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Abstract The association of physical activity with renal outcome and mortality in advanced chronic kidney disease (CKD; i.e., estimated glomerular filtration rate [eGFR]

Xiaojie Chen,1,2 Jianteng Xie,2 Yifan Zhang,2 Shaogui Zhang,2 Sheng Li,2 Min Lu,2 Danfeng Liu,2 Weiting He,2 Hokhim Yau,2 Runli Jia,2 Yaxi Zhu,2 Wenjian Wang2 1Department of Nephrology, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, People’s Republic of ChinaCorrespondence: Wenjian Wang, Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 106 Zhongshan Er Road, Main Building, Room 1436, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel +86 (20)83827812-61421, Email wangwenjian@gdph.org.cnObjective: Diabetic kidney disease (DKD) patients with anemia face an elevated risk of glomerular filtration rate decline. However, the association between hemoglobin and estimated Glomerular Filtration Rate (eGFR) progression remains to be elucidated.Methods: A retrospective cohort of 815 subjects with DKD was followed from January 2010 to January 2023. A Cox proportional hazard regression model was utilized to explore the predictive role of hemoglobin in renal outcomes. Renal outcomes were defined as a composite endpoint, including a 50% decline in eGFR from baseline or progression to End-Stage Renal Disease (ESRD). To unveil any nonlinear relationship between hemoglobin and renal outcomes, Cox proportional hazard regression with cubic spline functions and smooth curve fitting was conducted. Additionally, subgroup analyses were performed to identify specific patient populations that might derive greater benefits from higher hemoglobin.Results: Among the 815 DKD subjects, the mean age was 56.482 ± 9.924 years old, and 533 (65.4%) were male. The mean hemoglobin was 121.521± 22.960 g/L. The median follow-up time was 21.103± 18.335 months. A total of 182 (22.33%) individuals reached the renal composite endpoint during the study period. After adjusting for covariates, hemoglobin was found to exert a negative impact on the renal composite endpoint in patients with DKD (HR 0.975, 95% CI [0.966, 0.984]). A nonlinear relationship between hemoglobin and the renal composite endpoint was identified with an inflection point at 109 g/L. Subgroup analysis unveiled a more pronounced association between hemoglobin and renal prognosis in males.Conclusion: Hemoglobin emerges as a predictive indicator for the renal prognosis of diabetic kidney disease in China. This study reveals a negative and non-linear relationship between hemoglobin levels and the renal composite endpoint. A substantial association is noted when hemoglobin surpasses 109 g/L in relation to the renal composite endpoint.Keywords: hemoglobin, eGFR decline, ESRD, diabetic kidney disease, non-linear, Cox proportional-hazards regression

Context The components of metabolic syndrome (MetS) are interrelated and associated with renal complications in patients with type 2 diabetes (T2D). Objective We aimed to reveal prevalent metabolic profiles in patients with T2D and identify which metabolic profiles were risk markers for renal progression. Methods A total of 3556 participants with T2D from a hospital (derivation cohort) and 931 participants with T2D from a community survey (external validation cohort) were included. The primary outcome was the onset of diabetic kidney disease (DKD), and secondary outcomes included estimated glomerular filtration rate (eGFR) decline, macroalbuminuria, and end-stage renal disease (ESRD). In the derivation cohort, clusters were identified using the 5 components of MetS, and their relationships with the outcomes were assessed. To validate the findings, participants in the validation cohort were assigned to clusters. Multivariate odds ratios (ORs) of the primary outcome were evaluated in both cohorts, adjusted for multiple covariates at baseline. Results In the derivation cohort, 6 clusters were identified as metabolic profiles. Compared with cluster 1, cluster 3 (severe hyperglycemia) had increased risks of DKD (hazard ratio [HR] [95% CI]: 1.72 [1.39-2.12]), macroalbuminuria (2.74 [1.84-4.08]), ESRD (4.31 [1.16-15.99]), and eGFR decline [ P <.001]; cluster 4 (moderate dyslipidemia) had increased risks of DKD (1.97 [1.53-2.54]) and macroalbuminuria (2.62 [1.61-4.25]). In the validation cohort, clusters 3 and 4 were replicated to have significantly increased risks of DKD (adjusted ORs: 1.24 [1.07-1.44] and 1.39 [1.03-1.87]). Conclusion We identified 6 prevalent metabolic profiles in patients with T2D. Severe hyperglycemia and moderate dyslipidemia were validated as significant risk markers for DKD. [ABSTRACT FROM AUTHOR]

Rationale & Objective: Plasma proneurotensin/neuromedin N (pro-NT/NMN) is a precursor of neurotensin, a tridecapeptide linked with type 2 diabetes mellitus and other comorbid conditions associated with kidney disease. Whether pro-NT/NMN is directly associated with incident chronic kidney disease (CKD), and whether that association differs by race, is uncertain. We evaluated whether pro-NT/NMN levels were associated with increased risk of kidney outcomes. Study Design: Prospective cohort. Setting & Participants: Participants in Biomarker Mediators of Racial Disparities in Risk Factors, a nested cohort from the REasons for Geographic And Racial Differences in Stroke study, with available stored serum and urine samples from baseline and second visits for biomarker measurement. Exposure: Baseline log-transformed pro-NT/NMN. Outcomes: Incident CKD, progressive estimated glomerular filtration rate (eGFR) decline, incident albuminuria, and incident kidney failure within median follow-up time of 9.4 years. Analytical Approach: Logistic regression. Results: Among 3,914 participants, the mean ± SD age was 64 ± 8 (SD) years, 48% were women, and 51% were Black. Median baseline eGFR was 90 (IQR, 77-102) mL/min/1.73 m2. Each SD higher of pro-NT/NMN was associated with 9% higher odds of progressive eGFR decline (OR, 1.09; 95% CI, 1.00-1.20). There was no association observed with incident CKD (OR, 1.10; 95% CI, 0.96-1.27), incident albuminuria (OR, 1.08; 95% CI, 0.96-1.22), or incident kidney failure (OR, 1.10; 95% CI, 0.83-1.46). There were no differences in results by race or sex. Limitations: Single measurement of pro-NT/NMN and limited generalizability. Conclusions: Higher pro-NT/NMN was associated with progressive eGFR decline but no other manifestations of kidney disease incidence. Plain-Language Summary: Neurotensin is a peptide secreted by the small intestine in response to a meal. Higher levels of neurotensin and its stable precursor, proneurotensin/neuromedin N (pro-NT/NMN), have been associated with cardiovascular disease and type 2 diabetes mellitus, important risk factors for the development of kidney disease. Whether pro-NT/NMN is directly associated with kidney outcomes has been less studied and has been done so in largely homogenous cohorts of White participants. Using the REasons for Geographic And Racial Differences in Stroke study, we followed Black and White participants and evaluated the risk of developing kidney outcomes. We found that elevated levels of pro-NT/NMN were associated with kidney function decline. Pro-NT/NMN may help individuals who may benefit from closer monitoring of kidney function.

