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Biomarkers of tubular function such as epidermal growth factor (EGF) may improve prognostication of participants at highest risk for chronic kidney disease (CKD) after hospitalization. To examine this, we measured urinary EGF (uEGF) from samples collected in the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study, a multi-center, prospective, observational cohort of hospitalized participants with and without AKI. Cox proportional hazards regression was used to investigate the association of uEGF/Cr at hospitalization, three months post-discharge, and the change between these time points with major adverse kidney events (MAKE): CKD incidence, progression, or development of kidney failure. Clinical findings were paired with mechanistic studies comparing relative Egfexpression in mouse models of kidney atrophy or repair after ischemia-reperfusion injury. MAKE was observed in 20% of 1,509 participants over 4.3 years of follow-up. Each 2-fold higher level of uEGF/Cr at three months was associated with decreased risk of MAKE (adjusted hazards ratio 0.46, 95% confidence interval: 0.39-0.55). Participants with the highest increase in uEGF/Cr from hospitalization to three-month follow-up had a lower risk of MAKE (adjusted hazards ratio 0.52; 95% confidence interval: 0.36-0.74) compared to those with the least change in uEGF/Cr. A model using uEGF/Cr at three months combined with clinical variables yielded moderate discrimination for MAKE (area under the curve 0.73; 95% confidence interval: 0.69-0.77) and strong discrimination for kidney failure at four years (area under the curve 0.96; 95% confidence interval: 0.92-1.00). Accelerated restoration of Egfexpression in mice was seen in the model of adaptive repair after injury, compared to a model of progressive atrophy. Thus, urinary EGF/Cr may be a biomarker of distal tubular health, with higher concentrations and increased uEGF/Cr post-discharge independently associated with reduced risk of MAKE in hospitalized patients.

Background:Acute changes in serum creatinine are labeled clinically as acute kidney injury (AKI). However, not all acute changes in serum creatinine are deleterious and need to be acted upon. Summary:Intravenous fluids in response to AKI should be judiciously administered, and volume overload should be avoided. Since congestion is the driver of poor outcomes in patients with acute decompensated heart failure and must be managed, AKI that occurs at the expense of decongestion does not confer increased risk. We still do not have evidence of therapies that reduce AKI which will translate into any meaningful improvements in clinical outcomes. Finally, particularly in the setting of application of therapies designed to reduce cardiorenal risk, acute changes in serum creatinine are often in the opposite direction of the ultimate clinical outcomes, both renal and nonrenal. Key Messages:Given the complexities and the nuance of acute changes in serum creatinine, it has ruled itself as an unreliable surrogate for randomized controlled trials and often hinders appropriate care in the clinical setting.

The role of plasma soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 in the prognosis of clinical events after hospitalization with or without acute kidney injury (AKI) is unknown.

Biomarker studies in the setting of CKD have increased considerably within the past 15 years, but vary significantly by design and clinical context. The authors conducted a systematic review and meta-analysis to summarize the prognostic value of preclinical plasma and urine biomarkers for CKD outcomes (incident CKD, CKD progression, or incident ESKD), including 129 studies in the meta-analysis. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) among some of the most studied CKD biomarkers were 2.17 (95% CI, 1.91 to 2.47) for plasma TNFR1, 1.21 (95% CI, 1.15 to 1.28) for plasma FGF23, 2.07 (95% CI, 1.82 to 2.34) for plasma TNFR2, 1.10 (95% CI, 1.05 to 1.16) for urine KIM-1, and 1.12 (95% CI, 1.06 to 1.19) for urine NGAL. The study?s findings suggest these biomarkers merit assessment of their performance in clinical practice.

