eGFR Decline Research Articles

Urinary transforming growth factor beta-1 levels correlate with the effect of renorrhaphy on functional outcomes post-laparoscopic partial nephrectomy: A pilot-study

ABSTRACT Purpose Preservation of functional renal parenchyma is one of the main targets of partial nephrectomy. We investigated the effects of suture on renal parenchyma in tumor bed and on short-term renal function. Materials and Methods Patients with unilateral cT1 renal masses candidate for laparoscopic partial nephrectomy (PN) have been recruited. After tumor excision, medullary sutures were replaced by argon beam in Group 1, while Group 2 had conventional 2-layer renorrhaphy. Groups have been matched using propensity score. Transforming growth factor beta-1 (TGFb1) levels in urine have been measured at the 1st and 30th day post-PN. Glomerular filtration rate has been estimated (eGFR) at baseline and 3 months post-PN. Results Sixteen cases were matched in each group. There was no difference between groups regarding baseline, operative and perioperative data. Number of sutures in group 1 is nearly half that in group 2 (10 vs 19, respectively, p < 0.001). Group 1 showed lower urinary TGFb1 levels at the 1st and 30th day post-PN (p < 0.01 for each), higher eGFR after 3 months (p = 0.01), and less decline of eGFR from baseline (p = 0.046). Conclusion TGFb1 levels in urine after PN are related to the number of sutures. Reduced number of sutures in tumor bed has a positive effect on short term eGFR changes possibly by reducing tumor bed fibrogenic healing response as well as preserving renal parenchymal volume.

Assessment of total carotid plaque area progression in patients with chronic kidney disease. Good practices for decision-making.

Chronic kidney disease (CKD) increases cardiovascular risk, however,traditional cardiovascular risk factors cannot entirely explain it. A real-world investigation examined the concept that renal function decline is linked to carotid total plaque area progression, which strongly confirms cardiovascular risk. We analyzed CKD patients in stages 1-3 to find risk factor relationships before the onset of severe CKD. We monitored 328 patients for 16 ± 5months. Participants were classified at baseline by estimated glomerular filtration rate (eGFR) stage: G1 (≥ 90), G2 (60-89), and G3 (30-59ml/min/1.73m2). Ultrasound-guided total plaque area tracked atherosclerosis. Age, sex, blood pressure, lipids, and HbA1c were covariates. Total plaque area and variables were measured on day 1 and at the conclusion of observation. We used a multilevel mixed effects model to assess biological and behavioral factors on total plaque area progression in the general population. For validation, this research was conducted on 73 CKD patients with optimal traditional cardiovascular risk factor management during 15 ± 5months. Multiple analyses showed an inverse relationship between eGFR decline and total plaque area progression [β-exponent = 0.99 (95% CI = 0.98-0.99)], regardless of age, lipid profile, blood pressure, smoking, diabetes, or hypertension. The correlation remainedsignificant in the 73-patient sample with optimal traditional cardiovascular risk factor management (β-exponent = 0.99; 95% CI 0.97-0.99). Although traditional cardiovascular risk factor management was excellent, total plaque area increased considerably in G2-G3 patients compared to G1. CKD, total plaque area, and eGFR are inversely correlated, independent of traditional cardiovascular risk factors, suggesting that non-traditional mechanisms are responsible for resistant atherosclerosis. The combination of eGFR and total plaque area may be useful in identifying high-risk patients.

Association between urinary heavy metal/trace element concentrations and kidney function: a prospective study

