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Background After accounting for known risk factors for CKD progression in children, clinical outcomes among children with CKD still vary substantially. Biomarkers of tubular injury (such as KIM-1), repair (such as YKL-40), or inflammation (such as MCP-1, suPAR, TNF receptor-1 [TNFR-1], and TNFR-2) may identify children with CKD at risk for GFR decline. Methods We investigated whether plasma KIM-1, YKL-40, MCP-1, suPAR, TNFR-1, and TNFR-2 are associated with GFR decline in children with CKD and in subgroups defined by glomerular versus nonglomerular cause of CKD. We studied participants of the prospective CKiD Cohort Study which enrolled children with an eGFR of 30-90 ml/min per 1.73 m2 and then assessed eGFR annually. Biomarkers were measured in plasma collected 5 months after study enrollment. The primary endpoint was CKD progression, defined as a composite of a 50% decline in eGFR or incident ESKD. Results Of the 651 children evaluated (median age 11 years; median baseline eGFR of 53 ml/min per 1.73 m2), 195 (30%) had a glomerular cause of CKD. Over a median follow-up of 5.7 years, 223 children (34%) experienced CKD progression to the composite endpoint. After multivariable adjustment, children with a plasma KIM-1, TNFR-1, or TNFR-2 concentration in the highest quartile were at significantly higher risk of CKD progression compared with children with a concentration for the respective biomarker in the lowest quartile (a 4-fold higher risk for KIM-1 and TNFR-1 and a 2-fold higher risk for TNFR-2). Plasma MCP-1, suPAR, and YKL-40 were not independently associated with progression. When stratified by glomerular versus nonglomerular etiology of CKD, effect estimates did not differ significantly. Conclusions Higher plasma KIM-1, TNFR-1, and TNFR-2 are independently associated with CKD progression in children.

Objectives Therapies for patients with respiratory failure from coronavirus disease 2019 are urgently needed. Early implementation of prone positioning ventilation improves survival in patients with acute respiratory distress syndrome, but studies examining the effect of proning on survival in patients with coronavirus disease 2019 are lacking. Our objective was to estimate the effect of early proning initiation on survival in patients with coronavirus disease 2019-associated respiratory failure. Design Data were derived from the Study of the Treatment and Outcomes in Critically Ill Patients with coronavirus disease 2019, a multicenter cohort study of critically ill adults with coronavirus disease 2019 admitted to 68 U.S. hospitals. Using these data, we emulated a target trial of prone positioning ventilation by categorizing mechanically ventilated hypoxemic (ratio of PaO2 over the corresponding FIO2 ≤ 200 mm Hg) patients as having been initiated on proning or not within 2 days of ICU admission. We fit an inverse probability-weighted Cox model to estimate the mortality hazard ratio for early proning versus no early proning. Patients were followed until death, hospital discharge, or end of follow-up. Setting ICUs at 68 U.S. sites. Patients Critically ill adults with laboratory-confirmed coronavirus disease 2019 receiving invasive mechanical ventilation with ratio of PaO2 over the corresponding FIO2 less than or equal to 200 mm Hg. Interventions None. Measurements and main results Among 2,338 eligible patients, 702 (30.0%) were proned within the first 2 days of ICU admission. After inverse probability weighting, baseline and severity of illness characteristics were well-balanced between groups. A total of 1,017 (43.5%) of the 2,338 patients were discharged alive, 1,101 (47.1%) died, and 220 (9.4%) were still hospitalized at last follow-up. Patients proned within the first 2 days of ICU admission had a lower adjusted risk of death compared with nonproned patients (hazard ratio, 0.84; 95% CI, 0.73-0.97). Conclusions In-hospital mortality was lower in mechanically ventilated hypoxemic patients with coronavirus disease 2019 treated with early proning compared with patients whose treatment did not include early proning.

Acute kidney injury (AKI) has been reported to be associated with excess risks of death, kidney disease progression and cardiovascular events although previous studies have important limitations. To further examine this, we prospectively studied adults from four clinical centers surviving three months and more after hospitalization with or without AKI who were matched on center, pre-admission CKD status, and an integrated priority score based on age, prior cardiovascular disease or diabetes mellitus, preadmission estimated glomerular filtration rate (eGFR) and treatment in the intensive care unit during the index hospitalization between December 2009-February 2015, with follow-up through November 2018. All participants had assessments of kidney function before (eGFR) and at three months and annually (eGFR and proteinuria) after the index hospitalization. Associations of AKI with outcomes were examined after accounting for pre-admission and three-month post-discharge factors. Among 769 AKI (73% Stage 1, 14% Stage 2, 13% Stage 3) and 769 matched non-AKI adults, AKI was associated with higher adjusted rates of incident CKD (adjusted hazard ratio 3.98, 95% confidence interval 2.51-6.31), CKD progression (2.37,1.28-4.39), heart failure events (1.68, 1.22-2.31) and all-cause death (1.78, 1.24-2.56). AKI was not associated with major atherosclerotic cardiovascular events in multivariable analysis (0.95, 0.70-1.28). After accounting for degree of kidney function recovery and proteinuria at three months after discharge, the associations of AKI with heart failure (1.13, 0.80-1.61) and death (1.29, 0.84-1.98) were attenuated and no longer significant. Thus, assessing kidney function recovery and proteinuria status three months after AKI provides important prognostic information for long-term clinical outcomes., Graphical abstract

In this multicenter, prospective study of 288 children (half under 2 years of age) undergoing cardiac surgery, we evaluated whether the measurement of pre- and postoperative serum cystatin C (CysC) improves the prediction of acute kidney injury (AKI) over that obtained by serum creatinine (SCr). Higher preoperative SCr-based estimated glomerular filtration rates predicted higher risk of the postoperative primary outcomes of stage 1 and 2 AKI (adjusted odds ratios (ORs) 1.5 and 1.9, respectively). Preoperative CysC was not associated with AKI. The highest quintile of postoperative (within 6 h) CysC predicted stage 1 and 2 AKI (adjusted ORs of 6 and 17.2, respectively). The highest tertile of percent change in CysC independently predicted AKI, whereas the highest tertile of SCr predicted stage 1 but not stage 2 AKI. Postoperative CysC levels independently predicted longer duration of ventilation and intensive care unit length of stay, whereas the postoperative SCr change only predicted longer intensive care unit stay. Thus, postoperative serum CysC is useful to risk-stratify patients for AKI treatment trials. More research, however, is needed to understand the relation between preoperative renal function and the risk of AKI.

Purpose Myocardial necrosis and apoptosis have been observed following experimentally induced renal dysfunction (RD). Given that adverse cardiac outcomes remain strongly associated with acute kidney injury even after RD completely normalizes, many have theorized that the adverse outcomes directly result from RD-induced myocardial injury. However, it remains unclear whether this risk is the result of the RD itself, or if RD is identifying a “sicker” population. As such, we hypothesized that if the adverse cardiovascular outcomes associated with RD result primarily from irreversible RD-induced myocardial injury, transplantation of a heart from a donor with RD should lead to inferior graft survival. Methods and Materials Adult patients in the UNOS registry who underwent cardiac transplantation from 1994 through June 30, 2011 with donor creatinine and urine protein available were evaluated (n=20,438). Results Mean donor GFR was 90.5 ± 48.4 ml/min and 22.3% of donors had RD (GFR 40 (HR=1.4, p 4 hrs (HR=1.2, p Conclusions RD in cardiac allograft donors is not associated with reduced post-transplant graft survival. These data support the hypothesis that irreversible myocardial injury induced by RD is not primarily responsible for the strong epidemiologic association between RD and adverse cardiovascular outcomes.