Annual eGFR Decline Research Articles

504-P: Albuminuria Affects Prevention of Diabetic Kidney Disease Progression by Sodium–Glucose Transporter 2 Inhibitor

Objective: In type 2 diabetes(T2D), prevalence of chronic kidney disease (CKD) with normoalbuminuria is increasing. We assessed the annual eGFR decline rate (slope) in Japanese patients with T2D with CKD treated by sodium glucose transporter 2 inhibitor (SGLT2i). Methods: A total of 75 patients with T2D with CKD (eGFR<60ml/min/1.73m2) were recruited, whose initial eGFR slopes were calculated from 46±21 months period, and slopes after adding SGLT2 inhibitors (on empagliflozin 64% and others) were calculated from 21±8 months. Efficacy was compared between in patients with normo-/micro-alubuminuria (Norm/Micro) and with macroalbuminuria (Macro). Patients with Norm/Micro existed in 52% (39/75). At the time of recruitment, distribution in CKD stages are as follows, on stage 3A; eGFR 45-59 (21 vs. 8), stage 3B; eGFR 30-44, (13 vs. 15) and stage 4; eGFR<30 (5 vs. 13) respectively. Average age was 70.7±12.2 years old and duration of diabetes was 15.0±9.3 years. Results: 1) Average initial (first month) eGFR drop values are as follows, in Norm/Micro (51.2 to 47.9ml/min/1.73m2: P<0.01), in Macro (40.7 to 39.0ml/min/1.73m2: P=0.01). 2) Annual mean eGFR slopes were improved in each group, in Norm/Micro (-4.3±4.0 to -1.2±4.1ml/min/1.73m2/year; P<0.001), and in Macro (-8.9±12.2 to -2.3±3.6ml/min/1.73m2/year; P<0.01). 3) Proportion of showing reduction of eGFR slopes after adding SGLT2i are 69.2% (27/39) and 75.0% (27/36), respectively. And even in stage 4, 80.0% (4/5) and 76.9% (10/13), respectively. 4) Rapid decliner of eGFR (>10 ml/min/1.73m2/year) existed in 12.8% (5/39) and in 25.0% (9/36) respectively. Mean eGFR slopes in these rapid decliner were all improved and as follow, -12.2±2.1 to +1.2±3.4ml/min/1.73m2/year; P<0.001 and -22.3±19.0 to -1.6±4.0ml/min/1.73m2/year; P<0.01, respectively. Conclusion: SGLT2i could still have a remarkable renal benefit in Norm/Micro diabetic kidney disease. Slope analysis might be useful for safety and detecting rapid eGFR decliner. Disclosure K. Kashima: None. H. Shimizu: None. M. Yamada: None.

500-P: Renal Function Decline and the Related Risk Factors in a Cohort of Beijing Community Diabetes Study

Objective: To explore the renal function decline and the related risk factors in a cohort of Beijing Community Diabetes Study. Methods: A multi-center, prospective study with ten-year follow-up was conducted at Beijing communities between 2008 and 2018. The clinical information and physical examination were recorded. Laboratory test including hemoglobin A1c, serum uric acid, fasting blood glucose, serum creatinine, and blood lipid profile were conducted. The patients were divided into two groups according to their age (<65 and ≧ 65). Annual eGFR decline rate≧3ml/min/1.73m2 was defined as rapid renal function decline. The tendency of renal function change over 10 years in different age groups had been described. Logistic multivariable models were employed to investigate the risk factors of rapid renal function decline. Results: A total of 1655 patients with type 2 diabetes were enrolled. The median (quartile1, quartile3) annual rate of decline in eGFR of T2DM was 0.21(-2.51, 3.06) ml/min/1.73m2. Among them, 25.5% of the patients (n=422) showed rapid GFR decline, with an annual decrease of 5.28(3.85, 7.46) ml/min/1.73m2. Non-rapid decliner was 74.5% (n=1233), and the annual decrease was -0.99(-3.66, 0.82) ml/min/1.73m2. The patients with end-stage renal disease increased from 0.12% to 0.91% compared with the baseline. Uric acid was an independent risk factor for rapid GFR decline in both non-elder (OR=1.01, 95%CI: 1.00-1.01, P=0.001) and elder population (OR=1.01, 95%CI: 1.00-1.01, P=0.002), adjusting for age, sex and duration. Hyperfiltration was another independent risk factor for rapid GFR decline in non-elder (OR=14.72, 95%CI: 8.97-24.15, P<0.001) and elder population (OR=7.91, 95%CI: 4.04-15.48, P<0.001). Conclusions: A quarter of patients with type 2 diabetes showed rapid renal function decline over 10 years. Serum uric acid and glomerular hyperfiltration are independent risk factors to rapid renal function decline. Disclosure M. Yuan: None. S. Yuan: None. Funding Capital Health Research and Development (2016-1-2057)

Initial Estimated Glomerular Filtration Rate Decline and Long-Term Renal Function During Intensive Antihypertensive Therapy: A Post Hoc Analysis of the SPRINT and ACCORD-BP Randomized Controlled Trials.