Background: The effect of isolated hematuria without proteinuria on kidney function decline, and the modification by the severity of proteinuria in general population are not fully elucidated. Methods: Participants were included in the Japan Specific Health Checkups Study between 2008 and 2014. The exposure of interest was the frequency of dipstick hematuria during the observation. In each proteinuria frequency category (non-, occasional, persistent), hematuria-related decline in the eGFR rate was examined by analysis of covariance (ANCOVA). eGFR decline trajectories were also assessed using mixed-effects models. Results: Among the 552,951 participants, 146,753 (26.5%) had hematuria, and 56,021 (10.1%) and 8,061 (1.5%) had occasional and persistent proteinuria, respectively. During the median follow-up of 3.0 years, annual change in eGFR decline in participants with hematuria was significantly faster than in those without hematuria (mean [95% confidence interval]: − 0.95 [− 0.98 to − 0.92] vs − 0.86 [− 0.87 to − 0.84] mL/min/1.73 m2/year; P < 0.001). In ANCOVA, the hematuria-related annual eGFR decline rate increased as proteinuria frequency categories increased (differences in annual eGFR decline rate between participants with and without hematuria: 0.08 [0.06 to 0.09] in participants with non-proteinuria category, 0.17 [0.15 to 0.18] in occasional proteinuria category, and 0.68 [0.65 to 0.71] mL/min/1.73 m2/year in persistent proteinuria category; P for interaction < 0.001). Similar results were obtained by the linear mixed-effect model. Conclusions: Proteinuria has a synergistic effect on dipstick hematuria-related decline in kidney function. Among the general population without proteinuria throughout the observational period, the "isolated hematuria"-related eGFR decline was statistically significant but the difference was small. [ABSTRACT FROM AUTHOR]

We aimed to assess the potential socio-demographic, clinical, and lifestyle-related risk factors for kidney function decline (KFD), defined as ≥30% estimated glomerular filtration rate (eGFR) decline, in an Iranian cohort study. 7190 participants (4049 women) aged 20–90 years with 2–5 eGFR data from examinations (2001–2005 to 2015–2018) were included. Cox proportional hazard models were used to examine the association between potential risk factors and eGFR decline. During 11.5 years of follow-up, 1471 (889 women) participants had incident KFD with a crude incidence rate of 192.1 (182.6–202.2) per 10,000 person-year. Among the total population, older age, female gender, prehypertension, hypertension, diabetes, widowed/divorced states, higher triglycerides (TG), prevalent cardiovascular diseases (CVD), and higher baseline eGFR were significantly associated with higher, while moderate physical activity and a positive family history of diabetes were associated with lower risk of KFD (all p values <.05). Prevalent CVD in women but not men, diabetes, and hypertension among postmenopausal than premenopausal women were significant risk factors of KFD. According to the presence of chronic kidney disease (CKD) at baseline, higher eGFR decreased the risk of KFD in patients with CKD and increased KFD risk in those without CKD (all p for interactions <.05). KFD is associated with multiple modifiable risk factors among the Iranian urban population that is affected by gender, menopausal status, and initial kidney function. Interventions targeting these factors might potentially help reduce the burden of KFD. Menopausal status may influence the relationship between cardiometabolic risk factors and KFD; The impact of higher baseline eGFR on the risk of KFD differed between subjects with preserved kidney function and CKD patients. The interaction between gender, menopausal status, and baseline kidney function with different risk factors on KFD may help to make renal risk prediction scores to identify those in the general population at risk who may benefit from early prevention. [ABSTRACT FROM AUTHOR]

AbstractBackground and aims We aimed to assess the potential socio-demographic, clinical, and lifestyle-related risk factors for kidney function decline (KFD), defined as ≥30% estimated glomerular filtration rate (eGFR) decline, in an Iranian cohort study.Methods 7190 participants (4049 women) aged 20–90 years with 2–5 eGFR data from examinations (2001–2005 to 2015–2018) were included. Cox proportional hazard models were used to examine the association between potential risk factors and eGFR decline.Results During 11.5 years of follow-up, 1471 (889 women) participants had incident KFD with a crude incidence rate of 192.1 (182.6–202.2) per 10,000 person-year. Among the total population, older age, female gender, prehypertension, hypertension, diabetes, widowed/divorced states, higher triglycerides (TG), prevalent cardiovascular diseases (CVD), and higher baseline eGFR were significantly associated with higher, while moderate physical activity and a positive family history of diabetes were associated with lower risk of KFD (all p values

