Rates Of End-stage Kidney Disease Research Articles

#2051 Long-term follow-up of Israeli patients with lupus nephritis

Abstract Background and Aims Systemic lupus erythematosus (SLE) often affects the kidneys, and is associated with morbidity and mortality. Ethnic variations in clinical response to treatment and outcomes have been described. Information on real-life, long-term cohorts of the Middle Eastern Israeli population is lacking. We aimed to characterize the prevalence and long-term outcomes of kidney involvement in SLE patients in Israel and to identify variables associated with lupus nephritis (LN) and end-stage kidney disease (ESKD). Method This retrospective study, conducted between 2014-2023, included adult patients with SLE diagnosed for at least 12 months. Kidney involvement was based on a diagnosis of LN on a kidney biopsy. SLE patients without LN served as controls. Associated variables were collected including socio-demographics, disease-related characteristics, kidney-related factors, comorbidities, and all-cause mortality. Results A total of 182 adult patients with SLE were included. Of them, 54 (29.6%) had LN. Mean follow-up since diagnosis was 16.2 ± 13.8 years. Compared to the control group, patients with LN were diagnosed with SLE at younger ages (26.8 ± 12.9 vs. 35.5 ± 15.4 years, p < 0.01). Patients with LN and controls had similar proportions of females/males and Jewish/Arab patients (Table 1), and had comparable baseline eGFR before LN diagnosis (110 ± 48 vs. 107 ± 39 ml/min/m2, p = 0.66). The LN group had lower complement C3 levels at diagnosis and higher dsDNA titers (p = 0.001, 0.023 respectively; Table 1). Patients with LN had more hospitalization for SLE exacerbations [38.4% vs. 24.5%, odds ratio (OR) 1.9, 95% confidence interval (CI) 1-3.9, p = 0.06]. Of 54 patients with LN, 45 had available treatment information. All patients were treated with hydroxychloroquine, 19 patients (42.2%) were treated with cyclophosphamide, and 36 (80%) were treated with mycophenolate mofetil or mycophenolic acid. During follow-up of the LN patients, 5 patients (9.3%) were diagnosed with diabetes, 21 patients (38.9%) were diagnosed with hypertension, 5 patients (9.3%) had a stroke and 6 patients (11.1%) had an acute coronary syndrome. Eight of the LN patients (14.8%) developed ESKD as compared with one patient (0.8%) of the controls (OR 22.1, 95% CI 2.7-181.5, p < 0.001). On univariate analysis, ESKD was significantly associated with LN, hypertension, heart failure, and non-employment status. No difference in the rate of ESKD was found between Jewish and Arab patients. On multivariate regression analysis, LN and hypertension were the most important predictors for developing ESKD. Mortality among patients with ESKD was 22% vs. 4.6% among non-ESKD patients (p = 0.02) )Fig. 1). Conclusion This long-term study on Israeli SLE patients reveals that despite advances in SLE treatments, LN is associated with significant morbidity and mortality. The elevated risk of ESKD, particularly associated with LN and hypertension, underscores the imperative for targeted interventions to improve outcomes.

#1386 Hypertension is associated with deterioration of kidney function among patients with systemic lupus erythematosus, with or without lupus nephritis

Abstract Background and Aims Systemic lupus erythematosus (SLE) frequently involves the kidneys, contributing to morbidity and mortality among this population. While hypertension often coexists with kidney involvement, it is not represented in the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index. Its effect on the morbidity and mortality of the SLE population in the Middle East should be evaluated. Our aims is to characterize the role of hypertension in Israeli SLE patients and identify variables associated with decreased eGFR over time. Method This retrospective study, conducted between 2014–2023 included adult patients with a diagnosis of SLE for at least 12 months. Kidney involvement was assessed based on a diagnosis of lupus nephritis (LN) on kidney biopsy. Hypertension was diagnosed based on documented diagnosis. Systolic and diastolic blood pressures were collected as continuous variables at multiple time-points. Associated variables, including socio-demographics, disease-related characteristics, kidney-related factors, comorbidities and all-cause mortality were assessed. Results A total of 182 patients were followed for a mean duration of 16.2 ± 13.8 years. Fifty-nine patients (32.4%) had chronic hypertension. Hypertension was more prevalent among SLE patients with LN [odds ratio (OR) 1.5, 95% CI 0.8-2.9, p = 0.23] as well as patients with chronic kidney disease (OR 7.2, 95% CI 1.9-27.7, p = 0.001). Patients with chronic hypertension had significantly relatively high rate of proteinuria at last follow-up (54.7%). On univariate analysis, patients with hypertension had higher rates of end-stage kidney disease (ESKD) (11.9% vs 1.6%, p = 0.003), heart failure (20.3% vs. 0.8%, p < 0.001), and all-cause mortality (16.9% vs. 0%, p < 0.001). All deaths (n = 10) occurred among hypertensive patients. LN and age were the most important predictors of hypertension on multivariate analysis (OR 6.2, 95% CI 2.4-16, p < 0.001; OR 1.1, 95% CI 1.1-1.2 p < 0.001, respectively). Repeated measures analysis showed that hypertension was significantly associated with decreased eGFR among SLE patients with or without LN (Fig. 1). Systolic and diastolic blood pressure were significantly correlated with age and inversely correlated with eGFR at last follow-up (Spearman's correlation coefficient 0.4, p < 0.01; 0.1, p = 0.07; −0.4, p < 0.01; −0.2, p = 0.04, respectively). Conclusion Hypertension is prevalent among Israeli patients with SLE, constituting a substantial comorbidity associated with ESKD, heart failure and mortality, irrespective of LN presence. Routine assessment and vigorous treatment of hypertension should be part of the management of patients with SLE.