Abstract Background Chronic kidney disease (CKD) is an important public health problem. Although cross-sectional studies have identified many heavy metals/trace elements associated with reduced kidney function, prospective studies are needed to determine the pathogenic role of these elements in the development and progression of CKD. Methods To explore the association between baseline urinary heavy metal/trace element concentrations and long-term impaired kidney function (IKF)/CKD, as well as the incidence of rapid decline in kidney function in a population-based exploratory prospective study, we mean age 51.9 years at baseline) whose urinary trace elements concentrations have been determined by inductively coupled plasma mass spectrometry (ICP-MS). IKF was defined by a reduced estimated glomerular filtration rate (eGFR) between 60-90 mL/min/1.73 m2, and CKD was defined as an eGFR&amp;lt;60 mL/min/1.73 m2. Rapid eGFR decline was defined as a decrease≥3 mL/min/1.73 m2 /year. Results Over a mean follow-up of 12.5 years, 123 participants (2.6%) experienced rapid decline in kidney function, and 1455 (31.7%) developed IKF or CKD. After adjusting for covariates including baseline eGFR, we found that urinary vanadium (HR=1.07, 1.03-1.12), cobalt (HR=1.69, 1.21-2.37), nickel (HR=1.19, 1.08-1.3), copper (HR=1.03, 1.01-1.06), selenium (HR=1.33, 1.02-1.73), molybdenum (HR=1.48, 1.2-1.82) and iodine (HR=1.1, 1.02-1.2) were associated with an increased risk of new incident IKF or CKD cases during the follow-up. Also, urinary copper (OR=1.12, 1.04-1.21), silver (OR=1.83, 1-3.35), molybdenum (OR=1.02, 1.01-1.04) and cadmium (OR=1.05, 1.01-1.09) were associated with an increased risk of rapid eGFR decline. Conclusion In the general population, several urinary heavy metals/trace elements are associated with a rapid decline in kidney function or new cases of IKF/CKD.

Lower prognostic nutritional index is associated with a greater decline in long-term kidney function in general population

BackgroundThe prognostic nutritional index (PNI) is an integrated index of serum albumin and peripheral lymphocyte count, where low values may reflect poor nutritional status or inflammation. The long-term effect of PNI on renal function is not well known in the general population. Therefore, we investigated whether the PNI is related to renal function changes in the general population.MethodsData from participants who underwent a health check-up between 2002 and 2018 were retrospectively examined. PNI was computed by 10×serum albumin (g/dL) + 0.005×total lymphocyte count (per mm3). The primary exposure was PNI, divided into quintiles. The primary outcome was a 25% decline in eGFR from baseline over a 5-year follow-up period.ResultsThis study included 15,437 participants (mean [standard deviation, SD] age, 43.7 [7.9] years; 46% male). The median (interquartile ranges) 5-year change of eGFR was − 5.2 (− 18.8, − 3.3) mL/min/1.73m2. A total of 2,272 participants (14.7%) experienced a 25% decline in eGFR at 5 years. Compared to the highest PNI group, lower PNI groups were at greater risk for a 25% decline in eGFR; odds ratios and 95% confidence intervals were 1.42 (1.20, 1.68), 1.23 (1.04, 1.45), 1.21 (1.03, 1.43), and 1.19 (1.01, 1.40) for the first to fourth quintiles of PNI, respectively. In linear regression analyses, lower PNI groups also showed a larger decline in eGFR over 5 years compared to the highest PNI group.ConclusionsLower PNI was associated with a larger decline in renal function in the general population.

The prognostic impact of the Stress Hyperglycemia Ratio on End-Stage Renal Disease among patients with Diabetic Kidney Disease.

The Stress Hyperglycemia Ratio (SHR), a new biomarker calculated from glucose and HbA1c levels, has been linked to significant clinical outcomes in diabetes. This study investigates the potential of the SHR to predict End-Stage Renal Disease (ESRD) among patients with Diabetic Kidney Disease (DKD). We included 316 participants from the West China Hospital T2DM-DKD cohort (January 2008-September 2020), divided into three SHR tertiles: T1 (SHR <0.7), T2 (SHR ≥0.7 to <0.94) and T3 (SHR ≥0.94). A second retrospective cohort of 625 DKD patients was recruited from Sichuan University Hospital (January 2019-May 2022), with similar inclusion criteria. SHR was analysed using Restricted Cubic Spline, Kaplan-Meier curves and Cox proportional hazards models. Key confounders such as eGFR, proteinuria, hypoalbuminemia and glucose-lowering medications were adjusted for in the analysis. In Cohort 1 (median follow-up 42 months), 38.6% developed ESRD. Kaplan-Meier curves showed a higher incidence of ESRD in the lowest and highest SHR tertiles compared to the middle group (p < 0.01). Multivariate analysis confirmed that SHR <0.7 (HR 1.71, 95% CI: 1.01-2.90) and SHR ≥0.94 (HR 1.93, 95% CI: 1.16-3.20) were significantly associated with ESRD. In Cohort 2 (median follow-up 18.6 months), patients with SHR <0.7 and ≥0.94 had significantly higher risks of ≥30% eGFR decline or ESRD, with adjusted HRs of 2.18 (95% CI: 1.15-4.11) and 2.68 (95% CI: 1.38-5.23), respectively. This study observed a U-shaped relationship between SHR and ESRD in patients with DKD. Both very high and very low SHR values correlate with increased risks, highlighting the critical importance of glucose management in chronic diabetes care.