(1) Background: Chronic kidney disease (CKD) is extremely common against the backdrop of type 2 diabetes (T2D), accounting for nearly 30–40% of cases. The conventional management strategy relie predominantly on metabolic control and the renin–angiotensin–aldosterone system (RAAS) blockage. In the last decade, sodium glucose cotransporter 2 inhibitors (SGLT-2is) have emerged as the leading molecules preventing the development of, as well as retarding, the progression to CKD. Although the evidence in support of SGLT-2is is overwhelming, the definition of renal composite outcome in the trials varied considerably. The aim of the present meta-analysis was to explore the robustness of the renal composite benefits using a uniform definition. (2) Methods: A web-based search was conducted using the Cochrane Library to identify the relevant articles for meta-analysis. RStudio (1 July 2022, Build 554) software was used to conduct the meta-analysis. Hazard ratio (HR) was the effect size used to estimate the renal composite benefit, and prediction interval was used to detect heterogeneity. In view of the differing baseline characteristic of the trials as well as different molecules used, a random effects model was used. (3) Results: There were 12 trials including 78,781 patients, identified using the search strategy, and a five-point Cochrane risk-of-bias was used to assess quality of the publications. In the overall estimation (irrespective of the definition used for the renal composite) the HR was 0.68 (95% CI 0.60–0.76, prediction interval: 0.48–0.95) in favour of SGLT-2is, devoid of heterogeneity. While using a uniform definition of eGFR ≥ 40%decline, ESKD, or renal death, the HR was 0.64 (95% CI 0.53–0.78); using eGFR ≥ 50%decline, ESKD, or renal death the HR was 0.75 (95% CI 0.59–0.97); and with doubling of serum creatinine, renal replacement therapy, or renal death, the HR was 0.67 (95% CI 0.55–0.83) in favour of SGLT-2is. However, significant heterogeneity was encountered with all these three definitions. (4) Conclusion: There is a need to analyse the renal outcomes using a uniform definition in future trials. The presence of heterogeneity might disappear with the pooling of larger number of trials. However, if heterogeneity persists, we need to identify other clinical or laboratory attributes (in addition to SGLT-2is) responsible for the positive renal outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Glycemic variability (GV) is developing as a marker of glycemic control, which can be utilized as a promising predictor of complications. To determine whether long-term GV is associated with incident eGFR decline in two cohorts of Tehran Lipid and Glucose Study (TLGS) and Multi-Ethnic Study of Atherosclerosis (MESA) during a median follow-up of 12.2 years. Methods Study participants included 4422 Iranian adults (including 528 patients with T2D) aged ≥ 20 years from TLGS and 4290 American adults (including 521 patients with T2D) aged ≥ 45 years from MESA. The Multivariate Cox proportional hazard models were used to assess the risk of incident eGFR decline for each of the fasting plasma glucose (FPG) variability measures including standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of the mean (VIM) both as continuous and categorical variables. The time of start for eGFR decline and FPG variability assessment was the same, but the event cases were excluded during the exposure period. Results In TLGS participants without T2D, for each unit change in FPG variability measures, the hazards (HRs) and 95% confidence intervals (CI) for eGFR decline ≥ 40% of SD, CV, and VIM were 1.07(1.01–1.13), 1.06(1.01–1.11), and 1.07(1.01–1.13), respectively. Moreover, the third tertile of FPG-SD and FPG-VIM parameters was significantly associated with a 60 and 69% higher risk for eGFR decline ≥ 40%, respectively. In MESA participants with T2D, each unit change in FPG variability measures was significantly associated with a higher risk for eGFR decline ≥ 40%.Regarding eGFR decline ≥ 30% as the outcome, in the TLGS, regardless of diabetes status, no association was shown between FPG variability measures and risk of eGFR decline in any of the models; however, in the MESA the results were in line with those of GFR decline ≥ 40%.Using pooled data from the two cohorts we found that generally FPG variability were associated with higher risk of eGFR decline ≥ 40% only among non-T2D individuals. Conclusions Higher FPG variability was associated with an increased risk of eGFR decline in the diabetic American population; however, this unfavorable impact was found only among the non-diabetic Iranian population.

Objective: Atrial Fibrillation (AF) and chronic kidney disease frequently coexist in the elderly. Warfarin-like drugs (WLDs) may be associated with a relatively greater decrease of estimated glomerular filtration rate (eGFR) as compared to direct oral anticoagulants (DOACs), but there is no evidence on the medium- and long-term changes. To further elucidate this issue in elderly patients with AF, we investigated the renal function deterioration in the two groups of the study (DOACs or WLDs). Patients and Methods: A total of 420 AF patients were enrolled (mean age: 77.0 ± 6.0 years; 136 on WLDs and 284 on DOACs). These patients underwent three eGFR measurements during the follow-up period. The between-arms difference of eGFR decline over time was investigated by Linear Mixed Models and group-based trajectory model analyses. Results: In thewhole study cohort, after amedian follow-up of 4.9 years (interquartile range: 2.7-7.0 years), eGFR decreased from 67.4 ± 18.2 to 47.1 ± 14.3mL/min/1.73m² (p < 0.001). Remarkably, patients on DOACs experienced a significantly smaller eGFR decline thanWLDs patients (-21.3% vs. -45.1%, p < 0.001) and thiswas true both in the medium-term (-6.6 vs. -19.9 mL/min/1.73m²) and in the long-term (-13.5 versus -34.2 mL/min/1.73m²) period. After stratification into five subgroups according to trajectories of renal function decline over time, logistic regression showed that DOACs patients had from 3.03 to 4.24-fold greater likelihood to belong to the trajectory with lessmarked eGFR decline over time than WLDs patients. Conclusion: Elderly patients with AF on treatment with DOACs had a relatively smaller decline of eGFR over time compared to those on treatment with WLDs. This is consistent with what was partly reported in the literature. [ABSTRACT FROM AUTHOR]

