Risk Of Kidney Function Decline Research Articles

Canagliflozin Attenuates PromarkerD Diabetic Kidney Disease Risk Prediction Scores.

PromarkerD is a biomarker-based blood test that predicts kidney function decline in people with type 2 diabetes (T2D) who may otherwise be missed by current standard of care tests. This study examined the association between canagliflozin and change in PromarkerD score (Δ score) over a three-year period in T2D participants in the CANagliflozin cardioVascular Assessment Study (CANVAS). PromarkerD scores were measured at baseline and Year 3 in 2008 participants with preserved kidney function (baseline eGFR ≥60 mL/min/1.73 m2). Generalized estimating equations were used to assess the effect of canagliflozin versus placebo on PromarkerD scores. At baseline, the participants (mean age 62 years, 32% females) had a median PromarkerD score of 3.9%, with 67% of participants categorized as low risk, 14% as moderate risk, and 19% as high risk for kidney function decline. After accounting for the known acute drop in eGFR following canagliflozin initiation, there was a significant treatment-by-time interaction (p < 0.001), whereby participants on canagliflozin had decreased mean PromarkerD scores from baseline to Year 3 (Δ score: -1.0% [95% CI: -1.9%, -0.1%]; p = 0.039), while the scores of those on placebo increased over the three-year period (Δ score: 6.4% [4.9%, 7.8%]; p < 0.001). When stratified into PromarkerD risk categories, participants with high risk scores at baseline who were randomized to canagliflozin had significantly lower scores at Year 3 (Δ score: -5.6% [-8.6%, -2.5%]; p < 0.001), while those on placebo retained high scores (Δ score: 4.5% [0.3%, 8.8%]; p = 0.035). This post hoc analysis of data from CANVAS showed that canagliflozin significantly lowered PromarkerD risk scores, with the effect greatest in those T2D participants who were classified at study entry as at high risk of a subsequent decline in kidney function.

Association between Serum Uric Acid and the Early Marker of Kidney Function Decline among Chinese Middle-Aged and Older Population: Evidence from the China Health and Retirement Longitudinal Study

ObjectiveTo evaluate the association between serum uric acid (SUA) and kidney function decline. MethodsData was obtained from the China Health and Retirement Longitudinal Study on the Chinese middle-aged and older population for analysis. The kidney function decline was defined as an annual estimated glomerular filtration rate (eGFR) decrease by > 3 mL/min per 1.73 m2. Multivariable logistic regression was applied to determine the association between SUA and kidney function decline. The shape of the association was investigated by restricted cubic splines. ResultsA total of 7,346 participants were included, of which 1,004 individuals (13.67%) developed kidney function decline during the follow-up of 4 years. A significant dose-response relation was recorded between SUA and the kidney function decline (OR 1.14, 95% CI 1.03–1.27), as the risk of kidney function decline increased by 14% per 1 mg/dL increase in SUA. In the subgroup analyses, such a relation was only recorded among women (OR 1.22, 95% CI 1.03–1.45), those aged < 60 years (OR 1.22, 95% CI 1.05–1.42), and those without hypertension and without diabetes (OR 1.22, 95% CI 1.06–1.41). Although the dose-response relation was not observed in men, the high level of SUA was related to kidney function decline (OR 1.83, 95% CI 1.05–3.17). The restricted cubic spline analysis indicated that SUA > 5 mg/dL was associated with a significantly higher risk of kidney function decline. ConclusionThe SUA level was associated with kidney function decline. An elevation of SUA should therefore be addressed to prevent possible kidney impairment and dysfunction.

The association of dietary patterns with incident chronic kidney disease and kidney function decline among middle-aged Korean adults: a cohort study.

