Kidney Research and Clinical Practice最新文献

Background: In-depth investigation is imperative to scrutinize medical costs associated with the periods before and after biopsies for diverse kidney diseases in South Korea. Long-term epidemiological data, including follow-up information, is essential for comparing risks linked to various kidney diseases and their adverse outcomes.

Methods: Patients diagnosed with glomerulonephritis (GN), tubulointerstitial nephritis (TIN), and acute tubular necrosis (ATN) at Seoul National University Hospital between 2012 and 2018 were included. We linked the prospective cohort data of biopsy-confirmed kidney disease patients (KORNERSTONE) from our study hospital to the national claims database of Korea, covering both medical events and insured costs. We analyzed medical costs during the periods before and after kidney biopsies, categorized by specific diagnoses, and delved into adverse prognostic outcomes.

Results: Our study involved 1,390 patients with biopsy-confirmed GN, TIN, and ATN. After diagnosis, monthly average medical costs increased for most kidney diseases, excluding membranous nephropathy, Henoch-Schönlein purpura, and amyloidosis. The most substantial yearly average medical cost increase was observed in the ATN, acute TIN (ATIN), and chronic TIN (CTIN) groups. Costs rose for most kidney disease categories, except for amyloidosis. Higher myocardial infarction, stroke, and death rates were noted in CTIN, ATIN, and ATN compared to other types, with lupus nephritis displaying the highest end-stage kidney disease progression rate.

Conclusion: In South Korea, medical costs for the majority of GN, TIN, and ATN patients increased following kidney biopsy diagnosis. This current data provides valuable epidemiological insights into the medical costs and prognosis of various kidney diseases in the country.

Background: Tolvaptan, a selective vasopressin V2 receptor antagonist, was first approved by the Korean Ministry of Food and Drug Safety in 2015 as a treatment option for autosomal dominant polycystic kidney disease (ADPKD). To prescribe tolvaptan safely and effectively, we designed the phase 4 clinical trial among Korean ADPKD patients with chronic kidney disease stages 1 to 3.

Methods: A total of 117 Korean patients aged 19 to 50 years with rapidly progressing ADPKD were enrolled in the study. Tolvaptan was prescribed for 24 months with the maximum tolerable dose up to 120 mg/day. The primary outcome was the incidence of treatment-emergent adverse events (TEAEs) including hepatic adverse events. The secondary outcomes were the annual mean percent change of total kidney volume (TKV) and the annual mean change of estimated glomerular filtration rate (eGFR).

Results: A total of 489 TEAEs occurred in 106 patients (90.6%). A total of 17 cases of hepatic adverse events (14.5%) occurred during the study period and mostly within the first 18-month period. However, liver enzymes were normalized after drug discontinuation. Although it was not statistically significant, patients with a previous history of liver disease as well as those with mild elevation of liver enzyme showed a higher frequency of hepatic adverse events. Compared with the predicted value from the calculation, tolvaptan attenuated both TKV growth and eGFR decline rate.

Conclusion: Although the incidence of hepatic adverse events was higher in Korean ADPKD patients compared to the previous studies, tolvaptan can be prescribed safely and effectively using meticulous titration and 1-month interval monitoring.

Background: The aim of this study is to investigate the impact of sex on the clinical outcomes of spousal donor kidney transplantation.

Methods: We analyzed 456 spousal donor kidney transplantation recipients and categorized them into standard or high immunological risk groups according to panel-reactive antibody ≥50% or less. There were 366 recipients in the standard-risk group and 89 recipients in the high-risk group.

Results: When comparing biopsy-proven allograft rejection within 1 year from kidney transplantation, husband-to-wife recipients showed significantly higher incidence than wife-to-husband recipients in the high-risk group. By contrast, there was no significant difference between wife-to-husband and husband-to-wife recipients in the standard-risk group. Allograft function recovery was better in husband-to-wife recipients than in wife-to-husband recipients in each group, while husband-to-wife recipients in the high-risk group showed a more rapid decline than other recipients. The long-term patient and allograft survival rates showed no difference between husband-to-wife recipients and wife-to-husband recipients within the same groups.

Conclusion: The husband-to-wife recipients with high immunological risk showed a higher risk of biopsy-proven allograft rejection compared to wife-to-husband recipients, so careful monitoring and management may be required.

Background: Left ventricular hypertrophy (LVH) is a vital risk factor for mortality of dialysis patients. The association of the geometry and severity of LVH with cardiovascular and all-cause mortality in hemodialysis (HD) patients remains unknown. This study investigated clinical outcomes among HD patients with different LVH geometric patterns and severity.

Methods: The monocentric retrospective cohort study enrolled chronic HD patients who underwent echocardiography for the assessment of LVH. The patients with LVH were divided into concentric and eccentric groups and then subdivided into four groups based on LVH severity: mild-to-moderate eccentric, mild-to-moderate concentric, severe eccentric, and severe concentric LVH. The risks of cardiovascular and all-cause mortality between groups were evaluated using Cox proportional hazard analysis.

