Clinical and Experimental Nephrology最新文献

Background: Renal fibrosis is key histopathological lesion in chronic kidney disease progression. This study explored pyroptosis-related gene signatures, potential molecular pathways and chemicals, as well as immune infiltration in renal fibrosis.

Methods: Renal fibrosis datasets and pyroptosis-related genes were obtained and differentially expressed pyroptosis-related genes (DEPGs) were identified. Then functional enrichment analysis was performed and core DEPGs were screened by WGCNA and LASSO regression analysis. Subsequently, miRNA-core DEPG interactions and potential chemicals were established. Finally, immune cell subtype distribution was evaluated and the core DEPGs were externally validated.

Results: A total of 38 DEPGs were identified which were enriched in inflammatory- and immune-related pathways. Nine core DEPGs were identified and the risk core = (0.1003 × Bak1) + (0.0944 × Zbp1) + (0.0882 × Tlr2) + (0.0585 × Il18) + (0.0497 × Adora2b) + (0.0418 × Stat3) + (0.0325 × Icam1) + (0.0272 × Pycard) + (0.0132 × Epha2). Nine core DEPGs exhibited high sensitivity and specificity for predicting UUO occurrence. A total of 444 miRNA-core DEPG interactions were obtained and miR-124-3p, miR-92a-3p, and miR-6807-5p were identified as core miRNAs. Adenosine served as a potential chemical that directly bound to Adora2b. Immune cells, including naïve B cells, CD4⁺ effector memory T cells, (plasmacytoid) dendritic cells, monocytes, and neutrophils were significantly enriched in fibrotic kidneys. Finally, the differential expression, temporal expression patterns, and clinical correlation with renal function of core DEPGs were externally validated.

Conclusions: This study sheds light on the novel pyroptosis-related gene signatures in renal fibrosis.

Background: The study aims to investigate the impact of immunosuppressive therapy on clinical outcomes in patients with baseline negative PLA2R antibody, providing new therapeutic insights for this patient population.

Methods: This study included 133 patients with positive histological PLA2R antigen and baseline serum anti-PLA2R antibody data. ELISA (enzyme-linked immunosorbent assay) was used to measure serum anti-PLA2R antibody levels. Renal biopsy specimens were analyzed by light microscopy, immunofluorescence, and electron microscopy.

Results: Among the 133 patients, 84 (63.2%) were positive for serum antibodies (SAb +) and glomerular antigen (GAg +), while 49 (36.8%) were negative for serum antibodies (SAb-) but positive for glomerular antigen (GAg +). Compared with the Sab-/GAg + group, the SAb + /GAg + group exhibited more severe clinical features compared to the SAb-/GAg + group; however, there was no significant difference in the pathological characteristics between the two groups of patients. The complete remission (CR) rate was significantly higher in the SAb-/GAg + group (67.35% vs. 33.33%, P < 0.001), with higher CR rates at 12, 24, and 36 months. The SAb-/GAg + group also had a lower relapse rate than Sab + /GAg + (12.24% vs. 36.90%, P = 0.002). In the SAb-/GAg + group, 67.3% received conservative treatment, while 32.7% underwent immunotherapy. Patients receiving immunosuppressive therapy in the SAb-/GAg + group exhibited more severe proteinuria, more impaired renal function, and higher hyperlipidemia at baseline. Compared with conservative treatment, immunotherapy improved overall remission rates (100.00% vs. 75.76%, P = 0.041) in the SAb-/GAg + group. Cox regression analysis showed that immunotherapy significantly predicted urinary protein remission (HR 3.92, 95% CI 1.58-9.70, P = 0.003).

Conclusion: Immunosuppressive therapy in PLA2R-related membranous nephropathy patients with severe baseline clinical manifestations may help predict urine protein remission, even if they are serum anti-PLA2R antibody negative.

Background: This study aims to investigate the bidirectional causal relationship between chronic kidney disease (CKD) and sarcopenia using two-sample Mendelian randomization (MR) analysis.