Associations between plasma osteopontin, sex, and 2-year global and cardiorenal outcomes in older outpatients screened for CKD: a secondary analysis of the SCOPE study

Abstract Background plasma osteopontin is a promising aging-related biomarker among individuals with and without kidney disease. The interaction between sex, pOPN levels, and global and cardio-renal outcomes among older individuals was not previously evaluated. Methods In this study we investigated the association of pOPN with 24-month global, major cardiovascular events (MACEs), MACE + cardiovascular (CV) mortality, and renal decline among older individuals; we also evaluated whether sex modified observed associations. pOPN levels were measured in a cohort of 2 013 outpatients (908 men and 1 105 women) aged 75 years or more enrolled in the context of a multicenter prospective cohort study in Europe. Multivariable linear regression, Cox and Fine Gray models, and linear mixed regression models were fitted to evaluate whether sex modified the associations between biomarkers and study outcomes. Results 2 013 older participants with a median age of 79 years, and 54.9% women were included in the study; increased pOPN levels were associated with all-cause mortality specifically among women (reduced fully-adjusted model resulting from backward selection, HR, 95%CI: 1.84, 1.20–2.89). Addition of pOPN to models containing age, eGFR, and ACR improved time-dependent AUC at 6, 12, and 24 months, among women only. No significant association was found between the biomarker levels, MACE, and MACE + CV mortality. Conversely, increased baseline pOPN was associated with eGFR decline in all patients (-0.45, 95%CI:-0.68 to -0.22 ml/min/1.73 m2 year) but with slightly steeper declines in women compared to men (-0.57, -0.99 to -0.15 vs -0.47, -0.88 to -0.07). Conclusions pOPN levels were significantly lower in women than in men but associated with all-cause mortality in women only; increase in serum pOPN was associated with eGFR decline over time in all patients, but with stronger associations among women. Assessment of pOPN may help identifying older female participants at risk of poor outcomes.

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.

Citrate in autosomal dominant polycystic kidney disease: biomarker or therapeutic agent?

Purpose of review This review highlights the latest findings regarding hypocitraturia in autosomal dominant polycystic kidney disease (ADPKD), from both experimental and clinical studies, exploring the underlying pathophysiology and potential therapeutic approach. Recent findings Experimental studies have shown that the lodging of microcrystals in the tubules can trigger cyst formation and growth in polycystic kidney disease (PKD). ADPKD patients are prone to developing hypocitraturia in early stages, which could predispose to calcium microcrystal formation. Low urinary citrate excretion has been associated with a more rapid decline in eGFR and poorer renal survival in ADPKD patients. Animal studies employing citrate supplementation have shown promising effects on preserving the decline in estimated glomerular filtration rate (eGFR) and cyst growth. Summary Current knowledge suggests that urinary citrate could be incorporated into existing prognostic markers for disease progression and potential adjuvant therapy in ADPKD, but further clinical studies to support such hypothesis must be undertaken.

