[Results of systematic subtotal parathyroidectomy with thymectomy for tertiary hyperparathyroidism after renal transplantation - 70 patients]. / Résultats de la parathyroïdectomie subtotale de principe associée à une thymectomie systématique pour le traitement de l'hyperparathyroïdisme tertiaire après transplantation rénale chez 70 patients.

BACKGROUND: Due to the relatively small number of patients involved, there is currently no consensus on what operation should be performed in patients with tertiary hyperparathyroidism after renal transplantation. METHOD: Retrospective analysis of the 70 patients with tertiary hyperparathyroidism who all underwent subtotal parathyroidectomy with transcervical thymectomy in the same institution between 1978 and 2003. RESULTS: The delay between transplantation and parathyroidectomy was 4,1+/-4,3 years. Follow up was available for all patients. Mean follow-up was 5,6+/-5 years. Glomerular filtration rate (GFR) was 53+/-21 ml/min at parathyroidectomy and 42+/-29 ml/min at follow-up [<30 ml/min in 26 patients (37%), 30 - 60 ml/min in 25 patients (36%) et>60 ml/min in 19 patients (27%)]. One patient was successfully reoperated for persistent tertiary hyperparathyroidism during follow-up. No patient was hypercalcemic at follow-up. Four patients with a GFR<30 ml/min had a PTH level>fourfold normal values (6%) without signs or symptoms of hyperparathyroidism. One patient was hypocalcemic (1,5%) and two patients were normocalcemic with undetectable or infranormal PTH level (3%) under oral vitamin D and calcium medication. CONCLUSION: This approach permits not only to cure the majority of patients with tertiary hyperparathyroidism but also to avoid recurrence when the renal function declines. When medical management has failed, we recommend systematic subtotal parathyroidectomy with thymectomy for patients with tertiary hyperparathyroidism and this should usually be performed during the second year after transplantation.

Evolution pattern of auto-antibodies against oxidized low-density lipoproteins in renal transplant recipients.

An increased degree of oxidative stress in renal transplant recipients and a possible role of ciclosporin A (Cs-A) immunosuppressive therapy in this process have already been described. However, prospective data using in vivo markers and the influence of Cs-A in the oxidizability of low-density lipoprotein (LDL) are scarce. We aimed at investigating in this prospective study the evolution pattern of auto-antibodies directed against malondialdehyde-modified LDL (MDA-LDL) and Cu2+-oxidized LDL in 28 stable renal transplant recipients on Cs-A immunosuppressive therapy before and after 3 successive years of renal transplantation. Also, the effect of enrichment of LDL with Cs-A on the susceptibility of LDL to in vitro oxidation was tested. The results showed a significant increase of both auto-antibody titres (MDA-LDL and Cu2+-oxidized LDL) after 1 year, and the values remained high during the 2nd and the 3rd year following transplantation. The yearly mean relative variations of auto-antibodies against MDA-LDL and Cu2+-oxidized LDL during the follow-up period were 133, 149, and 137%, and 111, 115, and 117%, respectively. A significant correlation was observed during the 1st year between Cs-A trough blood level and Cu2+-oxidized LDL auto-antibody: r = 0.04 (p = 0.046). Incorporation of Cs-A into LDL from healthy volunteers showed no changes during the lag phase in comparison with Cs-A-free LDL, indicating that Cs-A had no effect on in vitro LDL oxidizability. Our results suggest that Cs-A may be involved earlier in the LDL oxidation, but the mechanism by which it acts is still unclear.

Apo(a) phenotypes and lp(a) concentrations in renal transplant patients.

Plasma lipoprotein (a) (LP(a)) concentrations are increased in patients with end-stage renal disease. Considering the influence of the apolipoprotein (a) (Apo(a)) polymorphism and the mode of dialysis in this prospective longitudinal study, we compared Lp(a) concentrations before and after the first 6 months of a successful kidney transplantation in 125 recipient patients. Apo(a) phenotyping was performed by using SDS-PAGE and SDS-agarose, isoforms were classified into high molecular weight (HMW) and low molecular weight (LMW). Before the graft, the Lp(a) concentrations were significantly higher in CAPD than in hemodialysis patients (p = 0.021). Six months after transplantation, Lp(a) fell in both treatment groups. This decrease occurred within both LMW and HMW but to a different extent: median relative variations were -35 and -50%, respectively (p = 0. 048). Among patients with Lp(a) concentration >30 mg/dl 6 months after transplantation, 74% had LMW Apo(a) isoform while the remaining 26% had HMW isoform. Successful renal transplantation leads rapidly to a correction of Lp(a) concentrations, especially in patients treated with CAPD who have higher Lp(a) levels. The most important factor seems to be the LMW status corresponding to high Lp(a) levels.