Cerebrovascular Disease Hospitalization Rates in End-Stage Kidney Disease Patients with Kidney Transplant and Peripheral Vascular Disease: Analysis Using the National Inpatient Sample (2005-2019).

Individuals with end-stage kidney disease (ESKD) face higher cerebrovascular risk. Yet, the impact of peripheral vascular disease (PVD) and kidney transplantation (KTx) on hospitalization rates for cerebral infarction and hemorrhage remains underexplored. Analyzing 2,713,194 ESKD hospitalizations (2005-2019) using the National Inpatient Sample, we investigated hospitalization rates for ischemic and hemorrhagic cerebrovascular diseases concerning ESKD, PVD, KTx, or their combinations. Patients hospitalized with cerebral infarction due to thrombosis/embolism/occlusion (CITO) or artery occlusion resulting in cerebral ischemia (AOSI) had higher rates of comorbid ESKD and PVD (4.17% and 7.29%, respectively) versus non-CITO or AOSI hospitalizations (2.34%, p < 0.001; 2.29%, p < 0.001). Conversely, patients hospitalized with nontraumatic intracranial hemorrhage (NIH) had significantly lower rates of ESKD and PVD (1.64%) compared to non-NIH hospitalizations (2.34%, p < 0.001). Furthermore, hospitalizations for CITO or AOSI exhibited higher rates of KTx and PVD (0.17%, 0.09%, respectively) compared to non-CITO or AOSI hospitalizations (0.05%, p = 0.033; 0.05%, p = 0.002). Patients hospitalized with NIH showed similar rates of KTx and PVD (0.04%) versus non-NIH hospitalizations (0.05%, p = 0.34). This nationwide analysis reveals that PVD in ESKD patients is associated with increased hospitalization rates with cerebral ischemic events and reduced NIH events. Among KTx recipients, PVD correlated with increased hospitalizations for ischemic events, without affecting NIH. This highlights management concerns for patients with KTx and PVD.

Synopsis of the Korean Society of Nephrology 2023 Practical Recommendations for the Management of Diabetic Kidney Disease

Korea has one of the highest rates of end-stage kidney disease (ESKD) worldwide and nearly half of all new cases are attributed to diabetes. Diabetes represents a critical aspect of chronic kidney disease (CKD)-related mortality that entails substantial treatment costs. Given the profound impact of ESKD, it is imperative to initiate robust initiatives to formulate and implement effective preventive and therapeutic strategies. These strategies should target the prevention of CKD development in individuals with diabetes and decelerate the progression of diabetic kidney disease. Recognizing this challenge, the Korean Society of Nephrology (KSN) has introduced the kidney health plan 2033, a comprehensive endeavor designed to alleviate the burdens associated with CKD and ESKD in Korea. As part of this initiative, KSN has undertaken the development of the KSN 2023 practical recommendations for the management of diabetic kidney disease. The hope is that implementation of this guideline will delay the onset of kidney-related complications in diabetic patients throughout the country.

Years of life lost and long-term outcomes due to glomerular disease in a Southeast Asian Cohort

Death and end-stage kidney disease (ESKD) are major outcomes of glomerular disease. (GD) The years of potential life lost (YLL) may provide additional insight into the disease burden beyond death rates. There is limited data on premature mortality in GD. In this retrospective observational cohort study, we evaluated the mortality, ESKD rates, and YLL in Thais with biopsy-proven GD. The mortality and combined outcome rates were determined by log-rank test and ESKD by using a competing risk model. YLL and premature life lost before age 60 were calculated for different GD based on the life expectancy of the Thai population. Patients with GD (n = 949) were followed for 5237 patient years. The death rate and ESKD rates (95%CI) were 4.2 (3.7–4.9) and 3.3 (2.9–3.9) per 100 patient-years, respectively. Paraprotein-related kidney disease had the highest death rate, and diabetic nephropathy had the highest ESKD rate. Despite not having the highest death rate, lupus nephritis (LN) had the highest YLL (41% of all GD) and premature loss of life before age 60. In conclusion, YLL provided a different disease burden assessment compared to mortality rates and identified LN as the major cause of premature death due to GD in a Southeast Asian cohort.

Data quality and patient characteristics in European ANCA-associated vasculitis registries: data retrieval by federated querying

ObjectivesThis study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil cytoplasmic antibody-associated vasculitis (AAV)...