Lowering blood pressure (BP) can lead to an initial decline in estimated glomerular filtration rate (eGFR). However, there is debate how much eGFR decline is acceptable. We performed a post hoc analysis of ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes-Blood Pressure) and SPRINT (Systolic Blood Pressure Intervention Trial), which randomized patients to intensive or standard systolic BP-targets. We determined the relation between initial decline in mean arterial pressure and eGFR. Subsequently, we stratified patients to BP-target and initial eGFR decrease and assessed the relation with annual eGFR decline after 1 year. A total of 13 266 patients with 41 126 eGFR measurements were analyzed. Up to 10 mm Hg of BP-lowering, eGFR did not change. Hereafter, there was a linear decrease of 3.4% eGFR (95% CI, 2.9%-3.9%) per 10 mm Hg mean arterial pressure decrease. The observed eGFR decline based on 95% of the subjects varied from 26% after 0 mm Hg to 46% with a 40 mm Hg mean arterial pressure decrease. There was no difference in eGFR slope (P=0.37) according to initial eGFR decline and BP-target, with a decrease of 1.24 (95% CI, 1.09-1.39), 1.20 (95% CI, 0.97-1.43), and 1.14 (95% CI, 0.77-1.50) in the 5%, 5% to 20%, and >20% stratum during intensive and 0.95 (95% CI, 0.81-1.09), 1.23 (95% CI, 0.97-1.49), and 1.17 (95% CI, 0.65-1.69) mL/minute per 1.73 m2 per year during standard treatment. In patients at high cardiovascular risk with and without diabetes mellitus, we found no association between initial eGFR and annual eGFR decline during BP-lowering treatment. Our results support that an eGFR decrease up to 20% after BP lowering can be accepted and suggest that the limit can be extended up to 46% depending on the achieved BP reduction. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000620, NCT01206062.

Spondyloarthritis-Associated IgA Nephropathy

IntroductionIgA nephropathy (IgAN) can be associated with spondyloarthritis (SpA). The course of SpA-associated IgAN remains largely unknown due to the absence of large cohorts.MethodsThis retrospective study included patients with biopsy-proven IgAN and definite SpA. Kidney biopsies were centrally examined and scored according to the IgAN Oxford Classification. Thirty-two patients fulfilled the inclusion criteria, with a male:female ratio of 9:1 and median age of 27 and 37 years at SpA and IgAN diagnosis, respectively. HLA-B27 was positive in 90% of cases, and most patients (60%) presented with ankylosing spondylitis. The mean baseline estimated glomerular filtration rate (eGFR) was 84 ± 26 ml/min per 1.73 m2, and the urine protein-to-creatinine ratio was 0.19 g/mmol.ResultsRenal biopsy revealed frequent presence of crescents (33%) and interstitial inflammation (18%). Despite almost constant use of renin-angiotensin system inhibitors, combined with steroids in 13 of 32 patients, renal outcome was particularly poor. After a median follow-up of 5.9 years, 4 patients (12.5%) reached end-stage renal disease and 41% of patients experienced a >50% decrease of eGFR. The mean annual eGFR decline rate was −4.3 ± 6.7 ml/min per 1.73 m2. The risk of reaching class IV or V chronic kidney disease (CKD) stage during follow-up was associated with the presence of hypertension, level of proteinuria, and baseline S- and T-scores of the Oxford.ConclusionSpA-associated IgAN is associated with a poor renal outcome, despite frequent use of steroids. Tumor necrosis factor (TNF)-α blockade did not appear to influence the rate of eGFR decline in this setting.

The Prognosis of Patients With Type 2 Diabetes and Nonalbuminuric Diabetic Kidney Disease Is Not Always Poor: Implication of the Effects of Coexisting Macrovascular Complications (JDDM 54).

