C3 and Bf complement types in chronic renal failure

Summary C3 and BF allele frequencies were studied in 55 patients with idiopathic membranous nephropathy (IMN) and unrelated normal individuals from North-East England. Eighteen of these IMN patients progressed to renal failure and C3^*S allele showed a significant increase in these patients. A possible mechanism for this increase is briefly discussed.     

Immunofixation for C2 typing: C2 allotypes in Spaniards in relation to HLA,Bf and C4

Summary C2 typing is performed by immunofixation with anti-C2 antiserum instead of by a hemolytic overlay. This method gives sharp band definition, is less cumbersome than the hemolytic overlay, gel files are easily made, and it also enables one to describe putative new nonhemolytic variants. C2 allele frequencies were studied in a sample of the normal Spanish population and were found to be similar to other Caucasoids. HLA-Bw62,-Cw3, and-DR4 were significantly associated with C2 B. Concordantly, the only C2^*B extended HLA haplotype found in family material was Bw62-Cw3-Bw6-(DR4)-Bf^*S-C2^*B-C4A^*3 B^*2-(GLO^*1). C4A^*4 B^*2 and C4A^*4 B^*4 are not found within the same haplotype together with C2^*B and Bw62 or Bw22 respectively, nor do other C2^*B haplotypes occur with common HLA-B alleles. These results may favour the hypothesis that the Bw62-C2^*B haplotype is produced by one mutation arising in the Bw62-C2^*C haplotype and that subsequent crossovers can explain other C2^*B haplotypes (including Bw22-C2^*B).     

Thyroid C cells in male and female rats with chronic renal failure

The kidneys are responsible for iodine and of thyroid hormone biodegradation. The aim of this study was the histomorphological and immunohistochemical evaluation of the influence of sex on parafollicular thyroid C cells in rats with chronic renal failure. The experiment included 40 Wistar rats after subtotal nephrectomy, after sham operation, and without any surgical procedure. Two weeks after nephrectomy, fragments of thyroids were collected from the examined animals. Paraffin sections were stained with H+E and by silver impregnation. Calcitonin (CT), synaptophysin (SPh), somatostatin (ST), and neuron-specific enolase (NSE) were detected immunohistochemically in C cells. In rats with experimental uremia, immunostaining for the examined substances increased significantly in comparison to the controls. We also observed higher number of C cells with a stronger reaction in the group of males, compared to the female rats.     

Hypersomatostatinemia in chronic renal failure

Plasma concentrations of somatostatin-like immunoreactivity (SLI) were determined in uremic patients on maintenance hemodialysis. Plasma SLI levels were significantly (p less than 0.001) elevated in 26 diabetic uremic patients (67.1 +/- 6.8 pg/ml, mean +/- SE) and in 24 non-diabetic uremic patients (43.5 +/- 7.2 pg/ml), when compared with 60 healthy subjects (5.0 +/- 0.7 pg/ml). Paired pooled plasma from uremic patients before and after hemodialysis was subjected to a reverse-phase octadecasilyl-silica (C-18) cartridge and then the extract was gel filtered on a Sephadex G-25 column (1.6 X 90 cm). Both elution profiles showed two peaks of SLI which coeluted with synthetic somatostatin (SS)-28 and SS-14 markers, respectively. The SS-28-like immunoreactivity (LI) peak, which was estimated by using SS-14 as a reference standard, was 3-fold larger than that for SS-14 LI. On the basis of immunoequivalency of the two components in the present assay, SS-28 LI constitutes approximately 75% of circulating somatostatin. In conclusion, plasma SLI is substantially high in uremic patients of both diabetic and non-diabetic etiology and the SS-28 is a predominant form of circulating SLI in these patients, probably, in part, for a lower clearance of this molecule.     