This study assessed the association of dietary patterns with the incidence of chronic kidney disease (CKD) and kidney function decline among Korean adults. Data were collected from the records of 20,147 men and 39,857 women who participated in the Health Examinees study. Principal component analysis was used to identify 3 dietary patterns (prudent, flour-based food and meat, and white rice-based), and CKD risk was defined using the Epidemiology Collaboration equation for estimated glomerular filtration rate: (eGFR) <60 mL/min/1.73 m2. A kidney function decline was defined as a >25% decrease in eGFR from baseline. During the 4.2-year follow-up, 978 participants developed CKD and 971 had a 25% decline in kidney function. After adjusting for potential impact variables, compared with the lowest quartile of the prudent dietary pattern, participants in the highest quartile had a 37% lower risk of kidney function decline among men (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.47 to 0.85); while higher adherence to the flour-based food and meat dietary pattern was associated with an increased risk of CKD in both men (HR, 1.63; 95% CI, 1.22 to 2.19) and women (HR, 1.47; 95% CI, 1.05 to 2.05) as well as a decline in kidney function in both men (HR, 1.49; 95% CI, 1.07 to 2.07) and women (HR, 1.77; 95% CI, 1.33 to 2.35). Although a higher adherence to the prudent dietary pattern was inversely associated with the risk of kidney function decline in men, there was no association with CKD risk. In addition, a higher adherence to the flour-based food and meat dietary pattern increased the risk of CKD and kidney function decline. Further clinical trials are needed to confirm these associations.

Urinary Biomarkers of Tubular Health and Risk for Kidney Function Decline or Mortality in Diabetes

Introduction: Diabetes is a leading cause of end-stage kidney disease (ESKD). Biomarkers of tubular health may prognosticate chronic kidney disease (CKD) progression beyond estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Methods: We examined associations of five urinary biomarkers of tubular injury and repair (NGAL, KIM-1, IL-18, MCP-1, YKL-40) with kidney function decline (first occurrence of a decrease in eGFR ≥30 mL/min/1.73 m2 if randomization eGFR ≥60 or ≥50% if randomization eGFR <60; ESKD) and all-cause mortality among 1,135 VA NEPHRON-D trial participants with baseline UACR ≥300 mg/g and available urine samples. Covariates included age, sex, race, BMI, systolic BP, HbA1c, treatment arm, eGFR, and UACR. In a subset of participants with 12-month samples (n = 712), we evaluated associations of KIM-1, MCP-1, and YKL-40 change (from baseline to 12 months) with eGFR decline (from 12 months onward). Results: At baseline, mean age was 65 years, mean eGFR was 56 mL/min/1.73 m2, and median UACR was 840 mg/g. Over a median of 2.2 years, 13% experienced kidney function decline and 9% died. In fully adjusted models, the highest versus lowest quartiles of MCP-1 and YKL-40 were associated with 2.18- and 1.76-fold higher risks of kidney function decline, respectively. One-year changes in KIM-1, MCP-1, and YKL-40 were not associated with subsequent eGFR decline. Higher baseline levels of NGAL, IL-18, MCP-1, and YKL-40 levels (per 2-fold higher) were independently associated with 10–40% higher risk of mortality. Conclusion: Among Veterans with diabetes and CKD, urinary biomarkers of tubular health were associated with kidney function decline and mortality.

Pregnancy outcomes in patients with IgA vasculitis with nephropathy (Henoch–Schönlein purpura nephritis) and those with IgA nephropathy: Childhood purpura nephritis is high risk for preeclampsia

Objective: Childhood IgA vasculitis in remission is not a known risk factor for pregnancy but can lead to complications such as preeclampsia, even in women with a low risk of kidney function decline.Methods: This retrospective study compared pregnancy outcomes between patients with IgA vasculitis with nephropathy (Henoch–Schönlein purpura nephritis) and those with IgA nephropathy who delivered at Osaka University Hospital between 2010 and 2020.Results: Seven patients with purpura nephritis and 37 patients with IgA nephropathy had a total of 9 and 53 pregnancies, respectively. Purpura nephritis patients had an earlier gestational age at delivery and higher frequency of preterm birth, fetal growth restriction, and preeclampsia than IgA nephropathy patients, although differences were not significant. Among pregnancies at low risk of kidney function decline, 35 were with IgA nephropathy and 9 were with purpura nephritis. The incidence of preeclampsia was significantly higher with purpura nephritis (44%: 4/9) than with IgA nephropathy (9%: 3/35 including 2 with oocyte donation). Severe and early-onset preeclampsia was noted in 2 pregnancies with purpura nephritis.Conclusion: Patients with childhood purpura nephritis in remission may develop preeclampsia, with a higher risk of severe and early-onset preeclampsia than patients with IgA nephropathy.