Nonalbuminuric diabetic kidney disease (DKD) has become the prevailing phenotype in patients with type 2 diabetes. However, it remains unclear whether its prognosis is poorer than that of other DKD phenotypes. A total of 2,953 Japanese patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, enrolled in an observational cohort study in 2004, were followed until 2015. On the basis of albuminuria (>30 mg/g creatinine) and reduced eGFR (<60 mL/min/1.73 m2) at baseline, participants were classified into the four DKD phenotypes-no-DKD, albuminuric DKD without reduced eGFR, nonalbuminuric DKD with reduced eGFR, and albuminuric DKD with reduced eGFR-to assess the risks of mortality, cardiovascular disease (CVD), and renal function decline. During the mean follow-up of 9.7 years, 113 patients died and 263 developed CVD. In nonalbuminuric DKD, the risks of death or CVD were not higher than those in no-DKD (adjusted hazard ratio 1.02 [95% CI 0.66, 1.60]) and the annual decline in eGFR was slower than in other DKD phenotypes. The risks of death or CVD in nonalbuminuric DKD without prior CVD were similar to those in no-DKD without prior CVD, whereas the risks in nonalbuminuric DKD with prior CVD as well as other DKD phenotypes were higher. Nonalbuminuric DKD did not have a higher risk of mortality, CVD events, or renal function decline than the other DKD phenotypes. In nonalbuminuric DKD, the presence of macrovascular complications may be a main determinant of prognosis rather than the renal phenotype.

SUN-120 ASSOCIATION BETWEEN SERUM MIDKINE AND RENAL OUTCOMES IN ELDERLY WOMEN

Midkine (MK) is heparin-binding cytokine which has been shown to mediate kidney injury and dysfunction via its immunomodulatory functions such as neutrophil and macrophage trafficking, lymphocyte activation, and induction of chemokines. While this has been demonstrated in a number of experimental studies, the extent of the association between Midkine and kidney disease at the population level remains largely unknown. The aims of this study were to determine the association between serum MK and longitudinal changes in kidney function and chronic kidney disease (CKD)-related clinical events in a large cohort of elderly women with long-term clinical follow-up. This was a prospective study of ageing women. Serum MK was measured in 1998 (baseline). Associations between baseline serum MK with change in estimated glomerular filtration rate (eGFR) at 5 and 10 years were analysed using linear regression analyses, adjusting for age, body mass index (BMI), diabetes, use of blood pressure lowering medications, use of statins and prevalent atherosclerotic vascular disease (ASVD). Associations between baseline serum MK and rapid renal decline at 5 years, defined as an annual eGFR decline of greater than 3 mL/min/1.73m2, and CKD-related hospitalisations and deaths at 14.5 years as a composite outcome were examined using logistic and Cox regression analyses respectively, adjusting for similar risk factors. The baseline cohort consisted of women aged over 70 years, with a median age of 75. Throughout the follow-up period of 15 years, there were a total of 206 deaths, and 46 CKD-related hospitalisations and deaths. Baseline serum MK was not associated with 5 and 10 year eGFR change (standardised β coefficient = -0.070, 95% CI = -3.548-0.843, p = 0.226; standardised β coefficient = -0.116, 95% CI = -6.470-0.514, p = 0.094, respectively), or the risk of rapid renal decline at 5 years (odds ratio = 1.85, 95% CI = 0.76-4.49, p = 0.175) in multivariable-adjusted models. Compared to below-median, above-median baseline serum MK was associated with a two-fold increased risk of CKD-related hospitalisations and deaths at 14.5 years (hazard ratio = 1.96, 95% CI = 1.07-3.62, p = 0.030) after adjusting for known risk factors. In older women with mild to moderate renal dysfunction, elevated serum MK is associated with CKD-related hospitalisation and death events. Further prospective studies are needed to determine the prognostic importance of increased MK activity with CKD.

DNA damage and expression of DNA methylation modulators in urine-derived cells of patients with hypertension and diabetes

Diabetes and hypertension have become the primary causes of chronic kidney disease worldwide. However, there are no established markers for early diagnosis or predicting renal prognosis. Here, we investigated the expression profiles of DNA repair and DNA methylation factors in human urine-derived cells as a possible diagnostic or renal prognosis-predicting marker. A total of 75 subjects, aged 63.3 ± 1.9 years old, were included in this study. DNA and RNA were extracted from 50 mL of urine samples. We evaluated DNA double-strand breaks (DSBs) by the quantitative long distance-PCR method and performed real-time RT-PCR analysis to analyze the expression of renal cell-specific markers, DNA DSB repair factor KAT5, DNA methyltransferases DNMTs, and demethylation enzymes TETs. In patients with hypertension and diabetes, DNA DSBs of the nephrin gene increased with decreased urine KAT5/nephrin expression, consistent with our previous study (Cell Rep 2019). In patients with hypertension, DNA DSBs of the AQP1 gene were increased with elevated urine DNMTs/AQP1 and TETs/AQP1 expression. Moreover, urine DNMTs/AQP1 expression was significantly correlated with the annual eGFR decline rate after adjustment for age, baseline eGFR, the presence of diabetes and the amount of albuminuria, suggesting a possible role as a renal prognosis predictor.

