Risk Of End-stage Renal Disease Research Articles

#1672 High level of HDL-C is associated with a higher risk of ESRD and all-cause mortality in patients with DM and CKD

Abstract Background and Aims Previous studies have regarded high-density lipoprotein cholesterol (HDL-C) as ‘good cholesterol’; however, recent research has unveiled a higher incidence of adverse events among individuals with extremely elevated HDL-C levels. Method Two cohorts of subjects were analyzed in this study. In the first cohort, a total of 375 participants with DKD who underwent renal-biopsy between January 2008 and September 2020, from West China Hospital T2DM-DKD cohort, were enrolled for the longitudinal observational study. Additionally, 3,262 participants with DM and chronic kidney disease (CKD) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included. Kaplan-Meier curves and Cox proportional hazard models were used to analyze the association between HDL-C concentration and the incidence of end-stage renal disease (ESRD) as well as all-cause mortality. Results Patients were divided into three groups based on HDL-C levels. After a median follow-up of 36 months, 44% of the patients developed ESRD in T2DM-DKD cohort. Patients in Group 3 (HDL-C ≥1.55 mmol/L) exhibited a higher risk of ESRD compared to Group 1 (HDL-C <1.03 mmol/L). After adjusting for confounders, Group 3 patients still had a significantly higher risk of ESRD (adjusted HR: 1.68, 95% CI: 1.03, 2.71). Analysis of HDL subfractions revealed that a higher HDL3/HDL2 ratio was associated with a lower risk of ESRD. Furthermore, in the NHANES cohort, higher HDL-C levels were linked to a higher risk of all-cause mortality during a median follow-up of 75 months as the result of the weighted Kaplan-Meier curves (p = 0.02). Notably, in patients with CKD stages 1-2, Group 3 participants had a significantly higher hazard ratio (HR: 1.61, 95% CI: 1.19, 2.19) after adjusting for confounders. Conclusion This study challenges the notion of HDL-C as ‘good cholesterol’ in patients with DKD, as higher HDL-C levels were associated with increased risks of ESRD and all-cause mortality. Additionally, the study highlights the potential protective effect of a higher HDL3/HDL2 ratio against ESRD. These findings contribute to reevaluating the role of HDL-C and its subfractions in DKD patients.

#209 Relation between exercise pattern changes and renal outcome in new-onset diabetes: a nationwide population-based study

Abstract Background and Aims Exercise reduced risk of diabetes and obesity. However, it remains unclear whether the pattern changes of exercise are increased risk of end-stage renal disease in new-onset diabetes mellitus (DM) patients. Method We assessed diabetes development in 2015 in 21,122,422 non-diabetic Koreans enrolled in Korean National Health Screening (KNHS) from 2009 to 2012 using International Classification of Diseases 10th (ICD-10) code and anti-diabetic medication prescription. Renal outcome (End-stage renal disease) was defined using V-code. The risk of ESRD evaluated in never exercise (none), after new-onset DM (post only), before new-onset DM and no exercise after new-onset DM (pre-only) and persistent exercise group (persistent group). Results During median 4.8-year follow-up, 275 (0.21%) of ESRD was occurred. After fully adjusted, the hazard ratio (HR) for ESRD was lowest in persistent exercise group 0.521 [0.302 to 0.899]. Post only exercise 0.674 [0.461 to 0.985] group showed better renal outcome compared to pre only exercise group 0.791 [0.535 to 1.169] or never exercise group [reference, 1.0]. Subgroup analysis for age, sex, history of chronic kidney disease, hypertension showed similar results. Even light exercise such as walking tended to reduce the risk of renal outcome 0.817 [0.634 to 1.037]. The higher 0.627 [0.441 to 0.892] or moderate 0.7 [0.514 to 0.953] strength of exercise type showed the lower risk of renal outcome in new-onset DM patients. Conclusion This study provides compelling evidence that exercise, particularly when maintained over time, is associated with a substantial reduction in the risk of ESRD in individuals with new-onset DM. These findings underscore the importance of incorporating regular physical activity as a crucial component of comprehensive health management strategies for individuals with diabetes, offering both clinicians and patients valuable insights for optimizing renal outcomes.

#2487 Deleterious renal outcome in patients with thrombotic microangiopathy after lung transplantation: the lung TMA trial

