Clinical and Experimental Nephrology最新文献

Background: The relationship between serum aspartate/alanine aminotransferase ratio (AST/ALT) and subsequent development of chronic kidney disease (CKD) in non-diabetic Asian adults has not yet been fully investigated in longitudinal studies.

Methods: The study included all middle-aged and older non-diabetic Japanese citizens who received health check-ups in Zentsuji, Kagawa, Japan (1998-2023). AST/ALT was classified into three categories: < 1.0 (reference), 1.0- < 1.5, and ≥ 1.5. CKD was defined as an estimated glomerular filtration rate of < 60 mL/min/1.73 m². The Weibull accelerated failure time model was used to examine the association between AST/ALT categories and subsequent CKD onset because the proportional hazards assumption was violated.

Results: Of 6309 men and 9192 women, 2966 men and 4395 women remained in the final cohort. After a mean follow-up of 7.50 years for men and 8.34 years for women, 33.7% of men and 34.0% of women developed CKD. Women had higher AST/ALT than men. In women, a dose-response relationship was observed, with a 9% shorter survival time to CKD onset for AST/ALT ≥ 1.5 compared with AST/ALT < 1.0. In contrast, men had a shorter survival time to CKD onset by point estimates, but the 95% confidence intervals crossed 1 in all models.

Conclusions: In this study comparing the risks of CKD development in non-diabetic men and women by AST/ALT levels, a dose-response relationship was only observed in women. Differences in the distribution of AST/ALT by sex may have affected the results. Therefore, in non-diabetic Japanese women, AST/ALT may be used as an indicator of future CKD development.

Background: miRNAs are non-coding RNA that are recognized as biomarkers of kidney disorders. There is limited information on the differential expression of miRNA and their target genes in idiopathic nephrotic syndrome of childhood.

Methods: We enrolled patients, 2-18 years old, with steroid-sensitive nephrotic syndrome, either at onset or during relapse, and steroid-resistant disease, at diagnosis of steroid-resistance. Patients with steroid-sensitive disease were off immunosuppressive medications, while those with steroid-resistance were on therapy with prednisolone at enrollment. Controls were healthy children attending the hospital for vaccinations or for minor non-infectious, non-kidney ailments. Following RNA extraction from whole blood, differential expression of 2549 miRNAs was examined to identify differentially expressed miRNA, defined as those with absolute log₂ fold change > 2 and adjusted P < 0.05. Target genes, predicted using miRNet, were compared against the genes for nephrotic syndrome in the NCBI database, and the ontology of selected genes was examined using DAVID.

Results: Comparison of miRNA expression in 36 patients and 12 controls led to the identification of 62 and 12 differentially expressed miRNA in patients with steroid-sensitive and steroid-resistant disease, respectively. Of 76 miRNAs that were differentially regulated between the two disease categories, 26 were unique to steroid-sensitive disease and 11 to steroid-resistance. Of 5955 and 2813 genes targeted by the miRNAs specific to steroid-sensitive and steroid-resistant nephrotic syndrome, respectively, 79 were relevant in context of the disease.

Conclusion: Steroid-sensitive and steroid-resistant nephrotic syndrome have distinct miRNA expression profiles, which can be examined as biomarkers and in pathogenetic pathways.

Mitochondrial nephropathy is a genetic renal disease characterized by oxidative phosphorylation abnormalities in the mitochondrial respiratory chain in kidney cells, caused by pathogenic gene variants located on mitochondrial or nuclear DNA. Recent advancements in genetic diagnostic techniques and their widespread adoption have led to the identification of various genes associated with mitochondrial nephropathy. This review investigates the causative genes and clinicopathological features of mitochondrial nephropathy, including the various phenotypes and associated complications, and suggests potential pathogenic mechanisms. Furthermore, the diagnostic methods of the disease are explained with particular emphasis on characteristic pathological findings and genetic analysis. We also analyze the available long-term observational prognostic data. Although there is currently no evidence-based treatment for mitochondrial nephropathy, an overview of the existing treatment options is discussed, including future expectations. The choice of renal replacement therapy in cases with progression to end-stage renal disease has also been discussed. Overall, this review highlights the importance of raising awareness about mitochondrial nephropathy and establishing appropriate diagnostic systems to facilitate rapid and effective treatment.

Background: Chronic kidney disease (CKD) significantly increases stroke risk and severity, posing challenges in both acute management and long-term outcomes. CKD contributes to cerebrovascular pathology through systemic inflammation, oxidative stress, endothelial dysfunction, vascular calcification, impaired cerebral autoregulation, and a prothrombotic state, all of which exacerbate stroke risk and outcomes.

Methods: This review synthesizes evidence from peer-reviewed literature to elucidate the pathophysiological mechanisms linking CKD and stroke. It evaluates the efficacy and safety of acute reperfusion therapies-intravenous thrombolysis and endovascular thrombectomy-in CKD patients with acute ischemic stroke. Considerations, such as renal function, drug dosage adjustments, and the risk of contrast-induced nephropathy, are critically analyzed. Evidence-based recommendations and research priorities are drawn from an analysis of current practices and existing knowledge gaps.

Results: CKD influences stroke outcomes through systemic and local pathophysiological changes, necessitating tailored therapeutic approaches. Reperfusion therapies are effective in CKD patients but require careful monitoring of renal function to mitigate risks, such as contrast-induced nephropathy and thrombolytic complications. The bidirectional relationship between stroke and CKD highlights the need for integrated management strategies to address both conditions. Early detection and optimized management of CKD significantly reduce stroke-related morbidity and mortality.

