Clinical and Experimental Nephrology最新文献

Background: Proteinuria is a key marker of chronic kidney disease, notably in diabetic nephropathy (DN) and IgA nephropathy (IgAN). This study examined urinary IgG fragmentation and its link to disease progression.

Methods: Urinary IgG fragments were analyzed via western blot in diabetic mice and human subjects (controls: n = 7; diabetics: n = 14; IgAN: n = 15). Mouse and human IgG cleavage with renal tubular and glomerular fractions was performed in the presence or absence of protease inhibitors. Urinary cathepsin B activity was also measured.

Results: In diabetic mice, a 31-kDa IgG fragment appeared in the urine before the onset of albuminuria. This process was mediated by cathepsin D in the tubular fraction. Analysis of human subjects showed that fragmented IgG, especially the 47 kDa fragment, was increased in the urine of diabetic patients and correlated with elevated glycated hemoglobin (HbA1c) levels, but not in IgAN patients. Cathepsin B generated the IgG fragment by the tubular fraction, and its urinary activity was lower in IgAN patients than in diabetics.

Conclusion: Distinct patterns of IgG fragmentation and cathepsin B activity in DN versus IgAN suggest urinary IgG fragments may serve as early biomarkers and reflect disease-specific proteolytic pathways.

Background: The phenotype of autosomal recessive polycystic kidney disease (ARPKD) can be quite variable: some patients progress to end-stage kidney disease (ESKD) in infancy, while others may not require kidney replacement therapy (KRT) until later childhood or adolescence. This study aimed to evaluate clinical, biochemical, imaging, and genetic findings that may influence kidney prognosis in pediatric patients with ARPKD.

Methods: The patients diagnosed before birth or in the first month were classified as perinatal presenters and later than 1 month as non-perinatal presenters. Additionally, groups were formed based on estimated glomerular filtration rate (eGFR) at the last visit and variant types.

Results: Seventeen patients (8 male, 9 female) were enrolled in the study. Kidney survival rates at 5 years was 71.4% in the perinatal group, whereas it was 100% in the non-perinatal group. The early height-adjusted kidney dimension (haKD) was positively correlated with perinatal presentation and antenatal diagnosis. At the last follow-up, the mean eGFR was significantly lower in the truncating group with four patients (23.5%) progressing to stage-5 chronic kidney disease (CKD).

Conclusions: The kidney survival rate is lower in patients with early presentation. Initial low eGFR and severe variants are important predictors of kidney survival. Additionally, early high haKD may be associated with poor kidney outcome. Further studies with larger patient populations and long-term follow-up are necessary to better understand the prognosis of pediatric patients with ARPKD.

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.

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.

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: 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: Pediatric kidney failure carries high cardiovascular risk. Kidney transplantation is the preferred therapy, yet residual endothelial dysfunction contributes to post-transplant morbidity. The current study determines whether pre-transplant hemodialysis versus peritoneal dialysis affects post-transplant levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), P-selectin, and nitric oxide (NO) in pediatric kidney transplant recipients.

Methods: In a cross-sectional study, we assessed 53 children 6-24 months after kidney transplantation. Fourteen had received peritoneal dialysis and 39 hemodialysis pre-transplant. Serum sICAM-1, sVCAM-1, and P-selectin were measured using a Luminex-based assay and NO by chemiluminescence.

Results: Baseline demographic characteristics were similar between groups. Peritoneal dialysis was associated with lower sICAM-1 (p= 0.028) and sVCAM-1 (p= 0.006) and higher NO (p< 0.001), whereas P-selectin did not differ (p= 0.308). sICAM-1 correlated positively with P-selectin (r= 0.286, p= 0.038) and dialysis duration (r= 0.303, p= 0.028) and inversely with glomerular filtration rate (r=-0.328, p= 0.016). sVCAM-1 correlated positively with dialysis exposure time (r= 0.340, p= 0.013) and negatively with NO (r=-0.393, p= 0.004). Dialysis type and duration predicted sVCAM-1 (R²=0.199), dialysis exposure time-predicted sICAM-1 (R²=0.203), and modality-predicted NO (R²=0.252).

Conclusions: In pediatric kidney transplant recipients, pre-transplant peritoneal dialysis is associated with reduced endothelial activation and enhanced NO bioavailability compared with hemodialysis, suggesting a vascular benefit that could inform dialysis selection prior to transplantation.

Background: The trajectory of the ankle-brachial index (ABI) over time in relation to death has not been fully described in patients undergoing hemodialysis. We modeled ABI trajectory pattern before death in patients undergoing maintenance hemodialysis.

Methods: Patients undergoing hemodialysis in a dialysis facility were retrospectively enrolled and categorized into two groups, deceased and surviving groups, based on their status at the end of the observation period. Linear mixed-effect model and a backward timescale from the year of death or study end date were used to compare ABI trajectory between the deceased and surviving groups during the observation period.

Results: A total of 442 patients (median age, 65 years; 60.2%, men) were included. During the observation period (median, 5.3 years; maximum, 8.5 years), 130 deaths were observed. Differences in ABI between the deceased and survivors were detected in the early stages (difference at 7 years before death, 0.08; p = 0.01), with the differences between these groups becoming more pronounced at 1 year before death (difference at 1 year before death, 0.11; p < 0.001).

Conclusions: Differences in ABI trajectory between the deceased and survivors were detected from the early stages to just before death.

Renal ischemia-reperfusion injury (RIRI) is a major cause of acute kidney failure. Recent studies have shown that RIRI mechanism is closely related to abnormal mitochondrial biogenesis, fusion, fission, and autophagy. Maintaining normal mitochondrial function is essential for RIRI treatment. Therefore, it is important to explore molecular mechanisms of RIRI and relevant therapeutic targets. This review describes the role of mitochondria in RIRI and summarises information about potential drugs that regulate mitochondrial function, with the aim of providing ideas for clinical targeting of mitochondria to prevent and treat RIRI.