Risk Of End-stage Kidney Disease Research Articles

POS-329 EFFECTS OF COMBINATION OF RTA dh404 AND DAPAGLIFLOZIN ON RENAL INVOLVEMENT AND BODY COMPOSITION IN EXPERIMENTAL RAT MODEL OF DIABETIC KIDNEY DISEASE

The Keap1-Nrf2 pathway is a major regulator of cytoprotective responses to metabolic and oxidative stress. Deletion of Keap1 activates Nrf2, and transcription of cytoprotective (and/or antioxidant) target genes. Indeed, it has been reported that bardoxolone methyl activates Nrf2 and subsequently increases eGFR. In post-hoc analysis of BEACON efficacy, bardoxolone methyl did not reduce the risk of end-stage kidney disease or death from cardiovascular causes due to the increase in volume overload, although eGFR increased significantly among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease.

Older Patients with Advanced Chronic Kidney Disease and Their Perspectives on Prognostic Information: a Qualitative Study.

Prognostic information is key to shared decision-making, particularly in life-limiting illness like advanced chronic kidney disease (CKD). To understand the prognostic information preferences expressed by older patients with CKD. Qualitative study of 28 consecutively enrolled patients over 65years of age with non-dialysis dependent CKD stages 3b-5, receiving care in a multi-disciplinary CKD clinic. Semi-structured telephone or in-person interviews to explore patients' preference for and perceived value of individualized prognostic information. Interviews were analyzed using inductive content analysis. We completed interviews with 28 patients (77.7 ± SD 6.8years, 69% men). Patients varied in their preference for prognostic information and more were interested in their risk of progression to end-stage kidney disease (ESKD) than in life expectancy. Many conflated ESKD risk with risk of death, perceiving a binary choice between dialysis and quick decline and death. Patients expressed that prognostic information would allow them to plan, take care of important business, and think about their treatment options. Patients were accepting of prognostic uncertainty and imagined leveraging it to nurture hope or motivate them to better manage risk factors. They endorsed the desire to receive prognosis of life expectancy even though it may be hard to accept or difficult to talk about but worried it could create helplessness for other patients in their situation. Most, but not all, patients were interested in prognostic information and could see its value in motivating behavior change and allowing planning. Some patients expressed concern that information on life expectancy might cause depression and hopelessness. Therefore, prognostic information is most appropriate as part of a clinical conversation that fosters shared decision-making and helps patients consider treatment risks, benefits, and burdens in context of their lives.

What is the impact of blood pressure on neurological symptoms and the risk of ESKD in primary and secondary thrombotic microangiopathies based on clinical presentation: a retrospective study

BackgroundThe impact of blood pressure on neurological symptoms and risk of end-stage kidney disease (ESKD) is unknown in primary and secondary thrombotic microangiopathies (TMAs).MethodsWe measured baseline systolic (SBP) and diastolic (DBP) BP in consecutive 563 patients with adjudicated primary and secondary TMAs, and assessed its association with the risk of ESKD.ResultsNormal BP, grade 1, 2 and 3 hypertension were present in 243 (43.1%), 132 (23.4%), 101 (17.9%) and 88 (15.6%), respectively.Significant BP differences were noted in relation to the cause of TMA: highest BP values were found in patients with atypical hemolytic-uremic syndrome (aHUS), pregnancy, transplantation and auto-immune-related TMAs. Normal BP or grade 1 hypertension was found in 17/18 (94.4%) patients with thrombotic thrombocytopenic patients (only 1/18 (5.6%) had a SBP value>150 mmHg). In contrast, BP values could not differentiate isolated “essential” malignant hypertension (MH) from MH associated with aHUS (isolated MH (n=15): BP (median (IQR)): 220 (182-249)/132 (101-150) mmHg; MH with aHUS (n=5): BP: 223 (196-245)/131 (111-144) mmHg).The risk of vigilance disturbances (6.9%, 15.0%, 25.0%, respectively), epileptic seizures (1.5%, 4.0%, 12.5%, respectively) and posterior reversible encephalopathy syndrome (0.76%, 2.97%, 6.82%, respectively) increased with increasing baseline BP values from grade 1 to grade 3 hypertension.ESKD occurred in 35/563 (6.2%) patients (1.23%, 2.27%, 11.9% and 19.3% of patients with normal BP, grade 1, 2 and 3 hypertension, respectively). As compared to patients with normal BP (<120/139 mmHg), grade 1, grade 2 and grade 3 hypertension were associated with a greater risk of ESKD in univariate (OR: 1.91 [0.83-4.40], 13.2 [3.56-48.9] and 34.8 [9.31-130], respectively) and multivariate (OR: 0.89 [0.30-2.69], 7.00 [1.57-31.3] and 19.7 [4.53-85.2], respectively) analyses. The association between BP and the risk of ESRD was unchanged after adjustment on eculizumab use (OR: 3.46 [1.41-8.49], 17.7 [4.44-70.0] and 70.6 [8.61-579], respectively). Patients with MH, regardless of its cause, had a greater risk of ESKD (OR: 26.4 [10.0-69.8] vs other patients).ConclusionsBaseline BP differs in primary and secondary TMAs. High BP reduces the neurological tolerance of TMAs and is a powerful independent risk factor of ESKD, even after adjustment on TMA’s cause.