Treatment Location Variation for Chronic Limb-Threatening Ischemia in Patients With Kidney Failure

IntroductionEnd-stage kidney disease (ESKD) is an established risk factor for chronic limb-threatening ischemia (CLTI). Procedural location for ESKD patients has not been well described. This study aims to examine variation in index procedural location in ESKD versus non-ESKD patients undergoing peripheral vascular intervention for CLTI and identify preoperative risk factors for tibial interventions. MethodsChronic limb-threatening ischemia (CLTI) patients were identified in the Vascular Quality Initiative (VQI) peripheral vascular intervention dataset. Patient demographics and comorbidities were compared between patients with and without ESKD and those undergoing index tibial versus nontibial interventions. A multivariable logistic regression evaluating risk factors for tibial intervention was conducted. ResultsA total of 23,480 procedures were performed on CLTI patients with 13.6% (n = 3154) with ESKD. End-stage kidney disease (ESKD) patients were younger (66.56 ± 11.68 versus 71.66 ± 12.09 y old, P = 0.019), more often Black (40.6 versus 18.6%, P < 0.001), male (61.2 versus 56.5%, P < 0.001), and diabetic (81.8 versus 60.0%, P < 0.001) than non-ESKD patients. Patients undergoing index tibial interventions had higher rates of ESKD (19.4 versus 10.6%, P < 0.001) and diabetes (73.4 versus 57.5%, P < 0.001) and lower rates of smoking (49.9 versus 73.0%, P < 0.001) than patients with nontibial interventions. ESKD (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.52-1.86, P < 0.001), Black race (OR 1.19, 95% CI 1.09-1.30, P < 0.001), and diabetes (OR 1.82, 95% CI 1.71-2.00, P < 0.001) were risk factors for tibial intervention. ConclusionsPatients with ESKD and CLTI have higher rates of diabetes and tibial disease and lower rates of smoking than non-ESKD patients. Tibial disease was associated with ESKD, diabetes, and Black race.

Translating the efficacy of dapagliflozin in chronic kidney disease to lower healthcare resource utilization and costs: a medical care cost offset analysis

AimsDapagliflozin was approved for use in patients with chronic kidney disease (CKD) based on results of the DAPA-CKD trial, demonstrating attenuation of CKD progression and reduced risk of cardio-renal outcomes and all-cause mortality (ACM) versus placebo, in addition to standard therapy. The study objective was to assess the potential medical care cost offsets associated with reduced rates of cardio-renal outcomes across 31 countries and regions.Materials and methodsA comparative cost-determination framework estimated outcome-related costs of dapagliflozin plus standard therapy versus standard therapy alone over a 3-year horizon based on the DAPA-CKD trial. Incidence rates of end-stage kidney disease (ESKD), hospitalizations for heart failure (HHF), acute kidney injury (AKI), and ACM were estimated for a treated population of 100,000 patients. Associated medical care costs for non-fatal events were calculated using sources from a review of publicly available data specific to each considered setting.ResultsPatients treated with dapagliflozin plus standard therapy experienced fewer incidents of ESKD (7,221 vs 10,767; number needed to treat, NNT: 28), HHF (2,370 vs 4,684; NNT: 43), AKI (4,110 vs. 5,819; NNT: 58), and ACM (6,383 vs 8,874; NNT: 40) per 100,000 treated patients versus those treated with standard therapy alone. Across 31 countries/regions, reductions in clinical events were associated with a 33% reduction in total costs, or a cumulative mean medical care cost offset of $264 million per 100,000 patients over 3 years.Limitations and conclusionsThis analysis is limited by the quality of country/region-specific data available for medical care event costs. Based on the DAPA-CKD trial, we show that treatment with dapagliflozin may prevent cardio-renal event incidence at the population level, which could have positive effects upon healthcare service delivery worldwide. The analysis was restricted to outcome-associated costs and did not consider the cost of drug treatments and disease management.

Standardization of Pre-operative Evaluation to Improve the Outcome of Arteriovenous Fistula for Vascular Access of Hemodialysis: A Review of 700 Cases.

Background With the advent of COVID-19, mortality rates of end-stage kidney disease (ESKD) rose by 37% which makes its treatment an important part of healthcare. Arteriovenous fistula (AVF) is linked to higher patient survival rates. Cimino-Brescia fistula is the most effective vascular access technique, but it has a high rate of primary failure (PF) and a several-week maturation period before it can be used. The current study aims to verify the preoperative evaluation in improving survival among AVF patients. Methodology The current study is a retrospective analysis of the hospital database from Jan 2022 to July 2023, with patients of a mean age of 60.2 years. The sample size was around 700, including the patients indicated for long-term hemodialysis (HD) with an estimated GFR of less than 20 mm/min/1.73m². Following AVF surgery, post-operative outcomes, PF, and maturation time were considered. Results Among the 757 AVF procedures, 588 (82%) were new cases, and 112 (16%) had prior AVF history on the same side. PF was observed in 126 (18%) AVFs, while 574 (84%) achieved maturation. Age at surgery did not correlate with PF. Male sex and brachiocephalic AVF (BCAVF) had lower PF rates, while female gender, non-BCAVF, and vascular chronic kidney disease (CKD) were independent predictors. Proximal fistulas had a higher failure risk (32%). During surgery, the PF occurred six times more frequently in patients with veins and arteries under 2 mm and without a bruit. Conclusion AVF maturation aims to achieve a functional AVF for easy dialysis, requiring meticulous vein selection, doppler vascular mapping, and a standardized process to reduce PF rates. Factors determining PF include thrill and bruit, flow rates, and comorbidities. These findings can help clinicians make informed decisions and improve outcomes for patients undergoing fistula surgery.

