Clinical and Experimental Nephrology最新文献

Background: The validity of the International Classification of Diseases 10th Revision (ICD-10) codes for chronic kidney disease (CKD) in Japan have not been evaluated. In this study we evaluated the validity of CKD-related ICD-10 codes in Japan.

Methods: This retrospective cohort study used the JMDC hospital-based database, which comprises claims and laboratory data from over 1,000 medical institutions in Japan. Patients who underwent two serum creatinine measurements between April 2014 and August 2022 were identified; the second measurement was obtained 90-365 days after the first. The estimated glomerular filtration rate (eGFR) was calculated. CKD was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria: an eGFR < 60 mL/min/1.73 m² for both measurements. Markers of kidney damage such as albuminuria were unavailable. Patients assigned CKD-related ICD-10 codes (N183, N184, N185, N189, N19, E102, E112, E142, and I120) within 365 days of the initial serum creatinine measurement were identified. Subsequently, the positive predictive value (PPV), sensitivity, specificity, and negative predictive value (NPV) were calculated.

Results: Among the 618,208 included patients, 59,139 were assigned CKD-related ICD-10 codes and 172,657 met the KDIGO criteria. The overall PPV, sensitivity, specificity, and NPV were 57.9%, 19.8%, 94.4%, and 75.2%, respectively. In contrast, the PPVs of N183, N184, N185, and N189 exceeded 80%.

Conclusions: In Japan, the PPV of the ICD-10 codes for CKD was 57.9%, marginally lower than values reported in the United States (86.1%) and Canada (60.1%). Several ICD-10 codes may be useful for identifying patients with CKD, despite their limited sensitivity.

Background: Patients undergoing hemodialysis have decreased skeletal muscle mass which is associated with higher mortality and lower physical functioning. Since these patients frequently experience hospitalizations, we hypothesized that hospital admissions could be a cause of loss of skeletal muscle mass.

Methods: This was a longitudinal observational study among patients on hemodialysis (N = 132). The outcome was the change in thigh muscle cross-sectional area (TMCSA) measured by computed tomography and standardized by squared height (cm²/m²) per year. The exposures were the presence or absence of hospital admissions, the total number of hospital admissions (times), and the total length of hospital stays (nights) between the TMCSA measurements. Association was analyzed by multivariable-adjusted linear regression analysis.

Results: During a median follow-up period of 3.95 years, 104 patients were hospitalized (hospitalization group), whereas 28 patients were not (non-hospitalization group). Both groups showed a significant decrease in TMCSA, and it was more rapid in the hospitalization group than the non-hospitalization group (P = 0.023). Multivariable-adjusted linear regression analysis showed that the total number of hospital admissions and the total length of hospital stays were the independent factors associated with the decrease in TMCSA.

Conclusion: This study showed for the first time that hospital admissions were independently associated with the longitudinal decrease in TMCSA in patients undergoing hemodialysis.

Objective: This study aimed to investigate the role of B7-H3-an immune checkpoint implicated in inflammation and vascular remodeling-in uremic vascular calcification (UVC), particularly its effects on calcium deposition, vascular smooth muscle cell (VSMC) phenotype, and VSMC-macrophage crosstalk.

Methods: An in vitro UVC model was established using β-glycerophosphate (β-GP) treated human aortic VSMCs (HA-VSMCs). B7-H3 expression was silenced using siRNA. Calcification was assessed by Alizarin Red S staining, ALP activity, and calcium content assays. VSMCs phenotype switching was evaluated by Western blot for contractile and osteogenic markers. Macrophage recruitment, adhesion, and polarization (M1/M2) were assessed using THP-1 cells in co-culture systems and analyzed by qRT-PCR and flow cytometry. The effect of macrophage polarization on VSMCs calcification was investigated in the presence or absence of B7-H3 knockdown.

Results: β-GP treatment induced HA-VSMC calcification, osteogenic differentiation, and upregulated B7-H3 expression. Silencing B7-H3 attenuated calcification, restored contractile markers, and reduced osteogenic markers in VSMCs. B7-H3 knockdown also suppressed the recruitment and adhesion of macrophages to HA-VSMCs, inhibited M1 polarization of co-cultured macrophages, and promoted their shift toward the M2 phenotype. Furthermore, silencing B7-H3 mitigated M1 macrophage-induced VSMC calcification and enhanced the protective effects of M2 macrophages.

Conclusion: B7-H3 promotes UVC directly by inducing osteogenic transformation of VSMCs and indirectly by enhancing macrophage recruitment and favoring pro-calcific M1 polarization. Thus, targeting B7-H3 may represent a promising therapeutic strategy to mitigate UVC.

Background: Although hypomagnesemia is theoretically induced by the peritoneal dialysis (PD) environment, its real-world risk and clinical correlates remain unclear, and its association with atrial fibrillation (AF) has not been evaluated.

