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Objectives: The epidemiology of hospitalized acute kidney injury (AKI) among people living with HIV (PLWH) in the era of modern antiretroviral therapy (ART) for all PLWH is not well characterized. We evaluated the incidence of and risk factors for hospitalized AKI from 2005 to 2015 among PLWH on ART. Methods: We conducted a retrospective analysis of PLWH from the Johns Hopkins HIV Clinical Cohort. We defined hospitalized AKI as a rise of ≥ 0.3 mg/dL in serum creatinine (SCr) within any 48‐h period or a 50% increase in SCr from baseline and assessed associations of risk factors with incident AKI using multivariate Cox regression models. Results: Most participants (75%) were black, 34% were female, and the mean age was 43 years. The incidence of AKI fluctuated annually, peaking at 40 per 1000 person‐years (PY) [95% confidence interval (CI) 22–69 per 1000 PY] in 2007, and reached a nadir of 20 per 1000 PY (95% CI 11–34 per 1000 PY) in 2010. There was no significant temporal trend (−3.3% change per year; 95% CI −8.6 to 2.3%; P = 0.24). After multivariable adjustment, characteristics independently associated with AKI included black race [hazard ratio (HR) 2.44; 95% CI 1.42–4.20], hypertension (HR 1.62; 95% CI 1.09–2.38), dipstick proteinuria > 1 (HR 1.86; 95% CI 1.07–3.23), a history of AIDS (HR 1.82; 95% CI 1.29–2.56), CD4 count < 200 cells/µL (HR 1.46; 95% CI 1.02–2.07), and lower serum albumin (HR 1.73 per 1 g/dL decrease; 95% CI 1.02–2.07). Conclusions: In this contemporary cohort of PLWH, the annual incidence of first AKI fluctuated during the study period. Attention to modifiable AKI risk factors and social determinants of health may further reduce AKI incidence among PLWH. [ABSTRACT FROM AUTHOR]

The article discusses the underrepresentation of chronic renal disease in randomized controlled trials of cardiovascular disease. Nine million people in the United States population have chronic kidney disease. And of these many have cardiovascular disease (CVD), specifically coronary artery disease and chronic congestive heart failure. Recent studies suggest that renal disease independently portends increased morbidity and mortality in CVD. Because renal disease is so prevalent in CVD and the pathophysiologic processes so different from those with normal renal functions, it is important to have data on the subgroup of renal diseases. Patients with renal diseases must not be excluded, but included in CVD trials which need to be designated for this population of chronic renal patients.

Chuang P, Parikh CR, Langone A. Urinary tract infections after renal transplantation: a retrospective review at two US transplant centers.Clin Transplant 2005 DOI: 10.1111/j.1399-0012.2005.00327.x© Blackwell Munksgaard, 2005Urinary tract infections (UTIs) are the most common infectious complication following renal transplantation. Previous studies uniformly report that renal transplant recipients develop UTIs more often than the general population, but widely differ on how frequently UTIs occur after transplantation. These studies also disagree on the risk factors associated with developing post-transplant UTIs, as well as the effect that UTIs may have on graft outcomes and patient mortality. We performed a retrospective cohort study including all the adult patients who received a renal transplant at two US transplant centers from January 1996 to December 2002 (500 patients). Two hundred and thirteen (43%) patients developed one or more post-transplant UTIs over a mean follow-up period of 42 months. Significant risk factors for post-transplant UTIs were advanced age, female gender, reflux kidney disease, use of azathioprine and cadaveric donor. UTIs did not increase risk for renal graft loss, but were associated with increased mortality (3.5 odds ratio, 95% confidence interval 1.68–7.23). We conclude UTIs may be associated with an increased mortality risk in renal transplant recipients. Prevention of UTIs in high-risk renal transplant patients or those with recurrent UTIs may possibly decrease post-transplant mortality. [ABSTRACT FROM AUTHOR]

Recipients of hematopoietic cell transplantation may be at risk for developing acute kidney injury (AKI), and this risk may be increased in patients who undergo transplantation for severe systemic sclerosis (SSc) due to underlying scleroderma renal disease. AKI after transplantation can increase treatment-related mortality. To better define these risks, we analyzed 91 patients with SSc who were enrolled in 3 clinical trials in the United States of autologous or allogeneic hematopoietic cell transplantation (HCT). Eleven (12%) of the 91 patients with SSc in these studies (8 undergoing autologous HCT, 1 undergoing allogeneic HCT, 1 pretransplantation, 1 given i.v. cyclophosphamide on a transplantation trial) experienced AKI, of whom 8 required dialysis and/or therapeutic plasma exchange. AKI injury in the 9 HCT recipients developed a median of 35 days (range, 0-90 days) after transplantation. Ten of 11 patients with AKI received angiotensin-converting enzyme inhibitor (ACE-I) therapy. The etiology of AKI was attributed to scleroderma renal crisis in 6 patients (including 2 with normotensive renal crisis), to AKI of uncertain etiology in 2 patients, and to AKI superimposed on scleroderma kidney disease in 3 patients. Eight of the 11 patients died, one each because of progression of SSc, multiorgan failure, gastrointestinal and pulmonary bleeding, pericardial tamponade and pulmonary complications, diffuse alveolar hemorrhage, pulmonary embolism, graft-versus-host disease, and malignancy. Limiting nephrotoxins, cautious use of corticosteroids, renal shielding during total body irradiation, strict control of blood pressure, and aggressive use of ACE-Is may be of importance in preventing renal complications after HCT for SSc. [Copyright &y& Elsevier]

Background: The prevalence of hypertension and uncontrolled hypertension may differ by age and sex., Methods: We included participants in the Atherosclerosis Risk in Communities study at seven study visits over 33 years (visit 1: 15 636 participants; mean age, 54 years; 55% women), estimating sex differences in prevalence of hypertension (systolic blood pressure ≥130 mm Hg; diastolic blood pressure ≥80 mm Hg; or self-reported antihypertension medication use) and uncontrolled hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) using unadjusted and comorbidity-adjusted models., Results: The prevalence of hypertension increased with age from 40% (ages, 43-46 years) to 93% (ages, 91-94 years). Within hypertensive individuals, the prevalence of uncontrolled hypertension was higher in men (33%) than women (23%) at ages 43 to 46 years but became higher in women than men starting at ages 61 to 64, with 56% of women and 40% men having uncontrolled hypertension at ages 91 to 94. This sex difference was not explained by differences in coronary heart disease, diabetes, body mass index, estimated glomerular filtration rate, number of antihypertension medications, classes of medications, or adherence to medications. In both sexes, uncontrolled hypertension was associated with a higher risk for chronic kidney disease progression (hazard ratio, 1.5 [1.2-1.9]; P =4.5×10 -4 ), heart failure (hazard ratio, 1.6 [1.4-2.0]; P =8.1×10 -7 ), stroke (hazard ratio, 2.1 [1.6-2.8]; P =1.8×10 -8 ), and mortality (hazard ratio, 1.5 [1.3-1.6]; P =6.2×10 -19 )., Conclusions: Sex differences in the prevalence of hypertension and uncontrolled hypertension vary by age, with the latter having implications for health throughout the life course., Competing Interests: The data reported here have been supplied by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the US government. USRDS data were used for Table 3. The opinions presented do not necessarily represent those of the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, the Department of Health and Human Services, or the US Government. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US Government.

Acute kidney injury is common among hospitalized individuals, particularly those exposed to certain medications, and is associated with substantial morbidity and mortality. In a pragmatic, open-label, National Institutes of Health-funded, parallel group randomized controlled trial (clinicaltrials.gov NCT02771977), we investigate whether an automated clinical decision support system affects discontinuation rates of potentially nephrotoxic medications and improves outcomes in patients with AKI. Participants included 5060 hospitalized adults with AKI and an active order for any of three classes of medications of interest: non-steroidal anti-inflammatory drugs, renin-angiotensin-aldosterone system inhibitors, or proton pump inhibitors. Within 24 hours of randomization, a medication of interest was discontinued in 61.1% of the alert group versus 55.9% of the usual care group (relative risk 1.08, 1.04 - 1.14, p = 0.0003). The primary outcome - a composite of progression of acute kidney injury, dialysis, or death within 14 days - occurred in 585 (23.1%) of individuals in the alert group and 639 (25.3%) of patients in the usual care group (RR 0.92, 0.83 - 1.01, p = 0.09). Trial Registration Clinicaltrials.gov NCT02771977., (© 2023. The Author(s).)

