eGFR Decline Research Articles

Nephroprotective effect of SGLT2 inhibitors in elderly patients with type 2 diabetes mellitus and hypertension: a real-world population-based cohort study

ABSTRACT Objectives This study aimed to investigate the nephroprotective effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in elderly patients with type 2 diabetes mellitus (T2DM) and hypertension based on real-world clinical data. The study aimed to provide a theoretical basis for evidence-based pharmacological treatment of chronic kidney disease in this population. Methods The ‘Health Cloud’ platform of the Shanghai Municipal Health Commission was employed to identify and screen elderly patients with T2DM and hypertension. The propensity score matching cohort was further constructed to estimate the effect of SGLT2i on the risk of rapid decline in renal function (∆eGFR≤-5 ml/min/1.73 m2 or ∆eGFR%≤-5%). Multiple sensitivity analyses were conducted to assess the robustness of the results. Results After propensity score matching, no significant differences of covariates were identified between the SGLT2i and non-SGLT2i groups. The results of multivariate logistic models demonstrated a consistent and inverse correlation between SGLT2i use and the risk of rapid eGFR decline, whether defined as ∆eGFR≤-5 ml/min/1.73 m2 (OR = 0.60, 95% CI:0.38-0.96) or ∆eGFR%≤-5%（OR = 0.57, 95% CI:0.37-0.89). In the stratification of renin-angiotensin system inhibitor (RASi) treatment, SGLT2i was associated with a lower risk of rapid eGFR decline in the RASi group (all ORs < 1, p < 0.05), with no interaction between SGLT2i and RASi (all P for interaction > 0.05) detected. Conclusions SGLT2i significantly reduced the risk of rapid eGFR decline in elderly patients with T2DM and hypertension, but the synergistic effect with RASi remains unclear.

Association of urinary EGF, FABP3, and VCAM1 levels with the progression of early diabetic kidney disease

Introduction Diabetic kidney disease (DKD) is a common cause of chronic kidney disease with around 25-40% of patients with diabetes being affected. The course of DKD is variable and estimated glomerular filtration rate (eGFR) and albuminuria, the currently used clinical markers, are not able to accurately predict the individual disease trajectory, in particular in early stages of the disease. The aim of this study was to assess the association of urine levels of selected protein biomarkers with the progression of DKD at an early stage of disease. Methods We measured 22 protein biomarkers using the Mesoscale Discovery platform in 461 urine samples of the PROVALID cohort, an observational study of patients with type 2 diabetes mellitus followed at the primary health care level for a minimum of four years. Odds ratios (OR) were estimated for the effect of marker values above median on fast progression using unadjusted and adjusted logistic regression models. RNA expression at the single cell level in kidney biopsy samples obtained from a cohort of young persons with type 2 diabetes mellitus was in addition determined for markers showing significant associations with disease progression. Results Increased urinary levels of epidermal growth factor (EGF) were linked to lower odds of fast progression (defined as annual eGFR decline greater than 2.58 ml/min per 1.73 m2) with an odds ratio (OR) of 0.60 (95% CI 0.46, 0.78). The association with outcome was even stronger when adjusting for a set of 14 baseline clinical parameters including age, biological sex, eGFR, body mass index, albuminuria, and HbA1c. Elevated urinary levels of fatty acid binding protein 3 (FABP3) and vascular cell adhesion molecule 1 (VCAM1) were each significantly associated with fast progression with an OR of 1.44 (95% CI 1.11, 1.87) and an OR of 1.41 (95% CI 1.08, 1.83), respectively. Enriched expression of EGF and FABP3 was observed in distal convoluted tubular cells and VCAM1 in parietal epithelial cells at single cell level from biopsies of patients with early DKD. Conclusion In summary we show that lower urinary levels of EGF and higher urinary levels of FABP3 and VCAM1 are significantly associated with DKD progression in early-stage disease.

Predictive values of four nutritional indices for adverse outcomes in patients with hypertension.

Malnutrition, evaluated by nutritional indices, is reportedly related to a poor prognosis in patients with hypertension. However, clinical evidence on which index is more suitable for predicting a kidney prognosis is limited, and it has not been evaluated in hypertension. The aim of the present study was to investigate and compare the predictive values of four nutritional indices: Geriatric Nutritional Risk Index (GNRI); Prognostic Nutrition Index (PNI); Triglycerides × Total cholesterol × Body weight Index (TCBI); and the controlling nutritional status (CONUT) score. A retrospective, cohort study of 1255 hypertensive patients under care in the Fukushima Cohort Study was conducted. The primary outcome was kidney events, defined as a combination of a 50% decline in eGFR from baseline and renal failure requiring dialysis therapy or kidney transplantation. Kaplan-Meier analyses and multivariate Cox regression analyses were conducted to examine associations between the four nutritional indices and kidney events. The area under the curve (AUC) values of the receiver-operating characteristic curves were also examined to compare the predictive values of these nutritional indices. Lower GNRI, lower PNI, and higher CONUT score were significantly related to a higher risk of kidney events. GNRI (AUC = 0.729, 95% confidence interval 0.681-0.777) and PNI (AUC = 0.710, 95% confidence interval 0.665-0.756) had significantly higher AUCs for kidney events than the TCBI and CONUT score. GNRI and PNI showed greater predictive values for kidney events than other nutritional indices in patients with hypertension.