Abstract Background and Aims Thrombotic microangiopathy (TMA) is a rare but severe complication following lung transplantation. The pathogenesis is poorly understood, involving endothelial damage and various risk factors, including calcineurin inhibitor (CNI) toxicity. We aimed to evaluate diagnostic accuracy, identify risk factors for and assess the renal and overall survival of TMA in this patient group. Method We performed a retrospective study of patients with TMA after lung transplant between 01/01/2000-01/01/2021. Matching controls were selected based on underlying lung disease, age, gender, CMV risk, and immunosuppressive regimen. Overall survival and baseline data (age, gender) were collected for the whole lung transplant group. Results A total of 29 TMA cases (2.9%) were identified out of 1025 lung transplantations. 48% of patients had a complete hematological assessment with Coombs testing as the most frequent (52%) missing test. The median time from transplantation to TMA was 5.9 months. 76% of the episodes occurred before 12 months. 77% of patients had organ damage with acute kidney injury in 72%. At the time of TMA 38% of patients had a cytomegalovirus (CMV) infection. Arterial hypertension was found in 31% and acute rejection in 11%. The immunosuppressive scheme consisted of tacrolimus/mycophenolate mofetil and corticosteroids in the majority of cases (56%). Tacrolimus (n = 22) and cyclosporine (n = 7) trough levels were respectively 11.8 and 207 µg/l at the time of TMA. Treatment consisted of change in immunosuppressive regimen (72%), 31% received plasmapheresis. When comparing the TMA patients with the control group a higher rate of donor specific antibodies were found (11% vs 1%), a lower median time till chronic lung allograft dysfunction (37 m vs 91 m) and a higher prevalence of end-stage renal disease (24% vs 6%) and overall death (97% vs 44%) with mortality being significantly higher (p < 0.01). Fig. 1 illustrates the overall outcome. Conclusion This study illustrates the clinical characteristics and outcomes of TMA after lung transplantation. Even though the prevalence is low the effects are deleterious with acute kidney injury in the majority of cases and higher risk of end-stage renal disease and mortality. Our study emphasizes the need for higher further research into risk factors, and therapeutic strategies to prevent and improve patient outcomes. Furthermore, the findings underscore the importance of vigilant monitoring and tailored interventions for TMA in lung transplant patients.

#1253 Predicting renal outcomes in ANCA-associated vasculitis—validation of ANCA Renal Risk Score in a Portuguese cohort

Abstract Background and Aims Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare cause of glomerulonephritis and clinical presentation can be diverse. Despite recent developments in immunosuppressive treatments, AAV with renal involvement is still associated with poor renal prognosis and a high risk of end-stage renal disease (ESRD). Kidney biopsy confirms the diagnosis, details the degree of active inflammation and chronicity of disease, also informing of renal prognosis. Berden histological classification categorizes renal histological findings into four classes but the ability to accurately predict renal outcomes varies among studied cohorts. In 2018 Brix et al developed and validated a new risk score, ANCA Renal Risk Score (ARRS), to determine renal outcomes based on histopathological and clinical indicators, with accurate ESRD prediction at 36 months. This study aims to assess the predictive value of ARRS in renal survival on a Portuguese cohort with newly diagnosed AAV with kidney involvement. Method We designed a retrospective study examining ANCA vasculitis in native kidney biopsies evaluated in a Portuguese kidney histomorphology-dedicated center between 2004 and 2023. Data collected from biopsies included percentage of normal glomeruli (PNG) and interstitial fibrosis/tubular atrophy (IFTA). Clinical and demographical data was also collected, including age, sex, estimated glomerular filtration rate (eGFR) at presentation, date of diagnosis, ESRD and date of death. We calculated ARRS based on eGFR, PNG and IFTA, and patients were classified as being at low, intermediate and high risk of developing ESRD by 36 months. Primary endpoint was established as difference in kidney survival at 36 months. Secondary endpoint included difference in overall survival at 36 months and the contribution of each of the ARRS parameters in a Cox regression model. Results A total of 143 patients were obtained, 46.2% female, with a mean age at diagnosis of 67.1 years. There was a predominancy of MPO-related disease (77.2%) and 69% presented with rapidly progressive renal insufficiency. Median ARRS was 6.5, with 10.8%, 44.3% and 44.9% classified as low, intermediate, and high risk, respectively. Kaplan Meier estimates for renal survival computed at 36 months revealed an overall mean time to dialysis of 20 months, which decreased with an increase in risk category [33.4 (low risk), 24.7 (intermediate risk), 12.7 months (high risk), Log-R test: χ2(2) = 24.9, p < 0.001] with an ESRD survival of 92.9%, 63.6% and 29.7% at 36 months, respectively. Regarding secondary endpoints, overall survival at 36 months was not different between groups [33.7 (low risk) vs. 33.2 (intermediate risk) vs. 32.2 months (high risk), Log-R test: χ2(2) = 0.3, p = 0.9]. Cox regression, plotted for ESRD at 36 months using the three score variables, revealed eGFR at presentation as the strongest predictor of kidney survival (HR: 0.96, 95% CI: 0.93-0.99, p = 0.004) whereas PNG and IFTA did not achieve significance (p = 0.189 and p = 0.066, respectively). Conclusion Our results corroborate Brix et al ARRS, accurately predicting ESRD in a Portuguese cohort of patients with renal involvement by ANCA vasculitis. Patients assessed as high-risk of developing ESRD had a lower mean time to dialysis, although overall survival did not differ between groups. Contrary to Brix et al findings, which revealed PGN as the only independent predictor of ESRD, in our study lower eGFR at the time of diagnosis was an independent risk factor. Type of immunosuppression used in each patient was not considered in this study and could maybe alter results of renal and overall survival. Despite this, Brix et al reported that, in their population, validity of ARRS was not influenced by immunosuppressive treatment. This new scoring system still requires validation in a larger cohort, but results seem promising and, in the future, may aid clinicians with treatment decisions. This is relevant since full immunosuppression induction schemes may be halted in patients with high probability of ESRD, diminishing infectious complications and potentially decreasing morbidity and mortality associated with AAV.