Competing Interests: Conflicts of Interest: See Disclosures at the end of the article.

Background and Objectives: Moderate coffee consumption has been associated with lower risk of CKD; however, the exact biologic mechanisms underlying this association are unknown. Metabolomic profiling may identify metabolic pathways that explain the association between coffee and CKD. The goal of this study was to identify serum metabolites associated with coffee consumption and examine the association between these coffee-associated metabolites and incident CKD., Design, Setting, Participants, & Measurements: Using multivariable linear regression, we identified coffee-associated metabolites among 372 serum metabolites available in two subsamples of the Atherosclerosis Risk in Communities study (ARIC; n =3811). Fixed effects meta-analysis was used to pool the results from the two ARIC study subsamples. Associations between coffee and metabolites were replicated in the Bogalusa Heart Study ( n =1043). Metabolites with significant associations with coffee in both cohorts were then evaluated for their prospective associations with incident CKD in the ARIC study using Cox proportional hazards regression., Results: In the ARIC study, mean (SD) age was 54 (6) years, 56% were daily coffee drinkers, and 32% drank >2 cups per day. In the Bogalusa Heart Study, mean (SD) age was 48 (5) years, 57% were daily coffee drinkers, and 38% drank >2 cups per day. In a meta-analysis of two subsamples of the ARIC study, 41 metabolites were associated with coffee consumption, of which 20 metabolites replicated in the Bogalusa Heart Study. Three of these 20 coffee-associated metabolites were associated with incident CKD in the ARIC study., Conclusions: We detected 20 unique serum metabolites associated with coffee consumption in both the ARIC study and the Bogalusa Heart Study, and three of these 20 candidate biomarkers of coffee consumption were associated with incident CKD. One metabolite (glycochenodeoxycholate), a lipid involved in primary bile acid metabolism, may contribute to the favorable kidney health outcomes associated with coffee consumption. Two metabolites ( O -methylcatechol sulfate and 3-methyl catechol sulfate), both of which are xenobiotics involved in benzoate metabolism, may represent potential harmful aspects of coffee on kidney health., (Copyright © 2021 by the American Society of Nephrology.)

AKI frequently occurs in patients with COVID-19, and kidney injury severe enough to require RRT is a common complication among patients who are critically ill. During the surge of the pandemic, there was a high demand for dialysate for continuous RRT, and this increase in demand, coupled with vulnerabilities in the supply chain, necessitated alternative approaches, including internal production of dialysate. Using a standard hemodialysis machine and off-the-shelf supplies, as per Food and Drug Administration guidelines, we developed a method for on-site dialysate production that is adaptable and can be used to fill multiple bags at once. The use of a central reverse osmosis unit, dedicated hemodialysis machine, sterile bags with separate ports for fill and use, and frequent testing will ensure stability, sterility, and-therefore-safety of the produced dialysate. The dialysate made in house was tested and it showed both stability and sterility for at least 30 hours. This detailed description of our process for generating dialysate can serve as a guide for other programs experiencing similar vulnerabilities in the demand versus supply of dialysate., Competing Interests: C.R. Parikh reports having consultancy agreements with Genfit Biopharmaceutical Company; serving as a scientific advisor for, or member of, Genfit Biopharmaceutical Company and RenalytixAI; having ownership interest in RenalytixAI; and receiving research funding from the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). D. Fine reports serving on the medical advisory board for Fresenius Medical Corporation, and having consultancy agreements with GlaxoSmithKline (data and safety monitoring board). S. Mohan reports serving as a member of the Angion Pharma scientific advisory board, as deputy editor for Kidney International Reports (International Society of Nephrology), receiving research funding from Angion Biomedica; receiving research funding from NIH (National Institute of Biomedical Imaging and Bioengineering, National Institute on Minority Health and Health Disparities, and NIDDK). All remaining authors have nothing to disclose., (Copyright © 2021 by the American Society of Nephrology.)

Background: Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes., Methods: Primary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and GF contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II in mouse macrophages., Results: Doubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 1.02-1.2), whereas OPN decreased dcGF risk (aHR, 0.94; 95% CI, 0.88-1). UMOD:OPN ratio ≤3 strengthened the association, with reduced dcGF risk (aHR, 0.57; 0.41-0.80) with similar associations for GF, and in the test dataset. A ratio ≤3 was also associated with lower DGF (aOR, 0.73; 95% CI, 0.60-0.89) and higher 6-month eGFR (adjusted β coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II expression elucidating a possible mechanism behind UMOD's association with GF., Conclusions: UMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR, and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation., Competing Interests: S.G.M. supported by the American Heart Association (18CDA34110151) and Patterson Trust Fund. P.P.R. supported by epidemiology consulting from COHRDATA related to dialysis outcomes. This study received grant/research support from Merck, CVS and initiated grants from Merck to the University of Pennsylvania to support the THINKER (kidney), USHER (heart), and SHELTER (lung) trials of transplanting organs from donors with Hepatitis C into Hepatitis C negative recipients. It initiated grants from CVS to the University of Pennsylvania to support studies of medication adherence. I.E.H. received NIH grant support from NCATS (UL1TR002538 and KL2TR002539). T.M.E.-A. received grant support from NIDDK and US Department of Veterans Affairs. M.D.D. obtained the salary support from NIDDK. S.M. received grant/research support from NIH (NIDDK/NIAID/NIHMD/NIBIB) and consulting fees from Angion Pharmaceuticals. A.Z.R. received NDAs with Pliant Therapeutics and xMD Diagnostics, advisory board of Escala Therapeutics. C.R.P. received consulting fee from Renalytix and grant/research support from National Institute of Diabetes and Digestion and Kidney Diseases, National Heart, Lung, and Blood Institute and Data Safety and Monitoring Board of Genfit, Abbott. M.N.H. received grant support from NIH/NIDDK. The other authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Patients undergoing cardiac surgery are placed under intense physiologic stress. Blood and urine biomarkers measured peri-operatively may help identify patients at higher risk for adverse long-term kidney outcomes.We sought to determine independent associations of various biomarkers with development or progression of chronic kidney disease (CKD) following cardiac surgery. In this sub-study of the prospective cohort -TRIBE-AKI Study, we evaluated 613 adult patients undergoing cardiac surgery in Canada in our primary analysis and tested the association of 40 blood and urinary biomarkers with the primary composite outcome of CKD incidence or progression. In those with baseline estimated glomerular filtration rate (eGFR) over 60 mL/min/1.73m 2 , we defined CKD incidence as a 25% reduction in eGFR and an eGFR under 60. In those with baseline eGFR under 60 mL/min/1.73m 2 , we defined CKD progression as a 50% reduction in eGFR or eGFR under 15. Results were evaluated in a replication cohort of 310 patients from one study site in the United States. Over a median follow-up of 5.6 years, 172 patients developed the primary outcome. Each log increase in basic fibroblast growth factor (adjusted hazard ratio 1.52 [95% confidence interval 1.19, 1.93]), Kidney Injury Molecule-1 (1.51 [0.98, 2.32]), N-terminal pro-B-type natriuretic peptide (1.19 [1.01, 1.41]), and tumor necrosis factor receptor 1 (1.75 [1.18, 2.59]) were associated with outcome after adjustment for demographic factors, serum creatinine, and albuminuria. Similar results were noted in the replication cohort. Although there was no interaction by acute kidney injury in continuous analysis, mortality was higher in the no acute kidney injury group by biomarker tertile. Thus, elevated post-operative levels of blood biomarkers following cardiac surgery were independently associated with the development of CKD. These biomarkers can provide additional value in evaluating CKD incidence and progression after cardiac surgery., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: AKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have focused on AKI treated with RRT (AKI-RRT)., Methods: We conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regression to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day mortality among such patients., Results: A total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD, men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher d-dimer, and greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1-123 days), 403 of the 637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hospitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39 (18.1%) remained RRT dependent 60 days after ICU admission., Conclusions: AKI-RRT is common among critically ill patients with COVID-19 and is associated with a hospital mortality rate of >60%. Among those who survive to discharge, one in three still depends on RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission., (Copyright © 2021 by the American Society of Nephrology.)

