BMC Nephrology最新文献

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.

Background: Onconephrology is a growing discipline that aims to improve the management of patients with cancer and kidney disease. If kidney histology is an essential key, the anatomopathological data remain weak although essential to this complex management.

Methods: Patients with active cancer who had a kidney biopsy (KB) between 2014 and 2020 were included, and their clinicobiological and histological data were analyzed retrospectively.

Results: Our cohort consisted of 154 patients (83 women) with a mean age of 58 years. One hundred twelve patients presented with proteinuria, 95 with acute kidney injury, and 59 with arterial hypertension. Histologically, interstitial fibrosis was found in 74% of KBs, tubular atrophy in 55.1%, arteriolar hyalinosis in 58.4%, and fibrous endarteritis in 54.4%. Regarding the main acute lesions, thrombotic microangiopathy (TMA) was found in 29.9% of biopsies, acute tubular necrosis (ATN) in 51.3%, and acute interstitial nephritis in 24.8%. The etiological diagnosis most often made was the nephrotoxicity of anticancer drugs (87 patients), followed by a pre-renal (15 patients) and kidney disease unrelated to cancer (13 patients). Sixty-seven patients presented with at least 2 associated diagnoses reflecting the complexity of kidney damage in cancer. Different clusters were found, highlighting that immunotherapy and anti-VEGF were the most commonly involved drugs.

Conclusions: During onconephrology practice, kidney toxicity of treatments is the most common etiology. Several mechanisms can be involved, underscoring the importance of kidney biopsy and the complexity of its management. Chronic histological lesions were very common.

Background: BK-polyomavirus (BKpyV) nephropathy (BKVN) is associated with end-stage kidney disease in kidney and non-kidney solid organ transplantation, with no curative treatment.

Case presentation: A 45-year-old woman with a past medical history of double lung transplantation subsequently developed end-stage kidney disease, of undetermined origin. One month after receiving a kidney transplant, a diagnosis of early BKVN was suspected, and in retrospect was a reasonable cause for the loss of her native kidneys. Minimisation of immunosuppression, achieved through extracorporeal photopheresis, allowed clearance of BKpyV and so prevented nephropathy. Both lung and kidney grafts had a satisfactory and stable function after one year of follow-up, with no rejection.

Conclusions: Extracorporeal photopheresis may have facilitated minimisation of immunosuppression and BKpyV clearance without lung allograft rejection.

Background: In chronic kidney disease (CKD), the durability of patient adherence to fluid and dietary restrictions may depend on the degree to which they have hope that they will enjoy life. Previous cross-sectional studies have shown that higher hope was associated with lower distress from fluid and dietary restrictions and better adherence in the short term. In this study, we aimed to examine the long-term relationship of hope with distress from fluid and dietary restrictions.

Methods: This prospective observational cohort study included 444 patients with CKD undergoing dialysis in one of five Japanese nephrology centers. Hope as a predictor was measured using an 18-item health-related hope scale. Outcomes were two-item measures of distress from fluid and dietary intake restrictions using the Japanese version of the Kidney Disease Quality of Life Short Form, Version 1.3 (higher scores indicate lower levels of distress). Multivariate linear mixed models were used to estimate the association of baseline health-related hope with distress from fluid and dietary restrictions at baseline and follow-up.

Results: The mean age of the participants was 67 years, and 31.1% of them were females. In total, 124, 98, and 222 had non-dialysis CKD, peritoneal dialysis, and hemodialysis, respectively. Higher levels of baseline health-related hope were associated with lower levels of distress from fluid restriction after one year (per 10-point increase, 2.6 points (95% confidence interval, 1.0 to 4.1)); whereas the baseline score was not associated with the distress from fluid restriction at 2 years. Similarly, higher levels of baseline health-related hope were associated with lower levels of distress from dietary restriction after one year (per 10-point increase, 2.0 points (95% confidence interval, 0.3 to 3.6)); whereas the baseline score was not associated with the distress from dietary restriction at 2 years.

Conclusions: Health-related hope, regardless of depression, can potentially mitigate long-term distress from fluid and dietary restrictions in patients with a wide range of CKD severities.

Trial registration: UMIN000054710.

Background: Chronic Kidney Disease (CKD) impacts over 10% of the global population, and recent advancements in high-throughput analytical technologies are uncovering the complex physiology underlying this condition. By integrating Genome-Wide Association Studies (GWAS), RNA sequencing (RNA-seq/RNA array), and single-cell RNA sequencing (scRNA-seq) data, our study aimed to explore the genes and cell types relevant to CKD traits.