Low-Dose Intravenous Methylprednisolone in Remission Induction Therapy for ANCA-Associated Vasculitis.

Glucocorticoids (GC) remain integral to the management of ANCA associated vasculitis (AAV), but are associated with significant adverse effects. Recent studies have shown reduced oral GC dosing to be safe and effective, however data guiding the use of intravenous (IV) methylprednisolone (MTP) is limited. A single centre, retrospective cohort of patients with AAV were divided into two groups; low-dose GC (patients receiving 250mg IV MTP followed by a tapering course of 30mg prednisolone daily) versus high-dose GC (1.5g IV MTP followed by tapering course of 40-60mg prednisolone daily). Primary outcomes included; end stage kidney disease (ESKD) and mortality, secondary outcomes; glucocorticoid related toxicity, remission and relapse rates. This study was applied to patients with newly diagnosed AAV, including those with severe or life-threatening disease. Sixty-five patients were included in the final analysis, 34 in the high dose and 31 in the low-dose treatment group. At diagnosis, more advanced renal impairment and histological disease was present in the low-dose cohort. The rate of ESKD was similar between groups at 6 and 12 months (P=0.22, P=0.60 respectively). More deaths occurred in the high-dose group (26.5% vs 6.5%, P=0.05) although on multivariable analysis this was not significant (P=0.06). Remission rates were comparable and there was no significant difference in relapses. Adverse events were seen in both groups but the high dose patients experienced a higher number of severe infections, weight gain and steroid induced diabetes. We demonstrate that markedly reduced dose IV MTP with a lower overall cumulative dose GC is safe and effective in the management of severe AAV disease, with no significant difference in primary outcomes.

Prevalence and outcomes of end-stage kidney disease in patients with systemic lupus erythematous: a population-based study.

This study aims to examine the prevalence and outcomes of end-stage kidney disease (ESKD) among systemic lupus erythematosus (SLE) patients. SLE patients identified from the national administrative datasets were linked to the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) to identify the ESKD cases. Period prevalence of ESKD among SLE patients was calculated. The risk of developing ESKD by ethnicity was explored with Cox Proportional Hazards model. The adjusted hazard ratio (HR) of all-cause mortality for Māori, Pacific, Asian compared to European/others was estimated. Of the 2837 SLE patients, 210 (7.4%) developed ESKD. The average period prevalence of ESKD among SLE patients was 5.7%. Men had twice the prevalence rate of ESKD than women (10.0% vs 5.2%). Māori and Pacific had higher prevalence rate than Asian and European/others (9.4%, 9.8% vs 4.4% and 3.8%). The adjusted HR of developing ESKD for men compared to women was 3.37 (95% CI 1.62-7.02). The adjusted HR of developing ESKD for Māori and Pacific compared to European/others was 4.63 (95% CI 1.61-13.29) and 4.66 (95% CI 1.67-13.00), respectively. Compared to European/others, Māori had an HR of 2.17 (95% CI 1.18-4.00) for all-cause mortality. SLE patients had a high prevalence rate of ESKD. Men, Māori, and Pacific patients with SLE were more likely to develop ESKD. Māori patients with ESKD had poorer survival than other patients. Interventions are needed to reduce the risk of ESKD and to improve the survival of ESKD patients for the disadvantaged groups.

Kidney Function and Long-Term Risk of End-Stage Kidney Disease and Mortality in a Multiethnic Population

Contemporary differences between South Asian and White ethnicities in the incidence of end-stage kidney disease (ESKD) and mortality are poorly described. Data for all South Asian patients who had an estimated glomerular filtration rate (eGFR) measure after January 1, 2006, and 1 million randomly selected participants of other ethnicities were extracted from the Clinical Practice Research Datalink (CPRD). All participants were followed-up with from index date until ESKD, all-cause mortality, or end of study. All-cause mortality rate and ESKD incidence rate by age were described among Whites and South Asians, and adjusted hazard ratios (HRs) of these 2 outcomes by baseline eGFR estimated using Cox proportional hazard model. A total of 40,888 South Asians and 236,634 Whites were followed for a median of 5.3 and 9.4 years for ESKD incidence and mortality outcomes, respectively. All-cause mortality rates were higher among Whites than South Asians; South Asian women aged between 70 and 85 years had a slightly higher ESKD incidence rate compared to their White counterparts. Compared to Whites with a baseline eGFR of 90 ml/min per 1.73 m2, adjusted HRs for all-cause mortality were significantly lower among South Asians than Whites; however, adjusted HRs for ESKD incidence by baseline eGFR were similar in both ethnicities. Calculating South Asian eGFRs using an ethnicity-specific equation had no impact on the results. South Asians experience lower mortality than Whites but not substantially higher rates of ESKD. Further research is warranted to better understand the reasons for these ethnic differences and possible impacts on chronic kidney disease (CKD) service delivery and patient outcomes.

