Clinical and Experimental Nephrology最新文献

Purpose: To investigate the safety and effectiveness of transcatheter arterial embolization (TAE) with tris-acryl gelatin microspheres in patients with symptomatic enlarged polycystic kidneys (PCKs).

Material and methods: This prospective study was planned as a safety trial for patients with symptomatic enlarged PCKs who complained of a marked abdominal distention, gastroesophageal reflux, or abdominal pain. We then assessed renal volume reduction and improvement in clinical symptoms as secondary endpoints. The patients after induction of dialysis therapy (urinary volume less than 500 mL per day) were included. Bilateral renal TAE with tris-acryl gelatin microspheres injection followed by metallic coils placement was performed, and adverse events, clinical symptoms, abdominal circumference, blood pressure, dry weight and laboratory data were evaluated at 1, 3, 6 and 12 months after TAE. Each kidney volume was calculated before TAE and at 3, 6 and 12 months after TAE.

Results: Six kidneys of three patients (65-, 58- and 54 years women) were treated. All three patients experienced abdominal pain, vomiting and inflammatory reactions immediately after TAE; however, abdominal pain and vomiting resolved within their hospitalization period, and inflammatory reactions improved during the follow-up period in all patients. Accelerated renal anemia was ameliorated by temporary blood transfusions and increased doses of erythropoiesis-stimulating agent or darbepoetin alpha during dialysis. The mean kidney volume was 3885 mL before TAE and 3025, 2320 and 1832 mL at 3, 6 and 12 months after TAE, respectively.

Conclusion: Renal TAE with tris-acryl gelatin microspheres is considered a safe and effective treatment for symptomatic enlarged PCKs.

Trial registration: This clinical trial was registered with the University Hospital Medical Information Network (UMIN) under the registration number UMIN000016576.

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.

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.