BMC Nephrology

Gautam, Samir C.; Awad, Alaa S.; Niyyar, Vandana Dua; Flythe, Jennifer E.; Abdel-Rahman, Emaad M.; Raimann, Jochen G.; Woldemichael, Jobira A.; Sheikh, Hiba I.; Gaurav, Raman; Kotanko, Peter; Yang, Xiwei; Gencerliler, Nihan; Divers, Jasmin; Murea, Mariana

doi: 10.1186/s12882-025-04659-2pmid: 41366335

BackgroundPragmatic randomized controlled trials (RCTs) must be embedded within routine clinical workflows, which require monitoring strategies that are feasible in everyday practice. Incremental hemodialysis—initiating treatment twice weekly in patients with preserved residual kidney function and escalating frequency as needed—differs from conventional thrice-weekly initiation. Implementing this approach in a pragmatic trial among providers and dialysis staff unfamiliar with incremental dialysis necessitated additional preparation and oversight. The TwoPlus trial is a multicenter pragmatic RCT evaluating incremental versus conventional initiation of chronic hemodialysis. We describe the patient monitoring framework developed for TwoPlus, which integrates digital infrastructure, human touchpoints, and provider engagement to ensure participant safety.Methods/DesignTwoPlus is an ongoing multicenter RCT enrolling adults initiating chronic hemodialysis with residual kidney function (urine urea clearance ≥ 2.0 mL/min and urine output ≥ 500 mL/24 hours). Participants are randomized to incremental hemodialysis—twice-weekly treatment supported by diuretics and sodium bicarbonate, with transition to thrice-weekly as clinically indicated—or conventional thrice-weekly initiation. The primary outcome is a composite of all-cause death, hospitalization, or emergency department visits. Secondary outcomes include preservation of residual kidney function and treatment adherence. The monitoring framework combines automated dialysis data downloads, manual data abstraction, assessments conducted by investigators or clinical research coordinators and reviewed at the site level, structured team reviews, and regular communication with treating providers.DiscussionThis layered monitoring model balances feasibility, safety, and fidelity in a pragmatic trial where provider engagement and site-specific adaptation were essential. The monitoring approach adopted in TwoPlus will inform the design of monitoring frameworks for future pragmatic nephrology trials.Trial registrationNCT05828823.

Tran, Dung N. T.; Dimitrov, Yves; Chantrel, Francois; Perrin, Peggy; Tubail, Zead; Fouque, Denis; Ducher, Michel; Fauvel, Jean-Pierre

doi: 10.1186/s12882-025-04715-xpmid: 41449356

BackgroundA few models have been developed in recent years to predict all-cause mortality in patients with chronic kidney disease (CKD). However, many have been developed using inappropriate methods and have not been externally validated. This study aims to improve our previously validated tool for predicting 2-year all-cause mortality in stage 4–5 CKD patients by enlarging the training dataset, thereby enhancing its robustness, which is further supported by a second external validation.MethodThe Bayesian network-based 2-year all-cause mortality prediction tool was trained on a comprehensive national dataset, which was further enriched by incorporating data from a previous external validation. Internal performance was assessed using 10-fold cross-validation, while external validity was confirmed through a second validation on the CERRENE cohort. The discriminatory ability of the prediction tool was evaluated both internally and externally using accuracy, c-statistic, sensitivity, and specificity. The calibration of the external validation was visualized with a calibration curve.ResultsThe prediction tool was developed using a training dataset of 1,061 patients (median age 72.3 years; 2-year mortality rate 21.2%) and externally validated using data from 409 patients (median age 77.5 years; 2-year mortality rate 17.6%) with CKD stage 4 or 5. The tool demonstrated satisfactory performance in both internal and external validation (accuracy: 77.2% and 77.8%; AUC-ROC: 0.76 and 0.74; sensitivity: 47.1% and 54.2%; specificity: 85.3% and 82.3%, respectively). The calibration curve demonstrated acceptable agreement between predicted and observed outcomes, and Brier score = 0.132.ConclusionThe updated prediction tool demonstrated satisfactory performance in both internal and external validation processes. Before it can be used in clinical practice, it must undergo national and international external validations, which are currently in progress.Graphical abstract[graphic not available: see fulltext]

