Clinical and Experimental Nephrology最新文献

Kidney transplantation is usually the optimal treatment option for patients living with kidney failure given its associations with improved survival, quality of life outcomes and a reduction in the personal, economic, and societal burden of long-term dialysis. While advantages of kidney transplantation are recognized, post-transplant complications, such as graft rejection, ischemia-reperfusion injury, surgical-related complications, and long-term consequences of immunosuppressive therapies, are commonly observed. There has been increased research on developing non-invasive biomarkers for the monitoring of transplanted kidneys over recent decades. The potential of urinary biomarkers to identify graft rejection, post-transplant acute tubular necrosis, detect progression of epithelial-to-mesenchymal transition toward tubulointerstitial fibrosis, and to differentiate between causes of graft dysfunction is an attractive alternative to invasive transplant biopsy. Innovative urinary biomarkers, such as those derived from omics technologies allow for a more holistic assessment of graft status through multi-parametric molecular analysis, although there remain questions on the consistency, reliability, and practicality of utilizing omics-based urinary biomarkers. The international nephrology community has continued to make concerted efforts to improve the procedures and cost-effectiveness of kidney transplant monitoring. In this article, we review the evidence and limitations of currently available urinary biomarkers and propose the application of urine-derived exfoliated kidney cells such as urinary exfoliated proximal tubule cells to prognosticate kidney transplant outcomes and monitor for post-transplant complications. Artificial intelligence and the incorporation of machine learning analysis of proximal tubular cell characteristics may optimize the process of differentiating graft rejection from other forms of kidney dysfunction non-invasively following kidney transplantation.

Background: Sepsis and acute kidney injury (AKI) are common, often co-occurring ICU syndromes with high mortality. Although illness severity scores such as the Simplified Acute Physiology Score II (SAPS II) are powerful prognostic tools, it is unclear whether baseline illness severity modifies the relationship between sepsis and mortality in AKI. We hypothesized that this association varies across the severity spectrum.

Methods: In a retrospective cohort of 35,926 adults with AKI, we examined the interaction between sepsis (Sepsis-3 criteria) and baseline illness severity (SAPS II) in relation to 30-day survival. We used multivariable logistic regression adjusted for demographics, comorbidities, and organ dysfunction.

Results: A significant interaction between sepsis and illness severity was observed (p < 0.001). At low severity (SAPS II = 20), sepsis was associated with a 4.3 percentage point reduction in 30-day survival, whereas at high severity (SAPS II = 90), it was associated with a 23.6 percentage point increase in survival, representing a net reversal of 27.9 percentage points. This pattern was robust in sensitivity analyses.

Conclusions: In critically ill patients with AKI, the impact of sepsis on survival is strongly modified by baseline illness severity, reversing from harm at low severity to improved survival at high severity. This paradox challenges the assumption of uniform sepsis risk and suggests that, in the sickest patients, sepsis may indicate a state of potentially reversible organ dysfunction. Incorporating illness severity into AKI prognostication may better capture recovery potential, as severity scores alone may underestimate the likelihood of recovery in severe septic AKI.

Background: With regard to complications of portal vein (PV) and inferior vena cava (IVC) thrombosis in autosomal dominant polycystic kidney disease (ADPKD), several cases have been reported based on imaging findings. However, only one autopsy case has been described and no systematic analysis has been conducted to date. This retrospective study aimed to review autopsy cases from our department over the past 37 years to clarify the frequency and background factors of thrombosis formation in ADPKD.

Methods: Among 4001 autopsies performed at our institution from 1987 to 2023, 10 ADPKD cases were identified. We examined the presence of thrombus in these 10 cases and compared pleural effusion and ascites volumes, major organ weights, and clinicopathological factors between cases with thrombus and those without.

Results: Among 10 ADPKD cases, thrombi were identified in four cases in which autopsies were performed relatively recently. These thrombi were distributed in the PV, IVC, and their branches. Compared to non-thrombotic cases, those with thrombi showed a statistically significant increase in kidney weight and tended to have a higher frequency of complications such as sepsis and severe aortic atherosclerosis.

