Risk Of End-stage Kidney Disease Research Articles

Kidney replacement therapy trends in end-stage kidney disease patients in South Korea during the COVID-19 pandemic.

The corona virus disease 2019 posed a major risk for end-stage kidney disease (ESKD) cases. Our study aimed to assess changes in kidney replacement therapy (KRT) trends and healthcare access for these patients during the pandemic. We retrospectively analyzed nationwide data from July 2017 to June 2022 to assess changes in KRT and ESKD incidence. KRT modalities included peritoneal dialysis (PD), hemodialysis (HD), and kidney transplantation (KT). We utilized the interrupted time series (ITS) method to compare changes in KRT modality before and after the incidence of the COVID-19 pandemic. ESKD incidence remained stable from 2018 to April 2022. The ITS analysis confirmed that the pandemic did not significant impact overall KRT incidence. PD cases decreased (5.7% to 1.3%), while HD cases increased (81.6% to 85%), and KT recipient remained relatively stable (12.7% to 17.3%). The hospitalization and hospital stay decreased in nursing hospital (165.01 days to 147.77 days) and general hospital (61.34 days to 55.58 days) during the pandemic, however, remained unchanged for PD and KT. Our findings indicate no significant changes in ESKD incidence in South Korea during the pandemic. However, there were shifts in modality distribution, with decreased PD and increased HD cases. Notably, HD cases showed a significant reduction in hospital admissions and length of stay. The healthcare system demonstrated stability during the pandemic, with minimal disruptions in ESKD care.

Exploring the Cardiorenal Benefits of SGLT2i: A Comprehensive Review

The history of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is so long and started in 1835 when Petersen extracted a compound called phlorizin from apple tree bark. About fifty years later, von Mering discovered its glucosuric properties. In the 1980s, it was discovered that the glucosuria resulted from inhibition by phlorizin of glucose reabsorption by the renal tubules, which lowered blood glucose levels in diabetic rats. Nowadays, beyond their glucose-lowering effects, growing evidence suggests significant cardiorenal benefits associated with SGLT2i therapy. Indeed, several clinical trials, including landmark studies such as EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58, have demonstrated robust reductions in cardiovascular events, particularly heart failure hospitalizations and cardiovascular mortality, among patients treated with SGLT2i. However, subsequent trials showed that SGLT2i benefits extend beyond the diabetic population, encompassing individuals with and without diabetes. Additionally, SGLT2i exhibit nephroprotective effects, manifesting as a slowing of the progression of chronic kidney disease and a reduction in the risk of end-stage kidney disease. The mechanisms underlying the cardiorenal benefits of SGLT2i are multifactorial and include improvements in glycemic control, reduction in arterial stiffness, modulation of inflammation and oxidative stress, reduction of intraglomerular pression and promotion of natriuresis and diuresis through inhibition of SGLT2 in the luminal brush border of the first segments of the proximal kidney tubule. This narrative review aims to explore the cardiorenal outcomes of SGLT2i, encompassing their mechanisms of action, clinical evidence, safety profile, and implications for clinical practice.

Steps to understanding diabetes kidney disease: a focus on metabolomics.

Diabetic nephropathy (DN), a leading cause of chronic kidney disease and end-stage kidney disease (ESKD), poses global health challenges given its increasing prevalence. DN increases the risk of mortality and cardiovascular events. Early identification and appropriate DN management are crucial. However, current diagnostic methods rely on general traditional markers, highlighting the need for DN-specific diagnostics. Metabolomics, the study of small molecules produced by metabolic activity, promises to identify specific biomarkers that distinguish DN from other kidney diseases, decode the underlying disease mechanisms, and predict the disease course. Profound changes in metabolic pathways are apparent in individuals with DN, alterations in the tricarboxylic acid cycle and amino acid and lipid metabolism, suggestive of mitochondrial dysfunction. Metabolomics aids prediction of chronic kidney disease progression; several metabolites serve as indicators of renal functional decline and the risk of ESKD. Integration of such information with other omics data will further enhance our understanding of DN, paving the way to personalized treatment. In summary, metabolomics and multi-omics offer valuable insights into DN and are promising diagnostic and prognostic tools.

