Clinical and Experimental Nephrology最新文献

Background: Serum phosphate (P) levels are generally lower in autosomal dominant polycystic kidney disease (ADPKD) than in other kidney disorders, potentially masking the clinical significance of hyperphosphatemia. This study aimed to determine if serum P levels can predict renal outcomes in ADPKD patients.

Methods: We included 235 patients with ADPKD who were not taking drugs to treat hyperphosphatemia. Survival analysis was performed for the renal outcome of a 50% reduction in estimated glomerular filtration rate or initiation of renal replacement therapy.

Results: Multivariable Cox regression analyses revealed that serum P (1 mg/dL increase, HR = 2.03, P < 0.0001) was a significant risk factor for kidney disease progression. Similarly, hyperphosphatemia (P > 3.5 mg/dL, HR = 2.05; P > 4.0 mg/dL, HR = 1.90; P > 4.5 mg/dL, HR = 2.78; P > 5.0 mg/dL, HR = 27.22) was significantly associated with renal prognosis. Kaplan-Meier analysis showed significantly lower kidney survival rates in patients with P > 3.5 mg/dL than in those without hyperphosphatemia (log-rank test, P < 0.0001), and similar Kaplan-Meier analysis results were found for P > 4.0 mg/dL, P > 4.5 mg/dL, and P > 5.0 mg/dL. The 2 year kidney survival rate for ADPKD patients with P > 3.5 mg/dL was 66.7% overall and 41.4% in those with stage 4-5 CKD. For patients with P > 4.0 mg/dL, the survival rate dropped to 46.8% overall and 28.2% in those with stage 4-5 CKD, indicating a very poor prognosis.

Conclusion: Hyperphosphatemia was associated with renal prognosis in patients with ADPKD. In these patients, attention should be paid to even mild serum P elevation of > 3.5 or > 4.0 mg/dL.

Background: Angiogenesis and inflammation are key events leading to peritoneal morphologic alteration and ultrafiltration failure in patients undergoing peritoneal dialysis (PD). The current study aims to explore the role of ADAM17 in the angiogenetic and inflammatory responses of endothelial cells.

Methods: Human umbilical vein endothelial cells (HUVECs) were cultured and treated with a high glucose-containing medium. In parallel experiments, the expression of ADAM17 in HUVECs was inhibited by SiRNA interference. The mRNA and protein expression of ADAM17, GRO-α and CXCR2 were assessed by qPCR and Western blotting, respectively. The concentrations of GRO-α, VEGF, IL-6 and TNF-α in the cellular supernatants were determined by ELISA. Tube formation and migration of HUVECs were evaluated by Matrigel and transwell migration apparatus.

Results: High glucose increased the expression of ADAM17, CXCR2 and GRO-α in cultured HUVECs. RNA silencing of ADAM17 abolished high glucose-mediated increase of GRO-α and CXCR2, which were accompanied by reduced secretion of VEGF, IL-6, TNF-α, as well as tube formation and cell migration in HUVECs.

Conclusions: Inhibition of ADAM17 ameliorates high glucose-induced angiogenic and inflammatory responses in endothelial cells partly through down-regulation of GRO-α/CXCR2 expression.

Background: For the development of pharmaceutical products in kidney field, appropriate surrogate endpoints which can predict long-term prognosis are needed as an alternative to hard endpoints, such as end-stage kidney disease. Though international workshop has proposed estimated glomerular filtration rate (GFR) slope reduction of 0.5-1.0 mL/min/1.73 m /year and 30% decrease in albuminuria/proteinuria as surrogate endpoints in early and advanced chronic kidney disease (CKD), it was not clear whether these are applicable to Japanese patients.

Methods: We analyzed J-CKD-DB and CKD-JAC, Japanese databases/cohorts of CKD patients, and J-DREAMS, a Japanese database of patients with diabetes mellitus to investigate the applicability of eGFR slope and albuminuria/proteinuria to the Japanese population. Systematic review on those endpoints was also conducted including the results of clinical trials published after the above proposal.

Results: Our analysis showed an association between eGFR slope and the risk of end-stage kidney disease. A 30% decrease in albuminuria/proteinuria over 2 years corresponded to a 20% decrease in the risk of end-stage kidney disease patients with baseline UACR ≥ 30 mg/gCre or UPCR ≥ 0.15 g/gCre in the analysis of CKD-JAC, though this analysis was not performed on the other database/cohort. Those results suggested similar trends to those of the systematic review.

Conclusion: The results suggested that eGFR slope and decreased albuminuria/proteinuria may be used as a surrogate endpoint in clinical trials for early CKD (including diabetic kidney disease) in Japanese population, though its validity and cutoff values must be carefully considered based on the latest evidence and other factors.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages, it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Background: This study aimed to evaluate the association between phase angle, muscle strength, and muscle mass in patients undergoing kidney transplantation.

Methods: Patients whose pre- and follow-up phase angles were measured after kidney transplantation were enrolled. Phase angle and body composition were measured using a multi-frequency bioimpedance analysis device before and at 7 and 14 days and 3, 6, and 12 months after transplantation. Muscle strength was evaluated using handgrip strength (HGS). Low HGS was defined as < 28 kg in males and < 18 kg in females. Low muscle mass was defined as an appendicular lean mass index of < 7.0 kg/m² in males and < 5.7 kg/m² in females.

