Risk Of End-stage Renal Disease Research Articles

The role of tubulointerstitial markers in differential diagnosis and prognosis in patients with type 2 diabetes and biopsy proven diabetic kidney disease

ObjectiveTo evaluate the potential application of tubularinterstitial biomarkers in the differential diagnosis of diabetic kidney disease (DKD) from non-diabetic kidney disease (NDKD), as well as investigate key clinical and pathological parameters to help improve the stratification of patients according to end-stage renal disease risk. Methods132 type 2 diabetic patients with chronic kidney disease were enrolled. Patients were categorized into 2 groups according to the renal biopsy results: DKD (n = 61) and NDKD (n = 71).The independent factors of the occurrence of DKD and the diagnostic implications of tubular biomarkers were explored by logistic regression and receiver-operating characteristic curve analysis. Furthermore, predictors were analyzed by least absolute shrinkage and selection operator regression, and constructed a new model for predicting the unfavorable renal outcomes through Cox proportional hazard regression analysis. ResultsSerum neutrophil gelatinase-associated lipocalin (sNGAL) (OR = 1.007; 95%CI = [1.003, 1.012], p = 0.001) was identified as an independent risk factor for the occurrence of DKD in diabetic patients with CKD. Tubular biomarkers including sNGAL, N-acetyl-β-D-glucosaminidase and β2 microglobulin (β2-MG) could complement albuminuria for DKD detection (AUC = 0.926, specificity = 90.14%, sensitivity = 80.33%).Moreover, among of the 47 variables, 4 predictors such as sNGAL, interstitial fibrosis and tubular atrophy (IFTA)score, β2-MG and estimated glomerular filtration rate were selected to construct a new model for predicting the unfavorable renal outcomes through regression analysis. sNGAL (HR = 1.004; 95%CI = [1.001, 1.007], p = 0.013), IFTA score of 2 (HR = 4.283; 95%CI = [1.086, 16.881], p = 0.038), and IFTA score of 3 (HR = 6.855; 95%CI = [1.766, 26.610], p = 0.005) were considered to be independent risk factors for unfavorable renal outcomes. ConclusionsTubulointerstitial injury in DKD is independently associated with renal function decline and routinely detected tubular biomarkers are able to enhance the level of non-invasive diagnosis of DKD beyond traditional factors.

Efficacy and Safety of Mizoribine in comparison with Cyclophosphamide for Treatment of Refractory Nephrotic Syndrome: Protocol for a Multi-center, Controlled, Open-label, Randomized Controlled Trial.

Nephrotic syndrome that is resistant to steroidal therapy is termed refractory nephrotic syndrome (RNS), a condition that is associated with an increased risk of end-stage renal disease (ESRD). Immunosuppressants are utilized to treat RNS, however prolonged may lead to significant adverse effects. Mizoribine (MZR) is a novel agent used in long-term immunosuppressive therapy that has few adverse effects, but data on its long-term use in patients with RNS are unavailable. We propose a trial to examine the efficacy and safety of MZR compared to cyclophosphamide (CYC) in Chinese adult patients with RNS. This is a multi-center, randomized, controlled interventional study with a screening phase (1 week) and a treatment phase (52 weeks). This study was reviewed and approved by the Medical Ethics Committees of all 34 medical centers. Patients with RNS consented to participation, and were enrolled and randomized into an MZR group or a CYC group (1:1 ratio), with each group receiving tapering doses of oral corticosteroids. Participants were assessed for adverse effects and collection of laboratory results at 8 visits during the treatment phase on week-4, week-8, week-12, week-16, week-20, week-32, week-44, and week-52 (exit visit). Participants were able to withdraw voluntarily and investigators were required to remove patients when there were safety concerns or deviations from protocol. The study started in November 2014, and was completed in March 2019. A total of 239 participants from 34 hospitals in China were enrolled. Data analysis is completed. The results are waiting to be finalized by Center for Drug Evaluation. The purpose of the current study is to evaluate the efficacy and safety of MZR in comparison with CYC for treatment of RNS in Chinese adult patients with glomerular diseases. It is the longest lasting and largest randomized controlled trial to examine MZR in Chinese patients. The results can help determine whether RNS should be considered as an additional indication for MZR treatment in China. ClinicalTrials.gov Register, NCT02257697. Registered 2014-10-01, https://clinicaltrials.gov/ct2/show/NCT02257697?term=MZR&rank=2.

