Clinical Kidney Journal最新文献

Genetic testing is becoming a routine-and increasingly time-sensitive-tool in nephrology, with implications for diagnosis, prognosis, targeted therapy, transplant planning, and family counselling. However, many nephrologists remain uncomfortable with genetic concepts in general, and variant interpretation specifically. This gap will increasingly limit their ability to fully leverage genetic testing in routine nephrology care-and to translate results into management decisions that improve patient outcomes. In this review, we provide 10 practical tips to help nephrologists integrate genetic testing safely and confidently into everyday practice. We emphasize early testing when a molecular diagnosis could plausibly change management, and the primacy of careful phenotyping (including extra-renal features) to guide efficient test selection (single-gene testing, targeted panels, exome, or genome). We outline a pragmatic approach to informed consent that addresses the family impact, secondary findings, and the possibility of misattributed parentage. We then walk through how to read genetic reports, recognize common technical 'blind spots' (e.g. copy number variants), and classify results in a clinically meaningful way (diagnostic, suggestive, or uninformative). We highlight how to handle variants of uncertain significance as hypotheses rather than diagnoses, and why periodic reanalysis is essential as gene-disease assertions and variant classifications evolve. Finally, we encourage clinicians to work within multidisciplinary pathways and to contribute to data-sharing efforts that advance nephrogenetics. Each tip concludes with a brief 'nephrogenetics nugget'-a practical takeaway, a useful metaphor, or a simple script-to help clinicians translate core concepts into real-world conversations and decisions at the point of care. Overall, these tips provide a practical framework for ordering, interpreting, and disclosing genetic test results in routine nephrology care.

Background: Chronic kidney disease (CKD) and renal cell carcinoma share a bidirectional relationship, with radical nephrectomy posing a significant risk for postoperative renal decline. This study identifies radical nephrectomy as a critical opportunity to evaluate the non-neoplastic renal parenchyma.

Methods: We conducted a prospective observational study on 30 adult patients diagnosed with renal or urothelial cancer who underwent radical nephrectomy. Samples of non-neoplastic renal parenchyma were collected during surgery and analyzed using optical microscopy and immunofluorescence. Renal function was assessed pre- and postoperatively using the CKD-EPI formula.

Results: The cohort comprised 30 patients (63.3% male) with a median age of 65.5 years (min 29-max 83). Following radical nephrectomy, 50% of patients with preserved preoperative renal function experienced a decline to estimated glomerular filtration rate < 60 ml/min/1.73 m². Histopathological evaluation of the non-neoplastic parenchyma revealed chronic tubulointerstitial damage in 41% (n = 12) and arteriosclerotic vascular damage in 38% (n = 11) of cases. Notably, occult nephropathies were identified in 24% (n = 7) of the cohort, comprising diabetic glomerulosclerosis (n = 2), membranous nephropathy (n = 2), fibrillary glomerulonephritis (n = 1), IgA nephropathy (n = 1), and minimal change disease (n = 1). Two cases (IgA nephropathy and minimal change disease) demonstrated spontaneous remission postsurgery, consistent with a paraneoplastic etiology.

Conclusions: The non-neoplastic renal parenchyma in renal cell carcinoma patients frequently exhibits occult pathological changes, predominantly tubulointerstitial damage likely driven by the tumor microenvironment. The study highlights a higher-than-expected prevalence of undiagnosed nephropathies (24%), including paraneoplastic cases. Routine histological evaluation during radical nephrectomy is essential for optimizing patient management, avoiding unnecessary subsequent biopsies, and guiding therapeutic decisions in the oncological setting.

