Hyperparathyroidism: is it really the major factor affecting glucose tolerance in uremia?

The effects of secondary hyperparathyroidism (sHPTH) on immunoreactive insulin (IRI) release and glucose (G) tolerance were studied in two groups of dialysis patients with normal (NPTH, n = 9) or elevated PTH levels (HPTH, n = 8), 27 +/- 24 and 660 +/- 440 pg/ml, respectively. The patients received an intravenous glucose tolerance test (IVGTT) using 0.33 g/kg of glucose solution. G, IRI and C-peptide (C-p) levels were determined calculating the G constant decay (K) and the relative incremental areas for each study. Regardless of PTH levels, all patients showed an impaired glucose tolerance (GT). IRI secretion and K values were not significantly different between the two groups. However, a significantly lower K value with a reduced (although not significant) early and late IRI secretion was found in the subgroup of patients with more severe. sHPTH (PTH: 560-1,500 pg/ml, n = 5) as compared to patients with moderate sHPTH (PTH: 87-341 pg/ml, n = 4) or normal (5-32 pg/ml, n = 8) PTH levels. No relationship was found between PTH and G, IRI or C-p levels. Our results point to a threshold limit for PTH's inhibitory effect on IRI secretion and suggest that other factors, known to affect IRI secretion and GT besides PTH levels, may modulate the role played by excess PTH levels on carbohydrate metabolism of dialysis patients.

Lipoprotein abnormalities in chronic renal failure and dialysis patients.

Lipoprotein abnormalities are common in patients with chronic renal failure (CRF) on either dialysis or conservative therapy. In order to investigate the changes in lipid and apolipoprotein pattern from early CRF to dialysis treatment, plasma lipids with apoproteins AI, B, E, CII, CIII, CII/CIII ratio, E/CIII ratio, parathyroid hormone (PTH) and insulin levels were examined in 72 patients with different degrees of CRF and 31 patients on hemodialysis (HD), and compared the values of 28 controls. A significant decrease in the Apo CII/CIII ratio was the earliest lipoprotein abnormality to occur in CRF. Hypertriglyceridemia (HTG) with reduced high-density lipoprotein cholesterol levels, increased Apo CIII and decreased Apo E/Apo CIII ratio only occurred in more advanced renal failure (creatinine clearance < 31 ml/min). HD patients showed a general worsening of the lipoprotein profile with elevated Apo E levels and indirect evidence of remnant accumulation. While PTH did not have any significant influence on lipoprotein pattern, increased insulin levels during HD might partly account for the HTG of these patients. Our results point to elevated Apo CIII, reduced Apo CII/Apo CIII and Apo E/ Apo CIII ratios as typical features of uremic hyperlipidemia and show that a defective triglyceride removal is the major pathogenetic mechanism of uremic HTG. HD treatment seems generally to worsen the lipid and apolipoprotein pattern observed in the predialytic stage of CRF.

Lipids and apolipoproteins change during the progression of chronic renal failure.

Uremic hyperlipidemia was recently suggested to contribute to progression of chronic renal failure (CRF). To investigate the relationship between lipoprotein abnormalities and decline of renal function, plasma lipids with apoproteins A1, B, E, CII, CIII, CII/CIII and E/CIII ratios, parathyroid hormone (PTH), insulin and glucose levels were examined in 72 patients with different degrees of CRF and compared to 28 patients of a reference group. A significant decrease of CII/CIII ratio was already evident below a Ccr of 60 ml/min, while increased apo-CIII and triglycerides (TG) with reduced HDL-cholesterol (HDL-C) levels occurred below a Ccr of 30 ml/min. Both TG and apo-CIII showed a positive correlation with creatinine levels. On the contrary, apo-CII/apo-CIII and HDL-C inversely correlated with the progression of renal failure. PTH and insulin showed a positive correlation with TG, the former being also inversely related to apo-CII/apo-CIII ratio. Our results point to early apolipoprotein changes in the course of CRF. Elevated apo-CIII and reduced apo-CII/apo-CIII ratio may be considered the most typical features of uremic hyperlipidemia and likely account for the impaired TG removal and the hypertriglyceridemia (HTG). Secondary hyperparathyroidism may contribute to reduce peripheral lipolytic activity and cause HTG. A contributory role of hyperlipidemia in the progression of renal disease is also supported.

Are lipid abnormalities reliable cardiovascular risk factors in dialysis patients?

Patients on chronic hemodialysis often present both hyperlipidemia and a high incidence of cardiovascular disease (CVD). Uremic hyperlipidemia has usually been regarded as one of the most important cardiovascular risk factors (CVRF) in these patients. In order to study whether the "uremia-induced" lipid abnormalities are actually associated with evidence of uremic CVD, and consequently may be considered reliable CVRF, 123 patients on chronic dialysis were reviewed for the presence of CVD and, at the same time, examined for their lipoprotein pattern and other clinical and biochemical variables. Lipids and lipoproteins did not prove helpful in our study in identifying patients with CVD. Despite the fact that they had been on dialysis for a shorter time, CVD patients were significantly older and had higher blood pressure than patients without CVD. Our data suggest that the uremia-induced lipid abnormalities are not reliable markers of CVD in dialysis patients, and support the hypothesis that dialysis per se does not accelerate the atherosclerotic process in uremic patients.

Leukocytes, eosinophils and complement function during hemodialysis with polysulphone and polymethylmethacrylate membranes: comparison with cuprophan and polyacrylonitrile.

The biocompatibility of the two new dialysis membranes, polysulphone (PS) and polymethylmethacrylate (PMMA), was evaluated versus cuprophan (CUP) and polyacrylonitrile (PAN) by studying the in vivo effects of the four different membranes on leukocyte counts, eosinophil levels and complement function both in the presence and absence of dialysis fluid. Complement function was also examined in vitro by studying the generation of chemotactic factors, whole complement activity and C3d serum conversion. Passive absorption of complement fractions by membranes has completed in vitro studies. PS, PMMA and PAN showed a higher biocompatibility than CUP, even if slight differences can be observed: PS showed a PAN-like biocompatibility pattern with a relatively high absorption of complement factors by the membrane and without complement activation. On the other hand, PMMA showed a CUP-like pattern and caused complement activation, even though to a lower intensity than CUP. PMMA biocompatibility appears to stand in-between CUP and the other two synthetic membranes PS and PAN. Our results confirm the important role played by membrane-induced complement activation on hemodialysis leukopenia. Dialysis fluid does not have a significant influence on membrane biocompatibility, but represents the major factor in determining intradialytic eosinopenia. Eosinophils seem to represent a more important marker of dialysis than of membrane biocompatibility.

Biofiltration in elderly uremic patients.

We treated five elderly patients with conventional hemodialysis (CH) or biofiltration (BF) to establish whether their dialytic tolerance was better. For three patients treatment time was reduced from twelve to nine hours a week; for the other two, treatment time remained unchanged (10.5-12 h/week) because of their high interdialytic weight gain. At the beginning and end of the study, clinical status, biochemical data, nutritional status and acid-base balance (ABB) were checked. Plasma levels of small molecules, potassium and phosphate were unchanged for all patients. All had a lower number of episodes or less severe hypotension and good control of ABB. No patients had metabolic alkalosis or worsened nutritional status. For all patients BF was an efficacious choice compared to CH, giving them good health.