BMC Nephrology最新文献

Background: Tuberous Sclerosis complex (TSC) is a multisystemic neurocutaneous genetic condition with high rates of morbidity and mortality from subependymal giant cell astrocytoma (SEGA), renal angiomyolipoma, and renal cyst complications. Everolimus is an inhibitor for mTORC1 and is currently used to treat TSC for its main role in rapidly reducing SEGA volume and seizure burden, although mainly studied in the adult population. It has also been shown to stabilize estimated glomerular filtration rate and reduce renal angiomyolipoma size in the adult population.

Case presentation: This case report illustrates three pediatric patients placed on everolimus for SEGA and seizure control with incidental findings of the disappearance of or decreased burden of cystic kidney disease after everolimus therapy. In one patient, the cyst burden remained stable even after the cessation of everolimus while the SEGA resumed growth.

Conclusions: This report demonstrates the utility of everolimus in not only renal angiomyolipomas but also cystic kidney disease particularly in pediatric patients with a promising role in preserving renal function and preventing long term sequelae such as hematuria and hemorrhage from larger renal cysts especially if used early on in disease course.

Background: Chronic kidney disease (CKD) is a significant public health concern associated with a high prevalence of carotid plaques, which are indicators of atherosclerosis and predictors of adverse cardiovascular outcomes. Inflammation is a hallmark of CKD, contributing to both renal dysfunction and cardiovascular complications. This study aims to investigate the association between inflammatory markers-systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), aggregate inflammatory status index (AISI), monocyte to high-density lipoprotein cholesterol ratio (MHR), neutrophil to high-density lipoprotein cholesterol ratio (NHR), neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR)-and carotid plaques in CKD patients, and to explore the potential mediating role of estimated glomerular filtration rate (eGFR) in this relationship.

Methods: A cross-sectional analysis was conducted on patients admitted to the Division of Nephrology between January 2023 and June 2023. The primary endpoint was the presence of carotid plaques assessed using ultrasound imaging. Multivariable logistic regression models were used to examine the associations between inflammatory markers and carotid plaques, and trend tests were performed to evaluate the trending association of carotid plaques risk and inflammatory markers in tertiles. Restricted cubic spline (RCS) analysis was used to assess potential non-linear relationships, and subgroup analyses were conducted to examine consistency across different strata. Mediation analysis was performed to explore the role of eGFR.

Results: Of the 609 participants, 387 were included in the final analysis after applying exclusion criteria. Elevated levels of LnSIRI (OR = 1.87, 95% CI = 1.25-2.80), LnSII (OR = 1.67, 95% CI = 1.09-2.56), LnAISI (OR = 1.70, 95% CI = 1.22-2.37), LnMHR (OR = 1.94, 95% CI = 1.15-3.26), LnNHR (OR = 1.82, 95% CI = 1.10-3.02), and LnMLR (OR = 2.26, 95% CI = 1.18-4.34) were significantly associated with the presence of carotid plaques. There were significant trends for increasing tertiles of SIRI, AISI, MHR and NHR. RCS analysis showed no significant non-linear associations. Subgroup analyses indicated similar associations across most strata. eGFR partially mediated these relationships, with proportions mediated ranging from 14.7 to 17.5%.

Conclusions: Inflammatory markers are significantly associated with carotid plaques in CKD patients, with eGFR playing a partial mediating role. These findings highlighted the importance of managing inflammation and maintaining renal function to mitigate the risk of atherosclerosis in CKD patients.

Trial registration: Not applicable.

Introduction: Previous randomized controlled trials (RCTs) and meta-analyses comparing Hemodiafiltration (HDF) with conventional hemodialysis (HD) on the effectiveness of HDF for mortality in end-stage renal disease (ESRD) patients have yielded contrasting results. Importantly, we sought to compile the available information to provide the most up-to-date and reliable evidence.

Methods: We systematically searched PubMed, Embase and Cochrane Library for RCTs up to January 14, 2024. Review Manager 5.3 software was used to analyze relevant data and evaluate the quality of evidence.

