Giuliano Mecca

Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia

In a randomized double-blind cross-over trial we gave either 1-deamino-8-D-arginine vasopressin or placebo to 12 patients with uremia, hemorrhagic tendencies, and prolonged bleeding times. After vasopressin infusion, all patients had shortened bleeding times, with the effect lasting for at least four hours in most cases. Platelet count, platelet cyclic AMP levels, platelet retention on glass beads, plasma fibronectin, serum thromboxane B2 and residual prothrombin, hematocrit, and plasma osmolarity were unchanged after vasopressin. A consistent post-infusion increase in factor VIII coagulant activity and, to a lesser extent, in factor VIII-related antigen and ristocetin cofactor accompanied the shortening of bleeding time. In addition, vasopressin induced the appearance in plasma of larger von Willebrand-factor multimers than those present in the resting state. The compound was given to nine additional patients with acute or chronic renal failure and prolonged bleeding times, before major surgery or renal biopsy. In these patients, shortening of the bleeding time was associated with normal hemostasis. Our findings indicate that 1-deamino-8-D-arginine vasopressin can be used for temporary correction of bleeding time and may prevent surgical bleeding in patients with uremia.

URAEMIC BLEEDING: ROLE OF ANAEMIA AND BENEFICIAL EFFECT OF RED CELL TRANSFUSIONS

Abstract Bleeding time, altered in most uraemic patients, may be influenced by packed cell volume (PCV). Uraemic patients are often anaemic, so the influence of PCV on bleeding time was assessed in several groups of patients with chronic uraemia. The findings were that bleeding times in uraemic patients are profoundly influenced by anaemia, and that the platelet-mediated haemorrhagic tendency in uraemia may be successfully managed by raising PCV values to above 30%.

Conjugated estrogens for the management of bleeding associated with renal failure.

Bleeding is a major complication of uremia. Both cryoprecipitate and desmopressin effectively shorten the prolonged bleeding time and favorably influence clinical bleeding, but the former carries the risk of transmitting blood-borne infectious diseases, and both cryoprecipitate and desmopressin have a short duration of action. Preliminary evidence has suggested that estrogens may be useful, and we therefore performed a randomized, double-blind, crossover trial comparing the effect of conjugated estrogens with that of placebo on hemorrhagic tendencies and the bleeding time in six patients with uremia who were on maintenance hemodialysis. Five daily infusions of placebo or conjugated estrogens were administered at the beginning of one-month trial periods. Estrogen shortened the bleeding time in all six patients. The effect was detectable six hours after the first infusion, reached its maximum in all patients between days 5 and 7, and lasted for 14 days. By day 16 after the last infusion, the bleeding time had returned to base line in four of the six patients. No side effects were noted during or after estrogen infusion. Estrogens did not influence the circulating level of von Willebrand factor or change its multimeric structure. Moreover, the defective platelet aggregation and thromboxane formation observed in the patients were not corrected by estrogens. We conclude that conjugated estrogens are an adequate alternative to cryoprecipitate or desmopressin for the treatment of bleeding associated with renal failure, especially when a longer duration of action is needed and immediate onset of the effect is not essential. The mechanism of action of estrogens remains to be clarified.

Adriamycin-Induced Glomerulosclerosis in the Rat

To evaluate long-term effect of sustained proteinuria induced by a single injection of adriamycin (ADR) on occurrence of focal segmental glomerulosclerosis (FSG), we treated 50 Sprague-Dawley (SD) rats, weighing 250 g with 5 mg/kg body weight of ADR. After six months of heavy proteinuria, 40% of ADR-treated rats did not develop FSG. In the remaining 60% of animals, a mild FSG was observed associated with the presence of large tubular casts and interstitial inflammation. Glomerulosclerosis was never observed in absence of tubulointerstitial lesions. Nine months after ADR, all rats exhibited FSG with renal insufficiency but the severest changes were restricted to the tubulointerstitial level. Our results indicate that chronic proteinuria induced by ADR is a relatively good model of glomerular sclerosis, however, the cause of glomerular sclerosis is probably different from that operating in other experimental models of FSG. Both sclerotic changes and progression of disease seem to be dependent on formation of tubular casts with consequent interstitial changes. This study raises the question of the relative role of tubulointerstitial changes in the subsequent development of FSG.

Plasmapheresis in the treatment of acute renal failure in multiple myeloma

Three patients with multiple myeloma and severe acute renal failure were treated by repeated plasmapheresis. Recovery of renal function was observed in all. The pathogenetic role of light chains and the possible mechanisms responsible for renal damage are discussed. It is suggested that the removal of light chains by plasmapheresis may be of therapeutic value in this condition.

Management of Myeloma Kidney: An Anti-Light-Chain Approach

This report describes the course of 23 patients with multiple myeloma and severe renal failure treated with a combination of plasmapheresis, chemotherapy, and supportive measures. Eight of ten patients with acute renal failure (ARF) obtained recovery of renal function, and in five of them serum creatinine concentration returned to normal. The remaining two patients died before the effect of treatment could be evaluated. Eleven of 13 patients with chronic renal failure (CRF) had substantial, albeit incomplete, improvement in renal function. The extent of functional recovery appeared to depend on the type of renal lesions, probably related to the duration of exposure to light chains. The median survival of the whole series of patients was 9 months, and five patients lived longer than 3 years. No clear-cut difference in survival was found between the group with ARF and that with CRF, although the latter presented higher values of serum creatinine at the time of diagnosis and residual renal insufficiency after the completion of treatment. Moreover, no significantly different survival times were found when the group with complete recovery of renal function was compared to that with minor improvement. Thus, renal failure, with the availability of effective forms of treatment of uremia, did not play a major prognostic role in our series. In contrast, the response to chemotherapy appeared to be the outstanding factor conditioning the duration of survival in these patients.

