Search

Acute kidney injury (AKI) is a growing epidemic and is independently associated with increased risk of death, chronic kidney disease (CKD) and cardiovascular events. Randomized-controlled trials (RCTs) in this domain are notoriously challenging and many clinical studies in AKI have yielded inconclusive findings. Underlying this conundrum is the inherent heterogeneity of AKI in its etiology, presentation and course. AKI is best understood as a syndrome and identification of AKI subphenotypes is needed to elucidate the disease's myriad etiologies and to tailor effective prevention and treatment strategies. Conventional RCTs are logistically cumbersome and often feature highly selected patient populations that limit external generalizability and thus alternative trial designs should be considered when appropriate. In this narrative review of recent developments in AKI trials based on the Kidney Disease Clinical Trialists (KDCT) 2020 meeting, we discuss barriers to and strategies for improved design and implementation of clinical trials for AKI patients, including predictive and prognostic enrichment techniques, the use of pragmatic trials and adaptive trials.

BackgroundPrevious studies in HIV-infected individuals have demonstrated serum albumin to be strongly associated with kidney function decline, independent of urine albumin and inflammatory markers. Lower serum albumin concentrations may be an under-appreciated risk factor for kidney function decline in elders.MethodsWe performed a cohort analysis in the Health Aging and Body Composition Study, a cohort of well-functioning, bi-racial, community-dwelling elders between the age of 70 and 79 years. We examined the associations of serum albumin concentration with longitudinal kidney function decline by estimated glomerular filtration rate (eGFR). Outcomes included linear eGFR decline, rapid kidney function decline defined as >30% decrease in eGFR, defined as a final eGFR 60 mL/min/1.73 m2 at baseline. Cystatin C-based eGFR was calculated at baseline, Year 3 and Year 10.ResultsMean age was 74 years, and mean eGFR was 73 mL/min/1.73 m2 at baseline. The mean rate of eGFR change was 1.81 mL/min/1.73 m2 per year. After multivariate adjustment, lower serum albumin concentrations were strongly and independently associated with kidney function decline (-0.11 mL/min/1.73 m2 per year for each standard deviation decrease serum albumin; -0.01 to - 0.20) with no attenuation after adjustment for urine albumin and inflammatory markers (-0.12, -0.03 to - 0.22). When divided into quartiles, serum albumin levels ≤3.80 g/dL were associated with increased odds of rapid kidney function decline (odds ratio 1.59; 1.12-2.26) and increased risk of incident chronic kidney disease (incident rate ratio 1.29; 1.03-1.62) relative to levels >4.21g/dL. Urine albumin to creatinine ratio (ACR) was also significantly and independently associated with kidney function decline (-0.08 mL/min/1.73 m2 per year for urine ACR >30 mg/g; -0.82 to - 0.13).ConclusionsLower serum albumin levels are strongly and independently associated with kidney function decline in elders, independent of clinical risk factors, urine albumin and measured inflammatory markers.

BackgroundAlthough individual urine biomarkers are associated with chronic kidney disease (CKD) incidence and all-cause mortality in the setting of HIV infection, their combined utility for prediction remains unknown.MethodsWe measured eight urine biomarkers shown previously to be associated with incident CKD and mortality risk among 902 HIV-infected women in the Women's Interagency HIV Study: N-acetyl-β-d-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1), alpha-1 microglobulin (α1m), interleukin 18, neutrophil gelatinase-associated lipocalin, albumin-to-creatinine ratio, liver fatty acid-binding protein and α-1-acid-glycoprotein. A group-based cluster method classified participants into three distinct clusters using the three most distinguishing biomarkers (NAG, KIM-1 and α1m), independent of the study outcomes. We then evaluated associations of each cluster with incident CKD (estimated glomerular filtration rate

