Kidney Research and Clinical Practice最新文献

Background: Posttransplantation diabetes mellitus (PTDM) is a crucial problem after kidney transplantation. We aimed to determine whether metformin affects cardiovascular and graft outcomes in patients with PTDM.

Methods: This retrospective cohort study included 1,663 kidney transplant recipients without preexisting diabetes mellitus. The patients were divided into metformin and non-metformin groups, with matched propensity scores. We also estimated metformin's effect on percutaneous coronary intervention (PCI), major adverse cardiovascular events (MACEs), acute rejection, and graft failure.

Results: Of 634 recipients with PTDM, 406 recipients were treated with metformin. The incidence of PCI was 2.4% and 7.1% in the metformin and non-metformin groups, respectively (p = 0.04). The metformin group exhibited a lower risk of PCI in Cox regression analyses (hazard ratio [HR], 0.27; 95% confidence interval [CI], 0.10-0.77; p = 0.014), especially in subgroups with male sex, age over 49 years (median), long-term metformin use (mean of ≥1,729 days), and simultaneous tacrolimus administration. Long-term metformin use was also associated with lower incidence of MACEs (HR, 0.09; 95% CI, 0.01-0.67; p = 0.02). Incidence of graft failure was 9.9% and 17.0% in the metformin and non-metformin groups, respectively (p = 0.046). Both long-term use and higher dose of metformin, as well as tacrolimus administration with metformin, were associated with a lower risk of graft failure (HR, 0.29; 95% CI, 0.11-0.75; p = 0.01; HR, 0.39; 95% CI, 0.18-0.85; p = 0.02; and HR, 0.39; 95% CI, 0.19-0.79; p = 0.009, respectively).

Conclusion: Metformin use is associated with a decreased risk of developing coronary artery disease and better graft outcomes in PTDM.

Renal fibrosis (RF) is a prevalent clinical symptom of numerous chronic kidney illnesses and a significant pathological alteration in end-stage renal disease resulting from various mechanisms, such as abnormally activated signaling pathways, microRNAs, aging, autophagy disorders, and fibrotic ecological niches, all of which contribute to RF development. Inhibiting, blocking, or delaying the aforementioned mechanisms may yield novel approaches for treating RF. This article explores advancements in the comprehension of the mechanisms and therapeutic approaches for RF.

Background: The heterogeneity of chronic kidney disease (CKD) and fragmented analysis methods hinder the precise identification of novel biomarkers. We addressed this challenge using two independent cohorts to integrate genomics and metabolomics, aiming to identify cause-specific biomarkers for CKD in the Korean population.

Methods: A longitudinal genome-wide association study using the Cox proportional hazards model was conducted using the Ansan and Ansung cohort. To validate these genomic biomarkers and integrate them with plasma metabolomics biomarkers, we utilized a hospital-based biopsy cohort to identify cause-specific CKD biomarkers. Within the biopsy cohort, we analyzed four disease subsets, including type 2 diabetic kidney disease (DKD), hypertensive nephropathy (HN), immunoglobulin A nephropathy (IgAN), and membranous nephropathy (MN), and compared them with healthy individuals. Significant single nucleotide polymorphisms(SNPs) and metabolites for each CKD subset were identified through logistic regression and correlation-based network analyses. Subsequently, we analyzed the risk of disease progression associated with the identified pairs.

Results: A total of 448 variants associated with CKD occurrence were identified, with significant differences in several genetic variants and metabolites observed among patients with DKD, HN, IgAN, and MN compared to healthy individuals. Among 36 SNP-metabolite pairs, those involing FOXB1 and ZFP42 were associated with DKD, whereas pairs involving MMRN1 and SYNJ2 were linked to MN. Notably, the rs1025170 variant in FOXB1 and tyrosine pair was correlated with DKD progression.

Conclusion: Integrating genomics and metabolomics across independent cohorts enables the discovery of cause-specific biomarkers for the occurrence and progression of CKD in the Korean population.