Results: Our study involved 10 randomized controlled trials with 4654 chronic dialysis patients. Compared to hemodialysis, hemodiafiltration demonstrated a reduction in all-cause mortality (relative risk [RR] 0.84, 95% confidence intervals [CI] 0.72-0.99, P = 0.04) and cardiovascular mortality (RR 0.74, 95% CI 0.61-0.90, P = 0.002). However, it did not reduce the rate of sudden death (RR 0.92, 95% CI 0.64-1.34, P = 0.68) and infection-related mortality (RR 0.70, 95% CI 0.47-1.03, P = 0.07). A subgroup analysis revealed that HDF demonstrated superiority over high-flux hemodialysis in terms of all-cause mortality, while not over low-flux hemodialysis (RR 0.81, 95% CI 0.69-0.96, P = 0.01; RR 0.93, 95% CI 0.77-1.12, P = 0.44, respectively). Furthermore, a subgroup analysis for convection volume found that hemodiafiltration with a convection volume of 22 L or more reduced all-cause and cardiovascular mortality (RR 0.76, 95% CI 0.65-0.88, P = 0.0002, RR 0.73, 95% CI 0.54-0.94, P = 0.01, respectively).

Conclusion: In maintenance hemodialysis patients, hemodiafiltration can reduce mortality compared to conventional hemodialysis. Furthermore, this effect is more pronounced in HDF with high convection volume.

Acute Kidney Injury (AKI) is frequently observed in hospitalized patients in intensive care units, often caused by renal ischemia-reperfusion injury (IRI). IRI disrupts the function of various 'remote organs' such as the lungs, pancreas, intestine, liver, heart, and brain through inflammation, oxidative stress, apoptosis, leukocyte infiltration, and increased urea and creatinine levels. Gender differences in renal IRI-induced injury are noted. H2S, an endogenous gaseous modulator, shows potential in vasodilation, bronchodilation, and hypotension and can regulate apoptosis, inflammation, angiogenesis, metabolism, and oxidative stress. This study aims to investigate the protective effects of NaHS on brain, heart, and lung injuries following renal IR and to assess the oxidative system status as a potential mechanism in male and female rats.Forty-eight Wistar rats were randomly divided into eight groups (n = 6): Control/Saline, Sham/Saline, IR/Saline, and IR/NaHS in both sexes. Forty-five minutes of bilateral renal ischemia followed by 24-hour reperfusion was induced in the IR groups. NaHS (100µM/Kg, IP) was administered 10 min before clamp release in treated groups. BUN, SCr, BUN/SCr, albuminuria, histopathology, and oxidative stress biomarkers of the brain, heart, and lung were assessed as remote organs. IR increased serum markers of renal function, albuminuria, malondialdehyde levels, and tissue injury scores while reducing nitrite levels and superoxide dismutase and glutathione peroxidase activities. NaHS treatment reversed the adverse effects of IR in remote organs in both sexes, although it showed limited improvement in renal function. Our findings demonstrate that NaHS has a beneficial effect on remote organ injury following renal IR by mitigating oxidative stress, with noted tissue-specific and gender-specific differences in response. These findings suggest NaHS as a potential therapeutic agent for mitigating multi-organ injury after renal IR, with effects varying by tissue and gender.

Background: Carotid intima-media thickness (cIMT) is a measure of atherosclerotic vascular disease and a surrogate biomarker for cardiovascular risk in patients with chronic kidney disease (CKD). Mineral and bone disorders (MBD) are complications of CKD, contributing to vascular calcification and accelerated atherosclerosis. Increased fibroblast growth factor 23 (FGF23)-the earliest detectable serum abnormality associated with CKD-MBD-has been linked with cardiovascular disease in patients with CKD. This study aimed to identify factors and analyze the relationship associated with high cIMT, high FGF23, and poor MBD control in children with CKD.

Methods: A cross-sectional study was conducted in Yogyakarta, Indonesia recruiting children with CKD. The correlations and factors between cIMT, FGF23, and MBD were explored.

Results: We recruited 42 children aged 2-18 years old with CKD stages 2 to 5D. There were no significant correlations between cIMT and factors including advanced CKD, use of dialysis, body mass index, hypertension, anemia, MBD, FGF23 levels, and left ventricular mass index (LVMI). Patients with advanced CKD had poorly controlled anemia, hypertension, and higher LVMI. In multivariate analysis, CKD stages, hypertension stages, the presence of MBD, and LVMI were associated with FGF23 levels (p < 0.05).

Conclusions: FGF23 levels increased with CKD progression, and MBD was more prevalent in advanced kidney disease. Elevated FGF23 is potentially associated with increased MBD prevalence in late-stage CKD. A larger study is needed to confirm the factors affecting cIMT in children with CKD.