Hyperlactatemia is associated with increased risks of long-term mortality and major adverse cardiovascular events in sepsis survivors

Introduction Serum lactate is a potentially valuable biomarker for risk assessment for patients with sepsis, as hyperlactatemia is associated with elevated short-term mortality risks. However, the associations between hyperlactatemia and long-term clinical outcomes in sepsis survivors remain unknown. The objective of this study was to investigate whether hyperlactatemia at the time of hospitalisation for sepsis was associated with worse long-term clinical outcomes in sepsis survivors. Methods In total, of 4983 sepsis survivors aged ≥ 20 years were enrolled in this study between January 1, 2012, and December 31, 2018. They were divided into low (≤18 mg/dL; n = 2698) and high (>18 mg/dL; n = 2285) lactate groups. The high lactate group was then matched 1:1 by propensity-score method to the low lactate group. The outcomes of interest were all-cause mortality, major adverse cardiac events (MACEs), ischaemic stroke, myocardial infarction, hospitalisation for heart failure, and end-stage renal disease. Results After propensity score matching, the high lactate group had greater risks of all-cause mortality (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.41–1.67), MACEs (HR 1.53, 95% CI 1.29–1.81), ischaemic stroke (HR 1.47, 95% CI 1.19–1.81), myocardial infarction (HR 1.52, 95% CI 1.17–1.99), and end-stage renal disease (HR 1.42, 95% CI 1.16–1.72). Subgroup analyses stratified by baseline renal function revealed almost similarity across groups. Conclusion We found that hyperlactatemia is associated with long-term risks of mortality and MACEs in sepsis survivors. Physicians may consider more aggressive and prompter management of sepsis in patients who present with hyperlactatemia to improve long-term prognoses.

Long-term survival and renal outcomes of thrombotic microangiopathy in pregnancy: A retrospective cohort study.

Thrombotic microangiopathy (TMA) in pregnancy can rapidly progress, leading to severe morbidities. This study aimed to compare baseline demographics and clinical outcomes between pregnant women with and without TMA. Using the National Health Insurance Research Database, 207 patients with pregnancy-related TMA from January 1, 2006 to December 31, 2015 were enrolled. Their data were compared with a 1:4 propensity score-matched cohort of 828 pregnant women without TMA to evaluate mortality and end-stage renal disease (ESRD) risks. Cox proportional hazards models were used to estimate the adjusted hazard ratio and 95% confidence intervals. A total of 1035 participants were included. The risks of mortality and ESRD were 4.46 and 5.97 times higher for the TMA cohort, respectively. Subgroup analysis revealed higher mortality and ESRD risks in patients with TMA aged >40 years with a history of hypertension, stroke, cancer, concomitant stroke, malignant hypertension, or gastroenterocolitis than in the matched cohort. Pregnant patients with TMA, especially those older and with comorbidities and organ involvement, faced increased mortality and ESRD risks. Physicians should collaborate with obstetricians throughout the prenatal and postpartum periods for these patients.

Validation of the international IgA nephropathy prediction tool in a French cohort beyond 10 years after diagnosis.

The International IgA Nephropathy Network developed a tool (IINN-PT) for predicting the risk of end-stage renal disease (ESRD) or a 50% decline in the estimated glomerular filtration rate (eGFR). We aimed to validate this tool in a French cohort with longer follow-up than previously published validation studies. The predicted survival of patients with biopsy-proven immunoglobulin A nephropathy (IgAN) from the Saint Etienne University Hospital cohort was computed with IINN-PT models with or without ethnicity. The primary outcome was the occurrence of either ESRD or a 50% decline in eGFR. The models' performances were evaluated through c-statistics, discrimination and calibration analysis. There were 473 patients with biopsy-proven IgAN, with a median follow-up of 12.4 years. Models with and without ethnicity showed areas under the curve (95% confidence interval) of 0.817 (0.765; 0.869) and 0.833 (0.791; 0.875) and R2D of 0.28 and 0.29, respectively, and an excellent discrimination of groups of increasing predicted risk (P<.001). The calibration analysis was good for both models up to 15 years after diagnosis. The model without ethnicity exhibited a mathematical issue of survival function after 15 years. The IINN-PT provided good performances even after 10 years post-biopsy as showed by our study based on a cohort with a longer follow-up than previous cohorts (12.4 versus <6 years). The model without ethnicity exhibited better performances up to 15 years but became aberrant beyond this point due to a mathematical issue affecting the survival function. Our study sheds light on the usefulness of integrating ethnicity as a covariable for prediction of IgAN course.

