Clinical and Experimental Nephrology最新文献

Background: Patients with IgA nephropathy (IgAN) occasionally present with nephrotic range proteinuria (NRP), but the clinical features and long-term renal prognosis of patients with IgAN-related NRP (IgAN-NRP) with or without nephrotic syndrome (NS) remain elusive.

Methods: A retrospective, multicenter, cohort study enrolled 788 patients with IgAN from 42 medical centers in 2002-2004. Patients were divided into NRP (group I, n = 39) and non-NRP (group II, n = 749) groups. Group I patients were subdivided into NRP with NS (I-A, n = 14) and NRP without NS (I-B, n = 25) groups. The primary outcome (PO) was a 1.5-fold increase in serum creatinine from baseline. Clinical remission (CR) was defined as both hematuria and proteinuria remission on ≥3 consecutive tests over at least 6 months.

Results: Compared with group II, group I had significantly more severe renal dysfunction and received steroid therapy more frequently. During a median follow-up of 90.0 months, more patients reached the PO in group I (38.5%) than in group II (11.0%). Multivariate analysis of all enrolled patients showed that NRP was a significant independent risk factor for the PO. However, in group I, 10 of 11 patients who achieved CR had a favorable renal prognosis, and corticosteroid therapy significantly attenuated the risk for the PO. When comparing groups I-A and I-B, baseline renal impairment and cumulative probabilities of the PO were comparable.

Conclusion: Regardless of the presence of NS, IgAN-NRP is a critical factor leading to a poor prognosis, unless CR is achieved. Intensive treatment might be vital for IgAN-NRP.

Background: Monoclonal gammopathy of renal significance (MGRS) results in kidney injury despite not meeting the hematological malignancy criteria necessitating treatment. Although kidney biopsy is crucial for diagnosis, it is an invasive procedure. Therefore, identifying patient characteristics associated with MGRS could aid in informing the decision to perform a biopsy.

Methods: This cross-sectional multicenter study included participants with monoclonal gammopathy (MG) who underwent kidney biopsy between 2018 and 2022. We excluded patients diagnosed with hematological malignancies requiring treatment or those with vasculitis. Patient factors associated with MGRS were evaluated using a logistic regression model. Additionally, we describe monoclonal protein-related kidney diseases associated with hematological malignancies.

Results: A total of 2972 kidney biopsies were performed, of which 166 (5.6%) were associated with MG. Among these 166 patients, 57 had hematological malignancies. Of the remaining 98 patients, excluding those with vasculitis, 44 (45%) exhibited MGRS lesions. Among the MGRS cases, 71% had amyloid light-chain amyloidosis, whereas nephrosclerosis and diabetic nephropathy were more common in non-MGRS cases. Multivariate analysis revealed that the clinical predictors associated with MGRS lesions were the presence of proteinuria ≥ 1.5 g/gCr, an abnormal free light chain (FLC) ratio, and the absence of diabetes. In hematological malignancy cases, monoclonal protein-related kidney diseases were observed in 49% of the cases, with kidney histology frequently exhibiting cast nephropathy or light chain deposition disease.

Conclusions: Among patients with MG who underwent kidney biopsy, 45% were diagnosed with MGRS. Predictors of MGRS included proteinuria ≥ 1.5 g/gCr, an abnormal FLC ratio, and the absence of diabetes.

Background: Elevated parathyroid hormone (PTH) levels are associated with cardiovascular events, bone disease, and mortality in patients undergoing maintenance hemodialysis. Although PTH levels vary widely in patients undergoing hemodialysis, whether this affects mortality is unclear.

Methods: A total of 315 maintenance hemodialysis patients who underwent PTH measurements at least twice a year were enrolled. The association between all-cause mortality, cardiovascular events, and fractures was evaluated in patients with PTH concentrations of 60-240 pg/mL (time-in-target range (TTR) 100%) and those with TTR values of 75% ≤ TTR < 100%, 50% ≤ TTR < 75%, and TTR < 50%.

