Background. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene determines the concentration of ACE in serum and local tissues. The role of this polymorphism in progressive chronic renal disease is still not fully clear.
Chronic renal insufficiency is accompanied by specific alterations of the lipoprotein metabolism. It has been suggested that the renal dyslipoproteinaemia of renal insufficiency contributes to the progression of glomerular and tubular lesions, with subsequent deterioration of renal function. The objective of this prospective study was to investigate whether the specific lipoprotein abnormalities of renal insufficiency are associated with the rate of decline of renal function in patients with moderately advanced chronic renal failure.A patient population of 73 adult non-diabetic patients with primary chronic renal disease were followed with repeated measurements of the glomerular filtration rate (GFR) for an average of 3.2 (SD 0.7) years. Forty-three of these patients had chronic glomerulonephritis as the underlying renal disease. Patient characteristics including plasma levels of lipids and apolipoproteins were determined at entry and were prospectively related, using linear regression, to the rate of progression.The mean GFR at entry was 41.3 (SD 15.3) ml/min x 1.73 m2 BSA. The average rate of progression was a decline in GFR of -2.8 (SD 3.7) ml/min x 1.73 m2 BSA per year. In the whole patient study group total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B (apoB) were all significantly associated with a more rapid decline in renal function, whereas triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoprotein A (apoA) were not. In the more homogeneous subgroup of patients with chronic glomerulonephritis the association between dyslipidaemia and the rate of progression was even more pronounced. In this subgroup of patients also serum triglycerides and apoE were significantly associated with a higher rate of progression. Both the initial blood pressure and proteinuria were also significantly associated with a more rapid decline in renal function in the whole study group as well as in patients with chronic glomerulonephritis. The associations between these variables with the rate of progression were all independent of the entry GFR values.These results indicate that the lipoprotein abnormalities of renal insufficiency contribute to the progression of renal failure in human chronic renal disease.
♦ Objective Conventional lactate-buffered peritoneal dialysis (PD) solutions have several bioincompatible characteristics, including acidic pH, lactate buffer, and the presence of glucose degradation products (GDPs). These characteristics, along with inflammation, are believed to contribute to membrane dysfunction in peritoneal dialysis patients. A new PD solution containing a bicarbonate/ lactate buffer system with physiologic pH and low GDPs has shown improved biocompatibility in both in vitro and ex vivo studies. In the present study, the concentrations of cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and vascular endothelial growth factor (VEGF), were measured in timed overnight effluents from PD patients continuously dialyzed with either lactate-based control solution (C) or bicarbonate/lactate–based solution (B/L) for 6 months. ♦ Methods Effluents from 92 continuous ambulatory peritoneal dialysis (CAPD) patients were collected when the patients were entered into the study (baseline, all patients on C for more than 3 months), and at 3 and 6 months following randomization to C ( n = 31) or to B/L ( n = 61). Effluent samples were filtered, stored frozen, and then assayed for IL-6, TNFα, and VEGF by ELISA. ♦ Results A significant decrease in effluent IL-6 was seen at 3 months and at 6 months in the B/L-treated patients. Levels of VEGF were significantly reduced at 3 months. No changes in the levels of IL-6 or VEGF were seen in the C-treated patients, and no changes in TNFα were seen in either group over time. ♦ Conclusions Treatment with B/L is associated with decreased IL-6 synthesis and decreased VEGF secretion. The data suggest that the use of B/L solution is associated with reduced intraperitoneal inflammation and potential for angiogenesis. The use of B/L solution may, over time, help to restore peritoneal homeostasis and therefore preserve the function of the membrane in peritoneal dialysis.
The clinical outcome for 100 consecutive patients with multiorgan failure including acute renal failure (ARF) was studied. Fifty-eight of the patients had acute renal failure due to complications during and after major surgery. Seventy-three of the patients had a urine output of less than 400 ml/24 hours. The majority of the patients also had complications such as septicemia or respiratory insufficiency and required vasopressor infusions. All patients were treated with continuous arteriovenous hemofiltration (CAVH). The duration of the CAVH treatment varied between a few hours and 90 days, with a mean of 8 days. The mean ultrafiltration volume per 24 hours was, on the average, 12 liters. CAVH resulted in adequate uremic control in 89 cases, but additional treatment with intermittent hemofiltration was necessary in 11 patients. The total survival rate was 45% including survival rates as high as 54% in patients with ARF complicating abdominal aortic surgery. Only three patients were referred for chronic dialysis therapy. In a subgroup of 17 patients with ARF complicating abdominal aortic surgery the nutritional aspects during CAVH were studied. It is concluded that during CAVH therapy it is possible to give adequate nutritional support even to hypercatabolic and anuric patients.
