Study
Design and Methods: 337 patients aged 18-70
were enrolled into this multicentre, prospective, open-label, randomised
controlled trial. Key inclusion criteria
included biopsy proven IgA Nephropathy, 0.75g/day proteinuria, together with
hypertension (defined as ≥140/90), impaired renal function (eGFR<90ml/min)
or both.
All patients underwent an initial six month
period of supportive care which included maximal recommended or tolerated RAAS
blockade, cholesterol lowering with statins and smoking cessation advice. At the end of this period those with proteinuria
between 0.75 and 3.5g per litre were eligible for randomisation into immunosuppression
or continuation of supportive care groups. This is important as previous
studies have discontinued RAAS inhibition before recruitment.
Allowing for dropout and exclusion, 162
patients were randomised with 80 for supportive care and 82 for immunosuppression. Demographics of the two arms were not
significantly different and enrolment was for three years. In the immunosupression arm, those with an
eGFR of ≥60 received 1g IV methylprednisolone on the first three days of months
1,3 and 5 and otherwise 0.5mg/kg prednisolone on all other days for the
duration of the study. Those with an
eGFR of ≤30 received cyclophosphamide 1.5mg/kg/day for three months, then azathioprine
1.5mg/kg/day for months 4 to 36 together with prednisolone daily at a dose of
40mg daily tapered to 7.5mg from month 7.
Endpoints were:
1) Remission of IgA nephropathy defined as urine protein: creatinine
ration <0.2g/24hours and stable renal function defined as a fall in eGFR of
<5ml per minute per 1.73m² from baseline.
2) Fall in eGFR >15ml per minute per 1.73m² from baseline.
Take
home messages:
Importantly, 34% of patients had <0.75g proteinuria per day at six
months, with supportive care alone, further underlining the importance of this
treatment strategy.
At three years, 5% of patients in the
supportive care as compared with 17% in the immunosuppression arm had achieved
a complete remission (p=0.001). However
between the same groups there was no significant difference in the number with
a stable eGFR.
At the end of three years there was also no
significant difference in those having a decrease in eGFR ≥15ml per minute per
1.73m², 22 of 80 in supportive care versus 21 of 82 in the immunosuppression
group. .
While there was no difference in overall
adverse events between the groups, predictably there was a significantly
increased rate of impaired glucose tolerance in the immunosuppression arm,
together with higher trends for infection, malignant neoplasm and indeed there
was one sepsis related death in the immunosuppression group.
Discussion: The authors should be commended
for the good design, adherence to and implementation of KDIGO guidance. I think what this trial demonstrates best is
that aggressive conservative therapy may lead to good outcomes in proteinuric
IgA Nephropathy. The benefit of immunosuppression has not been demonstrated,
particularly when the toxicity of the regimes are considered. Our practice will
therefore be unlikely to change based on these results.
Post by Andrew McClarey,
Royal Infirmary of Edinburgh
