 95% confidence interval, 1.12 to 1.27). Across a diverse group of kidney diseases, histopathologic lesions on kidney biopsy provide prognostic information, even after adjustment for proteinuria and eGFR.

Background-Chemokines play an essential role in regulating the infiltration of leukocytes into allografts in experimental models. Little is known of their expression or function after human cardiac transplantation. Methods and Results-We analyzed 169 sequential human endomyocardial biopsies by immunocytochemistry for infiltration by CD3 ϩ T cells and the expression of the chemokine receptors CCR1, CCR3, CCR5, and CXCR3. In both cross-sectional and longitudinal analyses, the expression of each of the chemokine receptors correlated with the degree of CD3 ϩ T-cell infiltration. In particular, the expression of CXCR3 was temporally and spatially associated with CD3

Our study demonstrates that a patient's potassium level at critical care initiation is robustly associated with the risk of death even at moderate increases above normal.

Background and objectivesNative kidney biopsies are commonly performed in the diagnosis of acute kidney diseases and CKD. Because of the invasive nature of the procedure, bleeding-related complications are not uncommon. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases–sponsored Kidney Precision Medicine Project requires that all participants undergo a kidney biopsy; therefore, the objective of this analysis was to study complication rates of native kidney biopsies performed using automated devices under kidney imaging.Design, setting, participants, & measurementsThis is a systematic review and meta-analysis of the literature published from January 1983 to March 2018. The initial PubMed search yielded 1139 manuscripts. Using predetermined selection criteria, 87 manuscripts were included in the final analysis. A random effects meta-analysis for proportions was used to obtain combined estimates of complication rates. Freeman–Tukey double-arcsine transformations were used to stabilize variance as complications were rare.ResultsA total of 118,064 biopsies were included in this study. Patient age ranged from 30 to 79 years, and 45% of patients were women. On the basis of our meta-analysis, pain at the site of biopsy is estimated to occur in 4.3% of biopsied patients, hematomas are estimated to occur in 11%, macroscopic hematuria is estimated to occur in 3.5%, bleeding requiring blood transfusions is estimated to occur in 1.6%, and interventions to stop bleeding are estimated to occur in only 0.3%. Death attributed to native kidney biopsy was a rare event, occurring only in an estimated 0.06% of all biopsies but only 0.03% of outpatient biopsies. Complication rates were higher in hospitalized patients and in those with acute kidney disease. The reported complications varied on the basis of study type and geographic location.ConclusionsAlthough the native kidney biopsy is an invasive diagnostic procedure, the rates of bleeding complications are low. Albeit rare, death can occur postbiopsy. Complications are more frequently seen after kidney biopsies of hospitalized patients with AKI.

Genome wide association studies (GWAS) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, SNPs at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1 and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFRdecline of 3ml/min/1.73m2 or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11 and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 hours after gentamicin treatment compared to controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.

The clinical assessment and management of patients with known or suspected kidney disease has been aided for decades by biomarkers, a term defined by a National Institutes of Health (NIH) working group as "A characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention." The characteristics of an ideal biomarker are given in Box 1. Historically, the first biomarker of kidney disease was the finding on physical examination of interstitial edema or ascites, a condition termed dropsy, that was not specific to what eventually became recognized as kidney failure but that rather encompassed a number of clinical conditions including congestive heart failure and cirrhosis. More objective biomarkers in the early days of nephrology included the examination of the urine sediment, followed by measurement of the blood urea nitrogen concentration and the serum creatinine concentration. Recently, there has been an explosive growth in the search for more sensitive, specific, and prognostically accurate biomarkers to assist in the care of patients with or at risk of kidney disease. In this review we aim to discuss both conventional and novel biomarkers of kidney disease in the settings of acute kidney injury (AKI), chronic kidney disease (CKD), nephrotoxin exposure, and glomerulonephritis. An anatomical localization of these biomarkers along the nephron is shown in figure 1. Additional Readings CONVENTIONAL BIOMARKERS OF KIDNEY FUNCTION AND DISEASE Modern definitions of CKD and AKI emphasize a stage of decreased glomerular filtration rate (GFR), and a stage of kidney damage, defined as structural or functional abnormalities before a decline in GFR. Corresponding biomarkers include filtration markers, such as