Alteration of the lipid and apolipoprotein contents of lipoprotein (a) in haemodialysis patients.

BACKGROUND: To examine the possible alteration in Lp(a) composition, protein and lipid contents of Lp(a) were determined in 10 haemodialysis patients (HD) matched with 10 controls (C) for apo(a) phenotypes. METHODS: All subjects (HD and C) had Lp(a) concentrations greater than 30 mg/dl (mean+/-SD : 82.3+/-41.4 vs 49. 3+22.5 mg/dl), a concentration which has been determined to be associated with an elevated cardiovascular risk. Apo(a)-containing particles were isolated by immunoaffinity chromatography using a monoclonal anti-apo(a) antibody. RESULTS: The molar concentrations of lipid and protein constituents of immunoaffinity isolated Lp(a) were expressed as number of moles per mole of apo(a). Lp(a) from HD patients were significantly richer in apo Cl11 (P<0.05) and triglycerides (TG) (P<0.05), compared to those of controls. Molar ratios of apo B, apo E, cholesterol and phospholipid s per apo(a)-containing particles were in the same range in both groups. CONCLUSION: Lp(a) from HD patients is characterized by an elevated content in TH and apo Cl11 in comparison with those of controls. Further studies are needed to evaluate in HD patients the contribution of changes in Lp(a) composition towards the metabolism of these particles.

Apolipoprotein AI and apolipoprotein B containing particle analysis in normolipidemic hemodialyzed patients: evidence of free apolipoprotein E.

Whole plasma from 6 normolipidemic chronic renal failure (CRF) patients undergoing hemodialysis treatment was passed through the anti-apolipoprotein (Apo) AI immunosorbent column connected to the anti-Apo B immunoaffinity column. Apo AI and B containing particles were analyzed for lipid and Apo contents. The results were compared with findings obtained in age-matched normolipidemic healthy controls. Although plasma Apo AI and AII levels decreased in CRF patients, the concentrations of Apo CII, CIII, and E coeluted with Apo AI were similar to those of the controls. The slightly elevated plasma concentrations of Apo CII and CIII in the CRF patients studied were shown to be associated with Apo B containing particles. The nonretained fraction from both groups contains no Apo AI and no Apo B, but still contains lipids and other Apo such as Apo AII and Apo CII. The occurrence of approximately 29% of plasma Apo E in this fraction constitutes the main abnormality found in these patients (< 5% in controls). A two-phase electroimmunoassay shows that this Apo E did not correspond to the plasma E-AII complex. These findings show that the compositional alterations of Apo AI and Apo B containing particles in CRF patients were observed even in normolipidemic patients and suggest that the kidney may play a metabolic role in the removal of free forms of lipoprotein particles such as free Apo E.

Expression of apolipoprotein B epitopes in low density lipoproteins of hemodialyzed patients.

Serum and isolated low-density lipoprotein (LDL) composition abnormalities were investigated in 20 hemodialyzed patients with chronic renal failure and 15 healthy normolipidemic subjects for comparison. LDL apolipoprotein B (apo B) epitope accessibility was determined by the use of seven monoclonal antibodies (Mabs). These Mabs recognize fragments on the N-terminal part of apo B (Mabs B1, B4), on the middle part (Mab BL7), on the C-terminal (Mabs BA11, BL3), and the two remaining Mabs recognize conformational epitopes of apo B (BL5, DA7). Mab BA11 recognizes a fragment of apo B which interacts with the B/E receptor. In hemodialyzed patients, LDL content of triglycerides (P < 0.001) and apo CIII (P < 0.005) was increased, while cholesteryl esters (P < 0.005) were decreased. The accessibility of BL5 epitopes of LDL apo B was enhanced (P < 0.05), while BA11 epitope expression was decreased (P < 0.01). The conformation of patients' LDL (CRF-LDL) was probably abnormal and seemed to be related to some modification of the lipidic environment. It is important to consider a structural modification as it alters the B/E receptor recognition domain of apo B. These results confirm LDL abnormalities in hemodialyzed patients and suggest a possible modification of the recognition of the LDL by cells.

Quantification of beta 2-microglobulin and albumin in plasma and peritoneal dialysis fluid by a noncompetitive immunoenzymometric assay.