Coffee Consumption and Risk of Kidney Function Decline in a Dutch Population-Based Cohort

Coffee Consumption and Risk of Kidney Function Decline in a Dutch Population-Based Cohort

Impact of Sleep Duration on Decline in Kidney Function in Adult Patients with Hypertension: A Community-Based Prospective Cohort Study.

BackgroundSleep duration is associated with various health conditions, including chronic kidney disease. However, the association between sleep duration and decline in kidney function in the South Korean population remains unclear. We aimed to investigate the impact of sleep duration on kidney function decline in adult patients with hypertension.MethodsThis cohort study was performed using data obtained from the Korean Genome and Epidemiology Study; 2,837 patients with hypertension who initially had normal kidney function were included. Glomerular filtration rates (GFRs) were estimated at baseline and throughout the 16 years of follow-up. A person was considered to have a decline in kidney function if they had a GFR <60 mL/min/1.73 m2. Sleep duration data were obtained through interviewer-assisted questionnaires. Sleep durations were classified as short (<6 hours), normal (≥6 hours but <9 hours), and long (≥9 hours). The Cox proportional hazards model was applied, with adjustments for covariates.ResultsAfter adjusting for covariates, sleep duration was not associated with a decline in kidney function. However, among men with poorly controlled hypertension at baseline, compared to men with normal sleep durations, men with sleep durations <6 hours had a significantly higher risk of kidney function decline (hazard ratio, 1.56; 95% confidence interval, 1.02–2.36).ConclusionShort sleep duration did not seem to be associated with an increased risk of decline in kidney function; however, it may be a risk factor for the decline in kidney function in men with poorly controlled hypertension.

Similar risk of kidney function decline between tenofovir alafenamide and besifovir dipivoxil maleate in chronic hepatitisB.

Although tenofovir alafenamide (TAF) and besifovir dipivoxil maleate (BSV) are potent antiviral agents in the treatment of chronic hepatitis B (CHB) infection, their renal safety profiles have not been previously compared. This study compared the risk of kidney function decline among patients with treatment-naïve CHB treated with TAF or BSV. This multicenter, retrospective, longitudinal cohort study included 556 patients with treatment-naïve CHB treated with TAF (n=366) or BSV (n=190) between November 2017 and August 2021. The primary outcome was chronic kidney disease (CKD) progression, defined as an increase in CKD stage by at least one stage for at least three consecutive months. 1:1 Propensity score matching yielded 154 patients in each treatment group. The mean estimated glomerular filtration rate (eGFR) was 100.4 vs. 100.3 ml/min/1.73 m2 in the TAF and BSV groups respectively. A total of 25 patients developed a progression in CKD stage ≥1, of which 13 and 12 patients were from the TAF and BSV treated groups respectively (3.1 vs. 3.3 per 1000 person-years; p=.751). The unadjusted hazard ratio for risk of progression in CKD stage ≥1 of the BSV group (vs. the TAF group) was 1.13 (95% confidence interval, 0.50-2.58; p=.758). This association persisted even after adjusting for potential confounders. Virological, serological and biochemical responses were also similar between the two treatment groups (all p > .05). TAF and BSV showed a similar risk of kidney function decline in patients with treatment-naïve CHB. Further prospective randomized studies are warranted for validation.

A kidney diagnostic's impact on physician decision-making in diabetic kidney disease.