New-onset anemia and associated risk of ESKD and death in non-dialysis CKD patients: a multicohort observational study.

ABSTRACTBackgroundAnemia is a common complication of chronic kidney disease (CKD), but its incidence in nephrology settings is poorly investigated. Similarly, the risks of adverse outcomes associated with new-onset anemia are not known.MethodsWe performed a pooled analysis of three observational cohort studies including 1031 non-anemic CKD patients with eGFR <60 mL/min/1.73 m2 regularly followed in renal clinics. We estimated the incidence of mild anemia (hemoglobin 11–12 g/dL in women and 11–13 g/dL in men) and severe anemia (hemoglobin <11 g/dL or use of erythropoiesis-stimulating agents) during a 3-year follow-up period. Thereafter we estimated the risk of end-stage kidney disease (ESKD) and all-cause death associated with new-onset mild and severe anemia.ResultsThe mean age was 63 ± 14 years, 60% were men and 20% had diabetes. The mean estimated glomerular filtration rate (eGFR) was 37 ± 13 mL/min/1.73 m2 and the median proteinuria was 0.4 g/day [interquartile range (IQR) 0.1–1.1]. The incidence of mild and severe anemia was 13.7/100 patients-year and 6.2/100 patients-year, respectively. Basal predictors of either mild or severe anemia were diabetes, lower hemoglobin, higher serum phosphate, eGFR <30 mL/min/1.73 m2 and proteinuria >0.50 g/day. Male sex, moderate CKD (eGFR 30–44 mL/min/1.73 m2) and moderate proteinuria (0.15–0.50 g/day) predicted only mild anemia. The incidence of anemia increased progressively with CKD stages (from 8.77 to 76.59/100 patients-year) and the proteinuria category (from 13.99 to 25.02/100 patients-year). During a median follow-up of 3.1 years, 232 patients reached ESKD and 135 died. Compared with non-anemic patients, mild anemia was associated with a higher adjusted risk of ESKD {hazard ratio [HR] 1.42 [95% confidence interval (CI) 1.02–1.98]} and all-cause death [HR 1.55 (95% CI 1.04–2.32)]. Severe anemia was associated with an even higher risk of ESKD [HR 1.73 (95% CI 1.20–2.51)] and death [HR 1.83 (95% CI 1.05–3.19)].ConclusionsNew-onset anemia is frequent, particularly in patients with more severe renal damage and in those with diabetes mellitus. The occurrence of anemia, even of a mild degree, is associated with mortality risk and faster progression towards ESKD.