There are limited data on the nonprocurement of kidneys from solid organ donors. Analysis of Standard Transplant Analysis and Research files was undertaken on all deceased donors in the United States with at least 1 solid organ recovered. From 2000 to 2018, 21 731 deceased donor kidneys (averaging 1144 kidneys per year) were not procured. No kidneys were procured from 8% of liver donors, 3% of heart donors, and 3% of lung donors. Compared to donors with all kidneys procured, those with none procured were older and more likely obese, black, hypertensive, diabetic, hepatitis C positive, smokers, Public Health Service - Increased Risk designated, deceased after cardiac death, or deceased after cerebrovascular accident. Although these donors had lower quality kidneys (median Kidney Donor Risk Index (interquartile range) 1.9 (1.0) vs 1.2 (0.7)), there was substantial overlap in quality between nonprocured and procured kidneys. Nearly one third of nonprocurements were attributed to donor history. Donors with elevated terminal creatinine likely resulting from acute kidney injury (AKI) had higher odds of kidney nonprocurement. Nonprocurement odds varied widely across Organ Procurement and Transplantation Network regions, with a positive correlation between donor kidney nonprocurements and kidney discards at the donation service area level. These findings suggest current discard rates underestimate the underutilization of deceased donor kidneys and more research is needed to optimize safe procurement and utilization of kidneys from donors with AKI., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Importance: The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19., Objectives: To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19., Design, Setting, and Participants: This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020., Exposures: Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds., Main Outcomes and Measures: The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes., Results: A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (≥80 vs <40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (≥40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (Pao2:Fio2<100 vs ≥300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2-4 vs 0: OR, 2.61; 95% CI, 1.30-5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46-4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs ≥100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies., Conclusions and Relevance: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.

Background and Objectives: The association of AKI after pediatric cardiac surgery with long-term CKD and hypertension development is unclear. The study objectives were to determine whether AKI after pediatric cardiac surgery is associated with incident CKD and hypertension., Design, Setting, Participants, & Measurements: This was a prospective cohort study of children of 1 month to 18 years old who were undergoing cardiac surgery at two tertiary care centers (Canada, United States). Participants were recruited before cardiac surgery and were followed during hospitalization and at 3, 12, 24, 36, and 48 months after discharge. Exposures were postoperative AKI, based on the Kidney Disease Improving Global Outcomes (KDIGO) definition, and age <2 years old at surgery. Outcomes and measures were CKD (low eGFR or albuminuria for age) and hypertension (per the 2017 American Academy of Pediatrics guidelines) at follow-up, with the composite outcome of CKD or hypertension., Results: Among 124 participants, 57 (46%) developed AKI. AKI versus non-AKI participants had a median (interquartile range) age of 8 (4.8-40.8) versus 46 (6.0-158.4) months, respectively, and higher preoperative eGFR. From the 3- to 48-month follow-up, the cohort prevalence of CKD was high (17%-20%); hypertension prevalence was also high (22%-30%). AKI was not significantly associated with the development of CKD throughout follow-up. AKI was associated with hypertension development at 12 months after discharge (adjusted relative risk, 2.16; 95% confidence interval, 1.18 to 3.95), but not at subsequent visits. Children aged <2 years old at surgery had a significantly higher prevalence of hypertension during follow-up than older children (40% versus 21% at 3-month follow-up; 32% versus 13% at 48-month follow-up)., Conclusions: CKD and hypertension burden in the 4 years after pediatric cardiac surgery is high. Young age at surgery, but not AKI, is associated with their development., (Copyright © 2020 by the American Society of Nephrology.)

Although over 90 000 people are on the kidney transplant waitlist in the United States, some kidneys that are viable for transplantation are discarded. Transplant surgeons are more likely to discard deceased donors with acute kidney injury (AKI) versus without AKI (30% versus 18%). AKI is defined using changes in creatinine from baseline. Transplant surgeons can use DonorNet data, including admission, peak, and terminal serum creatinine, and biopsy data when available to differentiate kidneys with AKI from those with chronic injury. Although chronic kidney disease is associated with reduced graft survival, an abundance of literature has demonstrated similar graft survival for deceased donors with AKI versus donors without AKI. Donors with AKI are more likely to undergo delayed graft function but have similar long-term outcomes as donors without AKI. The mechanism for similar graft survival is unclear. Some hypothesized mechanisms include (1) ischemic preconditioning; (2) posttransplant and host factors playing a greater role in long-term survival than donor factors; and (3) selection bias of transplanting only relatively healthy donor kidneys with AKI. Existing literature suggests transplanting more donor kidneys with stage 1 and 2 AKI, and cautious utilization of stage 3 AKI donors, may increase the pool of viable kidneys. Doing so can reduce the number of people who die on the waitlist by over 500 every year.

Rationale & Objective: There may be important transplant-related differences between right and left kidneys, including logistical/surgical considerations about vessel length for the right compared to the left kidney from the same donor. Because US centers choose between the right and left kidney when their recipient is ranked higher on a "match-run," we sought to determine whether deceased-donor right kidneys have had worse posttransplantation outcomes than left kidneys., Study Design: Paired Organ Procurement and Transplantation Network analysis., Setting & Participants: Deceased-donor kidney pairs transplanted during 1990 to 2016., Exposure: Right versus left kidney controlling for other significant factors., Outcomes: Delayed graft function (DGF), all-cause and death-censored graft failure, and mortality., Analytical Approach: Multivariable conditional logistic regression for DGF; proportional hazards models (conditional on same donor) for failure/mortality with right kidneys (operationalized as 6-month time-varying coefficients) adjusting for DGF and other confounders., Results: 87,112 recipient pairs shared the following donor characteristics: mean age of 41 ± 14 years, 60% males, and 11% with cardiac death. Recipient characteristics were numerically similar by donor kidney side but with some statistical differences given the sample size. Right kidneys had slightly longer cold ischemia time. DGF occurred more often for right kidneys (28% vs 25.8%; P < 0.001; adjusted OR, 1.15 [95% CI, 1.12-1.17]). The adjusted hazard ratio (aHR) for all-cause graft failure with right kidneys within 6 months was 1.07 (95% CI, 1.03-1.11), and was 0.99 (95% CI, 0.97-1.01) thereafter. The aHRs for death-censored graft failure with right kidneys before and after 6 months were 1.11 (95% CI, 1.06-1.16) and 0.96 (95% CI, 0.93-0.99), respectively; the corresonding aHRs for mortality were 0.99 (95% CI, 0.93-1.04) and 1.00 (95% CI, 0.98-1.03), respectively., Limitations: Registry data, different transplant eras, reasons for kidney side unavailable., Conclusions: There is modest association for transplantation of right kidneys with DGF and graft loss within the first 6 months, which is lost beyond this time point. These findings do not support the use of laterality of deceased-donor kidneys as an important factor in organ acceptance decisions., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Importance: The severity of acute kidney injury (AKI) is usually determined based on the maximum serum creatinine concentration. However, the trajectory of kidney function recovery could be an additional important dimension of AKI severity., Objective: To assess whether the trajectory of kidney function recovery within 72 hours after AKI is associated with long-term risk of clinical outcomes., Design, Setting, and Participants: This prospective, multicenter cohort study enrolled 1538 adults with or without AKI 3 months after hospital discharge between December 1, 2009, and February 28, 2015. Statistical analyses were completed November 1, 2018. Participants with or without AKI were matched based on demographic characteristics, site, comorbidities, and prehospitalization estimated glomerular filtration rate. Participants with AKI were classified as having resolving or nonresolving AKI based on previously published definitions. Resolving AKI was defined as a decrease in serum creatinine concentration of 0.3 mg/dL or more or 25% or more from maximum in the first 72 hours after AKI diagnosis. Nonresolving AKI was defined as AKI not meeting the definition for resolving AKI., Main Outcomes and Measures: The primary outcome was a composite of major adverse kidney events (MAKE), defined as incident or progressive chronic kidney disease, long-term dialysis, or all-cause death during study follow-up., Results: Among 1538 participants (964 men; mean [SD] age, 64.6 [12.7] years), 769 (50%) had no AKI, 475 (31%) had a resolving AKI pattern, and 294 (19%) had a nonresolving AKI pattern. After a median follow-up of 4.7 years, the outcome of MAKE occurred in 550 (36%) of all participants. The adjusted hazard ratio for MAKE was higher for patients with resolving AKI (adjusted hazard ratio, 1.52; 95% CI, 1.01-2.29; P = .04) and those with nonresolving AKI (adjusted hazard ratio 2.30; 95% CI, 1.52-3.48; P < .001) compared with participants without AKI. Within the population of patients with AKI, nonresolving AKI was associated with a 51% greater risk of MAKE (95% CI, 22%-88%; P < .001) compared with resolving AKI. The higher risk of MAKE among patients with nonresolving AKI was explained by a higher risk of incident and progressive chronic kidney disease., Conclusions and Relevance: This study suggests that the 72-hour period immediately after AKI distinguishes the risk of clinically important kidney-specific long-term outcomes. The identification of different AKI recovery patterns may improve patient risk stratification, facilitate prognostic enrichment in clinical trials, and enable recognition of patients who may benefit from nephrology consultation.