#2898 UNMET NEEDS AND POOR LONG-TERM RENAL OUTCOMES IN EUROPEAN PATIENTS WITH LUPUS NEPHRITIS

Abstract Background and Aims Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE), associated with substantial morbidity and increased risk of end-stage renal disease (ESRD). Despite currently used therapies, a notable proportion of patients may not achieve sustained remission, leading to adverse disease outcomes. This study aims to summarize evidence on the long-term outcomes, burden of comorbidities, and real-world (RW) effectiveness of therapy in European patients with LN. Method A targeted literature review was conducted using MEDLINE/Pubmed and Embase to identify studies in patients with LN. Search strategies were developed for each database to identify relevant peer-reviewed articles published in English from March 2012 - March 2022 and conference abstracts from 2019 – March 2022. All records were screened according to pre-specified inclusion/exclusion criteria. Only studies conducted in a European setting were summarized here. Results Of 4,216 total records, 55 studies reported long-term outcomes of LN and RW effectiveness of treatment in European adults. Up to 36% of patients with SLE developed LN, and nearly all LN cases occurred within 5 years of SLE diagnosis. Patients with LN often suffered from serious infection (19-35%), cardiovascular disease (CVD) (26%), chronic kidney disease (CKD)/ESRD (6-22%) and were more likely to experience cardio- and cerebrovascular events than patients with SLE only (p = 0.001). Patients with LN had a higher risk of mortality compared to those with SLE only or other lupus manifestations (p&amp;lt;0.001), and deaths were often due to infections (8-32%), CVD (22-58%), or malignancies (5-27%). CKD/ESRD also contributed to poor survival – patients with ESRD had 3-times higher risk of death compared to those with LN only (p&amp;lt;0.001). The majority of RW studies evaluated effectiveness of standard of care (SOC) induction and/or maintenance therapy, mostly with mycophenolate mofetil and cyclophosphamide. Treatment response rates varied across the studies likely due to heterogeneity in study design, drug dosing, and patient population; comparative studies did not find significant differences in response rates between the regimens. Overall, 30-86% of patients with LN achieved complete renal response/remission (CRR) within the first year of starting SOC therapy. However, one study reported that only 38% of patients maintained CRR while on SOC over a 5-year period, suggesting inadequate long-term maintenance on existing therapies. Patients who were non-responders (NR) after 1 year had a significantly increased risk of mortality and CKD compared to responders (p&amp;lt;0.005). Patients achieving CRR had significantly longer CKD-free survival compared to NR at 15 years (95% vs 55%, p&amp;lt;0.0001), further highlighting the value of achieving response in terms of long-term renal outcomes. Despite initial response to current therapies, 20-35% of patients experienced a renal relapse/flare while on maintenance therapy, with one study noting significantly increased risk of proteinuric flares with azathioprine compared to other maintenance therapies (p = 0.01). Limited studies focused on treatment-experienced/refractory patients, with the majority evaluating rituximab (RTX)-based regimens. After one year of therapy, 29-64% of patients with refractory LN and 35% of patients with active LN despite SOC achieved CRR on RTX or belimumab, respectively. Conclusion European adults with LN have considerable comorbidity burden and poor long-term renal outcomes. Few patients achieve and maintain remission on SOC, and a notable proportion of patients experience renal relapse despite initial response to therapy. Given the impact that achieving CRR has on long-term outcomes, there is a need for effective therapies that provide sustained remission, especially for patients with severe/refractory LN.

#3015 EFFECT OF DAPAGLIFLOZIN ON ALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES AND CKD