Estimated glomerular filtration rate (eGFR) and albuminuria, the current standard-of-care tests that predict risk of kidney function decline in early-stage diabetic kidney disease (DKD), are only modestly useful. We evaluated the decision-making impact of an artificial intelligence-enabled prognostic test, KidneyIntelX, in the management of DKD by primary care physicians (PCPs). This was a prospective web-based survey administered among PCPs in the United States. We used conjoint analysis with multivariable logit models to estimate PCP preferences. The survey included hypothetical patient profiles with 6 attributes: albuminuria, eGFR, age, blood pressure (BP), hemoglobin A1c (HbA1c), and KidneyIntelX result. Each PCP viewed 8 patient profiles randomly selected from 42 unique profiles having 1 level from each attribute. For each patient, PCPs were asked to indicate whether they would prescribe a sodium-glucose cotransporter-2 (SGLT2) inhibitor, increase angiotensin receptor blocker (ARB) dose, and/or refer to a nephrologist. A total of 401 PCPs completed the survey (response rate, 8.8%). The relative importance of the top 2 attributes for each decision were HbA1c (52%) and KidneyIntelX result (23%) for prescribing SGLT2 inhibitors, BP (62%) and KidneyIntelX result (13%) for increasing ARB dose, and eGFR (42%) and KidneyIntelX result (27%) for nephrologist referral. A high-risk KidneyIntelX result was associated with significantly higher odds of PCPs prescribing SGLT2 inhibitors (odds ratio [OR], 1.64; 95% CI, 1.29-2.08), increasing ARB dose (OR, 1.49; 95% CI, 1.17-1.89), and referring to a nephrologist (OR, 2.47; 95% CI, 1.99-3.08) compared with no test. The KidneyIntelX test had greater relative importance than albuminuria and eGFR to PCPs in making treatment decisions and was second only to eGFR for nephrologist referrals. Because of its significant impact on decision-making, KidneyIntelX has high clinical utility in DKD management.

Lifestyle changes and kidney function: A 10-year follow-up study in patients with manifest cardiovascular disease.

BackgroundPatients with cardiovascular disease (CVD) are at higher risk of kidney function decline. The current study aimed to examine the association of lifestyle changes with kidney function decline in patients with manifest CVD.MethodsA total of 2260 patients from the Utrecht Cardiovascular Cohort‐Second Manifestations of ARTerial disease cohort with manifest CVD who returned for a follow‐up visit after a median of 9.9 years were included. The relation between change in lifestyle factors (smoking, alcohol consumption, physical activity and obesity) and change in kidney function (eGFR and uACR) was assessed using linear regression models.ResultsAn increase in body mass index (β −2.81; 95% CI −3.98; −1.63 per 5 kg/m2) and for men also an increase in waist circumference (β −0.87; 95% CI −1.28; −0.47 per 5 cm) were significantly associated with a steeper decline in eGFR over 10 years. Continuing smoking (β −2.44, 95% CI −4.43; −0.45) and recent smoking cessation during follow‐up (β −3.27; 95% CI −5.20; −1.34) were both associated with a steeper eGFR decline compared to patients who remained as non‐ or previous smokers from baseline. No significant association was observed between physical exercise or alcohol consumption and kidney function decline. No significant relation between any lifestyle factor and change in uACR was observed.ConclusionsIn patients with CVD, continuing smoking, recent smoking cessation and an increase in obesity markers were related to a steeper kidney function decline. Although no definite conclusions from this study can be drawn, the results support the importance of encouraging weight loss and smoking cessation in high‐risk patients as a means of slowing down kidney function decline.

Effect of Oral Methylprednisolone on Decline in Kidney Function or Kidney Failure in Patients With IgA Nephropathy