Methods: A bidirectional MR analysis was performed using genetic data for CKD from the MEGASTROKE consortium and sarcopenia traits from the UK Biobank. SNPs associated with CKD and sarcopenia were used as instrumental variables. MR analysis was conducted with inverse variance weighting (IVW), weighted median, and MR-Egger methods. Sensitivity analyses included Cochran's Q test, MR-Egger intercept, and the leave-one-out method. Enrichment analysis was performed using GO and KEGG pathways.

Results: The results indicate a positive association between CKD and both left-hand grip strength (OR = 1.03, 95% CI 1.01-1.04, P < 0.001) and right-hand grip strength (OR = 1.03, 95% CI 1.02-1.04, P < 0.001) for both sides. In addition, appendicular lean mass (ALM) was found to be positively associated with an increased risk of CKD (OR = 1.35, 95% CI 1.19-1.53, P < 0.001). However, no significant causal relationships were observed between CKD and ALM or usual walking pace. Enrichment analysis identified several relevant biological processes and pathways, such as DNA transcription regulation, protein degradation, and immune response pathways, that may mediate the relationship between CKD and sarcopenia.

Conclusions: This study provides evidence for a bidirectional causal relationship between CKD and sarcopenia, with CKD contributing to decreased hand grip strength and ALM being associated with an increased risk of CKD.

Background: Acute hyperglycaemia is often accompanied by acid-base and electrolyte disorders as well as changes in serum osmolality which have a significant clinical impact. This study explores the prevalence of complex acid-base disorders in patients with hyperglycaemia, focusing on the limitations of current diagnostic criteria which primarily rely on pH, serum bicarbonate and anion gap.

Methods: A retrospective analysis of 1159 episodes of severe hyperglycaemia was performed. Arterial blood gas analysis, serum osmolality and electrolyte levels were measured at admission to hospital and patient's outcome was observed until day seven. Patients were evaluated for acid-base and electrolyte disorders as well as for changes in measured or calculated serum osmolality.

Results: Our findings reveal that 90.7% of patients exhibited some form of acid-base disorder, mixed acid-base disorders were the most prevalent (75%). Patients with an accompanying respiratory acidosis showed higher mortality rates (12%) than patients with respiratory alkalosis (6%, p = 0.006) or no respiratory disorder (5%, p = 0.003). An elevated serum osmolality was associated with higher mortality when using the calculated, effective osmolality (19% vs 4%, p < 0.001) as well as the measured osmolality (10% vs 4%, p = 0.001). Only 20% of our population had no electrolyte disorder. This group had a significantly lower mortality rate (2%) compared to patients with elevated or decreased sodium, potassium and phosphate levels.

Conclusion: Patients with severe hyperglycaemia often had complex acid-base and electrolyte disorders but current criteria for diagnosing diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) ignore combined disorders of acid-base homeostasis, potentially influencing patient management and outcomes.

Background: Cancer is one of the most common complications after kidney transplantation and an important cause of mortality. However, no large, nationally representative study has investigated cancer incidence post-kidney transplantation. This study aimed to determine the standardized incidence ratio (SIR) for cancer after kidney transplantation using the National Database of Health Insurance Claims (NDB).

Methods: We used NDB from April 2013 to March 2022; patients were included if they had been on dialysis for at least one year, were diagnosed with cancer related to post-kidney transplantation, and were prescribed immunosuppressant drugs in FY2014 or FY2015. We defined patients with cancer as those who were coded as ICD-10 for cancer in FY2016 or later. The number of patients and SIRs were tabulated according to the duration after kidney transplantation and cancer type.

Results: The total number of patients was 4484 (males: 2879; females: 1605). The SIRs of all cancers from the first to the seventh year after kidney transplantation were 232/291/235/248/257/187/149, respectively, showing a gradual downward trend over time. The predilection sites of cancer in both men and women were post-transplant lymphoproliferative disease, Kaposi sarcoma, and the kidney.