#4146 LIMITATIONS AND UNCERTAINTIES OF ASSESSING AND MANAGING OLDER PATIENTS WITH ANCA ASSOCIATED VASCULITIS

Abstract Background and Aims ANCA associated vasculitis (AAV) has a peak incidence in 65 -74 yr olds. As a result, it affects an ageing population who are vulnerable to co-morbidities, polypharmacy and frailty. Due to the high burden of morbidity and mortality in these patients, it is increasingly recognised that individualised management is needed. Whilst current immunotherapies are effective, there remains caution in treating older patients due to the potential risks. Yet despite AAV being a condition that predominantly affects older people, few studies have looked specifically at the benefit of treating AAV in such age groups, or at frailty assessments tools to guide treatment. Method We aimed to evaluate treatment outcomes in older AAV patients, as well as frailty assessment tools to aid prognostication and management. A cohort study evaluating outcomes of induction immunosuppression in patients ≥75yrs was constructed from 2 centres, with subsequent meta-analysis of published data [1]. In addition, studies identifying frail patients, who may be at risk of adverse outcomes, were carried out using the quantitative tools; Hospital Frailty Risk Score (HFRS) [2] and the Clinical Frailty Scale (CFS). Primary outcomes were mortality and end stage kidney disease (ESKD). The HFRS was calculated using hospital coding data from any hospital admissions between a patient's AAV diagnosis to 2yr follow up. Patients were categorized into low, intermediate and high HFRS groups. CFS scores at presentation were documented prospectively and then repeated a minimum of 6 weeks from diagnosis. A CFS score of ≥5 was used to categorise frailty. Differences in the scores were assessed and compared to clinical outcomes. Results Retrospective analysis of our AAV cohort aged ≥75 yrs demonstrated that induction immunosuppression was associated with a significant reduction in the 2yr mortality risk [HR 0.29 (95% CI 0.09–0.93)]. Following systematic review, with a study population of 290 patients, the pooled HR by meta-analysis confirmed a significant reduction in the risk of death with induction treatment [HR 0.31 (95% CI 0.16 - 0.57)]. Treated patients had a lower rate of ESKD, but this was not statistically significant [HR 0.71 (95% CI 0.15 – 3.35)]. Looking separately at frailty assessments, mortality and ESKD were assessed according to HFRS and CFS. Thirty-four patients with AAV aged ≥75 yrs were assessed using HFRS and categorised into the low (n = 18), intermediate (n = 13) and high (n = 3) HFRS groups. All patients in the high HFRS groups had ≥1 episodes of hospitalization after diagnosis of AAV. However, there was no difference in mortality or duration of hospitalisation between the 3 categories. Forty-one patients with AAV aged ≥65yrs were assessed using the CFS. The median CFS at diagnosis and follow-up was 4. There was no significant interval change in CFS (P = 0.16) suggesting that patients did not become frailer. Instead, there was a tendency towards improved frailty scores at reassessment (n = 17, 43%), with some patients going from a CFS of 6 (moderately frail) to 3 (managing well). There was no significant difference in ESKD between those categorised as frail and non-frail (P = 1.0), although crude mortality was higher among those initially categorised as frail (P = 0.03). Conclusion Our research shows that older patients with AAV benefit from standard remission-induction therapy and those treated had favourable mortality outcomes compared to those who were not. Furthermore, frailty assessment tools do not correlate clearly with clinical outcomes. Whilst there is evidence to support the use of HFRS and CFS in a many diseases, its utility in determining frailty and potential susceptibility to adverse effects of therapy in patients with multifaceted, autoimmune inflammatory disease remains limited. Patients may present ‘frail’ as a result of significant disease burden, which has the potential to improve with appropriate treatment. We suggest that age alone and frailty at assessment should not be a limiting factor when considering treatment and prospective studies of this population are needed.