Physical activity and renal outcome in diabetic and non-diabetic patients with chronic kidney disease stage G3b to G5

The association of physical activity with renal outcome and mortality in advanced chronic kidney disease (CKD; i.e., estimated glomerular filtration rate [eGFR] < 45 ml/min/1.73m2) is poorly studied. We examined this association in patients with advanced CKD in Japan. We used the Rapid Assessment of Physical Activity to assess baseline physical activity and classify patients as active or inactive. CKD progression was defined as 40% decline in eGFR, eGFR < 10, or requiring dialysis or transplantation. Among the 1,808 eligible patients, after adjusting for possible confounders, hazard ratios (HRs) for poor renal outcome in the active group were 0.68 (95% CI, 0.44–1.04), 1.09 (0.86–1.38), and 1.01 (0.82–1.25) in CKD stage G3b, G4, and G5, respectively, suggesting a renal benefit of exercise in CKD stage G3b. Adjusted HRs for death were 0.79 (0.40–1.57), 0.55 (0.38–0.80), and 0.75 (0.44–1.26) in stage G3b, G4, and G5, respectively. While the adjusted HRs of death were 0.84 (0.52–1.38) and 0.60 (0.43–0.83) in diabetic and non-diabetic patients, suggesting that exercise may reduce mortality in non-diabetic patients. Our study suggests that exercise is associated with better survival in non-diabetic patients with CKD stage G3b-5, and better renal outcome in diabetic and non-diabetic CKD stage G3b.

Chronic kidney disease in Bardet-Biedl syndrome: evidence supporting multifactorial etiology

IntroductionChronic kidney disease (CKD) is a critical prognostic factor in Bardet-Biedl syndrome (BBS). Early diagnosis and intervention are essential for improving patients’ outcomes. The present study has analyzed kidney function in BBS patients, with the aim to explore the impact of genetic variants and common risk factors for kidney diseases. MethodsA monocentric cross-sectional study has been conducted. Patients underwent genetic analysis via Next Generation Sequencing; renal function has been assessed and the relationship with (I) age, obesity and hypertension and with (II) genetic mutations has been analyzed. ResultsA total of 65 BBS patients were enrolled in the study; renal function was variable, with 25% of patients showing an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73m2. Patients’ age was inversely correlated with the eGFR (p=0.002). Reduced eGFR significantly correlated with truncating mutations in any BBS gene and hypertension; moreover, multivariate analysis using eGFR as an objective variable and multiple risk factors as explanatory variables, showed that body mass index (BMI) was independently associated with eGFR decline (β=-2.45, p<0.0001), in addition to age. Interestingly, significant discordance in renal phenotype was revealed in 50% of subgroups of consanguineous or non-consanguineous patients sharing the same pathogenic variants, indicating clinical variability even in this setting. ConclusionThe present study suggests that BBS is a condition of vulnerability to develop kidney disease and that age, hypertension and obesity are associated with eGFR decline in adult BBS patients; whether effective interventions to treat modifiable factors will reduce CKD risk requires further studies.

An updated systematic review of the risk factors for unplanned dialysis initiation

Abstract Background Previously, a comprehensive review of the risk factors for unplanned dialysis initiation (UDI) was conducted by Hassan et al. (2019), based on studies published up to end of 2017. They demonstrated that high quality data and well-designed studies on the subject are lacking. Thus, we updated their review to establish the modifiable factors associated with UDI. Methods MEDLINE and EMBASE were searched from January 2018 to August 2023. Following several rounds of screening, we identified 17 international studies (majority of which were based in Europe) that met the eligibility criteria. Results Many of the included studies were well designed, utilised very large datasets, and adopted multivariate analyses to examine associations between patient characteristics and UDI. Definitions of UDI varied across studies, i.e. timeliness of presentation, vascular access type, initiating dialysis as an inpatient/outpatient, or for life threatening indications. The most common risk factors reported were cardiovascular disease, increased age, cause of kidney disease, cancer, diabetes, lower serum albumin, increased rate of estimated glomerular filtration rate (eGFR) decline and fewer number of nephrology visits prior to dialysis start. These were in line with those reported by Hassan et al. However, our updated review revealed several other important predictors of UDI, i.e. worse coding of chronic kidney disease (CKD) in the GP health record, lower health literacy, and having an acute kidney injury (AKI). Conclusions Our review provides new insights into reasons why people start dialysis in an unplanned manner, many of which are modifiable, thus contributing to efforts in reducing the rate of UDI.