Conclusion: This observational study, which followed over 100 million people, is the first large-scale research to track kidney transplant recipients for under 10 years. It incorporates an unprecedented sample size and uniquely identified short-term cancer risk trends following kidney transplantation.

Background: Hyperparathyroidism (HPT) is a potential risk factor for graft loss after kidney transplantation (KTx). However, the effects of HPT management on graft outcomes remain unclear. This retrospective study aimed to investigate the impact of HPT status and its management on graft outcomes.

Methods: Patients who underwent KTx were categorized based on their HPT status and treatment at 1-year post-KTx into four groups: normal (no HPT), normocalcemic HPT, hypercalcemic HPT, or intervention (parathyroidectomy or calcimimetics within 1 year after KTx). Patients treated for HPT beyond the first year post-KTx were censored. The primary outcome was death-censored graft survival and the secondary outcome was the progression of interstitial fibrosis and tubular atrophy (IFTA) at 1-year post KTx.

Results: Among 1264 patients, the 10-year death-censored graft-survival rate was lowest in the hypercalcemic HPT group (79.7%), whereas the intervention group had a survival rate of 100.0%. In the multivariate Cox regression analysis, hypercalcemic HPT was associated with an increased risk of graft loss (fully adjusted hazard ratio [HR] = 4.25, P = 0.001, compared to the normal group). Contrarily, the intervention group did not show an increased risk of graft loss (fully adjusted HR = 0.28, P = 0.239). Additionally, hypercalcemia during the first year after KTx was significantly associated with IFTA progression (fully adjusted odds ratio = 1.91, P = 0.038).

Conclusion: Hypercalcemic HPT was associated with inferior graft survival and IFTA progression. Proactive management of HPT may reduce the risk of graft loss and mitigate IFTA progression.

Background: The stepwise initiation of peritoneal dialysis (PD) using Moncrief and Popovich's technique (SMAP) is widely used for systemic PD introduction and catheter-related infection prevention. This study aimed to investigate patients who would benefit from SMAP in terms of mortality and PD-related peritonitis development.

Methods: In total, 328 consecutive patients underwent PD catheter implantation at our institute. Inverse probability of treatment weights was calculated, and patients who benefited from SMAP were explored retrospectively.

Results: Overall, 285 patients were analyzed (direct group, n = 96; SMAP group, n = 189). Patients in the SMAP group tended to have a lower mortality risk than those in the direct group, whereas this tendency decreased in the IPW-adjusted population. Peritonitis was observed in 40 and 85 patients in the direct and SMAP groups, and PD catheters were removed in 59 and 118 patients in the direct and SMAP groups. The two main causes were peritonitis and insufficient dialysis. The risk of mortality decreased with SMAP among patients with a nutrition risk index score for Japanese hemodialysis patients ≥ 8, prognostic nutritional index score ≤ 40, serum creatinine level < 8 mg/dl, and body mass index < 23 kg/m². Additionally, the risk of peritonitis decreased in patients with emergent hemodialysis induction before PD and with previous abdominal surgery.

Conclusion: PD catheter implantation using SMAP may not be mandatory in clinical practice. However, this technique can be a good option, depending on the patient, in terms of mortality and peritonitis. Personalized treatment strategies should be considered to improve patient outcomes.

Background: Hypertension is a major risk factor for the progression of chronic kidney disease (CKD). However, the impact of blood pressure (BP) load, especially when office BP is normal, remains unclear. Thus, we conducted a retrospective cohort study to elucidate the impact of elevated BP load in patients with biopsy-proven CKD, BP load elevation, and a normal office BP compared with normotensive patients with CKD but without BP load elevation and those with hypertension.

Methods: We retrospectively analyzed patients with histologically confirmed atherosclerotic CKD who underwent kidney biopsy and 24-h ambulatory BP monitoring (ABPM). Patients were classified into normotension, isolated BP load elevation, and hypertension groups. The primary outcome was a ≥ 30% sustained decline in estimated glomerular filtration rate (eGFR) within 3 years.