Diabetic kidney disease induces transcriptome alterations associated with angiogenesis activity in human mesenchymal stromal cells

BackgroundTherapeutic interventions that optimize angiogenic activities may reduce rates of end-stage kidney disease, critical limb ischemia, and lower extremity amputations in individuals with diabetic kidney disease (DKD). Infusion of autologous mesenchymal stromal cells (MSC) is a promising novel therapy to rejuvenate vascular integrity. However, DKD-related factors, including hyperglycemia and uremia, might alter MSC angiogenic repair capacity in an autologous treatment approach.MethodsTo explore the angiogenic activity of MSC in DKD, the transcriptome of adipose tissue-derived MSC obtained from DKD subjects was compared to age-matched controls without diabetes or kidney impairment. Next-generation RNA sequencing (RNA-seq) was performed on MSC (DKD n = 29; Controls n = 9) to identify differentially expressed (DE; adjusted p < 0.05, |log2fold change|> 1) messenger RNA (mRNA) and microRNA (miRNA) involved in angiogenesis (GeneCards). Paracrine-mediated angiogenic repair capacity of MSC conditioned medium (MSCcm) was assessed in vitro using human umbilical vein endothelial cells incubated in high glucose and indoxyl sulfate for a hyperglycemic, uremic state.ResultsRNA-seq analyses revealed 133 DE mRNAs (77 upregulated and 56 down-regulated) and 208 DE miRNAs (119 up- and 89 down-regulated) in DKD-MSC versus Control-MSC. Interestingly, miRNA let-7a-5p, which regulates angiogenesis and participates in DKD pathogenesis, interacted with 5 angiogenesis-associated mRNAs (transgelin/TAGLN, thrombospondin 1/THBS1, lysyl oxidase-like 4/LOXL4, collagen 4A1/COL4A1 and collagen 8A1/COL8A1). DKD-MSCcm incubation with injured endothelial cells improved tube formation capacity, enhanced migration, reduced adhesion molecules E-selectin, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 mRNA expression in endothelial cells. Moreover, angiogenic repair effects did not differ between treatment groups (DKD-MSCcm vs. Control-MSCcm).ConclusionsMSC from individuals with DKD show angiogenic transcriptome alterations compared to age-matched controls. However, angiogenic repair potential may be preserved, supporting autologous MSC interventions to treat conditions requiring enhanced angiogenic activities such as DKD, diabetic foot ulcers, and critical limb ischemia.

Sex differences in risk factors for end-stage kidney disease and death in type 2 diabetes: A retrospective cohort study.

This study investigated the sex differences in the risk of end-stage kidney disease (ESKD) and mortality, as well as the effect modification of sex on associated factors in patients with type 2 diabetes. This multicenter observational cohort study included 4328 patients with type 2 diabetes. Hazard ratios (HRs) with 95% confidence intervals (CIs) of sex for ESKD and death were estimated using Cox proportional regression with adjustment for baseline covariates. For assessing risk modification, HRs and incidence rates for ESKD and death were compared between sexes across patient characteristics using Cox proportional and Poisson regression models. During a median follow-up of 7 years, 276 patients (70% men) developed ESKD, and 241 patients (68% men) died. Men had higher risks of ESKD (HR 1.34; 95% CI 1.02-1.75; p=.034) and death (HR 1.64; 95% CI 1.24-2.16; p=.001) versus women after adjusting for multiple covariates. Among patients with microalbuminuria, men had a substantially higher risk of ESKD versus women, compared to those with normo- and macroalbuminuria (p for interaction .04). Incidence rates were also increased in men versus women with albuminuria of around 300 mg/g. No differences were detected in the association of sex and death across baseline patient subgroups. In type 2 diabetes, men had an increased risk of ESKD and death versus women. Moderately increased albuminuria was strongly associated with sex difference in developing ESKD.

Incident heart failure and the subsequent risk for progression to end stage kidney disease in South East Asian people with type 2 diabetes

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Singapore National Medical Research Council grants: CSA-INV/0020/2017 and CS-IRG (MOH-000066) Background Heart failure (HF) is a common but often unrecognized complication of type 2 diabetes (T2D). Both low eGFR and high albuminuria are strong risk factors for development of HF in diabetic population. However, data on the role of HF in long-term kidney disease outcome are sparse. Aim We sought to study the risk for progression to end stage kidney disease (ESKD) after incident HF in multi-ethnic South East Asian people with type 2 diabetes. Participants and Methods A total of 1,756 individuals with type 2 diabetes recruited from a regional hospital were followed for a median of 7.3 (interquartile range 6.8-7.8) years. Incident HF was identified according to European Society of Cardiology 2016 criteria. HF was subtyped into preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) with ventricular ejection fraction (LVEF) cut-off at ≥50% and &amp;lt;50% respectively. Progression to ESKD was defined as patients with sustained eGFR &amp;lt;15ml/min per 1.73m2 with confirmation measurement 3 months apart, or on sustained dialysis for at least 3 months or death attributable to renal cause, whichever occurred first. The risk of progression to ESKD after HF was assessed using Cox proportional hazard models. Results Average age of participants was 57±11 years with diabetes duration of 11 (IQR 4-15) years. There were 52% Chinese, 22% Malay and 26% Asian Indian in the study participants. We identified 113 incident HF events (65 HFpEF and 48 HFrEF) during 11,869 patient-years (crude incidence rate 9.5 per 1000 patient-years). Individuals with HF occurrence were older, had a longer diabetes duration, higher body mass index, HbA1c and systolic blood pressure, and prevalent diabetic kidney disease (DKD). We identified 75 ESKD events in the follow-up (incidence rate 6.0 per 1000 patient-years) and 22 occurred after incident HF. Cox regression model showed that incident HF was associated with 7.4-fold (95% CI 4.5-12.2) unadjusted risk for progression to ESKD. The association of HF with subsequent risk for ESKD remained statistically significant (adjusted hazard ratio, HR 2.3, 95% CI 1.3-4.2) after adjustment for multiple clinical risk factors including baseline eGFR and albuminuria. Similar outcome was obtained when death attributable to non-renal cause was taken as a competing risk for ESKD. In a fully adjusted model, both HFpEF and HFrEF patients had a higher risk for progression to ESKD (adjusted HR 2.8, 95%CI 1.4-5.9, and 2.2, 95%CI 1.0-4.7, respectively), as compared to those with no HF events. The incidence rate of ESKD in patients with incident HF was 5.6 per 100 patient-years whilst in propensity score-matched patients without HF event, the rate was 2.1 per 100 patient-years. Conclusion Incident HF is a strong independent risk factor for progression to ESKD in individuals with T2D. Our data highlight the importance for prevention, early diagnosis and treatment of HF to improve the renal outcomes in individuals with type 2 diabetes.

