No abstract

No abstract

SUMMARY In an analysis of 160 patients with fulminant hepatic failure, the frequency of renal failure in the patients who had taken an overdose of paracetamol was not significantly higher than in those with hepatic failure due to other causes. The same was found in another group of patients with less severe hepatic damage. In both the latter group and the patients with fulminant hepatic failure, the development of renal failure was closely related to the occurrence of endotoxaemia as detected by the Limulus lysate assay. These findings do not support the concept that an overdose of paracetamol has a specific nephrotoxic effect.

1. In a group of patients with cirrhosis who showed a wide range of values for the rate of renal sodium excretion, the latter was found to be inversely related to both the plasma concentration and rate of renal excretion of aldosterone. However, for a given sodium excretion the values for aldosterone were significantly lower in the patients than for a group of healthy control subjects. These findings suggest either an increased renal tubular sensitivity to aldosterone or the participation of other factors in the pathogenesis of the sodium retention. 2. Based on measurements of the rate of urine flow and the clearances of free water and inulin during a maximal water diuresis, the fractional reabsorption of sodium by the 'proximal', 'diluting segment' and 'distal' segments of the nephron was estimated. For patients retaining sodium the enhanced reabsorption occurred at both proximal and distal sites, the latter being quantitatively more important. There was no significantly enhanced sodium reabsorption in the diluting segment.

1. The intrarenal distribution of plasma flow was determined with a technique based on the analysis of the transit time of sodium o-[131I]- iodohippurate through the kidney in 43 patients with cirrhosis with near-normal total renal perfusion. 2. Twenty-five of the patients had an abnormal pattern of transit times, suggesting a redistribution of plasma flow from outer cortical to juxtamedullary nephrons. 3. Plasma renin activity ranged from below normal to six times normal and high values were found only in patients showing an abnormal pattern of transit times. The latter was also found to be related to sodium retention and a reduced renal capacity to excrete free water.

No abstract

SUMMARY Renal function was evaluated in 40 patients with fulminant hepatic failure. They were divided into two groups on the basis of glomerular filtration rates greater than 40 ml/min or less than 25 ml/min. A number of patients in group 1 had markedly abnormal renal retention of sodium together with a reduced free water clearance and low potassium excretion which could be explained by increased proximal tubular reabsorption of sodium. The patients in group 2 had evidence that renal tubular integrity was maintained when the glomerular filtration rate was > 3 ml/min (functional renal failure), but evidence of tubular damage was present when this was <3 ml/min (acute tubular necrosis).A previous study of 48 patients with fulminant hepatic failure showed that 38 had evidence of renal impairment associated with a particularly poor prognosis (Wilkinson et al., 1974a). A number of patients from that study whose renal function otherwise appeared to be normal showed marked renal retention of sodium. In the present series we studied an additional consecutive group of 40 patients to establish more precisely the functional changes occurring within the kidney, particularly the renal handling of sodium when the glomerular filtration rate is relatively well maintained. MethodsFulminant hepatic failure was caused by viral hepatitis in 10 patients (two being HBAg positive), multiple anaesthetic exposures to halothane in nine, self-induced overdose with paracetamol (16) Renal function was evaluated by inulin clearance (glomerular filtration rate), para-aminohippurate clearance (effective renal plasma flow), free water clearance (a measure of the patient's ability to excrete a water load), urinary sodium and potassium excretion, and microscopy of the sediment of a fresh urine specimen. Each patient was given a water load of 20 ml/kg body weight intravenously as 5 % dextrose, over one hour. This procedure never reduced plasma sodium concentration by more than 3 mmol/l. Inulin and para-aminohippurate were then immediately infused intravenously, initially as a loading dose followed by a constant infusion. Urine collections were made from a three-way indwelling Foley bladder catheter every 30 minutes, ensuring by air displacement that the bladder was empty. Free water clearance was calculated as the difference between maximumurinaryflowand osmolar clearance (Smith, 1956) for the 30 minute period of maximal diuresis after the water load was given. Values for inulin and para-aminohippurate clearance, corrected to a body surface of 1-73 sq.m were calculated from the mean of three consecutive 30 minute clearances-the first beginning 30 minutes after the loading doses of inulin and para-aminohippurate. Blood samples for osmolality, inulin, and paraaminohippurate concentrations were taken at the midpoint of each clearance period. Inulin and para-501

Summary Abnormal renal retention of sodium is a characteristic finding in both cirrhosis and fulminant hepatic failure. In cirrhosis the pathogenesis varies according to the level of renal perfusion. When this is normal, hyperaldosteronism is probably the most important factor and this results from an increased release of renin by the kidney. The stimulus to the latter may be a shunting of blood from the outer cortical to juxtamedullary nephrons, although there is no direct relationship between the changes in intrarenal blood flow distribution and sodium excretion. The patients with hyperaldosteronism fail to escape from its sodium retaining effects because of impaired production of natriuretic hormone, which in turn is the result of a failure to expand the ‘effective’ extracellular fluid volume, because of ascites formation. In fulminant hepatic failure the site in the nephron of abnormal sodium retention appears to be predominantly the proximal tubule, but its cause is obscure.