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Introduction: Diabetes is a leading cause of end-stage kidney disease (ESKD). Biomarkers of tubular health may prognosticate chronic kidney disease (CKD) progression beyond estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Methods: We examined associations of five urinary biomarkers of tubular injury and repair (NGAL, KIM-1, IL-18, MCP-1, YKL-40) with kidney function decline (first occurrence of a decrease in eGFR ≥30 mL/min/1.73 m2 if randomization eGFR ≥60 or ≥50% if randomization eGFR <60; ESKD) and all-cause mortality among 1,135 VA NEPHRON-D trial participants with baseline UACR ≥300 mg/g and available urine samples. Covariates included age, sex, race, BMI, systolic BP, HbA1c, treatment arm, eGFR, and UACR. In a subset of participants with 12-month samples (n = 712), we evaluated associations of KIM-1, MCP-1, and YKL-40 change (from baseline to 12 months) with eGFR decline (from 12 months onward). Results: At baseline, mean age was 65 years, mean eGFR was 56 mL/min/1.73 m2, and median UACR was 840 mg/g. Over a median of 2.2 years, 13% experienced kidney function decline and 9% died. In fully adjusted models, the highest versus lowest quartiles of MCP-1 and YKL-40 were associated with 2.18- and 1.76-fold higher risks of kidney function decline, respectively. One-year changes in KIM-1, MCP-1, and YKL-40 were not associated with subsequent eGFR decline. Higher baseline levels of NGAL, IL-18, MCP-1, and YKL-40 levels (per 2-fold higher) were independently associated with 10–40% higher risk of mortality. Conclusion: Among Veterans with diabetes and CKD, urinary biomarkers of tubular health were associated with kidney function decline and mortality. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus 2019 (COVID-19) can increase catabolism and result in hyperuricemia. Uric acid (UA) potentially causes kidney damage by alteration of renal autoregulation, inhibition of endothelial cell proliferation, cell apoptosis, activation of the pro-inflammatory cascade, and crystal deposition. Hyperuricemia in patients with COVID-19 may contribute to acute kidney injury (AKI) and poor outcomes. Methods: We included 834 patients with COVID-19 who were >18 years old and hospitalized for >24 h in the Mount Sinai Health System and had at least 1 measurement of serum UA. We examined the association between the first serum UA level and development of acute kidney injury (AKI, defined by KDIGO criteria), major adverse kidney events (MAKE, defined by a composite of all-cause in-hospital mortality or dialysis or 100% increase in serum creatinine from baseline), as well as markers of inflammation and cardiac injury. Results: Among the 834 patients, the median age was 66 years, 42% were women, and the median first serum UA was 5.9 mg/dL (interquartile range 4.5–8.8). Overall, 60% experienced AKI, 52% experienced MAKE, and 32% died during hospitalization. After adjusting for demographics, comorbidities, and laboratory values, a doubling in serum UA was associated with increased AKI (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.9–4.1), MAKE (OR 2.5, 95% CI 1.7–3.5), and in-hospital mortality (OR 1.7, 95% CI 1.3–2.3). Higher serum UA levels were independently associated with a higher level of procalcitonin (β, 0.6; SE 0.2) and troponin I (β, 1.2; SE 0.2) but were not associated with serum ferritin, C-reactive protein, and interleukin-6. Conclusion: In patients admitted to the hospital for COVID-19, higher serum UA levels were independently associated with AKI, MAKE, and in-hospital mortality in a dose-dependent manner. In addition, hyperuricemia was associated with higher procalcitonin and troponin I levels. [ABSTRACT FROM AUTHOR]

The search for relevant kidney injury biomarkers has been a fervent one and well-documented over the past 15 years. Counterintuitively, patients with acute decompensated heart failure who have elevated injury biomarkers and clinical AKI actually have better post-discharge outcomes and better post-discharge kidney function [[10]]. These groups can be potentially broken down into patients with early and/or late diabetic kidney disease, non-diabetic or APOL1-associated kidney disease, various types of glomerulonephritides, patients with chronic heart failure, chronic liver disease and HIV-positive individuals. [Extracted from the article]

Introduction: Urine alpha-1-microglobulin (Uα1m) elevations signal proximal tubule dysfunction. In ambulatory settings, higher Uα1m is associated with acute kidney injury (AKI), progressive chronic kidney disease (CKD), cardiovascular (CV) events, and mortality. We investigated the associations of pre- and postoperative Uα1m concentrations with adverse outcomes after cardiac surgery. Methods: In 1,464 adults undergoing cardiac surgery in the prospective multicenter Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury (TRIBE-AKI) cohort, we measured the pre-and postoperative Uα1m concentrations and calculated the changes from pre- to postoperative concentrations. Outcomes were postoperative AKI during index hospitalization and longitudinal risks for CKD incidence and progression, CV events, and all-cause mortality after discharge. We analyzed Uα1m continuously and categorically by tertiles using multivariable logistic regression and Cox proportional hazards regression adjusted for demographics, surgery characteristics, comorbidities, baseline estimated glomerular filtration rate, urine albumin, and urine creatinine. Results: There were 230 AKI events during cardiac surgery hospitalization; during median 6.7 years of follow-up, there were 212 cases of incident CKD, 54 cases of CKD progression, 269 CV events, and 459 deaths. Each 2-fold higher concentration of preoperative Uα1m was independently associated with AKI (adjusted odds ratio [aOR] = 1.36, 95% confidence interval 1.14–1.62), CKD progression (adjusted hazard ratio [aHR] = 1.46, 1.04–2.05), and all-cause mortality (aHR = 1.19, 1.06–1.33) but not with incident CKD (aHR = 1.21, 0.96–1.51) or CV events (aHR = 1.01, 0.86–1.19). Postoperative Uα1m was not associated with AKI (aOR per 2-fold higher = 1.07, 0.93–1.22), CKD incidence (aHR = 0.90, 0.79–1.03) or progression (aHR = 0.79, 0.56–1.11), CV events (aHR = 1.06, 0.94–1.19), and mortality (aHR = 1.01, 0.92–1.11). Conclusion: Preoperative Uα1m concentrations may identify patients at high risk of AKI and other adverse events after cardiac surgery, but postoperative Uα1m concentrations do not appear to be informative. [ABSTRACT FROM AUTHOR]