IMPORTANCE: Observational evidence suggests that higher physical activity is associated with slower kidney function decline; however, to our knowledge, no large trial has evaluated whether activity and exercise can ameliorate kidney function decline in older adults. OBJECTIVE: To evaluate whether a moderate-intensity exercise intervention can affect the rate of estimated glomerular filtration rate per cystatin C (eGFRCysC) change in older adults. DESIGN, SETTING, AND PARTICIPANTS: This ancillary analysis of the Lifestyle Interventions and Independence For Elders randomized clinical trial enrolled 1199 community-dwelling, sedentary adults aged 70 to 89 years with mobility limitations and available blood specimens. The original trial was conducted across 8 academic centers in the US from February 2010 through December 2013. Data for this study were analyzed from March 29, 2021, to February 28, 2022. INTERVENTIONS: Structured, 2-year, partially supervised, moderate-intensity physical activity and exercise (strength, flexibility) intervention compared with a health education control intervention with 2-year follow-up. Physical activity was measured by step count and minutes of moderate-intensity activity using accelerometers. MAIN OUTCOMES AND MEASURES: The primary outcome was change in eGFRCysC. Rapid eGFRCysC decline was defined by the high tertile threshold of 6.7%/y. RESULTS: Among the 1199 participants in the analysis, the mean (SD) age was 78.9 (5.2) years, and 800 (66.7%) were women. At baseline, the 2 groups were well balanced by age, comorbidity, and baseline eGFRCysC. The physical activity and exercise intervention resulted in statistically significantly lower decline in eGFRCysC over 2 years compared with the health education arm (mean difference, 0.96 mL/min/1.73 m2; 95% CI, 0.02-1.91 mL/min/1.73 m2) and lower odds of rapid eGFRCysC decline (odds ratio, 0.79; 95% CI, 0.65-0.97). CONCLUSIONS AND RELEVANCE: Results of this ancillary analysis of a randomized clinical trial showed that when compared with health education, a physical activity and exercise intervention slowed the rate of decline in eGFRCysC among community-dwelling sedentary older adults. Clinicians should consider targeted recommendation of physical activity and moderate-intensity exercise for older adults as a treatment to slow decline in eGFRCysC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01072500

Recent research suggests that biomarkers of the TNF pathway (TNFR1 and TNFR2) are associated with worse kidney outcomes. Most of these studies, however, evaluated baseline levels rather than longitudinal changes. In two cohorts (AASK, which enrolled Black people with CKD attributed to hypertension, and VA NEPHRON-D, which enrolled veterans with albuminuric CKD and type 2 diabetes), greater longitudinal increases in serum or plasma TNFR1 and TNFR2 were associated with higher risks of ESKD in AASK and subsequent kidney function decline in VA NEPHRON-D. These associations were independent of baseline biomarker level and kidney function. Longitudinal trajectories in TNFR1 and TNFR2 may ultimately allow improved risk assessment for kidney failure in persons with CKD.

Mechanisms underlying long-term effects after AKI remain unclear. Because vessel instability is an early response to endothelial injury, the authors studied markers of blood vessel homeostasis (the plasma angiopoietins angiopoietin-1 and angiopoietin-2) in a multicenter prospective cohort that included 1503 adults, half of whom had AKI. Three months after hospitalization, the highest quartile of plasma angiopoietin-1:angiopoietin-2 ratio compared with the lowest quartile associated with 72% less risk of CKD progression, 94% less risk of heart failure, and 82% less risk of death among those with AKI; those without AKI exhibited similar but less pronounced reductions in risk of heart failure and mortality. Angiopoietins may serve as a common pathway to explain the progression of kidney and heart disease after AKI and may point to potential future interventions.

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Subphenotypes have been identified in patients with sepsis and ARDS and are associated with different outcomes and responses to therapies.

AbstractAimsThis study aimed to estimate the association of patiromer exposure vs.no potassium (K+) binder (NoKb) exposure with healthcare utilization and expenditures among a cohort of Medicare Advantage patients with hyperkalemia (HK).MethodsUsing Optum’s Clinformatics Data Mart (study period 2016–2019), the authors assessed propensity score-matched patients (1:1) with a serum K+concentration ≥5.0 mmol/L and an HK diagnosis that were exposed to patiromer or NoKb on baseline characteristics. The following outcomes were compared: (1) inpatient/emergency department (ED) encounters, (2) inpatient costs greater than or equal to mean Medicare Advantage inpatient cost (i.e. $14,900), and (3) the relative healthcare spending rate. Logistic regression and zero-inflated negative binomial regression were used to analyze the outcomes.ResultsThe study cohort included 1,539 patiromer and NoKb matched pairs. Baseline characteristics were (patiromer/NoKb): age 74/75 years; female 42/40%; serum K+5.6/5.6 mmol/L; eGFR rate 36/36 mL/min/1.73 m2; low-income subsidy 42/41%, chronic kidney disease 96/96%; end-stage renal disease 12/12%; and congestive heart failure 37/36%. A total of 253 matched pairs (506 patients) remained uncensored and were analyzed at 6 months. Inpatient/ED encounters were observed for 25% (patiromer) and 37% (NoKb) (odds ratio [OR] 0.58, 95% confidence interval [CI]: 0.38–0.89). The relative odds of having inpatient costs ≥$14,900 were ∼50% less for patients exposed to patiromer vs.NoKb (OR [95% CI]: 0.47 [0.25–0.89]). The relative total healthcare spending rate (including inpatient, outpatient, ED, and pharmacy costs) was 19% less for patients exposed to patiromer vs.NoKb (spending rate ratio [95% CI]: 0.81 [0.67–0.98]).Conclusion and limitationsAmong Medicare Advantage patients with HK, patiromer exposure (vs.NoKb) was associated with statistically significant reductions in the proportion with inpatient/ED encounters, inpatient costs ≥$14,900, and lower total healthcare spending. Further research, with larger sample size, is warranted to fully validate these findings.