The associations between functional vitamin K status and all-cause mortality, cardiovascular disease and end-stage kidney disease in persons with type 1 diabetes.

Vitamin K deficiency is common in persons with kidney disease, which is a known complication of diabetes. We aimed to assess the association of vitamin K status as reflected by plasma dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP) with mortality, cardiovascular disease (CVD) and progression to end-stage kidney disease (ESKD) in persons with type 1 diabetes. We analysed plasma dp-ucMGP in stored baseline samples from a cohort of 667 persons with type 1 diabetes (baseline visit: 2009-2011). Information on mortality and CVD was obtained through linkage to registers. Cox-proportional hazards models were applied to estimate hazard ratios (HRs) of mortality, CVD and ESKD per one doubling of dp-ucMGP. A total of 53 deaths were recorded during follow-up. Persons with higher dp-ucMGP (reflecting lower vitamin K status) had higher mortality in the unadjusted model (HR: 2.06 [95% confidence interval-CI: 1.22-3.45]), but not in the fully adjusted model (HR: 0.88 [95% CI: 0.44-1.73]). Particularly, adjustment for glomerular filtration rate and urinary albumin excretion rate attenuated the HR. A similar pattern was observed in unadjusted models for incidence of CVD (HR: 1.58 [95% CI: 1.03-2.42]) and risk of ESKD (HR: 7.62 [95% CI: 4.25-13.68]). In the fully adjusted models, the HRs became statistically insignificant. In persons with type 1 diabetes, lower vitamin K status was associated with higher mortality, CVD and progression to ESKD, however, not after adjustment for other risk factors. Interventional studies are needed to elucidate the role of vitamin K in persons with type 1 diabetes.

Predictive value of serum hepcidin levels for the risk of incident end-stage kidney disease in patients with chronic kidney disease: The KNOW-CKD

Introduction: Despite the pivotal role of hepcidin in the development of anemia among the patients with chronic kidney disease (CKD), the association between serum hepcidin levels and CKD progression has been never investigated. We here hypothesized that elevation in serum hepcidin levels might be associated with the risk of incident end-stage kidney disease (ESKD) among the patients with pre-dialysis CKD. Methods: A total of 2,109 patients with pre-dialysis CKD at stages 1 to pre-dialysis 5 were categorized into the quartiles by serum hepcidin levels. The study outcome was incident ESKD. The median duration of follow-up was 7.9 years. Results: The analysis of the baseline characteristics revealed that unfavorable clinical features were in general associated with higher serum hepcidin levels. The cumulative incidence of ESKD was significantly differed by serum hepcidin levels, with the highest incidence in the 4th quartile (P < 0.001, by log-rank test). Cox regression analysis demonstrated that, compared to the 1st quartile, the risk of incident ESKD is significantly increased in the 4th quartile (adjusted hazard ratio 1.372, 95% confidence interval 1.070 to 1.759). Penalized spline curve analysis illustrated a linear, positive correlation between serum hepcidin levels and the risk of incident ESKD. Subgroup analyses revealed that the association is significantly more prominent in the patients with advanced CKD (i.e., estimated glomerular filtration rate < 45 mL/min/1.73 m2). Conclusion: Elevation in serum hepcidin levels is significantly associated with the risk of incident ESKD among the patients with pre-dialysis CKD.

Elevated Risk of End-Stage Kidney Disease in Stroke Patients: A Population-Based Observational Study.