Prediction of subsequent CKD according to eGFR decline slope varies by the presence of hypertension

Abstract Background We reported that a declining slope in eGFR evaluated from 3-year observation could predict subsequent CKD among the relatively healthy population, even adjusted for baseline eGFR. However, its certainty may vary depending on the presence of comorbidities such as diabetes and hypertension, which are also recognized as the risk factors of CKD. Methods Annual health check-up data from a Japanese company spanning from 2009 to 2022 was used. The analyses included participants having 4 times continuous eGFR measurements for 3 years, undergoing health checkups at least once during a follow-up period, with negative for urinary protein (UP), and non-diabetic. Individual ‘eGFR slopes’ were calculated by the regression line with 4 times eGFR measurements. Participants with slopes of &amp;lt; -5 per year were categorized as the “decreased” group and -5 or more were categorized as the “stable” group. The cases of positive UP or less than 45mL/min/1.73m2 in eGFR during a follow-up period were defined as CKD. Cox regression analyses adjusted for sex, age, and eGFR at baseline were performed to calculate the hazard ratios and 95% CIs for CKD in the decreased group (reference; stable), stratified by hypertension. Results Out of 5598 study participants(men 36%, mean age 48.2±10.1years, mean follow-up period 4.3 years), 260 CKD cases (4.6%) were observed. CKD cases accounted for 4.5% (235/5218) in the stable group and 6.6% (25/380) in the decreased group. Multivariate-adjusted hazard ratios [95%CIs] of CKD by eGFR decline was 1.50[0.99-2.27]. The eGFR decline increased the risk of CKD only in participants with hypertension (2.09[1.09-4.04]), but not in those without hypertension (1.25[0.73-2.13]). After excluding individuals with eGFR slopes exceeding 10 per year to consider for hyperfiltration of eGFR, the results were consistent. Conclusions The eGFR decline over a 3-year observation may predict subsequent CKD only in individuals with hypertension. Key messages • With a relatively short-term evaluation period of three years, eGFR decline can predict subsequent CKD only in hypertensive individuals. • In middle-aged hypertensive patients, it would be important for the prevention of CKD to pay attention not only to low eGFR but also to the progression of eGFR decline.

Longitudinal and cross-sectional associations of NT-proBNP with kidney function and chronic kidney disease: results from KORA cohort studies

Abstract Background Chronic kidney disease (CKD) and cardiovascular disease (CVD) exhibit a bidirectional and complex relationship, and share common risk factors and mechanisms of disease development. Thus, important CVD-related biomarkers, such as N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), may serve as a biomarker for CKD development. Purpose We aimed to investigate the cross-sectional and longitudinal associations of NT-proBNP with kidney function and CKD in data from two population-based cohort studies. Methods We included 5854 men and women, aged 25-74 years, from the Cooperative Health Research in the Region of Augsburg (KORA) cohort studies S3 and S4, and their 1-2 subsequent follow-up surveys, with a median follow-up time of 9.4 and 13.4 years, respectively. Kidney function was assessed by 3 estimated glomerular filtration rate (eGFR) assessments, calculated using creatinine (eGFRcr), cystatin C, and combined creatinine and cystatin C. Serum NT-proBNP was logarithmically transformed followed by Z-score standardization and categorized into 4 groups (G1-4), &amp;lt;48.6, 48.6-125, 125-300, and ≥300 pg/ml. In cross-sectional analysis, linear regression and logistic regression were used to estimate β/odds ratio (OR) and their 95% confidence intervals (CIs) of continuous eGFR or prevalent CKD. For longitudinal analysis of repeated eGFR measurements during follow-up (5854 participants, 11870 observations), linear mixed-effects models were used. For incident CKD associations, interval-censored Cox regression models were performed in participants free of CKD at baseline. Results In cross-sectional analyses, higher NT-proBNP levels were associated with lower eGFR and higher prevalence of CKD across all 3 eGFR assessments. For example, results based on eGFRcr showed that the fully-adjusted β (95% CIs) for per 1 SD increase in log-transformed NT-proBNP were -1.03 (-1.42, -0.64) and -7.01 (-8.93, -5.09) 60 ml/min/1.73m2 for G4 compared to G1, respectively. Corresponding OR (95% CIs) were 2.22 (1.81, 2.74) and 13.8 (5.76, 36.4), respectively. In longitudinal analyses, participants with higher baseline NT-proBNP had a faster decline in eGFR during follow-up. The fully-adjusted β (95% CIs) for 5-year eGFRcr decline were -0.67 (-0.87, -0.47) per 1 SD increase, and -0.37 (-0.79, 0.05), -1.53 (-2.18, -0.88), -4.24 (-5.57, -2.90) 60 ml/min/1.73m2/year for G2-4. Higher NT-proBNP levels were associated with higher incident CKD risks. For associations with incident creatinine-based CKD, hazard ratio (95% CIs) were 1.16 (1.00, 1.33) per 1 SD increase and 1.03 (0.77, 1.38), 1.07 (0.75, 1.52), and 1.81 (1.07, 3.04) for G2-4. Conclusions We found associations of higher NT-proBNP with lower kidney function and higher CKD prevalence. Moreover, higher baseline NT-proBNP levels were associated with faster kidney function decline and higher incident CKD risks. Our findings indicate the potential utility of NT-proBNP as a biomarker of kidney health.Figure 1.Cross-sectional associationsFigure 2.Longitudinal associations

