Kanbay M, Copur S, Capasso G
… +15 more, Turkmen K, Delanaye P, Bruchfeld A, Abd ElHafeez S, Ferro CJ, Verhaar MC, Pesce F, Liakopoulos V, Boor P, Adamczak M, Vivarelli M, Navarro-González JF, Kramann R, Florquin S, Valdieso JM
Clin Kidney J
· 2026 May · PMID 42182977
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The field of nephrology is rapidly expanding and evolving with advancements in the areas of diagnostics including biomarkers, molecular genetics and imaging modalities, and therapeutics. As acute kidney injury affects a...The field of nephrology is rapidly expanding and evolving with advancements in the areas of diagnostics including biomarkers, molecular genetics and imaging modalities, and therapeutics. As acute kidney injury affects a substantial proportion of hospitalized patients with considerable morbidity and mortality risk and chronic kidney disease is among the leading causes of morbidity and mortality globally, the advancements in the field of nephrology are worth focusing on and highlighting. Novel biomarkers along with better imaging modalities, including functional tools such as positron emission tomography and contrast-enhanced ultrasound, may enable earlier diagnosis of kidney injury and potentially reverse injury state before the establishment of an irreversible state of injury. Moreover, there are multiple ongoing clinical trials evaluating novel therapeutic approaches, advancements in kidney replacement therapies or targeted approaches against kidney transplantation including xenotransplantation and plasma cell-directed therapies. In addition, artificial intelligence may become a game changer in nephrology, providing improved diagnostic and therapeutic alternatives. However, the limitations of current state of knowledge in those novel modalities should be adequately acknowledged and addressed. In this narrative review, our aim is to evaluate the current state of advancements in the field of nephrology in terms of diagnostics, imaging modalities, biomarkers, and therapeutics along with providing potential future perspectives.
Azzopardi G, Davies T, Lewis MJ
… +2 more, Puthucheary Z, Prowle JR
Clin Kidney J
· 2026 May · PMID 42164350
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BACKGROUND: Skeletal muscle wasting due to aging, acute illness, and chronic disease is associated with adverse outcomes including mortality, frailty, and multi-morbidity. We investigated the relationship of creatinine m...BACKGROUND: Skeletal muscle wasting due to aging, acute illness, and chronic disease is associated with adverse outcomes including mortality, frailty, and multi-morbidity. We investigated the relationship of creatinine muscle index (CMI), a serum biological signature of muscle mass, in UK Biobank participants with gold standard muscle measurement and adverse outcomes. METHOD: We compared CMI with Magnetic Resonance Imaging (MRI) measured muscle mass in 33 799 participants using linear regression. We then assessed CMI's ability to discriminate low muscle mass (≤2.5 SD below the mean). In the full UK Biobank cohort ( = 450 812), we utilized Cox-proportional hazards models to investigate associations between CMI with mortality, frailty and comorbidity. RESULTS: CMI demonstrated moderate to good linear correlation with gold-standard MRI muscle mass measurements [R males: 0.68 (0.60-0.76); females: 0.65 (0.56-0.73)], after accounting for data imbalance. CMI discriminated muscle mass ≤2.5 standard deviations from the mean, with an area under the curve of 0.80 (95% CI:0.75-0.86) in males and 0.84 (95% CI:0.78-0.89) in females. CMI consistently decreased with increasing age, frailty and comorbidity. Over an 8-year follow-up, lower CMI was associated with higher morality: adjusted hazard ratio for the 25th vs 75th CMI centiles were 0.61 (95% CI: 0.58-0.66) in males and 0.72 (95% CI: 0.66-0.78) in females. CONCLUSIONS: In over 450 000 UK Biobank participants, low CMI was significantly associated with baseline comorbidity, frailty and survival on follow-up (independent of age, sex, and comorbidity). This study supports CMI as a potential biological signature for skeletal muscle wasting in clinical and research settings.
