A recent Nephrology digest,
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Study Type: Expert commentary / guideline appraisal (KDOQI work group review of the 2025 AHA/ACC hypertension guideline). Not original research.

Key Question: How do the 2025 AHA/ACC blood pressure recommendations apply to people at risk of CKD or with non-dialysis CKD (stages 1-5)?

Key Findings:

• The AHA/ACC guideline adopts the PREVENT calculator, which incorporates kidney and metabolic parameters, addressing the historical omission of CKD from cardiovascular risk prediction.
• It retains a broad BP target of <130/80 mmHg and offers recommendations on complex and resistant hypertension.
• The work group supports most recommendations. Where the guideline is silent (medication interactions, electrolyte disturbance, kidney injury), it offers expert opinion and flags areas of limited evidence or needing CKD-specific consideration. The abstract does not specify which.

Clinical Relevance: UK clinicians should note the shift towards PREVENT-based risk assessment and consider how US-derived targets compare with NICE and UK Kidney Association guidance when managing hypertension in CKD.

Limitations: The abstract does not detail the specific areas of disagreement or the strength of evidence, and the commentary excludes dialysis patients and reflects US practice and expert consensus.

Study Type: Retrospective case series (n=18), two US nephropathology archives (Mayo Clinic, Columbia), 2011–2025.

Key Question: What are the clinicopathologic features, haematological associations and outcomes of glomerulopathy with striated deposits (GSD)?

Key Findings:

• Typical presentation was in older patients (median age 73) with CKD (median creatinine 2.6 mg/dl), nephrotic-range proteinuria (3.8 g/day) and haematuria (80%). Most (67%) showed an MPGN pattern; 88% had an associated haematological condition, mainly MGRS (56%).
• 56% had monotypic Ig deposits (IgGκ in 7), often masked on standard IF (6/10) and requiring pronase digestion; 6/10 had a matching circulating monoclonal Ig.
• Over median 14 months' follow-up, 40% (6/15) progressed to kidney failure (median 11 months), including one allograft recurrence. All 4 evaluable patients treated with clone-directed therapy had a kidney response.

Clinical Relevance: In older patients with MPGN-pattern disease and a paraprotein, GSD (with monotypic deposits) should be considered an MGRS lesion; requesting pronase-digested IF in apparent Ig-negative biopsies may unmask it.

Limitations: Small, retrospective, referral-based cohort without controls; treatment-response data are limited to four patients, so therapeutic conclusions are tentative.

Study Type: Prospective cohort study with external validation cohort (CRIC)

Key Question: Are urinary tryptophan-kynurenine pathway metabolites associated with CKD progression in people with type 2 diabetes?

Key Findings:

• In 1,892 Southeast Asian participants (224 events, median follow-up 7.2 years), each 1-SD rise in urinary kynurenine, 3-hydroxykynurenine, kynurenic acid and KTR conferred adjusted HRs of 1.60, 1.64, 1.47 and 1.97 respectively for kidney failure or creatinine doubling.
• Associations were stronger in those with eGFR <60 ml/min/1.73m².
• In CRIC validation (n=951), only tryptophan (HR 1.60) and kynurenine (HR 1.35) remained independently associated, so replication was partial.

Clinical Relevance: These metabolites may represent novel prognostic biomarkers or pathway targets in diabetic kidney disease, though they are not yet applicable to UK practice.

Limitations: Observational design with unmeasured confounding, and limited consistency between cohorts; incremental predictive value over established markers (eGFR, ACR) was not reported.

Study Type: Prospective paired cohort study (single centre, Thailand; n=100 hospitalised adults with AKI)

Key Question: How reliably do spot UPCR and UACR reflect 24-hour urinary excretion during active AKI compared with after resolution?

Key Findings:

• Agreement with 24-hour collections was lower during AKI (Lin's CCC: UACR 0.81, UPCR 0.68) than after resolution (UACR 0.89, UPCR 0.83; p=0.001).
• Limits of agreement were wide during AKI (UACR 0.22–8.37; UPCR 0.31–7.99) and narrowed after resolution (UACR 0.40–5.48; UPCR 0.47–4.91).
• Spot ratios overestimated 24-hour values by 36–56% in both phases. Unreliability was greatest with preserved baseline function, severe AKI and haemodynamic aetiology.

Clinical Relevance: Spot ACR/PCR are routinely used in UK practice, so caution is needed when using them to define baseline proteinuria or judge treatment response during AKI, particularly when deciding on investigation or immunosuppression.

Limitations: Single-centre, exclusively inpatient cohort with resolution defined by serum creatinine alone, limiting generalisability to milder or outpatient AKI.