Methods: We conducted a cross-sectional study using nationwide data from the 2019 annual survey of the Japanese Society for Dialysis Therapy. Adults (≥ 20 years) undergoing hemodialysis (HD) or PD were included. Serum magnesium (sMg) was categorized into five groups (≤ 1.5, > 1.5- ≤ 2.0, > 2.0- ≤ 2.5, > 2.5- ≤ 3.0, and > 3.0 mg/dL). The prevalence of hypomagnesemia (≤ 1.5 mg/dL) was compared among PD-only, hybrid, and HD patients. Among PD-only and hybrid patients, the association between sMg and AF was examined using logistic regression. Factors associated with sMg levels were further analyzed using a general linear model.

Results: A total of 2,347 PD, 806 hybrid, and 177,779 HD patients were analyzed. The prevalence of hypomagnesemia was 6.2% in PD-only, 3.6% in hybrid, and 0.5% in HD patients. Hypomagnesemia was significantly associated with AF (adjusted OR 2.96, 95% CI 1.64-5.33). Lower sMg levels were associated with higher renal Kt/V, higher total daily dialysate volume, use of icodextrin, and higher peritoneal equilibration test dialysate-to-plasma ratio, whereas higher sMg levels were associated with greater ultrafiltration volume, use of automated PD, and hybrid dialysis.

Conclusions: Hypomagnesemia is common in PD and is associated with an increased prevalence of AF. Further studies are warranted to identify the optimal sMg range for AF prevention and to develop PD prescription strategies for maintaining appropriate sMg levels.

Obesity can cause the progression of kidney disease through hemodynamic, structural, and metabolic changes, and predispose individuals to arterio-nephrosclerosis, diabetic nephropathy, and focal segmental glomerulosclerosis (FSGS), leading to chronic kidney disease (CKD). Obesity-Related Glomerulopathy (ORG) is defined as clinical obesity and biopsy-proven glomerulomegaly with or without the existence of FSGS. However, pathologic changes of ORG are not pathognomonic or specific. Glomerular hypertrophy, maladaptive segmental glomerulosclerosis, as well as in some cases diabetic-like changes may be seen secondary to any cause of acquired or congenital reduced nephron mass with compensatory hypertrophy as well as glomerular hypoxia. This review aims to provide a comprehensive overview of the mechanisms causing ORG and explore current diagnostic challenges and therapeutic strategies, emphasizing the role of weight management and emerging targeted therapies.

Amino acids are the building blocks of protein synthesis and play important roles in the generation of adenosine triphosphate (ATP), glucose, and fatty acids as metabolic precursors. Consequently, they serve as both structural components and energy sources for cells, supporting growth, differentiation, and function. Metabolic disorders involving amino acids have been associated with multiple clinical pathologies, including diabetic kidney disease (DKD). Increasing evidence suggests that amino acid metabolic pathways may act as novel contributors to the development of DKD. Thus, a deeper understanding of amino acid metabolism in DKD and the identification of key targets within amino acid metabolic pathways may facilitate the development of novel therapeutic strategies. To this end, this review focuses on three representative pathways-branched-chain amino acids, urea-cycle-related amino acids, and carnitine metabolism-that have emerged as key contributors to DKD progression, and discusses the advantages, limitations, and future directions of cell-specific therapeutic strategies.

Background: Cardiovascular-kidney-metabolic (CKM) syndrome, integrating cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic dysfunction, is a construct proposed by the American heart association. Although associations with CVD are well recognized, evidence linking CKM stage to renal outcomes remains limited.

Methods: We analyzed health checkup data of 266,256 Japanese aged 40-74 years. Participants were classified into CKM stages 0-4a. Outcomes included all-cause mortality, cardiovascular death, and a composite renal outcome (end-stage kidney disease [eGFR < 15 mL/min/1.73 m²], ≥ 40% eGFR decline, or doubling of serum creatinine). Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs), with CKM stage 0 as the reference.

Results: CKM stage 2 was the most prevalent stage (65.0%). Stage 4a showed the strongest association with all-cause and cardiovascular mortality (HRs 1.79, 3.16; 95% CIs 1.41-2.28, 1.92-5.20, respectively). In contrast, stage 3 conferred the highest risk of renal outcomes (HR 15.29, 95% CI 10.13-23.08). The number and type of metabolic risk factors correlated with outcomes, furthermore, severe CKD and prior CVD were stronger drivers of adverse outcomes than metabolic dysfunction.

Conclusion: CKM staging stratifies risk in the general population. No significant increase in risk was observed until CKM stage 2, and these findings underscore the progressive, cumulative nature of CKM syndrome. Metabolic dysfunction plays a crucial role in progression, stage 3 marks a pivotal inflection point for renal deterioration, and stage 4a identifies individuals at the greatest mortality risk. Early interventions targeting metabolic dysfunction may help prevent progression to advanced CKM stages and improve long-term outcomes.