The effect of glucocorticoids on major kidney outcomes and adverse events in IgA nephropathy has been uncertain. To evaluate the efficacy and adverse effects of methylprednisolone in patients with IgA nephropathy at high risk of kidney function decline. An international, multicenter, double-blind, randomized clinical trial that enrolled 503 participants with IgA nephropathy, proteinuria greater than or equal to 1 g per day, and estimated glomerular filtration rate (eGFR) of 20 to 120 mL/min/1.73 m2 after at least 3 months of optimized background care from 67 centers in Australia, Canada, China, India, and Malaysia between May 2012 and November 2019, with follow-up until June 2021. Participants were randomized in a 1:1 ratio to receive oral methylprednisolone (initially 0.6-0.8 mg/kg/d, maximum 48 mg/d, weaning by 8 mg/d/mo; n = 136) or placebo (n = 126). After 262 participants were randomized, an excess of serious infections was identified, leading to dose reduction (0.4 mg/kg/d, maximum 32 mg/d, weaning by 4 mg/d/mo) and addition of antibiotic prophylaxis for pneumocystis pneumonia for subsequent participants (121 in the oral methylprednisolone group and 120 in the placebo group). The primary end point was a composite of 40% decline in eGFR, kidney failure (dialysis, transplant), or death due to kidney disease. There were 11 secondary outcomes, including kidney failure. Among 503 randomized patients (mean age, 38 years; 198 [39%] women; mean eGFR, 61.5 mL/min/1.73 m2; mean proteinuria, 2.46 g/d), 493 (98%) completed the trial. Over a mean of 4.2 years of follow-up, the primary outcome occurred in 74 participants (28.8%) in the methylprednisolone group compared with 106 (43.1%) in the placebo group (hazard ratio [HR], 0.53 [95% CI, 0.39-0.72]; P < .001; absolute annual event rate difference, -4.8% per year [95% CI, -8.0% to -1.6%]). The effect on the primary outcome was seen across each dose compared with the relevant participants in the placebo group recruited to each regimen (P for heterogeneity = .11): full-dose HR, 0.58 (95% CI, 0.41-0.81); reduced-dose HR, 0.27 (95% CI, 0.11-0.65). Of the 11 prespecified secondary end points, 9 showed significant differences in favor of the intervention, including kidney failure (50 [19.5%] vs 67 [27.2%]; HR, 0.59 [95% CI, 0.40-0.87]; P = .008; annual event rate difference, -2.9% per year [95% CI, -5.4% to -0.3%]). Serious adverse events were more frequent with methylprednisolone vs placebo (28 [10.9%] vs 7 [2.8%] patients with serious adverse events), primarily with full-dose therapy compared with its matching placebo (22 [16.2%] vs 4 [3.2%]). Among patients with IgA nephropathy at high risk of progression, treatment with oral methylprednisolone for 6 to 9 months, compared with placebo, significantly reduced the risk of the composite outcome of kidney function decline, kidney failure, or death due to kidney disease. However, the incidence of serious adverse events was increased with oral methylprednisolone, mainly with high-dose therapy. ClinicalTrials.gov Identifier: NCT01560052.

Severe acute kidney disease is associated with worse kidney outcome among acute kidney injury patients

Acute kidney disease (AKD) comprises acute kidney injury (AKI). However, whether the AKD staging system has prognostic values among AKI patients with different baseline estimated glomerular filtration (eGFR) remains a controversial issue. Algorithm-based approach was applied to identify AKI occurrence and to define different AKD stages. Risk ratio for major adverse kidney events (MAKE), including (1) eGFR decline > 35% from baseline, (2) initiation of dialysis, (3) in-hospital mortality of different AKD subgroups were identified by multivariable logistic regression. Among the 4741 AKI patients identified from January 2015 to December 2018, AKD stages 1–3 after AKI was common (53% in the lower baseline eGFR group and 51% in the higher baseline eGFR group). In the logistic regression model adjusted for demographics and comorbidities at 1-year follow-up, AKD stages 1/2/3 (AKD stage 0 as reference group) were associated with higher risks of MAKE (AKD stage: odds ratio, 95% confidence interval [95% CI], AKD 1: 1.85, 1.56–2.19; AKD 2: 3.43, 2.85–4.12; AKD 3: 10.41, 8.68–12.49). Regardless of baseline eGFR, staging criteria for AKD identified AKI patients who were at higher risk of kidney function decline, dialysis and mortality. Post-AKI AKD patients with severer stage need intensified care and timely intervention.

Malnutrition Risk and Kidney Function and Decline in Community-Dwelling Older Adults