Life Course Socioeconomic Status, Allostatic Load, and Kidney Health in Black Americans.

Low socioeconomic status confers unfavorable health, but the degree and mechanisms by which life course socioeconomic status affects kidney health is unclear. We examined the association between cumulative lifetime socioeconomic status and CKD in black Americans in the Jackson Heart Study. We used conditional process analysis to evaluate allostatic load as a potential mediator of this relation. Cumulative lifetime socioeconomic status was an age-standardized z-score, which has 1-SD units by definition, and derived from self-reported childhood socioeconomic status, education, and income at baseline. Allostatic load encompassed 11 baseline biomarkers subsuming neuroendocrine, metabolic, autonomic, and immune physiologic systems. CKD outcomes included prevalent CKD at baseline and eGFR decline and incident CKD over follow-up. Among 3421 participants at baseline (mean age 55 years [SD 13]; 63% female), cumulative lifetime socioeconomic status ranged from -3.3 to 2.3, and 673 (20%) had prevalent CKD. After multivariable adjustment, lower cumulative lifetime socioeconomic status was associated with greater prevalence of CKD both directly (odds ratio [OR], 1.18; 95% confidence interval [95% CI], 1.04 to 1.33 per 1 SD and OR, 1.45; 95% CI, 1.15 to 1.83 in lowest versus highest tertile) and via higher allostatic load (OR, 1.09; 95% CI, 1.06 to 1.12 per 1 SD and OR, 1.17; 95% CI, 1.11 to 1.24 in lowest versus highest tertile). After a median follow-up of 8 years (interquartile range, 7-8 years), mean annual eGFR decline was 1 ml/min per 1.73 m2 (SD 2), and 254 out of 2043 (12%) participants developed incident CKD. Lower cumulative lifetime socioeconomic status was only indirectly associated with greater CKD incidence (OR, 1.04; 95% CI, 1.01 to 1.07 per 1 SD and OR, 1.08; 95% CI, 1.02 to 1.14 in lowest versus highest tertile) and modestly faster annual eGFR decline, in milliliters per minute (OR, 0.01; 95% CI, 0.00 to 0.02 per 1 SD and OR, 0.02; 95% CI, 0.00 to 0.04 in lowest versus highest tertile), via higher baseline allostatic load. Lower cumulative lifetime socioeconomic status was substantially associated with CKD prevalence but modestly with CKD incidence and eGFR decline via baseline allostatic load.

Treatment effects of Chinese medicine (Yi-Qi-Qing-Jie herbal compound) combined with immunosuppression therapies in IgA nephropathy patients with high-risk of end-stage renal disease (TCM-WINE): study protocol for a randomized controlled trial

BackgroundIgA nephropathy (IgAN) is the most common glomerular disease worldwide. It has a high incidence in Asians and is more likely to progress to end-stage renal disease (ESRD). For high-risk IgAN, which is clinically characterized by massive proteinuria and renal dysfunction, however, there has been no international consensus on treatment options. Compared with other developed countries, IgAN patients in China are often found to have severe kidney function loss at initial diagnosis. Yi-Qi-Qing-Jie formula (YQF; a compound recipe of Chinese medicinal herbs) has shown potential renal protection in our previous clinical studies. To further confirm the efficacy and safety of YQF in the treatment of high-risk IgAN, we have designed a prospective double-blind randomized placebo-controlled trial.Methods/designThe TCM-WINE study is a single-center, prospective, double-blind randomized placebo-controlled trial. We plan to randomize 60 participants with biopsy-proven IgAN to a YQF combined group (YQF compound combined with prednisolone, and cyclophosphamide if necessary) or an immunosuppression group (placebo-YQF combined with prednisolone, and cyclophosphamide if necessary). The two groups will enter a 48-week in-trial treatment phase and receive post-trial follow-up until study completion (3 years). All patients will receive optimal supportive care. The primary composite outcome is defined as the first occurrence of a 40% decrease in estimated glomerular filtration rate (eGFR) from the baseline lasting for 3 months, initiating continuous renal replacement treatment, or death due to chronic kidney disease (CKD) during the 3-year study phase. The secondary endpoint events are defined as the mean annual eGFR decline rate (eGFR slope, ml/min per 1.73 m2 per year), which is calculated by the eGFR regression curve for each eligible patient, and proteinuria remission (prescribed as proteinuria < 0.5 g/day) at weeks 24, 36, and 48 during the in-trial phase. The remission rate of symptoms and inflammation status will be evaluated at week 48. Safety monitoring and assessment will be undertaken during the study.DiscussionThe TCM-WINE study will evaluate the effects and safety of YQF combined therapy compared with immunosuppression monotherapy on the basis of the optimal supportive treatment in high-risk IgAN. The evidence from this study will provide a novel, effective, and safe Chinese characteristic therapy for high-risk IgAN patients.Trial registrationClinicalTrials.gov, NCT03418779. Registered on 18 June 2018.

