A recent Nephrology digest,
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Study Type: Case report

Key Question: Can a novel CFHR5 genetic variant cause postpartum atypical haemolytic uraemic syndrome with collapsing focal segmental glomerulosclerosis?

Key Findings:

• A 21-year-old woman developed postpartum aHUS with collapsing FSGS following HELLP syndrome, associated with a novel heterozygous CFHR5 deletion producing a truncated FHR5 protein
• Functional assays demonstrated abnormal C5b-9 complement formation on endothelial cells, confirming complement dysregulation
• Patient recovered with plasma infusion and supportive care, with only mild residual proteinuria

Clinical Relevance: This expands the genetic spectrum of complement-mediated aHUS and suggests complement testing should be considered in postpartum TMA cases within NHS nephrology services, even without overt complement consumption.

Limitations: Single case report limits generalisability of the novel CFHR5 variant's pathogenic role.

Study Type: Retrospective cohort study

Key Question: How does the PREVENT cardiovascular risk score perform compared to established risk calculators for predicting combined cardiovascular and kidney outcomes in patients with chronic kidney disease?

Key Findings:

• PREVENT-CVD demonstrated superior predictive accuracy for cardio-kidney outcomes (C-statistic 0.688, 95% CI 0.675-0.701) compared to PREVENT-ASCVD, Pooled Cohort Equation, and SCORE2 in 4,268 CKD patients
• The superiority was primarily driven by robust prediction of major adverse kidney events, with improvements in discrimination also seen for cardiovascular events and mortality
• Adding albuminuria to the PREVENT score further enhanced predictive performance for the primary composite outcome

Clinical Relevance: This validates PREVENT as a potentially useful tool for UK nephrology services to risk-stratify CKD patients for both cardiovascular and kidney outcomes, supporting integrated cardio-nephrology care pathways.

Limitations: The study was retrospective and may not fully represent the diversity of UK CKD populations given the Korean and US cohorts studied.

Study Type: Experimental study using rat and mouse models of ANCA-associated vasculitis

Key Question: Does canagliflozin have therapeutic effects in ANCA-associated vasculitis beyond its established nephroprotective properties?

Key Findings:

• Canagliflozin reduced kidney injury, pulmonary haemorrhage, and T-cell infiltration in experimental AAV models
• Treatment suppressed pathogenic Th1 and Th17 cell responses and reduced IFN-γ and IL-17A secretion upon restimulation
• The immunomodulatory effect was mediated through inhibition of p38 and ERK MAPK phosphorylation in activated T cells

Clinical Relevance: This suggests SGLT2 inhibitors may offer dual nephroprotective and immunomodulatory benefits in AAV patients, potentially informing treatment strategies beyond current immunosuppressive regimens in UK nephrology practice.

Limitations: Pre-clinical animal model findings may not translate directly to human AAV pathophysiology and treatment responses.

Study Type: Experimental study using mouse models with translational validation

Key Question: Does platelet activating factor receptor (PTAFR) in renal tubular epithelial cells contribute to AKI-to-CKD progression?

Key Findings:

• Tubule-specific PTAFR knockout mice showed reduced tubular injury and fibrosis after ischemia-reperfusion injury
• PTAFR promotes G2/M cell cycle arrest through suppressing MDM2-mediated p53 degradation, contributing to maladaptive repair
• Phosphatidylethanolamine (18:0/18:1) was identified as an endogenous PTAFR ligand, with urinary levels distinguishing AKI patients from controls and correlating with kidney dysfunction

Clinical Relevance: This identifies PTAFR as a potential therapeutic target for preventing CKD progression after AKI, with urinary phosphatidylethanolamine potentially serving as a biomarker for AKI in NHS practice.

Limitations: Findings are primarily from mouse models with limited human validation beyond urinary biomarker correlation.

Study Type: Systematic review and meta-analysis

Key Question: Does remote ischemic preconditioning prevent contrast-associated acute kidney injury in patients undergoing coronary angiography or percutaneous coronary intervention?

Key Findings:

• Remote ischemic preconditioning significantly reduced contrast-associated AKI (RR 0.54, 95% CI 0.45-0.65) across 30 RCTs involving 5,078 participants with high-certainty evidence
• In-hospital major adverse cardiovascular events were probably reduced (RR 0.51, 95% CI 0.26-0.98) with moderate-certainty evidence
• No significant differences in dialysis requirement, in-hospital mortality, or 30-day outcomes

Clinical Relevance: This provides high-quality evidence supporting remote ischemic preconditioning as a simple, cost-effective intervention to prevent contrast-associated AKI in NHS cardiac catheter laboratories, potentially reducing healthcare costs and improving patient outcomes.

Limitations: The meta-analysis included studies with varying definitions of contrast-associated AKI and different remote ischemic preconditioning protocols, which may affect generalisability.

Study Type: Retrospective cohort study

Key Question: What are the clinical safety limits and optimal strategies for HLA antigen delisting to expand transplant opportunities in highly sensitized kidney transplant candidates?

Key Findings:

• Delisting significantly improved transplant probability only for candidates with calculated panel-reactive antibody (cPRA) ≥96.6%, requiring 2-fold increase in donor offers at 99% cPRA and 3-fold increase at 98% cPRA
• Recipients with persistent donor-specific antibodies >2000 mean fluorescence intensity at transplant had significantly higher risk of graft loss or death (24.4% vs 10.7%)
• Patients whose historical antibodies fell below 2000 mean fluorescence intensity before transplant had comparable outcomes to antibody-negative recipients despite early post-transplant antibody rebound

Clinical Relevance: This evidence could inform UK transplant centres considering antigen delisting strategies for highly sensitized patients, particularly given similar challenges with organ allocation and sensitized populations in the NHS transplant system.

Limitations: Retrospective design from selected elite French centres may limit generalizability to broader transplant populations and different healthcare systems.

Study Type: Commentary/review

Key Question: How do existing KDIGO guidelines address the components of cardiovascular-kidney-metabolic (CKM) syndrome?

Key Findings:

• KDIGO guidelines comprehensively cover CKM syndrome components through disease-specific guidance on CKD, blood pressure, diabetes, lipids, and upcoming heart failure recommendations
• Guidelines emphasise early detection and intervention, comprehensive cardiovascular-kidney risk management, and multidisciplinary care approaches
• KDIGO framework addresses the interconnected nature of obesity, diabetes, hypertension, dyslipidemia, cardiovascular disease, and CKD within the formally recognised CKM syndrome

Clinical Relevance: UK nephrology clinicians should recognise that existing KDIGO guidelines already provide integrated approaches for managing the newly formalised CKM syndrome, supporting comprehensive care delivery within NHS multidisciplinary teams.

Limitations: This is a review of existing guidelines rather than original research evaluating clinical outcomes.

Study Type: Randomized controlled trial (phase 2a)

Key Question: Does CFTR inhibitor GLPG2737 slow kidney growth and preserve function in adults with rapidly progressing ADPKD?

Key Findings:

• No difference in height-adjusted total kidney volume growth between GLPG2737 and placebo (8.2% vs 9.2% increase; difference -0.91%, 95% CI -4.34% to 2.64%, p=0.61)
• No significant difference in eGFR decline between groups (difference -2.31 mL/min/1.73m², 95% CI -5.64 to 1.02, p=0.17)
• Similar safety profiles with treatment-related adverse events in 30% vs 27% of patients

Clinical Relevance: This negative study indicates CFTR inhibition is not a viable therapeutic target for ADPKD, informing UK nephrology practice away from this mechanism for slowing disease progression.

Limitations: Early termination after the double-blind period due to lack of efficacy may have limited assessment of longer-term effects.