Abstract Background and Aims Albuminuria in patients with diabetes presents a higher risk for adverse renal and cardiovascular (CV) outcomes. Sodium-glucose co-transporter 2 (SGLT2) inhibitors demonstrate improved albuminuria and reduces the risk of end-stage renal disease in patients with chronic kidney disease. The study aim was the impact of the SGLT2 inhibitor dapagliflozin on urine albumin-to-creatinine ratio (UACR) and GFR decline. Method In the single center trial, total 132 participants with CKD and type 2 diabetes (T2D) were randomly assigned to dapagliflozin (n = 78) 10 mg once daily or placebo (n = 54). Kidney inclusion criteria were eGFR 30-60ml/min/1.73 m2 and any UACR. The primary end point was a composite of sustained decline in eGFR ≥50%, end-stage renal disease, or kidney or cardiovascular death. Percentage treatment difference was estimated by geometric mean ratio for the overall cohort and by eGFR and UACR subgroups. Progression/regression of UACR were assessed. Hazard ratios, 95% confidence intervals (CI), and p-values were estimated by Cox proportional hazards model. Results Median baseline eGFR was 42.3ml/min/1.73 m2, with 5% at &amp;lt;30ml/min/1.73 m2. At baseline, median UACR was 103 mg/g, and 1/4 of patients had normoalbuminuria, 2/4 had micro, and 1/4 had macroalbuminuria. Median follow up was 18 months. The UACR difference for dapagliflozin vs placebo was -25.1% (95% CI -27.5, -23.2; p&amp;lt;0.001). Reductions were similar across eGFRs. In UACR 30-299mg/g and ≥300mg/g, reductions were significant in dapagliflozin (p&amp;lt;0.001). Progression risk was lower and regression risk higher in dapagliflozin vs placebo (p&amp;lt;0.001). Conclusion Dapagliflozin significantly slowed long-term eGFR decline in patients with CKD with T2D compared with placebo, and significantly reduced UACR and had favorable effects on UACR progression and regression.

Long-term end-stage renal disease risks after living kidney donation: a systematic review and meta-analysis

BackgroundRecent studies have shown that donor nephrectomy can induce renal function impairment. However, few meta-analysis studies about this have proceeded. Therefore, the objective of this systematic review and meta-analysis including all data of recent research studies was to determine whether living donor nephrectomy (LDN) could induce renal function impairment.MethodsBy November 2020, comprehensive literature searches were performed on PubMed, Embase, and Cochrane databases. Inclusion criteria were: (1) observational studies with data about overall end-stage renal disease (ESRD) or chronic kidney disease (CKD) of living kidney donors, (2) control group consisted of people without donor nephrectomy, and (3) outcomes of studies included long-term end-stage renal disease risks after living kidney donation. Risk of Bias in Non-randomized Studies of interventions (ROBINS-I) assessment tool was used to evaluate our methodological quality.ResultsThe qualitative review included 11 studies and the meta-analysis included 5 studies. In the meta-analysis, the integrated overall ESRD risk was 5.57 (95% CI: 2.03—15.30). Regarding the overall risk of bias using ROBINS-I assessment tool, 0 studies was rated as "Low", 7 studies were rated as "moderate", 2 studies were rated as "Serious", and two studies were rated as "Critical".ConclusionsOur study showed that LDN increased ESRD risk in LDN patients. However, in our meta-analysis, variables in included studies were not uniform and the number of included studies was small. To have a definite conclusion, meta-analyses of well-planned and detailed studies need to be conducted in the future.

Association between fatty liver index and risk of end-stage renal disease stratified by kidney function in patients with type 2 diabetes: A nationwide population-based study

ObjectiveThe effects of nonalcoholic fatty liver disease on the risk of end-stage renal disease (ESRD) remain unclear. We investigated the association between the fatty liver index (FLI) and risk of ESRD in patients with type 2 diabetes. MethodsThis population‐based observational cohort study enrolled patients with diabetes who underwent health screening between 2009 and 2012 and utilized data from the Korean National Health Insurance Services. The FLI functioned as a surrogate marker for the presence of hepatic steatosis. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m² calculated using the Modification of Diet in Renal Disease equation. We performed Cox proportional hazards regression. ResultsIncident ESRD developed in 19,476 of 1,900,598 patients with type 2 diabetes during a median follow-up of 7.2 years. After adjusting for conventional risk factors, patients with high FLI scores had a higher risk for ESRD: FLI, 30–59 [hazard ratio (HR) = 1.124; 95% confidence interval (CI), 1.083–1.166]; FLI ≥ 60 [HR = 1.278; 95% CI, 1.217–1.343] compared with those with FLI < 30. The association between a high FLI score (≥ 60) and incident ESRD was more prominent in women than in men (male, FLI ≥60: HR, 1.106; 95% CI = 1.041–1.176 and female, FLI ≥ 60: HR, 1.835; 95% CI = 1.689–1.995). The association between a high FLI score (≥ 60) and the risk of ESRD differed according to baseline kidney function. High FLI scores increased the risk of ESRD (HR = 1.268; 95% CI, 1.198–1.342) in patients with CKD at baseline. ConclusionHigh FLI scores are associated with a greater risk of ESRD in patients with type 2 diabetes with CKD at baseline. Close monitoring and appropriate management of hepatic steatosis may aid in preventing the progression of kidney dysfunction in patients with type 2 diabetes and CKD.