Importance: The shortage of deceased donor kidneys for transplants is an ongoing concern. Prior studies support transplanting kidneys from deceased donors with acute kidney injury (AKI), but those investigations have been subject to selection bias and small sample sizes. Current allocation practices of AKI kidneys in the United States are not well characterized., Objectives: To evaluate the association of deceased donor AKI with recipient graft survival and to characterize recovery and discard practices for AKI kidneys by organ procurement organizations., Design, Setting, and Participants: Registry-based, propensity score-matched cohort study from January 1, 2010, to December 31, 2013, in the United States. The dates of analysis were March 1 to November 1, 2019. From 2010 to 2013, a total of 6832 deceased donors with AKI and 15 310 deceased donors without AKI had at least 1 kidney transplanted. This study used a 1:1, propensity score-matched analysis to match deceased donors with AKI to deceased donors without AKI and investigated outcomes in their corresponding kidney recipients., Exposure: Deceased donor AKI, defined as at least 50% or 0.3-mg/dL increase in terminal serum creatinine level from admission., Main Outcomes and Measures: Recipients were assessed for the time to death-censored graft failure and the following secondary outcomes: delayed graft function, primary nonfunction, and the time to all-cause graft failure., Results: Ninety-eight percent (6722 of 6832) of deceased donors with AKI were matched to deceased donors without AKI. The mean (SD) age of the 13 444 deceased donors was 40.4 (14.4) years, and 63% (8529 of 13 444) were male. A total of 25 323 recipients were analyzed (15 485 [61%] were male), and their mean (SD) age was 52.0 (14.7) years. Recipients were followed up for a median of 5 (interquartile range, 4-6) years. Deceased donor AKI status had no association with death-censored graft failure (hazard ratio, 1.01; 95% CI, 0.95-1.08) or all-cause graft failure (hazard ratio, 0.97; 95% CI, 0.93-1.02). The results were consistent after examining by AKI stage and adjusting for recipient and transplant characteristics. More recipients of AKI kidneys developed delayed graft function (29% vs 22%, P < .001). Few recipients (120 of 25 323 [0.5%]) developed primary nonfunction regardless of deceased donor AKI status. Recovery and transplantation of AKI kidneys varied by organ procurement organization; most (39 of 58) had high recovery and high discard of AKI kidneys., Conclusions and Relevance: Deceased donor AKI kidneys transplanted in the study period had recipient graft survival comparable to that of non-AKI kidneys. This study's findings suggest that the transplant community should evaluate whether currently discarded AKI kidneys from donors without substantial comorbidities can be used more effectively.

Cardiac surgery results in a multifactorial systemic inflammatory response with inflammatory cytokines, such as interleukin-10 and 6 (IL-10 and IL-6), shown to have potential in the prediction of adverse outcomes including readmission or mortality. This study sought to measure the association between IL-6 and IL-10 levels and 1-year hospital readmission or mortality following cardiac surgery. Plasma biomarkers IL-6 and IL-10 were measured in 1,047 patients discharged alive after isolated coronary artery bypass graft surgery from eight medical centers participating in the Northern New England Cardiovascular Disease Study Group between 2004 and 2007. Readmission status and mortality were ascertained using Medicare, state all-payer claims, and the National Death Index. We evaluated the association between preoperative and postoperative cytokines and 1-year readmission or mortality using Kaplan-Meier estimates and Cox's proportional hazards modeling, adjusting for covariates used in the Society of Thoracic Surgeons 30-day readmission model. The median follow-up time was 1 year. After adjustment, patients in the highest tertile of postoperative IL-6 values had a significantly increased risk of readmission or death within 1 year (HR: 1.38; 95% CI: 1.03-1.85), and an increased risk of death within 1 year of discharge (HR: 4.88; 95% CI: 1.26-18.85) compared with patients in the lowest tertile. However, postoperative IL-10 levels, although increasing through tertiles, were not found to be significantly associated independently with 1-year readmission or mortality (HR: 1.25; 95% CI: .93-1.69). Pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10 may be postoperative markers of cardiac injury, and IL-6, specifically, shows promise in predicting readmission and mortality following cardiac surgery., (© Copyright 2019 AMSECT.)

Background: Recent pilot trials have demonstrated the safety of transplanting HCV-viremic kidneys into HCV-seronegative recipients. However, it remains unclear if allograft function is impacted by donor HCV-viremia or recipient HCV-serostatus., Methods: We used national United States registry data to examine trends in HCV-viremic kidney use between 4/1/2015 and 3/31/2019. We applied advanced matching methods to compare eGFR for similar kidneys transplanted into highly similar recipients of kidney transplants., Results: Over time, HCV-seronegative recipients received a rising proportion of HCV-viremic kidneys. During the first quarter of 2019, 200 HCV-viremic kidneys were transplanted into HCV-seronegative recipients, versus 69 into HCV-seropositive recipients, while 105 HCV-viremic kidneys were discarded. The probability of HCV-viremic kidney discard has declined over time. Kidney transplant candidates willing to accept a HCV-seropositive kidney increased from 2936 to 16,809 from during this time period. When transplanted into HCV-seronegative recipients, HCV-viremic kidneys matched to HCV-non-viremic kidneys on predictors of organ quality, except HCV, had similar 1-year eGFR (66.3 versus 67.1 ml/min per 1.73 m 2 , P =0.86). This was despite the much worse kidney donor profile index scores assigned to the HCV-viremic kidneys. Recipient HCV-serostatus was not associated with a clinically meaningful difference in 1-year eGFR (66.5 versus 71.1 ml/min per 1.73 m 2 , P =0.056) after transplantation of HCV-viremic kidneys., Conclusions: By 2019, HCV-seronegative patients received the majority of kidneys transplanted from HCV-viremic donors. Widely used organ quality scores underestimated the quality of HCV-viremic kidneys based on 1-year allograft function. Recipient HCV-serostatus was also not associated with worse short-term allograft function using HCV-viremic kidneys., (Copyright © 2019 by the American Society of Nephrology.)

Rationale & Objective: 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., Study Design: Prospective cohort., Setting & Participants: 1,444 adults undergoing cardiac surgery in the TRIBE-AKI (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) cohort., Exposures: Plasma concentrations of 2 proangiogenic markers (vascular endothelial growth factor A [VEGF] and placental growth factor [PGF]) and 1 antiangiogenic marker (soluble VEGF receptor 1 [VEGFR1]), measured pre- and postoperatively within 6 hours after surgery., Outcomes: AKI, long AKI duration (≥7 days), and 1-year all-cause mortality., Analytical Approach: Multivariable logistic regression., Results: Following cardiac surgery, plasma VEGF concentrations decreased 2-fold, and PGF and VEGFR1 concentrations increased 1.5- and 8-fold, respectively. There were no meaningful associations of preoperative concentrations of angiogenic markers with outcomes of AKI and mortality. Higher postoperative VEGF and PGF concentrations were independently associated with lower odds of AKI (adjusted ORs of 0.89 [95% CI, 0.82-0.98] and 0.69 [95% CI, 0.55-0.87], respectively), long AKI duration (0.65 [95% CI, 0.49-0.87] and 0.48 [95% CI, 0.28-0.82], respectively), and mortality (0.74 [95% CI, 0.62-0.89] and 0.46 [95% CI, 0.31-0.68], respectively). In contrast, higher postoperative VEGFR1 concentrations were independently associated with higher odds of AKI (1.56; 95% CI, 1.31-1.87), long AKI duration (1.75; 95% CI, 1.09-2.82), and mortality (2.28; 95% CI, 1.61-3.22)., Limitations: Angiogenesis markers were not measured after hospital discharge, so we were unable to determine long-term trajectories of angiogenesis marker levels during recovery and follow-up., Conclusions: Higher levels of postoperative proangiogenic markers, VEGF and PGF, were associated with lower AKI and mortality risk, whereas higher postoperative antiangiogenic VEGFR1 levels were associated with higher risk for AKI and mortality., (Copyright © 2019 National Kidney Foundation, Inc. All rights reserved.)