Safety and efficacy of initiation SGLT in heart failure with a reduced left ventricular ejection fraction and chronic kidney disease on top of standard therapy with ARNI or ACE-i

Abstract Quadruple therapy remains underused in cases of heart failure with a reduced ejection fraction (HFrEF). Among eligible patients most of them take ACE-i/ARB and B-blockers, less MRAs and ARNI. There are many questions of adding new foundational drugs, especially in the case of coexisting of HFrEF and chronic kidney disease (CKD). The aim was to compare the safety and effectiveness of initiation SGLT in patients (P) with HFrEF and CKD on standard therapy with ARNI or ACE-I. Methods we identified 54 symptomatic P with HFrEF (EF≤40%) and CKD 3 (eGFR between 30 and 60 ml/min) on standard therapy (ACE-I or ARNI, B-blockers, MRAs). All P were divided into 2 groups: group 1- 26 P on ARNI, B-blockers, MRAs; group 2- 28 P on ACE-I, B-blockers, MRAs. All P started on dapagliflozin (D) with a dose of 10 mg daily. The potassium (K), creatinine levels, eGFR, clinic BP were estimated at baseline and at weeks 1, 2, 4, 6, 8, 12. At baseline and at weeks 4, 12 NT-proBNP, urine albumin-to-creatinine ratio (UCAR) were estimated and P underwent 24-hour BP measurements. Results At week 1 after initiation of D a mean eGFR deсreased not significant in both group. At week 2 in group 1 mean eGFR decreased by 1,9±1.1 ml/min/1.73m2, P&amp;lt;.05 and group 2-2,5±1.9 ml/min/1.73m2, P&amp;lt;.05. At week 4 in both groups mean eGFR deсreased significantly, but in group 2 the decline of eGFR was more pronounced (-2,4±2.6 ml/min/1.73m2 vs.-3,3±2.5 ml/min/1.73m2, P=.04), with not significant decreasing to 6, 8, 12 weeks. At week 1mean K changed not significantly after start of therapy in both groups. At week 4 in group 1mean K deсreased significantly from 4.97±0.6 to 4.63±0.57 mEq/l (P&amp;lt;.05), in group 2 K deсreased not significant. At week 4 in group 1 was a greater reduction NT-proBNP than in group 2 (-234±42 vs. -143±32 ng/L, P&amp;lt;.05). At week 12 in both groups a significant decrease NT-proBNP were observed, but in group 1 more pronounced (-865±89 ng/L and -573±78 ng/L, (P&amp;lt;.01; P&amp;lt;.05 respectively). UCAR was also reduced significantly in both groups, but in group 1 more pronounced (P&amp;lt;.01; P&amp;lt;.05 respectively). In group 1, there were more cases of symptomatic hypotension (10 vs. 8, P&amp;lt;.05) and greater decrease mean BP than in group 2 (P&amp;lt;.05), but it didn’t result in a withdrew. In return, maen doses diuretics were carefully decreased in both groups. At baseline in patients with HFrEF was an inverse correlation between GFR and NT-proBNP level (r=−0.328, P&amp;lt;.05). By linear regression analysis the eGFR was associated with NT-proBNP change (P&amp;lt;.05). Conclusion In patients with HFrEF and CKD, adding SGLT to standard therapy with ARNI, B-blockers, MRAs were paralleled by marked improvements in the neurohumoral profile by significantly reduced NT-proBNP compared with ACE-I, B-blockers, MRAs. SGLT initiation caused an early drop in eGFR, but in group ARNI the decline of eGFR was less pronounced with greater reduction in the albuminuria and was accompanied by decreased potassium level.

Bidirectional relationship between kidney disease progression and cardiovascular events in type 2 diabetes: new Insights from the CANVAS Program and CREDENCE trial

