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Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods 1 . Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously undescribed cell populations. The multi-omic approach provides detailed transcriptomic profiles, regulatory factors and spatial localizations spanning the entire kidney. We also define 28 cellular states across nephron segments and interstitium that were altered in kidney injury, encompassing cycling, adaptive (successful or maladaptive repair), transitioning and degenerative states. Molecular signatures permitted the localization of these states within injury neighbourhoods using spatial transcriptomics, while large-scale 3D imaging analysis (around 1.2 million neighbourhoods) provided corresponding linkages to active immune responses. These analyses defined biological pathways that are relevant to injury time-course and niches, including signatures underlying epithelial repair that predicted maladaptive states associated with a decline in kidney function. This integrated multimodal spatial cell atlas of healthy and diseased human kidneys represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations., (© 2023. The Author(s).)

Background and Objectives: Uromodulin, produced exclusively in the kidney's thick ascending limb, is a biomarker of kidney tubular health. However, the relationship between urine uromodulin and histologic changes in the kidney tubulointerstitium has not been characterized. In this study, we test the association of urine uromodulin with kidney histologic findings in humans and mice., Design, Setting, Participants, & Measurements: We investigated the independent association of urine uromodulin measured at the time of kidney biopsy with histologic features in 364 participants at two academic medical centers from 2015 to 2018 using multivariable linear regression models. This relationship was further examined by comparison of uromodulin staining in murine models of kidney fibrosis and repair., Results: We found urine uromodulin to be correlated with serum creatinine (rho=-0.43; P <0.001), bicarbonate (0.20; P <0.001), and hemoglobin (0.11; P =0.03) at the time of biopsy but not with urine albumin (-0.07; P =0.34). Multivariable models controlling for prebiopsy GFR, serum creatinine at biopsy, and urine albumin showed higher uromodulin to be associated with lower severity of interstitial fibrosis/tubular atrophy and glomerulosclerosis (interstitial fibrosis/tubular atrophy: -3.5% [95% confidence intervals, -5.7% to -1.2%] and glomerulosclerosis: -3.3% [95% confidence intervals, -5.9% to -0.6%] per two-fold difference in uromodulin). However, when both interstitial fibrosis/tubular atrophy and glomerulosclerosis were included in multivariable analysis, only interstitial fibrosis/tubular atrophy was independently associated with uromodulin (interstitial fibrosis/tubular atrophy: -2.5% [95% confidence intervals, -4.6% to -0.4%] and glomerulosclerosis: -0.9% [95% confidence intervals, -3.4% to 1.5%] per two-fold difference in uromodulin). In mouse kidneys, uromodulin staining was found to be lower in the fibrotic model than in normal or repaired models., Conclusions: Higher urine uromodulin is independently associated with lower tubulointerstitial fibrosis in both human kidney biopsies and a mouse model of fibrosis., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022&#95;08&#95;10&#95;CJN04360422.mp3., (Copyright © 2022 by the American Society of Nephrology.)

Since the start of the COVID-19 pandemic, several manifestations of kidney involvement associated with infection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been described, including proteinuria, hematuria, and acute kidney injury. A growing body of literature has explored the risk factors and pathogenesis of COVID-19-associated acute kidney injury (AKI), including direct and indirect mechanisms, as well as early postdischarge outcomes that may result from various manifestations of kidney involvement. In this review, we explore the current state of knowledge of the epidemiology of COVID-19-associated AKI, potential mechanisms and pathogenesis of AKI, and various management strategies for patients in the acute setting. We highlight how kidney replacement therapy for patients with COVID-19-associated AKI has been affected by the increasing demand for dialysis and how the postacute management of patients, including outpatient follow-up, is vitally important. We also review what is presently known about long-term kidney outcomes after the initial recovery from COVID-19. We provide some guidance as to the management of patients hospitalized with COVID-19 who are at risk for AKI as well as for future clinical research in the setting of COVID-19 and the significance of early identification of patients at highest risk for adverse kidney outcomes.

Background: Differentiating etiologies of acute kidney injury (AKI) is critical in determining the course of care in clinical practice. For example, acute interstitial nephritis (AIN) requires withdrawal of the offending drug and immunosuppressive therapy, while acute tubular injury (ATI) does not have any disease-specific therapies. Failure to distinguish AIN from ATI in a timely manner can lead to kidney fibrosis and chronic kidney disease. In this review, we discuss current tests and novel biomarkers to distinguish ATI from AIN., Summary: In a prospective cohort study of 32 participants with AIN and 41 with ATI, clinical features and current, laboratory tests did not provide sufficient distinction between the 2 subpopulations of AKI. The findings in our cohort are consistent with our review of the literature. Given the limitations of clinical features and laboratory assessments, clinical practice relies on kidney biopsy for histological diagnosis, which is not always feasible, and is associated with bleeding complications in high-risk populations. In addition, histological diagnosis is prone to sampling errors and inter-rater variability. In the interest of identifying a novel biomarker, we compared urine and plasma levels of cytokines in the Th1, Th2, and Th9 pathways, which have been implicated in the pathogenesis of AIN. Urine TNF-α and interleukin-9 were higher in AIN participants than in ATI controls and helped discriminate AIN from ATI (area under curve 0.83 [0.73-0.92]). Key Messages: Differentiation between AIN and ATI in patients with AKI using currently available tests is challenging. Urine TNF-α and interleukin-9 may help clinicians separate AIN from ATI., (© 2019 S. Karger AG, Basel.)

Background and Objectives: Tenofovir disoproxil fumarate (tenofovir) is associated with elevated concentrations of biomarkers of kidney damage and dysfunction in individuals with HIV. The relationship of these kidney biomarkers with longitudinal kidney function decline is unknown., Design, Setting, Participants, & Measurements: We evaluated associations of 14 urinary biomarkers of kidney injury with changes in eGFR among 198 men and women with HIV who initiated tenofovir between 2009 and 2015 in the Multicenter AIDS Cohort Study and Women's Interagency HIV Study. Urinary biomarkers included albumin-to-creatinine ratio, α -1-microglobulin, β -2-microglobulin, cystatin C, kidney injury molecule-1 (KIM-1), IL-18, neutrophil gelatinase-associated lipocalin (NGAL), clusterin, osteopontin, uromodulin, monocyte chemoattractant protein-1, EGF, trefoil factor 3, and chitinase 3-like protein 1. We used multivariable linear mixed-effect models controlling for demographics, traditional kidney disease risk factors, and HIV-related risk factors to evaluate associations of baseline biomarkers with first-year changes in eGFR, and associations of year 1 and first-year change in biomarkers with changes in eGFR from year 1 to year 3. We used the least absolute shrinkage and selection operator method to identify a parsimonious set of biomarkers jointly associated with changes in eGFR., Results: Median eGFR before tenofovir initiation was 103 (interquartile range, 88-116) ml/min per 1.73 m 2 . During the first year of tenofovir use, eGFR decreased on average by 9.2 (95% confidence interval, 6.5 to 11.9) ml/min per 1.73 m 2 and was stable afterward (decrease of 0.62; 95% confidence interval, -0.85 to 2.1 ml/min per 1.73 m 2 per year). After multivariable adjustment, higher baseline β -2-microglobulin, KIM-1, and clusterin were associated with larger first-year eGFR declines, whereas higher baseline uromodulin was associated with a smaller eGFR decline. First-year increase in urinary cystatin C and higher year 1 IL-18 were associated with larger annual eGFR declines from year 1 to year 3. The parsimonious models identified higher pre-tenofovir clusterin and KIM-1, lower pre-tenofovir uromodulin, and higher year 1 IL-18 as jointly associated with larger eGFR declines., Conclusions: Urinary biomarkers of kidney injury measured before and after tenofovir initiation are associated with subsequent changes in eGFR in individuals with HIV., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018&#95;08&#95;28&#95;CJASNPodcast&#95;18&#95;9&#95;S.mp3., (Copyright © 2018 by the American Society of Nephrology.)