Patients receiving maintenance hemodialysis experience an exceptionally high cardiovascular risk, characterized by frequent recurrent events and a longstanding lack of effective preventive therapies. Most cardiovascular trials in this population have yielded neutral results, highlighting important limitations in both therapeutic strategies and outcome assessment. The PISCES trial recently reported significant reductions in both first and recurrent cardiovascular events with high-dose omega-3 fatty acids in patients undergoing hemodialysis, using a recurrent-event framework to capture overall cardiovascular burden. In this focused narrative review, we critically appraise the PISCES findings within the broader context of omega-3 research in chronic kidney disease and dialysis. Particular emphasis is placed on how biological exposure, population selection, and outcome frameworks influence the detectability of cardiovascular benefit in high-risk populations. PISCES challenges the prevailing notion that cardiovascular risk in hemodialysis is largely unmodifiable and underscores the importance of aligning therapeutic interventions with outcome measures that reflect total disease burden. More broadly, the trial illustrates how methodological choices may critically influence the interpretation of cardiovascular efficacy in populations with dense event clustering and high competing mortality.

Background: Protein-energy wasting, chronic inflammation, and functional decline are prevalent among patients undergoing haemodialysis (HD) and are associated with adverse outcomes and reduced quality of life. Although a substantial body of literature exists on nutritional management in HD, evidence has evolved considerably in recent years. Nutritional care in HD remains inconsistent and is limited by restrictive dietary paradigms and organizational barriers.

Objective: To map evidence published between 2015 and 2025 on nutritional management in adult patients undergoing HD, focusing on personalized strategies, barriers to effective nutritional care, and patient-centred, function-oriented implementation.

Methods: A scoping review was conducted following Joanna Briggs Institute methodology and reported according to PRISMA Extension for Scoping Reviews. PubMed/MEDLINE, Scopus, Web of Science, and Europe PMC were searched for English-language studies published between January 2015 and August 2025.

Results: A total of 30 studies were included. The literature describes diverse personalized nutritional approaches, including oral and intradialytic supplementation, plant-forward dietary patterns, microbiota-oriented strategies, and targeted nutrient supplementation. Reported outcomes included nutritional biomarkers, inflammation, body composition, functional measures, and patient-reported experience. Key barriers to effective nutritional care were poor dietary adherence, psychosocial burden, limited health literacy, inconsistent professional guidance, and organizational constraints. Morphofunctional assessment tools provided added value beyond biochemical parameters, and the studies highlighted specific considerations for nutritional risk assessment in older adults undergoing HD.

Conclusions: This scoping review highlights a shift towards more personalized and function-oriented nutritional care in HD, while underscoring persistent barriers and substantial evidence heterogeneity. The findings support future research and the development of more integrated, patient-centred, and sustainable nutritional care models.

Background: Arteriovenous access thrombosis is a major cause of morbidity in patients receiving maintenance hemodialysis, and conventional clinical and anatomical risk factors do not fully explain its occurrence. Trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite that accumulates in kidney failure and exhibits prothrombotic properties, has been linked to cardiovascular events in dialysis populations. Its relevance to dialysis arteriovenous access outcomes, however, remains unclear.

Methods: We conducted a multicenter prospective cohort study including 375 adult patients undergoing maintenance hemodialysis at 12 centers in Taiwan. Baseline serum TMAO concentrations were measured using liquid chromatography-tandem mass spectrometry and analyzed as tertiles and as a log-transformed continuous variable. Participants were followed for a median of 24 months. The primary outcome was time to first arteriovenous access thrombosis. Associations were evaluated using Cox proportional hazards models with multivariable adjustment and restricted cubic spline analyses.

Results: During a median follow-up of 24 months, 88 patients (23%) experienced arteriovenous access thrombosis. Thrombosis incidence increased stepwise across TMAO tertiles (13%, 23%, and 34%; P < .001). In unadjusted analysis, patients in the highest TMAO tertile had a higher risk of thrombosis compared with the lowest tertile [unadjusted hazard ratio 3.10; 95% confidence interval (CI): 1.75-5.51]. This association remained significant after multivariable adjustment (adjusted hazard ratio 2.87; 95% CI 1.60-5.17). Results were consistent in competing-risk analyses treating death as a competing event. Addition of TMAO to a baseline clinical model yielded modest improvement in discrimination (ΔC = 0.011, 95% CI: -0.047 to 0.070; P = .051).