Impact of arteriovenous fistula formation on trajectory of kidney function decline: a target trial emulation

Abstract Background Prior nonrandomised studies have suggested nephroprotective effects of arteriovenous fistula (AVF) formation, but these are plausibly susceptible to immortal time and selection biases. Methods We studied patients attending nephrology clinics in the West of Scotland during 2010-2022 with an eGFR ≤15mL/min/1.73m2 and no prior AVF. Using target trial emulation and a sequential trial design, we simulated a hypothetical trial that would randomise patients to either undergo AVF formation immediately or not to undergo AVF formation. The primary outcome was the difference in eGFR slope for the first six months of follow-up, estimated using a mixed-effects model. The secondary outcomes were 5-year absolute risks of dialysis and death, estimated using the Aalen-Johansen and Kaplan-Meier estimators respectively. Results 1,364 unique patients (mean age 51.1, 55.7% male) contributed 3,125 person-trials, with 561 in the AVF and 2,564 in the no AVF group. Mean eGFR was 12.6mL/min/1.73m2 and the median number of eGFR measurements per person-trial was 7 (IQR 4 – 12). Slope of eGFR decline did not differ significantly between the AVF and no AVF groups (between group difference -0.67mL/min/1.73m2/year, 95%CI -1.43, 0.10). The 5-year absolute risk of dialysis was 87% (95%CI 84, 91) in the AVF group and 75% (95%CI 73, 77) in the no AVF group and the 5-year survival probability was 77% (95%CI 70, 83) in the AVF group and 67% (95%CI 64, 69) in the no AVF group. Conclusions In this study of patients with advanced CKD, there was no evidence of a nephroprotective effect of AVF formation.

Primary glomerular diseases and long-term adverse health outcomes: A nationwide cohort study.

Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide, little is known about their long-term outcomes. In patients with chronic kidney disease (CKD) stage 3-5 enrolled in the Swedish Renal Registry, we compared risks of hospitalization, kidney replacement therapy (KRT), major cardiovascular events (MACE), and death of the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD], and membranous nephropathy [MN]), and patients with CKD due to the most common non-communicable diseases (control-CKD). We identified 2396 patients with glomerular disease (97% biopsy-proven, 69% men, 57 years, eGFR 29mL/min/1.73m2, uACR 88mg/mmol, 1524 with IgAN, 398 FSGS, 94 MCD, and 380 MN) and 37,697 controls (64% men, 74 years, eGFR 25mL/min/1.73m2, uACR 23mg/mmol), mainly with diabetic nephropathy and nephroangiosclerosis. The median follow-up was 6.3 (3.3; 9.9) years. Compared with control-CKD, patients with primary glomerular diseases generally had a lower risk of hospitalization, MACE (adjusted hazard ratios [HRs] ranging from 0.44 to 0.88 depending on the etiology) and death (HRs ranging 0.45-0.76). Patients with IgAN and FSGS had a faster eGFR decline and a higher rate of KRT (HRs 1.26 [95%CI: 1.15-1.37] and 1.34 [1.15-1.57], respectively). Conversely, patients with MN and MCD had a lower KRT rate and slower eGFR decline. Despite having a lower relative risk of hospitalization, cardiovascular events and mortality, patients with IgAN and FSGS are at higher risk of CKD progression than the most common etiologies of CKD, emphasizing the need for more stringent treatment strategies in these patients.

Abstract 4136289: Aortic Valve Calcium as a Predictor of Chronic Kidney Disease in a Multi-Ethnic Cohort: The MESA Study