Commentary: Rheumatoid arthritis and the risk of end-stage renal disease: a nationwide, population-based study.

Commentary: Rheumatoid arthritis and the risk of end-stage renal disease: a nationwide, population-based study.

The impact of non-alcoholic fatty liver disease and liver fibrosis on adverse clinical outcomes and mortality in patients with chronic kidney disease: a prospective cohort study using the UK Biobank

BackgroundChronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) frequently co-exist. We assess the impact of having NAFLD on adverse clinical outcomes and all-cause mortality for people with CKD.MethodsA total of 18,073 UK Biobank participants identified to have CKD (eGFR < 60 ml/min/1.73 m2 or albuminuria > 3 mg/mmol) were prospectively followed up by electronic linkage to hospital and death records. Cox-regression estimated the hazard ratios (HR) associated with having NAFLD (elevated hepatic steatosis index or ICD-code) and NAFLD fibrosis (elevated fibrosis-4 (FIB-4) score or NAFLD fibrosis score (NFS)) on cardiovascular events (CVE), progression to end-stage renal disease (ESRD) and all-cause mortality.Results56.2% of individuals with CKD had NAFLD at baseline, and 3.0% and 7.7% had NAFLD fibrosis according to a FIB-4 > 2.67 and NFS ≥ 0.676, respectively. The median follow-up was 13 years. In univariate analysis, NAFLD was associated with an increased risk of CVE (HR 1.49 [1.38–1.60]), all-cause mortality (HR 1.22 [1.14–1.31]) and ESRD (HR 1.26 [1.02–1.54]). Following multivariable adjustment, NAFLD remained an independent risk factor for CVE overall (HR 1.20 [1.11–1.30], p < 0.0001), but not ACM or ESRD. In univariate analysis, elevated NFS and FIB-4 scores were associated with increased risk of CVE (HR 2.42 [2.09–2.80] and 1.64 [1.30–2.08]) and all-cause mortality (HR 2.82 [2.48–3.21] and 1.82 [1.47–2.24]); the NFS score was also associated with ESRD (HR 5.15 [3.52–7.52]). Following full adjustment, the NFS remained associated with an increased incidence of CVE (HR 1.19 [1.01–1.40]) and all-cause mortality (HR 1.31 [1.13–1.52]).ConclusionsIn people with CKD, NAFLD is associated with an increased risk of CVE, and the NAFLD fibrosis score is associated with an elevated risk of CVE and worse survival.

Association between triglyceride-glucose index and risk of end-stage renal disease in patients with type 2 diabetes mellitus and chronic kidney disease.

It has been suggested that the triglyceride-glucose (TyG) index is a novel and reliable surrogate marker of insulin resistance (IR). However, its relationship with the risk of end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) remains uncertain. Accordingly, we sought to examine the relationship between the TyG index and ESRD risk in patients with T2DM and CKD. From January 2013 to December 2021, 1,936 patients with T2DM and CKD hospitalized at Peking University Third Hospital (Beijing, China) were enrolled into the study. The formula for calculating the TyG index was ln[fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. ESRD was defined as an estimated glomerular filtration rate of less than 15 mL/min/1.73 m2 or the commencement of dialysis or renal transplantation. The relationship between the TyG index and ESRD risk was analyzed using Cox proportional hazard regression. 105 (5.42%) participants developed ESRD over a mean follow-up of 41 months. The unadjusted analysis revealed a 1.50-fold (95% confidence interval [CI] 1.17-1.93; P = 0.001) increased risk for ESRD per one unit rise in the TyG index, and the positive association remained stable in the fully adjusted model (hazard ratio, 1.49; 95% CI, 1.12-1.99; P = 0.006). Analysis using restricted cubic spline revealed a significant positive association between the TyG index and ESRD risk. In addition, Kaplan-Meier analysis revealed significant risk stratification with a TyG index cutoff value of 9.5 (P = 0.003). In individuals with T2DM and CKD, a significant and positive association was shown between an elevated TyG index and the risk of ESRD. This conclusion provides evidence for the clinical importance of the TyG index for evaluating renal function decline in individuals with T2DM and CKD.

The place of cyclical therapy for the treatment of membranous nephropathy in the era of rituximab.

