Risk Of Kidney Function Decline Research Articles

Association of trimethylamine N-oxide and metabolites with kidney function decline in patients with chronic kidney disease

BackgroundTrimethylamine N-oxide (TMAO) is a gut microbial metabolite derived from dietary L-carnitine and choline. High plasma TMAO levels are associated with cardiovascular disease and overall mortality, but little is known about the associations of TMAO and related metabolites with the risk of kidney function decline among patients with chronic kidney disease (CKD). MethodsWe prospectively followed 152 nondialysis patients with CKD stages 3–5 and measured plasma TMAO and related metabolites (trimethylamine [TMA], choline, carnitine, and γ-butyrobetaine) via liquid chromatography‒mass spectrometry. An estimated glomerular filtration rate (eGFR) slope >3 ml/min/per 1.73 m2 per year was defined as a rapid decline. We performed logistic regression to determine the probability of rapid or slow eGFR decline, with each metabolite as the main predictor. The gut microbiota was profiled via whole metagenomic sequencing. ResultsThe participants had a median age of 66 years, 41.4% were women, 39.5% had diabetes, and the median eGFR was 23 mL/min/1.73 m2. A rapid decrease in the eGFR occurred in 65 patients (42.8%) over a median follow-up of 3.3 years. After adjustment for baseline eGFR, proteinuria, and clinical factors, plasma TMAO levels were independently associated with increased odds of rapid eGFR decline (odds ratio, 2.42; 95% CI, 1.36–4.32), whereas plasma TMA, choline, carnitine, and γ-butyrobetaine levels were not. Patients who exhibited rapid eGFR decline had a distinct gut microbial composition characterized by increased α-diversity and an abundance of TMA-producing bacteria, including those of the genera Desulfovibrio and Collinsella tanakaei, as well as increased expression of the TMA-producing enzymes bbuA and cutC. ConclusionOur findings suggest the relevance of plasma TMAO in the progression of kidney disease among patients with CKD.

Associations of physiologic subtypes based on HOMA2 indices of β-cell function and insulin sensitivity with the risk of kidney function decline, cardiovascular disease, and all-cause mortality from the 4C study

BackgroundPrevious studies have been limited by their inability to differentiate between the effects of insulin sensitivity and β-cell function on the risk of kidney function decline, cardiovascular disease (CVD), and all-cause mortality. To address this knowledge gap, we aimed to investigate whether the physiological subtypes based on homeostasis model assessment-2 (HOMA2) indices of β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) could be used to identify individuals with subsequently high or low of clinical outcome risk.MethodsThis retrospective cohort study included 7,317 participants with a follow-up of up to 5 years. Based on HOMA2 indices, participants were categorized into four physiologic subtypes: the normal phenotype (high insulin sensitivity and high β-cell function), the insulinopenic phenotype (high insulin sensitivity and low β-cell function), the hyperinsulinaemic phenotype (low insulin sensitivity and high β-cell function), and the classical phenotype (low insulin sensitivity and low β-cell function). The outcomes included kidney function decline, CVD events (fatal and nonfatal), and all-cause mortality. Cox regression models were used to calculate hazard ratios (HRs) for outcomes, and spline models were used to examine the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes.ResultsA total of 1,488 (20.3%) were classified as normal, 2,179 (29.8%) as insulinopenic, 2,173 (29.7%) as hyperinsulinemic, and 1,477 (20.2%) as classical subtypes. Compared with other physiological subtypes, the classical subtype presented the highest risk of kidney function decline (classical vs. normal HR 11.50, 95% CI 4.31–30.67). The hyperinsulinemic subtype had the highest risk of CVD and all-cause mortality (hyperinsulinemic vs. normal: fatal CVD, HR 6.56, 95% CI 3.09–13.92; all-cause mortality, HR 4.56, 95% CI 2.97–7.00). Spline analyses indicated the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes.ConclusionsThe classical subtype had the strongest correlation with the risk of kidney function decline, and the hyperinsulinemic subtype had the highest risk of CVD and all-cause mortality, which should be considered for interventions with precision medicine.Graphical abstract

Mildly decreased egfr modifies the association between uric acid and risk of kidney function decline: a 5-year population-based cohort study