Jongejan, Micha; van Oosten, Manon J. M.; Leegte, Martijn J. H.; Numans, Mattijs E.; de Wit, G. Ardine; van Buren, Marjolijn; Abrahams, Alferso C.; Bos, Willem Jan W.; Voorend, Carlijn G. N.

doi: 10.1186/s12882-025-04605-2pmid: 41372807

BackgroundPatients on kidney replacement therapy (KRT) face high symptom and treatment burden, especially at end of life. Yet insights into end-of-life healthcare utilisation and costs remain limited. We aimed to describe healthcare utilisation and costs during the last year of life across KRT modalities.MethodsWe used Dutch health insurance claims data to identify incident and prevalent patients aged ≥ 65 years, treated with KRT during the year preceding death, and who deceased between June 2016 and December 2021. Healthcare utilisation and costs in the last year of life were analysed for different KRT modalities and compared with controls without kidney disease-related claims, with controls being matched on sex, age, socio-economic status, and year of death.ResultsWe identified 7279 patients on KRT (4614 haemodialysis [HD] patients, 766 peritoneal dialysis [PD] patients and 1899 kidney transplant [KTx] recipients) and 14,558 controls. During their last year of life, 85% of patients on KRT experienced ≥ 1 hospital admission, with 27% requiring intensive care - representing to 2.6- and 3.5-fold higher proportions than in their controls, with minimal variation across KRT modalities. Similar differences were observed for emergency department visits, outpatient visits, and long-term care use. Healthcare utilisation significantly increased in the last three months preceding death, more markedly among patients on KRT than controls (p < 0.001). Average healthcare costs were 5.9, 5.5 and 3.0 times higher for patients on HD (€117,520), PD (€108.294), and KTx recipients (€59,489), respectively, compared to controls (€19,820). KRT-unrelated costs, encompassing 40% to 74% of total costs, were 2.2 to 2.6 times higher in patients on KRT compared to controls, with specialist hospital care costs being three times higher.ConclusionIn the last year of life, healthcare utilisation is higher for patients on KRT compared to controls, with a further increase towards end-of-life, along with higher KRT-unrelated costs.

Oweidat, Khaled; Field, Benjamin C. T.; Farmer, Christopher K.

doi: 10.1186/s12882-025-04691-2pmid: 41413776

Continuous glucose monitoring (CGM) has transformed diabetes management, offering real-time and dynamic insights into glucose variability and addressing the limitations of traditional glucose assessment methods. Kidney transplantation, the most common solid organ transplant, carries a considerable burden of post-transplant diabetes mellitus (PTDM), which is linked to increased cardiovascular events, graft dysfunction, and increased mortality. This review explores the role of CGM in kidney transplant recipients, particularly its impact on glycemic profiles and its predictive value for post-transplant diabetes mellitus (PTDM). At the time of this review, CGM had not yet been incorporated into standard transplant care protocols. Evidence shows that perioperative CGM outperforms traditional tests in identifying frequent hyperglycemia and glycemic variability in the first weeks after transplantation, enabling enhanced glycemic control and improving the recipient’s clinical outcome. Studies demonstrate higher glucose variability in kidney only recipients compared to other organ recipients, and in type 2 diabetes patients compared to those with PTDM. Poor perioperative glycemic control and glycemic variability detected by CGM have been linked to acute rejection and reduced graft survival. CGM-derived metrics outperform conventional glucose measures in predicting PTDM. CGM metric thresholds within the first month post-transplant achieved sensitivities above 85% and specificities up to 83% for PTDM risk. CGM-guided adjustment of immunosuppressants and steroid dosing have been shown to reduce hyperglycemia and variability. Comparative studies indicate that glycosylated hemoglobin A1c correlates poorly with CGM in the early post-transplant period, often misclassifying patients as normoglycemic. CGM appears to offer clinically relevant insights for the early detection, prediction, and management of dysglycemia in kidney transplant recipients.