Conclusion: Higher serum TMAO levels were independently associated with an increased risk of arteriovenous access thrombosis in patients undergoing hemodialysis. These findings suggest that TMAO reflects a systemic prothrombotic milieu relevant to dialysis arteriovenous access and support further studies to determine whether TMAO represents a modifiable pathway or a biomarker of uremic thrombotic susceptibility.

Background: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) often manifests with necrotizing glomerulonephritis. Neutrophil extracellular traps (NETs) are implicated in its pathogenesis; citrullinated histone H3 (H3Cit) is a specific marker of NET formation. To date, no studies have assessed the relationship between H3Cit-positive cells and disease activity in patients with AAV. In this study, we assessed whether H3Cit-positive cells in renal tissue were associated with disease activity.

Methods: We retrospectively evaluated 50 patients newly diagnosed with AAV by renal biopsy between January 2011 and August 2024. Paraffin-embedded specimens underwent immunohistochemical staining for H3Cit. Patients were classified as H3Cit-positive or H3Cit-negative groups based on the presence of H3Cit-positive cells in glomeruli and/or interstitium. Clinical parameters and histopathological features were compared. Additionally, correlations between H3Cit-positive cell counts and urinary biomarkers were evaluated.

Results: H3Cit-positive cells were detected in 42 cases (84%) within the interstitium; of these 42 cases, they were also detected in 23 within the glomeruli. Compared with H3Cit-negative cases, the positive group had significantly higher urinary β₂-microglobulin (β₂-MG) and N-acetyl-β-D-glucosaminidase index values. Interstitial H3Cit-positive cell counts positively correlated with urinary β₂-MG levels. The positive group showed more frequent crescent formation and peritubular capillaritis, and H3Cit-positive cells were present in all arteritic lesions.

Conclusions: H3Cit-positive cells in renal tissue were associated with active glomerular and tubulointerstitial lesions in AAV cases and correlated with urinary markers of interstitial injury. H3Cit immunostaining may serve as a pathological marker of renal disease activity in AAV cases and support clinical assessment at the time of biopsy.

Background: Syndrome of inappropriate antidiuresis (SIAD) is a common cause of hyponatraemia, with fluid restriction (FR) failing in nearly half of patients. Although furosemide combined with oral sodium chloride (NaCl) tablets is widely used as second-line therapy, evidence supporting its effectiveness after FR failure remains limited, and predictors of response have not been established.

Methods: This prospective multicentre cohort study enrolled hospitalized adults with SIAD who failed FR at two tertiary centres in Thailand between October 2022 and September 2025. Patients received oral NaCl tablets (3.6 g daily) and furosemide (40 mg daily) while continuing FR. The primary outcome was the daily rate of serum sodium correction. Predictors of response were identified using multivariable linear mixed-effects models.

Results: Among 88 patients (68% male; median age 65 years), the median baseline serum sodium was 124 mmol/l. Serum sodium increased by 1.51 mmol/l per day [95% confidence interval (CI) 1.37-1.66], reaching a median of 130 mmol/l by day 4 and 134 mmol/l by day 7. Three factors independently predicted faster correction: higher body weight (β 0.85 mmol/l per 10 kg; 95% CI 0.28-1.42), lower baseline sodium (β -0.58 per 1 mmol/l lower; 95% CI -0.77 to -0.39), and drug-induced aetiology (β 7.17 mmol/l; 95% CI 3.48-10.85). Adverse events included hypokalaemia (51%), hypomagnesaemia (29.5%), and acute kidney injury (18.2%). Overcorrection occurred in one (1.1%) patient.

Conclusions: Furosemide combined with oral NaCl tablets is a practical second-line option for SIAD after FR failure, achieving sodium correction of 1.5 mmol/l per day. Higher body weight, lower baseline sodium, and drug-induced aetiology predict faster correction. Randomized controlled trials are needed to confirm efficacy.