Conclusion: This study reports the first systematic autopsy-based investigation of PV and IVC thrombosis in ADPKD. Thrombosis was found at a high frequency of 40% and appears to have increased in recent years. Increased kidney weight was associated with thrombosis formation, and blood stasis due to compression by enlarged kidneys is considered the primary cause. Further case accumulation and elucidation of the pathophysiology involved are anticipated.

Background: Although proteinuria is a key prognostic marker in immunoglobulin A nephropathy (IgAN), the optimal post-biopsy timing for its assessment remains uncertain, particularly given variability in treatment type and timing. Using longitudinal data from the Japan IgA Nephropathy Prospective Cohort Study (J-IGACS), we sought to identify the post-biopsy time point at which proteinuria most reliably predicts kidney outcomes.

Methods: Proteinuria was assessed at baseline and at 6, 12, 18, and 24 months after biopsy. The primary outcome was defined as a ≥ 50% increase in serum creatinine or initiation of kidney replacement therapy in adults (≥ 20 years) and as a ≥ 25% decline in eGFR or initiation of kidney replacement therapy in patients aged < 20 years. Model performance was compared using the corrected Akaike Information Criterion.

Results: Among 588 patients (median age 38 years; mean eGFR 76.5 mL/min/1.73 m²; median proteinuria 0.64 g/day), 43 (7.3%) reached the primary outcome during a median 78-month follow-up. Proteinuria at all time points was independently associated with kidney outcomes, with the 18-month measurement providing the best model fit. A threshold of 0.44 g/day (or g/gCr) yielded 79% sensitivity and 81% specificity, and patients with proteinuria ≥ 0.44 g/day at 18 months had significantly worse outcomes. Cox regression confirmed a robust association for 18-month proteinuria, irrespective of treatment type or timing.

Conclusions: Proteinuria measured 18 months post-biopsy showed the strongest association with long-term kidney outcomes in IgAN, supporting its use as a universal treatment target across heterogeneous post-biopsy clinical courses.

Background: Renal involvement, occurring in approximately -1% to 5% of patients with sarcoidosis, is characterized mainly by granulomatous interstitial nephritis. Angiotensin-converting enzyme (ACE) reflects the presence of granuloma; accordingly, serum ACE (sACE) and tubular injury markers are measured in renal sarcoidosis (RS). However, these markers possess low diagnostic accuracy; therefore, we hypothesized that urinary ACE (uACE) could reflect granuloma in the kidneys and be a disease-specific marker for RS.

Methods: In this single-center retrospective study, the sACE and uACE levels were measured and the creatinine-corrected ratio of uACE and sACE (u/s ACE ratio) was calculated. Additionally, patients with sarcoidosis without renal insufficiency (RI), sarcoidosis with RI, and tubulointerstitial nephritis (TIN) without a sarcoidosis etiology were included as controls.

Results: This study included 18, 18, 14, and 10 patients in the RS, sarcoidosis without RI, sarcoidosis with RI, and TIN without sarcoidosis etiology groups, respectively. uACE and u/s ACE ratio in the RS group were higher than those in the control groups. In the RS group, u/s ACE ratio was positively correlated with the degree of tubulointerstitial injury (r = 0.69, P = 0.0045); the cutoff value of u/s ACE ratio for diffuse tubulointerstitial injury was 0.39%, with a sensitivity and specificity of 100.0% each. Furthermore, obvious positive correlations were observed among u/s ACE ratio, inflammatory cell infiltrates (r = 0.53, P = 0.044), and interstitial fibrosis (r = 0.56, P = 0.029) in the RS group.

Conclusion: u/s ACE ratio and sACE could be useful biomarkers for diagnosing RS in sarcoidosis and TIN, respectively. A simple uACE assay could help diagnose and assess disease severity in patients with RS.