Study Type: Observational target trial emulation (propensity-matched new-user cohort) using USRDS/Medicare data, 2014–2019.

Key Question: In haemodialysis patients with newly diagnosed AF, does initiating apixaban versus warfarin reduce ischaemic stroke and clinically important bleeding?

Key Findings:

• Among 3978 matched pairs (median CHA2DS2-VASc 4), apixaban was associated with 34% lower ischaemic stroke (HR 0.66; 95% CI 0.47–0.94) in intention-to-treat analysis.
• Clinically important bleeding was 28% lower with apixaban (HR 0.72; 95% CI 0.63–0.83).
• No difference in all-cause mortality; negative control outcomes (hip fracture, pneumonia) were null, and results held in patients with CHA2DS2-VASc ≥2.

Clinical Relevance: Supports apixaban as the preferred OAC over warfarin in UK haemodialysis patients with AF, though trial evidence in this population remains limited.

Limitations: Residual confounding is possible given the observational design, and median treatment durations were short (apixaban 58 days, warfarin 93 days), with US Medicare data limiting generalisability to UK practice.

Study Type: Prospective observational cohort study (CRIC), with Cox regression and mediation analysis.

Key Question: Are elevated depressive symptoms associated with incident peripheral arterial disease (PAD) in adults with mild to moderate CKD?

Key Findings:

• Of 2,757 participants, 25% had elevated depressive symptoms (BDI ≥11) at baseline; 24% developed incident PAD over a median 10 years. Incidence was 3.6 vs 2.2 events per 100 person-years with and without elevated symptoms.
• Adjusted HR for incident PAD was 1.23 (95% CI 1.02-1.47), with similar results for the composite of PAD or death and at higher BDI thresholds (>14, ≥16).
• Smoking and physical inactivity mediated about 20% and 10% of the association respectively.

Clinical Relevance: Depressive symptoms may be a modifiable marker of PAD risk in CKD, supporting mood screening and attention to smoking cessation and physical activity in UK renal clinics.

Limitations: Observational design with residual confounding, and depressive symptoms were measured by questionnaire without a clinical depression diagnosis (US cohort, mild to moderate CKD only).

Study Type: Longitudinal registry-based cohort study (Australia, dialysis initiation 1965–2023).

Key Question: How do mortality and transplant waitlisting after kidney failure differ between IgA nephropathy, diabetic kidney disease and other glomerular diseases?

Key Findings:

• Versus other glomerular disease, IgAN had lower all-cause mortality (HR 0.69, 95% CI 0.65–0.73) and cardiovascular mortality (HR 0.67, 0.60–0.74), and higher waitlisting rates (HR 1.55, 1.39–1.73).
• Versus IgAN, DKD had higher all-cause (HR 1.58, 1.53–1.64) and cardiovascular mortality (HR 1.81, 1.71–1.91), lower cancer mortality (HR 0.82, 0.70–0.95) and lower waitlisting (HR 0.64, 0.60–0.69).
• Age-standardised IgAN incidence was stable over two decades (EAPC −0.01%, −0.80 to 0.78).

Clinical Relevance: Reinforces the better prognosis of IgAN-related kidney failure and suggests that waitlisting disparities, particularly for DKD, may merit scrutiny in UK transplant assessment pathways, although the data are Australian.

Limitations: Residual confounding and diagnostic misclassification from variable biopsy practice, so aetiology attribution may be imperfect.

Study Type: Exploratory post hoc biomarker analysis of a Phase 2 RCT (SANCTUARY; n=60 IgAN participants vs 25 healthy donors).

Key Question: Does terminal complement (C5) inhibition with ravulizumab alter urinary biomarkers of complement activation, renal inflammation and tubular injury in IgAN?

Key Findings:

• At baseline, urinary sC5b-9, Ba, CD163 and KIM-1 (creatinine-normalised) were significantly higher in IgAN than healthy donors (P<0.001); 93% had elevated sC5b-9/Cr. Levels were higher with proteinuria >2 g/day, and sC5b-9 and Ba were highest at eGFR 30–60.
• Ravulizumab produced greater reductions than placebo in sC5b-9 and Ba from Week 2, and in CD163 and KIM-1 from Week 10 (all P<0.05).
• Reductions were sustained to Week 50 and seen after placebo-to-ravulizumab crossover at Week 26.

Clinical Relevance: Supports a mechanistic link between intrarenal complement activation, inflammation and tubular injury in IgAN, and suggests urinary sC5b-9 could aid identification of patients who might benefit from complement-targeted therapy.

Limitations: Small, exploratory analysis with no adjustment for multiplicity; biomarker changes are not shown to predict eGFR or long-term kidney outcomes.