Results: Eighty-eight patients (mean age 52.3 ± 10.1 years) were analyzed. The mean phase angle of pre-transplantation was 5.0 ± 1.0°. Body fat percentage was significantly higher at 6 and 12 months after transplantation than pre-transplantation (P < 0.0001). Twelve months after kidney transplantation, the prevalence of low HGS decreased (pre-transplantation vs. 12 months post-transplantation: 28.4% vs. 17.0%), and the prevalence of low muscle mass (pre-transplantation vs. 12 months post-transplantation: 21.6% vs. 28.4%) increased. The pre-transplantation phase angle was significantly associated with low muscle mass at 12 months after kidney transplantation (odds ratio [OR]: 0.34; 95% confidence interval [CI]: 0.16-0.72; P = 0.005). The pre-transplantation phase angle was not significantly associated with low HGS (OR: 0.37; 95% CI 0.12-1.17; P = 0.090) 12 months after kidney transplantation.

Conclusions: Pre-transplantation phase angle can predict muscle mass status 12 months after kidney transplantation.

Background: A streamlined and effective renal biopsy technique is essential for all nephrologists, particularly those who are less experienced, such as residents. Herein, we report the efficacy of a Straightforward and Immediate ultrasound-guided kidney biopsy using a Guide Needle (SIGN) technique, which allows operators to insert a biopsy gun through a guide needle placed into the fascia of the posterior abdominal wall.

Methods: A retrospective cross-sectional study was conducted at a nephrology training institution to compare the time spent on the procedure and the number of glomeruli obtained between a group using the SIGN (n = 81) and a group using the conventional ultrasound-guided kidney biopsy technique with a needle guide device (n = 143).

Results: The median procedure time in the SIGN group (2 min, interquartile range [IQR]: 1-3 min) was significantly shorter than that in the conventional group (3 min, IQR: 2-4 min) (P < 0.001). Multivariable linear regression and logistic regression analyses adjusted for covariates, including operators (board-certificated nephrologists or nephrology residents), showed that the use of the SIGN technique was independently associated with a high number of glomeruli obtained and a procedure time above 2 min as the median value (odds ratio: 0.17, 95% confidence interval CI 0.09-0.34). The prevalence of complications was comparable between the two groups (P = 0.681).

Conclusion: The SIGN technique reduces the procedure time and obtains adequate biopsy tissue regardless of the operator's experience. SIGN can be applied in nephrology training programs and used as a standard biopsy technique.

Background: Aortic stenosis (AS) and aortic valve calcification (AVC) are occasionally observed in patients receiving maintenance dialysis. However, their prevalence and factors associated with them in patients undergoing dialysis remain unknown. We aimed to elucidate the aortic valve status at the time of dialysis initiation and patient prognosis based on aortic valve status.

Methods: We analyzed 289 patients initiating dialysis (hemodialysis: peritoneal dialysis = 275:14) between 2016 and 2023. "AS and/or AVC" was detected using echocardiography. AS was defined as a maximum transaortic velocity > 2.0 m/s. Statistical analyses including multivariable logistic regression and Cox regression were used to assess the association between patient characteristics and survival outcomes.

Results: Aortic valve changes were observed in 121 (42%) patients, among which 33 (11%) met the AS criteria. The mean age of patients in the AS, AVC without AS, and control groups was 79.1 ± 8.9, 75.9 ± 9.2, and 68.3 ± 12.9, respectively (P < 0.001). Multivariable logistic regression models showed that only age was associated with aortic valve changes (P < 0.001). Age and other important factor-adjusted multivariable Cox regression models showed that AS was an independent risk factor for death after dialysis initiation (hazard ratio (HR): 1.95, 95% confidence interval (CI): 1.06 - 3.59, P = 0.04). However, aortic valve changes ("AS and/or AVC") were not a risk factor for death (HR: 1.51, 95% CI 0.95 - 2.39, P = 0.08).

Conclusions: With the growing older population undergoing dialysis, aortic valve changes should be closely monitored. Particularly, AS is crucial because of its impact on patient prognosis.

Background: Kidney transplantation (KT) in children and adolescents with severe motor and intellectual disabilities (SMID) has been a topic of controversy. A multicenter study in Japan showed that KT was not contraindicated for children with multiple handicaps, but no consensus has been reached on KT for patients with SMID. This study aimed to determine whether KT is a viable treatment option for children and adolescents with SMID.

Methods: A single-center, retrospective study was conducted on children and adolescents with SMID who underwent KT. SMID was defined based on Oshima's classification. Clinical information was collected through a review of medical records.

Results: Of 453 children and adolescents who underwent KT between 1983 and 2023 in our institution, six (1.3%) patients with SMID were identified. One patient received KT twice. All patients underwent living KT. Five patients used medical devices, including gastrostomy and a ventriculoperitoneal shunt, prior to KT. Perioperative complications, including hemothorax related to central venous catheter insertion, ventilator-associated pneumonia, and common iliac artery thrombosis requiring graftectomy, occurred in three patients. One patient required vesicostomy owing to refractory urinary tract infection. There was no significant difference in the graft survival rate between patients with SMID and those without SMID. One patient developed graft failure and died after selecting conservative kidney management.

Conclusion: Our study showed a favorable graft survival in children and adolescents with SMID who underwent KT. Although careful perioperative management and continued medical care are required, KT may be a viable option for these patients.