Background: Thrombin is a serine protease that plays an important role in blood coagulation and has been implicated in kidney diseases, particularly glomerular disorders. In this study, we aimed to evaluate urinary thrombin in different types of kidney disease and investigate whether it can be used as a biomarker for the presence of segmental sclerosis lesions in IgA nephropathy.

Methods: We enrolled 151 patients aged ≥ 18 years who underwent renal biopsy at Kumamoto University Hospital or two of its affiliate hospitals between November 2016 and September 2021. Urine samples were obtained from patients, and urinary thrombin antigen levels were measured using a previously established highly sensitive enzyme-linked immunosorbent assay. We evaluated urinary thrombin in different types of kidney disease, focusing on IgA nephropathy, and assessed the association between urinary thrombin and histological severity classification (Oxford classification), especially S lesions.

Results: Among the patients with kidney disease, thrombinuria was more prevalent in those with focal segmental glomerulosclerosis [60%; 9/15]. In 34 patients with IgA nephropathy, the logistic regression model, using the presence of S lesions as the outcome variable, demonstrated that the odds ratios for thrombinuria and proteinuria were 7.20 and 2.82, respectively. The areas under the receiver operating characteristic curve (AUROC) regarding the models for thrombinuria and proteinuria were 0.73 and 0.56, respectively, with both differences being significant (p = 0.04).

Conclusions: Our findings suggest that thrombinuria may be a novel biomarker for kidney disease, particularly for segmental sclerosis lesions in IgA nephropathy.

Infections at hemodialysis access sites remain a critical challenge in managing end-stage renal disease patients, significantly affecting morbidity and mortality. This comprehensive review synthesizes current knowledge on risk factors, surveillance methods, diagnostic approaches, treatment strategies, and preventive measures for these infections. Through systematic analysis of literature from major databases up to July 2024, we explore infection-related complications, pathogenic agents, and management strategies. Staphylococcus aureus emerges as a primary pathogen, with concerning increases in multidrug-resistant strains. The review emphasizes the superior safety profile of arteriovenous fistulas compared to central venous catheters, highlighting the importance of access type selection. Continuous monitoring and early detection through physical examinations and specialized tests are crucial. Diagnostic accuracy is optimized by combining clinical assessment with laboratory testing and imaging studies. Treatment strategies focus on empiric systemic antibiotic therapy, guided by local epidemiology and culture results, often necessitating catheter removal for persistent infections. Preventive measures, including strict adherence to aseptic techniques and targeted use of antimicrobial locks, are detailed. The study advocates for a multifaceted approach to infection management, emphasizing multidisciplinary collaboration and adherence to evidence-based guidelines. Promising future directions, such as novel antimicrobial surfaces and lock solutions, offer potential for further reducing infection risks. This review provides valuable insights for healthcare providers, aiming to improve long-term outcomes and quality of life for hemodialysis-dependent patients through enhanced infection control strategies.

Background: The initiation of hemodialysis exhibits winter-peak seasonal variations, possibly associated with increased cardiac events during winter. The season of cardiac disease onset affects prognosis; however, the relationship between the season of hemodialysis initiation and subsequent cardiac outcomes remains unclear. We aimed to evaluate this association to determine whether the season of hemodialysis initiation could influence subsequent cardiac events.

Methods: We used data from a Japanese multicenter prospective dialysis initiation cohort. We divided the patients into four groups based on the season of hemodialysis initiation: Spring, Summer, Autumn, and Winter. The outcome was 3-year cardiac events defined as a composite of ischemic heart disease, heart failure, and sudden death. Considering the competing risks, we compared the incidence of subsequent cardiac events with the hemodialysis initiation season.

Results: Among the 1396 eligible patients, hemodialysis was initiated in 402 (29%), 346 (25%), 270 (19%), and 378 (27%) patients in Spring, Summer, Autumn, and Winter, respectively. Total fluid removal, heart failure symptoms, and fluid overload during the first hemodialysis session were more frequent in Autumn and Winter. During the 3-year follow-up, 264 patients (19%) developed cardiac events. Autumn was associated with a higher risk of developing cardiac events than Summer. Compared with Summer, the adjusted subdistribution hazard ratios (95% confidence intervals) were 1.40 (0.97-2.02) in Spring, 1.50 (1.02-2.21) in Autumn, and 1.15 (0.80-1.67) in Winter.

