Carlo Smorlesi

Functional Renal Alterations in Chronic Liver Diseases

83 patients with chronic active hepatitis (CAH), 38 of them with cirrhosis, were studied and compared with 10 control subjects suffering from chronic persistent hepatitis (CPH). Tubular acidosis frequently was found in our cases. Renal plasma flow and glomerular filtration rate were significantly decreased in CAH when compared with CPH. Selective renal arteriography showed evident decrease of arterial flow in the outer cortex. Selective renal scan with 99mTc microspheres of human albumin showed a frequent escape of the tracer from the kidney to the lung. PGE1 and PGE2 levels appeared higher in the renal artery than in the vein and were significantly more elevated in 9 cases with cirrhosis vs. 13 controls. These results suggest the frequent functional impairment of the kidney also in the early stages of CAH, with an increase of PGE levels and an opening of intrarenal shunts.

HBV and HCV infection in i.v. drug addicts; coinfection with HIV

A group of 122 drug addict patients were studied to evaluate the incidence of HIV, HBV, HCV infections and of laboratory findings of hepatic damage. Our data show that hepatic damage is more frequent in patients affected by HBV-HCV coinfection than those with HBV or HCV infection alone and that HIV positivity supports HBV-HCV coinfection.

Systemic Hemodynamics and Renal Function in Cirrhotic Patients during Plasma Volume Expansion

Systemic hemodynamic impairment (hepatocirculatory failure) has been suggested as one of the possible factors which may explain the renal hemodynamic alterations found in the late stage of liver cirrhosis, typical of the hepatorenal syndrome. 20 patients, divided into two groups of 10 sodium retainers and 10 sodium excretors, affected by liver cirrhosis with portal hypertension and ascites, were studied. Renal functional parameters (diuresis, urinary and plasma electrolytes, urine to plasma osmolality and creatinine ratios and creatinine clearance) were evaluated before and after acute volume expansion with 1,000 ml of 10% dextran in saline, infused through a catheter located in the right atrium. Hemodynamic tests (cardiac index, systemic vascular resistance, right atrial pressure and capillary wedge pressure) were performed before, during and after expansion. Cardiac index decreased in 6 patients (sodium excretors) after a 500-ml infusion and rose again after 1,000 ml in 5 of them. The remaining 14 patients showed a progressive and significant increase of cardiac index. A strong inverse relationship between cardiac index and systemic vascular resistance was observed (r = -0.87; p less than 0.001). The mean left-ventricular function curve showed a slow response in most sodium excretors and a normal response in the sodium-retaining group, without significant difference between the two groups. Sodium excretion significantly improved after expansion in both groups of patients. No relationship was found between hemodynamic response and renal function. These data show that cardiocirculatory function is normal, even in sodium-retaining cirrhotics.

Vasoactive factors in the mechanism of renal sodium handling in cirrhotics: The effect of acute plasma expansion

Twenty cirrhotic patients with ascites, divided into two groups of 10 each, according to their daily urinary sodium excretion (sodium retainers and sodium excretors) and given a diet of 75 mEq of sodium daily, underwent acute plasma volume expansion with 1,000 ml of 10% dextran in saline, infused through a catheter located in the right atrium. Even if a significant increase in sodium excretion was observed in both groups (p less than 0.001 in sodium excretors and p less than 0.05 in sodium retainers), plasma expansion did not reverse sodium retention in sodium retainers. A significant increase in creatinine clearance was found only in sodium retainers (p less than 0.02). Basal plasma renin activity and plasma aldosterone were elevated only in a few patients of both groups. The renin-angiotensin-aldosterone system was highly responsive to plasma expansion. Sodium retainers, who showed an ineffective natriuretic response after expansion, were able to suppress both plasma renin activity and plasma aldosterone in an analogous manner to the sodium-excreting group. This result lends strong support to the concept that the elevated aldosterone level in cirrhosis is not the major determinant of sodium retention. The kallikrein-kinin system was responsive to volume stimulus, since a decrease in kallikrein excretion was noted. It was significant in sodium retainers (p less than 0.05). Plasma PGE1,2 levels were significantly higher in sodium retainers than in controls. This may suggest that there is an activation of the intrarenal prostaglandin system, which could play a protective role against renal ischaemia. After volume expansion, PGE1,2 increased, but not significantly. Octopamine appeared unrelated to sodium excretion and unresponsive to volume stimulus. Endotoxins did not seem to be involved in renal sodium handling. Plasma volume expansion seemed effective in inducing a reduction of vasoconstrictor and sodium-retaining factors, such as the renin-angiotensin-aldosterone system. It is possible to suggest that volume expansion could increase PGE1,2. Plasma volume expansion produced different rates of sodium excretion in the two groups of patients and this suggests that impaired sodium handling in cirrhosis could, to some extent, be independent of effective plasma volume.