#991 Estimated small dense low-density lipoprotein-cholesterol and the risk of renal and cardiovascular outcomes in diabetic kidney disease

Abstract Background and Aims This study aimed to investigate the correlations between estimated small dense low-density lipoprotein-cholesterol (esd-LDL-c) and the development of end-stage renal disease (ESRD), cardiovascular mortality, and all-cause mortality in individuals with diabetic kidney disease (DKD) or diabetes mellitus (DM) concomitant chronic kidney disease (CKD). Method We analyzed the data from a biopsy-proven DKD cohort conducted at West China Hospital of Sichuan University between 2009 and 2021 (the DKD cohort) and the participants with DM and CKD in the NHANES 2011-2014 (the NHANES DM-CKD cohort). Cox regression analysis was used to estimate associations between esd-LDL-c and the incidence of ESRD, cardiovascular mortality, and all-cause mortality. Results There were 175 ESRD events among 338 participants in the DKD cohort. Patients were divided into three groups based on esd-LDL-c tertiles (T1<33.7 mg/dL, T2≥33.7 mg/dL to <45.9 mg/dL, T3≥45.9 mg/dL). The highest tertile of esd-LDL-c was independently associated with ESRD (adjusted HR 2.016, 95% CI 1.144–3.554, P = 0.015). There were 99 death (39 cardiovascular) among 293 participants in the NHANES DM-CKD cohort. Participants were classified into three groups in line with the tertile values of esd-LDL-c in the DKD cohort. The highest tertile of esd-LDL-c was independently associated with cardiovascular mortality (adjusted HR 2.84, 95% CI 1.02–7.97, P = 0.047) and all-cause mortality (adjusted HR 2.18, 95% CI 1.08–4.4, P = 0.029). Conclusion Higher esd-LDL-c increased the risk of ESRD in people with DKD and the risk of cardiovascular and all-cause mortality among those with DM-CKD.

#2434 Literature review on the burden of herpes zoster in patients with kidney disease—a need for earlier prevention

Abstract Background and Aims Kidney disease (KD), including end stage renal disease (ESRD), is a global health problem. Both are associated with impaired immune systems, which can lead to infections. Complications such as cardiovascular disease and various infections are leading causes of morbidity and mortality in KD patients. Notably, patients with KD have an increased risk of herpes zoster (HZ). While the link between ESRD and renal transplant with increased HZ risk is understood, knowledge gaps regarding the burden of HZ across the KD spectrum still exist. This review aims to describe the risk and impact of HZ across the KD spectrum in order to guide preventive care strategies for patients with renal diseases. Method A structured literature review was conducted in PubMed using a combination of keywords and Medical Subject Heading (MeSH) terms to identify studies related to HZ risk in adult KD patients aged ≥18 years published in the English language between 01/11/2003–31/10/2023. Data extracted from published studies included the burden of HZ infection in patients with KD (risk of HZ and related complications), impact of HZ on underlying KD, and the efficacy/effectiveness of HZ vaccines among patients with KD. Results A total of 47 studies were identified (Randomized controlled trials [RCT] = 2; observational studies = 45) in this review (Fig. 1). Included studies presented evidence from regions in Europe (n = 18), Asia (n = 17), North America (n = 7), South America (n = 1), multinational (n = 2) and Australia (n = 1); country not reported in one study. Evidence from observational studies (n = 37) reported a high risk of HZ infection and related complications, such as disseminated HZ, and recurrent HZ across the KD spectrum, including chronic KD, polycystic KD, hemodialysis, peritoneal dialysis and kidney transplant patients. Infection with HZ was reported to accelerate KD progression and increased the risk of ESRD and cardiovascular events. In general, for ESRD patients with an inpatient HZ diagnosis, mortality increased with age, followed by malnutrition and bacteremia/septicemia. Studies reporting vaccine efficacy (n = 2) and effectiveness results (n = 8) suggest that HZ vaccination was associated with a reduced risk of HZ when compared to unvaccinated individuals. Furthermore, the recombinant zoster vaccine (RZV) was found to be immunogenic in kidney transplant recipients, with immunogenicity persisting through 12 months post-vaccination. An RCT post-hoc analysis showed high vaccine efficacy in patients aged ≥50 years with medical conditions at enrollment, including KD, which was consistent with the overall population. A favorable benefit-risk profile was reported in randomized and observational studies. Studies evaluating the effectiveness of the zoster live-attenuated vaccine (ZVL) found a lower risk of HZ in patients with ESRD immunized against HZ compared to unvaccinated individuals. In many countries, vaccination guidelines specifically recommended immunization of people with KD to protect against HZ. However, ZVL is contraindicated for immunocompromised (e.g. kidney transplant) patients. Conclusion Findings indicate that HZ has a significant HZ burden across the KD spectrum, which may negatively impact renal disease progression. With effective vaccines offering durable protection against HZ and its complications, the immunization of renal patients at earlier stages could enhance healthcare management and patient outcomes.