Background: Aortic valve calcium (AVC) is associated with an increased risk of cardiovascular disease, non-cardiovascular disease such as dementia, and all-cause mortality. Traditional atherosclerotic cardiovascular disease risk factors are associated with both AVC and chronic kidney disease (CKD), but whether there is an association between AVC and CKD is unknown. Objectives: To ascertain whether AVC quantified by cardiac CT scanning is independently associated with the long-term risk of incident CKD among individuals without a previous history of cardiovascular disease. Methods: We examined 6,346 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac CT scanning at Visit 1 (2000-02) and had an eGFR of ≥ 60 mL/min/1.73 m 2 . AVC was quantified using the Agatston method and categorized as 0, 1-99, and ≥100. Incident CKD was defined as an eGFR &lt; 60 mL/min/1.73 m 2 accompanied with an at least 40% decline in eGFR from baseline, and/or a diagnosis of CKD and indicators of end stage renal disease extracted from hospital records using the International Classification of Disease (ICD) codes. We performed Kaplan-Meier survival curve analyses along with multivariable Cox proportional hazard regression models, adjusted for age, gender, race/ethnicity, highest level of education and traditional cardiovascular risk factors along with coronary artery calcium (CAC), lipoprotein (a) (Lp[a]), and the APOE-ε4 genotype to examine the association between AVC (categorical and log-transformed) and incident CKD. Results: Participants had a mean age 62.2±10.1 years, 53% were women, and AVC &gt;0 was present in 795 (12%) participants. During a median follow-up time of 16.9 years, 982 (15%) participants developed incident CKD. AVC examined as a continuous variable was associated with a significantly increased risk of developing CKD (per log-unit [AVC+1] HR 1.06 [95% CI: 1.02-1.10]; p = 0.005). There was a stepwise increased risk for CKD with higher AVC levels ( Figure ). Similarly, in the multivariable adjusted Cox models, participants with AVC ≥100 had a higher risk of incident CKD, compared with the AVC=0 group (HR 1.48 [95% CI: 1.15-1.89]; p = 0.002). The observed associations remained after further adjusting for CAC score ( p = 0.024), Lp (a) ( p = 0.004), and the APOE-ε4 genotype ( p = 0.004). Conclusions: In a multi-ethnic cohort of participants free of CKD at baseline, AVC was independently associated with a higher risk of incident CKD.

A systematic review and meta-analysis of factors contributing to post-kidney transplant anemia and the effect of erythropoietin-stimulating agents

BackgroundThe effects of various risk and associated factors on post-kidney transplant anemia (PTA) have not been fully compared and estimated. This meta-analysis aims to elucidate factors contributing to PTA and determine the influence of erythropoietin-stimulating agents (ESAs) on renal outcomes, thus offering potential pathways for enhanced management strategies post-transplant.MethodsA systematic review was conducted in electronical database. Studies reporting on risk factors (with cause-effect relationships) and associated factors (without definite cause-effect relationships) of PTA, and the effects of ESAs on post-kidney transplant outcomes, were included. Pooled odds ratios (ORs) and weighted mean differences (WMDs) were analyzed using random-effects models.ResultsThis systematic review encompassed 38,233 patients from 85 studies. Factors increased PTA risk included African American, older donor age, human antigen leukocyte mismatches, and low pre-transplant hemoglobin levels. Poor allograft function, high interleukine-6, Cytomegalovirus, delayed graft function, allograft rejections, immunosuppressive medications, and renin-angiotensin system blockades were associated with PTA. Native autosomal dominant polycystic kidney disease was a protective factor against PTA. Administration of ESAs with the aim of normalizing hemoglobin levels in patients with chronic allograft dysfunction slowed the decline in eGFR and reduce the risk of death, with a pooled OR of 0.36 (95% CI: 0.14 to 0.89; p = 0.040).ConclusionsThe risks and associated factors for PTA have been elucidated, underscoring the need for individualized treatment approaches. Late ESA therapy, aimed at hemoglobin normalization, suggests a renal-protective effect and reduced mortality, which should be considered in the management of PTA.Systematic review registrationPROSPERO CRD42024545330.

Abstract 4117397: SGLT2i And Cardio-Renal Outcomes In Type 2 Diabetes Mellitus: A Systematic Review And Meta Analysis.