Lin, Shuai; Liu, Ruxin; Huang, Wenrui; Liu, Li; Zhang, Bing; Xu, Juan; Li, Yanlin

doi: 10.1186/s12882-025-04645-8pmid: 41366750

Cardiovascular–kidney–metabolic (CKM) syndrome is a recently defined multisystem disorder integrating metabolic, renal, and cardiovascular dysfunction. CKM syndrome stage 2 represents an early, potentially reversible phase that offers a critical window for intervention. This meta-analysis evaluated the effects of statin therapy on renal and lipid outcomes in this population. 7 randomized controlled trials involving 490 participants were included. In the primary analysis, statin therapy showed a directionally favorable but non-significant trend toward improved estimated glomerular filtration rate (eGFR) and reduced 24-hour urinary total protein excretion (24h UTP), with no significant change in serum creatinine (Scr). Statins significantly reduced LDL-C (MD = − 52.18) and total cholesterol (MD = − 52.70), while changes in HDL-C and triglycerides were not significant. Subgroup analyses indicated numerically greater renal and lipid benefits with high-intensity regimens, longer treatment duration (≥ 26 weeks), and lower baseline eGFR, though no significant subgroup interactions were detected. Sensitivity analysis including a borderline CKM syndrome 2–3 trial characterized by higher renal risk, longer duration, and high-intensity atorvastatin rendered both renal and lipid outcomes statistically significant without altering effect direction. These findings suggest that statin therapy confers robust lipid-lowering efficacy and potential renoprotective effects in early CKM syndrome stages, particularly under conditions of greater baseline metabolic or renal burden. Statins may therefore serve as an early metabolic–renal intervention, warranting further validation in larger, stage-specific clinical trials.

Bao, Daorina; Cui, Zhuan; Yao, Yao; Lu, Min; Zheng, Danxia; Wang, Yue

doi: 10.1186/s12882-025-04646-7pmid: 41327089

BackgroundRenal involvement in rheumatoid arthritis (RA) is relatively common, which may be due to the RA itself or may be associated with the use of nephrotoxic drugs. The widespread use of biological agents has led to an increasing number of reports of RA-related nephropathy.Case presentationWe report a rare case of sequential membranous nephropathy (MN) and ANCA-associated vasculitis (AAV) in a 74-year-old male with seropositive RA (RF 389 IU/mL, anti-CCP 360 U/mL). One month after initiating etanercept (25 mg twice weekly), he developed nephrotic syndrome (proteinuria 5.42 g/24 h, albumin 19.9 g/L) and elevated anti-PLA2R (33.78 RU/mL). Renal biopsy revealed stage I MN with granular IgG/C3 deposits. After rituximab therapy (1600 mg cumulative dose) proteinuria decreased to 1.6 g/24 h; yet after six months the patient presented with acute kidney injury (serum creatinine [SCr] 11.87 mg/dL), hematuria, and positive MPO-ANCA (169.8 RU/mL), which was consistent with AAV. Immunosuppression with methylprednisolone and cyclophosphamide reduced the SCr level to 6.60 mg/dL, although dialysis dependence persisted.ConclusionTo our knowledge, this represents the first documented case of sequential MN and AAV in an RA patient who received etanercept and rituximab therapy during the clinical course. While lacking definitive proof of causality, this case emphasizes that clinicians must be vigilant for complex renal complications in biologic-treated RA patients, irrespective of the underlying cause.

Xi, Yue; Zheng, Huiwen; Wang, Yonghong; Guo, Yajie; Xiao, Jing; Li, Feina; Qi, Hui; Jiao, Weiwei; Zhou, Nan; Chen, Zhi; Sun, Lin