Abstract Background the role of uric acid (UA) in chronic kidney disease (CKD) remains controversial. In this study, the effects of UA levels on risk of kidney function (KF) decline in patients with normal or mildly decreased KF at baseline were investigated. Methods Data were extracted from the community-based Tongzhou Cohort Study. The cohort of 4246 patients was divided into the normal KF group (estimated glomerular filtration rate [eGFR] ≥ 90 mL/min/1.73 m2) or mildly decreased KF group (60 ≤ eGFR < 90 mL/min/1.73 m2). The primary endpoint was the risk of kidney function decline, which defined as a composite of a ≥ 30% decrease in eGFR from baseline or new onset of CKD diagnosed during the annual checkups. Results A total of 284 participants reached the primary endpoint during the 5-year follow-up period. There was a significant interaction between UA levels and baseline eGFR (p < 0.001). Restricted cubic spline analysis revealed a U-shaped association between baseline UA levels and the risk of decreased KF for participants with normal KF (cut-off value = 5.0 mg/dL; pnonlinear = 0.025) and a linear association for participants with mildly decreased KF (pnonlinear = 0.384). The odds ratio of an increase in UA levels by 1 mg/dL was 1.15 [95% confidence interval (CI) 1.02–1.31, p = 0.028] for the primary endpoint and 1.15 (95% CI = 1.01–1.31, p = 0.037) for new onset of CKD for participants with mildly decreased KF. Conclusion The association between uric acid and risk of KF decline was U-shaped in participants with normal KF while linear in participants with mildly decreased KF.

Albuminuria and Rapid Kidney Function Decline as Selection Criteria for Kidney Clinical Trials in Type 1 Diabetes Mellitus.

The optimal criteria to select individuals with type 1 diabetes mellitus (T1D) and albuminuric or normoalbuminuric diabetic kidney disease (DKD), who are at risk of rapid kidney function decline, for clinical trials are unclear. This study analyzed data from the Preventing Early Renal Loss in Diabetes (PERL) clinical trial, which investigated whether allopurinol slowed kidney function decline in persons with T1D and early-to-moderate DKD. Rates of iohexol GFR (iGFR) and estimated GFR (eGFR) decline during the three-year study were compared by linear mixed effect regression between participants enrolled based on a history of moderately or severely increased albuminuria (N=394) and those enrolled based on a recent history of rapid kidney function decline (≥3 ml/min/1.73 m2/year) in the absence of a history of albuminuria (N=124). The association between baseline albuminuria and iGFR/eGFR decline during the trial was also evaluated. Rates of eGFR decline during the trial were higher in participants with a history of albuminuria than in those with a history of rapid kidney function decline (-3.56 [95% confidence intervals {CI} -3.17, -3.95] versus -2.35 [95% CI: -1.86, -2.84] ml/min/1.73 m2/year, p=0.001). Results were similar for iGFR decline, although the difference was not significant (p=0.07). Within the history of albuminuria group, the rate of eGFR decline was -5.30 (95% CI -4.52, -6.08) ml/min/1.73m2/year in participants with severely increased albuminuria as compared to -2.97 (95% CI 2.44, -3.50) and -2.32 (95% CI -1.61, -3.03) ml/min/1.73m2/year in those with moderately increased or normal/mildly increased albuminuria at baseline (p<0.001). Severely increased albuminuria at screening is a powerful criterion for selecting persons with T1D at high risk of kidney function decline. A history of rapid eGFR decline without a history of albuminuria is less effective for this purpose but it can still identify individuals with T1D who will lose kidney function more rapidly than expected from physiological aging. ClinicalTrials.gov, NCT02017171.

Abstract P339: Association of Pre-Donation Blood Pressure with Kidney Function in Living Kidney Donors

Background: Although BP is associated with kidney outcomes, its clinical significance in living kidney donors (LKD) is unknown. We aim to examine the association between pre-donation BP and the risk of kidney function decline in LKD. Methods: A retrospective cohort study using OPTN/SRTR including adult LKD, who underwent donation between 6/1972 and 9/2022, was utilized to examine the association of quartile (Q) of pre-donation SBP and DBP with time-to-event of ≥35% decline in post-donation eGFR from pre-donation eGFR by multiple Cox regression. Results: Of 174,311 adult LKD, mean±SD age was 41±12 years and 60% were female. Mean pre-donation SBP and DBP were 122±13 and 74±9 mmHg, respectively. Mean pre-donation SBP in Q 1, 2, 3, and 4 were 106±6, 117±2, 126±3, and 140±9 mmHg, respectively and the corresponding DBP were 62±5, 71±2, 78±2, and 86±5 mmHg, respectively. The median (IQR) of pre-donation eGFR was 91 (75, 111) mL/min/1.73 m 2 . Median(IQR) eGFR at immediate post-donation, 6-, 12-, and 24-months post-donation were 50 (40, 62), 54 (44, 67), 55 (45, 68), and 57 (47, 70) mL/min/1.73 m 2 , respectively. Out of 38,780 LKD with post-donation eGFR data at 6, 12, or 24 months, 31,054 had the event of ≥35% decline in post-donation eGFR from pre-donation eGFR with a median time to follow-up of 6.77 months(IQR 5.93, 12.67). The incidence rate of the event was 0.08 person-months. Compared to patients with SBP in Q 1, those with SBP in Q 2, 3, and 4 had a significantly increased risk for the event(HR SBP Q2,3,4 1.05, 1.08, and 1.15; P &lt;0.001 – 0.003) but only patients with DBP in Q 3 and 4 had a significantly increased risk for the event (HR SBP Q3,4 1.04 and 1.09). After adjusting for age, gender, race/ethnicity, U.S. citizenship, education level, history of pre-donation HTN, diabetes, pre-donation BMI, DBP, and urine protein:creatinine ratio, there was a J-shaped association between pre-donation SBP and post-donation eGFR decline and only patients in the Q 2 became significantly associated with lower the risk for the event (HR 0.87, 95%CI 0.76, 0.99; Fig1). The pre-donation DBP – post-donation eGFR association was similar to the SBP – eGFR association but there was no statistically significant in all Q (Fig2). There was no effect-measured modifier for all covariates. Conclusions: Pre-donation SBP in a normal range(113 - 120 mmHg) is associated with the lowest risk for a post-donation eGFR decline. BP control in the normal range should be achieved for potential LKD.