The Density of Renal Lymphatics Correlates With Clinical Outcomes in IgA Nephropathy

IntroductionIgA nephropathy (IgAN) is the most common primary glomerulonephritis (GN) worldwide. The disease course fluctuates, and the most important challenge is the considerable variation in the time lag between diagnosis and the development of a hard clinical end point, such as end-stage kidney disease (ESKD). The reaction of renal tissue to damage resembles the common wound-healing response. One part of this repair in IgAN is the expansion of lymphatic vessels known as lymphangiogenesis. The aim of this work was to establish the prognostic value of the density of lymphatic vessels in the renal biopsy at the time of diagnosis, for predicting the risk of ESKD in a Spanish cohort of patients with IgAN.MethodsWe performed a retrospective multicenter study of 76 patients with IgAN. The end point of the study was progression to ESKD. The morphometric analysis of lymphatic vessels was performed on tissue sections stained with antipodoplanin antibody.ResultsDensity of lymphatic vessels was significantly higher in patients with IgAN with mesangial hypercellularity >50%, segmental sclerosis, higher degrees of interstitial fibrosis, and tubular atrophy. Patients with more lymphatic vessels had significantly higher values of proteinuria and lower estimated glomerular filtration rate (eGFR). A density of lymphatic vessels ≥8 per mm2 was associated with a significantly higher rate of progression to ESKD at 3 years from biopsy. After adjustment for the International IgAN prediction score, at the multivariate logistic regression, high density of lymphatic vessels (≥8 per mm2) remained significantly associated with a higher rate of early progression to ESKD.ConclusionThis study contributes to the understanding of the natural history of the progression to ESKD in patients with IgAN revealing the density of lymphatics vessels may optimize the prognostic value of the International IgA predicting tool to calculate the risk of ESKD, favoring the evaluation of new targeted therapies.

Prediction of End-Stage Kidney Disease Using Estimated Glomerular Filtration Rate With and Without Race : A Prospective Cohort Study.

New estimated glomerular filtration rate (eGFR) equations removed race adjustment, but the impact of its removal on prediction of end-stage kidney disease (ESKD) is unknown. To compare the ESKD prediction performance of different eGFR equations. Observational, prospective cohort study. 7 U.S. clinical centers. 3873 participants with chronic kidney disease (CKD) from the CRIC (Chronic Renal Insufficiency Cohort) Study contributing 13902 two-year risk periods. ESKD was defined as initiation of dialysis or transplantation. eGFR was calculated using 5 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on serum creatinine and/or cystatin C, with or without race adjustment. The predicted 2-year risk for ESKD was calculated using the 4-variable Kidney Failure Risk Equation (KFRE). We evaluated the prediction performance of eGFR equations and the KFRE score using discrimination and calibration analyses. During a maximum 16 years of follow-up, 856 participants developed ESKD. Across all eGFR equations, the KFRE score was superior for predicting 2-year incidence of ESKD compared with eGFR alone (area under the curve ranges, 0.945 to 0.954 vs. 0.900 to 0.927). Prediction performance of KFRE scores using different eGFR equations was similar, but the creatinine equation without race adjustment improved calibration among Black participants. Among all participants, compared with an eGFR less than 20 mL/min/1.73 m2, a KFRE score greater than 20% had similar specificity for predicting 2-year ESKD risk (ranges, 0.94 to 0.97 vs. 0.95 to 0.98) but higher sensitivity (ranges, 0.68 to 0.78 vs. 0.42 to 0.66). Data are solely from the United States. The KFRE score better predicts 2-year risk for ESKD compared with eGFR alone, regardless of race adjustment. The creatinine equation with age and sex may improve calibration among Black patients. A KFRE score greater than 20% showed high specificity and sensitivity for predicting 2-year risk for ESKD. National Institutes of Health.

Rapidly progressive IgA nephropathy: clinicopathological characteristics and outcomes assessed according to the revised definition of the KDIGO 2021 Guideline.