Results: Of the 237 patients on HD with LVH, 131 had concentric LVH, and 106 had eccentric LVH, with 33, 44, 73, and 87 having mild-to-moderate eccentric, mild-to-moderate concentric, severe eccentric, and severe concentric LVH, respectively. Compared with eccentric LVH, the crude hazard ratio (cHR) of cardiovascular mortality of concentric LVH was 2.03 (95% confidence interval [CI], 1.13-3.65). Severe concentric LVH was a significant risk factor for all-cause and cardiovascular mortality compared with mild-to-moderate eccentric LVH (cHR: 2.58 [95% CI, 1.00-6.65] and 3.73 [95% CI, 1.13-12.33], respectively). After adjustment for all variables, concentric LVH and severe concentric LVH remained significant risk factors for cardiovascular mortality (adjusted HR: 2.13 [95% CI, 1.13-4.01] and 3.71 [95% CI, 1.07-12.82], respectively).

Conclusion: Concentric LVH, especially severe concentric LVH, was associated with a high risk of cardiovascular mortality among patients with chronic HD.

Background: The current study was initiated to evaluate renal nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathway activation and macrophage subtype distribution and their clinicopathological significance in a cohort of oxalate-induced acute kidney injury.

Methods: Twelve patients with biopsy-proven acute oxalate nephropathy (AON) from January 2016 to October 2022 were retrospectively enrolled, with estimated glomerular filtration rate (eGFR)-matched 24 patients with acute tubulointerstitial nephritis (ATIN) as disease control. Pathological lesions as well as markers of NLRP3 inflammasome pathway and macrophage phenotype detected by immunohistochemistry staining were semi-quantitatively analyzed.

Results: Oxalate depositions were found in 5% to 20% of tubules with a positive correlation with Sirius Red staining in AON specimens (rp = 0.668, p = 0.02). Disruption of tubular basement membrane and inflammatory cell reaction was more prominent in specimens of AON (both p < 0.05) as compared with ATIN specimens. The expressions of NLRP3, caspase-1, and gasdermin D were significantly increased in AON specimens as well (all p < 0.05). Patients with M1/M2 macrophage ratio <1 were found with more chronic tubulointerstitial lesions and presented with lower eGFR at the last follow-up (24.8  10.6 mL/min/1.73 m2 vs. 55.1  21.2 mL/min/1.73 m2, p = 0.02) in the AON group.

Conclusion: The NLRP3 inflammasome pathway was activated in the kidneys of AON patients, and the ratio of M1 and M2 macrophages was associated with chronicity of pathological changes, which needs further exploration.

Background: EW-7197, a potent oral ALK5 inhibitor, was assessed for its impact on transforming growth factor beta 1 (TGF-β1)-induced fibrosis in a three-dimensional (3D) renal fibrosis-on-a-chip and a mouse model. The evaluation included tubular epithelial-mesenchymal transition, angiogenesis, and inflammatory cytokine expression.

Methods: In a 3D renal fibrosis-on-a-chip model, three cell types (kidney fibroblasts, human proximal tubular cell line, and human umbilical vein endothelial cells) were cultured and treated with TGF-β1 and EW-7197. Expression of alpha smooth muscle actin (α-SMA) and keratin 8 (KRT-8) was assessed, angiogenesis was observed via confocal microscopy, and cytokine levels were measured using real-time polymerase chain reaction, immunoassay, and enzyme-linked immunosorbent assay. In a cisplatin-induced renal fibrosis mouse model, blood urea nitrogen levels, TGF-β, and Smad 2/3 were determined, and renal fibrosis was assessed with Masson's trichrome stain.

Results: The α-SMA expression was significantly lower in the EW-7197 group than in the TGF-β fibrosis group. TGF-β decreased the expression of the epithelial marker KRT-8, an effect that was reversed by EW-7197 and SB431542. In the TGF-β-induced fibrosis model, the length of the thick vessels was reduced, and the diameter of both thick and thin vessels was decreased, but EW-7197 reversed these effects. EW-7197 significantly reduced the messenger RNA expression of TGF-β and increased the levels of vascular endothelial growth factor receptor 2, interleukin (IL)-10, and IL-6. EW-7197 reduced the levels of secretory cytokines TGF-β1, TGF-β3, IL-1β. In the cisplatin-induced renal fibrosis mouse model, EW-7197 reduced renal fibrosis by down-regulating TGF-β signaling.

Conclusion: EW-7197 attenuated the TGF-β1-induced fibrotic cellular response in the 3D chip model and animal model. These findings indicate the potential effect of EW-7197 in attenuating renal fibrosis.

Background: Since hemodialysis (HD) patients are prone to various complications and high mortality, they need to be treated in HD units with professional personnel, proper equipment, and facilities. The Korean Society of Nephrology has been conducting an HD unit accreditation program since 2016. This study was performed to evaluate whether a qualified dialysis center (QDC) reduced the mortality of HD patients.