Background: HIV-infected (HIV+) persons are at increased risk of chronic kidney disease, but serum creatinine does not detect early losses in kidney function. We hypothesized that urine biomarkers of kidney damage would be associated with subsequent changes in kidney function in a contemporary cohort of HIV+ and HIV-uninfected (HIV-) men., Methods: In the Multicenter AIDS Cohort Study, we measured baseline urine concentrations of 5 biomarkers from 2009 to 2011 in 860 HIV+ and 337 HIV- men: albumin, alpha-1-microglobulin (α1m), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and procollagen type III N-terminal propeptide (PIIINP). We evaluated associations of urine biomarker concentrations with annual changes in estimated glomerular filtration rate (eGFR) using multivariable linear mixed models adjusted for demographics, traditional kidney disease risk factors, HIV-related risk factors, and baseline eGFR., Results: Over a median follow-up of 4.8 years, the average annual eGFR decline was 1.42 mL/min/1.73 m2/year in HIV+ men and 1.22 mL/min/1.73 m2/year in HIV- men. Among HIV+ men, the highest vs. lowest tertiles of albumin (-1.78 mL/min/1.73 m2/year, 95% CI -3.47 to -0.09) and α1m (-2.43 mL/min/1.73 m2/year, 95% CI -4.14 to -0.73) were each associated with faster annual eGFR declines after multivariable adjustment. Among HIV- men, the highest vs. lowest tertile of α1m (-2.49 mL/min/1.73 m2/year, 95% CI -4.48 to -0.50) was independently associated with faster annual eGFR decline. Urine IL-18, KIM-1, and PIIINP showed no independent associations with eGFR decline, regardless of HIV serostatus., Conclusions: Among HIV+ men, higher urine albumin and α1m are associated with subsequent declines in kidney function, independent of eGFR., (© 2019 S. Karger AG, Basel.)

Background: Accumulating evidence implicates the complement cascade as pathogenically contributing to ischemia-reperfusion injury and delayed graft function (DGF) in human kidney transplant recipients. Building on observations that kidney injury can initiate in the donor before nephrectomy, we tested the hypothesis that anaphylatoxins C3a and C5a in donor urine before transplantation associate with risk of posttransplant injury., Methods: We evaluated the effects of C3a and C5a in donor urine on outcomes of 469 deceased donors and their corresponding 902 kidney recipients in a subset of a prospective cohort study., Results: We found a threefold increase of urinary C5a concentrations in donors with stage 2 and 3 acute kidney injury (AKI) compared donors without AKI (P < 0.001). Donor C5a was higher for the recipients with DGF (defined as dialysis in the first week posttransplant) compared with non-DGF (P = 0.002). In adjusted analyses, C5a remained independently associated with recipient DGF for donors without AKI (relative risk, 1.31; 95% confidence interval, 1.13-1.54). For donors with AKI, however, urinary C5a was not associated with DGF. We observed a trend toward better 12-month allograft function for kidneys from donors with C5a concentrations in the lowest tertile (P = 0.09). Urinary C3a was not associated with donor AKI, recipient DGF, or 12-month allograft function., Conclusions: Urinary C5a correlates with the degree of donor AKI. In the absence of clinical donor AKI, donor urinary C5a concentrations associate with recipient DGF, providing a foundation for testing interventions aimed at preventing DGF within this high-risk patient subgroup.

Background: Hospital readmission within 30 days is associated with higher risks of complications, death, and increased costs. Accurate statistical models to stratify the risk of 30-day readmission or death after cardiac surgery could help clinical teams focus care on those patients at highest risk. We hypothesized biomarkers could improve prediction for readmission or mortality., Methods: Levels of ST2, galectin-3, N-terminal pro-brain natriuretic peptide, cystatin C, interleukin-6, and interleukin-10 were measured in samples from 1,046 patients discharged after isolated coronary artery bypass graft surgery from eight medical centers, with external validation in 1,194 patients from five medical centers. Thirty-day readmission or mortality were ascertained using Medicare, state all-payer claims, and the National Death Index. We tested and externally validated the clinical models and the biomarker panels using area under the receiver-operating characteristics (AUROC) statistics., Results: There were 112 patients (10.7%) who were readmitted or died within 30 days after coronary artery bypass graft surgery. The Society of Thoracic Surgeons augmented clinical model resulted in an AUROC of 0.66 (95% confidence interval: 0.61 to 0.71). The biomarker panel with The Society of Thoracic Surgeons augmented clinical model resulted in an AUROC of 0.74 (bootstrapped 95% confidence interval: 0.69 to 0.79, p < 0.0001). External validation of the model showed limited improvement with the addition of a biomarker panel, with an AUROC of 0.51 (95% confidence interval: 0.45 to 0.56)., Conclusions: Although biomarkers significantly improved prediction of 30-day readmission or mortality in our derivation cohort, the external validation of the biomarker panel was poor. Biomarkers perform poorly, much like other efforts to improve prediction of readmission, suggesting there are many other factors yet to be explored to improve prediction of readmission., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Previous 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., Methods: We 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 in those with an eGFR >60 mL/min/1.73 m2 at baseline. Cystatin C-based eGFR was calculated at baseline, Year 3 and Year 10., Results: Mean 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)., Conclusions: Lower 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.

Background: Kidneys with "high" Kidney Donor Profile Index (KDPI) are often biopsied and pumped, yet frequently discarded., Methods: In this multicenter study, we describe the characteristics and outcomes of kidneys with KDPI of 80 or greater that were procured from 338 deceased donors. We excluded donors with anatomical kidney abnormalities., Results: Donors were categorized by the number of kidneys discarded: (1) none (n = 154, 46%), (2) 1 discarded and 1 transplanted (n = 48, 14%), (3) both discarded (n = 136, 40%). Donors in group 3 were older, more often white, and had higher terminal creatinine and KDPI than group 1 (all P < 0.05). Biopsy was performed in 92% of all kidneys, and 47% were pumped. Discard was associated with biopsy findings and first hour renal resistance. Kidney injury biomarker levels (neutrophil gelatinase-associated lipocalin, IL-18, and kidney injury molecule-1 measured from donor urine at procurement and from perfusate soon after pump perfusion) were not different between groups. There was no significant difference in 1-year estimated glomerular filtration rate or graft failure between groups 1 and 2 (41.5 ± 18 vs 41.4 ± 22 mL/min per 1.73 m; P = 0.97 and 9% vs 10%; P = 0.76)., Conclusions: Kidneys with KDPI of 80 or greater comprise the most resource consuming fraction of our donor kidney pool and have the highest rates of discard. Our data suggest that some discarded kidneys with KDPI of 80 or greater are viable; however, current tools and urine and perfusate biomarkers to identify these viable kidneys are not satisfactory. We need better methods to assess viability of kidneys with high KDPI.

Background and Objectives: Data reported to the Organ Procurement and Transplantation Network (OPTN) are used in kidney transplant research, policy development, and assessment of center quality, but the accuracy of early post-transplant outcome measures is unknown., Design, Setting, Participants, & Measurements: The Deceased Donor Study (DDS) is a prospective cohort study at five transplant centers. Research coordinators manually abstracted data from electronic records for 557 adults who underwent deceased donor kidney transplantation between April of 2010 and November of 2013. We compared the post-transplant outcomes of delayed graft function (DGF; defined as dialysis in the first post-transplant week), acute rejection, and post-transplant serum creatinine reported to the OPTN with data collected for the DDS., Results: Median kidney donor risk index was 1.22 (interquartile range [IQR], 0.97-1.53). Median recipient age was 55 (IQR, 46-63) years old, 63% were men, and 47% were black; 93% had received dialysis before transplant. Using DDS data as the gold standard, we found that pretransplant dialysis was not reported to the OPTN in only 11 (2%) instances. DGF in OPTN data had a sensitivity of 89% (95% confidence interval [95% CI], 84% to 93%) and specificity of 98% (95% CI, 96% to 99%). Surprisingly, the OPTN data accurately identified acute allograft rejection in only 20 of 47 instances (n=488; sensitivity of 43%; 95% CI, 17% to 73%). Across participating centers, sensitivity of acute rejection varied widely from 23% to 100%, whereas specificity was uniformly high (92%-100%). Six-month serum creatinine values in DDS and OPTN data had high concordance (n=490; Lin concordance correlation =0.90; 95% CI, 0.88 to 0.92)., Conclusions: OPTN outcomes for recipients of deceased donor kidney transplants have high validity for DGF and 6-month allograft function but lack sensitivity in detecting rejection. Future studies using OPTN data may consider focusing on allograft function at 6 months as a useful outcome., (Copyright © 2016 by the American Society of Nephrology.)