An enzyme-linked immunosorbent assay (ELISA) was developed for measuring beta 2-microglobulin (beta 2m) and albumin in continuous ambulatory peritoneal dialysis (CAPD) fluid. Plasma concentrations of beta 2m were twofold greater in hemodialysis patients (41.3 +/- 13.3 mg/L) than in CAPD patients (23.6 +/- 5.5 mg/L) matched for duration of treatment. Measurement of beta 2m in CAPD fluid showed a substantial loss of this protein, approximately 31% of total body beta 2m, compared with a 5% loss of a protein of middle molecular mass (albumin). Because of the molecular sieving effects of the peritoneal membrane, peritoneal clearance of beta 2m was sixfold greater than that of albumin. Whether beta 2m losses prevent or delay the incidence of dialysis-induced amyloidosis in these patients remains to be established.

Plasma level of lipoprotein Lp(a) is high in predialysis or hemodialysis, but not in CAPD.

Plasma Lp(a) lipoprotein level was determined in chronic renal failure (CRF) patients, 24 before initiation of dialysis, 18 undergoing hemodialysis, and 24 on continuous ambulatory peritoneal dialysis (CAPD). Eighteen healthy subjects were studied as controls. Median of Lp(a) level in both predialysis and dialysis patients was significantly increased: 23.5 mg/dl (range: 0 to 109) and 24.0 mg/dl (range: 1.4 to 90), respectively, as compared to healthy controls: 4.7 mg/dl (range: 1.8 to 27; P less than 0.001). By contrast, the median Lp(a) level in CAPD patients, 2.4 mg/dl (range: 0 to 39.5), was similar to the control group. Whether the CAPD procedure reduces the Lp(a) level in CRF patients has to be established in a prospective study.

Apo AIV in plasma and dialysate fluid of CAPD patients: comparison with other apolipoproteins.

Plasma lipids and apolipoproteins were determined in 18 patients with chronic renal failure on haemodialysis (HD), 18 patients on continuous ambulatory peritoneal dialysis (CAPD), and 18 healthy controls. Significant differences were observed between the two dialysis procedures, CAPD patients showed elevated plasma cholesterol, apo AI and apoB. No significant difference in plasma apo AIV concentration was observed between the two dialysis groups. Measurement of apolipoproteins in the dialysate fluid of five patients on CAPD showed losses of all apolipoproteins (AI, AII, AIV, B, CII, CIII and E). Although daily losses of apo AI and apo AIV were similar (255 and 221 mg/day respectively), the peritoneal clearance of apo AIV was threefold that of apo AI and 12-fold that of apo B. In view of the inverse correlation between peritoneal clearance and the molecular mass of proteins, about 13% of total plasma apo AIV was lost daily as lipoprotein-free form.

[Auricular chondritis, malignant glomerulonephritis and pulmonary hemorrhage]. / Chondrite auriculaire, glomérulonéphrite maligne et hémorragies pulmonaires.

Relapsing polychondritis is a rare connective tissue disorder characterized by inflammation of cartilagenous structures such as ears, nose, joints, trachea and larynx. Renal disease is unusual. A 41 years old man presented with auricular chondritis, subacute renal failure and lung hemorrhage. A renal biopsy disclosed a diffuse proliferative glomerulonephritis with extensive crescents. Immunofluorescent studies suggested a GNRP type III so called "non immunologic disease". He was treated by prednisone and plasmapheresis with rapid disappearance of pulmonary hemorrhages and good renal functional improvement.

Lipoprotein particles in homozygous familial hypercholesterolemic patients treated with portacaval shunt and LDL apheresis.

Lipoprotein particles containing apolipoproteins (Apo) were studied by enzyme-linked-immunosorbent assay in two homozygous familial hypercholesterolemic patients (1 male and 1 female) with portacaval shunts, and in controls. Total Apo B, total cholesterol and LDL cholesterol were increased in both patients while complex Apo B containing particles, Lp CIII: B, were not increased in these FH patients. The dextran-sulfate cellulose columns (Liposorber LA-40) had an excellent adsorption selectivity and adsorption capacity for lipoprotein particles containing Apo B and a minimum adsorption capacity in Apo AI and Apo AII-containing particles. This apheresis technique selectively depleted plasma of atherogenic Apo B-containing particles with a minimal loss of antiatherogenic Apo AI-containing particles.

[Rapidly progressive glomerulonephritis in pneumoconiotic coal miners]. / Glomérulonéphrites rapidement progressives chez les mineurs de charbon pneumoconiotiques.

We review a series of 11 silicotic coal miners demonstrating a progressive renal failure with a syndrome of rapidly progressive glomerulonephritis. Renal biopsies reveal crescentic glomerulonephritides associated three times with angeitis. These cases confirm that silica induced glomerulonephritides can be an occupational hazard and warrant further clinical and epidemiological research.