Background: Chronic renal failure poses a significant global health challenge, exerting a substantial burden on both patients and their caregivers. Hemodialysis, a common treatment for end-stage renal disease, imposes extensive physical, emotional, and financial pressures on caregivers, often leading to a high care burden. This study uniquely examines the impact of peer support groups on reducing the care burden among caregivers of patients receiving hemodialysis in an Iranian healthcare setting, an aspect that has not been extensively explored before.

Methods: A parallel-controlled clinical trial was conducted involving 60 caregivers, divided into intervention and control groups. The intervention group participated in an 8-session peer support program tailored to their identified needs, including coping with stress, social isolation, and financial challenges. The Zarit Care Burden Interview Scale was used to measure care burden before and after the intervention.

Results: The study revealed statistically significant reductions in care burden, particularly in physical, social, and emotional dimensions, among caregivers in the intervention group compared to the control group. The total care burden score showed a marked decrease, indicating the effectiveness of the peer support intervention. While economic challenges remained a concern, the intervention had a limited impact in this domain.

Conclusion: This study demonstrates that peer support groups significantly alleviate the care burden experienced by caregivers of patients receiving hemodialysis, improving their well-being across several dimensions. The findings highlight the importance of integrating peer support strategies into healthcare programs for chronic disease management and underscore the need for supplementary economic support measures to comprehensively address caregivers' needs. Future research should explore the scalability and long-term sustainability of such interventions and address the unique economic challenges faced by these caregivers.

Trial registration: This study was registered in the Iranian Registry of Clinical Trials (IRCT) under the registration number IRCT20220724055540N1 on 11/08/2022.

Background: Pemetrexed is combined with cisplatin to treat cancer. Whether pemetrexed-cisplatin combination chemotherapy exacerbates cisplatin nephrotoxicity is unclear. Here, we investigated kidney injury in mice administered a non-lethal low-dose regimen of pemetrexed or cisplatin alone and compared it with a pemetrexed-cisplatin combination.

Methods: Mice were randomly divided into four groups and administered intraperitoneally the experimental drugs solubilized in captisol (sulfobutylether β-cyclodextrin). Group 1 received captisol, Group 2 pemetrexed (10 mg/kg), Group 3 cisplatin (1 mg/kg), and Group 4 pemetrexed (10 mg/kg) plus cisplatin (1 mg/kg). The mice were treated every other day for two weeks, three times per week. Glomerular filtration rate (GFR) was determined on the third day after the last treatment, followed by a necropsy.

Results: Whereas the relative kidney weight was comparable in the control vs. pemetrexed or cisplatin alone group, it was significantly increased in the combination group. Mice treated with cisplatin and pemetrexed-cisplatin combination exhibited reduced GFR. The pemetrexed-cisplatin combination caused significant increases in the plasma or urinary levels of kidney injury biomarkers, renal lipid peroxidation, and nitrosative stress compared with pemetrexed or cisplatin alone. Histopathology revealed that pemetrexed or cisplatin alone had minimal effects on the kidneys. By contrast, the pemetrexed-cisplatin combination caused tubular degeneration, dilatation, and granular casts. Live-cell imaging showed that the pemetrexed-cisplatin combination caused more severe apoptosis of primary renal epithelial cells than individual concentrations.

Conclusions: These findings suggest that combining pemetrexed and cisplatin causes oxidative kidney damage at individual doses that do not cause significant nephrotoxicity. Hence, the renal function of patients undergoing treatment with the pemetrexed-cisplatin combination needs extensive monitoring.

Background: Chronic Kidney Disease (CKD) is a progressive disorder that often leads to End-Stage Renal Disease (ESRD), necessitating hemodialysis (HD) treatment. Fatigue is a prevalent and debilitating symptom among HD patients, significantly affecting their quality of life. Recreational Therapy (RT) is a therapeutic recreational service designed to maintain and restore a person's level of performance and independence in daily activities. This study aimed to evaluate the effect of a smartphone-based recreational therapy intervention on fatigue in hemodialysis patients.

Methods: This randomized controlled trial was conducted on HD patients at a hospital in Mashhad, Iran. The intervention group received a custom-designed recreational therapy mobile application, including music, comedy, exercise, and educational content. The control group received standard care. Fatigue was assessed using the Multidimensional Fatigue Inventory (MFI-20) before and after the 30-day intervention.

Results: A total of 72 patients (36 per group) participated in the study. The intervention group demonstrated a significant reduction in overall fatigue scores and improvements across various fatigue dimensions, including general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation, compared to the control group (p < 0.001).