Estimating the incidence of End-stage kidney disease (ESKD) in stroke survivors is important to assess and predict clinical course, improve post-stroke quality of life, and ultimately reduce health burden. Our objective was to assess the risk of ESKD in patients compared to a matched stroke-free control cohort. A nationwide retrospective cohort study was conducted in 315,326 stroke subjects and 390,781 matched stroke-free control subjects. Health examination results and claims data were collected from the Korean National Health Insurance Service during 2010-2018. Cox proportional hazard models were used to assess the risk of ESKD in the stroke cohort. During a mean follow-up period of 4.3 years, the incidence of ESKD was 1.83 per 100,000 person-years in the stroke cohort versus 0.57 per 100,000 person-years in the control cohort. The stroke cohort exhibited a significantly higher risk of developing ESKD compared to the matched control, with an adjusted hazard ratio (aHR) of 1.79 (95% confidence interval [CI] 1.67-1.93). Stroke survivors were associated with a higher risk of developing ESKD, regardless of the severity of disability (aHRs of 1.93, 95% CI 1.69-2.21 for severe disability; 1.71, 95% CI 1.41-2.07 for mild disability; and 1.78, 95% CI 1.65-1.92 for no disability), compared to the matching control cohort. The elevated risk was observed in both hemorrhagic stroke (aHR 1.96, 95% CI 1.73-2.23) and ischemic stroke (aHR 1.75, 95% CI 1.62-1.89). This study demonstrates that stroke patients have a significantly higher risk of incident ESKD. This highlights the need for heightened clinical awareness and improved monitoring of kidney function in this population.

Lung-Kidney Axis in Cystic Fibrosis: Early Urinary Markers of Kidney Injury Correlate with Neutrophil Activation and Worse Lung Function.

Adult people with cystic fibrosis (PwCF) have a higher risk of end-stage kidney disease than the general population. The nature and mechanism of kidney disease in CF are unknown. This study quantifies urinary kidney injury markers and examines the hypothesis that neutrophil activation and lung infection are associated with early kidney injury in CF. Urinary total protein, albumin, and markers of kidney injury and neutrophil activation, normalized to creatinine, as well as urinary immune cells, were quantified in CF (n = 48) and healthy (n = 33) cohorts. Infection burden and chronicity were defined by sputum culture and serum titers of anti-bacterial antibodies. PwCF had increased urinary protein levels, consisting of low-molecular-weight tubular injury markers, independent of glomerular filtration rate (eGFR). This finding suggests subclinical renal injury processes. Urinary analysis of the CF cohort identified different associations of urinary injury markers with aminoglycoside exposure, lung function, and neutrophil activation. High urinary KIM-1 levels and increased prevalence of neutrophils among urine immune cells correlated with decreased lung function in PwCF. The relationship between tubular injury and decreased lung function was most prominent in patients harboring chronic Pseudomonas aeruginosa infection. Increased urinary tubular injury markers in PwCF suggest early subclinical renal injury not readily detected by eGFR. The strong association of high urinary KIM-1 and neutrophils with diminished lung function and high Pseudomonas aeruginosa burden suggests that pulmonary disease may contribute to renal injury in CF.

Adult-Onset IgA Vasculitis Complicated by Kidney Failure at Disease Onset in a Nepalese Patient: A Case Report

Introduction: Immunoglobulin A (IgA) vasculitis, previously known as Henoch-Schönlein purpura, is an immune complex-mediated small vessel vasculitis primarily affecting children. While rare in adults, it can present with more severe manifestations, particularly involving the kidneys. This case report details the presentation and management of adult-onset IgA vasculitis with significant renal involvement.  Case Report: A 43-year-old male with a history of bipolar disorder presented with facial swelling, shortness of breath, and decreased urine output following an upper respiratory infection. Initial investigations revealed elevated blood pressure and renal impairment. Despite supportive treatment, his condition worsened, leading to a referral to a tertiary care center. He exhibited symptoms consistent with IgA vasculitis, including joint pain, rash, and nephrotic-range proteinuria. The diagnosis was confirmed through a skin biopsy and 24-hour urine collection. The patient was treated with intravenous methylprednisolone, oral prednisone, and an ACE inhibitor. His renal function improved with this regimen.  Discussion: Adult-onset IgA vasculitis can present with severe kidney involvement, including nephrotic-range proteinuria and elevated serum creatinine, which are associated with poorer outcomes compared to pediatric cases. The patient's management, involving glucocorticoids and an ACE inhibitor, aligns with current treatment recommendations for significant renal involvement. Long-term prognosis in adults remains challenging, with a higher risk of end-stage kidney disease compared to children. Vigilant monitoring and tailored treatment strategies are crucial for improving outcomes.  Conclusion: This case underscores the potential severity of adult- onset IgA vasculitis and highlights the importance of early diagnosis and aggressive management to mitigate long- term renal complications. Ongoing research is necessary to refine treatment approaches and enhance outcomes for adults with this condition.