Abstract Background The extent to which chronic kidney disease (CKD) progression increases cardiovascular risk, and whether different types of cardiovascular events affect risk of CKD progression, is incompletely understood. Purpose We sought to explore risk of cardiovascular events before and after CKD progression, and CKD progression before and after different cardiovascular events in patients with type 2 diabetes. Methods We conducted a pooled individual participant data analysis of the CANVAS Program and CREDENCE trial. Using Poisson regression, we assessed the incidence of major adverse cardiovascular events ([MACE] stroke, myocardial infarction, or cardiovascular death) and hospitalised heart failure (HHF) or cardiovascular death before and after CKD progression (defined as 40% decline in estimated glomerular filtration rate [eGFR] or kidney failure), and CKD progression before and after nonfatal cardiovascular events, with no adjustment for confounding related to subgroups defined by post-randomization variables. We estimated the cumulative incidence of all-cause mortality after different nonfatal cardiovascular and kidney outcomes, including different thresholds of CKD progression (kidney failure, 40% or 50% decline in eGFR or doubling of serum creatine) using Cox regression models. Results Among 14,464 participants (mean age 63.7 years, 35.3% female, mean eGFR 55mL/min/1.73m2 and median urinary albumin:creatinine ratio 34mg/g) over a median follow-up of 2.5 years, 1,482, 1,076 and 1,020 experienced MACE, HHF or cardiovascular death, and CKD progression, respectively. After (vs. before) CKD progression, there was an approximate 3-fold increase in incidence of MACE (30.2 vs. 93.8 per 1000-patient-years) and 4-fold increase in HHF or cardiovascular death (21.0 vs. 79.3 per 1000-patient-years). Conversely, the incidence of CKD progression was approximately 1.5-fold higher after (vs. before) nonfatal myocardial infarction or stroke (21.7 vs. 34.1 per 1000-patient-years) and 5-fold higher after HHF (21.2 vs. 108.2 per 1000-patient-years). These patterns were consistent in both treatment arms, with unadjusted incidence rates for clinical events appearing numerically lower in canagliflozin compared to placebo-treated participants (Figure 1). Of all non-fatal cardio-kidney outcomes, HHF and doubling of serum creatine or kidney failure conferred the highest risk of death (Figure 2). Conclusion Atherosclerotic and heart failure risk increases substantially after CKD progression. CKD progression was accelerated after cardiovascular events, particularly HHF. Treatment with canagliflozin was associated with lower event rates before and after a serious cardio-kidney outcome, suggesting continued use of canagliflozin may be beneficial even after cardiovascular events and CKD progression.Figure 1.Figure 2.

Obesity and renal impairment in patients with heart failure and reduced ejection fraction: another obesity paradox?

Abstract Background Obesity is associated with poor cardiovascular outcomes in patients with HF and reduced ejection fraction (HFrEF). However, whether obesity is associated with worse kidney outcomes in HFrEF has not been evaluated. Purpose To estimate the association between obesity and change in estimated glomerular filtration rate (eGFR) over time in patients with HFrEF. Methods In this post hoc analysis of the PARADIGM-HF trial, body mass index (BMI) and eGFR was collected in 8,389 patients. Change in eGFR over time was assessed according to baseline BMI (normal weight: BMI &amp;lt;25.0, overweight: BMI 25-29.9, and obesity: BMI ≥30). Results The number of patients in each BMI category was: 2,421 (BMI &amp;lt;25.0), 3,249 (BMI 25-29.9), and 2,719 (BMI ≥30), respectively. Patients with obesity were younger but had worse health status (worse NYHA class and KCCQ scores) and had more comorbidities including diabetes mellitus and hypertension. At baseline, eGFR was lower in patients who were overweight (BMI 25-29.9) and obese (BMI ≥30), compared to those with normal weight. Urine albumin-creatinine ratio (UACR) and kidney injury molecule-1 (KIM-1) were also higher in patients with obesity. However, the rate of change in eGFR per year (eGFR "slope") in the overall cohort did not differ according to BMI: change in eGFR per year was -1.8 [-2.1, -1.6] mL/min/1.73m2 for the normal weight category, -1.6 [-1.8, -1.3] mL/min/1.73m2 for those who were overweight, and -1.5 [-1.8, -1.3] mL/min/1.73m2 for those with obesity; P=0.21) (Figure 1). Among those without diabetes at baseline, those who were obese had a significantly less steep eGFR slope compared to patients in the other BMI categories. In those with diabetes at baseline, the eGFR slope was steeper than in patients without diabetes but was similar across all three BMI categories (Figure 2). Conclusions Although baseline kidney function was more impaired in HFrEF patients with obesity, high BMI was not associated with a more rapid subsequent rate of decline in eGFR. Figure 1. eGFR slope over time according to BMI at baseline in patients with HFrEF in PARADIGM-HF Figure 2. eGFR slope over time according to BMI at baseline in patients with HFrEF in PARADIGM-HF with and without diabetes at baselineFigure 1Figure 2-A and 2-B

To analyse the correlation between UAER and eGFR and the risk factors for reducing eGFR in patients with type 2 diabetes

ObjectiveTo analyse the correlation between urinary albumin excretion rate (UAER) and estimated glomerular filtration rate (eGFR) and the risk factors for reducing eGFR in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 431 T2DM patients admitted between January 2019 and March 2020 were selected and divided into two groups according to eGFR level. Comparing the differences between baseline data and clinical indicators, multivariate logistic regression was used to analyse the risk factors of eGFR reduction and to analyse the association between UAER and eGFR.ResultsIn total, 167 patients were included in the study group and 264 patients were included in the conventional group. The study group participants were older, had longer diabetes duration, and had higher fatty liver, peripheral vascular disease (PVD), hypertension prevalence, and mean body mass index (P < 0.05). The levels of various indicators were lower than those of the conventional group (P < 0. 05). Additionally, PVD, nocturnal systolic blood pressure, fatty liver, and beta-2-microglobulin (β 2-MG) were independent risk factors for eGFR decline, with high density lipoprotein (HDL) and fasting C-peptide (CP) as protective factors. There was no obvious correlation between UAER and eGFR.ConclusionPeripheral vascular disease, systolic blood pressure, fatty liver, and beta-2-microglobulin are risk factors for decreased eGFR levels in patients with T2DM, which should be applied for control DKD. HDL and fasting CP have important effects on maintaining eGFR, and blood pressure and fasting CP can be used as new targets for subsequent diabetic kidney disease treatment.