The variability of glycated hemoglobin is associated with renal function decline in patients with type 2 diabetes.

Background:The effect of glucose control, especially variability of glycated hemoglobin (HbA1c), on estimated glomerular filtration rate (eGFR) decline in type 2 diabetes is still debatable.Methods:We used tertiles of coefficient of variation (CV) to determine the variability of HbA1c (HbA1c_CV). Mixed model repeated measures (MMRM) were used to evaluate the annual eGFR decline rate.Results:In 1383 type 2 diabetic patients, we found the greater the HbA1c_CV, the greater the eGFR decline (p = 0.01, −0.99 in low, −1.73 in mid, and −2.53 ml/min/1.73 m2/year in high HbA1c_CV). Regardless of eGFR (⩾60 or <60 ml/min/1.73 m2), the same result holds (p = 0.019 and p = 0.007, respectively). In subgroup analysis of baseline HbA1c (%) (HbA1c < 7, 7 ⩽ HbA1c < 9, and HbA1c ⩾ 9), tertiles of HbA1c_CV showed similar effects on annual decline of eGFR (p = 0.193, 0.300, 0.182, respectively), although a trend for a steeper decline in renal function in the highest HbA1c_CV tertile was observed for all HbA1c strata, and even for HbA1c < 7%. A similar behavior was observed in patients with macroalbuminuria or normoalbuminuria (p = 0.219, and 0.109, respectively), with a significant trend in those with microalbuminuria (p = 0.019). Even in patients with HbA1c < 7, high HbA1c_CV also predicts rapid eGFR decline. Before macroalbuminuria, minimizing HbA1c_CV also has renal benefit.Conclusions:HbA1c variability is an independent risk factor for deterioration of renal function. Even with well-controlled HbA1c levels (<7%), patients with high HbA1c_CV still experienced faster eGFR decline. Early minimization of glycemic variability (before macroalbuminuira) can curb deterioration of renal function. Monitoring and lowering of HbA1c_CV is highly recommended for diabetic care.

Minor Glomerular Abnormalities are Associated with Deterioration of Long-Term Kidney Function and Mitochondrial Injury.

Minor glomerular abnormalities (MGAs) are unclassified glomerular lesions indicated by the presence of minor structural abnormalities that are insufficient for a specific pathological diagnosis. The long-term clinical outcomes and pathogenesis have not been examined. We hypothesized that MGAs would be associated with the deterioration of long-term kidney function and increased urinary mitochondrial DNA (mtDNA) copy numbers. We retrospectively enrolled patients with MGAs, age-/sex-/estimated glomerular filtration rate (eGFR)-matched patients with immunoglobulin A nephropathy (IgAN), and similarly matched healthy controls (MHCs; n = 49 each). We analyzed the time × group interaction effects of the eGFR and compared mean annual eGFR decline rates between the groups. We prospectively enrolled patients with MGAs, age- and sex-matched patients with IgAN, and MHCs (n = 15 each) and compared their urinary mtDNA copy numbers. Compared to the MHC group, the MGA and IgAN groups displayed differences in the time × group effects of eGFR, higher mean annual rates of eGFR decline, and higher urinary mtDNA copy numbers; however, these groups did not significantly differ from each other. The results indicate that MGAs are associated with deteriorating long-term kidney function, and mitochondrial injury, despite few additional pathological changes. We suggest that clinicians conduct close long-term follow-up of patients with MGAs.

Dietary inflammatory index and the aging kidney in older women: a 10-year prospective cohort study.

Chronic inflammation plays a role in the pathogenesis of age-related renal disease and the diet can moderate systemic inflammation. The primary objective of this study was to examine the associations between a dietary inflammatory index (DII®) score and renal function, the trajectory of renal function decline, and renal disease-related hospitalizations and/or mortality over 10years. The study was conducted in 1422 Western Australian women without prevalent chronic kidney disease and aged ≥ 70years. Baseline dietary data, obtained from a validated food frequency questionnaire, were used to calculate a DII score for each individual. In this cohort, the mean [range] DII score was 0.19 [- 6.14 to 6.39]. A higher DII score was associated with poorer renal function at baselineand a greater renal function decline over 10years; after multivariable adjustments, a one-unit higher DII score was associated with a 0.55mL/min/1.73m2 lower eGFR at baseline (p = 0.01) and a 0.06mL/min/1.73m2 greater annual decline in eGFR over 10years (p = 0.05). Restricted cubic splines provide evidence of a non-linear association between baseline DII score and risk of a renal disease-related event. Compared to participants in the lowest quintile, those in the highest quintile of DII score were at a higher risk of experiencing a renal disease-related event (adjusted HR 2.06, 95% CI 0.97, 4.37). Recommending an increased consumption of foods with a higher anti-inflammatory potential could form part of a multifaceted approach to reduce the risk of renal disease through diet and lifestyle changes.