Touzot M, Amato S, Ridel C
… +1 more, Ureña-Torres P
Clin Kidney J
· 2026 May · PMID 42164349
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Prescribing off-label medications for patients undergoing dialysis presents significant clinical challenges that require careful judgement to optimize the risk-benefit ratio. The altered pharmacokinetic profile in this p...Prescribing off-label medications for patients undergoing dialysis presents significant clinical challenges that require careful judgement to optimize the risk-benefit ratio. The altered pharmacokinetic profile in this population, characterized by impaired renal elimination, modified non-renal clearance pathways, and complex polypharmacy, has traditionally led to numerous contraindications, not solely due to concerns about drug accumulation but also to prevent serious adverse events. While established dosing protocols exist for certain drug classes, robust pharmacological data remain insufficient for many contemporary medications, leaving clinicians without evidence-based guidance for commonly prescribed authorized therapies in participants without significant chronic renal disease. The categorical off-label medication contraindications in haemodialysis warrants new reconsideration in the light of emerging evidence that has successfully challenged these constraints through well-designed clinical studies and real-world experiences. In this review, we aim to examine the evidence on selected examples of off-label medications previously deemed contraindicated that have been successfully evaluated in patients treated by dialysis, and explore emerging therapeutic agents. Finally, we discuss the clinical, research, methodological, and regulatory barriers that must be addressed to improve evidence-based prescribing in patients on dialysis.
Carvalho MS, Kojima CA, Rocha EP
… +10 more, Costa DM, Magalhães AO, Borges CM, Rocha EVS, Fernandes AS, Resende LLG, Leal A, Alves L, Cuppari L, Elias RM
Clin Kidney J
· 2026 May · PMID 42164348
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Clin Kidney J
· 2026 May · PMID 42158382
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Chronic kidney disease (CKD) is commonly framed as a model of accelerated aging, yet clinical decisions still rely heavily on chronological age, which poorly captures heterogeneity in functional status, vascular health,...Chronic kidney disease (CKD) is commonly framed as a model of accelerated aging, yet clinical decisions still rely heavily on chronological age, which poorly captures heterogeneity in functional status, vascular health, cognition, and recovery potential. This narrative review argues that biologic age-a multidomain construct integrating frailty and physical performance, body composition, cardiovascular and vascular markers, inflammatory and metabolic profiles, and cognitive/psychosocial factors-should be treated as a "missing vital sign" in CKD. Such composite measures can refine risk stratification, guide choices between dialysis and conservative care, improve transplant candidate assessment, and inform cardiovascular prevention, ICU triage, and major surgery planning. The article also warns that biologic age metrics must be transparently developed and audited to prevent reinforcing existing inequities and to ensure they trigger supportive, not exclusionary, interventions.
Engole YM, Bukabau JB, Cavalier E
… +13 more, Pottel H, Nkodila AN, Nlandu YM, Makulo JRR, Mokoli VM, Kajingulu FPM, Longo AL, Zinga CV, Mboliasa PI, Ngonde AM, Nkolomoni B, Sumaili EK, Delanaye P
Clin Kidney J
· 2026 May · PMID 42147790
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INTRODUCTION: Sickle cell disease (SCD) carries a high risk of chronic kidney disease, necessitating accurate glomerular filtration rate (GFR) monitoring. This study evaluated the performance of creatinine-based (eGFR),...INTRODUCTION: Sickle cell disease (SCD) carries a high risk of chronic kidney disease, necessitating accurate glomerular filtration rate (GFR) monitoring. This study evaluated the performance of creatinine-based (eGFR), cystatin C-based (eGFR), and combined (eGFR) equations against directly measured GFR (mGFR). METHODS: Clinically stable Congolese adults with SCD were recruited in 13 medical centers from Kinshasa. GFR was measured using iohexol plasma clearance. We compared the bias, precision, and accuracy of Chronic Kidney Disease Epidemiology (CKD-EPI) and European Kidney Function Consortium (EKFC) equations. RESULTS: Among 207 patients included (24 [20;31] years and 58% of women), mean mGFR was 129 ± 38 ml/min/1.73 m with 41% of patients hyperfiltrating (mGFR >135 ml/min/1.73 m). Among eGFR equations, CKD-EPI was superior in hyperfiltrating patients, while EKFC performed better in normofiltrating patients. However, all eGFR equations were suboptimal with only around 80% of estimated GFR (eGFR) results within 30% of mGFR. eGFR equations showed severe underestimation and poor accuracy. eGFR equations offered no clear added value. CONCLUSION: All eGFR equations were suboptimal in this young SCD population, with cystatin C performing particularly poorly. Given the limitations of current biomarkers, measuring GFR by a reference method remains the recommended standard. However, given the cost and logistical challenges of mGFR in low-income settings, relying on creatinine-based EKFC equation for normofiltrating patients and on creatinine based Chronic Kidney Disease Epidemiology Equation (CKD-EPI) for hyperfiltrants appears to be a more feasible and pragmatic approach.