Association between malnutrition and adverse renal outcomes in patients with type 2 diabetes.

Nutritional management is crucial in patients with chronic kidney disease. Therefore, it is important to assess nutritional status and detect malnutrition, especially in patients with diabetes. However, there is currently a lack of evidence regarding the relationship between nutritional indices and renal function in patients with type 2 diabetes. This study investigated whether the geriatric nutritional risk index (GNRI) is related to renal prognosis in type 2 diabetes patients. The study included 946 type 2 diabetes patients enrolled in the Fukushima Cohort Study. The primary endpoint of this study was a renal event, defined as a combination of a 50% decline in eGFR from baseline and end-stage kidney disease. All-cause death and new cardiovascular events were also measured as secondary outcomes. The association between GNRI and these endpoints was assessed using Cox regression analysis. The median patient age was 66 years, 57% were men, the median eGFR was 67.9 mL/min/1.73 m2, and the median GNRI was 100.0. Compared to patients in the highest GNRI tertile, patients in the lowest tertile had a significantly increased risk of therenal event (HR 5.15, 95% CI 2.51-10.6) and all-cause death (HR 2.30, 95% CI 1.20-4.42). A significant association was not observed between GNRI levels and cardiovascular events. We observed an association between poor nutritional status, assessed by GNRI, and adverse outcomes in patients with type 2 diabetes. Nutritional status assessment has potential utility as a prognostic tool for individuals with type 2 diabetes.

Impact of Home-Based Rehabilitation on Renal Prognosis in Patients with Chronic Kidney Disease.

The increasing prevalence of chronic kidney disease (CKD) requires effective preventive measures, particularly due to an aging population. This study aimed to assess the effectiveness of home visit rehabilitation in preventing renal function decline among patients with CKD. In this retrospective study, patients with non-dialysis CKD undergoing home visit rehabilitation were compared with those receiving outpatient care at the Nippon Medical School Hospital between August 2017 and August 2023. Patients' backgrounds were matched using propensity scores derived from a logistic regression model. The primary endpoint was the annual change in the estimated glomerular filtration rate (eGFR), and the secondary endpoint was the annual change in blood parameters (Δblood urea nitrogen, Δcreatinine, Δtotal protein, Δalbumin, ΔC-reactive protein, Δhemoglobin, and Δhematocrit). Furthermore, the incidence of clinical outcomes, including mortality, hospitalization rate, and dialysis initiation rate, were analyzed within the additional 1-year observation period. Overall, 128 patients (64 matched pairs) were analyzed. After a mean follow-up period of 12.7 ± 4.6 months, there was no significant difference in the eGFR between both groups (40.1 ± 13.7 vs. 37.8 ± 13.8 mL/min/1.73 m2, p = 0.36), but the annual decline in eGFR (%/year) was significantly lower in the rehabilitation group (-1.1 ± 29.8% vs. -11.8 ± 27.7%/year, p = 0.037). The annual change in the level of each blood test parameter and clinical outcomes were not significantly different between the two groups. Home-based rehabilitation interventions may mitigate the progression of renal impairment in patients with CKD.

Development of a multivariate model predictive of post-adrenalectomy renal function decline in patients with primary aldosteronism: a large-cohort single-center study.

To develop a multivariate liniear model for predicting long-term (> 3 months) post-adrenalectomy renal function decline in patients with primary aldosteronism (PA). The model aims to help identify patients who may experience a significant decline in renal function after surgery. We retrospectively analyzed the clinical data of 357 patients who were diagnosed with PA and underwent adrenalectomy between September 2012 and February 2023. LASSO and multivariate linear regression analyses were used to identify significant risk factors for model construction. The models were further internally validated using bootstrap method. Age (P < 0.001), plasma aldosterone concentration (PAC) measured in the upright-position (PACU, P = 0.066), PAC measured after saline infusion (PACafterNS, P = 0.010), preoperative blood adrenocorticotropic-hormone level (ACTH, P = 0.048), preoperative estimated glomerular filtration rate (eGFR, P < 0.001) and immediate postoperative eGFR (P < 0.001) were finally included in a multivariate model predictive of post-adrenalectomy renal function decline and the coefficients were adjusted by internal validation. The final model is: predicted postoperative long-term (> 3 months) eGFR decline =-70.010 + 0.416*age + 6.343*lg PACU+4.802*lg ACTH + 7.424*lg PACafterNS+0.637*preoperative eGFR-0.438*immediate postoperative eGFR. The predicted values are highly related to the observed values (adjusted R = 0.63). The linear model incorporating perioperative clinical variables can accurately predict long-term (> 3 months) post-adrenalectomy renal function decline.