Long-term treatment with either enalapril or nitrendipine stabilizes albuminuria and increases glomerular filtration rate in non-insulin-dependent diabetic patients.

The effect of short- (98 days) and long-term (1 year) treatment with nitrendipine (10 to 40 mg/d) and enalapril (5 to 20 mg/d) on kidney function was studied prospectively in a parallel group design in 16 microalbuminuric non-insulin-dependent diabetic patients with mild hypertension and biopsy-proven diabetic glomerulopathy. At the end of the short-term treatment period diastolic blood pressure significantly decreased from 95.4 +/- 2.5 mm Hg to 83.5 +/- 3.5 mm Hg (P < 0.001) in the nitrendipine group and from 96.7 +/- 2.5 to 86.7 +/- 5.6 mm Hg (P < 0.001) in the enalapril group. Both overnight urinary albumin excretion rate and albumin fractional clearance tended to increase in the nitrendipine group and to decrease in the enalapril group, whereas the glomerular filtration rate and the renal plasma flow were similar to baseline in both study groups. At the end of the long-term treatment period diastolic blood pressure significantly decreased from 95.4 +/- 2.5 mm Hg to 86.0 +/- 6 mm Hg (P < 0.005) in the nitrendipine group and from 96.7 +/- 2.1 to 90.8 +/- 4.3 mm Hg (P < 0.05) in the enalapril group. Overnight urinary albumin excretion and albumin fractional clearance were similar to baseline in both study groups. The glomerular filtration rate significantly increased from 70.2 +/- 14.2 to 96.8 +/- 20.4 (P < 0.05) in the nitrendipine group and from 58.9 +/- 10.7 to 78.5 +/- 11.0 (P < 0.05) in the enalapril group. The renal plasma flow also significantly increased from 456.6 +/- 165.3 to 597.2 +/- 178.9 (P < 0.01) in the nitrendipine group.(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant human erythropoietin to correct uremic bleeding.

Recombinant human erythropoietin may improve hemostasis of uremic patients by correcting anemia. However, a complete correction of renal anemia carries the risk of hypertension, encephalopathy, thrombosis, and hyperkalemia. Our aim was to establish the minimum level of packed cell volume (PCV) achieved with recombinant human erythropoietin that corrects the prolonged bleeding time in uremia. Twenty patients with chronic renal failure, anemia, and very prolonged bleeding time (greater than or equal to 15 minutes) were randomly allocated to erythropoietin or no specific treatment. The initial dose of erythropoietin was 50 U/kg intravenously (IV) three times a week. Every 4 weeks, the dose was increased by 25 U/kg until a normalization of bleeding time was achieved. Erythropoietin at a dose ranging from 150 to 300 U/kg/wk induced an increase in PCV to a range of 27% to 32% in all patients but one, and normalized bleeding time in all patients. A significant negative correlation (r = 0.898, P less than 0.001) was found between PCV and bleeding time measurements. Erythropoietin also significantly (P less than 0.01) increased values for red blood cell (RBC) distribution width (basal, 11.3 +/- 0.6; 12 weeks, 13.1 +/- 1.3). Platelet count and platelet function parameters did not significantly change. In untreated patients, no changes were recorded in all the parameters considered. These results establish in a controlled fashion that erythropoietin shortens bleeding time of uremic patients and indicate that a partial correction of renal anemia is enough to normalize bleeding time.

Superimposed Nephritis: A Separate Entity Among Glomerular Diseases?

The concomitant occurrence of two glomerular diseases in the same patient was diagnosed in seven out of 105 patients undergoing renal biopsy for suspected glomerulopathy. The most frequently associated disease was a membranous type glomerulopathy. The follow-up was characterized by a rapid deterioration of renal function and two patients were required to start a chronic hemodialysis program soon after the diagnosis. It is suggested that the observed coexisting patterns of glomerular injury do not occur on the basis of chance alone and should be considered as a separate entity in glomerular pathology. In all cases, clinical and pathologic findings were strongly suggestive for two consecutive distinct pathologic processes, thus justifying the use of the term superimposed nephritis. It is reasonable to assume that the mechanisms responsible for glomerular damage and for the evolution of the disease in superimposed nephritis are different from those regulating the corresponding glomerulonephritis when occurring alone. The high prevalence of membranous pattern in superimposed nephritis indicates that pre-existing glomerular alterations might favor an immune reaction in the subepithelial space.

Immune response to hepatitis B vaccine in staff and patients in renal dialysis units

Anti-HBs response was detected in 96 per cent of staff members in three haemodialysis units after three 20 microgram doses of hepatitis B vaccine and in 82 per cent of adult patients treated with three 40 microgram doses. The percentage of responders and levels of antibody remained unchanged at 12 months from the beginning of the trial. Three out of six children injected with three 20 microgram doses in a paediatric haemodialysis unit remained free from markers of HBV infection and had high levels of anti-HBs after the second dose of vaccine. The other three children who developed serological markers of HBV infection seroconverted to anti-HBc within six months from the first dose and, in one of them, antigenaemia at three and four months was detected.