Primary membranous nephropathy (MN) is the most frequent cause of nephrotic syndrome in adults, due to a variety of autoantibodies, most frequently against phospholipase A2 receptor (PLA2R). In severe cases or when spontaneous remission is not achieved, immunosuppression is required. Cyclical therapy, based on glucocorticoids and cyclophosphamide on alternate months for 6months, has proven effective to induce remission and reduce the risk of end-stage renal disease. Since the early 2000s, rituximab (RTX) has emerged as a key player in the management of MN, showing overall comparable effectiveness and likely better safety compared with the cyclical regimen, despite the lack of adequately powered trials comparing the two approaches head to head. For these reasons, RTX is now considered the agent of choice for most patients with MN. However, there are still uncertainties. Around 20-40% of patients are resistant to RTX, especially in the setting of high anti-PLA2R levels, and this drug remains relatively unexplored in patients with the most severe disease. In these scenarios, although the expanding therapeutic armamentarium is probably going to provide further options, the cyclical regimen still plays a key role as a safety net. The aim of this article is to illustrate the role of cyclical therapy in the RTX era.

Sleep traits and risk of end-stage renal disease: a mendelian randomization study

BackgroundEpidemiological evidence relating sleep disorders to end-stage renal disease (ESRD) has been obscure. The present study is sought to examine the association between sleep traits and ESRD.MethodsFor this analysis, we selected genetic instruments for sleep traits from published genome-wide association studies (GWAS). As instrumental variables, independent genetic variations linked with seven sleep-related features (sleep duration, getting up in the morning, daytime napping, chronotype of morning/evening person, sleeplessness/insomnia, non-snoring, and daytime dozing) were chosen. A two-sample Mendelian randomization (TSMR) study was conducted to assess the causal relationship between sleep traits and ESRD (N = 33,061). The reverse MR analysis subsequently determined the causal relationship between ESRD and sleep traits. The causal effects were estimated using inverse variance weighted, MR-Egger, weighted median. To conduct sensitivity studies, Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plot were used. To study the potential mediators, multivariable mendelian randomization analyses were undertaken further.ResultsGenetically predicted sleeplessness/ insomnia (OR = 6.11, 95%CI 1.00-37.3, P = 0.049, FDR = 0.105), getting up in the morning easily(OR = 0.23, 95%CI 0.063–0.85; P = 0.0278, FDR = 0.105), non-snoring (OR = 4.76E-02, 95%CI 2.29E-03-0.985, P = 0.0488, FDR = 0.105) was suggestively associated with the risk of ESRD. However, we found no evidence favoring a causal association between other sleep traits and ESRD through the IVW method.ConclusionThe present TSMR found no strong evidence of a bidirectional causal association between genetically predicted sleep traits and ESRD.

Inequalities in end-stage renal disease: underprivileged and ethnic minority members are at higher risk.

Incidence of end-stage renal disease (ESRD) is higher in Israel than the European average. Socio-economic differences in ESRD have been reported globally, but many countries lack a national register. Using national data, we assessed which socio-demographic factors are associated with 5-year incidence of ESRD in Israel, where there is universal access to renal replacement therapy (RRT). Data on all incident ESRD cases aged ≥20 years receiving chronic RRT between 1 January 2014 and 31 December 2018 (N = 7883) were collected from Israel's National Dialysis & Renal Transplant Register. Individual-level data on ESRD cases requiring RRT included residential area, age, gender, ethnicity (Jewish or Arab) and ESRD cause (diabetes, other, unknown/missing). Area-level data included age and sex distribution, socio-economic status (SES) and proportion of Arab population. The associations between individual-level socio-demographic characteristics and ESRD cause were tested in bivariate comparisons. The risk of developing ESRD during the study period (from all and specific causes) was estimated using multiple Poisson regression models with negative binomial distribution, using four parameters, namely sex, ethnicity, SES category and age strata, based on area-level distribution of these parameters, and with the whole population (aged ≥20 years) as the denominator. A socio-economic gradient was seen for ESRD from all causes, more marked for diabetic aetiology [rate ratio (RR)=0.45, 95% CI: 0.39-0.52 highest vs lowest SES categories] than from other (RR = 0.64, 95% CI: 0.55-0.75) or unknown cause (RR = 0.79, 95% CI: 0. 62-0.99). Based on population area-level data, predominantly Arab neighbourhoods showed higher risk for ESRD requiring RRT for all causes, with the strongest association for diabetes (RR = 1.69, 95% CI: 1.53-1.86) adjusted for SES, age and sex. A strong socio-economic gradient was demonstrated for ESRD requiring RRT. Arab ethnicity was associated with higher risk for ESRD, especially due to diabetes. Our findings suggest the need for allocation of health resources according to needs and culturally appropriate interventions for improving control of modifiable risk factors for chronic renal failure.

