From January 1982 to December 1993, 30 patients with multiple myeloma (MM) required haemodialysis (HD) at our institution. The subgroup of 20 patients who survived more than 2 months on HD is the subject of this study. Four patients were already on HD, due to previous nephropathy, when MM was diagnosed. 13 patients presented with acute renal failure and were on dialysis from the time of diagnosis. The remaining three cases developed renal failure later in the course of the disease. The objective response rate was 40% (8/20). Only two patients could discontinue HD (one had a late partial recovery and one received a kidney graft). Mean hospitalization per year was 19.3 d. The subgroup of patients who survived < 1 year spent a mean of 38.3 d in hospital. Whereas in the subgroup with a survival > 1 year mean hospitalization days was 9.6 (P < 0.001). The median survival was 20 months and six patients survived for > 3 years. In summary, patients with MM and severe renal failure who survive the first 2 months on dialysis have an objective response rate to chemotherapy of 40% and a median survival of almost 2 years, with 30% long-term survivors.

The effect of recombinant human erythropoietin (rHuEPO) on primary hemostasis was tested in 19 hemodialyzed patients. Bleeding time, platelet aggregation and platelet interaction with vessel subendothelium (SE) under flow conditions were determined before treatment and after patients reached hematocrits greater than or equal to 30%. Two thrombotic events (an acute myocardial infarction and an AV fistula clotting) were recorded during the early stages of treatment. A shortening of average bleeding times (P less than 0.01), an increase in platelet count (P less than 0.01) and an improvement of platelet aggregation (P less than 0.01) and of platelet-SE interaction (P less than 0.01) were observed. A low correlation index was found between hematocrit and bleeding time (r = -0.351, P less than 0.05). To assess a possible effect of rHuEPO on platelet function, the same parameters were evaluated before and after receiving three doses of rHuEPO (40 U/kg i.v. post-hemodialysis) in 14 of the patients. No changes in platelet or erythrocyte counts were observed, the mean bleeding time remained unchanged, but platelet aggregation induced by arachidonic acid (P less than 0.05), ADP (P less than 0.01) and ristocetin (P less than 0.05) improved. Perfusion studies confirmed moderate but significant increases in the parameters that quantify platelet-SE interaction (P less than 0.05). Improvement of ADP-induced aggregation correlated with the increase of platelet adhesion to SE (r = 0.675, P less than 0.05). We conclude that rHuEPO treatment improves primary hemostasis in uremia through an increase of red cell mass but also through a beneficial effect on platelet function, which is independent of the hematocrit rise.

Serum levels and the incidence of elevated levels of several tumor markers were measured in 30 patients with chronic renal failure (CRF) of different degrees, as well as in 36 hemodialyzed (HD) patients without clinical evidence of neoplasia. The tumor markers evaluated were carcinoembryonic antigen (CEA), CA 125, CA 15.3, CA 19.9, CA 50, α-fetoprotein, neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC), prostatic acid phosphatase and prostatic-specific antigen. Serum levels of CEA were above the cutoff limit in 33% of patients with CRF and 47% of HD patients, CA 50 was higher than normal values in 37 and 44% of patients, respectively. SCC was elevated in 43 and 72% of patients, respectively. Serum levels of CA 125 were elevated in 18% of patients with CRF and NSE in 36% of HD patients. In CRF several tumor markers (CEA, SCC, CA 50 and NSE) show a high false positive rate and may be unreliable for monitoring malignancies in uremic patients, while the other markers evaluated appear to maintain their specificity in this situation.

Patients on maintenance haemodialysis are at increased risk for HGV infection. HGV infection itself does not seem to be a frequent cause of chronic liver disease in these patients. Since the prevalence of HGV infection in blood donors is high, blood transfusion could be one of the main factors implicated in HGV transmission in patients on haemodialysis.

SummaryWe have investigated the ability of serum from uremic patients to modify the thrombogenic properties of the endothelium. The effects of uremic medium on the morphology of endothelial cells (ECs), and their resistance to flow was analyzed. The influence of uremic media on the reactivity of the extracellular matrix (ECM) generated by ECs towards normal platelets was evaluated in a parallel-plate perfusion chamber. Exposure of ECs to uremic medium resulted in abnormal cell morphology and signs of an accelerated growth. Detachment of ECs exposed to circulating blood was increased when cells had been grown with media supplemented with uremic serum (21% vs. 14% non exposed). Platelet deposition was significantly elevated on ECMs generated in the presence of uremic media (uremicECMs) (p<0.01 vs. control studies). Effects of uremic serum were not observed at short incubation periods (5 h) but were evident after 24 or 72 h of incubation. Northern blot analysis revealed increased expression of tissue factor (TF) mRNA in ECs exposed to uremic conditions. Immunocytochemical methods detected an augmented expression of TF antigen on uremic ECMs. Incubation of ECMs with an antibody to human tissue factor prevented the increase in platelet deposition observed in uremic ECMs, suggesting that the presence of TF in ECM could be responsible for the enhanced platelet deposition. Results from our study indicate that uremic medium impairs the antithrombotic functions of cultured endothelial cells.