Background: Data regarding clinical outcomes of systemic therapy, including tyrosine kinase inhibitors (TKIs), for advanced renal cell carcinoma (RCC) after kidney transplantation (KTx) are limited.

Methods: We assessed clinical data of 13 patients with advanced RCC after KTx (KTx-RCC) who received first-line TKI monotherapy. Outcomes of the KTx-RCC group were compared with those of 275 patients with sporadic RCC and 37 patients receiving maintenance dialysis therapy for end-stage renal disease (ESRD) who received first-line TKIs.

Results: Overall survival (OS) was shorter in the KTx-RCC group than in the sporadic RCC group (p = 0.0007). However, multivariate analysis showed that the population type (i.e., KTx-RCC vs. sporadic RCC) was not an independent factor (p > 0.05). In contrast, other covariates such as non-clear cell histology (p = 0.0215), poor IMDC risk (p = 0.0304), and liver metastasis (p = 0.0016), which were frequently observed in the KTx-RCC group, were independent factors for shorter OS. Progression-free survival and OS were not significantly different between the KTx-RCC and ESRD-RCC groups (p > 0.05). Of the 13 patients in the KTx-RCC group, everolimus was administered to six patients (46%), but survival was not significantly different based on the administration (p > 0.05).

Conclusions: The survival of patients with KTx-RCC after TKI monotherapy was shorter than that of patients with sporadic RCC, possibly due to the presence of multiple poor prognosticators. Effective treatment strategies, including postoperative monitoring for early diagnosis, should be identified in this high-risk population.

Background: Obesity is a known risk factor for diabetes mellitus (DM) and chronic kidney disease (CKD), yet the relationship between various obesity-related indices and CKD remains unclear. This study evaluated the associations between eight obesity indices with CKD and identified the most useful index among patients with DM.

Methods: This study used data from the Korean National Health and Nutrition Examination Survey conducted from 2007 to 2018. A total of 5,067 participants aged ≥ 20 years with DM were included. The study evaluated four traditional anthropometric obesity indices (body mass index [BMI], waist-to-height ratio [WHtR], body roundness index [BRI], conicity index [CI]) and four biochemical-anthropometric indices, including two Asian-specific indices (lipid accumulation product [LAP], visceral adiposity index [VAI], Chinese visceral adiposity index [CVAI], and new visceral adiposity index [NVAI]).

Results: WHtR, BRI, CI, CVAI, and NVAI were higher in males with CKD, while only CI, CVAI, and NVAI were elevated in females. All eight indices were independently associated with CKD risk in males, whereas only the anthropometric-biochemical indices LAP, VAI, and CVAI were significantly associated with CKD in females. NVAI in males and CVAI in females exhibited the highest area under the curve values of 0.615 and 0.658, respectively.

Conclusions: Various obesity indices were associated with CKD in patients with DM, although the associations differed by sex. Asian-specific indices may be the most useful for reflecting CKD in patients with DM.

Nephrotic syndrome is a common kidney disease during childhood that is characterized by alterations in the glomerular filtration barrier and leads to protein loss in the urine. Approximately 90% of cases are classified as idiopathic nephrotic syndrome, most of which are histologically diagnosed as minimal change disease (MCD). Although the majority of patients achieve remission with steroid therapy, a subset develops steroid resistance and progresses to focal segmental glomerulosclerosis (FSGS) and kidney failure. Increasing evidence suggests that MCD and idiopathic FSGS represent a disease continuum, with FSGS reflecting a more advanced stage. Although several candidates have been proposed as circulating factors, none fully explains the disease pathogenesis. This landscape changed in 2022 with the discovery of anti-nephrin autoantibodies in MCD. Subsequently, we reported that circulating anti-nephrin autoantibodies were identified by ELISA in patients with post-transplant recurrent FSGS, and punctate IgG deposition colocalizing with nephrin was consistently detected in allograft biopsy specimens obtained during recurrence. Notably, these IgG deposits resolved following remission. Collectively, these findings suggest diffuse podocytopathies as autoantibody-mediated disorders and support a shift toward autoantibody-based disease classification. Experimental and clinical studies demonstrate that anti-nephrin autoantibodies induce nephrin phosphorylation. This process may be associated with nephrin endocytosis and subsequent cytoskeletal alterations. Additionally, autoantibodies targeting slit diaphragm molecules other than nephrin have been identified. However, the pathogenic roles of these autoantibodies remain to be clarified. Collectively, these findings highlight a complex, autoantibody-driven mechanism in diffuse podocytopathies and underscore the need for standardized assays and biomarker-driven classification strategies.