Early treatment with allopurinol in familial juvenile hyerpuricaemic nephropathy (FJHN) ameliorates the long-term progression of renal disease

Background: The efficacy of allopurinol in autosomal dominant familial juvenile hyperuricaemic nephropathy (FJHN) has been disputed. Aim: To address this question, in the absence of controlled trials. Design: Retrospective long-term follow-up study. Methods: All kindreds were biochemically screened. Measurements included uric acid clearance, creatinine clearance, serum creatinine, and glomerular filtration rate (GFR). We used five siblings who had died or progressed to transplantation, ten other deceased relatives, and two index cases (one untreated, one non-compliant) as controls to assess the effects of allopurinol. Results: Of eight families with FJHN, six had a strong history of renal disease and early parental death (mean age 41 years, n = 10). Of 27 patients started immediately on allopurinol and treated uninterruptedly, 21 responded well, including three children born subsequently. Eight siblings (mean age 19 years) with a normal plasma creatinine at start (< 120 mu mol/l, mean GFR 80 ml/min/1.73 m(2)) retained stable renal function (mean 14.5 years, mean age 34 years, GFR 85 ml/min/1.73 m(2)). Of the 13 other responders, treated for up to 34 years, 10 with a creatinine <200 mumol/l at diagnosis (mean age 28 years, mean creatinine 137 mumol/l at start) now have a mean creatinine of 210 mumol/l. In contrast, five patients (mean age 26 years) with a creatinine >200 mumol/l (GFR <35 ml/min/ 1.73 m(2)) when allopurinol commenced, plus one untreated index case, all progressed rapidly (mean 6 years) to end-stage renal failure. In two others (one non-compliant, one initially untreated), GFR fell by >50% in 7 years. Introduction of allopurinol in the latter has stabilized GFR. Discussion: Allopurinol reduced the morbidity and mortality from renal failure seen in untreated siblings and previous generations of these families. Early diagnosis of FJHN is important, so that treatment can begin before irreversible renal damage has developed.