Relatedness among Basques, Portuguese, Spaniards, and Algerians studied by HLA allelic frequencies and haplotypes

 HLA-A, -B, -DRB1, -DQA1, and DQB1 alleles were studied in Iberian and Algerian populations by serology and DNA sequence methodologies. The genetic and cultural relatedness among Basques, Spaniards, and paleo-North Africans (Berbers or Tamazights) was established. Portuguese people have also maintained a certain degree of cultural and ethnic-specific characteristics since ancient times. The results of the present HLA study in Portuguese populations show that they have features in common with Basques and Spaniards from Madrid: a high frequency of the HLA-haplotypes A29-B44-DR7 (ancient western Europeans), A2-B7-DR15 (ancient Europeans and paleo-North Africans), and A1-B8-DR3 (Europeans) are found as common characteristics. Portuguese and Basques do not show the Mediterranean A33-B14-DR1 haplotype, suggesting a lower admixture with Mediterraneans; Spaniards and Algerians do have this haplotype in a relatively high frequency, indicating a more extensive Mediterranean genetic influence. The paleo-North African haplotype A30-B18-DR3 present in Basques, Algerians, and Spaniards is not found in Portuguese either. The Portuguese have a characteristic unique among world populations: a high frequency of HLA-A25-B18-DR15 and A26-B38-DR13, which may reflect a still detectable founder effect coming from ancient Portuguese, i.e., oestrimnios and conios; Basques and Algerians also show specific haplotypes, A11-B27-DR1 and A2-B35-DR11, respectively, probably showing a relatively lower degree of admixture. A neighbor-joining dendrogram place Basques, Portuguese, Spaniards, and Algerians closer to each other and more separated from other populations. Genetic, cultural, geological, and linguistic evidence also supports the hypothesis that people coming from a fertile Saharan area emigrated towards the north (southern Europe, Mesopotamia, the Mediterranean Islands, and the North African coast) when the climate changed drastically to hotter and drier ca 10 000 years B.C. Received: 18 April 1997 / 17 June 1997     

Interleukin-1 receptor antagonist gene polymorphism affects the progression of chronic renal failure

End-stage renal disease (ESRD) involves an inflammatory process. Interleukin-1 receptor antagonist (IL-1Ra) and interleukin-1beta gene polymorphisms affect susceptibility to the disease in several inflammatory diseases. We investigated whether these polymorphisms are involved in ESRD by genotyping DNA from 602 dialyzed patients and 433 controls with polymerase chain reaction and digestion with restriction endonuclease. Allele 2 of the IL-1Ra VNTR polymorphism was associated with ESRD (OR=1.46, 95% CI 1.19-1.78). We also found a strong association between this allele and recurrent peritonitis in peritoneal dialysis patients. Odds ratio for the risk allele was higher compared to entire ESRD group (OR=3.6, 95% CI 1.70-7.44). The homozygosity for the allele 2 was associated with disease progression, especially in patients with diabetic nephropathy and glomerulonephritis. For the patients from these two subgroups having 2.2 genotype, the mean time from disease onset to ESRD was 1.5 and 2.2 years, respectively, compared to 6.4 and 9.8 years for those with 1.1 genotype. The IL-1Ra allele 2 is associated with ESRD in our dialyzed patients. Our results demonstrate for the first time the association of the IL-1Ra allele 2 with faster progression to ESRD. If confirmed in other populations, it might be a predictor of faster disease progression.     

Preliminary evaluation of thyroid C cells in rats with chronic renal failure

Numerous water-electrolyte and hormonal disturbances, including secondary hyperparathyroidism, occur in the course of chronic renal failure. It is assumed that chronic renal failure should affect the activity of C cells in the thyroid gland. Thus, the aim of the study was to evaluate immunohistochemically thyroid C cells in rats with experimental uremia. 30 days after nephrectomy, thyroid fragments were collected from experimental rats. Paraffin embedded sections were stained with H+E and by silver impregnation. Calcitonin (CT), synaptophysin (SY), somatostatin (ST), and neuron-specific enolase (NSE) were detected immunohistochemically in the C cells. A very distinct increase in C cell number in the thyroid and the weakening of majority of examined reactions were observed in rats with experimental uremia.     