Background: Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is becoming increasingly adopted for HIV prevention. Tenofovir can cause proximal tubular damage and chronic kidney disease in HIV-infected persons, but little is known regarding its nephrotoxic potential among HIV-uninfected persons. In this study, we evaluated the effects of PrEP on urine levels of the following: α1-microglobulin (α1m), a marker of impaired tubular reabsorption; albuminuria, a measure of glomerular injury; and total proteinuria., Setting: The Iniciativa Profilaxis Pre-Exposicion (iPrEx) study randomized HIV-seronegative men and transgender women who have sex with men to oral TDF/FTC or placebo. The iPrEx open-label extension (iPrEx-OLE) study enrolled former PrEP trial participants to receive open-label TDF/FTC., Methods: A cross-sectional analysis compared urine biomarker levels by study arm in iPrEx (N = 100 treatment arm, N = 100 placebo arm). Then, urine biomarker levels were compared before and after PrEP initiation in 109 participants of iPrEx-OLE., Results: In iPrEx, there were no significant differences in urine α1m, albuminuria, or proteinuria by treatment arm. In iPrEx-OLE, after 24 weeks on PrEP, urine α1m and proteinuria increased by 21% [95% confidence interval (CI): 10 to 33] and 18% (95% CI: 8 to 28), respectively. The prevalence of detectable α1m increased from 44% to 65% (P < 0.001) and estimated glomerular filtration rate declined by 4 mL/min/1.73 m (P < 0.001). There was no significant change in albuminuria (6%; 95% CI: -7% to 20%)., Conclusion: PrEP with TDF/FTC was associated with a statistically significant rise in urine α1m and proteinuria after 6 months, suggesting that PrEP may result in subclinical tubule dysfunction.

Background: Fibrosis is the unifying pathway leading to chronic kidney disease. Identifying biomarkers of fibrosis may help predict disease progression., Methods: We performed a systematic review to evaluate the reliability of blood and urine biomarkers in identifying fibrosis on biopsy as well as predicting renal outcomes. Using MEDLINE and EMBASE, a two-stage search strategy was implemented. Stage I identified a library of biomarkers correlating with fibrosis on biopsy. Stage II evaluated the association between biomarkers identified in stage I, and renal outcomes. Only biomarkers with moderate positive correlation with fibrosis (r > 0.40) or acceptable area under the curve (AUC >0.65) advanced to stage II., Results: Stage I identified 17 studies and 14 biomarkers. Five biomarkers met criteria to advance to stage II, but only three were independently associated with renal outcomes. Transforming growth factor β (TGF-β) correlated with fibrosis (r = 0.60), and was associated with 1.7-3.9 times the risk of worsening renal function in 426 patients. Monocyte chemoattractant protein-1 (MCP-1) diagnosed fibrosis with AUC of 0.66 and was associated with 2.3-11.0 times the risk of worsening renal function in 596 patients. Matrix metalloproteinase-2 (MMP-2) correlated with fibrosis (r = 0.41), and was associated with 2.5 times the risk of worsening renal function., Conclusions: Given the heterogeneity of the data due to diverse patient populations along with differing renal outcomes, a meta-analysis could not be conducted. Nonetheless we can conclude from the published data that TGF-β, MCP-1 and MMP-2 may identify patients at risk for renal fibrosis and hence worse renal outcomes.

Background: There is an epidemic of chronic kidney disease (CKD) of unknown etiology in Central American workers., Objectives: To investigate changes and job-specific differences in kidney function over a 6-month sugarcane harvest season, explore the potential role of hydration, and measure proteinuria., Methods: We recruited 284 Nicaraguan sugarcane workers performing seven distinct tasks. We measured urine albumin and serum creatinine and estimated glomerular filtration rate (eGFR)., Results: eGFR varied by job and decreased during the harvest in seed cutters (-8·6 ml/min/1·73 m(2)), irrigators (-7·4 ml/min/1·73 m(2)), and cane cutters (-5·0 ml/min/1·73 m(2)), as compared to factory workers. The number of years employed at the company was negatively associated with eGFR. Fewer than 5% of workers had albumin-to-creatinine ratio (ACR) >30 mg/g., Conclusions: The decline in kidney function during the harvest and the differences by job category and employment duration provide evidence that one or more risk factors of CKD are occupational.

Interest in developing and using novel markers of kidney injury is increasing. To maintain scientific rigour in these endeavors, a comprehensive understanding of statistical methodology is required to rigorously assess the incremental value of novel biomarkers in existing clinical risk prediction models. Such knowledge is especially relevant, because no single statistical method is sufficient to evaluate a novel biomarker. In this review, we highlight the strengths and limitations of various traditional and novel statistical methods used in the literature for biomarker studies and use biomarkers of AKI as examples to show limitations of some popular statistical methods., (Copyright © 2014 by the American Society of Nephrology.)

Background: In HIV-infected women, urine concentrations of novel tubulointerstitial injury markers, interleukin-18 (IL-18) and kidney injury marker-1 (KIM-1), are associated with kidney function decline and all-cause mortality. We hypothesized that HIV-infected individuals with preserved kidney filtration function would have more extensive kidney injury, as determined by urine injury markers, compared to the uninfected controls, and that risk factors for tubulointerstitial injury would differ from risk factors for albuminuria., Methods: In this cross-sectional study, we compared urine concentrations of IL-18, KIM-1 and albumin-to-creatinine ratio (ACR) in 908 HIV-infected and 289 HIV-uninfected women enrolled in the Women's Interagency HIV Study, utilizing stored urine specimens from visits between 1999 and 2000., Results: After multivariate-adjusted linear regression analysis, mean urine concentrations were higher in HIV-infected individuals by 38% for IL-18 (P<0.0001), 12% for KIM-1 (P=0.081) and 47% for ACR (P<0.0001). Higher HIV RNA level (15% per 10-fold increase; P<0.0001), lower CD4(+) lymphocyte count (8% per doubling; P=0.0025), HCV infection (30%; P=0.00018) and lower high-density lipoprotein (5% per 10 mg/dl; P=0.0024) were each associated with higher IL-18 concentrations. In contrast, hypertension (81%; P<0.0001) and diabetes (47%; P=0.018) were among the strongest predictors of higher ACR, though HIV RNA level (15% per 10-fold increase; P=0.0004) was also associated with higher ACR., Conclusions: HIV-infected women had more extensive tubulointerstitial and glomerular injury than uninfected women, but the associated factors differed among the urine biomarkers. Combinations of urinary biomarkers should be investigated to further characterize early kidney injury in HIV-infected women.