Background: Metabolic complications after kidney transplantation (KT) significantly affect graft and patient survival. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) offer cardio-renal benefits in the general population, but evidence in KT recipients remains limited.

Methods: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines (PROSPERO: CRD420251153352). PubMed, Scopus, Web of Science, Ovid MEDLINE, and Cochrane Library were searched up to September 2025 for studies evaluating GLP-1RA therapy in adult KT recipients. Random-effects models pooled outcomes for metabolic, renal, cardiovascular, and safety endpoints.

Results: Seventeen studies (n = 54 680 KT recipients) were included. GLP-1RAs use significantly reduced all-cause mortality (HR 0.53, 95% CI 0.36-0.79, k = 4) and major adverse cardiovascular events (OR 0.55, 95% CI 0.47-0.66, k = 3). Estimated glomerular filtration rate (eGFR) remained stable at 3 months, improved at 6 months (+1.99 ml/min/1.73 m², 95% CI 0.52-3.47, k = 5) and 12 months (+2.24 ml/min/1.73 m², 95% CI 0.02-4.46, k = 6), and was preserved at 24 months. GLP-1RAs lowered HbA1c (MD -0.54%, 95% CI -0.89 to -0.19, k = 13) and body mass index (SMD -0.32, 95% CI -0.49 to -0.15, k = 12) from baseline, with parallel reductions in insulin requirement and urinary albumin excretion. Tacrolimus levels were unaffected at 6 months and modestly decreased at 1 year without compromising graft function. Adverse events were mainly mild gastrointestinal intolerance (10%-20%), with rare discontinuations and no increased risk of hypoglycemia, pancreatitis, or infections.

Conclusion: GLP-1RAs are associated with improved glycemic control, weight, and cardiovascular outcomes, with no consistent signal of adverse effects on graft stability and immunosuppressive balance. GLP-1RA integration into individualized post-transplant care may be considered for patients with diabetes or metabolic syndrome, with close clinical monitoring.

Background: Lupus nephritis (LN) treatment response remains heterogeneous. We investigated associations between peripheral/renal T-cell profiles and treatment response, and explored renal T-cell infiltration as a mediator.

Methods: This retrospective cohort study analyzed data from 424 LN patients. Peripheral CD4⁺/CD8⁺ T-cell counts were measured via flow cytometry, and renal interstitial infiltrations were assessed immunohistochemically. Associations with treatment response were evaluated using generalized linear and logistic regression models, adjusting for clinicopathological factors. Mediation analysis examined renal T-cell infiltration in connecting peripheral immunity and treatment outcomes.

Results: The study cohort consisted of 424 patients with biopsy-confirmed LN, predominantly female (84.67%), with a mean age of 30.37 ± 11.18 years. Responders, comprising 68.4% of the cohort, exhibited significantly higher peripheral CD4⁺ T-cell counts (median 310 vs. 265 cells/μl, P = .002) and CD4/CD8 ratios (0.94 vs. 0.73, P < .01), with adjusted OR of 1.002 (95% CI 1.001-1.003) and 2.462 (95% CI 1.414-4.288), respectively. These associations remained significant after Bonferroni correction. Nonresponders showed increased renal interstitial CD8⁺ T-cell infiltration (148 vs. 80 cells/mm², P < .001), while higher renal interstitial CD4/CD8 ratios predicted remission (OR = 8.312, 95% CI 2.593-26.645). The peripheral CD4/CD8 ratio provided incremental predictive value over standard clinical-pathological indices (AUC improvement: 0.711 vs. 0.678, P = .022). Mediation analysis revealed that the renal interstitial CD4/CD8 ratio mediated 11.97% of the total effect of the peripheral CD4/CD8 ratio on treatment response (indirect effect β = 0.011, P = .016).

Conclusion: Peripheral and renal interstitial T-cell profiles, particularly CD4/CD8 ratios, are significantly associated with treatment response in LN. Renal interstitial T-cells partially mediate the impact of peripheral immune status on clinical outcomes.