AbstractAimTo evaluate the U.S. payer budget-impact of KidneyIntelX, an artificial intelligence-enabled in vitrodiagnostic to predict kidney function decline in Type 2 Diabetic Kidney Disease (T2DKD) patients, stages 1–3b.Materials and methodsWe developed an Excel-based model according to International Society of Pharmacoeconomics and Outcomes Research (ISPOR) good practices to assess U.S. payer budget impact associated with the use of the KidneyIntelX test to optimize therapy T2DKD patients compared to standard of care (SOC) (without KidneyIntelX). A hypothetical cohort of 100,000 stages 1–3b T2DKD patients was followed for 5 years. Peer-reviewed publications were used to identify model parameter estimates. KidneyIntelX costs incremental to SOC (without KidneyIntelX) included test cost, additional prescription medication use, specialist referrals and PCP office visits. Patients managed with KidneyIntelX experienced a 20% slowed progression rate compared to SOC (without KidneyIntelX) attributed to slowed DKD progression, delayed or prevented dialysis and transplants, and reduced dialysis crashes. Associated costs were compared to SOC (without KidneyIntelX). Sensitivity analyses were conducted by varying the definition of progression and the DKD progression rate associated with KidneyIntelX testing and related interventions.ResultsProjected undiscounted base case 5-year savings for 100,000 patients tested with KidneyIntelX were $1.052 billion, attributed mostly to slowed progression through DKD stages. The breakeven point for the health plan adopting KidneyIntelX is expected to occur prior to year 2 after adoption. Sensitivity analysis based on the assessment of the most conservative definition of progression and a 5% reduction in progression rate attributed to KidneyIntelX, resulted in a projected 5-year savings of $145 million associated with KidneyIntelX.Limitations and conclusionsLimitations included reliance on literature-based parameter estimates, including effect size of delayed progression supported by the literature. Incorporating KidneyIntelX in contemporary care of early-stage T2DKD patients is projected to result in substantial savings to payers.

Urinary tract stones have high heritability indicating a strong genetic component. However, genome-wide association studies (GWAS) have uncovered only a few genome wide significant single nucleotide polymorphisms (SNPs). Polygenic risk scores (PRS) sum cumulative effect of many SNPs and shed light on underlying genetic architecture. Using GWAS summary statistics from 361,141 participants in the United Kingdom Biobank, we generated a PRS and determined association with stone diagnosis in 28,877 participants in the Mount Sinai BioMeBiobank. In BioMe(1,071 cases and 27,806 controls), for every standard deviation increase, we observed a significant increment in adjusted odds ratio of a factor of 1.2 (95% confidence interval 1.13-1.26). In comparison, a risk score comprised of GWAS significant SNPs was not significantly associated with diagnosis. After stratifying individuals into low and high-risk categories on clinical risk factors, there was a significant increment in adjusted odds ratio of 1.3 (1.12-1.6) in the low- and 1.2 (1.1-1.2) in the high-risk group for every standard deviation increment in PRS. In a 14,348-participant validation cohort (Penn Medicine Biobank), every standard deviation increment was associated with a significant adjusted odds ratio of 1.1 (1.03 – 1.2). Thus, a genome-wide PRS is associated with urinary tract stones overall and in the absence of known clinical risk factors and illustrates their complex polygenic architecture.