Objective: Atrial Fibrillation (AF) and chronic kidney disease frequently coexist in the elderly. Warfarin-like drugs (WLDs) may be associated with a relatively greater decrease of estimated glomerular filtration rate (eGFR) as compared to direct oral anticoagulants (DOACs), but there is no evidence on the medium- and long-term changes. To further elucidate this issue in elderly patients with AF, we investigated the renal function deterioration in the two groups of the study (DOACs or WLDs).Patients and Methods: A total of 420 AF patients were enrolled (mean age: 77.0 ± 6.0 years; 136 on WLDs and 284 on DOACs). These patients underwent three eGFR measurements during the follow-up period. The between-arms difference of eGFR decline over time was investigated by Linear Mixed Models and group-based trajectory model analyses.Results: In the whole study cohort, after a median follow-up of 4.9 years (interquartile range: 2.7–7.0 years), eGFR decreased from 67.4 ± 18.2 to 47.1 ± 14.3 mL/min/1.73 m2 (p < 0.001). Remarkably, patients on DOACs experienced a significantly smaller eGFR decline than WLDs patients (−21.3% vs. −45.1%, p < 0.001) and this was true both in the medium-term (−6.6 vs. −19.9 mL/min/1.73 m2) and in the long-term (−13.5 versus −34.2 mL/min/1.73 m2) period. After stratification into five subgroups according to trajectories of renal function decline over time, logistic regression showed that DOACs patients had from 3.03 to 4.24-fold greater likelihood to belong to the trajectory with less marked eGFR decline over time than WLDs patients.Conclusion: Elderly patients with AF on treatment with DOACs had a relatively smaller decline of eGFR over time compared to those on treatment with WLDs. This is consistent with what was partly reported in the literature.

Background: Glycemic variability (GV) is developing as a marker of glycemic control, which can be utilized as a promising predictor of complications. To determine whether long-term GV is associated with incident eGFR decline in two cohorts of Tehran Lipid and Glucose Study (TLGS) and Multi-Ethnic Study of Atherosclerosis (MESA) during a median follow-up of 12.2 years. Methods: Study participants included 4422 Iranian adults (including 528 patients with T2D) aged ≥ 20 years from TLGS and 4290 American adults (including 521 patients with T2D) aged ≥ 45 years from MESA. The Multivariate Cox proportional hazard models were used to assess the risk of incident eGFR decline for each of the fasting plasma glucose (FPG) variability measures including standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of the mean (VIM) both as continuous and categorical variables. The time of start for eGFR decline and FPG variability assessment was the same, but the event cases were excluded during the exposure period. Results: In TLGS participants without T2D, for each unit change in FPG variability measures, the hazards (HRs) and 95% confidence intervals (CI) for eGFR decline ≥ 40% of SD, CV, and VIM were 1.07(1.01–1.13), 1.06(1.01–1.11), and 1.07(1.01–1.13), respectively. Moreover, the third tertile of FPG-SD and FPG-VIM parameters was significantly associated with a 60 and 69% higher risk for eGFR decline ≥ 40%, respectively. In MESA participants with T2D, each unit change in FPG variability measures was significantly associated with a higher risk for eGFR decline ≥ 40%.Regarding eGFR decline ≥ 30% as the outcome, in the TLGS, regardless of diabetes status, no association was shown between FPG variability measures and risk of eGFR decline in any of the models; however, in the MESA the results were in line with those of GFR decline ≥ 40%.Using pooled data from the two cohorts we found that generally FPG variability were associated with higher risk of eGFR decline ≥ 40% only among non-T2D individuals. Conclusions: Higher FPG variability was associated with an increased risk of eGFR decline in the diabetic American population; however, this unfavorable impact was found only among the non-diabetic Iranian population. [ABSTRACT FROM AUTHOR]

Background Despite substantial improvements in short-term kidney allograft survival, median long-term survival remains at a standstill. It is unclear whether and to what extent a transplant centre's post-transplant care influences long-term outcomes. Methods We retrospectively analysed 501 single kidney transplant recipients (KTRs) who underwent transplantation between 2009 and 2018 and did not develop rejection or de novo donor-specific antibodies (dnDSA) within the first post-transplant year. After that, KTRs were either followed exclusively every 3 months by the transplant centre (n  = 197) or every 3 months by local nephrologists (n  = 304) with only yearly follow-up by the transplant centre. We analysed kidney allograft outcomes regarding estimated glomerular filtration rate (eGFR) decline, proteinuria, development of dnDSA and rejection. Results No differences between the two groups were observed in the baseline characteristics and the characteristics at the end of the first post-transplant year (P  > .05). KTRs followed by local nephrologists were comparable to KTRs followed by the transplant centre concerning patient survival (P  = .541), kidney allograft survival (P  = .385), eGFR decline (P  = .488), progression of proteinuria (P  > .05), the development of dnDSA (P  = .335) and T-cell-mediated rejection (P  = .480). KTRs followed by the transplant centre were more likely to undergo indication biopsies in case of allograft dysfunction and dnDSA (P  < .001). Antibody-mediated rejection was diagnosed earlier and more frequently (P  = .059), recurrent glomerulonephritis was diagnosed earlier and more frequently (P  = .026) and immunosuppression was modified earlier and more frequently in response to histological findings (P  = .038). Conclusions Our findings suggest that close collaboration between local nephrologists and the transplant centre ensures good allograft outcomes independent of the caregiver. Greater biopsy activity in the transplant centre allows for earlier diagnosis of allograft dysfunction as the basis for novel treatment options. [ABSTRACT FROM AUTHOR]

