Clinical Kidney Journal最新文献

Background: Membranous nephropathy (MN) is a frequent cause of nephrotic syndrome in adults with variable response to rituximab (RTX) therapy. While traditional markers like proteinuria and anti-phospholipase A2 receptor (PLA2R) antibodies exhibit predictive value, their limitations necessitate more robust biomarkers.

Methods: We prospectively analysed 149 MN patients receiving RTX over 12 months. Inflammatory indices such as neutrophil:lymphocyte ratio (NLR), monocyte:lymphocyte ratio (MLR) and systemic inflammation response index (SIRI) together with B cell levels were measured alongside conventional markers at baseline, 3 months and 6 months. Predictive models for 6- and 12-month remission (complete/partial) were developed using multivariate regression and receiver operating characteristics (ROC) analysis.

Results: Non-responders exhibited persistently elevated inflammatory markers (NLR, MLR, SIRI) throughout the entire observation period. Among the three, only SIRI can independently predict the remission of MN. At 3 months, SIRI ≤1.25 {odds ratio [OR] 3.68 [95% confidence interval (CI) 1.39-9.72]} and B cell proportion ≤0.2% [OR 2.90 (95% CI 1.00-8.35)] independently predicted 6-month response. Incorporating these two newly added indicators into the traditional variable model, which includes the levels of proteinuria, albumin and anti-PLA2R antibody at 3 months, markedly enhances prediction accuracy [area under the curve (AUC) 0.86 versus 0.81]. By 6 months, only SIRI ≤0.9 [OR 4.84 (95% CI 1.43-16.40)] and albumin change [OR 1.11 (95% CI 1.03-1.19)] predicted 12-month prognosis, as B cell and anti-PLA2R antibody levels lost significance. The prediction model incorporating SIRI also had better performance (AUC 0.82 versus 0.79).

Conclusions: B lymphocyte levels constitute a robust predictive biomarker for assessing short-term therapeutic response in patients with MN receiving RTX therapy. Furthermore, SIRI emerges as a valuable prognostic indicator capable of predicting both short-term efficacy and long-term renal outcomes. These findings suggest that concurrent monitoring of B lymphocyte levels and SIRI values warrants integration into standardized monitoring frameworks within clinical management protocols.

Background: Existing population research has evaluated inequities in health outcomes for people in deprived communities who have early kidney disease, but not the differences in their self-reported overall health and ability to manage daily life activities when they first present, or the additional burden for people of working age. Using their responses to the national Census in Scotland, we studied the self-reported overall health and impact on day-to-day life of people in deprived and affluent households who newly presented with evidence of kidney disease.

Methods: Of 458 897 adult North Scotland residents, we included all 24 775 individuals who presented with new onset kidney disease (eGFR <60 ml/min/1.72 m²) in 2011-2014. We measured deprivation based on household (Census) and resident neighbourhood (index of multiple deprivation). We fitted proportional odds regression models that accounted for age, sex, comorbidities, and additional impairments (e.g. vision, hearing, learning difficulties). We further adjusted for self-reported mental health and living alone as potential mediators, and tested for interactions with working age (18-65 years), sex, and mental health.

Results: Of 24 775 people newly presenting with kidney disease, already 11 115 (45%) reported limitations in their daily lives. People in the most deprived (vs least) neighbourhoods and households experienced 2-fold greater odds of worse self-reported health (adjusted odds ratio, OR 2.05, 1.81-2.32 neighbourhood; OR 1.93, 1.64-2.26 household); and greater limitation in day-to-day activities (OR 1.70, 1.49-1.95 neighbourhood; OR 1.65, 1.39-1.96 household). This pattern of inequity was even more pronounced (3-fold) among those of working age (interaction P < .0001).

Conclusion: The association of deprivation with health and daily life represents an additional dimension of health inequity that is substantial, and evident from the earliest stages for people with kidney disease.

Background: The involvement of the complement system in anti-glomerular basement membrane (GBM) disease is well known but incompletely characterized. The ability of autoantibodies to trigger the classical pathway is evident, while the lectin and alternative pathways also seem to be of importance. We studied complement activation in patients treated with imlifidase, which leads to rapid IgG depletion, to elucidate the role of complement in anti-GBM disease.