Age-Dependent Effects of Acute Kidney Injury on End-Stage Kidney Disease and Mortality in Patients with Moderate to Severe Chronic Kidney Disease

Introduction: Old age has been considered as a positive modifier of chronic kidney disease (CKD), but the progression of CKD is often accelerated by acute kidney injury (AKI) in older adults. This study aimed to investigate this paradoxical interplay and identify age-specific predictors of end-stage kidney disease (ESKD). Methods: This retrospective cohort included 6,101 patients with CKD stage 3B-5 followed at a single center during 2005–2018. Participants were stratified into four age groups to explore age-dependent influences on the risk of ESKD and all-cause mortality. Multivariate Cox proportional hazard regression model with competing risk analysis was used to identify predictors of outcomes. Results: During a median follow-up of 2.68 years, 1,650 (27.0%) patients developed ESKD and 541 (8.9%) patients died. The rate of ESKD decreased with advancing age, being lowest in the very old-aged (>75 years) group who displayed the slowest rate of estimated glomerular filtration rate (eGFR) decline. Multivariate Cox proportional hazard regression adjusted for competing death showed that younger ages, compared with patients aged >75 years, together with AKI episodes and several traditional risk factors were identified as predictors for ESKD. The impact of AKI episodes on ESKD development was most prominent in patients aged >75 years. These results were confirmed with subgroup analyses in patients with outcomes of different ages. Conclusion: Older adults with CKD exhibited a slower decline rate of eGFR, yet they were more likely to develop ESKD following AKI episodes. These results suggest tackling AKI is needed to prevent accelerated initiation of renal replacement therapy in elderly patients with pre-existing CKD.

A low rate of end-stage kidney disease in membranous nephropathy: A single centre study over 2 decades.

Membranous nephropathy is the commonest cause of nephrotic syndrome in non-diabetic Caucasian adults over the age of 40 years. Primary membranous nephropathy is limited to the kidneys. Clinical management aims to induce remission, either spontaneously with supportive care, or with immunosuppression. Here, we describe the natural history of this condition in a large tertiary centre in the UK. 178 patients with primary membranous nephropathy were identified over 2 decades. We collected data on demographics, baseline laboratory values, treatment received and outcomes including progression to renal replacement therapy and death. Analysis was performed on the whole cohort and specific subgroups. Univariate and multivariate Cox regression was also performed. Median age was 58.3 years with 63.5% male. Median baseline creatinine was 90μmol/L and urine protein-creatinine ratio 664g/mol. Remission (partial or complete) was achieved in 134 (75.3%), either spontaneous in 60 (33.7%) or after treatment with immunosuppression in 74 (41.6%), and of these 57 (42.5%) relapsed. Progression to renal replacement therapy was seen in 10.1% (much lower than classically reported) with mortality in 29.8%. Amongst the whole cohort, those who went into remission had improved outcomes compared to those who did not go into remission (less progression to renal replacement therapy [4.5% vs 28%] and death [20.1% vs 67%]. Those classified as high-risk (based on parameters including eGFR, proteinuria, serum albumin, PLA2R antibody level, rate of renal function decline) also had worse outcomes than those at low-risk (mortality seen in 52.6% vs 10.8%, p<0.001). The median follow-up period was 59.5 months. We provide a comprehensive epidemiologic analysis of primary membranous nephropathy at a large tertiary UK centre. Only 10.1% progressed to renal replacement therapy. For novelty, the KDIGO risk classification was linked to outcomes, highlighting the utility of this classification system for identifying patients most likely to progress.

Attenuated Risk Association of End-Stage Kidney Disease with Metformin in Type 2 Diabetes with eGFR Categories 1-4.