Conclusion: The smartphone-based recreational therapy intervention effectively reduced fatigue in hemodialysis patients. This approach could be a valuable complementary strategy for managing fatigue in this population. Further research is needed to explore the long-term sustainability of these benefits and the intervention's impact on other patient-reported outcomes.

Trial registration: This study was registered in the Iranian Registry of Clinical Trials (no. IRCT20220803055608N1) on 29/08/2022.

Background: Although peritoneal dialysis (PD) is an efficient therapy for renal replacement, the long-term survival rate of patients undergoing PD remains low. The platelet-to-albumin ratio (PAR), recently identified as a parameter of inflammatory and nutritional status, is associated with an adverse prognosis for various diseases. However, the association between the serum PAR and prognosis of patients undergoing PD is poorly understood. This study aimed to evaluate whether the PAR is a reliable predictor of cardiovascular disease (CVD) and all-cause mortality in patients undergoing PD.

Methods: This multicenter cohort study enrolled patients undergoing PD from January 1, 2009, to September 30, 2018. The patients were divided into four groups according to the quartiles of their baseline PAR. The primary endpoint was all-cause and CVD-related mortality. Cox proportional hazard models were used to determine the association between the PAR and all-cause or CVD-related mortality. The receiver operating characteristic (ROC) curve was utilized to compare the performance among PAR and other inflammatory indicators. C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were applied to examine the incremental prognostic value of PAR compared with baseline model for predicting all-cause and CVD mortality.

Results: A total of 2825 patients were included. During the follow-up period of 47.5 ± 28.3 months, 747 (26.4%) mortality cases were observed, of which 415 (55.6%) were CVD-related. Compared with the Q1 (PAR < 4.43), placement in Q4 (PAR > 7.27) was associated with an increased risk of all-cause mortality and CVD mortality (p < 0.001). The adjusted restricted cubic spline analysis indicated that the relationship of the PAR with all-cause and cardiovascular mortality was linear (p for nonlinearity = 0.289 and 0.422, respectively). No positive correlations were shown in the interaction tests. PAR exhibited superior predictive value for mortality compared to other inflammatory indicators, with a respective AUC value of 0.611 (P < 0.001) for all-cause mortality and 0.609 (P < 0.001) for cardiovascular mortality. According to the C-statistic, continuous NRI and IDI, the addition of PAR to the baseline model yielded a moderate but significant improvement in outcome prediction.

Conclusions: The PAR is an independent prognostic factor associated with all-cause and cardiovascular mortality in patients undergoing PD.

Background: Gastrointestinal bleeding (GIB) is a clinical challenge in kidney failure. INSPIRE group assessed if machine learning could determine a hemodialysis (HD) patient's 180-day GIB hospitalization risk.

Methods: An eXtreme Gradient Boosting (XGBoost) and logistic regression model were developed using an HD dataset in United States (2017-2020). Patient data was randomly split (50% training, 30% validation, and 20% testing). HD treatments ≤ 180 days before GIB hospitalization were classified as positive observations; others were negative. Models considered 1,303 exposures/covariates. Performance was measured using unseen testing data.

Results: Incidence of 180-day GIB hospitalization was 1.18% in HD population (n = 451,579), and 1.12% in testing dataset (n = 38,853). XGBoost showed area under the receiver operating curve (AUROC) = 0.74 (95% confidence interval (CI) 0.72, 0.76) versus logistic regression showed AUROC = 0.68 (95% CI 0.66, 0.71). Sensitivity and specificity were 65.3% (60.9, 69.7) and 68.0% (67.6, 68.5) for XGBoost versus 68.9% (64.7, 73.0) and 57.0% (56.5, 57.5) for logistic regression, respectively. Associations in exposures were consistent for many factors. Both models showed GIB hospitalization risk was associated with older age, disturbances in anemia/iron indices, recent all-cause hospitalizations, and bone mineral metabolism markers. XGBoost showed high importance on outcome prediction for serum 25 hydroxy (25OH) vitamin D levels, while logistic regression showed high importance for parathyroid hormone (PTH) levels.

Conclusions: Machine learning can be considered for early detection of GIB event risk in HD. XGBoost outperforms logistic regression, yet both appear suitable. External and prospective validation of these models is needed. Association between bone mineral metabolism markers and GIB events was unexpected and warrants investigation.

Trial registration: This retrospective analysis of real-world data was not a prospective clinical trial and registration is not applicable.