Rapidly progressive immunoglobulin A nephropathy (RPIgAN) is a severe clinical phenotype of IgAN associated with a poor outcome. The recently published Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Guideline for the Management of Glomerular Diseases has proposed a new definition for RPIgAN that is based simply on a ≥50% decline in the estimated glomerular filtration rate (eGFR) over ≤3 months. In 1677 IgAN patients followed at a single centre in China, we evaluated the utility of this new definition to identify the highest-risk IgAN patients who might be suitable for combination immunosuppressive therapy. The proportion of a ≥50% decline in eGFR over ≤3 months was 5.2%. The majority of these patients had reversible causes, with only 2.3% (39/1677) meeting the KDIGO 2021 criteria for RPIgAN. These patients had a significantly higher risk for end-stage kidney disease (ESKD) than non-RPIgAN patients (logrank P < 0.001). RPIgAN was an independent risk factor for ESKD [hazard ratio 3.99 (95% confidence interval 2.25-7.09); P <0.001]. A minority of the RPIgAN patients (25.6%) had ≥50% crescents. There was no significant difference in the risk for ESKD between patients in the RPIgAN group with ≥50% crescents and ˂50% crescents (logrank P = 0.27). Patients with RPIgAN and ≥50% crescents had a higher risk for ESKD than patients with non-RPIgAN and ≥50% crescents (logrank P = 0.04). These data support the validity of the KDIGO 2021 definition but require independent validation in other non-Chinese cohorts.

Use of the kidney failure risk equation to inform clinical care of patients with chronic kidney disease: a mixed-methods systematic review

Rationale and objectiveThe Kidney Failure Risk Equation (KFRE) predicts the risk of end-stage kidney disease in patients with chronic kidney disease (CKD). This study aimed to evaluate the impact of...

Predictive Risk Models to Identify Patients at High-Risk for Severe Clinical Outcomes With Chronic Kidney Disease and Type 2 Diabetes.

Introduction/Objective:Predictive risk models identifying patients at high risk for specific outcomes may provide valuable insights to providers and payers regarding points of intervention and modifiable factors. The goal of our study was to build predictive risk models to identify patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) at high risk for progression to end stage kidney disease (ESKD), mortality, and hospitalization for cardiovascular disease (CVD), cerebrovascular disease (CeVD), and heart failure (HF).Methods:This was a retrospective observational cohort study utilizing administrative claims data in patients with CKD (stage 3-4) and T2D aged 65 to 89 years enrolled in a Medicare Advantage Drug Prescription plan offered by Humana Inc. between 1/1/2012 and 12/31/2017. Patients were enrolled ≥1 year pre-index and followed for outcomes, including hospitalization for CVD, CeVD and HF, ESKD, and mortality, 2 years post-index. Pre-index characteristics comprising demographic, comorbidities, laboratory values, and treatment (T2D and cardiovascular) were evaluated and included in the models. LASSO technique was used to identify predictors to be retained in the final models followed by logistic regression to generate parameter estimates and model performance statistics. Inverse probability censoring weighting was used to account for varying follow-up time.Results:We identified 169 876 patients for inclusion. Declining estimated glomerular filtration rate (eGFR) increased the risk of hospitalization for CVD (38.6%-61.8%) and HF (2-3 times) for patients with eGFR 15 to 29 mL/min/1.73 m2 compared to patients with eGFR 50 to 59 mL/min/1.73 m2. Patients with urine albumin-to-creatinine ratio (UACR) ≥300 mg/g had greater chance for hospitalization for CVD (2.0 times) and HF (4.9 times), progression to ESKD (2.9 times) and all-cause mortality (2.4 times) than patients with UACR <30 mg/g. Elevated hemoglobin A1c (≥8%) increased the chances for hospitalization for CVD (21.3%), CeVD (45.4%), and death (20.6%). Among comorbidities, history of HF increased the risk for ESKD, mortality, and hospitalization for CVD, CeVD, and HF.Conclusions:The predictive models developed in this study could potentially be used as decision support tools for physicians and payers, and the risk scores from these models can be applied to future outcomes studies focused on patients with T2D and CKD.

Impact of early glomerular filtration rate decline in response to antihypertensive treatment on risk of end-stage kidney disease and cardiovascular outcomes: a systematic review and meta-analysis.

Blood pressure control, which can induce a slight decrease in the glomerular filtration rate (GFR), plays a nephron- and cardioprotective role. However, the more important early decline in GFR associated with antihypertensive therapy and strict blood pressure targets is still of concern. Since few data are available from trials and observational studies, and the phenomenon is relatively rare, we performed a meta-analysis of available studies. We conclude that major reductions in the glomerular filtration rate occurring soon after starting angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and/or under intensive blood pressure control predict end-stage kidney disease.

Fasting Glucose Variability as a Risk Indicator for End-Stage Kidney Disease in Patients with Diabetes: A Nationwide Population-Based Study.