Investigation of end-stage kidney disease risk prediction in an ethnically diverse cohort of people with type 2 diabetes: use of kidney failure risk equation

IntroductionThe four variable kidney failure (KF) risk equation (KFRE) is recommended to estimate KF risk (ie, need for dialysis or kidney transplantation). Earlier referral to clinical kidney services for people...

Homelessness and Risk of End-Stage Kidney Disease and Death in Veterans With Chronic Kidney Disease

Adults experiencing homelessness in the US face numerous challenges, including the management of chronic kidney disease (CKD). The extent of a potentially greater risk of adverse health outcomes in the population with CKD experiencing homelessness has not been adequately explored. To evaluate the association between a history of homelessness and the risk of end-stage kidney disease (ESKD) and death among veterans with incident CKD. This retrospective cohort study was conducted between January 1, 2005, and December 31, 2017. Participants included veterans aged 18 years and older with incident stage 3 to 5 CKD utilizing the Veterans Health Administration health care network in the US. Patients were followed-up through December 31, 2018, for the occurrence of ESKD and death. Analyses were performed from September 2022 to October 2023. History of homelessness, based on utilization of homeless services in the Veterans Health Administration or International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Homelessness was measured during the 2-year baseline period prior to the index date of incident CKD. The primary outcomes were ESKD, based on initiation of kidney replacement therapy, and all-cause death. Adjusted hazard ratios (HRs) were calculated to compare veterans with a history of homelessness with those without a history of homelessness. Among 836 361 veterans, the largest proportion were aged 65 to 74 years (274 371 veterans [32.8%]) or 75 to 84 years (270 890 veterans [32.4%]), and 809 584 (96.8%) were male. A total of 26 037 veterans (3.1%) developed ESKD, and 359 991 (43.0%) died. Compared with veterans who had not experienced homelessness, those with a history of homelessness showed a significantly greater risk of ESKD (adjusted HR, 1.15; 95% CI, 1.10-1.20). A greater risk of all-cause death was also observed (HR, 1.48; 95% CI, 1.46-1.50). After further adjustment for body mass index, comorbidities, and medication use, results were attenuated for all-cause death (HR, 1.09; 95% CI, 1.07-1.11) and were no longer significant for ESKD (HR, 1.04; 95% CI, 0.99-1.09). In this cohort study of veterans with incident stage 3 to 5 CKD, a history of homelessness was significantly associated with a greater risk of ESKD and death, underscoring the role of housing as a social determinant of health.

Annual variation of estimated glomerular filtration rate in health check-ups associated with end-stage kidney disease

Estimated glomerular filtration rate (eGFR) variation is associated with end-stage kidney disease (ESKD) development in patients with chronic kidney disease; whether annual variations in eGFR at health check-ups is associated with ESKD risk in the general population is unclear. We conducted a retrospective cohort study using Japanese national medical insurance claims from 2013 to 2020. Individuals who had their eGFR levels measured three times in annual health check-ups were included (N = 115,191), and the coefficient of variation of eGFR (CVeGFR) was calculated from 3-point eGFR. The end-point was ESKD as reported in the claims data. We analyzed the association between CVeGFR and ESKD incidence after adjusting for conventional ESKD risk factors. The CVeGFR median distribution was 5.7% (interquartile range: 3.5–8.5%). During a median follow-up period of 3.74 years, 164 patients progressed to ESKD. ESKD incidence was significantly higher in the highest quartile group (CVeGFR ≥ 8.5%) than in the other groups (P < 0.0001). After adjusting for risk factors, individuals with CVeGFR ≥ 8.5% had a significantly high ESKD incidence (adjusted hazard ratio: 3.01; 95% CI 2.14–4.30). High CVeGFR in annual health check-ups was associated with high ESKD incidence, independent of its other conventional risk factors, in the general population.