Rate and risk factors of kidney function decline among South Asians with type 2 diabetes: analysis of the CARRS Trial

IntroductionPeople with diabetes are at risk of developing chronic kidney disease. However, limited data are available to quantify their risk of kidney function decline in South Asia. This study evaluates...

Protein Intake and Mortality in Older Adults With Chronic Kidney Disease

Avoiding high protein intake in older adults with chronic kidney disease (CKD) may reduce the risk of kidney function decline, but whether it can be suboptimal for survival is not well known. To estimate the associations of total, animal, and plant protein intake with all-cause mortality in older adults with mild or moderate CKD and compare the results to those of older persons without CKD. Data from 3 cohorts (Study on Cardiovascular Health, Nutrition and Frailty in Older Adults in Spain 1 and 2 and the Swedish National Study on Aging and Care in Kungsholmen [in Sweden]) composed of community-dwelling adults 60 years or older were used. Participants were recruited between March 2001 and June 2017 and followed up for mortality from December 2021 to January 2024. Those with no information on diet or mortality, with CKD stages 4 or 5, or undergoing kidney replacement therapy and kidney transplant recipients were excluded. Data were originally analyzed from June 2023 to February 2024 and reanalyzed in May 2024. Cumulative protein intake, estimated via validated dietary histories and food frequency questionnaires. The study outcome was 10-year all-cause mortality, ascertained with national death registers. Chronic kidney disease was ascertained according to estimated glomerular filtration rates, urine albumin excretion, and diagnoses from medical records. The study sample consisted of 8543 participants and 14 399 observations. Of the 4789 observations with CKD stages 1 to 3, 2726 (56.9%) corresponded to female sex, and mean (SD) age was 78.0 (7.2) years. During the follow-up period, 1468 deaths were recorded. Higher total protein intake was associated with lower mortality among participants with CKD; adjusted hazard ratio (HR) for 1.00 vs 0.80 g/kg/d was 0.88 (95% CI, 0.79-0.98); for 1.20 vs 0.80 g/kg/d, 0.79 (95% CI, 0.66-0.95); and for 1.40 vs 0.80 g/kg/d, 0.73 (95% CI, 0.57-0.92). Associations with mortality were comparable for plant and animal protein (HRs, 0.80 [95% CI, 0.65-0.98] and 0.88 [95% CI, 0.81-0.95] per 0.20-g/kg/d increment, respectively) and for total protein intake in participants younger than 75 years vs 75 years or older (HRs, 0.94 [95% CI, 0.85-1.04] and 0.91 [95% CI, 0.85-0.98] per 0.20-g/kg/d increment in total protein intake, respectively). However, the hazards were lower among participants without CKD than in those with CKD (HRs, 0.85 [95% CI, 0.79-0.92] and 0.92 [95% CI, 0.86-0.98] per 0.20-g/kg/d increment, respectively; P = .02 for interaction). In this multicohort study of older adults, higher intake of total, animal, and plant protein was associated with lower mortality in participants with CKD. Associations were stronger in those without CKD, suggesting that the benefits of proteins may outweigh the downsides in older adults with mild or moderate CKD.

#900 Endotrophin is associated with long-term risk of kidney function decline in normoalbuminuric persons with type 2 diabetes in the Joslin Kidney Study