National data on patient characteristics, treatment, and outcomes of critically ill coronavirus disease 2019 (COVID‐19) solid organ transplant (SOT) patients are limited. We analyzed data from a multicenter cohort study of adults with laboratory‐confirmed COVID‐19 admitted to intensive care units (ICUs) at 68 hospitals across the United States from March 4 to May 8, 2020. From 4153 patients, we created a propensity score matched cohort of 386 patients, including 98 SOT patients and 288 non‐SOT patients. We used a binomial generalized linear model (log‐binomial model) to examine the association of SOT status with death and other clinical outcomes. Among the 386 patients, the median age was 60 years, 72% were male, and 41% were black. Death within 28 days of ICU admission was similar in SOT and non‐SOT patients (40% and 43%, respectively; relative risk [RR] 0.92; 95% confidence interval [CI]: 0.70‐1.22). Other outcomes and requirement for organ support including receipt of mechanical ventilation, development of acute respiratory distress syndrome, and receipt of vasopressors were also similar between groups. There was a trend toward higher risk of acute kidney injury requiring renal replacement therapy in SOT vs. non‐SOT patients (37% vs. 27%; RR [95% CI]: 1.34 [0.97‐1.85]). Death and organ support requirement were similar between SOT and non‐SOT critically ill patients with COVID‐19. Solid organ transplant recipients with critical SARS‐CoV‐2 infection have a similar risk of death, acute respiratory distress syndrome, and requirement for organ support as nonsolid organ transplant patients.

The purpose of this study was to investigate real world safety and efficacy of hypertonic saline therapy in cases of refractory acute decompensated heart failure (ADHF) at a large U.S. academic medical center.

Symptoms are common in patients on maintenance hemodialysis but identification is challenging. New informatics approaches including natural language processing (NLP) can be utilized to identify symptoms from narrative clinical documentation. Here we utilized NLP to identify seven patient symptoms from notes of maintenance hemodialysis patients of the BioMeBiobank and validated our findings using a separate cohort and the MIMIC-III database. NLP performance was compared for symptom detection with International Classification of Diseases (ICD)-9/10 codes and the performance of both methods were validated against manual chart review. From 1034 and 519 hemodialysis patients within BioMeand MIMIC-III databases, respectively, the most frequently identified symptoms by NLP were fatigue, pain, and nausea/vomiting. In BioMe, sensitivity for NLP (0.85 - 0.99) was higher than for ICD codes (0.09 - 0.59) for all symptoms with similar results in the BioMevalidation cohort and MIMIC-III. ICD codes were significantly more specific for nausea/vomiting in BioMeand more specific for fatigue, depression, and pain in the MIMIC-III database. A majority of patients in both cohorts had four or more symptoms. Patients with more symptoms identified by NLP, ICD, and chart review had more clinical encounters. NLP had higher specificity in inpatient notes but higher sensitivity in outpatient notes and performed similarly across pain severity subgroups. Thus, NLP had higher sensitivity compared to ICD codes for identification of seven common hemodialysis-related symptoms, with comparable specificity between the two methods. Hence, NLP may be useful for the high-throughput identification of patient-centered outcomes when using electronic health records.

Introduction/Objective: The KidneyIntelX is a multiplex, bioprognostic, immunoassay consisting of 3 plasma biomarkers and clinical variables that uses machine learning to predict a patient’s risk for a progressive decline in kidney function over 5 years. We report the 1-year pre- and post-test clinical impact on care management, eGFR slope, and A1C along with engagement of population health clinical pharmacists and patient coordinators to promote a program of sustainable kidney, metabolic, and cardiac health.Methods: The KidneyIntelX in vitro prognostic test was previously validated for patients with type 2 diabetes and diabetic kidney disease (DKD) to predict kidney function decline within 5 years was introduced into the RWE study (NCT04802395) across the Health System as part of a population health chronic disease management program from [November 2020 to April 2023]. Pre- and post-test patients with a minimum of 12 months of follow-up post KidneyIntelX were assessed across all aspects of the program.Results: A total of 5348 patients with DKD had a KidneyIntelX assay. The median age was 68 years old, 52% were female, 27% self-identified as Black, and 89% had hypertension. The median baseline eGFR was 62 ml/min/1.73 m2, urine albumin-creatinine ratio was 54 mg/g, and A1C was 7.3%. The KidneyIntelX risk level was low in 49%, intermediate in 40%, and high in 11% of cases. New prescriptions for SGLT2i, GLP-1 RA, or referral to a specialist were noted in 19%, 33%, and 43% among low-, intermediate-, and high-risk patients, respectively. The median A1C decreased from 8.2% pre-test to 7.5% post-test in the high-risk group (P< .001). UACR levels in the intermediate-risk patients with albuminuria were reduced by 20%, and in a subgroup treated with new scripts for SGLT2i, UACR levels were lowered by approximately 50%. The median eGFR slope improved from −7.08 ml/min/1.73 m2/year to −4.27 ml/min/1.73 m2/year in high-risk patients (P= .0003), −2.65 to −1.04 in intermediate risk, and −3.26 ml/min/1.73 m2/year to +0.45 ml/min/1.73 m2/year in patients with low-risk (P< .001).Conclusions: Deployment and risk stratification by KidneyIntelX was associated with an escalation in action taken to optimize cardio-kidney-metabolic health including medications and specialist referrals. Glycemic control and kidney function trajectories improved post-KidneyIntelX testing, with the greatest improvements observed in those scored as high-risk.