The association of malnutrition with chronic kidney disease (CKD) is well established. However, there is a paucity of studies of the effect of malnutrition risk (MR) on kidney function decline among older persons who do not have end-stage or dialyzable CKD. This study aimed to examine the association between MR status and kidney function, and future risks of kidney function decline and CKD progression in community-dwelling older adults. Nutrition Screening Initiative's DETERMINE Your Nutritional Health Checklist and estimated glomerular filtration rate (eGFR) were assessed at baseline among 5,122 participants free of end-stage renal failure or dialyzed CKD in the Singapore Longitudinal Aging Studies (SLAS-1 and SLAS-2). Follow-up eGFR was assessed in a subcohort of SLAS-2 participants without CKD (eGFR > 60mL/min/1.73m2) at baseline (N=786) who were followed up at 3-5years. In baseline cross-sectional analyses adjusting for other risk factors, low, moderate, and high MR was significantly associated with decreasing eGFR coefficients of -1.5, -3.3, and -5.0mL/min/1.73m2 respectively, and increasing CKD odds ratios of 1.81, 2.18, and 3.11 respectively. In longitudinal analysis, low, moderate, and high MR was significantly associated with increased risk of eGFR (>25%) decline (odds ratio of 2.37, 3.34, and 2.18 respectively). Among older adults without advanced kidney disease, MR is associated with poor kidney function and increased risk of kidney function decline and CKD. Preventive interventions to modify MR may help to reduce the deterioration of renal function in older people.

Contribution of phosphate and FGF23 to CKD progression.

Progressive forms of chronic kidney disease (CKD) exhibit kidney inflammation and fibrosis that drive continued nephron loss; however, factors responsible for the development of these common pathologic features remain poorly defined. Recent investigations suggest pathways involved in maintaining urinary phosphate excretion in CKD may be contributing to kidney function decline. This review provides an update on recent evidence linking altered phosphate homeostasis to CKD progression. High dietary phosphate intake and increased serum concentrations of fibroblast growth factor 23 (FGF23) both increase urinary phosphate excretion and are associated with increased risk of kidney function decline. Recent investigations have discovered high concentrations of tubular phosphate promote phosphate-based nanocrystal formation that drives tubular injury, cyst formation, and fibrosis. Studies presented in this review highlight important scientific discoveries that have molded our current understanding of the contribution of altered phosphate homeostasis to CKD progression. The collective observations from these investigations implicate phosphaturia, and the resulting formation of phosphate-based crystals in tubular fluid, as unique risk factors for kidney function decline. Developing a better understanding of the relationship between tubular phosphate handling and kidney pathology could result in innovative strategies for improving kidney outcomes in patients with CKD.

Higher risk of kidney function decline with entecavir than tenofovir alafenamide in patients with chronic hepatitis B.

Entecavir (ETV) and tenofovir alafenamide (TAF) are the preferred agents in patients with predisposing factors for nephrotoxicity, but no studies to date have directly compared the renal safety of the two antiviral agents. Hence, we compared the risk of kidney function decline among patients with treatment-naïve chronic hepatitis B (CHB) treated with ETV or TAF. This study included 1988 patients with treatment-naïve CHB who were treated with ETV (n = 1839) or TAF (n = 149) between 2007 and 2020 for ETV and between 2017 and 2020 for TAF. The primary outcome was chronic kidney disease (CKD) progression, defined as an increase in CKD stage by at least one stage for at least three consecutive months. A 1:1 propensity score match yielded 149 patients in each treatment group. The mean estimated glomerular filtration rate (eGFR) was 100.6ml/min/1.73m2 vs. 101.3ml/min/1.73m2 in the ETV and TAF groups respectively. A total of 61 patients developed a progression in CKD stage≥1, of which 47 and 14 patients were from the ETV- and TAF-treated groups respectively (19.9 vs. 5.1 per 1000 person-years; p<.001). The risk of progression in CKD stage ≥1 was significantly higher in patients treated with ETV, even when adjusted for potential confounders (adjusted hazard ratio 4.05; 95% CI 2.14-7.68; p<.001). ETV was associated with a higher risk of kidney function decline than TAF in patients with treatment-naïve CHB. Therefore, further prospective randomized studies are needed.

Kidney outcomes and all-cause mortality in people with type 2 diabetes exhibiting non-albuminuric kidney insufficiency.