Abstract Background and Aims Endotrophin is a pro-fibrotic and pro-inflammatory molecule derived from the post-translational processing of type VI collagen. Evidence for an association of increased circulating levels of endotrophin with increased risk of kidney and cardiovascular-related outcome and all-cause mortality in persons with type 2 diabetes have recently emerged. Here we want to investigate endotrophin as an early marker of kidney-related outcome risk in persons with type 2 diabetes with normal levels of albuminuria. Method Endotrophin was measured using the nordicPRO-C6TM assay (Nordic Bioscience, Herlev, Denmark) in serum of 1088 individuals with type 2 diabetes from the Joslin Diabetes Study. 635 individuals had normal to mildly increased albuminuria (&amp;lt;30 mg/g), 379 had moderately increased albuminuria (30-300 mg/g) and 74 had severely increased albuminuria (&amp;gt;300 mg/g). All patients had eGFR &amp;gt;60 and where hence classified as CKD stage 1 and 2. Risk of kidney disease progression was defined as a 40% decline in eGFR within 10 years. Results In the cohort (n = 1088), a total of 128 patients progressed to 40% eGFR decline. High levels of circulating endotrophin were associated with an increased risk of kidney disease progression in unadjusted logistic regression analysis (OR for T3 vs T1+T2 (PRO-C6): 2.1 [95% CI: 1.4-3.0], p = 0.0001) and after adjustment for eGFR, HbA1c, age and sex (OR for T3 vs T1+T2 (PRO-C6): 1.8 [95% CI: 1.1-2.6], p = 0.005). When looking at patients classified in albuminuria stages, endotrophin was significantly associated with kidney disease progression in the individuals with normal to mildly increased albuminuria (39 events) (OR for T3 vs T1+T2 (PRO-C6): 2.6 [95% CI: 1.3-4.9], p = 0.005 in unadjusted analysis and 2.3 [95% CI: 1.1-4.5], p = 0.02 after adjustment for eGFR, HbA1c, age and sex, but it was not significantly associated to kidney progression in the groups with moderately (49 events) and severely (40 events) increased albuminuria. Conclusion This study sheds further light on the potential of endotrophin as an early marker of long-term adverse kidney outcome in persons with type 2 diabetes. The association of circulating endotrophin with increased risk of kidney disease progression had already been reported both in CKD and DKD patients (for shorter-term outcome), and this study further expands on the applicability of endotrophin as a biomarker in persons with type 2 diabetes without an overt kidney disease, who will nevertheless progress to develop CKD in a 10-year time horizon.

#960 Trends in eGFR and ultra-processed food intake in relationship to income among United States adults

Abstract Background and Aims Ultra-processed foods (UPF) are formulations of ingredients that are mostly of exclusive industrial use and may contain additives like artificial colors, flavors, or stabilizers. The sale and consumption of these foods has been increasing despite their associations with increased risk for several non-communicable diseases including chronic kidney disease. Ultra-processed foods are widely accessible, more shelf-stable and convenient while tending to be more affordable and lower in nutritional quality. The aim of this study was to evaluate trends in kidney function and UPF intake and temporal effect of income among United States (US) adults. Method We used dietary intake data collected with 24-hour dietary recalls from 35160 US adults across 8 cycles of the National Health and Nutrition Examination Survey (NHANES) (from 2003-2004 to 2017-2018 cycles) to categorize intake using the Nova processed food classification system. Poisson regression models were used to assess the 15-year trends in populations at risk for kidney function decline (measured by estimated glomerular filtration rate [eGFR]) and higher percentage of calories from UPF (PC-UPF) consumed along with the temporal effect of income in select subpopulations and adjusted for age and gender and non-linear effects of income and age). Results Over the past 15 years eGFR, PC-UPF, and self-reported income continue to increase among US adults. However, the associations between eGFR, PC-UPF and income are quite complex, vary by subpopulation and non-linearly depend on age. Specifically, among Black adults adjusted for age (age2) and gender, eGFR was the lowest (85 mL/min/1.73 m2, 95% CI: 84.9, 85.0 mL/min/1.73 m2) among those with the lowest ($2,500) and highest ($125,000) income (p = 0.0000000579 for a quadratic term of income), respectively. Hispanic and Mexican Americans also have similar pattern eGFR with the lowest and highest income though the eGFR is consistently higher than White and Black Americans. Across cycles, White Americans with the lowest income ($2,500) have the highest PC-UPF (range: 57-62%, p &amp;lt;2e-16; mean: 59.4%, 95% CI: 59.3, 59.6%) while Black Americans with the lowest ($2,500) and highest income ($125,000) have the highest PC-UPF (range: 53-58%, p &amp;lt;2e-16; mean: 54.8%, 95% CI: 54.3, 55.4%). Income levels does not predict PC-UPF among Mexican Americans. Overall, the PC-UPF is steadily increasing in all population subgroups. Conclusion Among Non-White US adults, higher eGFR was associated with higher income until reaching a group-specific threshold when the relationship reversed. We observed a similar threshold pattern in the association between PC-UPF and income among Black and Hispanic Americans. These complex non-linear relationships between eGFR, PC-UPF and income are driven in part by age-related association and warrant further exploration.