Rationale & objectiveRandom assignment to intensive blood pressure (BP) lowering (systolic BP

BackgroundRandom assignment to the intensive systolic blood pressure (SBP) arm (

BackgroundPrior studies have suggested that arteriovenous fistula (AVF) or graft (AVG) creation may be associated with slowing of estimated glomerular filtration rate (eGFR) decline. It is unclear if this is attributable to the physiological benefits of a mature access on systemic circulation versus confounding factors.MethodsWe examined a nationwide cohort of 3026 US veterans with advanced chronic kidney disease (CKD) transitioning to dialysis between 2007 and 2011 who had a pre-dialysis AVF/AVG and had at least three outpatient eGFR measurements both before and after AVF/AVG creation. Slopes of eGFR were estimated using mixed-effects models adjusted for fixed and time-dependent confounders, and compared separately for the pre- and post-AVF/AVG period overall and in patients stratified by AVF/AVG maturation. In all, 3514 patients without AVF/AVG who started dialysis with a catheter served as comparators, using an arbitrary 6-month index date before dialysis initiation to assess change in eGFR slopes.ResultsOf the 3026 patients with AVF/AVG (mean age 67 years, 98% male, 75% diabetic), 71% had a mature AVF/AVG at dialysis initiation. eGFR decline accelerated in the last 6 months prior to dialysis in patients with a catheter (median, from -6.0 to -16.3 mL/min/1.73 m2/year, P < 0.001), while a significant deceleration of eGFR decline was seen after vascular access creation in those with AVF/AVG (median, from -5.6 to -4.1 mL/min/1.73 m2/year, P < 0.001). Findings were independent of AVF/AVG maturation status and were robust in adjusted models.ConclusionsThe creation of pre-dialysis AVF/AVG appears to be associated with eGFR slope deceleration and, consequently, may delay the onset of dialysis initiation in advanced CKD patients.

BackgroundIt is not clear whether the pattern of kidney function decline in patients with chronic kidney disease (CKD) may relate to outcomes after reaching end-stage renal disease (ESRD). We hypothesize that an abrupt decline in kidney function prior to ESRD predicts early death after initiating maintenance hemodialysis therapy.Study designProspective cohort study.Setting & participantsThe Chronic Renal Insufficiency Cohort (CRIC) Study enrolled men and women with mild to moderate CKD. For this study, we studied 661 individuals who developed chronic kidney failure that required hemodialysis therapy initiation.PredictorsThe primary predictor was the presence of an abrupt decline in kidney function prior to ESRD. We incorporated annual estimated glomerular filtration rates (eGFRs) into a mixed-effects model to estimate patient-specific eGFRs at 3 months prior to initiation of hemodialysis therapy. Abrupt decline was defined as having an extrapolated eGFR≥30mL/min/1.73m(2) at that time point.OutcomesAll-cause mortality within 1 year after initiating hemodialysis therapy.MeasurementsMultivariable Cox proportional hazards.ResultsAmong 661 patients with CKD initiating hemodialysis therapy, 56 (8.5%) had an abrupt predialysis decline in kidney function and 69 died within 1 year after initiating hemodialysis therapy. After adjustment for demographics, cardiovascular disease, diabetes, and cancer, abrupt decline in kidney function was associated with a 3-fold higher risk for death within the first year of ESRD (adjusted HR, 3.09; 95% CI, 1.65-5.76).LimitationsRelatively small number of outcomes; infrequent (yearly) eGFR determinations; lack of more granular clinical data.ConclusionsAbrupt decline in kidney function prior to ESRD occurred in a significant minority of incident hemodialysis patients and predicted early death in ESRD.

Aims: Relationship between baseline eGFR and the rate of decline in eGFR was investigated in diabetic kidney disease. Materials and methods: Patients with type 2 diabetes with microalbuminuria (MI) (n = 124) or macroalbuminuria (MA) (n = 81) received team-based medical care to prevent the development of diabetic kidney disease. The decline in eGFR over 4 years, divided into the first year and subsequent 3 years, was estimated by linear-mixed modeling. Results: The eGFR showed a rapid decline during the first year, followed by a slower decline. On multiple regression analysis, the baseline eGFR was positively correlated with HbA1c in MI and negatively correlated with carotid plaque in MI and in MA. Subsequent eGFR decline following 1-year intervention was negatively correlated with the baseline eGFR and HbA1c level at 1 year in MI, whereas it was positively correlated with baseline eGFR and negatively correlated with the amount of proteinuria at 1 year in MA. Even in maintained baseline eGFR(≧ 60 ml/min/1.73 m2) at the first year, when HbA1c ≧ 7.5%, eGFR reduction rate and years to ESKD were much faster and shorter, compared to the group of HbA1c < 7.5% [− 3.44 (SE 1.137) vs. − 1.695 (SE 0.431) ml/min/1.73 m2/year, and 19.4 vs. 35.7 years, respectively]. In MA, lower eGFR (< 60 ml/min/1.73 m2) and higher proteinuria (≧ 2.25 g/gCre) had a much faster eGFR decline and shorter time to ESKD, compared to the group of maintained eGFR and lower proteinuria (< 2.25 g/gCre) [− 5.240 (SE 1.537) vs. − 2.67 (SE 0.997) ml/min/1.73 m2/year, and 4.41 vs. 22.8 years, respectively]. Conclusions: In MI, even in maintained eGFR, the continued increase in eGFR in response to hyperglycemia (HbA1c ≧ 7.5%) led to a faster decline in renal function and in MA, lower eGFR, with an increase in proteinuria, contributed to rapid decline of renal function. [ABSTRACT FROM AUTHOR]

