Hypertriglyceridemia is often present in chronically uremic patients treated with maintenance hemodialysis and has been considered a risk factor in the accelerated development of atheroma. Muscle carnitine content is low in hemodialyzed patients. This abnormality may help to explain the myopathy and cardiomyopathy often observed in these subjects. In addition, carnitine might play a role in the hypertriglyceridemia in renal failure. Carnitine, which is necessary for fatty acid oxidation, has been recently reported to lower serum triglycerides in patients with type IV hyperlipoproteinemia. Carnitine was administered intravenously three times weekly at the end of hemodialysis in eight patients. Carnitine was given in 0.5 g doses for 8 weeks and then in 1.0 g doses for 6 additional weeks. There was a significant decrease in serum triglycerides at the end of treatment. In contrast, serum lipids in eight hemodialysis patients receiving placebo did not change significantly. Carnitine administration does not cause any side effect except some euphoria. These results suggest that carnitine may be effective in the treatment of hypertriglyceridemia in dialysis patients.

The study was carried out in order to evaluate in maintenance hemodialysis (MH) patients: (1) the reliability of serum ferritin (SF) measurement in iron deficiency diagnosis and therapy; (2) the possibility to improve iron stores assessment through laboratory indexes routinely used in clinical practice; (3) the most effective iron deficiency treatment. After a preliminary assessment of SF reference values in 250 healthy volunteers, we studied 72 MH patients divided into three groups according to their SF baseline values: high (group A), normal (group B), low (group C) (normal range 19–191 ng/ml). Each group was further divided into three subgroups receiving three different iron treatments for 6 months: (1) oral administration of 67.5 mg/day of Fe³⁺ as Fe-ferritin (subgroups A1, B1, C1); (2) oral administration of 60 mg/day of Fe³⁺ as Fe-condroitin sulfate (subgroups A2, B2, C2); (3) i.v. administration at the end of each dialytic session of 31 mg of Fe³⁺ as Fe-gluconate-Na (subgroups A3, B3, C3). The response to the iron therapy was considered positive when the hemoglobin (Hb) and the hematocrit (Ht) increased to > 15% of the baseline values. The rate of positive responses in each subgroup was as follows: Al 0/5, A2 0/5, A3 0/7, B12/10, B2 1/6, B3 5/11, C11/7, C2 3/7, C3 10/16. We concluded that SF values above 191 ng/ml allow to exclude iron deficiency whereas SF values ≤ the normal range are inadequate. In an attempt to improve diagnostic sensitivity we divided patients of subgroup B3 and C3 into responders (R) and nonresponders (NR). In these patients the hematological indexes assessed prior to iron therapy and significantly different between the two groups were used to calculate a discriminant function (DF). Compared to NR, R showed significantly lower values of SF, blood iron, transferrin saturation, mean corpuscular volume, mean corpuscular hemoglobin, and significantly higher vlaues of total iron-binding capacity and red cell distribution width. Nevertheless, none of these parameters alone allows a reliable discrimination between the patients of the two groups. On the contrary through DF, diagnostic sensitivity rises to 93.3% with a specificity of 91.7%. Discriminant scores resulted as 796 for NR, 41 for R, and 450 resulted as the best discriminant value. In order to assess the validity of the iron deficiency diagnosis and treatment criteria developed in the previous parts of the study 20 mg of Fe³⁺ as Fe-gluconate-Na were given i.v. at the end of each dialytic session to 11 new patients diagnosed as iron deficient by our criteria. All patients showed a positive response to the therapy. SF values increased slowly during the phase of Hb increment and rapidly when Hb values reached stabler values. Finally, we can summarize the following: Diagnostic criteria – SF > 191 ng/ml: no iron deficiency; SF < 191 ng/ml use DF: score > 796 no iron deficiency, 450≤ score < 796 doubtful iron deficiency, score≤450: iron deficiency; and treatment modalities ...

To explain mechanisms responsible for derangement of insulin release in uremia, we investigated glucose metabolism through three different tests in 14 patients with end-stage chronic renal failure. These tests were: intravenous glucose tolerance test with 0.33 g/kg of glucose solution (IVGTT); IVGTT with 0.5 g/kg of glucose solution (IVGTT2); IVGTT during aminophylline infusion (IVGTT + A). Twelve of the patients had IVGTT repeated after two to four months of thrice-weekly regular hemodialysis (IVGTT3). In each test we measured plasma glucose (G), immunoreactive insulin (IRI) and C-peptide. We also calculated glucose constant decay (K), insulin production (IRI area), insulinogenic index (IGI), and insulin resistance index (RI). Twenty-nine healthy volunteers formed the normal controls for IVGTT. As compared to controls, during IVGTT uremic patients showed significantly lower values in K, IRI area and IGI, and showed a significant RI value increase. During IVGTT2, IRI are values were higher than during IVGTT but IGI and K values were unchanged. During IVGTT + A both IRI area and IGI values were higher than during IVGTT. After hemodialysis treatment (IVGTT3) K, IRI areas and IGI increased significantly as compared to the predialysis period. K increase after hemodialysis correlated directly to IGI increase and inversely to RI changes. IGI increase during IVGTT3 was directly correlated to IGI rise during IVGTT + A. From these data we infer that defective insulin release in uremia is due to a decrease of beta-cell glucose sensitivity rather than to their functional exhaustion. An impaired adenyl cyclase-cAMP system may have an important role in the pathogenesis of this abnormality.

The effects of recombinant human erythropoietin (rHuEPO) on the glucose metabolism were evaluated by intravenous glucose tolerance test in 20 maintenance hemodialysis patients. In 8 cases the glucose tolerance tests were performed before and after a single intravenous injection of 50 IU/kg of rHuEPO and in 12 cases before and after 3 months of rHuEPO therapy at doses of 50 IU/kg three times/week and 2 weeks after rHuEPO withdrawal. For each test glucose, immunoreactive insulin (IRI), and C peptide (C-p) plasma values were measured, and glucose constant decay, whole IRI (area IRI) and C-p (area C-p) production, insulinogenic index, and insulin resistance index were calculated. After 3 months of rHuEPO therapy, the glucose constant decay increased significantly, area IRI, area C-p, and insulin resistance index decreased significantly, and the insulinogenic index did not change. No correlations were found between changes in hemoglobin values and changes in glucose metabolism parameters. Acute rHuEPO administration and rHuEPO withdrawal had no effect on glucose metabolism, despite significant changes in plasma erythropoietin levels. Long-term rHuEPO therapy improves glucose metabolism in maintenance hemodialysis patients significantly, mainly by reduction of insulin resistance. Neither anemia correction nor a direct effect of rHuEPO on some metabolic steps seem to be responsible of these effects.

L-carnitine supplementation was associated with protein-sparing effects in maintenance haemodialysis patients during hyperinsulinemia.