Predicting renal disease progression in a large contemporary cohort with type 1 diabetes mellitus

Aims/hypothesisThe aim of this study was to provide data from a contemporary population-representative cohort on rates and predictors of renal decline in type 1 diabetes.MethodsWe used data from a cohort of 5777 people with type 1 diabetes aged 16 and older, diagnosed before the age of 50, and representative of the adult population with type 1 diabetes in Scotland (Scottish Diabetes Research Network Type 1 Bioresource; SDRNT1BIO). We measured serum creatinine and urinary albumin/creatinine ratio (ACR) at recruitment and linked the data to the national electronic healthcare records.ResultsMedian age was 44.1 years and diabetes duration 20.9 years. The prevalence of CKD stages G1, G2, G3 and G4 and end-stage renal disease (ESRD) was 64.0%, 29.3%, 5.4%, 0.6%, 0.7%, respectively. Micro/macroalbuminuria prevalence was 8.6% and 3.0%, respectively. The incidence rate of ESRD was 2.5 (95% CI 1.9, 3.2) per 1000 person-years. The majority (59%) of those with chronic kidney disease stages G3–G5 did not have albuminuria on the day of recruitment or previously. Over 11.6 years of observation, the median annual decline in eGFR was modest at −1.3 ml min−1 [1.73 m]−2 year−1 (interquartile range [IQR]: −2.2, −0.4). However, 14% experienced a more significant loss of at least 3 ml min−1 [1.73 m]−2. These decliners had more cardiovascular disease (OR 1.9, p = 5 × 10−5) and retinopathy (OR 1.3 p = 0.02). Adding HbA1c, prior cardiovascular disease, recent mean eGFR and prior trajectory of eGFR to a model with age, sex, diabetes duration, current eGFR and ACR maximised the prediction of final eGFR (r2 increment from 0.698 to 0.745, p < 10−16). Attempting to model nonlinearity in eGFR decline or to detect latent classes of decliners did not improve prediction.ConclusionsThese data show much lower levels of kidney disease than historical estimates. However, early identification of those destined to experience significant decline in eGFR remains challenging.

Impact of Arteriovenous fistula creation on estimated glomerular filtration rate decline in Predialysis patients

BackgroundArteriovenous fistula (AVF) is the vascular access of choice for patients on hemodialysis. Recent evidence suggests that AVF creation may slow estimated glomerular filtration rate (eGFR) decline. The study objective was to assess the impact of the AVF creation on eGFR decline, after controlling for key confounding factors.MethodsThis retrospective cohort study included adult patients followed in a single-center predialysis clinic between 1999 and 2016. Patients with a patent AVF were followed up to 2 years pre- and post-AVF creation. Estimated GFR trajectory was reported using linear mixed models adjusted for demographic characteristics, comorbidities and use of renin-angiotensin-aldosterone blockade.ResultsA total of 146 patients were studied with a median age 68.7 (60.5–75.4) years and a median eGFR at time of AVF creation of 12.8 (11.3–13.9) mL/min/1.73m2. The crude annual eGFR decline rates were − 3.60 ± 4.00 mL/min/1.73 m2 pre- and − 2.28 ± 3.56 mL/min/1.73 m2 post-AVF, resulting in a mean difference of 1.28 mL/min/1.73 m2 (95% CI 0.49, 2.07). In a mixed effect linear regression model, monthly eGFR decline was − 0.63 (95% CI -0.81, − 0.46; p < 0.001) mL/min/1.73m2/month. The period after AVF creation was associated with a relatively higher eGFR (β 0.94, 95% CI 0.61–1.26, p < 0.001). There was a significant association between follow-up time and the period pre/post AVF (β 0.19, 95% CI 0.16, 0.22; p < 0.001) such that eGFR decline was more attenuated each month after AVF creation.ConclusionsIn this cohort, AVF creation was associated with a significant reduction of eGFR decline. Further prospective studies are needed to confirm this association.

Metabolic syndrome is a predictor of decreased renal function among community-dwelling middle-aged and elderly Japanese.