Role of baseline soluble tumor necrosis factor receptor 2 as a biomarker in primary podocytopathy: Implications for renal impairment and disease progression

BackgroundPodocytopathies, including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and collapsing glomerulopathy (CG), are kidney diseases that damage glomerular podocytes, leading to heavy proteinuria and nephrotic syndrome (NS). Inflammation plays a critical role in the progression of chronic kidney disease (CKD), with recent studies linking inflammatory biomarkers to declining kidney function. Tumor necrosis factor-alpha (TNF-α), an essential inflammatory cytokine, interacts with its circulating receptors, TNFR1 and TNFR2. The TNF-α pathway has been implicated in the pathogenesis of FSGS and MCD. Increased circulating TNFR2 levels have been associated with worsening renal function in podocytopathies, suggesting that the TNF-α inflammatory pathway significantly contributes to disease progression.MethodsWe conducted a study involving 53 patients with biopsy-proven MCD or FSGS and 53 healthy, age- and gender-matched controls. All patients were followed for 18 months. We analyzed serum and urine TNFR2 levels and gene expression at baseline and after three months. To assess the ability of TNFR2 to predict persistent decline in estimated glomerular filtration rate (eGFR < 30 mL/min/1.73m2), remission, and relapse, we employed Cox regression analysis. Additionally, we evaluated its prognostic utility for predicting progression to stage 4 CKD using ROC curve analysis.ResultsSerum and urine TNFR2 levels were significantly elevated in patients compared to controls. Serum TNFR2 was a significant predictor in univariate Cox regression analysis for persistent eGFR decline (HR 1.017, 95% CI: 1.003 to 1.032, p = 0.018), remission (HR 0.995, 95% CI: 0.992 to 0.999, p = 0.006), and relapse (HR 1.005, 95% CI: 1.001 to 1.010, p = 0.029). The ROC curve analysis demonstrated that serum TNFR2 levels had a strong prognostic ability for predicting progression to stage 4 CKD, with an AUC of 0.848 (95% CI: 0.737—0.960), sensitivity of 81%, and specificity of 71%.ConclusionThis study underscores the critical role of circulating TNFR2 in kidney injury among patients with primary podocytopathy. Elevated TNFR2 levels are significant predictors of persistent eGFR decline and disease relapse, highlighting their potential as biomarkers for disease progression and prognosis.

Association between change in serum uric acid and rapid decline in kidney function in China

While the elevation of serum uric acid (SUA) is acknowledged as a risk factor for chronic kidney disease, the independent extent to which variations in SUA levels are correlated with temporal changes in estimated glomerular filtration rate (eGFR) remains uncertain. In light of this uncertainty, our research endeavored to elucidate the temporal associations between change in SUA and rapid eGFR decline in China. In this longitudinal study of China’s middle-aged and elderly between 2011 and 2015, we analyzed 5421 individuals with complete SUA and eGFR data. Logistic regression was applied to evaluate the risk factors associated with a rapid eGFR decline (defined by a 5 mL/min/1.73 m2 decrease or falling to less than 15 mL/min/1.73 m2 by 2015), adjusted for age, gender, marital, residence, income, BMI, hypertension, diabetes, dyslipidemia, CRP, Hba1c, baseline eGFR and baseline SUA. Linear regression was used to evaluate the relationship between variations in SUA and changes in eGFR. After multivariable adjustments, the risk factors of a rapid eGFR decline included aging (OR per 1-year increase: 1.1, 95% CI 1.08–1.12, P < 0.001), being female, being single, having hypertension, a higher baseline eGFR, a higher baseline SUA (OR per-1 mg/dL increase: 1.68, 95% CI 1.48–1.90, P < 0.001), and increase in change in SUA (OR per-1 mg/ dL increase: 1.92,95% CI 1.71–2.16, P < 0.001). Pearson’s analysis showed a significant inverse correlation between SUA changes and eGFR decline, particularly pronounced in females, with correlation coefficients of − 0.349 for females and − 0.306 for males (95% CI − 0.347 to − 0.299, P < 0.001). A significant correlation was found between the change in SUA and the rapid decline in eGFR, with this association being particularly pronounced in females.

Impact of baseline proteinuria level on long-term outcomes in lupus nephritis.