Conclusion: Hemodialysis initiation in autumn may be a potential indicator of subsequent cardiac events. Further studies are required to elucidate the underlying pathophysiological mechanisms.

Background: Hepcidin-25 plays an important role in regulating iron metabolism; however, the association between hepcidin-25 levels and hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is controversial. We aimed to clarify the associations between serum hepcidin-25 levels and hyporesponsiveness to ESAs in Japanese patients receiving hemodialysis, and between hepcidin-25 levels and other factors.

Methods: This observational cross-sectional study included hemodialysis patients recruited at Heisei-Hidaka Clinic in Japan from August 2023 to June 2024. Serum hepcidin-25 levels were measured by latex immunoassay. Hyporesponsiveness to ESAs was determined by the ESA resistance index (ERI). The correlation between hepcidin-25 levels and ERI was evaluated using Pearson's correlation coefficient. We also investigated the patient characteristics associated with hepcidin-25 levels using multiple regression analysis.

Results: Hepcidin-25 levels were significantly negatively correlated with ERI (r = - 0.438, p = 0.0005). Hepcidin-25 levels also showed significant positive correlations with serum iron, transferrin saturation (TSAT), serum ferritin, and high sensitive C-reactive protein (hs-CRP), and significant negative correlations with hematocrit, unsaturated iron-binding capacity, total iron-binding capacity, and serum erythropoietin levels. Hepcidin-25 levels were significantly higher in the patients who received oral iron-containing preparations than in those without these preparations. Multiple regression analysis showed significant partial regression coefficients for ERI, hematocrit, TSAT, serum ferritin, hs-CRP, and the administration of oral iron-containing preparations.

Conclusion: Serum hepcidin-25 levels were significantly negatively correlated with the ERI. The results suggest that hepcidin-25 levels might be associated with ERI, hematocrit, TSAT, serum ferritin, hs-CRP, and the administration of oral iron-containing preparations.

Background: Cardiogenic shock (CS) after myocardial infarction remains associated with high mortality. Acute kidney injury (AKI), a common complication, substantially impacts outcomes. We investigated the prognostic relevance of AKI and renal replacement therapy (RRT) in CS.

Methods: In this retrospective study, 369 patients with infarct-related CS admitted to a tertiary center were analyzed. AKI was defined by KDIGO criteria. Clinical, laboratory, and hemodynamic data, including RRT use and in-hospital outcomes, were evaluated. Multivariable logistic regression identified independent predictors of AKI and RRT. Discriminatory power was assessed using AUC.

Results: AKI occurred in 42.8% of patients (n = 143), with 60.1% developing AKI within 48 h and 35.0% classified as stage 3. AKI patients were older (70.5 vs. 67.2 years; p = 0.010), had more pre-existing CKD (100 vs. 83.3%; p = 0.002), and required longer ventilation (168 vs. 65.5 h; p < 0.001). Inflammatory, renal, and perfusion markers were significantly elevated from day 2 onward. RRT was initiated in 8.9% overall and 23.1% of AKI patients, with 60.6% mortality. Predictors of AKI included age (OR 2.40; 95% CI 1.10-5.12) and norepinephrine dose (OR 1.001 per µg/kg; p = 0.042; AUC = 0.71). Predictors of RRT were admission creatinine (OR 2.05 per mg/dL; p = 0.003) and absence of CPR (OR 0.22; p = 0.008; AUC = 0.75). Overall mortality was 57.7%, higher in women (66.4% vs. 53.4%; p = 0.021).

Conclusions: AKI is common in infarct-related CS and linked to poor outcomes. Early identification of high-risk patients may enable timely renoprotective strategies.