Background: Differentiation of HF-induced renal dysfunction (RD) from irreversible intrinsic kidney disease is challenging, likely related to the multifactorial pathophysiology underlying HF-induced RD. In contrast, HF-induced liver dysfunction results in characteristic laboratory abnormalities. Given that similar pathophysiologic factors are thought to underlie both conditions, and that the liver and kidneys share a common circulatory environment, patients with laboratory evidence of HF-induced liver dysfunction may also have a high incidence of potentially reversible HF-induced RD., Methods and Results: Hospitalized patients with a discharge diagnosis of HF were reviewed (n = 823). Improvement in renal function (IRF) was defined as a 20% improvement in estimated glomerular filtration rate (eGFR). An elevated international normalized ratio (INR; odds ratio [OR] 2.8; P < .001), bilirubin (BIL; OR 2.2; P < .001), aspartate aminotransferase (AST; OR 1.8; P = .004), and alanine aminotransferase (ALT; OR 2.1; P = .001) were all significantly associated with IRF. Among patients with baseline RD (eGFR ≤45 mL min(-1) 1.73 m(-2)), associations between liver dysfunction and IRF were particularly strong (INR: OR 5.7 [P < .001]; BIL: OR 5.1 [P < .001]; AST: OR 2.9 [P = .005]; ALT: OR 4.8 [P < .001])., Conclusions: Biochemical evidence of mild liver dysfunction is associated with reversible RD in decompensated HF patients. In the absence of methodology to directly identify HF-induced RD, signs of HF-induced dysfunction of other organs may serve as an accessible method by which HF-induced RD is recognized., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine., Design: Retrospective cohort analysis., Methods: Cystatin C and creatinine were measured from specimens taken and stored during the 1999-2000 examination among 908 HIV-infected participants in the Women's Interagency HIV study (WIHS). Mean follow-up was 10.2 years. Predictors of differential glomerular filtration rate (GFR) estimates were evaluated with multivariable linear regression. The associations of baseline categories (<60, 60-90, and >90 ml/min per 1.73 m) of creatinine estimated GFR (eGFRcr), cystatin C eGFR (eGFRcys), and combined creatinine-cystatin C eGFR (eGFRcr-cys) with all-cause mortality were evaluated using multivariable Cox regression. The net reclassification index (NRI) was calculated to evaluate the effect of cystatin C on reclassification of CKD staging., Results: CKD risk factors were associated with lower eGFRcys and eGFRcr-cys values compared with eGFRcr. Relative to eGFR more than 90, the eGFR less than 60 category by eGFRcys (Adjusted hazard ratio: 2.56; 95% confidence interval: 1.63-4.02), eGFRcr-cys (3.11; 1.94-5.00), and eGFRcr (2.34; 1.44-3.79) was associated with increased mortality risk. However, the eGFR 60-90 category was associated with increased mortality risk for eGFRcys (1.80; 1.28-2.53) and eGFRcr-cys (1.91; 1.38-2.66) but not eGFRcr (1.20; 0.85-1.67). The overall NRI for mortality was 26% when reclassifying from eGFRcr to eGFRcys (P < 0.001) and was 20% when reclassifying from eGFRcr to eGFRcr-cys (P < 0.001)., Conclusion: The addition of cystatin C may improve mortality risk prediction by stages of kidney function relative to creatinine. CKD risk factors are associated with an overestimate of GFR by serum creatinine relative to cystatin C.

Background: Fibric acid derivatives (fibrates) have been shown to increase serum creatinine level in randomized trials., Objective: To assess renal outcomes in elderly adults within 90 days of a new fibrate prescription., Design: Population-based cohort study., Setting: Ontario, Canada., Patients: Patients aged 66 years or older with a new outpatient prescription for a fibrate or ezetimibe (comparator drug) between January 2004 and December 2008., Measurements: Hospitalization for an increase in serum creatinine level (primary outcome) and consultation with a nephrologist, receipt of dialysis for severe acute kidney injury, all-cause mortality, and increases in serum creatinine level (secondary outcomes). All outcomes were assessed within 90 days of a new prescription for ezetimibe or a fibrate., Results: Compared with ezetimibe users (n = 61,831), fibrate users (n = 19,072) were more likely to be hospitalized for an increase in serum creatinine level (adjusted odds ratio, 2.4 [95% CI, 1.7 to 3.3]) and were more likely to consult a nephrologist (absolute risk difference, 0.15% [CI, 0.01% to 0.29%]; adjusted odds ratio, 1.3 [CI, 1.0 to 1.6]). There were no differences between groups in the risk for all-cause mortality or receiving dialysis for severe acute kidney injury. In a subpopulation of 1110 patients (fibrates, n = 220; ezetimibe, n = 890), 9.1% of fibrate users and 0.3% of ezetimibe users had an increase in serum creatinine level of 50% or more (absolute difference, 8.8% [CI, 4.5% to 13.1%]; odds ratio, 29.6 [CI, 8.7 to 100.5]). Risks were greater among fibrate users with chronic kidney disease., Limitations: Because hospitalizations for an increase in serum creatinine level were underestimated, absolute differences may be misleading. Most patients (91%) were prescribed fenofibrate. Serum creatinine levels were measured as part of routine care and were not available for everyone or at predefined times., Conclusion: New fibrate use in elderly adults was associated with an increase in serum creatinine level and a small 90-day absolute increase in hospitalizations and nephrologist consultations. There was no detectable effect on dialysis for severe acute kidney injury or on mortality. The mechanism and clinical significance of the increase in serum creatinine level with fibrates is unclear., Primary Funding Source: Ontario Ministry of Health and Long-Term Care Drug Innovation Fund.