Healthy dietary patterns have been associated with a lower risk of chronic kidney disease (CKD). We aimed to investigate the association of a fully food-based diet quality score assessed by the Lifelines Diet Score (LLDS) with either incident CKD or eGFR decline in the general population. For this study, data from a prospective general population-based Lifelines cohort in the Northern Netherlands was used. Diet was assessed with a 110-item food frequency questionnaire at baseline. The LLDS, based on international evidence for diet–disease relations at the food group level, was calculated to assess diet quality. For the analysis, the score was divided into tertiles. Logistic regression was performed to evaluate the association of the LLDS at baseline with either incident CKD (eGFR <60 mL/min/1.73 m2) or a ≥20% eGFR decline at the second study visit, adjusted for relevant confounders. A total of 78 346 participants free of CKD at baseline were included. During a mean (SD) follow-up of 3.6 ± 0.9 years, 2071 (2.6%) participants developed CKD and 7611 (9.7%) had a ≥20% eGFR decline. Participants in the highest tertile of LLDS had a lower risk of incident CKD (fully adjusted OR 0.83, [95% CI: 0.72–0.96]) and ≥20% eGFR decline (fully adjusted OR 0.80, [95% CI: 0.75–0.86]), compared with those in the lowest tertile. Similar dose–response associations were observed in continuous LLDS. Higher adherence to a high-quality diet was associated with a lower risk of incident CKD or ≥20% eGFR decline in the general population. [ABSTRACT FROM AUTHOR]

Background: Disease-specific trajectories of renal function in advanced chronic kidney disease (CKD) are not well defined. Here, we compared these trajectories in the estimated glomerular filtration rate (eGFR) by CKD stages. Methods: Patients with multiple eGFR measurements during the 5-year preregistration period of the REACH-J study were enrolled. Mean annual eGFR declines were calculated from linear mixed effect models with the adjustment variables of baseline CKD stage, age, sex and the current CKD stage and the level of proteinuria (CKDA1-3). Results: Among 1,969 eligible patients with CKDG3b-5, the adjusted eGFR decline (ml/min/1.73 m2/year) was significantly faster in diabetic kidney disease (DKD) patients and polycystic kidney disease (PKD) patients than in patients with other kidney diseases (DKD, − 2.96 ± 0.13; PKD, − 2.82 ± 0.17; and others, − 1.95 ± 0.05, p < 0.01). The declines were faster with higher CKD stages. In DKD patients, the eGFR decline was significantly faster in CKDG5 than CKDG4 (− 4.10 ± 0.18 vs − 2.76 ± 0.20, p < 0.01), while these declines in PKD patients were similar. The eGFR declines in PKD patients were significantly faster than DKD patients in CKDG4 (− 2.92 ± 0.23 vs − 2.76 ± 0.20, p < 0.01) and in CKDA2 (− 3.36 ± 0.35 vs − 1.40 ± 0.26, p < 0.01). Conclusion: Our study revealed the disease-specific annual eGFR declines by CKD stages and the level of proteinuria. Comparing to the other kidney diseases, the declines in PKD patients were getting faster from early stages of CKD. These results suggest the importance of CKD managements in PKD patients from the early stages. [ABSTRACT FROM AUTHOR]

Anjay Rastogi,1 Khalid Mohammed Ameen,1 Maha Al-Baghdadi,1 Kelly Shaffer,1 Niloofar Nobakht,1 Mohammad Kamgar,1 Edgar V Lerma21Department of Medicine, Division of Nephrology, David Geffen School of Medicine, Los Angeles, CA, USA; 2Department of Medicine, Divison of Nephrology, University of Illinois at Chicago/Advocate Christ Medical Center, Section of Nephrology, Oak Lawn, IL, USACorrespondence: Edgar V LermaUniversity of Illinois at Chicago/Advocate Christ Medical Center, 4400 W 95th, Oak Lawn, IL 60453, USATel +1 708 227 7305Email nephron0@gmail.comAbstract: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited multisystem disorder, characterized by renal and extra-renal fluid-filled cyst formation and increased kidney volume that eventually leads to end-stage renal disease. ADPKD is considered the fourth leading cause of end-stage renal disease in the United States and globally. Care of patients with ADPKD was, for a long time, limited to supportive lifestyle measures, due to the lack of therapeutic strategies targeting the main pathways involved in the pathophysiology of ADPKD. As the first FDA approved treatment of ADPKD, Vasopressin (V2) receptor blocking agent, tolvaptan, is an urgently awaited advance for ADPKD patients. In our review, we also shed some lights on what is beyond Tolvaptan as there are other medications in the pipeline and many medications have been or are currently being studied in clinical trials such as Tesevatinib, Metformin and Pravastatin, with the goal of slowing the rate of progression of ADPKD by reducing the increase in total kidney volume or maintaining eGFR. Here, we review updates in the perspectives and management of ADPKD.Keywords: vasopressin receptor antagonist, tolvaptan, metformin, total kidney volume, chronic kidney disease, hypertension