Asthma and increased risk of myocardial infarction and mortality among hypertensive Korean patients.

This study aimed to evaluate the effects of asthma on cardiovascular disease incidence in patients with hypertension. A total of 639,784 patients with hypertension from the Korea National Health Insurance Service database were included, of whom 62,517 had history of asthma after propensity score matching. The risks of all-cause mortality, myocardial infarction (MI), stroke, and end-stage renal disease (ESRD) were assessed according to the presence of asthma, long-acting β2-agonist (LABA) inhaler usage, and/or systemic corticosteroid usage for up to 11 years. In addition, whether these risks were modified by average blood pressure (BP) levels during the follow-up period was examined. Asthma was associated with an increased risk of all-cause mortality (hazard ratio [HR], 1.203; 95% confidence interval [CI], 1.165-1.241) and MI (HR, 1.244; 95% CI, 1.182-1.310) but not the risk of stroke or ESRD. LABA inhaler usage was associated with a higher risk of all-cause mortality and MI, and systemic corticosteroids usage showed a higher risk of ESRD as well as all-cause mortality and MI among hypertensive patients with asthma. Compared to patients without asthma, there was a graded increase in the risk of all-cause mortality and MI in those with asthma without LABA inhaler/systemic corticosteroid usage and in those with asthma with LABA inhaler/systemic corticosteroid usage. These associations were not significantly modified by BP levels. This nationwide population-based study supports that asthma may be a clinical factor that increases the risk of poor outcomes in patients with hypertension.

Association between familial aggregation of chronic kidney disease and its incidence and progression

This study aimed to examine the association between familial aggregation of chronic kidney disease (CKD) and risk of CKD development and its progression. This nationwide family study comprised 881,453 cases with newly diagnosed CKD between 2004 and 2017 and 881,453 controls without CKD matched by age and sex, using data from the Korean National Health Insurance Service with linkage to the family tree database. The risks of CKD development and disease progression, defined as an incident end-stage renal disease (ESRD), were evaluated. The presence of any affected family member with CKD was associated with a significantly higher risk of CKD with adjusted ORs (95% CI) of 1.42 (1.38–1.45), 1.50 (1.46–1.55), 1.70 (1.64–1.77), and 1.30 (1.27–1.33) for individuals with affected parents, offspring, siblings, and spouses, respectively. In Cox models conducted on patients with predialysis CKD, risk of incident ESRD was significantly higher in those with affected family members with ESRD. The corresponding HRs (95% CI) were 1.10 (1.05–1.15), 1.38 (1.32–1.46), 1.57 (1.49–1.65), and 1.14 (1.08–1.19) for individuals listed above, respectively. Familial aggregation of CKD was strongly associated with a higher risk of CKD development and disease progression to ESRD.

Risk of End-Stage Renal Disease in Patients With Systemic Lupus Erythematosus and Diabetes Mellitus: A Danish Nationwide Cohort Study.

The risk of end-stage renal disease (ESRD) is increased in patients with systemic lupus erythematosus (SLE). This study was undertaken to determine whether diabetes mellitus (DM) increases ESRD risk in a large inception cohort of SLE patients. By means of the Danish National Patient Registry, we identified 3,178 adult patients diagnosed as having SLE between January 1, 1996, and July 31, 2018. DM was defined as the date of first hospital contact for DM or date of a first prescription of an antidiabetic drug. ESRD was defined as first registration of dialysis, renal transplant, or terminal renal insufficiency in the Danish National Patient Registry. ESRD incidence was compared between SLE patients with DM (SLE-DM) and those without DM (SLE-non-DM). Hazard ratios (HRs), adjusted for sex, age, educational level, and occupational status at baseline were calculated for sex, age, educational level, and hypertension (at baseline or during follow-up) strata. The overall hazard ratio (HR) was also adjusted for hypertension. The SLE-DM group included 290 patients, of whom 77% were female, compared with 85% of the 2,859 patients in the SLE-non-DM group. SLE-DM patients had a 3 times higher risk of ESRD compared with SLE-non-DM patients (multivariable-adjusted HR 3.3 [95% confidence interval 1.8-6.1]). In stratified multivariable-adjusted analyses, DM increased the rate of ESRD in women and men, patients ≥50 years old at baseline, those with low educational level at baseline, and those with concomitant hypertension. Our findings indicate that SLE patients with DM have a markedly higher risk of developing ESRD compared with SLE patients without DM.