Evaluation of a proteomic signature coupled with the kidney failure risk equation in predicting end stage kidney disease in a chronic kidney disease cohort.

The early identification of patients at high-risk for end-stage renal disease (ESRD) is essential for providing optimal care and implementing targeted prevention strategies. While the Kidney Failure Risk Equation (KFRE) offers a more accurate prediction of ESRD risk compared to static eGFR-based thresholds, it does not provide insights into the patient-specific biological mechanisms that drive ESRD. This study focused on evaluating the effectiveness of KFRE in a UK-based advanced chronic kidney disease (CKD) cohort and investigating whether the integration of a proteomic signature could enhance 5-year ESRD prediction. Using the Salford Kidney Study biobank, a UK-based prospective cohort of over 3000 non-dialysis CKD patients, 433 patients met our inclusion criteria: a minimum of four eGFR measurements over a two-year period and a linear eGFR trajectory. Plasma samples were obtained and analysed for novel proteomic signals using SWATH-Mass-Spectrometry. The 4-variable UK-calibrated KFRE was calculated for each patient based on their baseline clinical characteristics. Boruta machine learning algorithm was used for the selection of proteins most contributing to differentiation between patient groups. Logistic regression was employed for estimation of ESRD prediction by (1) proteomic features; (2) KFRE; and (3) proteomic features alongside KFRE. SWATH maps with 943 quantified proteins were generated and investigated in tandem with available clinical data to identify potential progression biomarkers. We identified a set of proteins (SPTA1, MYL6 and C6) that, when used alongside the 4-variable UK-KFRE, improved the prediction of 5-year risk of ESRD (AUC = 0.75 vs AUC = 0.70). Functional enrichment analysis revealed Rho GTPases and regulation of the actin cytoskeleton pathways to be statistically significant, inferring their role in kidney function and the pathogenesis of renal disease. Proteins SPTA1, MYL6 and C6, when used alongside the 4-variable UK-KFRE achieve an improved performance when predicting a 5-year risk of ESRD. Specific pathways implicated in the pathogenesis of podocyte dysfunction were also identified, which could serve as potential therapeutic targets. The findings of our study carry implications for comprehending the involvement of the Rho family GTPases in the pathophysiology of kidney disease, advancing our understanding of the proteomic factors influencing susceptibility to renal damage.

Protocol for a systematic review of the application of the kidney failure risk equation and Oxford classification in estimating prognosis in IgA nephropathy

BackgroundIgA nephropathy (IgAN) is a common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Outcomes are highly variable and predicting risk of disease progression at an individual level is challenging. Accurate risk stratification is important to identify individuals most likely to benefit from treatment. The Kidney Failure Risk Equation (KFRE) has been extensively validated in CKD populations and predicts the risk of ESRD at 2 and 5 years using non-invasive tests; however, its predictive performance in IgAN is unknown. The Oxford classification (OC) describes pathological features demonstrated on renal biopsy that are associated with adverse clinical outcomes that may also inform prognosis. The objective of this systematic review is to compare the KFRE with the OC in determining prognosis in IgAN.MethodsA systematic review will be conducted and reported in line with PRISMA guidelines (PRISMA-P checklist attached as Additional file 1). Inclusion criteria will be cohort studies that apply the KFRE or OC to determine the risk of CKD progression or ESRD in individuals with IgAN. Multiple databases will be searched in duplicate to identify relevant studies, which will be screened first by title, then by abstract and then by full-text analysis. Results will be collated for comparison. Risk of bias and confidence assessments will be conducted independently by two reviewers, with a third reviewer available if required.DiscussionIdentifying individuals at the highest risk of progression to ESRD is challenging in IgAN, due to the heterogeneity of clinical outcomes. Risk prediction tools have been developed to guide clinicians; however, it is imperative that these aids are accurate and reproducible. The OC is based on observations made by specialist renal pathologists and may be open to observer bias, therefore the utility of prediction models incorporating this classification may be diminished, particularly as in the future novel biomarkers may be incorporated into clinical practice.Systematic review registrationPROSPERO CRD42022364569

External Validation of the International IgA Nephropathy Prediction Tool in Older Adult Patients.