Metabolic syndrome (MetS) is increasing worldwide with the continuous increase in obesity prevalence. Chronic kidney disease (CKD) is also a major public health problem, but there is controversy over whether baseline MetS is a predictor of decreased renal function among Japanese community-dwelling middle-aged and elderly Japanese. We conducted a prospective cohort study designed as part of the Nomura study. We recruited a random sample of 410 men aged 68 ± 8 (mean ± standard deviation; range, 50-95) years and 549 women aged 69 ± 7 (50-84) years during their annual health examination in a single community. We examined the relationship between baseline MetS and renal dysfunction after a 3-year evaluation based on estimated glomerular filtration rate (eGFRCKDEPI) using the CKD-EPI equations modified by the Japan coefficient. CKD was defined as dipstick-positive proteinuria (> or = 1 +) or a low eGFRCKDEPI (< 60mL/min/1.73m2). Of the 959 participants, 413 (43.1%) had MetS at baseline. Annual eGFR decline rate was significantly greater in those with MetS than in those without MetS, and the annual eGFR decline rate of < - 1.2mL/min/1.73m2/year increased significantly in relation to presence of baseline MetS, especially low HDL cholesterol (HDL-C). Moreover, the incidence rate of CKD after 3years was 13.5% and increased significantly in relation to presence of baseline MetS, especially its components such as elevated HbA1c. The multivariate-adjusted odd ratio (OR) for CKD in participants with MetS versus those without MetS was 1.55 (0.99-2.43).The multivariate-adjusted ORs for rapid annual eGFR decline rate were significantly high in patients aged ≥ 65years and presence of medication, regardless of gender and eGFR value. Low HDL-C and elevated HbA1c levels correlated significantly with eGFR decline in a short period of 3years. MetS also showed a significant association with eGFR decline. This study suggests the importance of low HDL-C and elevated HbA1c in the effect of MetS on eGFR decline rather than obesity among Japanese community-dwelling middle-aged and elderly Japanese without CKD.

Association of Statin Use With Kidney Damage and Function Among HIV-Infected Men.

Chronic kidney disease (CKD) occurs commonly among HIV-infected persons. Statins may delay CKD onset and progression through their cholesterol-lowering and pleiotropic effects. Among 850 HIV-infected men from the Multicenter AIDS Cohort Study with stored urine samples (2009-2011), we evaluated cross-sectional associations of statin use with urine biomarkers of kidney damage [albumin-to-creatinine ratio (ACR), alpha-1-microglobulin, interleukin-18, kidney injury molecule-1, and procollagen type III N-terminal propeptide] using multivariable linear regression. We evaluated the longitudinal associations of statin use with annual change in estimated glomerular filtration rate by creatinine (eGFR) using linear mixed models, and with incident proteinuria and incident CKD (eGFR <60 mL/min/1.73 m) using Cox proportional hazards regression. We used inverse probability weighting to address potential confounding related to statin use. Statin users comprised 30% of participants. In adjusted analyses, each year of cumulative statin use was associated with 4.0% higher baseline ACR levels (P = 0.05), but there was no association with baseline levels of other urine biomarkers. Statin use had no overall association with annual eGFR decline. Among participants with baseline proteinuria, statin use was modestly associated with slower annual eGFR decline compared to non-use (adjusted difference: 1.33 mL/min/1.73 m per year; 95% confidence interval: -0.07 to 2.70). Statin use was not associated with risk of incident proteinuria or incident CKD. Statin use was associated with higher baseline ACR, but not with biomarkers of tubulointerstitial injury. Statin use was associated with modestly slower eGFR decline only among participants with baseline proteinuria. Although these findings may be susceptible to confounding by indication, they suggest a limited effect of statins on CKD risk among HIV-infected men.

P3472Modifications of renal function in atrial fibrillation patients treated with different oral anticoagulants: a multicentre cohort study