Given the fact that diabetes remains a leading cause of end-stage kidney disease (ESKD), multi-aspect approaches anticipating the risk for ESKD and timely correction are crucial. We investigated whether fasting glucose variability (FGV) could anticipate the development of ESKD and identify the population prone to the harmful effects of GV. We included 777,192 Koreans with diabetes who had undergone health examinations more than three times in 2005–2010. We evaluated the risk of the first diagnosis of ESKD until 2017, according to the quartile of variability independent of the mean (VIM) of FG using multivariate-adjusted Cox proportional hazards analyses. During the 8-year follow-up, a total of 7290 incidents of ESKD were found. Subjects in the FG VIM quartile 4 had a 27% higher risk for ESKD compared to quartile 1, with adjustment for cardiovascular risk factors and the characteristics of diabetes. This effect was more distinct in patients aged < 65 years; those with a long duration of diabetes; the presence of hypertension or dyslipidemia; and prescribed angiotensin-converting enzyme inhibitors, metformin, sulfonylurea, α-glucosidase inhibitors, and insulin. In contrast, the relationship between baseline FG status and ESKD risk showed a U-shaped association. FGV is an independent risk factor for kidney failure regardless of FG.

Outcomes of Kidney Donors With Impaired Fasting Glucose.

Many kidney donor candidates with impaired fasting glucose (IFG) and all candidates with diabetes are currently excluded from kidney donation, fearing the development of an accelerated course of diabetic kidney disease in the remaining kidney. We studied mortality, proteinuria, and end-stage kidney disease (ESKD) in 8280 donors who donated between 1963 and 2007 according to donation fasting plasma glucose (FPG): <100 mg/dL (n = 6204), 100-125 mg/dL (n = 1826), and ≥126 mg/dL (n = 250). Donors with IFG and those with FPG ≥126 mg/dL were older, less likely to be non-Hispanic White, had a higher body mass index, and were more likely to be related to their recipient. After 15.7 ± 10.5 y from donation to study close, 4.4% died, 29.4% developed hypertension, 13.8% developed proteinuria, and 41 (0.5%) developed ESKD. In both the logistic and Cox models, IFG was associated with a higher diabetes risk (adjusted hazard ratio [aHR], 1.65; 95% confidence interval [CI], 1.18-2.30) and hypertension (aHR, 1.35; 95% CI, 1.10-1.65; P = 0.003 for both), but not higher risk of proteinuria or ESKD. The multivariable risk of mortality in donors with ≥126 mg/dL was higher than the 2 other groups, but risks of proteinuria, cardiovascular disease, and reduced estimated glomerular filtration rate were similar to those with FPG <126 mg/dL. Three cases of ESKD developed in the 250 donors with FPG ≥126 mg/dL at 18.6 ± 10.3 y after donation (aHR, 5.36; 95% CI, 1.0-27.01; P = 0.04). Donors with IFG and the majority of donors with ≥126 mg/dL do well and perhaps should not be routinely excluded from donation.

Relative leucocyte telomere length is associated with incident end-stage kidney disease and rapid decline of kidney function in type 2 diabetes: analysis from the Hong Kong Diabetes Register

Aims/hypothesisFew large-scale prospective studies have investigated associations between relative leucocyte telomere length (rLTL) and kidney dysfunction in individuals with type 2 diabetes. We examined relationships between rLTL and incident end-stage kidney disease (ESKD) and the slope of eGFR decline in Chinese individuals with type 2 diabetes.MethodsWe studied 4085 Chinese individuals with type 2 diabetes observed between 1995 and 2007 in the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data. rLTL was measured using quantitative PCR. ESKD was diagnosed based on the ICD-9 code and eGFR.ResultsIn this cohort (mean ± SD age 54.3 ± 12.6 years) followed up for 14.1 ± 5.3 years, 564 individuals developed incident ESKD and had shorter rLTL at baseline (4.2 ± 1.2 vs 4.7 ± 1.2, p < 0.001) than the non-progressors (n = 3521). On Cox regression analysis, each ∆∆Ct decrease in rLTL was associated with an increased risk of incident ESKD (HR 1.21 [95% CI 1.13, 1.30], p < 0.001); the association remained significant after adjusting for baseline age, sex, HbA1c, lipids, renal function and other risk factors (HR 1.11 [95% CI 1.03, 1.19], p = 0.007). Shorter rLTL at baseline was associated with rapid decline in eGFR (>4% per year) during follow-up (unadjusted OR 1.22 [95% CI 1.15, 1.30], p < 0.001; adjusted OR 1.09 [95% CI 1.01, 1.17], p = 0.024).Conclusions/interpretationrLTL is independently associated with incident ESKD and rapid eGFR loss in individuals with type 2 diabetes. Telomere length may be a useful biomarker for the progression of kidney function and ESKD in type 2 diabetes.Graphical abstract