The availability of recombinant human erythropoietin (rh-Epo) has revolutionized the treatment of renal anaemia. Subcutaneous (s.c.) administration of rh-Epo offers significant advantages over the intravenous (i.v.) route, and numerous studies have demonstrated its efficacy and tolerability when administered two or three times weekly. Most of these studies showed a significant reduction in rh-Epo dosage requirements with s.c. administration compared with the i.v. route, offering clear benefits in terms of reduced costs. In addition, s.c. administration is more convenient and flexible than i.v. administration, and is recommended by European and US guidelines. Dosing frequency of rh-Epo is also an important issue in clinical practice, particularly when customizing therapy to meet individual patient needs. A few small-scale studies have shown comparable efficacy and tolerability of different s.c. dosing frequencies. Recently, a comprehensive randomized controlled trial has shown that once weekly s.c. epoetin beta effectively manages anaemia in haemodialysis patients, even in patients requiring a high dose. Once weekly dosing of s.c. epoetin beta adds greater flexibility and an improved capacity to tailor dosing frequency to patient needs. This reduces clinic time for patients who do not self-administer and, together with improved convenience of new formulations and delivery systems, has the potential to improve compliance and encourages self-administration.
Background: Renal dyslipoproteinemia is characterized by the accumulation of intact and partially metabolized triglyceride-rich lipoproteins. Reduced lipolytic enzyme activities may be one of the major pathophysiological mechanisms contributing to a retarded catabolism of these lipoproteins in patients with renal insufficiency. Objective: To evaluate the effect of gemfibrozil treatment on renal dyslipoproteinemia. Study design: A randomized, controlled open study with 2 parallel groups. Outcome variables: Plasma concentrations of lipids, apolipoproteins and lipoprotein particles. Patients and methods: Fifty-seven non-nephrotic, non-diabetic patients with moderately advanced renal insufficiency were randomized to either treatment with gemfibrozil at dosages from 300 to 900 mg/day (n = 28) or dietary counseling (n = 29). The intervention period was 12 months. Plasma concentrations of lipids, apolipoproteins and apoA- and apoB-containing lipoprotein particles were determined at the entry and after 6 and 12 months of treatment. Results: No serious adverse effects occurred during the study. Six patients experienced mild gastrointestinal symptoms and prematurely withdrew from the drug treatment. In the group treated with gemfibrozil the plasma concentrations of triglycerides, total cholesterol, very low density lipoprotein (VLDL) and low density (LDL) cholesterol decreased significantly by 47, 13, 43 and 14%, respectively, in comparison to baseline. High density lipoprotein (HDL) cholesterol increased significantly by 18%. ApoB, apoC-III, apoC-III in heparin-manganese precipitate (reflecting apoC-III in VLDL and LDL) and apoE decreased significantly by 21, 18, 26 and 49%, respectively. Furthermore, gemfibrozil treatment resulted in the reduction of plasma concentrations of complex (LP-Bc) and simple (LP-B) apoB-containing lipoprotein particles by 22 and 7%, respectively. However, these changes were not statistically significant. There was a slight, insignificant increase in the levels of LP-A-I:A-II particles and no change in the levels of LP-A-I particles. In contrast to the effect of the pharmacological intervention, the dietary counseling only resulted in minor changes in the plasma lipid and apolipoprotein profiles. The only significant changes were a 10% increase in HDL cholesterol and a 35% decrease in apoE. Conclusions: Gemfibrozil treatment significantly reduces both plasma lipids and apoB, apoC-III and apoE concentrations in patients with moderately advanced renal insufficiency. The results of this study indicate that gemfibrozil enhances the clearance of apoB-containing triglyceride-rich lipoproteins.