An Investigation on the Efficacy of Glucagon-Like Peptide 1 Receptor Agonists Drugs in Reducing Urine Albumin-to-Creatinine Ratio in Patients With Type 2 Diabetes: A Potential Treatment for Diabetic Nephropathy.

As diabetes mellitus becomes increasingly prevalent globally, so does diabetic nephropathy, a complication leading to one of the world's leading causes of end-stage renal disease (ESRD). Current research has linked an increase in the urine albumin-to-creatinine ratio (UACR), a marker for kidney damage, to a greater risk of adverse renal outcomes and ESRD in patients with diabetes. Of the diabetes medications studied and implemented in clinical settings, glucagon-like peptide-1 receptor agonist (GLP1-RA) drugs have been shown to not only help control HbA1c in diabetes but have also demonstrated numerous cardiovascular, hepatic, and renal benefits. The objective of our study was to assess the efficacy of GLP1-RA drugs in reducing UACR in patients with type 2 diabetes mellitus (T2 DM) to determine if GLP1-RAs could be used to provide renoprotection in diabetic nephropathy in addition to their glucose-lowering effects. Upon a comprehensive review of the literature, we conducted a statistical analysis to determine the efficacy of GLP1-RA monotherapy and combination therapy in reducing UACR in comparison to placebo and insulin glargine. Of the studies analyzed, GLP1-RAs exhibited a statistically significant effect in reducing UACR in comparison to a placebo but not in comparison to insulin glargine. GLP1-RA combination therapy (GLP1-RA used with either insulin glargine, metformin, or dapagliflozin) did not exhibit statistically significant UACR reductions in comparison with insulin glargine. However, GLP1-RA combination therapy showed a trend suggestive of being more effective than insulin glargine in reducing UACR, but due to the limited literature studying this treatment method, further studies in a more focused group of patients with diabetic nephropathy may produce stronger and more definitive results. GLP1-RA monotherapy or combination therapy has been determined to be an effective method for reducing UACR and decreasing the incidence of adverse renal outcomes associated with diabetic kidney disease. GLP1-RA therapy could serve as an alternative treatment in diabetic nephropathy to insulin glargine, which carries a higher risk of hypoglycemia and unintentional weight gain while potentially being less cost-effective.

Triglycerides and Renal Outcomes According to Albuminuria and in Consideration of Other Metabolic Syndrome Components in Diabetic US Veterans

Introduction: Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Previous studies have shown that the relationship of triglycerides (TGs) with outcomes changes across stages of CKD. Our objective was to examine the association of TG independent of other metabolic syndrome components with renal outcomes in diabetic patients with or without CKD. Methods: This retrospective cohort study included diabetic US veteran patients with valid data on TGs, estimated glomerular filtration rate (eGFR), and albuminuria (urinary albumin/creatinine ratio) between fiscal years 2004 and 2006. Using Cox models adjusted for clinical characteristics and laboratory markers, we evaluated the relationship of TG with incident albuminuria (stratified by eGFR category) and based on eGFR (stratified by baseline albuminuria categories). To evaluate the relationship of TG with time to end-stage renal disease (ESRD), we stratified models by baseline CKD stage (eGFR category) and baseline albuminuria stage ascertained at time of TG measurement. Results: In a cohort of 138,675 diabetic veterans, the mean ± SD age was 65 ± 11 years old and included 3% females and 14% African Americans. The cohort also included 28% of patients with non-dialysis-dependent CKD (eGFR <60 mL/min/1.73 m²), as well as 28% of patients with albuminuria (≥30 mg/g). The median (IQR) of serum TG was 148 (100, 222) mg/dL. We observed a slight positive linear association between TG and incident CKD after adjustment for Case-Mix and Laboratory variables among non-albuminuric and microalbuminuric patients. The relationship of high TG trended towards a higher risk of ESRD in CKD 3A non-albuminuric patients and in CKD 3A and 4/5 patients with microalbuminuria. Conclusion: In a large cohort, we have shown that elevated TGs are associated with all kidney outcomes tested independently of other metabolic syndrome components in diabetic patients with normal eGFR and normal albumin excretion rate, but the association is weaker in some groups of diabetic patients with preexisting renal complications.