Extracellular vesicles (EVs) are nanosized membranous particles released by nearly all cell types, playing a crucial role in mediating cell-to-cell communication. The molecular profile of EVs often reflects that of their originating cells, rendering them valuable for therapeutic and diagnostic purposes. The kidney comprises various cell types, and urinary EVs are predominantly produced from tubular, glomerular, and urinary bladder cells. Within the nephron, EVs produced from the upper segments, such as glomerular tufts and proximal tubules, can be taken up by their downstream counterparts, thereby altering the physiology of recipient cells. Recent studies have demonstrated that this proximal-distal intra-nephron crosstalk via EVs is crucial for normal kidney physiology. Additionally, EVs from interstitial cells (e.g., fibroblasts and macrophages) have been demonstrated to mediate the exacerbation of kidney damage. This review provides up-to-date findings on the function of renal EVs during the progression of renal diseases. Furthermore, we discussed future directions to use the clinical potential of renal EVs as an early biomarker for renal disorders.

Background: Immunoglobulin G4 (IgG4)-related disease (RD) is a newly recognized disease, and a few epidemiologic studies about this disorder have been published. This research aimed to demonstrate the clinical features and outcomes of IgG4-related kidney disease (RKD) and IgG4-related retroperitoneal fibrosis (RPF) compared to other organs' involvement.

Methods: Patients who were diagnosed with IgG4-RD from January 2009 to July 2019 at three medical institutions in South Korea were included. They were classified into three groups: RKD, RPF, and Others groups. The differences in symptoms, laboratory, histological and radiological findings, treatment, and outcomes among the three groups were evaluated.

Results: Of 94 patients, 13 (13.8%) and 22 patients (23.4%) were classified into the RKD and RPF groups, respectively. There were older (p = 0.004) and more asymptomatic patients (p = 0.02) in the RKD and RPF groups. In the RKD group, hypocomplementemia (p = 0.003) and eosinophilia (p = 0.001) were more frequently identified. In logistic regression analysis, hypocomplementemia (odds ratio [OR], 14.04; 95% confidence interval [CI], 1.38-142.95) and decreased renal function at the time of diagnosis (OR, 0.95; 95% CI, 0.91-0.98) were associated with renal involvement. Older age (OR, 1.05; 95% CI, 1.00-1.11), male (OR, 6.11; 95% CI, 1.41-26.61), and higher serum IgG4 levels (OR, 1.00; 95% CI, 1.00-1.00) were associated with retroperitoneal involvement. The treatment duration was longer in the RKD and RPF groups (p = 0.01) with glucocorticoids.

Conclusion: Renal and retroperitoneal involvement in IgG4-RD presented clinical features that distinguish it from other organs' involvement, such as incidental diagnosis, hypocomplementemia, eosinophilia, and the need for a longer duration of maintenance treatment.

Background: With the aging population and advancements in medical care worldwide, the number of older patients with end-stage kidney disease continues to rise. This study aimed to identify factors associated with osteoporosis and osteopenia in older patients undergoing incident hemodialysis and assess their impact on mortality.

Methods: We analyzed a large multicenter retrospective cohort of patients aged ≥70 years undergoing incident hemodialysis to identify factors associated with osteoporosis using logistic regression analysis and to assess the association of death with osteoporosis and osteopenia using Cox multivariable analysis.

Results: Among 710 patients, 39.0% and 19.6% had osteoporosis and osteopenia, respectively. Osteoporosis was significantly associated with female sex, a history of fractures, and the absence of phosphate binder use. During a median follow-up of 36.8 months, 348 participants (58.8%) died. Mortality rates were the highest in the osteoporosis group (79.8%), followed by the osteopenia (77.2%) and normal bone mineral density (BMD) groups (35.2%). Cox regression analysis revealed that even after adjusting for covariates, the osteoporosis group was significantly associated with a higher mortality risk than the normal BMD group. Osteoporosis at the start of hemodialysis was significantly associated with higher mortality.