Ritter A, Bührer L, Fuster DG
… +15 more, Dhayat NA, Bonny O, Wuerzner G, Ernandez T, Buchkremer F, Segerer S, Keller L, Sabev M, Engeler DS, Roth B, Ferraro PM, Held U, Mohebbi N, Wagner CA, Seeger H
Clin Kidney J
· 2026 May · PMID 42147788
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BACKGROUND: Citrate is frequently applied in kidney stone formers (KSFs), yet long-term safety data are lacking. We evaluated the effects of prolonged citrate therapy on metabolic health, urinary risk factors and stone r...BACKGROUND: Citrate is frequently applied in kidney stone formers (KSFs), yet long-term safety data are lacking. We evaluated the effects of prolonged citrate therapy on metabolic health, urinary risk factors and stone recurrence in high-risk KSFs in Switzerland. METHODS: The Swiss Kidney Stone Cohort (SKSC) is a multicenter study including KSFs and controls. Blood and urine analyses were performed at baseline and longitudinally over 2 years in KSFs, with subsequent telephone follow-up for stone events. A total of 654 KSFs (110 with citrate, 544 without) and 207 controls were included. Outcomes comprised anthropometric indices (body mass index, body roundness index, waist-to-hip ratio), metabolic parameters, urinary relative supersaturation ratios (RSR), stone recurrence and stone composition. RESULTS: No evidence for between-group differences in 1- to 2-year changes in anthropometric, glucose or lipid outcomes was identified. Anthropometric indices remained stable in both groups. HbA1c rose in non-citrate (NC) but not in citrate (C) group patients. High-density lipoprotein (HDL) cholesterol increased in both groups, while low-density lipoprotein (LDL) decreased only in C patients. Propensity score-matched analyses showed no between-group differences in 1- to 2-year changes in anthropometric, glucose or lipid outcomes, with only modest within-group changes in the C group (hemoglobin A1c, HDL- and LDL-cholesterol). Urine analyses showed a greater reduction in RSR for brushite among NC patients, whereas C patients had a stronger decline in uric acid (UA) RSR. Calcium oxalate RSR decreased similarly across groups. Stone recurrence was more frequent in C patients, with 43% versus 30% of NC patients changing stone type during follow-up. No shift toward calcium phosphate stones was observed in citrate users. CONCLUSIONS: Long-term citrate therapy appeared metabolically safe, and selectively reduced UA supersaturation, while non-treated patients showed a more pronounced decrease for brushite. Higher recurrence among treated patients may reflect different baseline risk. A prospective trial is warranted to clarify additive benefits of citrate beyond dietary-guided counseling.