doi: 10.1186/s12882-025-04652-9pmid: 41291513

ObjectivesTuberculosis screening in pediatric lupus nephritis (LN) patients presents unique diagnostic challenges. This study aimed to analyze the frequency of indeterminate QuantiFERON-TB Gold Plus (QFT-Plus) results among children with LN and the potential influence factors.MethodsA retrospective cohort study was conducted among patients under 18 years old with a confirmed diagnosis of LN screened for tuberculosis infection from January 2023 and August 2024. Demographic and clinical data were extracted from their electronic medical record, with categorical variables presented as frequencies and continuous variables as medians. Using SPSS 18.0 (Chicago, IL), we first performed univariate logistic regression to identify factors associated with indeterminate IFN-γ results (P < 0.05), then entered significant variables into multivariate models to determine independent predictors, reporting results as ORs, with statistical significance set at P < 0.05.ResultsOf 111 patients with LN, 49 (44.14%) had indeterminate QFT-Plus results, with 43 (87.76%) due to positive control failure. In the 30-day period prior to the QFT-Plus test, 46 (41.44%) patients were treated with immunotherapy. Univariable logistic regression analysis indicated that the indeterminate group had significantly lower levels of hemoglobin, albumin, and alkaline phosphatase, fewer hospitalizations, and more frequent use of immunotherapy, and higher triglyceride and D-dimers levels. Multivariable logistic regression analysis revealed that triglycerides level (OR 1.847; 95% CI 1.195–2.856; P = 0.006) and immunotherapy use (OR 12.306; 95% CI 3.937–38.463; P<0.0001) were independently associated with increased risk of indeterminate QFT-Plus results. The area under the ROC curve for a triglycerides level of 2.155 mmol/L, and it was 0.751 for discriminating between indeterminate and determinate QFT-Plus results.ConclusionsHospitalized patients with LN had a high rate of an indeterminate QFT-Plus result, predominantly in positive control failure. Besides, our data showed that the use of immunotherapy agents and high triglycerides level represent factors associated with indeterminate QFT-Plus results in our cohort of pediatric lupus nephritis patients.

Huang, Haiting; Lu, Jun; Lin, Jingtian; Huang, Peng; Ma, Jing; Huang, Tingman; Qin, Honglian; Mo, Yuyi; Wang, Jie; Qin, Chao

doi: 10.1186/s12882-025-04507-3pmid: 41353129

ObjectiveUremic tumoral calcinosis (UTC) is a relatively rare but challenging complication in dialysis patients, characterized by abnormal calcium salt deposition. Parathyroidectomy (PTX) is a commonly used treatment; however, some patients experience limited postoperative symptom improvement, suggesting potential factors that affect PTX efficacy. This study aims to investigate the mechanisms underlying suboptimal remission of UTC after PTX to optimize treatment strategies and improve patient outcomes.MethodsWe report a case of a maintenance hemodialysis patient whose UTC worsened after PTX. Following discontinuation of active vitamin D and intensified phosphorus management, the patient’s calcium-phosphorus product significantly decreased, accompanied by marked regression of calcified lesions. To further explore possible mechanisms, we reviewed and analyzed previous literature on PTX treatment for UTC and compared our case with related reports.ResultsOur findings demonstrate considerable individual variability in PTX efficacy for UTC treatment, with calcium-phosphorus product (Ca×P) levels playing a critical role in patient prognosis. This study suggests that calcium-phosphorus metabolism may be a key factor influencing PTX outcomes.ConclusionsThis case highlights the importance of controlling the calcium-phosphorus product in treating UTC.Postoperative management should focus on optimizing calcium-phosphorus metabolism, with particular attention to individualized phosphorus control strategies and appropriate use of active vitamin D.These approaches are crucial for enhancing PTX efficacy and improving long-term patient prognosis.Clinical trial numberNot applicable.