Anti–Tumor Necrosis Factor Therapy and Risk of Kidney Function Decline and Mortality in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is associated with adverse clinical outcomes, including chronic kidney disease and mortality, due in part to chronic inflammation. Little is known about the effects of anti-tumor necrosis factor (TNF) therapy on kidney disease progression and mortality among patients with new-onset IBD. To examine the association of incident use of TNF inhibitors with subsequent decline in kidney function and risk of all-cause mortality. This retrospective cohort study used data from the US Department of Veterans Affairs health care system. Participants were US veterans with new-onset IBD enrolled from October 1, 2004, through September 30, 2019. Data were analyzed from December 2022 to February 2024. Incident use of TNF inhibitors. The main outcomes were at least 30% decline in estimated glomerular filtration rate (eGFR) and all-cause mortality. Among 10 689 patients (mean [SD] age, 67.4 [12.3] years; 9999 [93.5%] male) with incident IBD, 3353 (31.4%) had diabetes, the mean (SD) baseline eGFR was 77.2 (19.2) mL/min/1.73 m2, and 1515 (14.2%) were newly initiated on anti-TNF therapy. During a median (IQR) follow-up of 4.1 (1.9-7.0) years, 3367 patients experienced at least 30% decline in eGFR, and over a median (IQR) follow-up of 5.0 (2.5-8.0) years, 2502 patients died. After multivariable adjustments, incident use (vs nonuse) of TNF inhibitors was significantly associated with higher risk of decline in eGFR (adjusted hazard ratio [HR], 1.34 [95% CI, 1.18-1.52]) but was not associated with risk of all-cause mortality (adjusted HR, 1.02 [95% CI, 0.86-1.21]). Similar results were observed in sensitivity analyses. In this cohort study of US veterans with incident IBD, incident use (vs nonuse) of TNF inhibitors was independently associated with higher risk of progressive eGFR decline but was not associated with risk of all-cause mortality. Further studies are needed to elucidate potentially distinct pathophysiologic contributions of TNF inhibitor use to kidney and nonkidney outcomes in patients with IBD.

Association between blood pressure variability and risk of kidney function decline in hypertensive patients without chronic kidney disease: a post hoc analysis of Systolic Blood Pressure Intervention Trial study.

Blood pressure variability (BPV) is a risk factor for poor kidney function independent of blood pressure (BP) in chronic kidney disease (CKD). Little is known about the association between kidney function decline and BPV in hypertensive patients without CKD. A post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) was performed. BPV was measured as standard deviation (SD) and average real variability (ARV). Cox proportional hazard models were employed to explore the relationship between BPV and incident CKD and albuminuria. A total of 5700 patients were included, with a mean age of 66.4 years old. During a median of 3.29 years follow-up, 150 (2.6%) patients developed CKD and 222 (7.2%) patients developed albuminuria. Patients were divided into four groups according to the quartiles of BPV. Compared with SBPV Q1, the incidence of CKD was higher in SBPV Q2-Q4; hazard ratios and 95% confidence interval were 1.81 (1.07-3.04), 1.85 (1.10-3.12) and 1.90 (1.13-3.19), respectively. The association between incident CKD and albuminuria with DBPV was less significant than SBPV. Similar results were found when measuring BPV as ARV and SD. No interaction was detected in BP-lowering strategy and SBPV on incident CKD and albuminuria ( P > 0.05). This study found that BPV was a risk factor for incident CKD and albuminuria in patients without CKD, especially SBPV. Although intensive BP control increased the risk of CKD, the association between SBPV and kidney function decline did not differ between the two treatment groups. URL: https://clinicaltrials.gov/ , Unique identifier: NCT01206062.

Serum High-Density Lipoprotein Cholesterol Levels and the Risk of Kidney Function Decline: The Japan Specific Health Checkups (J‑SHC) Study.

Both low and high serum levels of high-density lipoprotein cholesterol (HDL-C) were reported to be associated with adverse kidney outcomes. However, this association has not been well investigated in the general Japanese population. This nationwide longitudinal study used data from the Japan Specific Health Checkups Study conducted between 2008-2014. The association between serum HDL-C levels and 40% decline in estimated glomerular filtration rate (eGFR) was analyzed using Cox regression analysis. Trajectories of eGFR were compared using mixed-effects model. Among 768,495 participants, 6,249 developed 40% decline in eGFR during the median follow-up period of 34.6 (interquartile range: 14.8-48.4) months. Using serum HDL-C levels of 40-59 mg/dL as a reference, the adjusted hazard ratios (95% confidence intervals) for the kidney outcome of serum HDL-C levels of ＜40, 60-79 and ≥ 80 mg/dL were 1.26 (1.14-1.39), 0.91 (0.86-0.96), and 0.86 (0.78-0.93), respectively. Restricted cubic spline analysis showed that HDL-C levels of less than approximately 60 mg/dL were associated with an increased risk of kidney outcomes. Subgroup analysis showed that baseline eGFR and proteinuria modified the effects of serum HDL-C levels on kidney outcomes. The mixed-effects model showed that the lower category of HDL-C level was associated with a higher eGFR decline rate (p for interaction ＜0.001). Low HDL-C levels were associated with kidney function decline; however, high HDL-C levels were not associated with adverse kidney outcomes in the general Japanese population.