Clin Kidney J
· 2026 May · PMID 42137551
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Residual kidney function (RKF) is a key determinant of outcomes in patients undergoing peritoneal dialysis (PD), contributing to solute clearance, volume regulation, reduced inflammation, and improved survival. Neverthel...Residual kidney function (RKF) is a key determinant of outcomes in patients undergoing peritoneal dialysis (PD), contributing to solute clearance, volume regulation, reduced inflammation, and improved survival. Nevertheless, RKF commonly declines after PD initiation, often due to potentially modifiable clinical and treatment-related factors. This narrative review summarizes current evidence on the mechanisms underlying RKF loss in PD and evaluates established and emerging strategies to preserve RKF in contemporary practice. Major contributors to RKF decline include hemodynamic instability, cumulative glucose exposure, inflammation and peritonitis, nephrotoxic medications, dialysis-related volume shifts, and kidney disease-specific conditions. Conventional strategies such as incremental and individualized PD prescriptions, use of biocompatible and glucose-sparing solutions, careful volume and blood pressure management, renin-angiotensin-aldosterone system blockade, infection prevention, and tailored management after kidney allograft failure are reviewed. Importantly, current guideline-based strategies largely address these factors in isolation. We propose that RKF preservation should be approached through an integrated, mechanism-based framework, in which cumulative glucose exposure represents a central modifiable mediator linking multiple pathways of kidney injury. In this context, remote monitoring and artificial intelligence-based tools may serve as enabling platforms that integrate longitudinal clinical and treatment data, supporting individualized and proactive care. Preserving RKF should remain a central therapeutic goal in PD, and combining established physiological principles with modern digital technologies may provide a more effective framework for improving long-term patient outcomes.
Barratt J, Floege J, Zoccali C
… +1 more, Lafayette R
Clin Kidney J
· 2026 May · PMID 42137548
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The expanding therapeutic armamentarium for IgA nephropathy (IgAN) has brought to the forefront a key strategic dilemma: whether to intervene simultaneously on IgAN-specific pathogenic mechanisms and the downstream, non-...The expanding therapeutic armamentarium for IgA nephropathy (IgAN) has brought to the forefront a key strategic dilemma: whether to intervene simultaneously on IgAN-specific pathogenic mechanisms and the downstream, non-specific consequences of nephron loss, or to follow a sequential, stepwise approach in which therapies are added only as residual risk becomes evident. This debate article contrasts these philosophies. Proponents of early, combined treatment, in line with KDIGO 2025 guidance, argue that the traditional paradigm of first maximizing 'supportive' care-renin-angiotensin system blockade, strict blood pressure and sodium control, and more recently SGLT2 inhibitors and mineralocorticoid receptor antagonists-before initiating immunosuppressive or other disease-directed agents embeds harmful delay. They emphasize that IgAN is driven by continuous immune activity, with ongoing production of pathogenic IgA, immune complex formation, complement activation, and glomerular injury that proceeds even when proteinuria is hemodynamically reduced. Once a critical threshold of nephron loss is crossed, self-perpetuating hyperfiltration, fibrosis, and microvascular rarefaction limit reversibility. Advocates of a more sequential strategy highlight heterogeneity in disease course, the risks and costs of polypharmacy, and the need for individualized escalation based on dynamic risk assessment. Together, the opposing yet complementary viewpoints underscore that future algorithms will likely integrate baseline risk stratification, evolving biomarkers of immune activity and chronic damage, and patient preferences to balance early, comprehensive disease control against overtreatment and toxicity in IgAN.
Russ P, Einloft J, Morgenschweis ML
… +8 more, Bedenbender S, Giesen J, Meyer HL, Rimpl LD, Hirsch MC, Ganser A, Bonventre JV, Grgic I
Clin Kidney J
· 2026 May · PMID 42131872
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BACKGROUND: Rapidly progressive glomerulonephritis (RPGN) is a prototypical nephrology emergency requiring rapid recognition and treatment. Despite the promise of immersive virtual reality (VR), nephrology lacks VR-based...BACKGROUND: Rapidly progressive glomerulonephritis (RPGN) is a prototypical nephrology emergency requiring rapid recognition and treatment. Despite the promise of immersive virtual reality (VR), nephrology lacks VR-based emergency training. Building on our initial VR simulation, we evaluated the feasibility, acceptance and effectiveness of large-scale curricular implementation. METHODS: On the STEP-VR platform, we embedded a custom three-dimensional RPGN case as a mandatory internal medicine module for fifth-year students. Knowledge was measured pre- and post-training. Instructional design effects were tested by comparing tutor-guided versus tutorless sessions and by examining a pretesting effect. Acceptance and simulation sickness were surveyed. RESULTS: A total of 408 students participated (mean age 25.4 years, 59.6% female). In the pretest-posttest cohort, knowledge increased after training (overall relative gain +101%; < .001, Cohen's = 1.30). After adjustment, tutor-guided sessions yielded higher posttest scores than tutorless sessions (+5.5 points on a 0-49 scale). Between-cohort posttest comparisons suggested an exploratory forward-testing effect ( ≤ .01). Improvements spanned RPGN recognition, urine sediment examination, laboratory and histology interpretation and hyperkalaemia management. Acceptance was high and simulation sickness was infrequent. CONCLUSIONS: This study demonstrates the successful large-scale curricular integration of VR-based training for nephrology emergencies, confirming its feasibility and educational effectiveness. By sustainably embedding immersive VR into medical education, this approach bridges a long-standing training gap in nephrology, enhances clinical competencies, increases student engagement with the specialty and may contribute to long-term efforts to address the nephrology workforce shortage.