Prevalence and clinical determinants of rapid eGFR decline among patients with newly diagnosed type 2 diabetes

BackgroundDiabetic kidney disease is the most common cause of end-stage kidney disease (ESKD) in the western world. Rapid estimated glomerular filtration rate (eGFR) decline is an independent predictor of ESKD and death in the general population and in subjects with type 2 diabetes mellitus (T2D). AimWe investigated in a large sample of subjects with newly diagnosed T2D the prevalence and clinical determinants of fast eGFR decline, taking advantage from the dataset of the Associazione Medici Diabetologi (AMD) Annals initiative. MethodsThe eGFR trajectories were evaluated by applying a linear mixed model for repeated measures (LMMRM) and rapid eGFR decline defined as an eGFR decline greater than 5 mL/min/1.73 m2 per year at 3 years. ResultsAmong 105,163 (57.7% M) subjects with newly diagnosed T2D, 13,587 (12.9 %) subjects showed a rapid eGFR loss. The independent significant predictors were age, female gender, HbA1c, smoking, high baseline eGFR, albuminuria and retinopathy. ConclusionOur study demonstrates that a significant percentage of newly diagnosed T2D subjects have a rapid eGFR decline. Given the association between dynamic changes in eGFR and the risk of ESKD or death, we suggest to include this variable in the definition of CKD.

Associations of Urine Epidermal Growth Factor With Kidney and Cardiovascular Outcomes in Individuals With CKD in SPRINT

IntroductionUrine epidermal growth factor (uEGF) has been found to be inversely associated with kidney function loss, while its associations with cardiovascular disease (CVD) and mortality have not been studied. MethodsWe measured baseline uEGF levels among 2,346 Systolic Blood Pressure Intervention Trial (SPRINT) participants with an eGFR<60 ml/min/1.73m2. A linear mixed-effects model was used to investigate the associations of uEGF with the annual eGFR change, Cox proportional hazards regression models were used to analyze its associations with the ≥30% eGFR decline, CVD, and all-cause mortality outcomes. To account for the competing risk of death, the Fine and Gray method was utilized for acute kidney injury (AKI) and end-stage kidney disease (ESKD) outcomes. ResultsAt baseline, study participants had mean age of 73±9 years, mean eGFR of 46±11 ml/min/1.73m2, and median urine albumin-to-creatinine ratio of 15 mg/g (interquartile range: 7-49). In the multivariable-adjusted analysis including baseline urine albumin and eGFR, each 50% lower uEGF concentration was associated with 0.74% (95% confidence interval: 0.29, 1.19) per year faster decline in eGFR and 1.17 times higher risk of ≥30% eGFR decline (95% confidence interval: 1.00, 1.36). Lower uEGF concentrations were found to be associated with increased risks of ESKD, AKI, CVD, and all-cause mortality; however, these associations did not reach statistical significance when models were controlled for baseline urine albumin and eGFR. ConclusionAmong hypertensive adults with CKD, lower baseline uEGF concentration was associated with faster eGFR decline independent of baseline albuminuria and eGFR; but not with ESKD, AKI, CVD, and all-cause mortality.

Urinary renal tubular epithelial cells and casts as predictors of renal outcomes in patients with biopsy-proven diabetic nephropathy.