It remains unclear whether people with diabetes exhibiting non-albuminuric kidney insufficiency have higher risk of kidney function decline and mortality compared with those exhibiting preserved kidney function without albuminuria. Furthermore, information regarding the incidence of albuminuria in people with this unique phenotype is sparse. Here, we aimed to elucidate the risk of the kidney outcomes and all-cause mortality in people with diabetes exhibiting non-albuminuric kidney insufficiency. In this retrospective cohort study, 8320 Japanese adults with type 2 diabetes were classified into four groups based on the presence of albuminuria and kidney insufficiency at baseline, defined as urinary albumin/creatinine ratio of equal to or above 30mg/g and eGFR of less than 60 ml min-1 1.73 m-2, respectively. The primary composite kidney endpoint was a 50% decrease in eGFR from baseline or the initiation of kidney replacement therapy. The annual percentage change in eGFR slope and progression of albuminuria category were evaluated as the secondary and tertiary kidney endpoints, respectively. All-cause death was also set as the endpoint. Compared with people exhibiting non-albuminuric preserved kidney function, those with non-albuminuric kidney insufficiency had the higher risk for the primary kidney endpoint (HR 4.1; 95% CI 2.5, 6.7; p < 0.001), steep percentage change in eGFR slope (-1.96%/year vs -1.36%/year, p < 0.001), incidence of albuminuria (HR 2.1; 1.7, 2.6; p < 0.001) and all-cause mortality (HR 1.5; 1.2, 2.0; p = 0.003). In the sensitivity analyses treating the incidence of albuminuria as a competing risk, people with non-albuminuric kidney insufficiency still had higher risk for the primary kidney endpoint and all-cause mortality than those with non-albuminuric preserved kidney function (subdistribution HR 2.8; 1.4, 5.6; p = 0.004; and 1.6; 1.1, 2.2; p = 0.014, respectively). People with type 2 diabetes exhibiting non-albuminuric kidney insufficiency had poorer kidney outcomes and life prognosis than those exhibiting non-albuminuric preserved kidney function.

Kidney Tubulointerstitial Fibrosis and Tubular Secretion

Tubular secretion plays an important role in the efficient elimination of endogenous solutes and medications, and lower secretory clearance is associated with risk of kidney function decline. We evaluated whether histopathologic quantification of interstitial fibrosis and tubular atrophy (IFTA) is associated with lower tubular secretory clearance in persons undergoing kidney biopsy. Cross-sectional. The Boston Kidney Biopsy Cohort is a study of persons undergoing native kidney biopsies for clinical indications. Semiquantitative score of IFTA reported by 2 trained pathologists. We measured plasma and urine concentrations of 9 endogenous secretory solutes using a targeted liquid chromatography/mass spectrometry assay. We used linear regression to test associations of urine-to-plasma ratios (UPRs) of these solutes with IFTA score after controlling for estimated glomerular filtration rate (eGFR) and albuminuria. Among 418 participants, mean age was 53 years, 51% were women, 64% were White, and 18% were Black. Mean eGFR was 50mL/min/1.73m2, and median urinary albumin-creatinine ratio was 819mg/g. Compared with individuals with≤25% IFTA, those with>50% IFTA had 12%-37% lower UPRs for all 9 secretory solutes. Adjusting for age, sex, race, eGFR, and urine albumin and creatinine levels attenuated the associations, yet a trend of lower secretion across groups remained statistically significant (P<0.05 for trend) for 7 of 9 solutes. A standardized composite secretory score incorporating UPR for all 9 secretory solutes using the min-max method showed similar results (P<0.05 for trend). Single time point and spot measures of secretory solutes. Greater IFTA severity is associated with lower clearance of endogenous secretory solutes even after adjusting for eGFR and albuminuria.

Proteins Associated with Risk of Kidney Function Decline in the General Population.

