The edition · Nephrology
Obinutuzumab beat tacrolimus six-fold on complete remission in membranous nephropathy - and the eGFR endpoint did not follow
In MAJESTY, 37% versus 6% reached complete remission at two years. But the hierarchical testing stopped at sustained eGFR decline, which showed no significant effect - so everything below it in the sequence is descriptive.
The edition in brief
Four findings and a pearl for the nephrology desk. A meta-analysis of 14 randomised trials in 934 patients on maintenance haemodialysis found intradialytic exercise improved left ventricular ejection fraction by 2.21% (95% CI 0.28 to 4.15), reduced pulse wave velocity by 1.36 m/s (-2.58 to -0.13) and diastolic blood pressure by 4.54 mmHg (-7.57 to -1.51), with peak oxygen uptake up 2.76 mL/kg/min but heterogeneity of 90%; left ventricular mass index and systolic pressure were unchanged, and certainty was moderate at best. A randomised crossover trial in 32 patients across two Turkish units found standardised intradialytic feeding did not compromise urea reduction ratio or Kt/V and did not worsen fatigue, but was associated with larger falls in blood pressure, particularly in the second hour. A meta-analysis of 15 trials published between 1974 and 2021 found nandrolone decanoate increased lean body mass by 2.63 kg (95% CI 1.60 to 3.65) in CKD, with haemoglobin and haematocrit estimates favouring it at very low certainty and sparse long-term safety data. The practice-changer is MAJESTY, published in June: 142 adults with primary membranous nephropathy randomised to intravenous obinutuzumab or oral tacrolimus, with complete remission at week 104 in 37% versus 6%, an adjusted difference of 31 percentage points (95% CI 18 to 44). Grade 3 or higher adverse events were 22% against 19%. The hierarchical testing sequence stopped at sustained eGFR reduction, which showed no significant treatment effect. Plus a pearl on why eGFR should not be used in a patient whose creatinine is moving.
Intradialytic exercise moves ejection fraction and arterial stiffness, not ventricular mass
Set up structured intradialytic exercise for its effect on fitness, ejection fraction and arterial stiffness - and do not expect it to reduce ventricular mass.
Feeding during dialysis did not reduce clearance - but did lower blood pressure
Allow intradialytic feeding for nutritional reasons - clearance is unaffected - but monitor blood pressure closely through the second hour.
Nandrolone adds 2.6 kg of lean mass in CKD, on evidence largely from the 1980s
Nothing to prescribe: the lean mass signal is real but the evidence base is decades old and the safety data are absent.
An eGFR is meaningless while the creatinine is moving
While creatinine is moving, dose from the trend and the clinical picture - the automatically reported eGFR is invalid and will overestimate function.
Obinutuzumab reached complete remission in 37% of primary membranous nephropathy against 6% on tacrolimus
In primary membranous nephropathy needing immunosuppression, obinutuzumab produced complete remission six times more often than tacrolimus at two years - though the renal function endpoint was not met.
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