Integrated Proteomic and Metabolomic Modules Associated with Risk of Kidney Function Decline

Integrated Proteomic and Metabolomic Modules Associated with Risk of Kidney Function Decline

Coffee consumption and risk of kidney function decline in a Dutch population-based cohort

Background and aimsWhether coffee consumption is associated with changes in estimated glomerular filtration rate (eGFR) is unknown. We investigated the relationship between coffee consumption and annual eGFR change in a large Dutch population-based study. Methods and resultsThis study was performed in 78,346 participants without chronic kidney disease (CKD) in the population-based Lifelines Cohort Study. Coffee consumption was assessed at baseline using food frequency questionnaires. Outcomes were annual eGFR change and a composite kidney outcome (defined as eGFR <60 mL/min per 1.73 m2 or >20 % eGFR decline). Multivariable linear and logistic regression analyses were used to evaluate the associations of coffee consumption (categories and cups/day) with kidney outcomes. Overall, 90 % of the participants drank coffee daily and 36 % drank >2–4 cups/day. Unadjusted mean ± SD annual eGFR change ranged from −2.86 ± 2.96 (for non-coffee drinkers) to −2.35 ± 2.62 (for participants consuming >6 cups/day) mL/min per 1.73 m2. During 3.6 ± 0.9 years follow-up, 11.1 % of participants reached the composite kidney outcome. As compared to non-coffee drinkers, higher coffee consumption was associated with less annual eGFR decline in multivariable models (β [95 % CIs] ranged from 0.15 [0.07, 0.22] for >0–2 cups/day to 0.29 [0.20, 0.38] for >6 cups/day, P-trend <0.001). Consumption of one more cup of coffee per day was associated with a 3 % lower risk of the composite kidney outcome (OR [95%CI], 0.97 [0.96, 0.99]). The inverse association was more pronounced in a subgroup of individuals with diabetes. ConclusionCoffee consumption was inversely associated with annual eGFR change and CKD risk in a large Dutch population-based cohort.

The role of a low protein diet supplemented with ketoanalogues on kidney progression in pre-dialysis chronic kidney disease patients

In slowing kidney progression, numerous pre-dialysis chronic kidney disease (CKD) patients could not adhere to the well-established dietary pattern, including a very low protein diet, 0.3–0.4 g/kg/day, plus a full dose ketoanalogues (KAs) of amino acids. We evaluated the role of a low protein diet (LPD), 0.6–0.8 g/kg/day, combined with KAs (LPD–KAs) on CKD progression. We extracted data in the retrospective cohort using electronic medical records (n = 38,005). Participants with LPD–KAs for longer than six months were identified. An unmatched control group, LPD alone, was retrieved from the same database. Cox proportional hazard models were performed to examine the associations between LPD–KAs and outcomes. The primary outcome was either a rapid estimated glomerular filtration rate (eGFR) decline > 5 mL/min/1.73m2/year or commencing dialysis. Other secondary outcomes include changes in proteinuria, serum albumin, and other metabolic profiles were also assessed. A total of 1042 patients were finally recruited (LPD–KAs = 543). Although patients with LPD–KAs had significantly lower eGFR and a prevalence of diabetes, age, and dietary protein intake were comparable between LPD–KAs (0.7 ± 0.2 g/kg/day) and LPD alone groups (0.7 ± 0.3 g/kg/day, p = 0.49). During a median follow-up of 32.9 months, patients treated with LPD–KAs had a significantly lower risk of kidney function decline (HR 0.13; 95% CI 0.09–0.19, p < 0.001) and dialysis initiation (HR 0.24; 95% CI 0.12–0.49, p < 0.001) than LPD alone after adjusting for confounders. The annual rate of eGFR decline in patients receiving LPD–KAs was 4.5 [3.4–5.5] mL/min/1.73m2 compared with 7.7 [6.0–9.4] mL/min/1.73m2 in LPD alone (p = 0.001). According to KAs dose–response analysis, the daily dose of ≤ 5 tablets was conversely associated with a higher risk of the primary endpoint, whereas the association disappeared among patients receiving a dose of > 6 tablets. The spot urine protein creatinine ratio and serum phosphate levels were not significantly different between groups. LPD–KAs could retard kidney progression compared with LPD alone. This favorable effect was significant among CKD patients receiving a daily KAs dose of more than six tablets. Future randomized controlled trials should be performed to verify these findings.

The Impact of Sedentary Behavior on Renal Function Decline in 132,123 Middle Aged and Older Adults: A Nationwide Cohort Study.