Methods: The GOOD-IDES-01 trial included 15 anti-GBM disease patients treated with one dose of imlifidase in addition to standard therapy with 6 months of follow-up. Plasma samples were analyzed for C3, C4 and complement activation products [C4d, C3bBbP and soluble terminal complement complexes (sTCC)]. Ratios of C4d/C4 and C3bBbP/C3 were calculated to correct for plasmapheresis. Serum samples were analyzed for anti-drug antibodies (ADA) directed against imlifidase.

Results: The C4d/C4 ratio decreased rapidly from its pre-dose level, while sTCC decreased more slowly. sTCC and C3bBbP/C3 were above the reference level throughout the trial. We observed a transient increase in C4d/C4 and C3bBbP/C3, but not sTCC, immediately following treatment with imlifidase, which tended to be more pronounced in patients with more pre-existing ADA.

Conclusions: Classical pathway activation decreased rapidly after autoantibody removal by imlifidase and increased again in most of those that experienced a rebound, but terminal complement activation remained elevated throughout the trial. However, due to the small sample size our results must be interpreted with caution.

Background: A hemodialysis catheter may serve as a short- or medium-term vascular access solution. Current guidelines suggest restricting non-tunneled catheter use to 2 weeks, partially based on studies using straight non-tunneled jugular catheters, which have now been widely replaced with pre-curved catheters. We compared the rate of catheter-related blood stream infections (CRBSIs) and possible CRBSIs (PCRBSIs) of pre-curved non-tunneled and tunneled catheters in our hemodialysis center.

Methods: This was a retrospective study including patients dialyzed on an outpatient basis between 1 January 2018 and 1 July 2024, with a follow-up until 1 March 2025. The primary aim was to compare the rates of CRBSIs.

Results: In 301 patients, 625 non-tunneled single lumen catheter pairs and 53 double lumen tunneled catheters were used. There were 53 CRBSIs in non-tunneled and 10 in tunneled catheters, with identical incidence rate (0.48/1000 catheter-days in both groups). Analyzing CRBSIs and PCRBSIs together also showed similar infection rates [0.66 vs 0.58, incidence rate ratio (IRR) with 95% confidence interval 1.14 (0.6-2.1), P = .68]. Two subanalyses were made: CRBSI IRR in 27 patients with both types of catheters during study period was 1.37 (0.55-3.41, P = .49) and 2.01 (0.52-7.72, P = .47) in 36 patients after their first CRBSI. Time to CRBSI was also comparable in all analyses.

Conclusions: Our study found no significant difference in the incidence of CRBSIs. We conclude that prolonged use of non-tunneled pre-curved catheters, which are easily managed, is a viable option for patients awaiting construction of arteriovenous fistula, insertion of a peritoneal catheter or kidney transplantation in a reasonable time. Promising results on long-term use from this study need to be confirmed in prospective studies.

The treatment of volume overload has vexed physicians for centuries. References to herbal remedies for the treatment of fluid retention date as far back as 1550 BC in the Ebers Papyrus from Ancient Egypt [1]. The term edema originates from the Greek "to swell," and the Greek hero Oedipus, meaning "swollen foot," was so named due to the swelling of his feet from injuries inflicted by his mother to prevent the fulfillment of a prophecy. There are several references to edema in the writings of Hippocrates, with various proposed treatments, ranging from herbal remedies, purgatives, phlebotomy, and cranial decompression. The word dropsy, from the Greek word for water, originated in the Middle English period and came to describe conditions associated with an accumulation of fluid in body tissue, preceding more sophisticated knowledge of distinctive disease states. Physicians often prescribed treatments such as bloodletting, purgatives, leeches, and Southey tubes, which were invented in 1877 by English physician Reginald Southey. These were small cannulas placed in a patient's swollen extremities to relieve edema, used until the 1960s [2]. It was not until the serendipitous discovery of the diuretic properties of the mercurial agent Novasurol by Alfred Vogl, while working as a medical student at the Wenckebach clinic in Vienna, used to treat a young patient with congenital syphilis [3], that spurred the interest in synthetic diuretic agents. Despite being the first agent synthesized, acetazolamide became the "forgotten diuretic" until a recent resurgence has reinvigorated interest in its utility in patients with acute decompensated heart failure. This review will describe the background, clinical trials, and proposed utility of acetazolamide in states of volume overload.