Proteomic profiling may allow identification of plasma proteins that associate with subsequent changesin kidney function, elucidating biologic processes underlying the development and progression of CKD. We quantified the association between 4877 plasma proteins and a composite outcome of ESKD or decline in eGFR by ≥50% among 9406 participants in the Atherosclerosis Risk in Communities (ARIC) Study (visit 3; mean age, 60 years) who were followed for a median of 14.4 years. We performed separate analyses for these proteins in a subset of 4378 participants (visit 5), who were followed at a later time point, for a median of 4.4 years. For validation, we evaluated proteins with significant associations (false discovery rate <5%) in both time periods in 3249 participants in the Chronic Renal Insufficiency Cohort (CRIC) and 703 participants in the African American Study of Kidney Disease and Hypertension (AASK). We also compared the genetic determinants of protein levels with those from a meta-analysis genome-wide association study of eGFR. In models adjusted for multiple covariates, including baseline eGFR and albuminuria, we identified 13 distinct proteins that were significantly associated with the composite end point in both time periods, including TNF receptor superfamily members 1A and 1B, trefoil factor 3, and β-trace protein. Of these proteins, 12 were also significantly associated in CRIC, and nine were significantly associated in AASK. Higher levels of each protein associated with higher risk of 50% eGFR decline or ESKD. We found genetic evidence for a causal role for one protein, lectin mannose-binding 2 protein (LMAN2). Large-scale proteomic analysis identified both known and novel proteomic risk factors for eGFR decline.

Circulating ANGPTL8 levels and risk of kidney function decline: Results from the 4C Study

BackgroundANGPTL8, an important regulator of lipid metabolism, was recently proven to have additional intracellular and receptor-mediated functions. This study aimed to investigate circulating levels of ANGPTL8 and its potential association with the risk of kidney function decline in a cohort study.MethodsWe analysed 2,311 participants aged 40 years old and older from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Kidney function decline was defined as an estimated glomerular filtration rate (eGFR) less than 60 mL per minute per 1.73 m2 of body surface area, a decrease in eGFR of ≥ 30% from baseline, chronic kidney disease (CKD)-related hospitalization or death, or end-stage renal disease. The association between baseline ANGPTL8 levels and kidney function decline was assessed using multivariable-adjusted Cox proportional hazards models, and inverse possibility of treatment weight (IPTW) was utilized to prevent overfitting.ResultsThere were 136 (5.9%) cases of kidney function decline over a median of 3.8 years of follow-up. We found that serum ANGPTL8 levels at baseline were elevated in individuals with kidney function decline compared to those without kidney function decline during follow-up (718.42 ± 378.17 vs. 522.04 ± 283.07 pg/mL, p < 0.001). Compared with the first quartile, multivariable-adjusted hazard ratio (95% confidence intervals [CIs]) for kidney function decline was 2.59 (95% CI, 1.41–4.77) for the fourth ANGPTL8 quartile. Furthermore, compared with patients in the first ANGPTL8 quartile, those in the fourth ANGPTL8 quartile were more likely to report a higher stage of CKD (relative risk: 1.33; 95% CI, 1.01–1.74). The conclusions of the regression analyses were not altered in the IPTW models. Multivariable-adjusted restricted cubic spline analyses suggested a linear relationship of ANGPTL8 with kidney function decline (p for nonlinear trend = 0.66, p for linear trend < 0.001).ConclusionsParticipants with higher circulating ANGPTL8 levels were at increased risk for kidney function decline, highlighting the importance of future studies addressing the pathophysiological role of ANGPTL8 in CKD.

Association of urinary vanin-1 with kidney function decline in hypertensive patients.

Previously, the authors reported the utility of urinary vanin‐1 as an early biomarker of kidney injury in spontaneously hypertensive rats and in humans. However, little is known about whether urinary vanin‐1 can be used to predict the clinical outcome. This study aimed to evaluate the predictive power of urinary vanin‐1 based on kidney function decline in hypertensive patients. The authors measured urinary vanin‐1 in 147 patients at the baseline and examined its association with the incidence of ≥20% decline in the estimated glomerular filtration rate (eGFR) using the Cox regression analysis. The mean age of the patients averaged 72.9 ± 8.2 years, and 39% were women. Median (interquartile range) urinary vanin‐1 was 0.33 (0–2.6) ng/mg Cr During a median follow‐up of 12 months, 14 patients showed kidney function decline. A higher urinary vanin‐1 level was associated with an increased risk of kidney function decline (hazard ratio, 9.87; 95% CI, 1.11–87.5) (p = .04) in the fully adjusted model. In conclusion, urinary vanin‐1 is an independent risk factor for kidney function decline in hypertensive patients and it could be useful in clinical settings. The underlying pathophysiologic mechanisms warrant additional investigation.