BACKGROUND Prior studies suggest that sedentary behavior is a well-known risk factor for cardiometabolic diseases. However, the longitudinal association between overall siting time and kidney function decline is not known. MATERIAL AND METHODS We performed a nationwide prospective cohort study in individuals aged more than 40 years enrolled in the China Cardiometabolic Disease and Cancer Cohort (4C) study. A total of 132 123 individuals were included in this study. Sitting time was measured with the short version of the International Physical Activity Questionnaire (IPAQ). Kidney function decline was defined as an eGFR <60 mL/min/1.73 m² or more than a 30% decrease in eGFR from baseline. Multivariate Cox proportional hazards regression analyses were conducted to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of the relation between kidney function decline and sitting time. RESULTS During a mean follow-up of 3.8 years, 3890 (2.9%) participants experienced kidney function decline. Longer sitting time was significantly associated with the risk of kidney function decline (aHR, 1.136; 95% CI, 1.036-1.247, P=0.007, comparing participants with baseline sitting time in the lowest quartile with those in the highest quartile) after adjustment for potential confounders. CONCLUSIONS Longer sitting time was independently and prospectively associated with a higher risk of kidney function decline. Sedentary behavior might represent a modifiable risk factor for chronic kidney disease (CKD) prevention.

Association Between Risperidone Use and Kidney Function Decline in Patients with Schizophrenia: A Retrospective Cohort Study

PurposeSeveral D-amino acids have been shown to be protective against kidney injury in mice. Risperidone, a currently used atypical antipsychotic agent for schizophrenia, is also known to inhibit the activity of D-amino acid oxidase, which degrades certain D-amino acids. Based on the hypothesis that risperidone would prevent kidney disease progression, this study investigated the association between risperidone use and kidney function decline in patients with schizophrenia. MethodsThis retrospective cohort study included patients who were diagnosed with schizophrenia and had data available from two or more serum creatinine measurements between April 1, 2010, and March 31, 2020. Patients who used risperidone for at least 30 days were included in the risperidone group, whereas those who had no record of risperidone use were included in the control group. Cox regression models were used to evaluate the risk for 40% decline in estimated glomerular filtration rate (eGFR) in patients treated with risperidone compared to that in the control group. FindingsOverall, 212 patients used risperidone and 1468 patients had no record of risperidone use. The mean age was 55 years, 759 (45%) of the patients were male, and the mean eGFR at baseline was 88 mL/min/1.73 m2. The mean age in the risperidone group was less than that in the control group (52 vs 56 years); other baseline characteristics were comparable between the two groups. During a mean follow-up of 1.6 years, 267 patients (16%) had a 40% eGFR decline. The incidence rate of 40% eGFR decline was lower in the risperidone group than in the control group (60 vs 104 per 1000 person-years). After adjustment for baseline age, sex, and eGFR, risperidone use was associated with a decreased risk for 40% eGFR decline (hazard ratio = 0.54; 95% CI, 0.33–0.87; P = 0.01). ImplicationsRisperidone use may be associated with decreased risk for kidney function decline in patients with schizophrenia. Further studies are warranted to validate these findings.

Cardiovascular Autonomic Neuropathy and Risk of Kidney Function Decline in Type 1 and Type 2 Diabetes: Findings From the PERL and ACCORD Cohorts.

Previous studies have suggested that cardiovascular autonomic neuropathy (CAN) may predict rapid kidney function decline among persons with diabetes. We analyzed the association between baseline CAN and subsequent glomerular filtration rate (GFR) decline among individuals with type 1 diabetes (T1D) from the Preventing Early Renal Loss in Diabetes (PERL) study (N=469) and with type 2 diabetes (T2D) from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (N=7,973). Baseline CAN was ascertained using ECG-derived heart rate variability indices. Its association with GFR slopes, rapid kidney function decline (GFR loss ≥-5 ml/min/1.73 m2/year), and ≥40% GFR loss was evaluated by linear mixed effect, logistic, and Cox regression, respectively. Participants with CAN experienced more rapid GFR decline, by an excess 1.15 (95%CI [-1.93, -0.37], P= 4.0x10-3) ml/min/1.73m2/year in PERL and 0.34 (95%CI [-0.49, -0.19], P= 6.3x10-6) ml/min/1.73m2/year in ACCORD. This translated in 2.11 (95% CI [1.23-3.63], P=6.9x10-3) and 1.39 (95% CI [1.20-1.61], P=1.1x10-5) odds ratios of rapid kidney function decline in PERL and ACCORD, respectively. Baseline CAN was also associated with a greater risk of ≥40% GFR loss events during follow-up (HR=2.60, 95%CI [1.15-5.45], p=0.02 in PERL and HR=1.54, 95%CI [1.28-1.84], P=3.8×10-6 in ACCORD). These associations remained significant after adjustment for potential confounders, including baseline GFR and albuminuria. Our findings indicate that CAN is a strong, independent predictor of rapid kidney function decline in both T1D and T2D. Further studies of the link between these two complications may help develop new therapies to prevent kidney function decline in patients with diabetes.