The International IgA Nephropathy Prediction Tool (IIgAN-PT) can predict the risk of End-stage renal disease (ESRD) or estimated glomerular filtration rate (eGFR) decline ≥ 50% for adult IgAN patients. Considering the differential progression between older adult and adult patients, this study aims to externally validate its performance in the older adult cohort. We analyzed 165 IgAN patients aged 60 and above from six medical centers, categorizing them by their predicted risk. The primary outcome was a ≥50% reduction in estimated glomerular filtration rate (eGFR) or kidney failure. Evaluation of both models involved concordance statistics (C-statistics), time-dependent receiver operating characteristic (ROC) curves, Kaplan-Meier survival curves, and calibration plots. Comparative reclassification was conducted using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). The study included 165 Chinese patients (median age 64, 60% male), with a median follow-up of 5.1 years. Of these, 21% reached the primary outcome. Both models with or without race demonstrated good discrimination (C-statistics 0.788 and 0.790, respectively). Survival curves for risk groups were well-separated. The full model without race more accurately predicted 5-year risks, whereas the full model with race tended to overestimate risks after 3 years. No significant reclassification improvement was noted in the full model without race (NRI 0.09, 95% CI: -0.27 to 0.34; IDI 0.003, 95% CI: -0.009 to 0.019). : Both models exhibited excellent discrimination among older adult IgAN patients. The full model without race demonstrated superior calibration in predicting the 5-year risk.

Cardiorenal outcomes and mortality after sodium-glucose cotransporter-2 inhibitor initiation in type 2 diabetes patients with percutaneous coronary intervention history.

To evaluate the effects of initiating sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiorenal outcomes and mortality compared to dipeptidyl peptidase-4 (DPP-4) inhibitors as active comparators in patients diagnosed with type 2 diabetes with a history of percutaneous coronary intervention (PCI). We used an active-comparator, new-user design and nationwide data from the National Health Insurance Service in South Korea from 2014 to 2019. Of the 56 392 patients who underwent PCI, 4610 new SGLT2 inhibitor users were paired 1:1 with DPP-4 inhibitor users for analysis using propensity-score matching. During 13 708.59 person-years of follow-up, the initiation of SGLT2 inhibitors, compared with the initiation of DPP-4 inhibitors, was associated with a significantly lower risk of composite repeat revascularization, myocardial infarction, stroke, heart failure (HF), all-cause death and end-stage renal disease (ESRD). The beneficial effects of SGLT2 inhibitor use were consistent with the components of stroke, HF, all-cause death and ESRD. In the cohort that included health examination data, including anthropometric and metabolic factors, new use of SGLT2 inhibitors was associated with a significantly lower risk of HF (hazard ratio [HR] 0.574, 95% confidence interval [CI] 0.36-0.915), all-cause death (HR 0.731, 95% CI 0.567-0.942), and ESRD (HR 0.076, 95% CI 0.018-0.319). The effects of SGLT2 inhibitor use were consistent regardless of the timing of the previous PCI. The initiation of SGLT2 inhibitors in patients with type 2 diabetes and a history of PCI was significantly associated with a reduced risk of cardiorenal consequences and mortality, irrespective of time since the last PCI.

Predictive factors of developing lupus nephritis in systemic lupus erythematosus

Renal involvement is common in systemic lupus erythematosus (SLE), and even without elevated serum creatinine, there is a high proportion of abnormal urine analysis in these patients. Lupus nephritis (LN) develops early in the course of the disease in 50% of SLE patients, and end stage renal disease (ESRD) occurs in 4.3-10.1%. We performed a keyword-based literature search and included 31 articles published from 2004 to 2023. Ethnic and racial differences may affect LN, including higher incidence of LN in Black, Hispanic and Asian compared with white patients. In addition, male sex, longer disease duration, smoking, low albumin globulin ratio, low complement, anti-double stranded DNA, high anti-Sm is associated with disease progression to LN. High serum creatinine (>1.5 mg/dL) at disease onset is the most commonly reported independent clinical laboratory predictor for ESRD in patients with SLE. Other factors indicating an increased risk for ESRD are higher chronicity index, high systolic blood pressure, black race, male sex, hypocomplementemia, class of LN (III, IV and V) and older age.

A new index for the outcome of focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is a common pathological form of nephrotic syndrome. This study analyzed the value of pathological lesions and clinical prognosis of different segmental glomerulosclerosis ratios in FSGS. Two hundred and six FSGS patients were collected from Dec 2013 to Apr 2016. The patients were divided into two groups according to the proportion of glomerular segmental sclerosis: F1 (SSR ≤ 15%, n = 133) and F2 (SSR > 15%, n = 73). The clinical and pathological data were recorded and analyzed, and statistical differences were observed between the serum uric acid level and the percentage of chronic renal failure. The pathological results showed significant differences in interstitial fibrosis and tubular atrophy (IFTA), degree of mesangial hyperplasia, vascular lesions, synaptopodin intensity, and foot process effacement between the two groups. Multivariate logistic regression analysis showed significant differences in creatinine (OR: 1.008) and F2 group (OR: 1.19). In all patients, the prognoses of urine protein and serum creatinine levels were statistically different. Multivariate Cox regression analysis revealed that F2 (hazard ratio: 2.306, 95% CI 1.022–5.207) was associated with a risk of ESRD (end stage renal disease). The proportion of segmental glomerulosclerosis provides a guiding value in the pathological diagnosis and clinical prognosis of FSGS.