Background: Tyrosine kinase inhibitors (TKIs) are essential anticancer agents associated with substantial nephrotoxic potential. Although TKI-induced renal injury is increasingly recognized, comprehensive histopathological characterization remains limited due to insufficient renal biopsy data. This study characterizes the clinicopathological spectrum and outcomes of biopsy-proven TKI nephrotoxicity.

Methods: This retrospective study analyzed 21 patients with biopsy-proven TKI-associated renal injury identified between 2015 and 2025. Demographic characteristics, renal function indices, oncological profiles and histopathological features were analyzed.

Results: The cohort included 16 patients with solid tumors and 5 with hematologic malignancies exposed to four major TKI classes: vascular endothelial growth factor receptor, platelet-derived growth factor receptor, human epidermal growth factor receptor and Bruton's tyrosine kinase TKIs. The median time from TKI initiation to symptom onset was 9.5 months. Clinical manifestations included proteinuria (95%), edema (52%) and new-onset/worsened hypertension (47%). At biopsy, median serum creatinine was 1.07 mg/dL (94.6 µmol/L) and proteinuria was 1.83 g/day. Histopathological analysis demonstrated thrombotic microangiopathy (TMA)-like lesions in 17 of 21 cases (80%), with concurrent immunoglobulin A nephropathy in 3 cases and focal segmental glomerulosclerosis in 3 cases. Among 18 patients with available follow-up data, 14 discontinued their initial TKI therapy, with 5 transitioning to alternative TKIs. Treatment strategies included angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker monotherapy (n = 13) and combination therapy with corticosteroids/immunosuppressants (n = 5). During a median follow-up period of 9.5 months, complete and partial proteinuria remission occurred in five cases each. Four patients died due to cancer progression, while renal function remained stable in the remaining patients without progression to end-stage renal disease.

Conclusion: TKI-induced renal injury characteristically presents with edema, hypertension and significant proteinuria, with renal-limited TMA as the predominant histopathological finding. Timely recognition and prompt discontinuation of the offending TKI, coupled with appropriate supportive nephroprotective management, generally yield favorable long-term renal outcomes with preservation of kidney function.

[This corrects the article DOI: 10.1093/ckj/sfaf289.].

Background: Culture-negative peritoneal dialysis-associated peritonitis (CNPDP) carries a high risk of treatment failure but lacks validated prediction tools. This study aimed to develop and validate a clinical nomogram for individualized risk assessment of treatment failure in CNPDP patients.

Methods: In this multicenter retrospective study, 288 CNPDP patients treated at Jining Medical University Affiliated Hospital (2013-23) were randomly allocated to training (n = 173) and internal validation (n = 115) cohorts. An independent external cohort (n = 103) from Zaozhuang Municipal Hospital and Heze Municipal Hospital assessed generalizability. First, we used Random Forest to estimate missing data for variables with <30% missing values. Then, we used LASSO regression to analyze 32 candidate predictors. These predictors covered areas like patient demographics, clinical scores and lab test results. The final multivariate logistic regression model was visualized as a clinical nomogram. Performance was rigorously evaluated through area under receiver operating characteristic curve (AUC), calibration plots and decision curve analysis. The primary endpoint was composite treatment failure (catheter removal or peritonitis-related mortality ≤30 days).

Results: LASSO identified five independent predictors: effluent white blood cell count on Day 3 (Eff_WBC_D3), serum albumin (ALB), total cholesterol (TC), magnesium (Mg) and phosphorus (P). The nomogram achieved excellent discrimination: training cohort AUC = 0.897 (95% confidence interval 0.817-0.978), internal validation AUC = 0.861 (0.770-0.952) and external validation AUC = 0.849 (0.750-0.948) with minimal optimism (ΔAUC = 0.036). Eff_WBC_D3 demonstrated the strongest univariate predictive power (AUC = 0.830). Calibration curves showed optimal fit (Hosmer-Lemeshow P = .32), while decision curve analysis confirmed clinical utility across probability thresholds of 5%-50%. For bedside implementation, an interactive web tool was developed (https://liuliangmianhua.shinyapps.io/dynnomapp/).

Conclusion: This externally validated five-variable nomogram, deployed as a freely accessible online tool, offers a robust, practical tool for predicting treatment failure in CNPDP. Its integration of dynamic dialysate markers with routine laboratory data enables personalized early intervention and supports timely clinical decision-making.