Acute kidney injury may increase the risk for chronic kidney disease and end-stage renal disease. In an attempt to summarize the literature and provide more compelling evidence, we conducted a systematic review comparing the risk for CKD, ESRD, and death in patients with and without AKI. From electronic databases, web search engines, and bibliographies, 13 cohort studies were selected, evaluating long-term renal outcomes and non-renal outcomes in patients with AKI. The pooled incidence of CKD and ESRD were 25.8 per 100 person-years and 8.6 per 100 person-years, respectively. Patients with AKI had higher risks for developing CKD (pooled adjusted hazard ratio 8.8, 95% CI 3.1-25.5), ESRD (pooled adjusted HR 3.1, 95% CI 1.9-5.0), and mortality (pooled adjusted HR 2.0, 95% CI 1.3-3.1) compared with patients without AKI. The relationship between AKI and CKD or ESRD was graded on the basis of the severity of AKI, and the effect size was dampened by decreased baseline glomerular filtration rate. Data were limited, but AKI was also independently associated with the risk for cardiovascular disease and congestive heart failure, but not with hospitalization for stroke or all-cause hospitalizations. Meta-regression did not identify any study-level factors that were associated with the risk for CKD or ESRD. Our review identifies AKI as an independent risk factor for CKD, ESRD, death, and other important non-renal outcomes.

Background and Objectives: Serum creatinine concentration at the time of nephrology consultation is not necessarily indicative of the severity of acute kidney injury (AKI). Although urine microscopy is useful to differentiate AKI, its role in predicting adverse clinical outcomes has not been well described., Design, Setting, Participants, & Measurements: The relationship between urine microscopy findings at the time of nephrology consultation for AKI and clinical outcomes was evaluated prospectively. A urinary sediment scoring system was created on the basis of the number of renal tubular epithelial cells and granular casts. The primary outcome was worsening of AKI (progressing to higher AKI Network stage, dialysis, or death) during hospitalization., Results: Of 249 patients consulted for AKI, 197 had acute tubular necrosis or prerenal AKI and were included in the analysis. At consultation, 80 (40%) had stage 1, 53 (27%) had stage 2, and 66 (33%) had stage 3 AKI. The urinary sediment combined scores were lowest in those with stage 1 and highest in stage 3 AKI. Seventy-nine patients (40%) experienced worsening of AKI from the time of consultation. The urinary scoring system was significantly associated with increased risk of worsening AKI (adjusted relative risk: 7.3; 95% confidence interval: 4.5 to 9.7 for worsening with score of > or =3 versus score of 0) and was more predictive than AKI Network stage at the time of consultation., Conclusions: The urinary sediment score may be a useful tool to predict worsening of AKI due to either acute tubular necrosis or prerenal AKI during hospitalization.

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.

Background and Objectives: Patients receiving dialysis have a high burden of cardiovascular disease. Some receive coronary artery revascularization but the optimal method is controversial., Design, Setting, Participants, & Measurements: The authors reviewed any randomized controlled trial or cohort study of 10 or more patients receiving maintenance dialysis which compared coronary artery bypass graft (CABG) to percutaneous intervention (PCI) for revascularization of the coronary arteries. The primary outcomes were short-term (30 d or in-hospital) and long-term (at least 1 year) mortality., Results: Seventeen studies were found. There were no randomized trials: all were retrospective cohort studies from years 1977 to 2002. There were some baseline differences between the groups receiving CABG compared with those receiving PCI, and most studies did not consider results adjusted for such characteristics. Given the variability among studies and their methodological limitations, few definitive conclusions about the optimal method of revascularization could be drawn. In an exploratory meta-analysis, short-term mortality was higher after CABG compared to PCI. A substantial number of patients died over a subsequent 1 to 5 yr, with no difference in mortality after CABG compared to PCI., Conclusions: Although decisions about the optimal method of coronary artery revascularization in dialysis patients are undertaken routinely, it was surprising to see how few data has been published in this regard. Additional research will help inform physician and patient decisions about coronary artery revascularization.

Background and Objectives: Randomized controlled trials (RCTs) with atrial natriuretic peptide (ANP) have shown inconsistent effects for renal end-points. The authors aimed to systematically review these trials to ascertain the benefit of ANP in prevention and treatment of acute kidney injury (AKI)., Design, Setting, Participants, & Measurements: The authors searched MEDLINE, EMBASE, and Cochrane Renal Health Library that investigated ANP in adult patients considered with or at risk for AKI. Outcomes were analyzed separately for prevention and treatment of AKI., Results: Nineteen RCTs (11 prevention, 8 treatment) involving 1861 participants were included. Pooled analysis of prevention trials showed a trend toward reduction in renal replacement therapy in the ANP group (OR = 0.45, 95% CI, 0.21 to 0.99) and good safety profile, but no improvement in mortality. For the treatment of established AKI, ANP, particularly in high doses, was associated with a trend toward increased mortality and more adverse events. Subgroup analysis of AKI after a major surgery (14 RCTs, 817 participants) showed a significant reduction in renal replacement therapy requirement in the ANP group (OR = 0.49, 95% CI, 0.27 to 0.88). Included RCTs were mostly low- or moderate-quality, underpowered studies., Conclusions: There are an insufficient number of high-quality studies to make any definite statement about the role of ANP in AKI. Analysis of the existing literature suggests ANP might be associated with beneficial clinical effects when administered in patients undergoing major surgery such as cardiovascular surgery. Its use, in low doses, should be explored further in this setting.

Background: Contrast-induced nephropathy (CIN) is a common cause of acute kidney injury. Several preventive therapies for this injury have been tested; however, there is still no consensus on the optimal protocol., Methods: We performed a systematic search of the National Library of Medicine and the Cochrane Library databases from January 1985 to November 2008 to identify randomized controlled studies examining sodium bicarbonate as a preventive measure for CIN in humans. We also reviewed conference abstracts from cardiology nephrology and radiology meetings from 2004 to 2008. A change in serum creatinine levels defined by an absolute (>or=0.5 mg/dl) or percentage (>or=25%) increase in the serum creatinine level is defined as CIN. The primary outcome measure was the incidence of CIN, and the secondary outcome measures were: change in serum creatinine from baseline, requirement for renal replacement therapy and death., Results: Seventeen randomized controlled trials have investigated the role of sodium bicarbonate for prophylaxis of CIN. The overall incidence of CIN was 11.3%. Using the results from all 17 studies that compared bicarbonate versus saline, the pooled relative risk of developing CIN was 0.54 (95% CI, 0.36-0.83) in the intervention arm, indicating a significant benefit from sodium bicarbonate. The pooled relative risk of CIN was 0.57 (95% CI, 0.35-0.95) when we analyzed for the studies that compared the effects sodium bicarbonate to NAC on development of CIN. There was no difference in the rates of requirement for renal replacement therapy and death., Conclusions: The use of sodium bicarbonate appears to reduce the incidence of CIN when compared to other preventive strategies for CIN without a significant difference in the requirement of renal replacement therapy and mortality. There are study heterogeneity and publication biases. Further adequately powered randomized controlled studies are needed to determine whether sodium bicarbonate will reduce the clinically meaningful outcomes (e.g., need for dialysis or death) and optimal hydration strategy in high-risk patients.