Native T1-mapping as a predictor of progressive renal function decline in chronic kidney disease patients

BackgroundTo investigate the potential of Native T1-mapping in predicting the prognosis of patients with chronic kidney disease (CKD).MethodsWe enrolled 119 CKD patients as the study subjects and included 20 healthy volunteers as the control group, with follow-up extending until October 2022. Out of these patients, 63 underwent kidney biopsy measurements, and these patients were categorized into high (25–50%), low (< 25%), and no renal interstitial fibrosis (IF) (0%) groups. The study's endpoint event was the initiation of renal replacement therapy, kidney transplantation, or an increase of over 30% in serum creatinine levels. Cox regression analysis determined factors influencing unfavorable kidney outcomes. We employed Kaplan–Meier analysis to contrast kidney survival rates between the high and low T1 groups. Additionally, receiver-operating characteristic (ROC) curve analysis assessed the predictive accuracy of Native T1-mapping for kidney endpoint events.ResultsT1 values across varying fibrosis degree groups showed statistical significance (F = 4.772, P < 0.05). Multivariate Cox regression pinpointed 24-h urine protein, cystatin C(CysC), hemoglobin(Hb), and T1 as factors tied to the emergence of kidney endpoint events. Kaplan–Meier survival analysis revealed a markedly higher likelihood of kidney endpoint events in the high T1 group compared to the low T1 value group (P < 0.001). The ROC curves for variables (CysC, T1, Hb) tied to kidney endpoint events demonstrated area under the curves(AUCs) of 0.83 (95%CI: 0.75–0.91) for CysC, 0.77 (95%CI: 0.68–0.86) for T1, and 0.73 (95%CI: 0.63–0.83) for Hb. Combining these variables elevated the AUC to 0.88 (95%CI: 0.81–0.94).ConclusionNative T1-mapping holds promise in facilitating more precise and earlier detection of CKD patients most at risk for end-stage renal disease.

Prediction of cardiovascular and renal risk among patients with apparent treatment-resistant hypertension in the United States using machine learning methods.

Apparent treatment-resistant hypertension (aTRH), defined as blood pressure (BP) that remains uncontrolled despite unconfirmed concurrent treatment with threeantihypertensives, is associated with an increased risk of developing cardiovascular and renal complications compared with controlled hypertension. We aimed to identify the characteristics of aTRH patients with an elevated risk of major adverse cardiovascular events plus (MACE+; defined as stroke, myocardial infarction, or heart failure hospitalization) and end stage renal disease (ESRD). This retrospective cohort study included aTRH patients (BP ≥140/90mmHg and taking ≥3antihypertensives) from the United States-based Optum® de-identified Electronic Health Record dataset and used machine learning models to identify risk factors of MACE+ or ESRD. Patients had claims for ≥3antihypertensive classes within 30 days between January 1, 2015andJune 30, 2021, and two office BP measures recorded 1-90 days apart within 30 days to 11 months after the index regimen date. Of a total 18797 070 patients identified with any hypertension, 71100 patients had aTRH. During the study period (mean 25.5 months), 4944 (7.0%) patients had a MACE+ and 2403 (3.4%) developed ESRD. In total, 22risk factors were included in the MACE+ model and 16 in the ESRD model, and most were significantly associated with study outcomes. The risk factors with the largest impact on MACE+ risk were congestive heart failure, stages 4 and 5 chronic kidney disease (CKD), age ≥80years, and living in the Southern region of the United States. The risk factors with the largest impact on ESRD risk, other than pre-existing CKD, were anemia, congestive heart failure, and type 2 diabetes. The overall study cohort had a 5-year predicted MACE+ risk of 13.4%; this risk was increased in those in the top 50% and 25% high-risk groups (21.2% and 29.5%, respectively). The overall study cohort had a predicted 5-year risk of ESRD of 6.8%, which was increased in the top 50% and 25% high-risk groups (10.9% and 17.1%, respectively). We conclude that risk models developed in our study can reliably identify patients with aTRH at risk of MACE+ and ESRD based on information available in electronic health records; such models may be used to identify aTRH patients at high risk of adverse outcomes who may benefit from novel treatment interventions.