Although the association between Chronic Kidney Disease (CKD) and all-cause fractures was addressed in previous studies, the association between estimated glomerular filtration rate (eGFR) decline and fractures was poorly addressed. For the first time we examined the association between rapid kidney function decline (RKFD) and fracture incidence among Iranian general population. In a Tehranian community-based cohort, RKFD was defined as a 30 % decline in eGFR over 2–3 years. Cox proportional hazards models, adjusted for age, sex, current eGFR, diabetes mellitus, hypertension, dyslipidemia, current smoking, obesity status, waist circumference, prevalent cardiovascular diseases, aspirin, steroid use, education level, and marital status, were used to examine the association of RKFD with different fracture outcomes. Among 5305 (3031 women) individuals aged ≥30 years, during the median follow-up of 9.62 years, 226 fracture events were observed. The multivariable hazard ratio of RKFD for any-fracture events, lower-extremity, and major osteoporotic fractures were 2.18 (95 % CI, 1.24–3.85), 2.32 (1.15–4.71), and 2.91 (1.29–6.58), respectively. These associations remained significant after accounting for the competing risk of death. The impact of RKFD on the development of incident all-cause fractures was not modified by gender [men: 2.64 (1.11–6.25) vs. women: 2.11 (1.00–4.47)] and according to current CKD status [without CKD: 2.34 (1.00–5.52) vs. with CKD: 2.59 (1.04–6.44)] (all P for interaction >0.5). RKFD can increase the incidence of fractures among general population, the issue that was equally important among non-CKD individuals, emphasizing the need for early identification and management in those with rapidly declining eGFR. • Kidney function decline is a known risk factor for various adverse health outcomes. • Previous studies have shown a link between CKD and increased fracture risk. • First general population-based study to assess the link between RKFD & fracture risk. • ≥30 % eGFR decline over 2–3 yrs., independent of current eGFR markedly ups fracture risk • These findings robustly apply to both genders and with/without CKD. [ABSTRACT FROM AUTHOR]

Geographic variation in the prevalence of chronic kidney disease and incidence of end-stage renal disease has been previously reported. However, the geographic epidemiology of rapid estimated glomerular filtration rate (eGFR) decline has not been examined. Methods: We built a longitudinal cohort of 2,107,570 US veterans to characterize the spatial epidemiology of and examine the associations between US county characteristics and rapid eGFR decline. Results: There were 169,029 (8.02%) with rapid eGFR decline (defined as eGFR slope < –5 ml/min per 1.73 m2/year). The prevalence of rapid eGFR decline adjusted for age, race, gender, diabetes, and hypertension varied by county from 4.10%–6.72% in the lowest prevalence quintile to 8.41%–22.04% in the highest prevalence quintile (P for heterogeneity < 0.001). Examination of adjusted prevalence showed substantial geographic variation in those with and without diabetes and those with and without hypertension (P for heterogeneity < 0.001). Cohort participants had higher odds of rapid eGFR decline when living in counties with unfavorable characteristics in domains including health outcomes (odds ratio [OR] = 1.15; confidence interval [CI] = 1.09–1.22), health behaviors (OR = 1.08; CI = 1.03–1.13), clinical care (OR = 1.11; CI = 1.06–1.16), socioeconomic conditions (OR = 1.15; CI = 1.09–1.22), and physical environment (OR = 1.15; CI = 1.01–1.20); living in counties with high percentage of minorities and immigrants was associated with rapid eGFR decline (OR = 1.25; CI = 1.20–1.31). Spatial analyses suggest the presence of cluster of counties with high prevalence of rapid eGFR decline. Discussion: Our findings show substantial geographic variation in rapid eGFR decline among US veterans; the variation persists in analyses stratified by diabetes and hypertension status; results show associations between US county characteristics in domains capturing health, socioeconomic, environmental, and diversity conditions, and rapid eGFR decline.

Background. Prior studies have suggested that arteriovenous fistula (AVF) or graft (AVG) creation may be associated with slowing of estimated glomerular filtration rate (eGFR) decline. It is unclear if this is attributable to the physiological benefits of a mature access on systemic circulation versus confounding factors. Methods. We examined a nationwide cohort of 3026 US veterans with advanced chronic kidney disease (CKD) transitioning to dialysis between 2007 and 2011 who had a pre-dialysis AVF/ AVG and had at least three outpatient eGFR measurements both before and after AVF/AVG creation. Slopes of eGFR were estimated using mixed-effects models adjusted for fixed and time-dependent confounders, and compared separately for the pre- and post-AVF/AVG period overall and in patients stratified by AVF/AVG maturation. In all, 3514 patients without AVF/AVG who started dialysis with a catheter served as comparators, using an arbitrary 6-month index date before dialysis initiation to assess change in eGFR slopes. Results. Of the 3026 patients with AVF/AVG (mean age 67 years, 98% male, 75% diabetic), 71% had a mature AVF/AVG at dialysis initiation. eGFR decline accelerated in the last 6 months prior to dialysis in patients with a catheter (median, from -6.0 to -16.3 mL/min/1.73 m²/year, P < 0.001), while a significant deceleration of eGFR decline was seen after vascular access creation in those with AVF/AVG (median, from -5.6 to -4.1 mL/min/1.73 m²/year, P < 0.001). Findings were independent of AVF/AVG maturation status and were robust in adjusted models. Conclusions. The creation of pre-dialysis AVF/AVG appears to be associated with eGFR slope deceleration and, consequently, may delay the onset of dialysis initiation in advanced CKD patients. [ABSTRACT FROM AUTHOR]

Aims: To assess the association between dipstick hematuria and estimated glomerular filtration rate (eGFR) decline in Japanese patients with type 2 diabetes.Methods: Longitudinal data were obtained from 3068 Japanese patients with type 2 diabetes. To assess the independent association between dipstick hematuria and eGFR decline, we used Cox proportional hazard model adjusted for potential confounders.Results: Median follow-up period was 699.7days. Mean age, body mass index (BMI), and HbA1c level were 65.7years, 24.6kg/m2, and 7.5% (58.1mmol/mol), respectively. Positive dipstick hematuria was significantly associated with baseline eGFR and severity of albuminuria (p<0.001). The multivariable-adjusted hazard ratio for eGFR decline in patients with dipstick hematuria compared with those without dipstick hematuria was 2.19 [95% confidence interval (CI): 1.22-3.91]; this association remained significant even after the exclusion of patients who did not have diabetic retinopathy (hazard ratio: 2.39; 95% CI: 1.13-5.04).Conclusion: Positive dipstick hematuria was associated with severity of albuminuria and renal function. A significant association was found between dipstick hematuria and increased risk of eGFR decline among patients with type 2 diabetes. Therefore, our results suggest that dipstick hematuria is perhaps indicative of more severe diabetic nephropathy. [ABSTRACT FROM AUTHOR]