Biomarkers have been used to screen for kidney disease since creatinine was recognized to be correlated with renal function. The measurement of serum creatinine as a screening test for kidney disease falls short, however, because serum creatinine is not particularly sensitive for the diagnosis of kidney disease. Creatinine reflects renal filtering capacity, which has a lot of reserve and is therefore not sensitive to acute or chronic kidney injury unless the injury is substantial enough to compromise the filtering ability. The sensitivity of serum creatinine is further diminished in certain patient populations that are prone to kidney disease because of the physiology of creatinine. Therefore, researchers are seeking new biomarkers that can aid in the diagnosis of both acute and chronic kidney diseases. The limitations of creatinine in screening for kidney diseases in specific patient populations as well as new potential biomarkers that are actively being researched are discussed in this review.

Background and Objectives: Urine microscopy is the oldest and one of the most commonly used tests for differential diagnosis of acute kidney injury (AKI), but its performance has not been adequately studied in the setting of AKI., Design, Setting, Participants, & Measurements: Fresh urine samples were obtained from 267 consecutive patients with AKI, and urinary sediment was examined. The cause of AKI was assessed at two time points: (1) Before urine microscopy diagnosis and (2) after patient discharge or death (final diagnosis). A urinary scoring system also was created on the basis of casts and renal tubular epithelial cells (RTEC) to differentiate acute tubular necrosis (ATN) from prerenal AKI., Results: The urinary sediment scoring system was highly predictive of the final diagnosis of ATN. In patients with a high pretest probability of ATN (initial diagnosis of ATN), any casts or RTEC (score > or =2) resulted in very high positive predictive value and low negative predictive value for a final diagnosis of ATN. In patients with a low pretest probability of ATN (initial diagnosis of prerenal AKI), lack of casts or RTEC on urinary sediment examination had a sensitivity of 0.73 and specificity of 0.75 for a final diagnosis of prerenal AKI. The negative predictive value of lack of casts or RTEC in patients with low pretest probability of disease was 91%., Conclusions: Urine sediment examination is a valuable diagnostic tool for confirming the diagnosis of ATN. A score of > or =2 on an ATN urinary sediment scoring system is an extremely strong predictor of ATN.

Background and Objectives: Differences in defining acute kidney injury (AKI) may impact incidence ascertainment. We assessed the effects of different AKI definition interpretation methods on epidemiology ascertainment., Design, Setting, Participants, & Measurements: Two groups were studied at Texas Children's Hospital, Houston, Texas: 150 critically ill children (prospective) and 254 noncritically ill, hospitalized children receiving aminoglycosides (retrospective). SCr was collected for 14 d in the prospective study and 21 d in the retrospective study. Children with known baseline serum creatinine (bSCr) were classified by the pediatric Risk, Injury, Failure, Loss, End-Stage Kidney Disease (pRIFLE) AKI definition using SCr change (pRIFLE(DeltaSCr)), estimated creatinine clearance (eCCl) change (pRIFLE(DeltaCCl)), and the Acute Kidney Injury Network (AKIN) definition. In subjects without known bSCr, bSCR was estimated as eCCl = 100 (eCCl(100)) and 120 ml/min per 1.73 m(2) (eCCl(120)), admission SCr (AdmSCr) and lower/upper normative values (NormsMin, NormsMax). The differential impact of each AKI definition interpretation on incidence estimation and severity distribution was evaluated., Results: pRIFLE(DeltaSCr) and AKIN led to identical AKI distributions. pRIFLE(DeltaCCl) resulted in 14.5% (critically ill) and 11% (noncritical) more patients diagnosed with AKI compared to other methods (P 0.05). Different bSCr estimates led to differences in AKI incidence, from 12% (AdmSCr) to 87.8% (NormsMin) (P 0.05) in the critically ill group and from 4.6% (eCCl(100)) to 43.1% (NormsMin) (P 0.05) in the noncritical group., Conclusions: AKI definition variation causes interstudy heterogeneity. AKI definition should be standardized so that results can be compared across studies.

The evaluation and initial management of patients with acute kidney injury (AKI) should include: (1) an assessment of the contributing causes of the kidney injury, (2) an assessment of the clinical course including comorbidities, (3) a careful assessment of volume status, and (4) the institution of appropriate therapeutic measures designed to reverse or prevent worsening of functional or structural kidney abnormalities. The initial assessment of patients with AKI classically includes the differentiation between prerenal, renal, and postrenal causes. The differentiation between so-called "prerenal" and "renal" causes is more difficult, especially because renal hypoperfusion may coexist with any stage of AKI. Using a modified Delphi approach, the multidisciplinary international working group, generated a set of testable research questions. Key questions included the following: Is there a difference in prognosis between volume-responsive and volume-unresponsive AKI? Are there biomarkers whose patterns (dynamic changes) predict the severity and recovery of AKI (maximal stage of AKI, need for RRT, renal recovery, mortality) and guide therapy? What is the best biomarker to assess prospectively whether AKI is volume responsive? What is the best biomarker to assess the optimal volume status in AKI patients? In evaluating the current literature and ongoing studies, it was thought that the answers to the questions posed herein would improve the understanding of AKI, and ultimately patient outcomes.

Acute kidney injury (AKI) occurs frequently after nonmyeloablative hematopoietic cell transplantation (HCT). The severity of AKI after nonmyeloablative HCT has association with short-term mortality. However, the long-term effect of AKI on survival after nonmyeloablative HCT is not known. We performed a retrospective analysis of patients who underwent an HLA matched nonmyeloablative HCT between 1997 and 2006. Patients were followed for a median of 36 (range: 3-99) months. AKI occurring up to day 100 was defined as a >2-fold increase in serum creatinine or requirement of dialysis. Of the 358 patients who were included in the analysis, 200 (56%) had AKI, 158 (44%) had no AKI. Overall, 158 patients (43%) died during follow-up. After controlling for potential confounders, the adjusted hazard ratio for overall mortality associated with AKI was 1.57 (95 % confidence interval [CI] 1.2-2.3; P = .0006). The adjusted hazards ratio of nonrelapse mortality (NRM) associated with AKI was 1.72 (95% CI 0.9-3.1; P = .07). AKI is an independent predictor of overall mortality after nonmyeloablative HCT. This finding reiterates the importance of identifying preventative strategies in nonmyeloablative HCT for attenuating incidence and severity of AKI.

Renal function predicts mortality after acute myocardial infarction (AMI), but it is unknown whether the prognostic importance of renal function persists over time. This study examined how the association between renal function and mortality changed in the 10 yr after AMI in a cohort of patients. In 118,753 patients (age >/=65 yr) from the Cooperative Cardiovascular Project, mean Cockcroft-Gault creatinine clearance was 55 +/- 24 ml/min and estimated GFR was 57 +/- 21 ml/min per 1.73 m(2) at baseline. By 10 yr, 68% of patients had died. Compared with normal renal function, even mild renal impairment increased the 10-yr risk for mortality risk by 10%. Severe renal impairment more than doubled the risk for mortality at 1 yr, and this increased risk persisted at both 5 and 10 yr. At 1 yr, the contribution of creatinine clearance to mortality risk rivaled traditional factors such as BP and systolic function; by 10 yr, creatinine clearance surpassed these other risk factors, rivaled only by patient age. Associations with estimated GFR demonstrated similar trends. In conclusion, renal function in hospitalized patients with AMI is an important and consistent predictor of mortality for up to 10 yr.