Long-term ozone exposure and mortality in patients with chronic kidney disease: a large cohort study

BackgroundEpidemiologic studies on the effects of long-term exposure to ozone (O3) have shown inconclusive results. It is unclear whether to O3 has an effect on chronic kidney disease (CKD). We investigated the effects of O3 on mortality and renal outcome in CKD.MethodsWe included 61,073 participants and applied Cox proportional hazards models to examine the effects of ozone on the risk of end-stage renal disease (ESRD) and mortality in a two-pollutants model adjusted for socioeconomic status. We calculated the concentration of ozone exposure one year before enrollment and used inverse distance weighting (IDW) for interpolation, where the exposure was evenly distributed.ResultsIn the single pollutant model, O3 was significantly associated with an increased risk of ESRD and all-cause mortality. Based on the O3 concentration from IDW interpolation, this moving O3 average was significantly associated with an increased risk of ESRD and all-cause mortality. In a two-pollutants model, even after we adjusted for other measured pollutants, nitrogen dioxide did not attenuate the result for O3. The hazard ratio (HR) value for the district-level assessment is 1.025 with a 95% confidence interval (CI) of 1.014–1.035, while for the point-level assessment, the HR value is 1.04 with a 95% CI of 1.035–1.045. The impact of ozone on ESRD, hazard ratio (HR) values are, 1.049(95%CI: 1.044–1.054) at the district unit and 1.04 (95%CI: 1.031–1.05) at the individual address of the exposure assessment. The ozone hazard ratio for all-cause mortality was 1.012 (95% confidence interval: 1.008–1.017) for administrative districts and 1.04 (95% confidence interval: 1.031–1.05) for individual addresses.ConclusionsThis study suggests that long-term ambient O3 increases the risk of ESRD and mortality in CKD. The strategy to decrease O3 emissions will substantially benefit health and the environment.

The effectiveness of extended postpartum comprehensive health care bundle selected outcomes of women with preeclampsia at 6 months: protocol of a randomized controlled trial

Background: Women who have experienced pre-eclampsia (PE) may also face additional health problems in later life, as the condition is associated with an increased risk of death from 2-fold increased risk of long-term cardiovascular disease (CVD), hypertension, stroke, an approximate 5-12-fold increased risk of end-stage renal disease (ESRD), metabolic syndrome, and diabetes. Methods: Method was randomized controlled trial. Women with PE who delivered in PGIMER will be enrolled and will be allocated into experimental ad control group using a computer random table with allocation concealment. Enrolment will be done at the time of discharge; baseline assessment will be done 6 weeks and the intervention bundle will be implemented to the women in experimental group. The women in control group will receive routine care. Women in both the groups will be followed up at 6 months. Conclusions: This study aims to determine the effectiveness of “extended postpartum comprehensive health care bundle (EP CHC bundle)” on selected outcomes of women with preeclampsia at 6 months. The comprehensive health care bundle will be designed with the inputs from all stakeholders, has the potential to suit the dynamic nature of management of women with preeclampsia after delivery. CTRI registration number: CTRI/2021/04/032749 ON 12/4/2021

Causal factors of cardiovascular disease in end-stage renal disease with maintenance hemodialysis: a longitudinal and Mendelian randomization study.

The risk factors of cardiovascular disease (CVD) in end-stage renal disease (ESRD) with hemodialysis remain not fully understood. In this study, we developed and validated a clinical-longitudinal model for predicting CVD in patients with hemodialysis, and employed Mendelian randomization to evaluate the causal 6study included 468 hemodialysis patients, and biochemical parameters were evaluated every three months. A generalized linear mixed (GLM) predictive model was applied to longitudinal clinical data. Calibration curves and area under the receiver operating characteristic curves (AUCs) were used to evaluate the performance of the model. Kaplan-Meier curves were applied to verify the effect of selected risk factors on the probability of CVD. Genome-wide association study (GWAS) data for CVD (n = 218,792,101,866 cases), end-stage renal disease (ESRD, n = 16,405, 326 cases), diabetes (n = 202,046, 9,889 cases), creatinine (n = 7,810), and uric acid (UA, n = 109,029) were obtained from the large-open GWAS project. The inverse-variance weighted MR was used as the main analysis to estimate the causal associations, and several sensitivity analyses were performed to assess pleiotropy and exclude variants with potential pleiotropic effects. The AUCs of the GLM model was 0.93 (with accuracy rates of 93.9% and 93.1% for the training set and validation set, sensitivity of 0.95 and 0.94, specificity of 0.87 and 0.86). The final clinical-longitudinal model consisted of 5 risk factors, including age, diabetes, ipth, creatinine, and UA. Furthermore, the predicted CVD response also allowed for significant (p < 0.05) discrimination between the Kaplan-Meier curves of each age, diabetes, ipth, and creatinine subclassification. MR analysis indicated that diabetes had a causal role in risk of CVD (β = 0.088, p < 0.0001) and ESRD (β = 0.26, p = 0.007). In turn, ESRD was found to have a causal role in risk of diabetes (β = 0.027, p = 0.013). Additionally, creatinine exhibited a causal role in the risk of ESRD (β = 4.42, p = 0.01). The results showed that old age, diabetes, and low level of ipth, creatinine, and UA were important risk factors for CVD in hemodialysis patients, and diabetes played an important bridging role in the link between ESRD and CVD.

Empagliflozin Use Is Associated With Lower Risk of All-Cause Mortality, Hospitalization for Heart Failure, and End-Stage Renal Disease Compared to DPP-4i in Nordic Type 2 Diabetes Patients: Results From the EMPRISE (Empagliflozin Comparative Effectiveness and Safety) Study.