Acetylcholinesterase activity in chronic renal failure

Twenty healthy subjects and 39 Chronic Renal Failure patients (CRF-patients) maintained on chronic hemodialysis were used in this investigation to study the changes in acetylcholinesterase (AChE) activity of red blood cells (RBCs). The CRF-patients were all undergoing hemodialysis treatment. AChE activity from the CRF-patients was determined before and after dialysis. An additional objective was to study the effect of chronic renal failure on human red blood cell aging. Blood samples were drawn from controls and CRF-patients in tubes containing EDTA or sodium heparin as an anticoagulant. Red blood cells were purified to avoid interference with monocytes, reticulocytes and leukocytes. The purified RBCs were subfractionated into young (y) (1.08-1.09), mid (m) (1.09-1.11) and old (o) (1.11-1.12) percoll density (g/mL) fractions using a discontinous percoll gradient. The mean +/- SD AChE per gram hemoglobin (U/g Hgb) activities in whole blood (WB), purified human red blood cells (PRBCs), young human red blood cells (y-RBCs), mid age human red blood cells (m-RBCs) and old human red blood cells (o-RBCs) in CRF-patients were 31.2+/-3.43, 29.3+/-3.26, 30.4+/-3.91, 25.1+/-5.25, 17.1+/-6.02 in females and 29.8+/-5.39, 28.8+/-5.29, 28.7+/-5.29, 23.7+/-5.39 and 16.0+/-5.60 in males. AChE activity from CRF-patients were higher than that found in the control subjects. The aging of human RBCs in both the controls and CRF-patients showed a progressive reduction in AChE activity. AChE activity of RBCs from female CRF-patients were significantly higher (p < 0.05) than that of the female control subjects. The RBCs isolated from male CRF-patients showed a higher AChE activity than control males, but a significant difference was only observed with the mid-age-cells. These studies further indicate that AChE activity remained insignificantly different in the various density based age subfractions of RBCs of both CRF-patients and controls.     

Oxidative stress in chronic renal failure

Cardiovascular disease is the major cause of morbidity and mortality in chronic renal failure. The aim of this review is to summarise current evidence suggesting that there is increased free radical production, antioxidant depletion and changes in lipoprotein composition in renal failure which will lead to oxidation of LDL and hence to accelerated development of atherosclerosis.     

Fecal methylamine and dimethylamine in chronic renal failure

Determinations of methylamine and dimethylamine in the fecal samples from normal subjects (n = 22), nonhemodialysis patients (n = 10), and hemodialysis patients (n = 14) with chronic renal failure have been made by high-performance liquid chromatography of their 2,4-dinitrophenyl derivatives. Fecal methylamine level was significantly lower in the normal group than in the nonhemodialysis group (P less than 0.05) and in the hemodialysis group (P less than 0.05). The mean dimethylamine value of the hemodialysis group was significantly higher than that of the nonhemodialysis group (P less than 0.01) and that of the normal group (P less than 0.005). The method has also been applied to the determination of the two amines in the fecal samples from two patients with leukemia who had been isolated and sterilized in the laminar air flow rooms. Preliminary in vitro experiments were given of the possible pathway for the production of these amines by the incubation of normal fecal samples with added creatinine.     

Endothelin-1 in chronic renal failure and hypertension

Investigation into the role of endothelin-1 (ET-1) in renal function has revealed two major direct actions leading to the control of extracellular volume and blood pressure. These are the regulation of renal hemodynamics and glomerular filtration rate and the modulation of sodium and water excretion. In the rat remnant kidney model of chronic renal failure, ET-1 production is increased in blood vessels and renal tissues. These changes are related to an increase in preproET-1 expression and correlate with the rise in blood pressure, the development of cardiovascular hypertrophy, and the degree of renal insufficiency and injury. Selective ETA receptor blockade prevents the progression of hypertension and the vascular and renal damage, supporting a role for ET-1 in chronic renal failure progression. The increase in ET-1 production can be associated with other local mediators, including angiotensin II, transforming growth factor-beta1 and nitric oxide, the local production of which is also altered in chronic renal failure. In human patients with essential hypertension, atherosclerosis, and nephrosclerosis, plasma ET-1 levels are increased compared with patients with uncomplicated essential hypertension. Similarly, plasma ET-1 concentrations are markedly increased in patients with end-stage renal disease undergoing dialysis, and this correlates with blood pressure, suggesting that ET-1 may contribute to hypertension in these patients. The treatment of anemia in patients with renal failure with human recombinant erythropoietin increases blood pressure by accentuating the underlying endothelial dysfunction and the elevated vascular ET-1 production. Overall, these results support a role for ET-1 in hypertension and the end-organ damage associated with chronic renal failure. ETA receptor blockade may then represent a potential target for the management of hypertension and cardiovascular and renal protection.     

C3 polymorphism in Greece

The polymorphism of the third component of the human complement (C3) was investigated in a sample of 1,055 unrelated healthy individuals from nine different areas of Greece. The estimated gene frequencies were: C3S = 0.786 and C3F = 0.211. Three individuals were found to have rare variant C3 types. The allele frequencies resemble those reported for other Caucasian populations.