Background: Severe acute kidney injury (AKI) that requires dialytic support, a relatively uncommon complication in severely burned adults, is associated with a substantially increased mortality rate. It is not known whether milder forms of AKI have prognostic importance in burns., Methods: We performed an observational cohort analysis of consecutive patients with major burns admitted to the burn care unit of a tertiary-care center from 1998 to 2003. Our main outcome measures were AKI stratified by the Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage kidney disease (RIFLE) classification and mortality., Results: AKI occurred in 81 of 304 patients (26.6%) with burns on 10% or greater total-body surface area. Risk factors for AKI on multivariate analysis were inhalational injury, catheter infection, and sepsis. Patients with AKI stratified by using the RIFLE classification had greater mortality, greater requirement of artificial ventilation, and longer durations of intensive care unit and hospital stays. Mortality was not significantly different among those with the "Risk" and "Injury" strata of RIFLE AKI compared with those without AKI, but mortality increased significantly with the "Failure" (60%) strata. In multivariate analysis, age, greater total-body surface area, inhalational injury, and the RIFLE classification of Failure were each independent predictors of death., Conclusion: In conclusion, the mortality of patients with burns with severe AKI remains high and unchanged in the modern era of critical care medicine. The RIFLE classification added prognostic information regarding morbidity in patients with milder forms of AKI.

Background: Little is known about the impact of chronic kidney disease (CKD) on health-related quality-of-life outcomes after coronary artery bypass grafting (CABG)., Methods: Our objective was to examine the changes in physical function (PF) and mental health (MH) 6 months after CABG in 1055 patients with and without CKD. The primary end points were mean change in score and status of "improved" or "worsened" in both PF and MH subscales of the Medical Outcomes Trust Short Form 36-Item Health Survey from baseline to 6 months after CABG, stratified by CKD stage (0-5)., Results: Absolute PF and MH scores at baseline and at 6 months varied by renal impairment level. Patients with severe CKD (stages 4-5) had a mean (SD) decrease in PF score at 6 months of 3 (3) compared with increases in the rest of the cohort (P<.001). After adjustment for baseline score, 21% of patients with advanced CKD experienced worsened PF scores, compared with 0% of patients with stages 0 to 2 and stage 3 CKD (P<.001). In contrast to PF scores, patients with and without CKD had similar improvements in mean MH scores at 6 months, and patients with stages 4 to 5 CKD had the highest frequency of those with improved MH scores (77%). After adjustment, no patients experienced worsened MH scores., Conclusions: After 6 months, patients with severe CKD who underwent CABG had improvement in MH but not improvement in PF and may have had worsened PF compared with those without severe CKD. Comparable evidence regarding quality-of-life outcomes in the absence of CABG is needed to more fully inform decision making regarding patients with severe CKD and coronary artery disease.

Context: Patients with renal disease are at high risk for cardiovascular mortality. Determining which interventions best offset this risk remains a health priority., Objective: To quantify the representation of patients with renal disease in randomized controlled trials for interventions proven efficacious for cardiovascular disease., Data Sources: We searched MEDLINE for trials published from 1985 through 2005 in 11 major medical and subspecialty journals., Study Selection: Randomized controlled trials for chronic congestive heart failure and acute myocardial infarction of treatments that are currently listed as class I or II recommendations in the current American College of Cardiology/American Heart Association guidelines were included., Data Extraction: Two reviewers independently abstracted data on study and patient characteristics, renal measurements, outcomes, and prognostic features., Data Synthesis: A total of 153 trials were reviewed. Patients with renal disease were reported as excluded in 86 (56%) trials. Patients with renal disease were more likely to be excluded from trials that were multicenter; of moderate enrollment size; North American; that tested renin-angiotensin-aldosterone system antagonists and anticoagulants; and that tested chronic congestive heart failure. Only 8 (5%) original articles reported the proportion of enrolled patients with renal disease, and only 15 (10%) reported mean baseline renal function. While 81 (53%) trials performed subgroup analyses of some baseline characteristic in the original article, only 4 (3%) subgroup analyses of treatment stratified by renal disease were performed., Conclusion: Major cardiovascular disease trials frequently exclude patients with renal disease and do not provide adequate information on the renal function of enrollees or the effect of interventions on patients with renal disease.

Background: Kidney disease has long been recognized to adversely affect fetal and maternal outcomes during pregnancy. The goal of this study is to better describe the population of women with kidney disease and provide a contemporary assessment of their risk for adverse events caused by kidney disease after adjustment for other contributing factors., Methods: We used Colorado birth and death certificate data for 1989 to 2001. Of 747,368 births during this period, 911 births from women with kidney disease were identified, and 4,606 births from women without kidney disease were randomly selected for comparison. Adverse fetal outcomes included fetal prematurity, low birth weight, or neonatal death, whereas adverse maternal outcomes included preeclampsia, eclampsia, or abruptio placenta., Results: Women with kidney disease were more likely to have comorbid illnesses, including chronic hypertension, anemia, diabetes, and lung and cardiac disease. Women with kidney disease had a greater frequency of adverse fetal (18.2% versus 9.5%) and maternal outcomes (13.7% versus 4.3%) compared with women without kidney disease (P < 0.0001). The presence of kidney disease independently increased the likelihood of adverse fetal outcomes (adjusted odds ratio [OR], 1.76; 95% confidence interval [CI], 1.40 to 2.21) and occurrence of adverse maternal outcomes, especially in the middle 1990s, among nulliparous women (adjusted OR, 4.07; 95% CI, 2.17 to 7.66)., Conclusion: This analysis shows that independent of other risk factors, kidney disease significantly increases the likelihood of unfavorable pregnancy outcomes for both mother and child.

Background: Allogeneic hematopoietic cell transplantation (HCT), formerly called bone marrow transplantation, can potentially cure various malignant and non-malignant diseases, but it is associated with a high risk of toxicity. We have previously shown an overall 21% incidence of severe acute renal failure in patients undergoing autologous HCT. The present study evaluated renal dysfunction in patients undergoing allogeneic HCT., Methods: The clinical course of 88 adult patients who received allogeneic HCT at the University of Colorado Health Science Center was analyzed. Renal dysfunction was classified as follows: Grade 0 = normal renal function; Grade 1 =>25% decrement in GFR but twofold increase in serum creatinine; Grade 3 =>twofold increase in serum creatinine and need for dialysis., Results: Of the 88 patients, 81 (92%) patients had some degree of renal dysfunction (Grade 1, 20 patients; Grade 2, 32 patients; Grade 3, 29 patients). Severe nephrotoxicity (Grade 2 and Grade 3 renal dysfunction) was associated with significantly higher frequencies of sepsis, hepatic toxicity and hepatic veno-occlusive disease (VOD), and lung toxicity. The overall mortality rate at the end of 6 months was 58%. Grade 3 renal dysfunction was associated with a significantly increased risk of mortality (82.6%)., Conclusion: A 92% incidence of renal dysfunction in allogeneic HCT patients was found. Lung and liver toxicities were significantly correlated with developing renal dysfunction, and the mortality rates for patients with Grade 3 renal failure exceeded 80%.