Relationship of serum lipid parameters with kidney function decline accompanied by systemic arterial stiffness: a retrospective cohort study.

Dyslipidemia is associated with kidney function decline (KFD), although the non-linear relationship of lipid parameters to KFD has not been fully elucidated. We aimed to determine the detailed relationship of baseline lipid parameters with KFD, considering the mediation of arterial stiffness. A total of 27 864 urban residents with estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73 m2 at baseline, who participated in a median of three (range two to eight) consecutive annual health examinations were studied. Arterial stiffness was assessed by cardio-ankle vascular index (CAVI). KFD was defined as development of eGFR <60mL/min/1.73 m2. During the study period, 1837 participants (6.6%) developed KFD. Receiver operating characteristic analysis determined that the cutoff values independently associated with KFD are 123mg/dL for low-density lipoprotein cholesterol (LDL-C) [area under the curve (95% confidence interval) 0.570 (0.557-0.583)], 65mg/dL for high-density lipoprotein cholesterol (HDL-C) [0.552 (0.539-0.566)], 82mg/dL for triglycerides (TG) [0.606 (0.593-0.618)] and 1.28 for TG/HDL-C ratio [0.600 (0.587-0.612)]. These cut-offs were independently associated with KFD in Cox analysis. Regarding the contribution of each lipid parameter to KFD, a linear relationship was observed for both TG and TG/HDL-C, and a U-shaped relationship for HDL-C. A adjusted mediating effect of CAVI on the relationship of TG or TG/HDL-C ratio with KFD was observed (mediating rate: 2.9% in TG, 2.5% in TG/HDL-C ratio). Regarding the association to KFD, a linear relationship was observed for both TG and TG/HDL-C, and a U-shaped relationship for HDL-C. A mediating effect of CAVI on the relationship of TG or TG/HDL-C ratio with KFD was observed after adjustment for confounders. TG and TG/HDL-C ratio related linearly to KFD and this was partially mediated by CAVI. A U-shaped relationship was observed between HDL-C and KFD risk. LDL-C showed no significant association. Further study should investigate whether intensive TG-lowering treatment prevents KFD via decreasing CAVI.

The Association of Intravitreal Anti-VEGF Injections With Kidney Function in Diabetic Retinopathy

To examine whether patients with diabetic retinopathy receiving intravitreal anti-VEGF injections are at increased risk of kidney function decline. Retrospective cohort study. Included 187 patients who received intravitreal anti-VEGF injections for proliferative diabetic retinopathy (PDR) and/or diabetic macular edema (DME), and 929 controls with non-PDR who did not receive injections, at a large tertiary care center in Chicago, Illinois. We queried our institutional enterprise data warehouse to identify patients with diabetic retinopathy, determined whether they received intravitreal anti-VEGF injections, and followed kidney function for all patients over time. We assessed time to sustained 40% decline in estimated glomerular filtration rate (eGFR) from baseline in patients receiving intravitreal anti-VEGF injections and compared it with controls using Kaplan-Meier and multivariable adjusted Cox proportional hazards regression models. This study included 1116 patients (565 female [50.6%]; mean [standard deviation {SD}] age, 57.3 [13.6] years; mean [SD] eGFR, 65.3 [32.1] ml/min/1.73 m2). Of these, 187 patients received ≥ 1 intravitreal anti-VEGF injection (mean [SD], 11.4 [13.1] injections) for PDR and/or DME, and 929 controls with non-PDR received no injections. Intravitreal anti-VEGF injection use was not associated with an increased risk of kidney function decline (hazard ratio [HR], 1.44; 95% confidence interval [CI], 0.97-2.15). Subgroup analyses revealed that use of intravitreal anti-VEGF injections was associated with increased risk of kidney function decline in male patients (HR, 1.87; 95% CI, 1.11-3.14) but not female patients (HR, 0.97; 95% CI, 0.50-1.89). Intravitreal anti-VEGF injection use was also associated with an increased risk of kidney function decline in patients with baseline eGFR > 30 ml/min/1.73 m2 (HR, 1.86; 95% CI, 1.15-3.01), but not in individuals with baseline eGFR ≤ 30 ml/min/1.73 m2 (HR, 0.97; 95% CI, 0.45-2.10). Among patients who received injections, receiving ≥ 12 injections was not associated with risk of kidney function decline (HR, 1.13; 95% CI, 0.52-2.49). Intravitreal anti-VEGF injections for patients with diabetic retinopathy are overall well-tolerated with respect to kidney function, but the use of intravitreal anti-VEGF injections was associated with an increased risk of kidney function decline in certain subgroups of patients. Proprietary or commercial disclosure may be found after the references.