Abstract 11152: Peripheral Artery Disease and 30-Year Risk of Kidney Outcomes in the Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Peripheral artery disease (PAD) increases the risk of various adverse outcomes such as other cardiovascular diseases, lower-extremity amputation, and infection. However, its impact on kidney outcomes is yet to be characterized. Hypothesis: Both symptomatic and asymptomatic PAD will be associated with kidney outcomes. Methods: Using data from the ARIC study (1987-1989), we categorized 13,864 participants with estimated glomerular filtration rate (eGFR) &gt;15 mL/min (mean age 54 [SD 6 years]) into symptomatic PAD (clinical history or intermittent claudication); asymptomatic PAD (ankle-brachial index [ABI] ≤0.90 but not symptomatic PAD); and ABI categories of 0.91-1.00, 1.01-1.10, 1.11-1.20 (reference), 1.21-1.30, and &gt;1.30. Incident end-stage kidney disease (ESKD) was defined by the need for renal replacement therapy or death due to chronic kidney disease (CKD), and incident CKD was defined by ≥25% decline in eGFR to &lt;60 mL/min or hospitalizations with CKD diagnosis among those with ≥eGFR 60 at baseline. We ran multivariable Cox models. Results: There were 580 ESKD cases and 4,602 CKD cases over ~30 years of follow-up. Both symptomatic PAD and asymptomatic PAD were significantly associated with incident ESKD with hazard ratios (HR) of 2.21 (95%CI 1.16-4.22) and 1.59 (1.07-2.36), respectively, after adjusting for potential confounders such as other cardiovascular diseases and diabetes (Table). The corresponding HRs for incident CKD were 1.43 (1.05-1.95) and 1.60 (1.35-1.90). Borderline low ABI 0.91-1.00 showed an elevated risk of kidney outcomes in demographically- adjusted Model 1. Conclusions: Symptomatic PAD and asymptomatic PAD were independently associated with a higher long-term risk of ESKD and CKD. These results further support the close link between atherosclerosis and kidney prognosis and highlight the need for kidney monitoring in persons with PAD regardless of leg symptoms.

Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome.

Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome.

Hematuria and subsequent long-term risk of end-stage kidney disease: A Danish population-based cohort study

BackgroundHematuria is a frequent incidental clinical finding and may be a symptom of pre-existing underlying benign or malignant urinary tract or kidney disease. However, in patients with no apparent underlying cause of hematuria, long-term prognosis of hematuria remains unknown. ObjectivesTo assess the long-term risk of end-stage-kidney disease (ESKD) in patients with a hospital-based hematuria diagnosis and no apparent underlying cause. MethodsPatients with a hospital diagnosis of hematuria were included and matched in a 1:5 ratio with comparison persons from the background population by age, sex and residency. We calculated the cumulative risk of ESKD considering death as a competing risk. Furthermore, we computed unadjusted and adjusted hazard ratios with 95% confidence intervals using Cox hazard regression with adjustment for age, sex, and comorbidities. ResultsWe included 170,189 hematuria-diagnosed patients. The absolute 10-year risk of ESKD was 0.7% (95%CI: 0.7–0.8) in patients with hematuria and 0.4% (95%CI: 0.3–0.4) in comparison persons, hence yielding an overall adjusted hazard ratio of 1.6 (95%CI: 1.4–1.7). Hematuria also increased the risk of EKSD in patients with pre-existing comorbidities like diabetes (adjusted HR: 1.3 [95%CI: 1.1–1.5]) and urogenital cancer (adjusted HR: 1.4 ([95%CI: 1.1–1.9]), whereas no association was observed in patients with previous kidney disease (adjusted HR: 0.9 (95%CI: 0.8–1.0). ConclusionA hospital-based hematuria diagnosis in patients with no apparent underlying cause of hematuria is a marker of an increased risk of future ESKD.