Urine sediment examination is a time-tested and non-invasive diagnostic tool. Thisstudy investigated the characteristics of urine sediment and its association with severity and renal outcomes in diabetic nephropathy (DN) patients. A total of 201 biopsy-proven diabetic nephropathy patients (according to the pathological classification of diabetic nephropathyproposed by the Renal Pathology Society in 2010)who underwent manual urine sediment microscopic examination were included. We compared the clinicopathologicalcharacteristics of diabetic nephropathy patients with and without urinary renal tubular epithelial cells (RTECs) or renal tubular epithelial cell casts. The predictive value of urinary renal tubular epithelial cells or renal tubular epithelial cell casts for renal outcomes in diabetic nephropathy was analyzed. Fifty of 201 (24.9%) diabetic nephropathy patients had renal tubular epithelial cells or renal tubular epithelial cell casts in urine sediment. Diabetic nephropathy patients with renal tubular epithelial cells or renal tubular epithelial cell casts in urine sediment had a significantly higher level of proteinuria [6.0 (3.1, 9.7)vs.3.6 (1.8, 6.8) g/24h, p = 0.001], higher serum creatinine [227.9 (151.6, 338.1)vs.177.0 (104.4, 288.4) μmol/L, p = 0.016] and lower estimated glomerular filtration rate (eGFR) [25.8 (15.8, 44.8)vs.35.7 (19.9, 65.0) mL/min/1.73m2, p = 0.025] than those without.Cox regression analysis demonstrated that the presence of urinaryrenal tubular epithelial cells or renal tubular epithelial cell casts was independently associated with the development of end-stage kidney disease (ESKD) in diabetic nephropathy patients [HR 1.670, 95% CI (1.042, 2.676), p = 0.033]. Adding the presence of urinary renal tubular epithelial cells or renal tubular epithelial cell casts to the predictive model could improve the effectiveness of the model for predicting the risk of ESKD within one year after renal biopsy. The presence of urinary renal tubular epithelial cells or renal tubular epithelial cell casts was associated with more severe kidney injury and worse renal outcomes in patients with diabetic nephropathy, thus perhaps providing a noninvasive biomarker for predicting diabetic nephropathy.

The effect of preeclampsia on long-term kidney function among pregnant women with chronic kidney disease.

The association between superimposed preeclampsia and an elevated risk of long-term kidney function decline or end-stage kidney disease (ESKD) in patients with chronic kidney disease (CKD) has not been determined. This study aimed to analyze the association between preeclampsia and kidney function deterioration in CKD patients. This was a retrospective cohort study that included the clinical information of 103 pregnant CKD patients with preeclampsia and 103 matched CKD patients without preeclampsia who were followed-up for a minimum of 1 year after their first pregnancy from January 1, 2009, to May 31, 2022. Robust Cox regression analysis was also conducted to evaluate the effects of preeclampsia on long-term kidney function decline or ESKD in CKD patients. K-M curves were used to compare renal survival within different subgroups via the log-rank test. During the follow-up period, 44 (42.72%) CKD patients with preeclampsia and 20 (19.42%) without preeclampsia had an estimated glomerular filtration rate (eGFR) decrease >30% or developed ESKD. Compared with CKD patients without preeclampsia, the eGFR decreased more significantly in patients with preeclampsia [98.43 (79.48, 116.47) to 81.32 (41.20, 102.97) mL/min/1.73 m2 vs. 99.43 (79.00, 118.50) to 89.44 (63.69, 105.30) mL/min/1.73 m2; P=0.034]. The rate of eGFR decrease was more pronounced in patients with preeclampsia (17.38% vs. 10.05%, p<0.05). Multivariate analysis revealed that early-onset preeclampsia (preeclampsia that developed before 34 weeks of gestation) (HR=2.61, 95% CI=1.32-5.16, P=0.006) and late-onset preeclampsia (HR=2.54, 95% CI=1.34-4.83, P=0.004) were both risk factors for an eGFR decrease >30% or ESKD. Preeclampsia was associated with a greater risk of long-term kidney function decline or ESKD among CKD patients, especially in patients with early-onset preeclampsia.

Increased Risk of End-Stage Kidney Disease in Patients with Chronic Kidney Disease and Heart Failure with Reduced Ejection Fraction.

The prevalence of heart failure (HF) is more common in people with advanced non-dialysis chronic kidney disease (ND-CKD) compared to the general population. It is well known that HF with reduced ejection fraction (HFrEF) is associated with a higher risk of mortality in people with ND-CKD. However, the impact of HFrEF on progression into end-stage kidney disease (ESKD) is not well studied. Our study aimed to examine the independent association of HFrEF on progression to ESKD after correcting for confounding factors using two methods of propensity scoring. This study used data from the Salford Kidney Study, a longitudinal study which has recruited more than 3,000 patients with ND-CKD since 2002. Patients without a history of HF during the recruitment questionnaire were included in the control group. Patients with a reported history of HF and echo showing left ventricular ejection fraction &lt;40% at enrolment were included in the HFrEF group. Two propensity score methods were used to attenuate the effects of confounding factors between the two groups - propensity score matching (PSM) and inverse probability weighting (IPW). Univariate and multivariate Cox-regression analyses were performed. A total of 2,383 patients were included in the analysis. Patients with HFrEF had significantly higher median age and a higher percentage of male gender compared to patients with no HF (72.5 vs. 66.6 years and 71.8 vs. 61.1%, respectively). Univariate and 5 models of multivariate Cox-regression analysis showed that HFrEF in people with CKD was a strong predictor for a higher incidence of ESKD (model 5: hazard ratio 1.38; 95% confidence interval = 1.01-1.90; p = 0.044). The association between HFrEF and the risk of ESKD remained significant after using the PSM and the IPW methods. Patients with concomitant advanced ND-CKD and prevalent HFrEF were found to have a higher risk of ESKD when compared to patients with no HF. This risk persists despite the adjustment of confounding factors using PSM and IPW.