Chinnappa S, Van Craenenbroeck AH, Dounousi E
… +8 more, Fernandez-Fernandez B, Iatridi F, Piko N, Stegbauer J, Torino C, Vogt L, Valdivielso JM, Mark PB
Clin Kidney J
· 2026 May · PMID 42125079
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Hypertension is extremely common among individuals with kidney disease undergoing haemodialysis, with an estimated prevalence exceeding 80%. However, uncertainties remain on how best to manage hypertension in this group....Hypertension is extremely common among individuals with kidney disease undergoing haemodialysis, with an estimated prevalence exceeding 80%. However, uncertainties remain on how best to manage hypertension in this group. This review discusses in detail the diagnosis, mechanism, and more importantly the management of hypertension in patients on haemodialysis presented as '10 tips' for easy application in day-to-day clinical practise.
Pacini GS, Manfro AG, Schuchmann RA
… +7 more, Junior VCB, Perez AV, Schneider ET, Backes LLA, Steckert GV, Manfro RC, Bauer AC
Clin Kidney J
· 2026 May · PMID 42111898
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BACKGROUND: Percutaneous kidney allograft biopsy is essential for evaluating graft dysfunction, but post-procedural bleeding remains the most frequent complication, particularly among recipients with impaired renal funct...BACKGROUND: Percutaneous kidney allograft biopsy is essential for evaluating graft dysfunction, but post-procedural bleeding remains the most frequent complication, particularly among recipients with impaired renal function. Desmopressin (DDAVP) is often used prophylactically to reduce bleeding risk, yet its efficacy in the transplant setting remains uncertain. METHODS: We conducted a single-center, double-blind, randomized, placebo-controlled trial at a quaternary transplant center in Brazil. Adult kidney transplant recipients with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² undergoing allograft biopsy were randomized (1:1) to receive intravenous desmopressin (0.3 μg/kg) or placebo before biopsy. All procedures were ultrasound-guided and performed by experienced nephrologists. The primary endpoint was any biopsy-related bleeding complication. Secondary outcomes included major bleeding (transfusion, embolization, nephrectomy, or death), minor bleeding (macroscopic hematuria, hematoma, hemoglobin drop >20%), and hyponatremia. RESULTS: A total of 96 biopsies were randomized (48 per group). Baseline demographics, clinical, and procedural characteristics were well balanced. Any biopsy-related bleeding complication occurred in 29.1% of procedures overall, without a significant difference between the desmopressin and placebo groups (35.4% vs. 22.9%, = .262). One major bleeding event occurred in the desmopressin group (2.1%) and none in the placebo group ( = 1.00). Minor bleeding was more frequent with desmopressin-treated patients (35.4% vs. 22.9%, = .262) than in placebo, but without statistical significance. In adjusted analyses using penalized logistic regression, desmopressin was not associated with reduced bleeding risk [OR 1.61 (95%CI 0.63-4.20)]. By contrast, surveillance biopsies were independently associated with a markedly higher risk of minor bleeding compared with indication biopsies (adjusted OR 10.2; 95%CI 1.8-68.7). No cases of hyponatremia were documented, and adverse events were rare and balanced across groups. CONCLUSIONS: In this trial of high-risk kidney transplant recipients, prophylactic desmopressin did not reduce biopsy-related bleeding complications compared with placebo. Routine pre-biopsy administration is not supported when biopsies are performed under optimal technical conditions and patient preparation.