Methods: GWAS summary data for end-stage renal failure (ESRD) and decreased eGFR (CKD) with or without diabetes and (micro)proteinuria were obtained from the GWAS Catalog and the UK Biobank (UKB) database. Two gene Expression Omnibus (GEO) transcriptome datasets were used to establish glomerular and tubular gene expression differences between CKD patients and healthy individuals. Two scRNA-seq datasets were utilized to obtain the expression of key genes at the single-cell level. The expression profile, differentially expressed genes (DEGs), gene-gene interaction, and pathway enrichment were analysed for these CKD risk genes.

Results: A total of 779 distinct SNPs were identified from GWAS across different CKD traits, involving 681 genes. While many of these risk genes are specific to the CKD traits of renal failure, decreased eGFR, and (micro)proteinuria, they share common pathways, including extracellular matrix (ECM). ECM modeling was enriched in upregulated glomerular and tubular DEGs from CKD kidneys compared to healthy controls, with the expression of relevant collagen genes, such as COL1A2, prevalent in fibroblasts/myofibroblasts. Additionally, immune responses, including T cell differentiation, were dysregulated in CKD kidneys. The late podocyte signature gene THSD7A was enriched in podocytes but downregulated in CKD. We also highlighted that the regulated risk genes of CKD are mainly expressed in tubular cells and immune cells in the kidney.

Conclusions: Our integrated analysis highlight the genes, pathways, and relevant cell types associational with the pathogenesis of kidney traits, as a basis for further mechanistic studies to understand the pathogenesis of CKD.

Background: Altitude influences bicarbonate levels, it is a variable that is hardly considered in diagnosing Renal Tubular Acidosis (RTA), so it should be a factor to consider when diagnosing this pathology, especially at 2250 mts over the sea level as it is the case of Mexico City. RTA is most often misdiagnosed. Regarding of this, the present study established reference limits for bicarbonate levels in healthy children without pathologies associated with alterations in the acid-base balance in Mexico City and it´s metropolitan area.

Methods: A total of 267 healthy pediatric patients were included, within normal estimated glomerular filtration rate (eGFR), and without any associated pathology of any alteration in the acid-base balance.

Results: Compared to older children, children younger than two years of age showed statistically higher levels of calcemia and cystatin C. On the other hand, this same group showed lower values of creatininemia, pCO₂, and HCO₃^-. Percentile 50 of bicarbonate in children under two years of age were 19.9 mEq/L and 21.9 mEq/L in those over that age. A correlation was identified between HCO₃^- levels and pCO₂ (r = 0.68; p < 0.001).

Conclusions: In the study population, an effect of altitude on blood levels of pCO₂ and HCO3- was observed.

Objectives: To explore the influencing factors and relationships associated with decisional conflict of dialysis modality in End-stage kidney disease (ESKD) patients.

Methods: This study was a survey-based cross-sectional investigation conducted on 150 ESKD patients in a third-class hospital in Wuhan. The general information questionnaire, decisional conflict scale, Montreal cognitive assessment, frail scale, perceived social support scale, and brief health literacy screen were used for investigation. SPSS 25.0 was used to compare the differences between the decisional and non-decisional conflict groups, and AMOS 23.0 was used to construct a structural equation model to explore the influencing factors.

Results: The incidence of decisional conflict in 150 ESKD patients was 33.3% (50/150). Binary logistic regression analysis showed that the independent risk factors for decisional conflict of dialysis modality in ESKD patients included monthly household income (OR = 0.184), cognitive function (OR = 7.0), social support (OR = 0.891), health literacy (OR = 0.608), the level of eGFR (OR = 1.488), and the level of cTnI (OR = 9.558). The constructed path analysis model had a good fit (x2/df = 1.499, GFI = 0.957, AGFI = 0.911, NFI = 0.906, CFI = 0.967, RMSEA = 0.055). The path analysis showed that health literacy (0.577) had the greatest impact on the decisional conflict, with a direct effect of 0.480 and an indirect effect of 0.097 through cognitive function and monthly household income. Next was social support, with an effect value of 0.434.

Conclusions: In clinical practice, it is important to enhance the health literacy of patients and their families and to provide advanced education on dialysis plans. Additionally, in managing and planning chronic kidney disease progression and dialysis, it is recommended to regularly and systematically assess cognitive function, particularly before the patient's cognitive impairment worsens or the severity of the disease progresses. Advanced care planning can be established through collaboration between healthcare professionals and patients to ensure appropriate decision-making and management.

Implications for the profession and patient care: This paper finds that the factors that influence and relate to dialysis methods in end-stage renal disease patients help nurses exercise autonomy better, assist patients in reducing their decisional conflict, and improve clinical outcomes.

Patient or public contribution: Patients received a relevant questionnaire survey, and caregivers assisted in conducting the study.