Erythropoietin can deteriorate glucose control in uraemic non-insulin-dependent diabetic patients.

Two patients with non-insulin-dependent diabetes mellitus (NIDDM) and moderate chronic renal failure experienced a worsening of glycaemic control when recombinant human erythropoietin (r-HuEPO) was introduced, leading to insulin therapy. A 71-year-old woman with a 20-year history of NIDDM had presented histologically documented diabetic nephropathy for 2 years during which glucose control was stabilized by a diet and glibenclamide 10 mg. In the 6 months following introduction of r-HuEPO, hyperglycaemic symptoms developed, and HbA1C increased from 8.9% to 12.3%. During this period, no intercurrent events occurred, except epistaxis due to accelerated hypertension one month after r-HuEPO was started. A 62-year-old man had a 15-year history of NIDDM, with proliferative retinopathy, macroproteinuria and chronic renal failure for 4 years. The day after the first injection of r-HuEPO, capillary glucose level rose dramatically. In both of these cases, antihypertensive treatment was increased and insulin introduced. The role of r-HuEPO in hyperglycaemia was probable in the first case and highly probable in the second. Reports about the effects of r-HuEPO on glucose metabolism in uraemic patients are conflicting. Short- and long-term effects can differ, although long-term benefit is likely. The fact that our patients were not dialized may have been important. Clinicians should be aware that glucose control may deteriorate with r-HuEPO, requiring some uraemic NIDDM patients to undergo insulin therapy.

[Spontaneous rupture of the esophagus (Boerhaave syndrome) in a patient with scleroderma treated by continuous ambulatory peritoneal dialysis]. / Rupture spontanée de l'oesophage (syndrome de Boerhaave) chez une patiente sclérodermique traitée par dialyse péritonéale continue ambulatoire.

Esophageal involvement is a common situation found in 50 to 80% of patients with scleroderma, but Boerhaave's syndrome is rare in this context. The authors report the first case of spontaneous esophageal rupture occurring in a chronic renal failure patient treated by continuous ambulatory peritoneal dialysis. In this observation, sclerodermal esophageal dyskinesia, chronic renal failure which is a classical cause of vomiting and the peritoneal dialysis which play an increasing role in the intraabdominal pressure are potential contributing factors to Boerhave's syndrome. In such patients presenting risk factors, even if they are asymptomatic, it seems reasonable to propose esophageal explorations with manometry or/and endoscopy looking for dyskinesia or other complications of gastro-esophageal reflux.

A low-protein diet improves insulin sensitivity of endogenous glucose production in predialytic uremic patients.

A low-protein, low-phosphorus diet (LPD) has been shown to improve insulin sensitivity in uremic patients; however, this improvement has not been studied at low physiologic concentrations of plasma insulin, and the metabolic pathways concerned with this improvement have not been located. We used the glucose clamp technique at a low (0.25 mU.kg-1.min-1) level of hyperinsulinemia associated with the infusion of D[6,6-2H2] glucose to assess the insulin sensitivity of endogenous glucose production (EGP). Eight nondialyzed uremic patients were studied before and after 3 mo on an LPD providing 0.3 g/kg protein, 5-7 mg P/kg, and 146 kJ/kg (67% of energy as carbohydrates and 30% as lipids) per day, supplemented with ketoanalog amino acids. Postabsorptive plasma glucose and insulin declined after 3 mo of the diet (plasma glucose: 5.0 +/- 0.1 mmol/L before compared with 4.7 +/- 0.1 mmol/L after the LPD, P < 0.05; plasma insulin: 82.4 +/- 20.7 pmol/L before compared with 48.8 +/- 6.0 pmol/L after, P < 0.05). Postabsorptive glucose turnover rates did not change with the diet (2.06 +/- 0.14 mg.kg-1.min-1 before compared with 2.11 +/- 0.17 mg.kg-1.min-1 after LPD; NS). The insulin metabolic clearance rate was enhanced after the diet, so a lower level of hyperinsulinemia was obtained during the clamp (168.8 +/- 28.1 pmol/L before compared with 115.2 +/- 14.7 pmol/L after; P < 0.05). However, EGP was more easily inhibited after the diet (0.90 +/- 0.31 mg.kg-1.min-1 before compared with 0.30 +/- 0.17 mg.kg-1.min-1 after; P < 0.05), providing evidence of an improved insulin sensitivity of this parameter. This beneficial influence takes place at a physiologic level of hyperinsulinemia, and it probably plays an important role in the better glucose tolerance that has been reported in uremic patients on an LPD. An abnormal insulin sensitivity of EGP may participate in the disturbances of glucose metabolism in chronic renal failure.

Low protein diet in uremia: effects on glucose metabolism and energy production rate.

Low-protein diets (LPD) increase insulin-mediated glucose disposal in chronic renal failure (CRF), but the fate of the better utilized glucose and the effect on energy production rate are unknown. Using a two-step (1 and 5 mU x kg(-1) x min(-1)) euglycemic hyperinsulinemic clamp combined with indirect calorimetry, we studied the effects of a LPD (0.3 g x kg(-1) x day(-1), supplemented with essential amino acids and ketoanalogs) in six patients suffering from chronic renal failure. After three months of diet, no significant change was observed concerning glomerular filtration rate, body wt, or arterial pH. In the postabsorptive state, plasma glucose and insulin levels were significantly lower, and energy production rose from 15.72 +/- 0.48 to 17.16 +/- 0.67 Cal x kg(-1) x min(-1) (P < 0.05). Insulin-stimulated glucose oxidation (2.36 +/- 0.29 vs. 3.37 +/- 0.35 mg x kg(-1) x min(-1); P < 0.05 at first clamp step) and nonoxidative disposal (P < 0.05 at both clamp steps) increased after LPD. This confirms that LPD ameliorates insulin sensitivity in CRF, even for low plasma insulin concentrations. Since energy production rate is increased by LPD, the caloric intake should be increased when protein intake is restricted.