We assessed the effect of atrasentan therapy on a pre-specified panel of 13 urinary metabolites known to reflect mitochondrial function in patients with diabetic kidney disease. This post-hoc analysis was performed using urine samples collected during the RADAR study which was a randomized, double-blind, placebo-controlled trial that tested the effects of atrasentan on albuminuria reduction in patients with type 2 diabetes and nephropathy. At baseline, 4 of the 13 metabolites, quantified by gas-chromatography mass spectrometry, were below detectable levels, and 6 were reduced in patients with eGFR < 60 mL/min/1.73 m2. After 12 weeks of atrasentan treatment in patients with eGFR < 60 mL/min/1.73 m2, a single-value index of the metabolites changed by −0.31 (95%CI −0.60 to −0.02; P = .035), −0.08 (−12 to 0.29; P = .43) and 0.01 (−0.21 to 0.19; P = .913) in placebo, atrasentan 0.75 and 1.25 mg/d, respectively. The metabolite index difference compared to placebo was 0.13 (−0.17 to 0.43; P = .40) and 0.35 (0.05-0.65; P = .02) for atrasentan 0.75 and 1.25 mg/d, respectively. These data corroborate previous findings of mitochondrial dysfunction in patients with type 2 diabetes, nephropathy and eGFR < 60 mL/min/1.73 m2, suggesting that atrasentan may prevent the progression of mitochondrial dysfunction common to this specific patient population. Future studies of longer treatment duration with atrasentan are indicated. [ABSTRACT FROM AUTHOR]

The prevalence of hyperuricemia in patients with chronic kidney disease (CKD) is high, but the management is suboptimal under traditional treatment. This study was conducted to clarify whether febuxostat achieves better renal survival and patient outcome compared with traditional urate-lowering agents (ULAs). In total, 2,460 adults who had continuously received ULAs for at least three months before enrollment were investigated. Three groups were compared prospectively including non-conversion (n = 2,214), conversion (n = 206), and febuxostat first (n = 40). We evaluated laboratory changes, estimated glomerular filtration rate (eGFR) change, eGFR decline, renal survival, and all-cause mortality. The Cox proportional hazard risk analysis were also used for risk prediction. Multiple prescriptions for ULAs were found in both the non-conversion and conversion groups. However, improved median eGFR was noted in the febuxostat group (p

The prevalence of hyperuricemia in patients with chronic kidney disease (CKD) is high, but the management is suboptimal under traditional treatment. This study was conducted to clarify whether febuxostat achieves better renal survival and patient outcome compared with traditional urate-lowering agents (ULAs). In total, 2,460 adults who had continuously received ULAs for at least three months before enrollment were investigated. Three groups were compared prospectively including non-conversion (n = 2,214), conversion (n = 206), and febuxostat first (n = 40). We evaluated laboratory changes, estimated glomerular filtration rate (eGFR) change, eGFR decline, renal survival, and all-cause mortality. The Cox proportional hazard risk analysis were also used for risk prediction. Multiple prescriptions for ULAs were found in both the non-conversion and conversion groups. However, improved median eGFR was noted in the febuxostat group (p < 0.001), median serum uric acid (SUA) level decreased from 9.45 to 6.7 mg/dL in the febuxostat group (p = 0.010), and median SUA decreased from 8.5 to 6.3 mg/dL in the conversion group (p < 0.001). Decline rate was retarded in the conversion (p = 0.050). Using the Cox proportional model, the multivariate analysis showed conversion group, young age, and relatively good baseline eGFR were associated with better renal outcome [Hazard ratio (HR) = 0.51, 95% confidence interval (CI) = 0.39-0.69]. Febuxostat had a beneficial effect on renal outcome and hyperuricemia in CKD patients. In summary, our results support the use of aggressive treatment with febuxostat in CKD patients. [ABSTRACT FROM AUTHOR]

Background: Restriction of dietary sodium is routinely recommended for patients with chronic kidney disease (CKD). Whether or not sodium intake is associated with the progression of CKD and mortality remains controversial. We evaluated the association of urinary sodium excretion (as a surrogate for sodium intake) on the need for renal replacement therapy and mortality in patients with advanced CKD.Methods: We conducted a retrospective study of patients followed at a CKD clinic of a tertiary care hospital from January 2010 to December 2012. Adult patients with advanced CKD (estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m(2)) were included. Using a time-to-event analysis, we examined the association of urinary sodium excretion as a continuous and also as a categorical variable (categorized as low sodium diet - LSD (<100 mEq/day), medium sodium diet - MSD (100-150 mEq/day), and high sodium diet - HSD (>150 mEq/day) and the outcomes of interest. The primary outcome was defined as composite of progression to end-stage renal disease requiring any type of renal replacement therapy and mortality. The secondary outcome was change in eGFR/year.Results: 341 patients (82 LSD, 116 MSD and 143 HSD) were included in the study (mean follow up of 1.5 years) with a mean eGFR decline of 2.7 ml/min/1.73 m(2)/year. 105 patients (31 %) required renal replacement therapy and 10 (3 %) died. There was no association between urinary sodium excretion and change in the eGFR or need for renal replacement therapy and mortality in crude or adjusted models (unadjusted HR 1.002; 95%CI 1.000-1.004, adjusted HR 1.001; 95%CI 0.998-1.004).Conclusion: In patients with advanced CKD (eGFR < 30 ml/min/1.73 m(2)), sodium intake does not appear to impact the progression of CKD to end-stage renal disease; however, more definitive studies are needed. [ABSTRACT FROM AUTHOR]