Clinical and Experimental Nephrology最新文献

Background: Nephrotic syndrome (NS) carries a high risk of severe complications and kidney failure, necessitating reliable prognostic markers. Given the link between tubular injury and poor remission of proteinuria, markers of tubular function may be informative in NS. The urine-to-blood urea nitrogen ratio (UBUR) reflects tubular urea handling, yet its prognostic value in NS is unclear. We evaluated whether baseline UBUR predicts proteinuria remission in adult NS.

Methods: This multicenter retrospective study included patients with NS who underwent kidney biopsy between January 2012 and June 2022. Patients were followed from kidney biopsy until complete remission, dialysis initiation, death, or the end of the observation period (12 months after kidney biopsy).

Results: A total of 237 patients (median age, 63 years; 47% female) were included, and divided into two groups based on a UBUR cutoff of 25.4 determined by the receiver operating characteristic curve. Patients with high UBUR had a significantly higher cumulative incidence of complete remission compared to those with low UBUR (P < 0.001, log-rank test). In multivariable Cox regression analysis, high UBUR independently predicted a greater likelihood of complete remission (hazard ratio 2.30 [95% confidence interval 1.47-3.61]). This association persisted in the subgroup analyses for podocytopathies, defined as minimal change disease and focal segmental glomerulosclerosis.

Conclusions: High UBUR independently predicts proteinuria remission in adults with NS. UBUR could have potential as a simple, valuable biomarker to help guide the management of NS.

Background: Catheter exit-site infection is a major cause of withdrawal from peritoneal dialysis (PD). However, methods for caring for the peritoneal catheter and exit sites are not established and vary among facilities. No survey has been conducted on exit-site management in Japan. Here, we aimed to identify successful examples that led to best practices.

Methods: The Japanese Society for Peritoneal Dialysis-led PD-related infection project was launched in 2023, under which a survey was conducted at 14 facilities nationwide that provide PD therapy. The survey content included questions about the timing of the initiation of exit-site care, the materials used in exit-site protection, and the disinfectants used for exit-site care.

Results: Seventy-one percent of the exit-site direction was downward. In all facilities, the exit site was dressed immediately after its creation for several days up to a certain period. Many facilities started exit-site care within 1-2 weeks of PD initiation. Notably, 50% of the facilities did not use disinfectants. Twelve facilities used gauze or film dressings to protect the exit site. The catheter was secured in many facilities; however, the distance of fixation varied. The timing for starting a shower after exit-site creation was commonly 1-4 weeks post-surgery. Nine facilities allowed bathing without a cover, typically after > 1 month. Of these, 7 did not use Spa Clean.

Conclusions: These findings provide insights into exit-site care trends across facilities. Further studies and trials are needed to establish the best practice on exit-site care for Japanese patients undergoing PD.

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: Acute kidney injury (AKI) caused by red yeast rice Cholestehelp® (CP) tablets has become a public health issue in Japan. Puberulic acid (PA) contaminated in CP tablets may cause AKI; however, we detected silica nanoparticles in a CP patient. CP-related kidney injury was examined in rats that underwent left nephrectomy to increase silica nanoparticle loading.

Methods: Six male Sprague-Dawley rats were administered CP and underwent left nephrectomy on day 4. Blood and urine samples were collected on day 11. Renal tissues were observed by electron microscopy and low-vacuum scanning electron microscopy-energy dispersive X-ray spectroscopy (LVSEM-EDS). The amount of PA in CP was measured, and PA was administered to normal rats and unilaterally nephrectomized rats.

Results: Normal rats receiving CP (2KCP) had increased urine volume and lower urine specific gravity than controls, but no significant changes were observed in urinary protein, renal function, electrolytes, or blood gasses. Unilaterally nephrectomized rats receiving CP (1KCP) had increased water intake and urine volume, decreased urine specific gravity, and increased low-molecular-weight proteinuria. The glomeruli of 1KCP rats showed expanded subendothelial space and increased endocytic vesicles were observed in the proximal tubules relative to 2KCP rats. The accumulation of nanoparticles in the endosomes of the proximal tubules, and LVSEM-EDS detected silicon in renal tissue. Administration of PA at the doses in CP tablet did not result in significant renal injury.

Conclusions: Uninephrectomized rats administered CP tablets showed accumulation of silicon-containing nanoparticles in the proximal tubules and renal injury.

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.

Background: Proteinuria reduction is considered a potential surrogate endpoint predictive of reflecting long-term kidney prognosis in IgA nephropathy (IgAN), but quantitative evidence in Japanese patients is limited. We aimed to examine the association between short-term proteinuria reduction at 12 months and long-term kidney outcomes in Japan IgA Nephropathy Cohort Study (J-IGACS).

Methods: Participants from J-IGACS were categorized into tertiles based on their 12-month proteinuria-to-baseline proteinuria ratios. The primary outcome was a composite of ≥ 40% estimated glomerular filtration rate (eGFR) decline or initiation of kidney-replacement therapy. Associations between proteinuria ratio and outcomes were assessed using Cox proportional hazards models and restricted cubic splines. Multivariable analyses adjusted for age, sex, baseline eGFR, log-transformed proteinuria, Oxford classification scores, and use of corticosteroids and renin-angiotensin-aldosterone system inhibitors within 12 months.

Results: Among 792 patients, those in the greatest proteinuria reduction had significantly lower risk of the primary endpoint (P for trend < 0.001) and a more favorable eGFR slope. Spline analysis showed a continuous, dose-response association between proteinuria ratio and improved outcomes. These findings remained robust in sensitivity analyses restricted to patients likely qualifying for clinical trials. The results showed that patients with lower proteinuria ratios tended to have slower rates of eGFR decline (P for trend < 0.001).

Conclusion: Proteinuria reduction within the first-year post-diagnosis is independently associated with lower risk of adverse kidney outcomes and a slower decline in kidney function in patients with IgAN. These results support the use of proteinuria reduction as a surrogate endpoint in both clinical trials and disease management.

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.