Type 2 diabetes (T2D)-associated end-stage kidney disease (ESKD) is a global burden, while the renoprotective effects of metformin remain controversial. In a population-based cohort (2002–2018) including 96,643 patients with T2D observed for 0.7 million person-years, we estimated the risk association of metformin and its dose-relationship with ESKD in a propensity-score overlap-weighting (PS-OW) cohort by eGFR categories. Amongst 96,643, 83,881 (86.8%) had eGFR-G1/G2 (≥60 mL/min/1.73 m2), 8762 (9.1%) had eGFR-G3a (≥45–60 mL/min/1.73 m2), 3051 (3.2%) had eGFR-G3b (≥30–45 mL/min/1.73 m2), and 949 (1.0%) had eGFR-G4 (≥15–30 mL/min/1.73 m2). The respective proportions of metformin users in these eGFR categories were 95.1%, 81.9%, 53.8%, and 20.8%. In the PS-OW cohort with 88,771 new-metformin and 7872 other oral glucose-lowering-drugs (OGLDs) users, the respective incidence rates of ESKD were 2.8 versus 22.4/1000 person-years. Metformin use associated with reduced risk of ESKD (hazard ratio (HR) = 0.43 [95% CI: 0.35–0.52] in eGFR-G1/G2, 0.64 [0.52–0.79] in eGFR-G3a, 0.67 [0.56–0.80] in eGFR-G3b, and 0.63 [0.48–0.83] in eGFR-G4). Metformin use was associated with reduced or neutral risk of major adverse cardiovascular events (MACE) (7.2 versus 16.0/1000 person-years) and all-cause mortality (14.6 versus 65.1/1000 person-years). Time-weighted mean daily metformin dose was 1000 mg in eGFR-G1/G2, 850 mg in eGFR-G3a, 650 mg in eGFR-G3b, and 500 mg in eGFR-G4. In a subcohort of 14,766 patients observed for 0.1 million person-years, the respective incidence rates of lactic acidosis and HR in metformin users and non-users were 42.5 versus 226.4 events/100,000 person-years (p = 0.03) for eGFR-G1/G2 (HR = 0.57, 0.25–1.30) and 54.5 versus 300.6 events/100,000 person-years (p = 0.01) for eGFR-G3/G4 (HR = 0.49, 0.19–1.30). These real-world data underscore the major benefits and low risk of lactic acidosis with metformin use down to an eGFR of 30 mL/min/1.73 m2 and possibly even 15 mL/min/1.73 m2, while reinforcing the importance of dose adjustment and frequent monitoring of eGFR.

Long-term prognosis of primary focal segmental glomerulosclerosis in children

Objective: To investigate risk factors for the long-term prognosis of primary focal segmental glomerulosclerosis (FSGS) and associated with renal prognosis in children. Methods: A retrospective study was conducted by collecting clinical data including general information, clinical features and renal pathological findings of 124 children with primary FSGS in Department of Pediatrics of Jinling Hospital from January 2003 to December 2019. The cumulative renal survival rate was calculated by Kaplan-Meier survival analysis. The risk factors related to renal prognosis were identified by Cox regression risk model analysis and receiver operating characteristic (ROC) curve. Results: Among 124 children, 94 were males (75.8%) and 30 were females (24.2%). The children were 16 (14, 17) years of age at the time of kidney biopsies. There were 102 cases (82.3%) aged from 13 to 18 years. The period of follow-up was 64.8 (32.1, 86.0) months. There were 49 cases (39.5%) with nonspecific variant, 33 cases (26.6%) with tip variant, 22 cases (17.7%) with collapsing variant, 14 cases (11.3%) with cellular variant and 6 cases (4.8%) with periportal variant. The data of Kaplan-Meier survival analysis showed that cumulative renal survival rates of end-stage kidney disease (ESKD) or ≥50% decline in estimated glomerular filtration rate (eGFR) from baseline at the year of 5, 10 and 15 after renal biopsies were 66.9%, 51.4% and 21.0% respectively. Multivariate Cox regression analysis showed that hypertension, glomerular segmental sclerosis ratio, moderate to severe chronic tubulointerstitial lesions were independent risk factors for progressing to ESKD or ≥50% reduction in eGFR from baseline in pediatric FSGS (HR=5.28, 1.03, 7.81, 95%CI 2.77-10.05, 1.01-1.04, 4.08-14.98, all P<0.01). ROC curve analysis showed glomerular segmental sclerosis ratio (AUC=0.734, P<0.05, optimal cut-off value=25.4%, sensitivity=50.0%, specificity=88.6%), moderate and severe chronic renal tubulointerstitial lesions (AUC=0.724, P<0.05, sensitivity=46.3%, specificity=98.6%) had good efficacy in evaluating renal outcomes of FSGS. Conclusions: The long-term prognosis of FSGS in children is poor. The risk factors of poor prognosis in children with FSGS are hypertension, moderate to severe chronic renal tubulointerstitial lesions and glomerular segmental sclerosis (≥25.4%).