Remnant cholesterol and the risk of diabetic nephropathy progression to end-stage kidney disease in patients with type 2 diabetes mellitus: a longitudinal cohort study.

Diabetic nephropathy (DN) is the most common cause of end-stage kidney disease (ESKD). Remnant cholesterol has been investigated as a predictor for the progression of DN in type 1 diabetes mellitus patients, as well as the incidence of DN in type 2 diabetes mellitus (T2DM) patients. This study aimed to evaluate the longitudinal relationship between baseline remnant cholesterol and kidney outcomes using a Chinese T2DM with biopsy-confirmed DN cohort. We included 334 patients with T2DM and biopsy-confirmed DN during 2010-2019 West China Hospital T2DM-DN cohort. Remnant cholesterol was defined by Martin-Hopkins equation. Patients were divided into four groups based on the median (IQR) remnant cholesterol concentration at the time of renal biopsy. The kidney outcome was defined as ESKD, which was defined as the need for chronic kidney replacement therapy or estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2. The relationship between remnant cholesterol and kidney outcome was analyzed using the Kaplan‒Meier method and Cox regression analysis. The mean age was 51.1 years, and 235 (70%) were men. During follow-up, a total of 121 (36.2%) patients reached ESKD. The Kaplan‒Meier analysis showed that patients in the highest quartile (quartile 4) group had lower cumulative renal survival (log-rank test, p = 0.033) and shorter median renal survival time [34.0 (26.4-41.6) vs. 55.0 (29.8-80.2) months] than patients in the lowest quartile (quartile 1) group. By univariate analysis, the high remnant cholesterol group was associated with a higher risk of progression to ESKD. Moreover, the risk of progression to ESKD in the highest quartile was still 2.857-fold (95% CI 1.305-6.257, p = 0.009) higher than that in the lowest quartile, and one-SD increase of remnant cholesterol was associated with a higher risk (HR = 1.424; 95% CI 1.075-1.886, p = 0.014) of progression to ESKD, after adjusted for confounding factors. High remnant cholesterol is independently associated with a higher risk of ESKD in patients with T2DM-DN, and it may be a new noninvasive marker of ESKD. Calculated remnant cholesterol has the advantages of being economical and clinically accessible. Moreover, to our knowledge, there are no longitudinal cohort studies for investigating the risk of progression of T2DM-DN to ESKD. In our study, higher remnant cholesterol was associated with a higher risk of ESKD in patients with T2DM-DN, and it may be a new noninvasive predictor of ESKD.