Proteinuria is a marker of lupus nephritis (LN) activity and damage. We aimed to explore the impact of baseline proteinuria level on long-term outcomes. We included 249 patients diagnosed with their first biopsy-proven LN. We divided patients based on baseline proteinuria into low-level (≤1 g/day, group 1; 62 patients), moderate-level (>1 and <3 g/day, group 2; 90 patients), and high-level proteinuria (≥3 g/day, group 3; 97 patients). Outcomes included complete proteinuria recovery (CPR) at 1 year, an adverse composite outcome (ESKD, a sustained ≥40% decline in eGFR, or death), and LN flares. Cox proportional hazard models were used to examine the association between baseline characteristics and long-term outcomes. At baseline, the median [IQR] age was 33.2 [26.4, 42.4] years; median proteinuria level was 2.2 [1.0, 3.8] g/day. 177 (71%) patients had proliferative lesions on biopsy; 59.7% in group 1, 78.9% in group 2, and 71.4% in group 3.The rate of achievement of CPR at 1 year was highest for group 1 and lowest for group 3. For long-term outcomes (median follow-up 8.4 years), the frequency of the adverse composite outcome was 27.4%, 26.7%, and 48.5% in groups 1, 2, and 3, respectively; p= 0.003. The corresponding frequency of flares was 27.4%, 38.2%, and 61.9%, respectively; p< 0.001. In the multivariable model for factors associated with long-term outcomes, there was no significant difference between groups 1 and 2; group 3 was associated with the worst prognosis. Low-level proteinuria is commonly associated with proliferative LN and adverse long-term outcomes.

Long-term safety and efficacy of endovascular ultrasound renal denervation in resistant hypertension: 8-year results from the ACHIEVE study.

Ultrasound renal sympathetic denervation (uRDN) reduces blood pressure (BP) in the absence and presence of antihypertensive treatment at 2months. Beyond 3years, there is a lack of follow-up data. This study investigated the long-term safety and efficacy of uRDN. This prospective observational study recruited patients previously included in the international multicenter ACHIEVE study, with office systolic blood pressure (SBP) ≥160 mmHg, 24h ambulatory SBP ≥130mmHg, ≥3 antihypertensive drugs and estimated Glomerular Filtration Rate (eGFR) ≥45 ml/min/1.73m2 undergoing uRDN. The primary efficacy outcome was 24h ambulatory SBP, adjusted for the number of defined daily dosages (DDD) of antihypertensive drugs. Statistical analyses were performed using linear mixed-effects models and inverse probability weighting. A total of 27 out of the initially enrolled 96 patients underwent prospective follow-up at a median of 8.2 [7.6-8.9]years. Mean age was 62.6±9.3years (37.0% female). Preprocedural 24h ambulatory BP was 151.9/84.1±11.5/11.1 mmHg and the median number of DDDs was 5.0 [4.3-7.0]. At 8years after uRDN, the change in 24h ambulatory SBP was -19.5 [95%CI -26.7,-12.4] mmHg (p<0.001). The 8-year change in the number of DDDs was -1.7 [-2.8,-0.6] (p = 0.003). The 8-year decline in eGFR was -8.9 [-13.2,-4.7] ml/min/1.73m2 (p<0.001). Clinical event data were available for all 96 patients (median follow-up 3.5 [1.0-8.0]years). Renal failure occurred in one patient and no cases of renal artery stenosis were detected. A significant BP reduction was observed up until 8years following uRDN in parallel to a decrease in drug burden over time, in the absence of procedure-related adverse events.

Proteomic Analysis Uncovers Multi-Protein Signatures Associated with Early Diabetic Kidney Disease in Youth with Type 2 Diabetes Mellitus.

The onset of diabetic kidney disease (DKD) in youth with type 2 diabetes mellitus often occurs early, leading to complications in young adulthood. Risk biomarkers associated with the early onset of DKD are urgently needed in youth with type 2 diabetes. We conducted an in-depth analysis of 6596 proteins (SomaScan 7K) in 374 baseline plasma samples from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study to identify multi-protein signatures associated with the onset of albuminuria (urine albumin-to-creatinine ratio [UACR] ≥30 mg/g), a rapid decline in estimated glomerular filtration rate (eGFR) [annual eGFR decline >3 mL/min/1.73m2 and/or ≥3.3% at two consecutive visits], and hyperfiltration (≥135 mL/min/1.73m2 at two consecutive visits). Elastic net Cox regression with 10-fold cross-validation was applied to the top 100 proteins (ranked by p-value) to identify multi-protein signatures of time to development of DKD outcomes. Participants in the TODAY study (14±2 years old, 63% female, 7±6 months diabetes duration) experienced high rates of early DKD: 43% developed albuminuria, 48% hyperfiltration, and 16% rapid eGFR decline. Increased levels of seven and three proteins were predictive of shorter time to develop albuminuria and rapid eGFR decline, respectively; 118 proteins predicted time to development of hyperfiltration. Elastic net Cox proportional hazards model identified multi-protein signatures of time to incident early DKD with concordance for models with clinical covariates and selected proteins between 0.81 and 0.96, while the concordance for models with clinical covariates only was between 0.56 and 0.63. Our research sheds new light on proteomic changes early in the course of youth-onset type 2 diabetes that associate with DKD. Proteomic analyses identified promising risk factors that predict DKD risk in youth with type 2 diabetes and could deepen our understanding of DKD mechanisms and potential interventions.