Background: Studies suggest that in patients with heart failure (HF), high serum erythropoietin is associated with risk of recurrent HF and mortality. Trials of erythropoietin-stimulating agents in persons with kidney disease have also suggested an increased incidence of adverse clinical events. No large studies of which we are aware have evaluated the association of endogenous erythropoietin levels with clinical outcomes in the community-living older adults., Methods and Results: Erythropoietin concentration was measured in 2488 participants aged 70-79 years in the Health, Aging and Body Composition Study. Associations of erythropoietin with incident HF, coronary heart disease, stroke, mortality, and ≥ 30% decline in estimated glomerular filtration rate were examined using Cox proportional hazards and logistic regression over 10.7 years of follow-up. Mean (SD) age was 75 (3) years and median (quartile 1, quartile 3) erythropoietin was 12.3 (9.0, 17.2) mIU/mL. There were 503 incident HF events, and each doubling of serum erythropoietin was associated with a 25% increased risk of incident HF 1.25 (95% confidence interval 1.13, 1.48) after adjusting for demographics, prevalent cardiovascular disease, cardiovascular disease risk factors, kidney function, and serum hemoglobin. There was no interaction of serum erythropoietin with chronic kidney disease or anemia (P > 0.50). There were 330 incident coronary heart disease events, 161 strokes, 1112 deaths, and 698 outcomes of ≥ 30% decline in estimated glomerular filtration rate. Serum erythropoietin was not significantly associated with these outcomes., Conclusions: Higher levels of endogenous erythropoietin are associated with incident HF in older adults. Studies need to elucidate the mechanisms through which endogenous erythropoietin levels associate with specific outcomes., (© 2015 American Heart Association, Inc.)

Background: Children undergoing cardiac surgery may exhibit a pronounced inflammatory response to cardiopulmonary bypass (CPB). Inflammation is recognized as an important pathophysiologic process leading to acute kidney injury (AKI). The aim of this study was to evaluate the association of the inflammatory cytokines interleukin (IL)-6 and IL-10 with AKI and other adverse outcomes in children after CPB surgery., Methods: This is a sub-study of the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) cohort, including 106 children ranging in age from 1 month to 18 years undergoing CPB. Plasma IL-6 and IL-10 concentrations were measured preoperatively and postoperatively [day 1 (within 6 h after surgery) and day 3]., Results: Stage 2/3 AKI, defined by at least a doubling of the baseline serum creatinine concentration or dialysis, was diagnosed in 24 (23%) patients. The preoperative IL-6 concentration was significantly higher in patients with stage 2/3 AKI [median 2.6 pg/mL, interquartile range (IQR) 2.6 0.6-4.9 pg/mL] than in those without stage 2/3 AKI (median 0.6 pg/mL, IQR 0.6-2.2 pg/mL) (p = 0.03). After adjustment for clinical and demographic variables, the highest preoperative IL-6 tertile was associated with a sixfold increased risk for stage 2/3 AKI compared with the lowest tertile (adjusted odds ratio 6.41, 95 % confidence interval 1.16-35.35). IL-6 and IL-10 levels increased significantly after surgery, peaking postoperatively on day 1. First postoperative IL-6 and IL-10 measurements did not significantly differ between patients with stage 2/3 AKI and those without stage 2/3 AKI. The elevated IL-6 level on day 3 was associated with longer hospital stay (p = 0.0001)., Conclusions: Preoperative plasma IL-6 concentration is associated with the development of stage 2/3 AKI and may be prognostic of resource utilization.

Background and Objectives: Despite advances in therapy, HIV-infected individuals remain at higher risk for kidney dysfunction than uninfected individuals. It was hypothesized that urine levels of α1-microglobulin, a biomarker of proximal tubular dysfunction, would predict kidney function decline and mortality risk in HIV-infected and uninfected women., Design, Setting, Participants, & Measurements: In the Women's Interagency HIV Study, urine α1-microglobulin and creatinine concentrations were measured in 903 HIV-infected and 287 uninfected women using stored urine from 1999 to 2000, when prevalence of tenofovir use was <1%. Participants were categorized into three categories by level of α1-microglobulin-to-creatinine ratio, and associations with kidney decline and all-cause mortality over 8 years were evaluated., Results: Urine α1-microglobulin was detectable in 60% of HIV-infected and 40% of uninfected women (P<0.001). Among HIV-infected women, there were 177 (22%), 61 (7%), and 128 (14%) patients with incident CKD, with 10% annual eGFR decline, and who died, respectively. Compared with HIV-infected women in the lowest α1-microglobulin category, HIV-infected women in the highest α1-microglobulin category had a 2.1-fold risk of incident CKD (95% confidence interval, 1.3 to 3.4), 2.7-fold risk of 10% annual eGFR decline (95% confidence interval, 1.2 to 5.9), and 1.6-fold mortality risk (95% confidence interval, 1.0 to 2.6) in models adjusting for kidney risk factors, baseline eGFR, and albuminuria. Among uninfected women, the highest α1-microglobulin category was associated with 3% (relative risk, 2.2; 95% confidence interval, 1.4 to 3.5) and 5% (relative risk, 2.2; 95% confidence interval, 1.1 to 4.3) annual eGFR decline relative to the lowest α1-microglobulin category., Conclusions: Proximal tubular dysfunction, indicated by urine α1-microglobulin, was independently associated with kidney function decline in HIV-infected and uninfected women and mortality risk among HIV-infected women., (Copyright © 2015 by the American Society of Nephrology.)

Background: Serum albumin concentrations are a strong predictor of mortality and cardiovascular disease in human immunodeficiency virus (HIV)-infected individuals. We studied the longitudinal associations between serum albumin levels and kidney function decline in a population of HIV-infected women., Study Design: Retrospective cohort analysis., Setting & Participants: Study participants were recruited from the Women's Interagency HIV Study (WIHS), a large observational study designed to understand risk factors for the progression of HIV infection in women living in urban communities. 908 participants had baseline assessment of kidney function and 2 follow-up measurements over an average of 8 years., Predictor: The primary predictor was serum albumin concentration., Outcomes: We examined annual change in kidney function. Secondary outcomes included rapid kidney function decline and incident reduced estimated glomerular filtration rate (eGFR)., Measurements: Kidney function decline was determined by cystatin C-based (eGFR(cys)) and creatinine-based eGFR (eGFR(cr)) at baseline and follow-up. Each model was adjusted for kidney disease and HIV-related risk factors using linear and relative risk regression., Results: After multivariate adjustment, each 0.5-g/dL decrement in baseline serum albumin concentration was associated with a 0.56-mL/min faster annual decline in eGFR(cys) (P < 0.001), which was attenuated only slightly to 0.55 mL/min/1.73 m(2) after adjustment for albuminuria. Results were similar whether using eGFR(cys) or eGFR(cr). In adjusted analyses, each 0.5-g/dL lower baseline serum albumin level was associated with a 1.71-fold greater risk of rapid kidney function decline (P < 0.001) and a 1.72-fold greater risk of incident reduced eGFR (P < 0.001)., Limitations: The cohort is composed of only female participants from urban communities within the United States., Conclusions: Lower serum albumin levels were associated strongly with kidney function decline and incident reduced eGFRs in HIV-infected women independent of HIV disease status, body mass index, and albuminuria., (Published by Elsevier Inc.)

