Ammonia-complement interaction in the pathogenesis of progressive renal injury

K. A. Nath, M. K. Hostetter, T. H. Hostetter

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Our studies lead us to propose enhanced ammoniagenesis as a maladaptive component of the response of surviving nephrons to loss of renal mass. An initial renal injury of any type leads to reduction in nephron number. Residual nephrons respond by increasing ammoniagenesis. In a teleologic sense, this serves to maintain net acid excretion over the short term. However, the elevations in ammonia concentrations lead to reaction with the complement component C3 circulating through adjacent peritubular capillaries and the promotion of interstitial inflammation and tubular cell injury. This event would complete a vicious cycle whereby further nephron mass would be lost and the perpetuation of renal injury achieved. Such a mechanism may underlie the peritubular deposition of complement components including C5b-9 noted in a wide variety of renal diseases including nephritic and non-nephritic disorders. While assorted immunoglobulin classes may contribute to complement activation in nephritic, immunologic disorders, the mechanism activating complement in such non-nephritic diseases as diabetic and hypertensive renal disease is unknown. Increased ammoniagenesis with attendant alternative pathway activation provides a potential mechanism. These studies also raise issues of whether the beneficial effects of dietary protein restriction may reside, in part, on the obligate and concomitant diminution in net acid load, and whether clinically salutary results could be obtained in patients with reduction of dietary acid by general restriction of dietary protein, by selective reduction in the acid components of the diet, or by exogenous alkali supplements.

Original languageEnglish (US)
Pages (from-to)S52-S54
JournalKidney international
Issue numberSUPPL. 27
StatePublished - Jan 1 1989

ASJC Scopus subject areas

  • Nephrology


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