Familial gout and renal failure.

Abstract

SUMMARY Clinical gout and renal failure was seen in a 9-year-old girl. The family tree showed that 9 out of 11 young females in three generations suffered from hyperuricaemia and normal (n = 1), or impaired (n =8), renal function. One set of twins occurred in each generation and there is only one living male subject. In members with renal failure there was no improvement in renal function after treatment of hyperuricaemia, and in 2 sisters oral contraceptives appeared to precipitate hypertension. This clinical picture may be more common than is generally realised because of failure to compare blood uric acid values with suitable age-and sex-matched controls. The evidence from this family suggests that hyperuricaemia preceded the development of renal failure.Classical gout occurs most commonly in middle-aged men,1 and is extremely rare in premenopausal women or children. In children a specific metabolic abnormality resulting in gross uric acid over-productionsuch as the Lesch-Nyhan syndrome-can often be identified.2 Although at one time renal failure was common in gouty patients3 Berger and Yu4 could find no case in which death might be attributed to renal failure in 524 men with gout. Conversely, in renal failure from other causes, hyperuricaemia occurring as part of the general retention of nitrogenous waste is invariably mild even if there is severe reduction in glomerular filtration rate. Gout is rare as a primary cause of renal failure and accounts for only 08 8% in 69 400 European patients treated by dialysis (A J Wing, 1979, personal communication).

Familial Nephropathy with Hyperuricemia and Gout

“…Farebrother et al [5], therefore, hypothesized that a similar mechanism might have been working in their gouty family. With respect to our family, which is, indeed, very similar to the one just cited [27], this possibility remains purely speculative. Notably, glomerular function was al ready considerably reduced and interstitial fibrosis was present in the younger sister (case 2) at a time when serum uric acid was only moderately increased.…”

“…A few similar observations have been published [3,10,15,18,20,21,[24][25][26][27] which suggest that familial interstitial nephropathy with hyperuricemia represents a distinct en tity [11], The family mentioned above has now been fol lowed for 11 years, and the clinical data and renal biopsy findings will be described.…”

“…No salt wasting or severe anemia, a leading symptom in nephronophthisis, were reported. The blood pressure was normal in most cases, but in two families a high frequency of hypertension was noted [3,26], Interestingly enough, 2 patients described by Warren et al [27] developed malignant hypertension on oral contraceptives like our case 3.…”

“…These differences could, how ever, be coincidental. A few cases had presumably isolated hyperuricemia [3,10,18,24], but they were not sufficiently examined in order to exclude renal disease with the possible exception of the case reported by Warren et al [27] and Farebrolher et al [5], Renal disease had often been over looked in these patients, since proteinuria and hematuria were lacking. Renal concentrating capacity was always diminished as might be expected in chronic interstitial renal disease, but polyuria was never prominent.…”

“…Inheritance of renal disease has been autosomal dominant, with the exception of one family [28] with X-linked recessive inheritance which, however, differs clinically also from the other observations. In some families, members of both sexes were affected [3,10,15,24,26], but in others there were only male [18] or female [9,21,27] patients. These differences could, how ever, be coincidental.…”