Conclusion: We should consider the importance of bone health in patients undergoing incident hemodialysis and pay attention to the use of phosphate binders and fracture prevention.

Chronic kidney disease (CKD) is a progressive condition characterized by declining kidney function principally driven by diabetes mellitus, glomerulonephritis, and hypertension. Although renal biopsy is the gold standard for diagnosing CKD, its invasive nature restricts its use for early detection and routine clinical applications. Current noninvasive biomarkers, including the estimated glomerular filtration rate and albumin-to-creatinine ratio, are useful indicators of kidney dysfunction but fall short in specificity and sensitivity required to distinguish between CKD subtypes, including diabetic kidney disease and glomerulonephritis. Recently, urinary extracellular vesicles (uEVs), nano-sized lipid bilayer entities ranging from 30 to 1,000 nm in diameter and secreted by renal cells, have emerged as promising biomarkers for CKD. uEVs encapsulate a diverse array of proteins, nucleic acids, and lipids that mirror kidney pathophysiology, presenting a noninvasive means to assess disease progression, inflammation, fibrosis, and oxidative stress within the urinary system. Furthermore, uEVs offer a molecular fingerprint of kidney health, positioning them as potential tools for precision medicine. This review explores the diagnostic potential of uEVs, underscoring the need for standardization in urine collection, normalization techniques, and uEV isolation methodologies. We also highlight uEV-based biomarkers that distinguish various CKD subtypes and mirror pathological changes within the kidneys and urogenital system. As molecular proxies of their cells of origin, uEVs hold significant promise in enhancing CKD diagnostics to enable early detection, disease classification, and the development of novel therapeutic strategies.

Background: This study was performed to evaluate the prognostic utility of a positive T wave in lead augmented vector right (TaVR) and elevated E/e' ratio in predicting major adverse cardiovascular events (MACE) in patients receiving maintenance hemodialysis.

Methods: We retrospectively examined 296 adults on thrice-weekly hemodialysis with baseline electrocardiography and transthoracic echocardiography (October 2018-April 2024). TaVR positivity was T-wave amplitude, >0 mV and high E/e', ≥19. Primary outcome was the first MACE-cardiovascular death, myocardial infarction, stroke, heart-failure admission, or revascularization. Multivariable Cox models adjusted for clinical covariates; incremental value was gauged with Harrell's C-index, integrated discrimination improvement (IDI), and continuous net reclassification improvement (NRI). Sensitivity analysis was performed using a guideline-recommended E/e' threshold of ≥15 to assess robustness.

Results: Over 56.5 months (1,325 patient-years), 118 MACE occurred (8.9/100 patient-years). Incidence was higher with TaVR positivity than negativity (16.0/100 patient-years vs. 3.7/100 patient-years; log-rank p < 0.001). Adjusted hazard ratios were 3.19 (95% confidence interval [CI], 2.00-5.08) for TaVR and 2.92 (95% CI, 1.71-4.96) for high E/e'. Adding both markers to the clinical model increased the C-index from 0.65 to 0.75 (Δ 0.10) and improved IDI (0.10) and NRI (0.16) (all p < 0.01). A significant negative interaction (hazard ratio, 0.21; p = 0.01) indicated complementary but partly overlapping information. Sensitivity results were similar.

Conclusion: TaVR positivity is a strong independent electrocardiography predictor of cardiovascular events in hemodialysis. Combining TaVR with E/e' adds prognostic value and supports a pragmatic two-step strategy- electrocardiography triage followed by focused echocardiography-for cardiovascular risk stratification in this high-risk population.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly.

Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease.

Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13-1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84-1.11), 1.10 (0.96-1.27), 1.24 (1.06-1.45), 1.37 (1.12-1.66), and 1.99 (1.42-2.79), respectively (p for trend < 0.001).

Conclusion: In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.