Objective: To evaluate the effectiveness of empagliflozin in reducing all-cause mortality (ACM), hospitalization for heart failure (HHF), myocardial infarction (MI), stroke, cardiovascular mortality (CVM), and end-stage renal disease (ESRD) in routine clinical practice in the Nordic countries of the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) study. Methods: This noninterventional, multicountry cohort study used secondary data from four Nordic countries (Denmark, Sweden, Finland, and Norway). Propensity score (PS) matched (1:1) adults with type 2 diabetes (T2D) initiating empagliflozin (a sodium-glucose cotransporter-2 inhibitor) during 2014-2018 who were compared to those initiating a dipeptidyl peptidase-4 inhibitor (DPP-4i). Cox proportional hazards regression modelling was used to assess the risk for ACM, HHF, MI, stroke, CVM, and ESRD. Meta-analyses were conducted and hazard ratios (HRs) with 95% confidence intervals (CIs) from random-effects models were calculated. Results: A total of 43,695 pairs of PS-matched patients were identified. Patients initiating empagliflozin exhibited a 49% significantly lower risk of ACM (HR: 0.51, 95% CI 0.40-0.64) compared to DPP-4i. Additionally, empagliflozin was associated with a 36% significantly lower risk of HHF (HR: 0.64, 95% CI 0.46-0.89), a 52% significantly lower risk of CVM (HR: 0.48, 95% CI 0.37-0.63), and a 66% significantly lower risk of ESRD (HR: 0.34, 95% CI 0.15-0.77) compared to DPP-4i. No significant differences were observed in the risk of stroke and MI between patients initiating empagliflozin compared with those initiating a DPP-4i. Results were generally consistent for subgroups (with/without pre-existing CV disease or congestive heart failure) and in sensitivity analyses. Conclusion: Empagliflozin initiation was associated with a significantly reduced risk of ACM, HHF, CVM, and ESRD compared with initiation of DPP-4i in patients with T2D when examining routine clinical practice data from Nordic countries.

The early diagnostic value of serum renalase level in diabetic kidney disease and diabetic macroangiopathy: a retrospective case-control study.

Diabetic kidney disease (DKD) is a severe complication of diabetes mellitus and is associated with an increased risk of end-stage renal disease (ESRD) and cardiovascular events. Early diagnosis and monitoring of DKD are crucial for implementing appropriate interventions. This study aimed to investigate the relationship between serum renalase (RNLS) levels, DKD, and diabetic macroangiopathy in patients with type 2 diabetes mellitus (T2DM). This study aims to evaluate the diagnostic value of serum renalase levels in DKD and diabetic macroangiopathy. This is a retrospective case-control study. A total of 233 participants were recruited for the study, including 115 T2DM patients without DKD or diabetic retinopathy, and 118 T2DM patients with DKD. Serum RNLS levels were measured using an enzyme-linked immunosorbent assay. Kidney function parameters and diabetic macroangiopathy risk factors were evaluated in relation to serum RNLS levels. Serum RNLS levels were significantly higher in DKD patients compared to T2DM controls (34.82 (31.68, 39.37) vs 30.52 (28.58, 33.16), p < 0.01). Multiple linear regression analysis indicated that kidney function parameters and carotid intima-media thickness were independently related to RNLS levels. The study population was divided into four groups: no DKD and no diabetic macroangiopathy, DKD without diabetic macroangiopathy, diabetic macroangiopathy without DKD, and both DKD and diabetic macroangiopathy. Analysis results showed that patients with both DKD and diabetic macroangiopathy had the highest RNLS levels. Receiver operating characteristic curve analysis demonstrated the diagnostic value of RNLS for DKD (0.76 (95% confidence interval (CI) = 0.70-0.82, p < 0.01)) and diabetic macroangiopathy (0.75 (95% CI = 0.66-0.84, p < 0.01)). Circulating RNLS levels were significantly increased in patients with DKD and diabetic macroangiopathy, suggesting that RNLS may serve as an early diagnostic marker.

Delaying Renal Aging: Metformin Holds Promise as a Potential Treatment.

Given the rapid aging of the population, age-related diseases have become an excessive burden on global health care. The kidney, a crucial metabolic organ, ages relatively quickly. While the aging process itself does not directly cause kidney damage, the physiological changes that accompany it can impair the kidney's capacity for self-repair. This makes aging kidneys more susceptible to diseases, including increased risks of chronic kidney disease and end-stage renal disease. Therefore, delaying the progression of renal aging and preserving the youthful vitality of the kidney are crucial for preventing kidney diseases. However, effective strategies against renal aging are still lacking due to the underlying mechanisms of renal aging, which have not been fully elucidated. Accumulating evidence suggests that metformin has beneficial effects in mitigating renal aging. Metformin has shown promising anti-aging results in animal models but has not been tested for this purpose yet in clinical trials. These findings indicate the potential of metformin as an anti-renal aging drug. In this review, we primarily discuss the characteristics and mechanisms of kidney aging and the potential effects of metformin against renal aging.