Abstract Background A decline of estimated glomerular filtration rate (eGFR) has been described in atrial fibrillation (AF) patients on Vitamin K antagonists (VKAs). Few real-world data on the modifications of eGFR in AF patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) do exist. Purpose To evaluate changes of renal function in AF patients treated with VKAs or NOACs. Methods Multicentre prospective cohort study including 1,667 patients with non-valvular AF from 5 clinical centres of Internal Medicine and Cardiology in Italy. Renal endpoints were: 1) median annual decline of eGFR; 2) transition to eGFR &lt;50 ml/min/1.73 m2; 3) eGFR class worsening according to KDIGO 2012 classification. The eGFR was assessed by the CKD-EPI formula at baseline and during follow-up. Results Median age was 73.7±9.1 years and 43.3% were women. 743 patients were on VKAs and 924 on NOACs (Dabigatran, Rivaroxaban e Apixaban). Median annual eGFR decline was −2,11 (Interquartile Range [IQR] −5,68/−0,62] in patients on VKAs, −0,27 [IQR −9,00/4,54] with Dabigatran (p&lt;0.001 vs. VKAs), −1,21 [IQR −9,98/4,02] with Rivaroxaban (p=0.004 vs. VKAs) and −1,32 [IQR −8,7/3,99] with Apixaban (p=0.003, vs. VKAs). Use of Dabigatran and Apixaban was associated to a lower transition to eGFR &lt;50 mL/min/1.73 m2, compared to VKAs: adjusted Odds Ratio (aOR) 0.492, 95% Confidence Interval (CI) 0.298–0.813, p=0.006 for Dabigatran; aOR 0.449, 95% CI 0.276–0.728, p=0.001 for Apixaban). Regarding the eGFR class worsening, Dabigatran (aOR 0.70, 95% CI 0.503–0.975, p=0.035), Rivaroxaban (aOR 0.591, 95% CI 0.423–0.825, p=0.002), and Apixaban (aOR 0.591, 95% CI 0.429–0.815, p=0.001) were all associated to a lower rate of eGFR class worsening compared to VKAs. Forest plot Conclusions In this prospective multicentre cohort study, NOACs use was associated with a lower decline of renal function compared to VKAs. Patients on Dabigatran showed the lowest annual rate of eGFR decline and those on Apixaban and Rivaroxaban a lower eGFR class worsening. Acknowledgement/Funding None

Associations of Urine Biomarkers with Kidney Function Decline in HIV-Infected and Uninfected Men

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

Association between alcohol intake and measures of incident CKD: An analysis of nationwide health screening data.

To evaluate the association between alcohol intake and incident chronic kidney disease measures as well as the sex differences in this association, we analyzed health screening data of 14,190,878 adults who underwent health screening ≥3 times and had glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and normal proteinuria at baseline. eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration equation. Proteinuria was defined as ≥1+ dipstick proteinuria and low eGFR as <60 mL/min/1.73 m2. The risk of incident proteinuria and low eGFR was analyzed with an extended Cox model with alcohol intake level as a time-varying determinant and the annual change of eGFR with generalized linear model. A J-shape association of alcohol intake with the incident proteinuria was observed in men (adjusted hazard ratio [aHR], 0.961, 95% confidence interval [CI], 0.953–0.970 in men drinking alcohol <10 g/day; aHR 1.139, 95% CI, 1.123–1.154 in men drinking alcohol ≥40 g/day, compared with non-drinking men), and a positive association was seen in women (aHR, 1.034, 95% CI, 1.023–1.044 in women drinking alcohol <10 g/day; aHR, 1.094, 95% CI, 1.034–1.158 in women drinking alcohol ≥40 g/day, compared with non-drinking women). In both sexes, an inverse association of alcohol intake with the annual eGFR decline and incident low eGFR was observed. This study observed a beneficial effect of moderate alcohol intake on incident proteinuria in men and a protective effect of alcohol intake of any amount on the annual eGFR decline and incident low eGFR in both sexes. The long-term implications of these observations need to be elucidated with future studies.

Validation of a protein biomarker test for predicting renal decline in type 2 diabetes: The Fremantle Diabetes Study Phase II

AimsTo validate the prognostic utility of a novel plasma biomarker panel, PromarkerD, for predicting renal decline in an independent cohort of people with type 2 diabetes. MethodsModels for predicting rapid estimated glomerular filtration rate (eGFR) decline defined as i) incident diabetic kidney disease (DKD), ii) eGFR decline ≥30% over four years, and iii) annual eGFR decline ≥5 mL/min/1.73 m2 were applied to 447 participants from the longitudinal observational Fremantle Diabetes Study Phase II. Model performance was assessed using discrimination and calibration. ResultsDuring 4.2 ± 0.3 years of follow-up, 5–10% of participants experienced a rapid decline in eGFR. A consensus model comprising apolipoprotein A-IV (apoA4), CD5 antigen-like (CD5L), insulin-like growth factor–binding protein 3 (IGFBP3), age, serum HDL-cholesterol and eGFR showed the best performance for predicting incident DKD (AUC = 0.88 (95% CI 0.84–0.93)); calibration Chi-squared = 5.6, P = 0.78). At the optimal score cut-off, this model provided 86% sensitivity, 78% specificity, 30% positive predictive value and 98% negative predictive value for four-year risk of developing DKD. ConclusionsThe combination of readily available clinical and laboratory features and the PromarkerD biomarkers (apoA4, CD5L, IGFBP3) proved an accurate prognostic test for future renal decline in an independent validation cohort of people with type 2 diabetes.