Results: A total of 57 patients were analyzed. The isolated BP load elevation and hypertension groups showed a significantly higher incidence of adverse kidney events than the normotension group (p < 0.01). After adjusting for confounding factors (age, sex, urinary protein, and Mayo Clinic Chronicity Score), the hazard for kidney outcomes remained significant in the isolated BP load elevation group (hazard ratio, 9.25; 95% confidence interval, 1.29-66.30).

Conclusions: Isolated BP load elevation is a significant risk factor for CKD progression even in patients with normal office BP. Normalization of BP load may be a potential therapeutic target in patients with CKD. Comprehensive BP assessment using 24-h ABPM is crucial for CKD management, as it reveals clinically important abnormalities that conventional measurements may not capture.

Background: The association between blood pressure (BP) and adverse outcomes in peritoneal dialysis (PD) remains uncertain. This study aims to address this knowledge gap.

Materials and methods: We systematically searched five databases (1964-2025) for observational studies assessing associations between BP and mortality or cardiovascular (CV) outcomes in adults on PD. Risk of bias was evaluated using the Newcastle-Ottawa Scale and ROBINS-I. Meta-analyses were performed using random- or fixed-effects models, and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for continuous and categorical BP exposures.

Results: Twenty-four studies comprising 28,016 patients (55% males; hypertension prevalence ranging from 39 to 95%) were included. Higher pulse pressure (PP) was consistently associated with increased all-cause (HR per 10 mmHg: 1.20; 95%CI 1.02-1.40) and CV (HR per 10 mmHg: 1.35; 95%CI 1.16-1.58) mortality. For systolic BP (SBP), no significant association was found when analyzed as a continuous variable. However, predefined thresholds revealed that all-cause mortality was significantly associated with SBP < 120 mmHg (HR: 1.55; 95%CI 1.15-2.11) and with SBP > 140 mmHg (HR: 1.18; 95%CI 1.07-1.31). Diastolic BP was not significantly associated with mortality. Additional studies linked higher BP to left ventricular hypertrophy and non-fatal CV events.

Conclusion: In PD patients, SBP < 120 mmHg and > 140 mmHg are associated with increased all-cause mortality, while elevated PP robustly predicts all-cause and CV mortality. These findings identify SBP and PP as key prognostic markers and potential targets in PD management.

Background: Accurate liver volume measurement is crucial for evaluating liver cyst severity and treatment efficacy in polycystic liver disease (PLD). Previous methods are impractical because they are time-consuming and labor-intensive. This study developed and validated two simplified CT imaging methods: the Bi-axial Simplified Measurement Method (BASiM) and the Quadri-dimensional Simplified Measurement Method (QDSiM).

Methods: This retrospective study analyzed 76 CT images from 26 PLD patients who underwent transarterial hepatic artery embolization (TAE). Images were obtained before TAE, 24 weeks after TAE and during the follow-up period. Liver volumes were measured using semi-automatic volumetry, BASiM, and QDSiM. BASiM calculates liver volume based on cranio-caudal, anterior-posterior, and medial-lateral dimensions, while QDSiM divides the liver into left- and right-side sections. This study assessed inter-assessor reliability, measurement accuracy, volume change rate, and calculation times.

Results: BASiM demonstrated strong inter-assessor reliability (intraclass correlation coefficient [ICC]: 0.991, 95% confidence interval [CI] 0.986-0.994) superior to QDSiM (ICC: 0.851, 95% CI 0.205-0.949). Calibrated liver volumes using BASiM and QDSiM were consistent with semi-automatic volumetry (ICC: 0.924, 95% CI 0.858 to 0.957, and ICC: 0.934, 95% CI 0.806-0.970, respectively). BASiM showed better alignment with volume changes (ICC: 0.835, 95% CI 0.537-0.927) compared to QDSiM (ICC: 0.607, 95% CI 0.203-0.800) and required less measurement time (61 ± 4 s vs. 107 ± 9 s, p < 0.01).

Conclusion: BASiM provided superior reliability, accuracy, and efficiency for liver volume measurement in PLD, thus useful for the clinical management of PLD.