Glomerular disorders have a highly variable clinical course and biomarkers that reflect molecular mechanisms underlying progression are needed. Based on our previous work identifying plasminogen as a direct cause of podocyte injury, we designed this study to test the association between urine plasmin(ogen) (i.e., plasmin and its precursor plasminogen) and end-stage kidney disease (ESKD).

The process of angiogenesis after kidney injury may determine recovery and long-term outcomes. We evaluated the association of angiogenesis markers with acute kidney injury (AKI) and mortality after cardiac surgery.

Acute kidney injury (AKI) is a major public health problem that complicates 10–40% of hospital admissions. Importantly, AKI is independently associated with increased risk of progression to chronic kidney disease, end-stage renal disease, cardiovascular events, and increased risk of in-hospital and long-term mortality. The chloride content of intravenous fluid has garnered much attention over the last decade, as well as its association with excess use and adverse outcomes, including AKI. Numerous studies show that changes in serum chloride concentration, independent of serum sodium and bicarbonate, are associated with increased risk of AKI, morbidity, and mortality. This comprehensive review details the complex renal physiology regarding the role of chloride in regulating renal blood flow, glomerular filtration rate, tubuloglomerular feedback, and tubular injury, as well as the findings of clinical research related to the chloride content of intravenous fluids, changes in serum chloride concentration, and AKI. Chloride is underappreciated in both physiology and pathophysiology. Although the exact mechanism is debated, avoidance of excessive chloride administration is a reasonable treatment option for all patients and especially in those at risk for AKI. Therefore, high-risk patients and those with “incipient” AKI should receive balanced solutions rather than normal saline to minimize the risk of AKI.

Novel biomarkers are needed to predict kidney function decline in patients with type 2 diabetes, especially those with preserved glomerular filtration rate (GFR). There are limited data on the association of markers of endothelial dysfunction with longitudinal GFR decline. We used banked specimens from a nested case-control study in the Action to Control Cardiovascular Disease (ACCORD) trial (n=187 cases: 187 controls) and from a diverse contemporary cohort of type 2 diabetic patients from the Mount Sinai BioMeBiobank (n=871) to assess the association of plasma endostatin and kidney outcomes. We measured plasma endostatin at enrollment and examined its association with a composite kidney outcome of sustained 40% decline in estimated GFR or end-stage renal disease. Baseline plasma endostatin levels were higher in participants with the composite outcome. Each log2increment in plasma endostatin was associated with approximately 2.5-fold higher risk of the kidney outcome (adjusted odds ratio [OR] 2.5; 95% confidence interval [CI] 1.5-4.3 in ACCORD and adjusted hazard ratio [HR] 2.6; 95% CI 1.8-3.8 in BioMe). Participants in the highest vs. lowest quartile of plasma endostatin had approximately four-fold higher risk for the kidney outcome (adjusted OR 3.6; 95% CI 1.8-7.3 in ACCORD and adjusted HR 4.4; 95% CI 2.3-8.5 in BioMe). The AUC for the kidney outcome improved from 0.74 to 0.77 in BioMewith the addition of endostatin to a base clinical model. Plasma endostatin was strongly associated with kidney outcomes in type 2 diabetics with preserved eGFR and improved risk discrimination over traditional predictors.

Random assignment to intensive blood pressure (BP) lowering (systolic BP<120mmHg) compared to a less intensive BP target (systolic BP<140mmHg) in the Action to Control Cardiovascular Risk in Diabetes BP (ACCORD-BP) trial resulted in a more rapid decline in estimated glomerular filtration rate (eGFR). Whether this reflects hemodynamic effects or intrinsic kidney damage is unknown.