Background Patients with acute interstitial nephritis (AIN) can present without typical clinical features, leading to a delay in diagnosis and treatment. We therefore developed and validated a diagnostic model to identify patients at risk of AIN using variables from the electronic health record. Methods In patients who underwent a kidney biopsy at Yale University between 2013 and 2018, we tested the association of >150 variables with AIN, including demographics, comorbidities, vital signs and laboratory tests (training set 70%). We used least absolute shrinkage and selection operator methodology to select prebiopsy features associated with AIN. We performed area under the receiver operating characteristics curve (AUC) analysis with internal (held-out test set 30%) and external validation (Biopsy Biobank Cohort of Indiana). We tested the change in model performance after the addition of urine biomarkers in the Yale AIN study. Results We included 393 patients (AIN 22%) in the training set, 158 patients (AIN 27%) in the test set, 1118 patients (AIN 11%) in the validation set and 265 patients (AIN 11%) in the Yale AIN study. Variables in the selected model included serum creatinine {adjusted odds ratio [aOR] 2.31 [95% confidence interval (CI) 1.42–3.76]}, blood urea nitrogen:creatinine ratio [aOR 0.40 (95% CI 0.20–0.78)] and urine dipstick specific gravity [aOR 0.95 (95% CI 0.91–0.99)] and protein [aOR 0.39 (95% CI 0.23–0.68)]. This model showed an AUC of 0.73 (95% CI 0.64–0.81) in the test set, which was similar to the AUC in the external validation cohort [0.74 (95% CI 0.69–0.79)]. The AUC improved to 0.84 (95% CI 0.76–0.91) upon the addition of urine interleukin-9 and tumor necrosis factor-α. Conclusions We developed and validated a statistical model that showed a modest AUC for AIN diagnosis, which improved upon the addition of urine biomarkers. Future studies could evaluate this model and biomarkers to identify unrecognized cases of AIN. [ABSTRACT FROM AUTHOR]

Urine markers of kidney tubule cell injury and kidney function decline in SPRINT trial participants with CKD. Table 2: Association of (A) blood and (B) urine biomarkers of kidney tubule injury and dysfunction with longitudinal relative change in SBP in community-living individuals without diabetes or CKD. Hypertension (HTN) is the leading cause of premature death worldwide, affecting >1 billion people, and is a major risk factor for the onset and progression of chronic kidney disease (CKD) and cardiovascular disease (CVD) [[1]]. [Extracted from the article]

Background We previously demonstrated that urine interleukin (IL)-9 and tumor necrosis factor (TNF)-α can distinguish acute interstitial nephritis (AIN) from other causes of acute kidney injury. Here we evaluated the role of these biomarkers to prognosticate kidney function in patients with AIN. Methods In a cohort of participants with biopsy-proven, adjudicated AIN, we tested the association of histological features and urine biomarkers (IL-9 and TNF-α) with estimated glomerular filtration rate measured 6 months after diagnosis (6 m-eGFR) controlling for eGFR before AIN and albuminuria. We also evaluated subgroups in whom corticosteroid use was associated with 6 m-eGFR. Results In the 51 (93%) of the 55 participants with complete data, median (interquartile range) eGFR before and 6 m after AIN were 41 (27–69) and 28 (13–47) mL/min/1.73 m2, respectively. Patients with higher severity of interstitial fibrosis had lower 6 m-eGFR, whereas those with higher tubulointerstitial infiltrate had higher 6 m-eGFR. IL-9 levels were associated with lower 6 m-eGFR only in the subset of patients who did not receive corticosteroids [6m-eGFR per doubling of IL-9, −6.0 (−9.4 to −2.6) mL/min/1.73 m2]. Corticosteroid use was associated with higher 6 m-eGFR [20.9 (0.2, 41.6) mL/min/1.73 m2] only in those with urine IL-9 above the median (>0.66 ng/g) but not in others. Conclusions Urine IL-9 was associated with lower 6 m-eGFR only in participants not treated with corticosteroids. Corticosteroid use was associated with higher 6 m-eGFR in those with high urine IL-9. These findings provide a framework for IL-9-guided clinical trials to test efficacy of immunosuppressive therapy in patients with AIN. [ABSTRACT FROM AUTHOR]