Results: There were 122 patients with TTR 100%, 81 patients with 75% ≤ TTR < 100%, 52 patients with 50% ≤ TTR < 75%, and 74 patients with TTR < 50%. Over the 4-year observation period, patients with TTR of 100% had significantly lower all-cause mortality than those with TTR < 50%. (HR 2.26, 95% CI 1.33-3.86) Subgroup analysis by presence or absence of pharmacological intervention showed no statistically significant difference in all-cause mortality in the treatment group (HR 2.08, 95% CI 1.16-3.72), but showed significant differences in the no-treatment group (HR 1.58, 95% CI 0.92-2.70).

Conclusion: A prolonged period of deviation from the optimal PTH range was associated with increased all-cause mortality, particularly among patients not receiving SHPT medication. However, this effect was not observed in patients who received pharmacological interventions. These results suggest that early intervention is desirable when PTH levels vary from the optimal range in patients with secondary hyperparathyroidism.

Background: Exercise is recommended to prevent dialysis; however, the involvement of physical therapists is not a criterion for reimbursable medical fee calculation in Japan. Consequently, eligible patients may not receive appropriate exercise guidance. We aimed to clarify the extent of physical therapist participation in dialysis-prevention interventions reimbursed under the current Japanese healthcare system and to identify reasons for non-participation related to reimbursement criteria.

Methods: In January 2025, a 30-item questionnaire was distributed to all facility representatives registered with the Japan Physical Therapist Association to investigate medical fees and physical therapist involvement in dialysis prevention. Dialysis-prevention interventions were defined as those reimbursed under the Japanese healthcare system: Lifestyle-Related Disease Management, Diabetes Dialysis Prevention Guidance and Management (including Guidance of Patients with Severe Renal Impairment), and Chronic Kidney Disease (CKD) Dialysis Prevention Guidance and Management.

Results: Of the 10,285 facilities surveyed, 1322 (12.9%) responded. Among these, physical therapists participated in Lifestyle-Related Disease Management, Diabetes Dialysis Prevention Guidance and Management, and CKD Dialysis Prevention Guidance and Management in 4.8%, 3.5%, and 2.3% of facilities, respectively. The most frequently cited reasons for exclusion were "Inclusion of physical therapists is not a strict requirement for medical fee reimbursement," "Insufficient personnel or time," and "No role assigned by the dialysis-prevention team."

Conclusion: Physical therapist involvement in dialysis-prevention interventions was limited, primarily due to current medical fee reimbursement criteria. Revising the healthcare system to facilitate their inclusion may enhance the delivery of exercise-based preventive care.

Background: Comprehensive epidemiological information regarding Alport syndrome, particularly from national cohorts, is limited.

Methods: Utilizing a national Alport syndrome cohort in Japan established in October 2022, we analyzed clinical characteristics according to genotype. Only baseline data collected retrospectively at enrollment were used. We present longitudinal trends in estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio.

Results: Of the 121 patients included, 105 (86.8%) underwent genetic testing and 82 (67.8%) had a kidney biopsy. Among those with genetic testing, 77 (73.3%) had X-linked Alport syndrome. Kidney function was normal at disease onset, with a median eGFR of 112.9 (interquartile range, 99.3-131.1) mL/min/1.73 m². Although a steep decline during adolescence was observed in some male patients with X-linked Alport syndrome, eGFR decline was relatively slow during childhood and adolescence; the point estimate of eGFR at age 20 was 88.6 mL/min/1.73 m². Six patients transitioned to end-stage kidney disease during the follow-up period. Eighty-one patients (66.9%) used renin-angiotensin system (RAS) inhibitors, and the rate of eGFR decline was slower after RAS inhibitor initiation. Notably, the median ages at onset and diagnosis were 3.0 and 5.1 years, respectively, because Japan's widespread urinalysis screening program for 3-year-old children enables initiation of early treatment.

Conclusions: In our cohort, which consisted mainly of patients who did not require kidney replacement therapy in childhood and adolescence, kidney function was preserved throughout this period except for some male patients with X-linked Alport syndrome. RAS inhibitor use may be associated with a reduced rate of eGFR decline.

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.