BackgroundPre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is becoming increasingly adopted for HIV prevention. Tenofovir can cause proximal tubular damage and chronic kidney disease in HIV-infected persons, but little is known regarding its nephrotoxic potential among HIV-uninfected persons. In this study, we evaluated the effects of PrEP on urine levels of the following: α1-microglobulin (α1m), a marker of impaired tubular reabsorption; albuminuria, a measure of glomerular injury; and total proteinuria.SettingThe Iniciativa Profilaxis Pre-Exposicion (iPrEx) study randomized HIV-seronegative men and transgender women who have sex with men to oral TDF/FTC or placebo. The iPrEx open-label extension (iPrEx-OLE) study enrolled former PrEP trial participants to receive open-label TDF/FTC.MethodsA cross-sectional analysis compared urine biomarker levels by study arm in iPrEx (N = 100 treatment arm, N = 100 placebo arm). Then, urine biomarker levels were compared before and after PrEP initiation in 109 participants of iPrEx-OLE.ResultsIn iPrEx, there were no significant differences in urine α1m, albuminuria, or proteinuria by treatment arm. In iPrEx-OLE, after 24 weeks on PrEP, urine α1m and proteinuria increased by 21% [95% confidence interval (CI): 10 to 33] and 18% (95% CI: 8 to 28), respectively. The prevalence of detectable α1m increased from 44% to 65% (P < 0.001) and estimated glomerular filtration rate declined by 4 mL/min/1.73 m (P < 0.001). There was no significant change in albuminuria (6%; 95% CI: -7% to 20%).ConclusionPrEP with TDF/FTC was associated with a statistically significant rise in urine α1m and proteinuria after 6 months, suggesting that PrEP may result in subclinical tubule dysfunction.

Experimental models suggest an important role for mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD) and acute kidney injury (AKI), but little is known regarding the impact of common mitochondrial genetic variation on kidney health. We sought to evaluate associations of inherited mitochondrial DNA (mtDNA) variation with risk of CKD and AKI in a large population-based cohort. We categorized UK Biobank participants who self-identified as white into eight distinct mtDNA haplotypes, which were previously identified based on their associations with phenotypes associated with mitochondrial DNA copy number, a measure of mitochondrial function. We used linear and logistic regression models to evaluate associations of these mtDNA haplotypes with estimated glomerular filtration rate by serum creatinine and cystatin C (eGFRCr-CysC, N = 362,802), prevalent (N = 416 cases) and incident (N = 405 cases) end-stage kidney disease (ESKD), AKI defined by diagnostic codes (N = 14,170 cases), and urine albumin/creatinine ratio (ACR, N = 114,662). The mean age was 57 ± 8 years and the mean eGFR was 90 ± 14 ml/min/1.73 m2. MtDNA haplotype was significantly associated with eGFR (p = 2.8E−12), but not with prevalent ESKD (p = 5.9E−2), incident ESKD (p = 0.93), AKI (p = 0.26), or urine ACR (p = 0.54). The association of mtDNA haplotype with eGFR remained significant after adjustment for diabetes mellitus and hypertension (p = 1.2E−10). When compared to the reference haplotype, mtDNA haplotypes I (β = 0.402, standard error (SE) = 0.111; p = 2.7E−4), IV (β = 0.430, SE = 0.073; p = 4.2E−9), and V (β = 0.233, SE = 0.050; p = 2.7E−6) were each associated with higher eGFR. Among self-identified white UK Biobank participants, mtDNA haplotype was associated with eGFR, but not with ESKD, AKI or albuminuria. [ABSTRACT FROM AUTHOR]

The article discusses the importance of kidney functional reserve (KFR) in the early detection of subclinical chronic kidney disease (CKD). CKD affects a significant portion of the global population, particularly in low- to middle-income countries, and is a major risk factor for end-stage renal disease and cardiovascular disease. Current biomarkers for CKD, such as serum creatinine and estimated glomerular filtration rate, are inefficient in detecting early-stage CKD. The study by Taylor et al. demonstrates that a reduction in KFR can detect subclinical CKD that is otherwise undetectable using traditional biomarkers. This finding has significant diagnostic and translational value and can guide early intervention to prevent the progression of CKD. [Extracted from the article]

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

Background/Objectives: Non‐steroidal anti‐inflammatory drugs (NSAIDs) can cause kidney injury, especially in older adults. However, previously reported associations between NSAID use and kidney health outcomes are inconsistent and limited by reliance on serum creatinine‐based GFR estimates. This analysis investigated the association of NSAID use with kidney damage in older adults using multiple kidney health measures. Design: Cross‐sectional and longitudinal analyses. Setting: Multicenter, community‐based cohort. Participants: Two thousand nine hundred and ninty nine older adults in the Health ABC Study. A subcohort (n = 500) was randomly selected for additional biomarker measurements. Exposure: Prescription and over‐the‐counter NSAID use ascertained by self‐report. Measurements: Baseline estimated glomerular filtration rate (eGFR) by cystatin C (cysC), urine albumin‐to‐creatinine ratio (ACR), kidney injury molecule‐1 (KIM‐1), and interleukin‐18 (IL‐18) were measured in 2,999 participants; alpha‐1 microglobulin (α1m), neutrophil gelatinase‐associated lipocalin (NGAL), propeptide type III procollagen (PIIINP), and uromodulin (UMOD) were measured in 500 participants. GFR was estimated three times over 10 years and expressed as percent change per year. Results: Participants had a mean age of 74 years, 51% were female, and 41% African‐American. No eGFR differences were detected between NSAID users (n = 655) and non‐users (n = 2,344) at baseline (72 ml/min/1.73 m2 in both groups). Compared to non‐users, NSAID users had lower adjusted odds of having ACR greater than 30 mg/g (0.67; 95% confidence interval (CI) = 0.51–0.89) and lower mean urine IL‐18 concentration at baseline (−11%; 95% CI = −4% to −18%), but similar mean KIM‐1 (5%; 95% CI = −5% to 14%). No significant differences in baseline concentrations of the remaining urine biomarkers were detected. NSAID users and non‐users did not differ significantly in the rate of eGFR decline (−2.2% vs ‐2.3% per year). Conclusion: Self‐reported NSAID use was not associated with kidney dysfunction or injury based on multiple measures, raising the possibility of NSAID use without kidney harm in ambulatory older adults. More research is needed to define safe patterns of NSAID consumption. [ABSTRACT FROM AUTHOR]