Guidelines for clinical evaluation of chronic kidney disease in early stages

BackgroundFor the development of pharmaceutical products in kidney field, appropriate surrogate endpoints which can predict long-term prognosis are needed as an alternative to hard endpoints, such as end-stage kidney disease. Though international workshop has proposed estimated glomerular filtration rate (GFR) slope reduction of 0.5–1.0 mL/min/1.73 m /year and 30% decrease in albuminuria/proteinuria as surrogate endpoints in early and advanced chronic kidney disease (CKD), it was not clear whether these are applicable to Japanese patients.MethodsWe analyzed J-CKD-DB and CKD-JAC, Japanese databases/cohorts of CKD patients, and J-DREAMS, a Japanese database of patients with diabetes mellitus to investigate the applicability of eGFR slope and albuminuria/proteinuria to the Japanese population. Systematic review on those endpoints was also conducted including the results of clinical trials published after the above proposal.ResultsOur analysis showed an association between eGFR slope and the risk of end-stage kidney disease. A 30% decrease in albuminuria/proteinuria over 2 years corresponded to a 20% decrease in the risk of end-stage kidney disease patients with baseline UACR ≥ 30 mg/gCre or UPCR ≥ 0.15 g/gCre in the analysis of CKD-JAC, though this analysis was not performed on the other database/cohort. Those results suggested similar trends to those of the systematic review.ConclusionThe results suggested that eGFR slope and decreased albuminuria/proteinuria may be used as a surrogate endpoint in clinical trials for early CKD (including diabetic kidney disease) in Japanese population, though its validity and cutoff values must be carefully considered based on the latest evidence and other factors.

High premature atrial complex burden and risk of renal function decline.

Atrial arrhythmia, particularly atrial fibrillation (AF), is known to be associated with renal function decline and increased risk of end-stage kidney disease. In recent years, premature atrial complexes (PACs) as subclinical arrhythmia have been proposed to be a marker of atrial cardiomyopathy and associated with poor clinical outcomes. However, the relationship between excessive daily PAC burden and renal outcomes remains unexplored. This retrospective, all-comers cohort study analyzed 30488 consecutive Holter monitoring records obtained from a validated Holter databank at a referral medical center in Taiwan between 2011 and 2018. After exclusion, 10981 patients were categorized into three groups: high daily PAC burden (≥100 beats per day), low PAC burden (<100 beats per day) and the AF group. We used parallel propensity score matching to balance confounding factors between groups. The primary study interest was major adverse kidney events, including an estimated glomerular filtration rate (eGFR) decline of 40%, eGFR <15mL/min/1.73 m2 or the initiation of hemodialysis. After a mean follow-up of 4.07±3.03years, patients with high PAC burden had a 1.24-fold higher incidence of major adverse kidney events compared with the low PAC burden group [95% confidence interval (CI) 1.03-1.50]. The risk of major adverse kidney events was similar between patients with AF and those with high PAC burden [adjusted hazard ratio (HR) 1.05, 95% CI 0.87-1.25], but significantly higher in the AF group than in the low PAC burden group (adjusted HR 1.29, 95% CI 1.07-1.56). Excessive daily PAC burden is associated with a higher risk of major adverse kidney events and has a comparable impact as AF.

Serum Wnt3A levels are significantly associated with cross-sectional vasculitis activity and end-stage kidney disease during follow-up of patients with antineutrophil cytoplasmic antibody-associated vasculitis.

In this study, we investigated whether serum Wnt3A levels at diagnosis reflected cross-sectional activity and predicted poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study included 80 patients who were newly diagnosed with AAV at a tertiary hospital. At diagnosis, whole blood was obtained from patients and sera was immediately isolated and stored at -80℃. Moreover, AAV activity was assessed using the Birmingham Vasculitis Activity Score (BVAS), and a high BVAS was defined as the highest tertile. Poor outcomes including all-cause mortality and end-stage kidney disease (ESKD) were recorded. The patients had a median age of 63.5 years, with 40% being male and 60% female patients. Serum levels of Wnt3A at diagnosis were correlated with the cross-sectional BVAS and serum Wnt3A ≥411.7 pg/mL exhibited an increased risk of high BVAS. In addition, serum Wnt3A levels at diagnosis significantly correlated with cross-sectional acute-phase reactants and serum albumin levels. Furthermore, serum Wnt3A levels at diagnosis were associated with AAV exacerbation, leading to ESKD. Particularly, serum Wnt3A ≥407.1 pg/mL also demonstrated an elevated risk of ESKD (relative risk 3.867). Additionally, patients with serum Wnt3A ≥407.1 pg/mL exhibited a significantly lower cumulative ESKD-free survival rate than those with lower serum Wnt3A levels. This study is the first to demonstrate the clinical potential of serum Wnt3A levels at diagnosis for estimating cross-sectional activity and partially predicting the advancement to ESKD during follow-up in patients with AAV.