[Association of sarcoidosis and polycystic kidney in two brothers].
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Biomedical subjects
Publications and source records attributed to M Aparicio.
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Nephrotic syndrome causes hypercholesterolemia. Chronic renal failure results in hypertriglyceridemia, low HDL cholesterol and, more often, apolipoprotein abnormalities. This dyslipidemia is not corrected by hemodialysis. Transplantation corrects it but leads to other kinds of lipid abnormalities. Whether the treatment of these potentially atherogenetic abnormalities is beneficial of not remains unproved. There is some evidence of lipid contribution to the constitution of glomerulosclerosis in animals but it remains hypothetical in man.
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The effects of a very low-protein diet (VLPD) supplemented with amino acids and ketoanalogues (KA) and with 1 g of calcium carbonate and 1000 IU of vitamin D2, were studied in 17 patients with advanced renal failure (GFR < or = 20 ml/min) over a period of one year. The protein intake was 0.3 g protein/kg body wt/day. Daily phosphorus and calcium intake were respectively 1,500 mg and 300 mg. Sequential bone densitometry was performed and bone histomorphometry after double tetracycline labeling was evaluated, before and after one year of diet. Calcium and phosphate metabolism parameters were monitored every two months. In spite of a significant decrease of GFR, phosphorus, parathyroid hormone (1-84) and osteocalcin plasma levels decreased significantly, while low plasma bicarbonate normalized, and calcitriol and calcium levels remained respectively low and normal. Before the diet, histological study disclosed four cases of mixed osteopathy: osteomalacia associated with osteitis fibrosa (OM/OF), nine pure osteitis fibrosa (OF) and four with normal bone remodeling (NB). After one year of diet, the OM component of OM/OF disappeared, as evidenced by a normalization of the mineral apposition rate and osteoid thickness. In the patients presenting pure OF, a significant decrease in osteoblastic and osteoclastic surfaces, in the number of osteoclasts, and in the bone formation rate (BFR) were found. Vertebral mineral density measured by quantitative computerized tomodensitometry did not change significantly. In conclusion, this study not only confirms the beneficial effects of VLPD + KA + calcium on uremic hyperparathyroid bone disease in advanced renal failure assessed using static bone histomorphometry, but also shows a correction of histodynamic bone parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
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The development of necrosis and macrophage infiltration increases the risk of renal graft rejection. But the macrophages secrete the alpha form of the tumour necrosing factor (TNF) which is also involved in several immunologic and inflammatory phenomena. We therefore studied the expression of the gene TNF alpha by in situ hybridization during advanced stage rejection after renal transplantation: the grafts were infiltrated with macrophage-like cells expressing the mRNA of the TNF alpha gene, particularly deep in the cortex and in the medulla. These cells then secrete the TNF alpha molecule since they are recognized by anti-TNF alpha antibodies. These antibodies also recognize certain other glomerular endothelial and tubular epithelial cells which do not express the TNF alpha gene: these cells are undoubtedly the TNF target cells. These findings confirm the synthesis of TNF alpha in advanced stage renal graft rejection.
Cyclosporin is a very potent immunosuppressant, but it often produces renal disturbances which limit its clinical use. Using an image analyzer which determines the areas of isolated glomerules, we were able to demonstrate that cyclosporin in various concentrations exerts a direct vasoconstrictive effect on human and murine glomerules. We also showed that verapamil has an almost total inhibitory effect on cyclosporin-induced vasoconstriction. These findings seem to be of interest in clinical practice to reduce the nephrotoxicity of cyclosporin.
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The incidence of infection within six months of cadaveric kidney transplantation was reviewed in 183 consecutive patients. Prior to June, 1985, 91 patients received azathioprine 2 mg/kg/day and prednisone 0.5 mg/kg/day; 63 patients (group A1) also received antilymphocyte globulin 15 mg/kg/day for the first ten days, whereas for the 28 other patients (group A2) antilymphocyte globulin had to be withdrawn before 72 hours because of general intolerance. The next 92 patients received cyclosporine 5-8 mg/kg/day and prednisone 0.25 mg/kg/day (group B). The three groups were similar for all studied parameters except for the number of patients with anti-HLA antibodies. At six months the mortality rate was not significantly different between the three groups. After six months the number of infections per patient was 1.47, 1.03 and 0.84 (p less than 0.01) in groups A1, A2 and B respectively; the percentage of patients developing one or more infections was 81, 58 and 57% (p less than 0.01); bacterial infections: 57, 50 and 34% (p less than 0.01); viral infections: 40, 14 and 10% (p less than 0.01); cytomegalovirus infections: 27, 11 and 4% (p less than 0.001). After adjustment with logistic regression upon factors which might facilitate infections, the results showed a significantly lower incidence of infection for the cyclosporine-treated group, especially for cytomegalovirus, as compared with the antilymphocyte globulin-treated group.
Leucocytic Na+ K+ pump activity was assessed in 20 patients with advanced renal failure. Na+ K(+)-ATPase activity was reduced when compared with the values obtained from normal subjects (101.8 +/- 48.6 versus 165.13 +/- 8.9 microM of Pi hr-1.g-1; P less than 0.001) and the mean 86Rb uptake by U 937 cells was depressed by 38% after the addition of patients' sera. Subsequently, patients were put on a diet providing 0.3 g protein/kg body weight daily and supplemented with ketoacids. After three months of dietary treatment Na+ K(+)-ATPase activity increased to 142 +/- 48.3 (P less than 0.01) and reached normal values at the sixth month (162.8 +/- 54.70 microM of Pi hr-1.g-1; P less than 0.001) whereas 86Rb uptake increased by 23 percent when compared to initial values. These data suggest that among the different mechanisms which have been advanced to explain the defects in the Na+ pump observed in uremic patients, circulating inhibitors deriving from alimentary protein intake may affect cation transport.
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Tissue insulin sensitivity was measured by the glucose clamp technique in 8 uremic insulin-dependent diabetic patients before and after 3 months on a low-protein diet (LPD) providing daily 35 kcal/kg body weight, 60% of the caloric supply being obtained from carbohydrates. An improvement in tissue insulin sensitivity was observed for each steady state of the clamp and daily insulin requirements decreased significantly from 38.3 +/- 3.2 to 28.2 +/- 2.5 units (p less than 0.01) in spite of an increased carbohydrate intake. It is suggested that LPD lowers the production and accumulation of uremic toxins interfering with insulin sensitivity.
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