Methods: This longitudinal, observational cohort study included 31,227 HD from 832 facilities. HD units were classified into two groups: the hospitals that have been certified as QDC between 2016 and 2018 (n = 219) and hospitals that have never been certified as QDC (non-QDC, n = 613). Baseline characteristics and patient mortality were compared between QDC vs. non-QDC groups using Korean HD quality assessment data from 2018. Multivariate logistic regression and the Cox proportional hazards model were used to compare patient mortality between the two groups.

Results: Among study subjects, 30.6% of patients were treated at QDC and 69.4% were treated at non-QDC. The patients in the QDC were younger and had a longer dialysis duration, lower serum phosphorus and calcium levels, and higher hemoglobin and single-pool Kt/V levels compared to the patients from the non-QDC group. After adjusting for demographic and clinical parameters, QCD independently reduced mortality risk (hazard ratio, 0.897; 95% confidence interval, 0.847-0.950; p < 0.001).

Conclusion: The HD unit accreditation program may reduce the risk of death among patients undergoing HD.

The disease burden of chronic kidney disease (CKD) and its impact on healthcare systems has been poorly studied in Asia, a socioeconomically diverse region with wide variations in availability, access, and quality of CKD care. The high CKD burden in this region is predominantly driven by an increased prevalence of risk factors including diabetes mellitus, hypertension, obesity, and use of traditional medicines and is further aggravated by challenges associated with effective implementation of population-based screening and surveillance systems in early detection and intervention of CKD. The Asian continent mostly comprised of low- and middle-income countries with resource restraints lacks robust population-based CKD registries resulting in a paucity of data on CKD incidence and prevalence, various treatment modalities, uptake of current guidelines, and the overall impact of implementation of developmental programs. There is an urgent need for a collaborative action plan between the healthcare community and governments in this region to detect CKD in its early stages and prevent its complications including kidney failure, cardiovascular disease, and death. Research-based evidence on the impact of early detection, sustainable treatment options, quality of life, delay or avoidance of dialysis, and related cost analysis is the need of the hour. We highlight successful implementation of strategic and policy-sharing programs adopted in a few countries; also, consolidate available region-specific data, quantify estimates of CKD burden and propose strategies with a multidisciplinary approach involving patients, the healthcare community and governmental bodies to combat CKD and its complications.

Background: Persistent proteinuria is an important indicator of kidney damage and requires active evaluation and intervention. However, tubular proteinuria of genetic origin typically does not improve with immunosuppression or antiproteinuric treatment. Recently, defects in CUBN were found to cause isolated proteinuria (mainly albuminuria) due to defective tubular albumin reuptake. Unlike most other genetically caused persistent albuminuria, CUBN C-terminal variants have a benign course without progression to chronic kidney disease according to the literature. Here, we present Korean cases with persistent proteinuria associated with C-terminal variants of CUBN.

Methods: We identified Korean patients with CUBN variants among those with an identified genetic cause of proteinuria and evaluated their clinical features and clinical course. We also reviewed the literature on CUBN-associated isolated proteinuria published to date and compared it with Korean patients.

Results: All patients presented with incidentally found, asymptomatic isolated proteinuria at a median age of 5 years. The proteinuria was in the subnephrotic range and did not significantly change over time, regardless of renin- angiotensin system inhibition. Initial physical examination, laboratory findings, and kidney biopsy results, when available, were unremarkable other than significant proteinuria. All patients maintained kidney function throughout the follow-up duration. All patients had at least one splicing mutation, and most of the variants were located C-terminal side of the gene.

Conclusion: We report Korean experience of CUBN-related benign proteinuria, that aligns with previous reports, indicating that this condition should be considered in cases with incidentally found asymptomatic isolated proteinuria, especially in young children.

Regardless of the underlying etiology, renal fibrosis is the final histological outcome of progressive kidney disease. Unilateral ureteral obstruction (UUO) is an ideal and reproducible experimental rodent model of renal fibrosis, which is characterized by tubulointerstitial inflammatory responses, accumulation of extracellular matrix, tubular dilatation and atrophy, and fibrosis. The magnitude of UUO-induced renal fibrosis is experimentally manipulated by the species chosen, animal age, and the severity and duration of the obstruction, while relief of the obstruction allows the animal to recover from fibrosis. The pathogenesis of renal fibrosis is complex and multifactorial and is orchestrated by activation of renin-angiotensin system (RAS), oxidative stress, inflammatory response, transforming growth factor beta 1-Smad pathway, activated myofibroblasts, cell death (apoptosis, autophagy, ferroptosis, and necroptosis), destruction of intracellular organelles, and signaling pathway. The current therapeutic approaches have limited efficacy. Inhibition of RAS and use of antioxidants and antidiabetic drugs, such as inhibitors of sodium-glucose cotransporter 2 and dipeptidyl peptidase-4, have recently gained attention as therapeutic strategies to prevent renal scarring. This literature review highlights the state of the art regarding the molecular mechanisms relevant to the management of renal fibrosis caused by UUO.