Renin–angiotensin–aldosterone system inhibitors have proven clinical benefit in management of patients with heart failure with reduced ejection fraction. However, there are no guidelines to manage decline in kidney function that occurs with initiation and titration of renin–angiotensin–aldosterone system agents during management of heart failure. We discuss the complex interplay of kidney function and heart failure in the presence of renin–angiotensin–aldosterone system agents and suggest a clinical algorithm for management of acute decline in kidney function.

G1/G2 variants in the Apolipoprotein L1 (APOL1) gene are associated with end-stage renal disease (ESRD) in people with African ancestry. Plasma biomarkers may have utility for risk stratification in APOL1high-risk individuals of African ancestry. To evaluate this, we measured tumor necrosis factor receptor 1/2 (TNFR1/2) and kidney injury molecule-1 (KIM1) in baseline plasma specimens from individuals of African ancestry with high-risk APOL1genotype. Biomarker association with a composite renal outcome of ESRD or 40% sustained decline in estimated glomerular filtration rate (eGFR) was then determined and then assessed as improvement in area under curve. Among the 498 participants, the median age was 56 years, 67.7% were female, and the baseline eGFR was 83.3 ml/min/1.73 m2with 80 reaching outcome over 5.9 years. TNFR1, TNFR2, and KIM1 at enrollment were independently associated with renal outcome continuously (adjusted hazard ratio 2.0 [95% confidence interval 1.3-3.1]; 1.5 [1.2-1.9]; and 1.6 [1.3-1.9] per doubling in levels, respectively) or by tertiles. The area under the curve significantly improved from 0.75 with the clinical model to 0.79 with the biomarker-enhanced model. The event rate was 40% with all 3 biomarkers elevated (adjusted odds ratio of 5.3 (2.3-12.0) vs. 17% (adjusted odds ratio 1.8 [0.9-3.6] with 1 or 2 elevated and 7% with no biomarkers elevated. Thus, plasma concentrations of TNFR1, TNFR2, and KIM1 are independently associated with renal outcome and improve discrimination or reclassification of African ancestry individuals with a high-risk APOL1genotype and preserve renal function. Elevation of all markers had higher risk of outcome and can assist with better clinical prediction and improved clinical trial efficiency by enriching event rates.

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HLA matching and mismatching, while inversely related, are not exact opposites. Here we determined the independent effects of HLA matching and mismatching on outcomes in deceased donor kidney transplant recipients. The United Network for Organ Sharing database (1995–2012) was utilized and analyzed for delayed graft function, one-year acute rejection, and death-censored graft survival using combined multivariable models including HLA matching and mismatching. Sensitivity analyses were performed using the subgroup of deceased donor kidney transplant patients after 2003 with more uniform HLA nomenclature and resampling analyses using bootstrapping on complete data available from 96,236 recipients. Individually, both HLA matching and mismatching showed significant associations with graft survival. Adjusting the model to take into account both matching and mismatching simultaneously, the degree of HLA mismatching lost significance while matching continued to have a significant prediction for delayed graft function, the one-year acute rejection rate, and graft survival. Sensitivity analyses and bootstrapping showed similar results for all studied outcomes. Thus, analysis of this large cohort demonstrates the apparent greater association of HLA matching over HLA mismatching on both early allograft events as well as graft survival. Future analyses should preferentially utilize HLA matching as a covariate over mismatching for accurately reflecting impact on graft outcomes.

The diagnosis of acute kidney injury (AKI), which is currently defined as an increase in serum creatinine (Scr) concentration, provides little information on the condition’s actual cause. To improve phenotyping of AKI, many urinary biomarkers of tubular injury are being investigated. Because AKI cases are not frequently biopsied, the diagnostic accuracy of concentrations of Scr and urinary biomarkers for histologic acute tubular injury is unknown.

Analyses of the Grampian Laboratory Outcomes Morbidity and Mortality Study-II cohort support the notion that acute kidney injury (AKI) increases the risk of progression of glomerular filtration rate after recovery from AKI to a new baseline. However, the findings have to be considered in the bigger context of the absolute event rates for de novoprogression versus nonrecovery and the competing risk of death after AKI. Examination of the data raises important implications for the design and implementation of clinical trials with interventions that target the AKI-to–chronic kidney disease transition.