Zhao, Liang; Su, Huimei; Guo, Wenjuan; Lei, Junfeng

doi: 10.1186/s12882-025-04632-zpmid: 41419874

IntroductionUremia and Kidney Renal Clear Cell Carcinoma (KIRC) are two significant health conditions that place a considerable burden on patients globally. This study aims to identify and validate common hub genes in uremia and KIRC, investigate their molecular roles, and explore their potential as biomarkers for diagnosis and prognosis.MethodWe retrieved two publicly available datasets (GSE37171 for uremia and GSE66272 for KIRC) from the Gene Expression Omnibus (GEO) and identified differentially expressed genes (DEGs) using the limma package in R. A Venn analysis was conducted to identify shared DEGs between the two conditions. The identified genes were subjected to protein-protein interaction (PPI) network construction using the STRING database and Cytoscape software, followed by hub gene identification with the CytoHubba plugin. Hub gene expression was validated in 9 KIRC cell lines and 5 normal control kidney cell lines using RT-qPCR. Functional assays, including gene knockdown, cell proliferation, colony formation, and wound healing assays were performed.ResultsA total of 114 shared DEGs were identified between uremia and KIRC. ALDH18A1, CALU, DERL1, and SUCLG2 were identified as hub genes with the highest connectivity in the PPI network. These genes were significantly upregulated in KIRC cell lines compared to normal controls. Validation using the KIRC TCGA dataset confirmed their upregulation in tumor samples and across different KIRC subtypes. Further analyses revealed hypomethylation of the hub genes, along with significant mutation frequencies and CNV amplifications. High expression of these hub genes was associated with poor survival in KIRC patients, and their correlation with immune cells and drug resistance was also observed. Gene knockdown of ALDH18A1 and CALU in 786-O and Uremic-786-O significantly reduced cell proliferation, colony formation, and migration, emphasizing their role in KIRC and Uremia pathogenesis. Additionally, silencing these genes decreased the expression of PDK1 and IDH1, key activators of the Citrate cycle, suggesting their involvement in metabolic dysregulation in KIRC.ConclusionThis study identifies ALDH18A1, CALU, DERL1, and SUCLG2 as potential biomarkers for KIRC diagnosis and prognosis. Our findings suggest that these hub genes are involved in the dysregulation of key metabolic pathways, including the citrate cycle, and may serve as therapeutic targets in KIRC.Clinical trial numberNot applicable.

Briggs, Datonye Christopher; Hlongwa, Khanyisile; McCulloch, Mignon; Nourse, Peter; Brink, Anita; Coetzee, Ashton

doi: 10.1186/s12882-025-04667-2pmid: 41318409

IntroductionMulticystic dysplastic kidney disease (MCDK) is a notable congenital anomaly of the kidney and urinary tract, with potential risk for chronic kidney disease, yet data from sub-Saharan Africa remain scarce. This study examined the pattern of MCDK, associated contralateral kidney abnormalities, determined the predictors of MCDK involution and assessed short-term outcomes in children followed beyond one year in South Africa.MethodThis retrospective study involved children under 13 years of age with suspected unilateral MCDK, confirmed on kidney ultrasound and [99mTc]Tc-MAG3 scans at the Red Cross War Memorial Children’s Hospital between January 1, 2014, and December 31, 2023. Demographic, clinical, and radiologic data were obtained. The Log-rank test and Cox Proportional Hazards regression analyses were used to identify predictors of MCDK involution.ResultsAmong 1,581 new cases, 98 (6.2%) had unilateral MCDK. 50% were male, and 57.1% had left-sided involvement. Median follow-up was 60 months (IQR: 12–72). Contralateral kidney abnormalities occurred in 17 (17.3%), most commonly duplex kidney (35.3%) and ureteropelvic junction obstruction (29.4%), but no vesicoureteric reflux was noted. Of 81 children followed beyond a year, 80.2% demonstrated contralateral hypertrophy, and 69.1% exhibited involution of the affected kidney. Initial kidney size ≤ 5.0 cm was the sole predictor of involution (Hazard Ratio: 2.42, 95% CI: 1.31–4.48). Urinary tract infections occurred in 18.5%, proteinuria in 2.5%, hypertension in 1.2%, and 2.5% developed chronic kidney disease related to contralateral dysplasia. One nephrectomy was performed, and no malignancies or deaths. At last follow-up, 28.4% were lost to follow-up, and 12.3% had transitioned to adolescent clinics.ConclusionAll MCDK cases were unilateral, with duplex kidney being the most common contralateral abnormality, a distinctive finding previously unreported. Follow-up into adolescence may be beneficial, as progression of chronic kidney disease is rare in those without contralateral anomalies. Multicentre long-term studies are needed to provide standardised follow-up guidelines.