Urinary biomarkers of AKI provide prognostic value for in-hospital outcomes, but little is known about their association with longer-term mortality after surgery. We sought to assess the association between kidney injury biomarkers and all-cause mortality in an international, multicenter, prospective long-term follow-up study from six clinical centers in the United States and Canada composed of 1199 adults who underwent cardiac surgery between 2007 and 2009 and were enrolled in the Translational Research in Biomarker Endpoints in AKI cohort. On postoperative days 1-3, we measured the following five urinary biomarkers: neutrophil gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 (KIM-1), liver fatty acid binding protein, and albumin. During a median follow-up of 3.0 years (interquartile range, 2.2-3.6 years), 139 participants died (55 deaths per 1000 person-years). Among patients with clinical AKI, the highest tertiles of peak urinary neutrophil gelatinase-associated lipocalin, IL-18, KIM-1, liver fatty acid binding protein, and albumin associated independently with a 2.0- to 3.2-fold increased risk for mortality compared with the lowest tertiles. In patients without clinical AKI, the highest tertiles of peak IL-18 and KIM-1 also associated independently with long-term mortality (adjusted hazard ratios [95% confidence intervals] of 1.2 [1.0 to 1.5] and 1.8 [1.4 to 2.3] for IL-18 and KIM-1, respectively), and yielded continuous net reclassification improvements of 0.26 and 0.37, respectively, for the prediction of 3-year mortality. In conclusion, urinary biomarkers of kidney injury, particularly IL-18 and KIM-1, in the immediate postoperative period provide additional prognostic information for 3-year mortality risk in patients with and without clinical AKI., (Copyright © 2014 by the American Society of Nephrology.)

Background and Objectives: The influence of deceased-donor AKI on post-transplant outcomes is poorly understood. The few published studies about deceased-donor preimplant biopsy have reported conflicting results regarding associations between AKI and recipient outcomes., Design, Setting, Participants, & Measurements: This multicenter study aimed to evaluate associations between deceased-donor biopsy reports of acute tubular necrosis (ATN) and delayed graft function (DGF), and secondarily for death-censored graft failure, first adjusting for the kidney donor risk index and then stratifying by donation after cardiac death (DCD) status., Results: Between March 2010 and April 2012, 651 kidneys (369 donors, 4 organ procurement organizations) were biopsied and subsequently transplanted, with ATN reported in 110 (17%). There were 262 recipients (40%) who experienced DGF and 38 (6%) who experienced graft failure. DGF occurred in 45% of kidneys with reported ATN compared with 39% without ATN (P=0.31) resulting in a relative risk (RR) of 1.13 (95% confidence interval [95% CI], 0.9 to 1.43) and a kidney donor risk index-adjusted RR of 1.11 (95% CI, 0.88 to 1.41). There was no significant difference in graft failure for kidneys with versus without ATN (8% versus 5%). In stratified analyses, the adjusted RR for DGF with ATN was 0.97 (95% CI, 0.7 to 1.34) for non-DCD kidneys and 1.59 (95% CI, 1.23 to 2.06) for DCD kidneys (P=0.02 for the interaction between ATN and DCD on the development of DGF)., Conclusions: Despite a modest association with DGF for DCD kidneys, this study reveals no significant associations overall between preimplant biopsy-reported ATN and the outcomes of DGF or graft failure. The potential benefit of more rigorous ATN reporting is unclear, but these findings provide little evidence to suggest that current ATN reports are useful for predicting graft outcomes or deciding to accept or reject allograft offers.

Normal aging results in a predictable decrease in glomerular filtration rate (GFR), and low GFR is associated with worsened survival. If this survival disadvantage is directly caused by the low GFR, as opposed to the disease causing the low GFR, the risk should be similar regardless of the underlying mechanism. Our objective was to determine if age-related decreases in estimated GFR (eGFR) carry the same prognostic importance as disease-attributable losses in patients with ventricular dysfunction. We analyzed the Studies Of Left Ventricular Dysfunction limited data set (n = 6,337). The primary analysis focused on determining if the eGFR-mortality relation differed by the extent to which the eGFR was consistent with normal aging. Mean eGFR was 65.7 ml/min/1.73 m(2) (SD = 19.0). Across the range of age in the population (27 to 80 years), baseline eGFR decreased by 0.67 ml/min/1.73 m(2)/year (95% confidence interval [CI] 0.63 to 0.71). The risk of death associated with eGFR was strongly modified by the degree to which the low eGFR could be explained by aging (p for interaction <0.0001). For example, in a model incorporating the interaction, uncorrected eGFR was no longer significantly related to mortality (adjusted hazard ratio 1.0 per 10 ml/min/1.73 m(2), 95% CI 0.97 to 1.1, p = 0.53), whereas a disease-attributable decrease in eGFR above the median carried significant risk (adjusted hazard ratio 2.8, 95% CI 1.6 to 4.7, p <0.001). In conclusion, in the setting of left ventricular dysfunction, renal dysfunction attributable to normal aging had a limited risk for mortality, suggesting that the mechanism underlying renal dysfunction is critical in determining prognosis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In response to the recently released 2012 KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for acute kidney injury (AKI), the National Kidney Foundation organized a group of US experts in adult and pediatric AKI and critical care nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI. While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States. The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of effective therapies beyond hemodynamic optimization and avoidance of nephrotoxins for the prevention and treatment of AKI., (Published by Elsevier Inc.)

Background: Although some studies have found an association between delayed graft function (DGF) after kidney transplantation and worse long-term outcomes, a causal relationship remains controversial. We investigated this relationship using an instrumental variables model (IVM), a quasi-randomization technique for drawing causal inferences., Methods: We identified 80,690 adult, deceased-donor, kidney-only transplant recipients from the Scientific Registry of Transplant Recipients between 1997 and 2010. We used cold ischemia time (CIT) as an instrument to test the hypothesis that DGF causes death-censored graft failure and mortality at 1 and 5 years after transplantation, controlling for an array of characteristics known to affect patient and graft survival. We compared our IVM results with a multivariable linear probability model., Results: DGF occurred in 27% of our sample. Graft failure rates at 1 and 5 years were 6% and 22%, respectively, and 1-year and 5-year mortality rates were 5% and 20%, respectively. In the linear probability model, DGF was associated with increased risk of both graft failure and mortality at 1 and 5 years (P<0.001). In the IVM, we found evidence suggesting a causal relationship between DGF and death-censored graft failure at both 1 year (13.5% increase; P<0.001) and 5 years (16.2% increase; P<0.001) and between DGF and mortality at both 1 year (7.1% increase; P<0.001) and 5 years (11.0% increase; P<0.01). Results were robust to exclusion of lower quality as well as pumped kidneys and use of a creatinine-based definition for DGF., Conclusion: Instrumental variables analysis supports a causal relationship between DGF and both graft failure and mortality.

Acute kidney injury (AKI) is primarily defined and staged according to the magnitude of the rise in serum creatinine. Here we sought to determine if the duration of AKI adds additional prognostic information above that from the magnitude of injury alone. We prospectively studied 35,302 diabetic patients from 123 Veterans Affairs Medical Centers undergoing their first noncardiac surgery. The main outcome was long-term mortality in those who survived the index hospitalization. AKI was stratified by magnitude according to AKI Network stages and by the duration (short (less than 2 days), medium (3-6 days) or long (7 days or more)). Overall, 17.8% of patients experienced at least stage 1 AKI or greater following surgery. Both the magnitude and duration of AKI were significantly associated with long-term survival in a dose-dependent manner. Within each stage, longer duration of AKI was significantly associated with a graded higher rate of mortality. However, within each of the duration categories, the stage was not associated with mortality. When considered separately in multivariate analyses, both a higher stage and duration were independently associated with increased risk of long-term mortality. Hence, the duration of AKI adds additional information to predict long-term mortality.

Background and Objectives: Ensuring follow-up of living kidney donors (LKDs) is essential to long-term preventive care. We sought information on health insurance status of US LKDs, with particular attention to age, gender, and ethnicity., Design, Setting, Participants, & Measurements: The United Network for Organ Sharing/Organ Procurement Transplantation Network database was queried for associations among age at donation, race, gender, and health insurance status. We studied all US LKDs between July 2004 and September 2006., Results: A total of 10,021 LKDs with known health insurance status were studied, 1765 (18%) of whom lacked health insurance at donation. There were 4852 donors without health insurance information. Younger kidney donors had higher rates of being uninsured (age 18 to 34: 26.2%; age 35 to 49: 15.2%; age 50 to 64: 11.2%; age >65: 3.8%; P < 0.0001), as did men (19.5 versus 16.3% for women; P < 0.0001), and ethnic minorities (white 13.4%, black 21%, Hispanic 35.6%, Asian 26.7%; P < 0.0001)., Conclusions: This study confirms that younger patients, ethnic minorities, and men are less likely to have health insurance when donating a kidney, which could negatively affect adherence to long-term follow-up.