Background: Diabetes Mellitus (DM) significantly impacts global health through cardiovascular and renal complications. SGLT2 inhibitors (SGLT2i) have emerged as beneficial for cardiovascular outcomes in Type 2 Diabetes Mellitus (T2DM). However, only few studies report outcomes related to renal function. Aim: This study aims to analyse the efficacy of SGLT2i on cardiorenal outcomes in adults with T2DM. Methods: A systematic review and meta-analysis, following PRISMA-2020 guidelines was conducted. We evaluated the efficacy of SGLT2i on cardiorenal outcomes in adults with T2DM. We included randomized controlled trials(RCT) and post hoc analyses that compared SGLT2i with placebo, focusing on cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalizations, and renal outcomes such as the progression of albuminuria and the decline of eGFR. Dichotomous outcomes were calculated using relative risk (RR) with 95% confidence interval (CI). Results: We identified 2753 studies, registered in PubMed(=788), Embase(n=538), WoS(n=369), Scopus(n=908), and Cochrane(n=150). We included 11 studies 6 RCT and 7 Post Hoc Analysis, sample size of 50.653 patients. Meta-analysis showed that SGLT2i improve cardiovascular outcomes such as reduced cardiovascular mortality (RR 0.84 [95% CI 0.73–0.97] p=0.02), heart failure hospitalizations (RR 0.65 [95%CI 0.54–0.77]p&lt;0.00001), and their composites outcomes. Furthermore, renal outcomes with SGLT2i significantly improve Urinary Albumin-to-Creatinine Ratio (RR1.10 [95%CI 1.03–1.18]p=0.004), Improvement of the decline of the eGFR (RR1.08 [95%CI 1.04–1.11] p&lt;0.00001) and progression of albuminuria (RR 0.69[95%CI 0.66–0.72]p&lt;0.00001). Slower Doubling of serum creatinine (RR 0.71 [95% CI 0.61–0.82] p&lt;0.00001), end-stage kidney disease (RR 0.66 [95% CI 0.53–0.83] p=0.0003). Reduced Acute Kidney Injury (RR 0.72 [95% CI 0.58–0.89] p=0.002) and renal impairment (RR 0.57 [95% CI 0.34–0.95] p=0.03). Regarding death from renal causes, we identified a 46% relative reduction in the risk in SGLT2i group, although was not statistically significant (RR 0.54 [95% CI: 0.23, 1.27] p=0.16). The observed heterogeneity across studies calls for careful application of these results to individual patients. Conclusion: SGLT2i confers notable advantages in managing cardiorenal complications in T2DM, demonstrating a reduction in cardiovascular mortality and heart failure hospitalizations and offering a nephroprotective effect.

Kidney hyperfiltration and mitochondrial changes are associated with eGFR decline in young people with type 1 diabetes.

To examine the relationship between kidney hyperfiltration during adolescence and subsequent changes in estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR) in a young cohort of participants with type 1 diabetes. Additionally, to explore urinary mitochondrial DNA:nuclear DNA ratio (mtDNA:nDNA) as a marker of metabolic stress and its association with early changes in kidney function. Eighty adolescents were studied at baseline [mean (SD) age 14.2 (1.5) years; mean diabetes duration 6.7 (3.0) years] and followed up 9.2 (1.3) years later. Blood pressure, HbA1c, lipids, eGFR, UACR and heart rate variability were assessed at each visit. Urinary mtDNA:nDNA was measured by quantitative PCR (qPCR). Overall, 4.2% of participants had diabetic kidney disease (DKD) at follow-up. Hyperfiltration at baseline (>135 mL/min/1.73m2) was seen in 31% of adolescents and was associated with a decline in eGFR at follow-up when adjusted for sex, diabetes duration and HbA1c [hyperfiltration -1.46 (3.07) mL/min/1.73 m2/year vs non-hyperfiltration -0.51 (2.48) mL/min/1.73m2/year, P=0.02]. Participants with hyperfiltration also had higher odds of undergoing rapid eGFR decline (>3 mL/min/1.73m2/year) compared to those without hyperfiltration [OR 14.11, 95% CI (2.30-86.60), P=0.004]. Baseline urinary mtDNA:nDNA was significantly associated with both greater annual rate of eGFR decline and rapid eGFR decline in univariable but not multivariable modelling. Hyperfiltration during adolescence is significantly associated with greater reduction in eGFR and higher risk of rapid eGFR decline after ∼9 years, following transition into young adulthood in type 1 diabetes. Urinary mtDNA:nDNA measured during adolescence may be a novel predictor of early changes in kidney function.

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.

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