Deoxycholic Acid and Risks of Cardiovascular Events, ESKD, and Mortality in CKD: The CRIC Study

Rationale & ObjectiveElevated levels of deoxycholic acid (DCA) are associated with adverse outcomes and may contribute to vascular calcification in patients with chronic kidney disease (CKD). We tested the hypothesis that elevated levels of DCA were associated with increased risks of cardiovascular disease, CKD progression, and death in patients with CKD.Study DesignProspective observational cohort study.Setting & ParticipantsWe included 3,147 Chronic Renal Insufficiency Cohort study participants who had fasting DCA levels. The average age was 59 ± 11 years, 45.3% were women, 40.6% were African American, and the mean estimated glomerular filtration rate was 42.5 ± 16.0 mL/min/1.73 m2.PredictorFasting DCA levels in Chronic Renal Insufficiency Cohort study participants.OutcomesRisks of atherosclerotic and heart failure events, end-stage kidney disease (ESKD), and all-cause mortality.Analytical ApproachWe used Tobit regression to identify predictors of DCA levels. We used Cox regression to examine the association between fasting DCA levels and clinical outcomes.ResultsThe strongest predictors of elevated DCA levels in adjusted models were increased age and nonuse of statins. The associations between log-transformed DCA levels and clinical outcomes were nonlinear. After adjustment, DCA levels above the median were independently associated with higher risks of ESKD (HR, 2.67; 95% CI, 1.51-4.74) and all-cause mortality (HR, 2.13; 95% CI, 1.25-3.64). DCA levels above the median were not associated with atherosclerotic and heart failure events, and DCA levels below the median were not associated with clinical outcomes.LimitationsWe were unable to measure DCA longitudinally or in urinary or fecal samples, and we were unable to measure other bile acids. We also could not measure many factors that affect DCA levels.ConclusionsIn 3,147 participants with CKD stages 2-4, DCA levels above the median were independently associated with ESKD and all-cause mortality.

Aging is associated with slower renal progression in patients with chronic kidney disease

Objectives:Chronic kidney disease (CKD) is prevalent among the elderly. However, little is known about how the clinical course of CKD vary with age. The purpose of this study was to examine the impact of aging on the risk of end-stage kidney disease (ESKD) in patients with moderate to advanced CKD.Materials and Methods:A total of 454 patients with stages 3–5 CKD were prospectively followed for a median of 5.1 years. The primary outcome was ESKD needing chronic dialysis therapy or preemptive kidney transplantation. The secondary outcome was a composite of ESKD or all-cause mortality.Results:The mean age of the patients was 65 ± 13 years. 65.4% were men, 44.9% had diabetes mellitus, and 22.7% had cardiovascular disease. Overall, 142 participants progressed to ESKD and 63 participants died. Compared with young patients (age <65 years, n = 205), elderly patients (age ≥65 years, n = 249) were associated with a significantly decreased risk of ESKD in Cox proportional hazards models adjusted for sex, smoking history, diabetes mellitus, cardiovascular disease, systolic blood pressure, estimated glomerular filtration rate, urine protein: Creatinine ratio, use of renin-angiotensin-aldosterone blocker, hemoglobin, phosphate, interleukin-6, body mass index, and N-terminal pro-brain natriuretic peptide (hazard ratio [HR]: 0.66; 95% confidence interval [CI]: 0.45, 0.96; P = 0.028). The results remained statistically significant when death as a competing risk was taken into account (subdistribution HR: 0.65; 95% CI: 0.45, 0.95, P = 0.026). Notably, elderly did not predict a higher risk for the composite outcome (HR: 0.94; 95% CI: 0.67, 1.32; P = 0.723).Conclusion:Elderly confers a decreased risk of ESKD in Taiwanese patients with moderate to advanced CKD. Our findings suggest that age is an important effect modifier for CKD progression.

