The edition · Nephrology
A blood test for NELL1 membranous nephropathy that tracks proteinuria, and ferric citrate matches sevelamer while treating the anaemia
A luciferase immunoassay detects and monitors NELL1 autoantibodies without a biopsy, an iron-based binder is non-inferior on phosphate and better on haemoglobin, and low vitamin D tracks with CKD progression on evidence graded very low.
The edition in brief
A luciferase immunoprecipitation assay for NELL1 autoantibodies, built on an N-terminal fragment of the protein, showed 90% sensitivity and 100% specificity against 20 biopsy-proven NELL1-positive and 20 PLA2R-positive comparison sera, with better specificity than ELISA. In an independent cohort of 63 membranous nephropathy cases and 20 controls it identified six positives, and in three patients followed longitudinally antibody levels tracked proteinuria - the pattern that makes PLA2R antibody monitoring useful. In a phase 3 open-label non-inferiority trial, 239 Chinese patients on maintenance haemodialysis received ferric citrate or sevelamer carbonate for 12 weeks. Serum phosphate fell 0.70 mmol/L with ferric citrate and 0.61 with sevelamer (least-squares mean difference -0.09, 95% CI -0.24 to 0.05, non-inferiority margin 0.32). Target achievement was 49.1% against 48.3%. Ferric citrate improved iron parameters and haemoglobin; gastrointestinal events were the commonest adverse events in both arms. An eleven-study dose-response meta-analysis found vitamin D deficiency associated with 33% higher odds of chronic kidney disease progression (OR 1.33, 95% CI 1.06-1.67), and 18% higher odds per 10 ng/mL lower 25-hydroxyvitamin D. Heterogeneity was extreme (I-squared 98.2%) and GRADE certainty was rated very low, so the authors explicitly do not support routine screening or supplementation on this basis. An Indian open-label pilot randomised 60 adults with type 2 diabetes and subclinical hypothyroidism on background SGLT2 inhibitor therapy to levothyroxine or none. Albuminuria fell in the treated group and rose in controls, significant per protocol but not by intention to treat. The FDA acted on a supplemental application for empagliflozin-metformin (Synjardy).
Ferric citrate matched sevelamer on phosphate and raised the haemoglobin as well
Ferric citrate was non-inferior to sevelamer for phosphate control in haemodialysis and improved iron parameters and haemoglobin, making it the sensible binder where iron deficiency coexists.
Low vitamin D tracks with kidney disease progression, on evidence graded very low
Lower vitamin D was associated with faster chronic kidney disease progression, but with very low certainty and extreme heterogeneity, so it is not a reason to screen or supplement for renal protection.
Levothyroxine and albuminuria: an Indian pilot that says the trial is worth doing
In a 60-patient pilot, levothyroxine for subclinical hypothyroidism reduced albuminuria per protocol but not by intention to treat, which makes it a reason for a larger trial and not a reason to prescribe.
FDA acts on a supplement for empagliflozin-metformin
The FDA acted on a supplement for empagliflozin-metformin with no published detail; the standing clinical point is to unbundle fixed-dose combinations as eGFR falls, because only the metformin component needs stopping.
Send the PLA2R antibody before the biopsy report comes back
Send a PLA2R antibody with a baseline titre at the presentation of adult nephrotic syndrome, because it informs the biopsy decision and gives you the marker that moves before proteinuria does.
A serum assay for NELL1 membranous nephropathy that follows the disease
A new serum assay identified NELL1-associated membranous nephropathy with 90% sensitivity and 100% specificity and its titres tracked proteinuria, pointing to serological monitoring for a subtype that currently needs a biopsy - though the test is not yet available.
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