Objectives: To examine the effect of hepatitis C virus (HCV) on the prevalence of chronic kidney disease (CKD) among veterans with HIV and to evaluate independent associations of HCV and CKD with mortality., Methods: We studied a national cohort of HIV-infected patients receiving care through the Veterans Healthcare Administration from 1998 to 2004. CKD was defined as an estimated glomerular filtration rate [eGFR (mL/min/1.73 m2)] < 60. Poisson regression was used to assess relationships between CKD, HCV, and mortality., Results: Among 23,155 HIV-infected veterans, 12% had CKD. Forty percent of the cohort was coinfected with HCV, and a higher proportion of coinfected subjects had CKD compared with monoinfected subjects (14% vs 11%, P < 0.001). During the median follow-up of 7.6 years, 37% of subjects died and a graduated increase in adjusted mortality rates occurred with lower levels of eGFR (P < 0.001). Adjusted mortality rates were consistently higher in HCV-coinfected subjects across all levels of eGFR (P < 0.001). HCV was independently associated with increased mortality (incidence rate ratio 1.23, 95% confidence interval 1.17-1.29)., Conclusions: CKD is prevalent in HIV-infected veterans and associated with substantially higher mortality. Compared with their monoinfected counterparts, veterans coinfected with HCV have significantly higher rates of CKD and mortality.

When evaluating a living kidney donor and recipient with a father-child relationship, it may be discovered that the two are not biologically related. We analyzed data from the United Network for Organ Sharing and the Canadian Organ Replacement Registry to determine how frequently this occurs. We surveyed 102 potential donors, recipients, and transplant professionals for their opinion on whether such information should be disclosed to the donor-recipient pair. We communicated with transplant professionals from 13 Canadian centers on current practices for handling this information. In the United States and Canada, the prevalence of father-child living kidney donor-recipient pairs with less than a one-haplotype human leukocyte antigen match (i.e., misattributed paternity) is between 1% and 3%, or approximately 0.25% to 0.5% of all living kidney donations. Opinions about revealing this information were variable: 23% strongly favored disclosure; whereas, 24% were strongly opposed to it. Current practices are variable; some centers disclose this information, whereas others do not. Discovering misattributed paternity in living donation is uncommon but can occur. Opinions on how to deal with this sensitive information are variable. Discussion among transplant professionals will facilitate best practices and policies. Strategies adopted by some centers can be considered.

Background: Living kidney donation rates are increasing in the United States and internationally. Major consensus statements on the care of living kidney donors recommend communicating all potential health and psychosocial risks to donors. We evaluated the degree of international variation in the process of informed consent of potential donors during their evaluation., Methods: Transplant professionals attending the 2006 World Transplant Congress responded to a survey assessing their process of informed consent, evaluation and communication of living donor risk. US-based respondents were compared to non-US respondents., Results: There were 221 respondents from 177 transplant centers and 40 countries (48% US respondents). Across US and non-US transplant centers, potential donors were most likely to receive written material about living donor risk by mail prior to evaluation, receive risk information in person during evaluation, have a psychosocial evaluation, which usually lasted longer than 30 min and sign an official donation consent form presented to them by a surgeon or nephrologist. Although over 75% of respondents stated that donors received information about medical risks such as hypertension, chronic kidney disease and potential need for dialysis, there was less consistency regarding whether or not respondents conveyed an increased risk of these medical complications to donors. Additionally, the financial and psychosocial costs associated with being a living donor were inconsistently communicated to donors during the informed consent process. Compared to non-US respondents, US respondents were more likely to use written material and visual aids to convey risks to donors, have mandatory psychosocial evaluations and provide access to donor support groups. US transplant centers were also more likely to discuss the possibility of the donors needing dialysis or a transplant if their remaining kidney fails in the future, possible travel expenses and loss of work income due to donation recovery. Conversely, the US respondents were less likely to offer long-term follow-up and to utilize nephrologists to obtain written donor consent for donation., Conclusions: As dependence on living organ donation increases best practices for informed consent, donor evaluation and uniform risk conveyance need to be established. This may be accomplished by using a model informed consent template to ensure that informed consent from donors is consistently obtained.

Background: Acute kidney injury (AKI) is a common complication during hospitalization and is an accepted risk factor for in-hospital mortality. However, the association of severity of AKI with the long-term risk of death is not well defined., Methods: To examine the independent effect of the severity of AKI on long-term risk of death following acute myocardial infarction (AMI), we performed an observational study of 147007 elderly Medicare patients admitted for AMI from January 1994 through February 1996 as a part of the Cooperative Cardiovascular Project. We evaluated the association between AKI and all-cause mortality. We defined AKI as absolute changes in serum creatinine level, categorized as none (creatinine level increase, < or =0.2 mg/dL), mild (0.3-0.4 mg/dL increase), moderate (0.5-0.9 mg/dL increase), and severe (> or =1.0 mg/dL increase)., Results: Overall, 19.4% of the patients had AKI, including 7.1% with mild AKI, 7.1% with moderate AKI, and 5.2% with severe AKI. Less than 10% of patients who had severe AKI were alive at 10 years compared with 12.2%, 21.1%, and 31.7% patients with moderate, mild, and no AKI, respectively. The adjusted hazard ratio for death for in-hospital survivors at 10 years was 1.15 (95% confidence interval [CI], 1.12-1.18) for mild AKI, 1.23 (95% CI, 1.20-1.26) for moderate AKI, and 1.33 (95% CI, 1.28-1.38) for severe AKI. Similar results were obtained in several secondary analyses that included inpatient mortality, excluded mortality in the first 3 years, and stratified by some specified high-risk groups. Moderate or severe AKI were comparable in strength with other known correlates of cardiovascular mortality., Conclusions: Acute kidney injury has an independent and graded association with long-term mortality. These results should stimulate additional mechanistic and interventional studies and plans for follow-up of patients with AKI after discharge.

Background: Chronic kidney disease is now recognized as an independent risk factor for cardiovascular events. We sought to determine if cardiovascular medications were utilized less in patients with renal dysfunction following coronary artery bypass grafting (CABG) and if the association of decreased medication use was independent of comorbid conditions. We also examined associations between cardiovascular medication use and mortality at 6 months., Methods: Data from the National Veterans Adminstration (VA) Continuous Improvement in Cardiac Surgery Program were merged with the national VA pharmacy database. Prescription rates within 6 months of discharge for CABG were obtained for four classes of medicines: beta blockers, lipid-lowering agents, antiplatelet agents, and angiotensin antagonists. Utilization of medications in patients with estimated glomerular filtration rate (GFR) 60 to 90, 30 to 60, and <30 were compared with the reference group of GFR >90., Results: In a retrospective analysis of 19,411 patients, the frequency of nonprescription increased with declining GFR. Decreased utilization for patients with GFR 30 to 60 and <30 remained highly significant after adjustment for age, race, hypertension, diabetes, and prior myocardial infarction. In patients with more advanced renal dysfunction (GFR <60), cardiovascular medication use for all medication classes was associated with survival at 6 months after adjusting for demographic and clinical variables. Cumulative protection was seen with use of medication from each additional class., Conclusion: In a large VA population undergoing CABG, renal disease is associated with highly significant decreases in utilization of cardiovascular medications. Nonprescription of medications was associated with adverse outcomes in those with renal dysfunction.

Systemic sclerosis (SS) may lead to sclerodema renal crisis, an unusual cause of end-stage renal disease (ESRD) with historically poor hemodialysis outcomes. Little information is available on outcomes after kidney transplantation. Information from the UNOS registry was obtained on SS patients in the United States, listed for kidney transplants between 1985-2002. We compared survival at 1 and 3 years in patients who received cadaveric transplants with patients who remained on the waiting list. Graft survival, cause of graft loss, frequency of early graft loss and pre- and post-transplant skin scores were analyzed. Two hundred and fifty-eight patients with SS were listed for transplantation. Survival was significantly prolonged in patients receiving transplants (p = 0.005). Graft survival at 1 and 3 years was 68% and 60%. Early graft loss was common. Skin scores improved in all four subjects at our center, with an average decline of 60.7% (p = 0.024). Kidney transplantation confers a survival benefit in ESRD due to SS. Transplantation may be associated with an improvement in systemic manifestations of disease. Despite suboptimal graft survival, kidney transplant should be considered the treatment of choice in ESRD due to SS.