Longitudinal Follow-Up and Outcomes for Chinese Patients with Stage 1–4 Chronic Kidney Disease

Introduction: Understanding heterogeneity in the prognosis of chronic kidney disease (CKD) has implications in management of patients. We aimed to evaluate the comparative risk of end-stage kidney disease (ESKD), cardiovascular (CV) events, and death among patients with CKD in China. Methods: In total, 3,700 patients with CKD stage 1–4 were recruited from 39 clinical centers in China between 2011 and 2016. New occurrence of ESKD, CV events, and all-cause mortality was recorded until the end of 2017. The crude incidence rate was calculated for each outcome. Ratios of incidence between different outcomes were generated with 95% confidence interval (CI) estimated by 1,000 times of bootstrapping. Multivariable adjusted Cox regression models accounting for competing risk between the outcomes were used to evaluate the association of risk factors with the outcomes. Results: The population mean age was 50 ± 14 years, with 58.2% male and 60.3% of glomerulonephritis. After a median follow-up of 4.65 years (interquartile range [IQR]: 3.71–5.60 years) for ESKD, 4.76 years (IQR: 3.97–5.76 years) for CV events, and 4.84 years (IQR: 3.97–5.76 years) for death, the incidence rates of the 3 outcomes were 3.1, 1.5, and 0.92/100 patient-years, respectively. The ratio for the incidence of ESKD and CV events was 2.15 (95% CI: 1.87, 2.53) and that for incidence of ESKD and death was 3.41 (95% CI: 2.88, 4.08). Significant differences regarding the ratios were detected through levels of age, history of CV disease, the estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (uACR), and etiology of CKD. In the Cox regression model adjusting for traditional CV and kidney-specific risk factors, older age was associated with a higher risk of CV events and death but a lower risk of ESKD (hazard ratios [HRs] = 1.45 [95% CI: 1.29, 1.64], 1.48 [95% CI: 1.29, 1.70], and 0.78 [95% CI: 0.73, 0.84] per 10 year increase, respectively). By comparison, reduced eGFR was associated with a higher risk of ESKD and death, rather than CV events (HRs = 3.62 [95% CI: 2.96, 4.43], 1.30 [95% CI: 1.02, 1.66], and 1.22 [95% CI: 0.99, 1.49] per 30.26 mL/min/1.73 m2 increase, respectively). Similar patterns were seen for increased uACR (HRs = 1.42 [95% CI: 1.30, 1.55], 1.17 [95% CI: 1.05, 1.30], and 1.07 [95% CI: 0.99, 1.17] per 1 natural log-transformed value increase, respectively). Conclusion: ESKD was more likely to occur than CV events and death in the population with CKD stage 1–4 in China. Traditional risk factors contributed differently to the comparative risk of the outcomes.

Associations of kidney tests at medical facilities and health checkups with incidence of end-stage kidney disease: a retrospective cohort study

No study has assessed the association between no health checkup and end-stage kidney disease (ESKD). This retrospective cohort study, including 69,147 adults aged ≥ 40 years in Japan who were insured by the National Health Insurance and the Late-Stage Medical Care System for the Elderly, assessed the associations of kidney tests at medical facilities and health checkups with incident ESKD. The main exposure was the histories of kidney tests using dipstick urinalysis and/or serum creatinine measurement at medical facilities and checkups in the past year: “checkups,” “no kidney test (without checkup),” and “kidney tests (without checkup)” groups. During the median observational period of 5.0 years, ESKD was observed in 246 (0.8%) men and 124 (0.3%) women. The “no kidney test” group was associated with ESKD in men (adjusted subhazard ratio of “no kidney test” vs. “checkups”: 1.66 [95% confidence interval, 1.04–2.65], but not in women. Age-specific subgroup analyses identified the “no kidney test” group as a high-risk population of ESKD in elderly men (1.30 [0.70–2.41] and 2.72 [1.39–5.33] in men aged 40–74 and ≥ 75 years, respectively). Elderly men with no kidney test at medical facilities and no health checkup were at higher risk of ESKD.