Improvement in lipid profiles and triglyceride removal in patients on polyamide membrane hemodialysis.

Cardiovascular morbidity and mortality in hemodialyzed patients are increased due to the frequently abnormal lipid metabolism. It has been reported that this abnormal lipid metabolism could be partially corrected by some highly permeable membranes, such as polysulfone or cellulose triacetate. We investigated the influence of 4 months of dialysis with a polyamide membrane upon the course of lipid parameters in 6 patients presenting a hypertriglyceridemia > 2 mmol/l while on bicarbonate dialysis with a cellulose membrane. Lipid parameters improved after 4 months of hemodialysis with a polyamide membrane. Serum triglyceride and cholesterol levels decreased, while HDL cholesterol and HDL levels rose significantly (p < 0.05). Apolipoprotein B decreased significantly (p < 0.05). Following heparin administration, lipoprotein lipase activity improved (p < 0.02), associated with a decrease apolipoprotein C3 (p < 0.05). The fractional clearance rate of triglycerides rose significantly (p < 0.01). The use of highly permeable polyamide membranes results in a significant improvement in lipid disturbances of dialysis patients due to an increased lipoprotein lipase activity, induced perhaps by the removal of circulating inhibitors such as apolipoprotein C3.

[Role of phosphorus in hyperparathyroidism secondary to non-dialysed adult chronic renal insufficiency]. / Le rôle du phosphore dans l'hyperparathyroïdie secondaire de l'insuffisant rénal chronique adulte non dialysé.

Secondary hyperparathyroidism (HPT II) occurs early in the course of chronic renal failure (CRF), mainly because of decreased calcitriol levels, low levels of serum calcium, retention of phosphorus, abnormal parathyroid gland function and hyperplasia, and peripheral resistance to the action of parathormone (PTH). Amongst these factors, phosphorus retention plays a crucial role in moderate and advanced CRF, by inhibiting renal calcitriol synthesis, lowering serum calcium levels and stimulating PTH secretion. In patients with mild CRF, phosphorus restriction prevents the development of HPT II by increasing renal calcitriol secretion. In patients with advanced CRF, the suppressive effect of phosphorus restriction may be obtained independent of any changes in plasma calcitriol levels, suggesting a direct effect of phosphorus on parathyroid function. Phosphorus restriction should be used in the early stages of CRF, together with a sufficient intake of calcium in the form of phosphorus chelating salts. When phosphorus and calcium serum concentrations are normalised but PTH levels are not in the target range, 1 alpha hydroxy vitamin D3 derivatives may be used, with a careful monitoring to avoid high serum levels of phosphorus or calcium.

Correction of chronic metabolic acidosis in haemodialysed patients by acetate-free biofiltration does not influence parathyroid function.

In eight patients remaining acidotic after more than 1 year of bicarbonate haemodialysis, we studied the effect of correcting the chronic metabolic acidosis using acetate-free biofiltration for 4 months on the course of secondary hyperparathyroidism. An AN69 capillary membrane was employed with a bicarbonate infusion rate initially set at 1.8 l/h in all patients and then adjusted in each one to obtain a predialysis bicarbonate of > or = 23 mmol/l. Standard blood chemistry parameters were determined every 2 weeks. Measurements of PTH, calcifediol and calcitriol, as well as calcium-PTH curves were determined at the beginning and end of the study. While acetate-free biofiltration appears to be an adequate technique for the correction of chronic metabolic acidosis when bicarbonate dialysis fails, this study indicates that it does not influence secondary hyperparathyroidism in haemodialysed patients. The level of intact PTH did not vary significantly and the calcium-PTH curves at 0 and 4 months were superimposable with no significant differences in the set point and the slope of the curves.

Long-term control of hyperparathyroidism in advanced renal failure by low-phosphorus low-protein diet supplemented with calcium (without changes in plasma calcitriol).

Phosphorus (Pi) retention linked to chronic renal failure (CRF) favors secondary hyperparathyroidism (HPT). Reduction of Pi and protein intake has been shown to prevent the development of HPT in CRF. The aim of the present study was to assess in patients with advanced CRF the long-term effects on phosphate and calcium metabolism of a low-Pi (5-7 mg/kg/day), low-protein (0.4 g/kg/day) diet providing 300 mg/day calcium (Ca) and supplemented with amino acids and ketoacids, Ca carbonate (400-800 mg/day) and vitamin D2 (1,000 IU/day). Twenty-nine patients with advanced CRF (glomerular filtration rate (GFR) 13.7 +/- 4.5 ml/min) were selected for the study, on the basis of a follow-up of a least 2 years and a satisfactory compliance to the prescribed diet. At the start of the study, biological evidence of HPT was present with increased plasma PTH concentration (144 +/- 95 pg/ml), increased plasma Pi (1.57 +/- 0.33 mmol/l), an increase in alkaline phosphatase activity and plasma osteocalcin concentration. Plasma PTH concentration was positively correlated with plasma Pi and inversely with plasma Ca concentrations and GFR. Pi and protein restriction induced a significant correction of HPT within 3 months after starting the diet. After 2 years of diet, despite the diminution of GFR (11.1 +/- 3.7 ml/min, p < 0.0001), plasma PTH was still lower than at the start of the diet (88 +/- 57 pg/ml, p < 0.01), as was plasma Pi (1.32 +/- 0.24 mmol/l, p < 0.001), total plasma Ca being higher (p < 0.01). Plasma PTH levels were correlated only to plasma Ca concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)