Conclusion: Optimizing stroke care in CKD patients requires a comprehensive understanding of their pathophysiology and clinical management challenges. This article provides evidence-based recommendations, emphasizing individualized treatment decisions and coordinated care. It underscores the importance of integrating renal considerations into stroke treatment protocols and highlights the need for future research to refine therapeutic strategies, address knowledge gaps, and consider tailored interventions to improve outcomes and quality of life for this high-risk population.

Background: Conservative kidney management (CKM) is a treatment alternative for patients with end-stage kidney disease (ESKD). Despite the increasing population of elderly dialysis patients in Japan, CKM is not as readily available compared with that in North America and Europe. Therefore, it is important to clarify the barriers to CKM in Japan.

Methods: We interviewed 11 experts to explore their beliefs and issues regarding CKM. Based on the interviews, we categorized the CKM barriers into eight categories and created a 24-item questionnaire. A questionnaire survey was conducted among 112 medical professionals involved in ESKD management. To investigate the types of barriers, we conducted an exploratory factor analysis using the questionnaire results.

Results: Responses were obtained from 53 (47.3%) of 112 subjects (18 doctors, 29 nurses, 6 clinical engineers), with 94.3% considering CKM as a treatment option for ESKD. Factor analysis categorized the questions into the following: (1) Lack of palliative care experience, (2) Ethics and responsibility, (3) Patient's problem, (4) Dialog with patients and families, and (5) Lack of support system. Regarding barriers to CKM, "lack of experience in palliative care" and "lack of support system" scored the highest, and "ethics and responsibility" scored the lowest.

Conclusions: Barriers to CKM may be classified into five factors, with "lack of experience in palliative care" and "lack of support system" being the important barriers to overcome. Additionally, most healthcare professionals consider CKM as the fourth option for renal replacement therapy.

In individuals with diabetes, chronic kidney disease (CKD) is a major comorbidity. However, it appears that there is worldwide confusion regarding which term should be used to describe CKD complicated with diabetes: diabetic nephropathy, diabetic kidney disease (DKD), CKD with diabetes, diabetes and CKD, etc. Similar confusion has also been reported in Japan. Therefore, to provide clarification, the Japanese Diabetes Society and the Japanese Society of Nephrology collaborated to update the corresponding Japanese term to describe DKD and clearly define the concept of DKD. In this review, we briefly described the history of kidney complications in individuals with diabetes and the Japanese definition of the DKD concept and provided our rationale for these changes.

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: Blood pressure (BP) control is an important factor in the management of chronic kidney disease (CKD). Several studies have shown that BP in many patients with CKD remained uncontrolled even with multiple medications. Sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), has been newly approved for treating hypertension in Japan. However, the renoprotective effects remain unclear, particularly in patients with advanced CKD. Here, we investigated the effects on proteinuria of this ARNI in patients with stage 4-5 CKD.

Methods: We retrospectively collected data from outpatients with stage 4-5 CKD who started ARNI from January until December 2023. The primary outcome was the change in urine protein creatinine ratio (UPCR) at 6 months after ARNI initiation. Secondary outcomes were systolic and diastolic BP, estimated glomerular filtration rate (eGFR), serum potassium, and serum uric acid (UA). We analyzed factors associated with 50% UPCR reduction by multivariate analysis.

Results: In total, 47 patients were analyzed. ARNI reduced UPCR from 2.14 g/gCr (interquartile range; 1.09-2.91) to 1.05 g/gCr (0.42-1.95; p < 0.001). Systolic BP fell from 150.0 mmHg (139.5-160.0) to 134.0 mmHg (124.5-140.0; p < 0.001). No significant changes in eGFR, serum potassium, and serum uric acid were observed, except for a slight decrease in eGFR among patients with conversion from a renin-angiotensin system inhibitor to ARNI. In multivariate regression analysis, higher systolic BP (per 10-mmHg increase) was significantly associated with reduced proteinuria (odds ratio 2.51, 95% confidence interval 1.35-4.66; p = 0.004).

Conclusions: ARNI reduced proteinuria in patients with stage 4-5 CKD, particularly for those with uncontrolled hypertension.

Background: Tonsillectomy with steroid pulse therapy (TSP) and tonsillectomy monotherapy (T) have improved the prognosis of patients with immunoglobulin A nephropathy (IgAN). However, a consensus has not been reached on the best treatment for these patients. This study aimed to compare the efficacies of TSP and T.

Methods: Data of patients with IgAN who received TSP or T were retrospectively analyzed. The exclusion criterion was a serum creatinine level > 1.5 mg/dL. The clinical remission and renal survival rates were compared.

Results: Patients were divided into groups based on the treatment method: the TSP (n = 82) and T groups (n = 41). No significant differences were observed in patient characteristics, except for the observation period (TSP: 60 months, T: 113 months). The log-rank test revealed that the clinical remission rate was significantly higher in the TSP group than in the T group (p < 0.05). The superiority of TSP was also observed in the urinary protein excretion (> / = or < 1 g/day) of the two subgroups. According to the Cox proportional-hazards model, the treatment method and daily urinary protein extraction were independent factors affecting clinical remission. The 10-year renal survival rates in the TSP and T groups were 100% and 92.5%, respectively. The log-rank test revealed a tendency for a higher renal survival rate in the TSP group than in the T group (p = 0.09).

Conclusion: The clinical remission rate was significantly higher with TSP than with T, regardless of urinary protein levels. TSP tended to have a better renal survival rate than T.