Management of acute toxic nephrosis

Abstract Acute toxic nephrosis is a distinctive clinical syndrome, with a striking uniformity of clinical manifestations, clinical course, laboratory findings, and pathology despite a varied etiology. This discussion is restricted to the acute renal injury resulting from carbon tetrachloride poisoning, hemolytic transfusion reaction and crush syndrome. The disorder usually terminates either in death or in spontaneous, complete recovery within two weeks after the initial injury. The details of a case of carbon tetrachloride poisoning (Case I) and a case of hemolytic transfusion reaction (Case II) are presented to illustrate the clinical and laboratory features of this syndrome. These cases are not presented as models of therapy. Rather, they reflect the lack of any specific therapy, the problems of management, and the fallacy of imputing therapeutic value to medical and surgical measures that are currently advocated. Both cases recovered spontaneously, diuresis occurring on the eleventh and twelfth day of illness, respectively. Recovery was substantially complete. The acute renal insufficiency of this syndrome is manifested by severe impairment of excretion of water and marked depression of tubular function. The acute, initial and persistent oliguria-anuria is followed, at times very rapidly, by fluid retention, increased circulating blood volume, circulatory overload, cardiac strain, rapid cardiac failure and pulmonary edema. Azotemia and hypertension are of subsidiary importance. Both cases demonstrate clearly that the striking clinical improvement that occurred promptly after the onset of diuresis resulted from the release of retained fluid and the relief of circulatory overload. This improvement bore no relationship to the degree of azotemia or hypertension. The generally accepted therapy of intravenous fluids in acute toxic nephrosis is challenged as being harmful as well as ineffective. Intravenous fluids, ranging from "adequate" to "massive," consistently fail to improve urinary output. The cumulative harm of excess of intake over output lies not only in aggravation of the consequences of fluid retention but also in the fact that this harm is potentiated by another, hitherto unrecognized, source of fluid retention, endogenous fluid derived from tissue destruction. Restriction of fluids, on the contrary, does not hinder the diuresis that heralds recovery. Death in acute toxic nephrosis usually occurs in from seven to eight days. Uremia is not the usual cause of death. The cardiovascular complications deserve the greater emphasis and wider recognition. Selective tubular damage is the outstanding pathological feature of this syndrome. The objections to the therapeutic implications drawn from the pathological studies in this syndrome are stated. The pathogenesis of acute toxic nephrosis still remains obscure and the mechanism of recovery is unknown. Tubular regeneration and diuresis parallel each other although evidences of tubular dysfunction persist for months after clinical recovery. None of the numerous medical and surgical procedures advocated in the treatment of acute toxic nephrosis has been found effective in a significant number of cases. The basic approach to the present treatment of this syndrome should therefore be the selection of a plan of management that will tide the patient over the acute renal injury and that will favor spontaneous recovery. It is believed that fluid restriction is the keystone of this plan of management. Fluids should be restricted below the amount that will produce manifest edema or aggravation of circulatory overload. An initial daily intake of 700 cc. of physiological saline, not necessarily intravenously, is advocated; this amount should be increased or decreased as clinical observations indicate. Other features of management and various therapeutic adjuvants are discussed. Acute toxic nephrosis can be induced experimentally by a variety of agents. Such experiments are urged to determine the efficacy of proposed therapeutic procedures and to assess the value of plans of management.