Background: Whether the increased incidence of chronic kidney disease (CKD) during intensive systolic blood pressure (SBP) lowering is accompanied by intrinsic kidney injury is unknown.Objective: To compare changes in kidney damage biomarkers between incident CKD case participants and matched control participants as well as between case participants in the intensive (<120 mm Hg) versus the standard (<140 mm Hg) SBP management groups of SPRINT (Systolic Blood Pressure Intervention Trial).Design: Nested case-control study within SPRINT.Setting: Adults with hypertension without baseline kidney disease.Participants: Case participants (n = 162), who developed incident CKD during trial follow-up (128 in the intensive and 34 in the standard group), and control participants (n = 162) without incident CKD, who were matched on age, sex, race, baseline estimated glomerular filtration rate, and randomization group.Measurements: 9 urinary biomarkers of kidney damage were measured at baseline and at 1 year. Linear mixed-effects models were used to estimate 1-year biomarker changes.Results: Higher concentrations of urinary albumin, kidney injury molecule-1, and monocyte chemoattractant protein-1 at baseline were significantly associated with greater odds of incident CKD (adjusted odds ratio per doubling: 1.50 [95% CI, 1.14 to 1.98], 1.51 [CI, 1.05 to 2.17], and 1.70 [CI, 1.13 to 2.56], respectively). After 1 year of blood pressure intervention, incident CKD case participants in the intensive group had significantly greater decreases in albumin-creatinine ratio (ACR), interleukin-18, anti-chitinase-3-like protein 1 (YKL-40), and uromodulin than the matched control participants. Compared with case participants in the standard group, those in the intensive group had significantly greater decreases in ACR, β2-microglobulin, α1-microglobulin, YKL-40, and uromodulin.Limitation: Biomarker measurements were available only at baseline and 1 year.Conclusion: Incident CKD in the setting of intensive SBP lowering was accompanied by decreases, rather than elevations, in levels of kidney damage biomarkers and thus may reflect benign changes in renal blood flow rather than intrinsic injury.Primary Funding Source: National Institute for Diabetes and Digestive and Kidney Diseases. [ABSTRACT FROM AUTHOR]

Kidney involvement is common in patients with acute SARS-CoV-2 infection, and subclinical inflammation and injury may persist for many months, resulting in a progressive decline in kidney function that leads to chronic kidney disease. Continued research is imperative to understand these long-term sequelae and identify interventions to mitigate them. [ABSTRACT FROM AUTHOR]

Kidney involvement is common in coronavirus disease-2019 (COVID-19), and our understanding of the effects of COVID-19 on short- and long-term kidney outcomes has evolved over the course of the pandemic. Initial key questions centered on the spectrum and degree of acute kidney injury (AKI) in patients hospitalized with severe COVID-19. Investigators worldwide have explored the association between COVID-19-associated AKI and short-term outcomes, including inpatient mortality and disease severity. Even as treatments evolved, vaccinations were developed, and newer viral variants arose, subsets of patients were identified as at continued high risk for major adverse kidney outcomes. In this review, we explore key topics of continued relevance including the following: (1) a comparison of COVID-19-associated AKI with AKI developing in other clinical settings; (2) the ongoing controversy over kidney tropism in the setting of COVID-19 and the potential for competitive binding of the severe acute respiratory syndrome coronavirus 2 virus with angiotensin converting enzyme-2 to prevent viral cell entry; and (3) the identification of high-risk patients for adverse outcomes to inform long-term outpatient management. Patients at particularly high risk for adverse kidney outcomes include those with APOL1 high-risk genotype status. Biomarkers of injury, inflammation, tubular health, and repair measured in both the blood and urine may hold prognostic significance. [ABSTRACT FROM AUTHOR]

The article focuses on a systematic review of literature aimed at summarizing the benefits of intensive and conventional glucose control on kidney-related outcomes among adults with type 2 diabetes. The review found that intensive glucose control reduced the risk for microalbuminuria and macroalbuminuria compared to conventional glucose control. The authors concluded that there is no evidence showing that intensive glycemic control reduces the risk for significant clinical renal outcomes.

Objective: The study objective was to examine the utility of using proteinuria in preoperative risk stratification for acute kidney injury. Acute kidney injury is a common and important complication for patients undergoing cardiac surgery. Proteinuria, which reflects structural damage to the glomeruli or renal tubules, may aid the prediction of acute kidney injury. Methods: The urine albumin to creatinine ratio and dipstick proteinuria concentration were prospectively measured in 1159 patients undergoing cardiac surgery. The cohort was organized into 4 clinical risk categories based on the preoperative urine albumin to creatinine ratio: 10 mg/g or less (≤1.1 mg/mmol), 11 to 29 mg/g (1.2–3.3 mg/mmol), 30 to 299 mg/g (3.4–33.8 mg/mmol), and 300 mg/g or greater (≥33.9 mg/mmol). The primary outcome was postoperative acute kidney injury, defined by the Acute Kidney Injury Network stage I criterion (serum creatinine increase ≥ 50% or ≥ 0.3 mg/dL; 26.5 μmol/L). Results: An increase in the incidence of acute kidney injury was noted across the urine albumin to creatinine ratio categories. Adding the urine albumin to creatinine ratio to the clinical model to predict acute kidney injury improved the area under the curve from 0.67 to 0.70 (P < .001), and the continuous net reclassification improvement was 29% (P < .001). The urine albumin to creatinine ratio was also independently associated with the risk of in-hospital dialysis and intensive care unit and hospital lengths of stay. Surgery status and preoperative glomerular filtration rate were effect modifiers; the association was stronger among those undergoing elective surgery and those with an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or greater. Conclusions: Preoperative proteinuria provides graded stratification risk for acute kidney injury and is an independent predictor of other outcomes in patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the use of renal ultrasonography (RUS) in the evaluation of acute kidney injury (AKI). The group observed adult Yale-New Haven Hospital inpatients totaling 997 from January 2005 to May 2009. Risk strata for hydronephrosis (HN) and HN requiring intervention (HNRI) were created. The researchers found that in inpatients with AKI, specific factors can identify patients unlikely to have hydronephrosis HN or HNRI on RUS. Factors associated with HN include a history of HN and recurrent urinary tract infections.

The article discusses about long-term prognosis of acute kidney injury after acute myocardial infraction. According to the article, acute kidney injury is a usual complication, though the severity with the long-term risk of death is not well established. An observational study was conducted on elderly medicare patients. The research concludes that acute kidney injury has an independent and evaluated relation with long-term mortality. The conclusions should infuse additional mechanistic and interventional researches and plans for follow-up of acute kidney injury patients.

The article introduces new and promising novel biomarkers for acute kidney injury (AKI), with potential high sensitivity and specificity. These biomarkers are classified into plasma panel, which consists of gelatinase-associated lipocalin and cystatin C, and urine panel, which includes neutrophil gelatinase-associated lipocalin, interleukin 18 and kidney injury-molecule 1.