[Application of the immunoenzyme technic in double determination of antibodies for the study of hyperlipoproteinemia]. / Application de la méthode immunoenzymatique à double détermination d'anticorps à l'exploration des hyperlipoprotéinémies.

Antibodies directed against designed apolipoprotein, were absorbed on microtiter plates, the other apolipoprotein present on the retained particles was evaluated by using corresponding peroxidase labeled antibodies. This differential antibody immunosorbent assay was applied to evaluate lipoprotein particles concentration in familial type IIa, IIb, III, IV, and in the type IV secondary to chronic renal failure. Type IIa and IIb, were characterized by the increasing plasma concentration of lipoprotein particles containing both apo B and apo E (LpE-B). Although type IIa have high level of apo CIII, the plasma concentration of lipoprotein containing both apo B and apo CIII was within the normal range. The high concentration of apo E in type III hyperlipoproteinemia, revealed the accumulation of LpB-CIII-E but mainly lipoproteins containing both apo B and apo E (LpE-B). The latter represents 0.94 +/- 0.51 g/l when compared to normolipidemic subjects: 0.29 +/- 0.06 g/l. The decrease concentration of apo AI affects essentially lipoprotein containing apo AI without apo AII (LpAI) in primary type IV hyperlipoproteinemic patients, while in chronic renal failure, both populations of apo AI (with and without apo AII) were affected. The differential antibody immunosorbent assay may be used in the future as a new approach to classify lipid transport disorders.

Effects of fish oil rich in polyunsaturated fatty acids on hyperlipidemia of hemodialysis patients.

Hemodialysis (HD) patients have a high incidence of hyperlipidemia. Hypertriglyceridemia is the most frequent abnormality encountered. It results mainly from a defect in the degradation of triglycerides. The aim of this study was to evaluate the efficacy of a fish oil (Max-EPA) rich in polyunsaturated fatty acids (PUFA), such as eicosapantenoic acid (EPA), on lipid abnormalities of hemodialysis patients. Thirteen hyperlipidemic HD patients were investigated (7 males, 6 females; mean age 57 years; mean duration of HD 72 months). None were diabetic or treated with antihypertensive drugs. All patients had hypertriglyceridemia (greater than 200 mg/dl) and an increase (greater than 1) in the ratio of serum apolipoprotein B to serum apolipoprotein A1 (ApoB/ApoA1). They received for one month, 6 g/day of Max-EPA providing 1 g of EPA. After treatment, serum triglyceride levels fell by 38% from 231 +/- 40 (SD) mg/dl to 140 +/- 38 mg/dl (P less than 0.01). Total cholesterol did not change significantly (before therapy 241 +/- 33 mg/dl, after therapy 249 +/- 38 mg/dl). Apolipoprotein A1 levels (116 +/- 17 mg/dl) were not modified after therapy, 117 +/- 11 mg/dl. Apolipoprotein B decreased significantly from 182 +/- 26 mg/dl to 150 +/- 21 mg/dl after treatment (P less than 0.01). The ApoB/ApoA1 ratio showed a significant decrease from 1.56 +/- 0.26 to 1.3 +/- 0.16 after therapy (P less than 0.01). Also, the greatest reductions were found in the patients who had both the highest serum triglyceride levels and the highest ApoB/ApoA1 ratios. No side effects were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein B metabolism in homozygous familial hypercholesterolemia.

This report describes the metabolism of apolipoprotein B-containing lipoproteins in seven familial hypercholesterolemic (FH) homozygotes and compares the results to the values obtained from five healthy control subjects. The concentration, composition, and metabolism of large, triglyceride-rich very low density lipoproteins (VLDL1, Sf 60-400) were the same in the control and FH groups, indicating that this component of the VLDL delipidation cascade ws unaffected by the absence of receptors. In contrast, familial hypercholesterolemic small VLDL2 (Sf 20-60) was enriched with cholesterol and depleted in triglyceride. Moreover, its plasma concentration was elevated as a result of an increase in its synthesis and a defect in the removal of a remnant population within this density interval. The latter accounted for up to 50% of the total mass of the fraction. Onward transfer of apolipoprotein B (apoB) from small VLDL through intermediate density lipoprotein (IDL) to low density lipoprotein (LDL) was retarded, suggesting that receptors were involved in this supposedly lipase-mediated event. IDL and LDL concentrations increased up to fourfold above normal in the plasma of the FH patients due partly to the delay in maturation and partly to defective direct catabolism. We conclude that the LDL receptor plays multiple and important roles in the metabolism and transformation of apoB-containing particles in the Sf 0-400 flotation interval.

Apolipoprotein B immunochemical heterogeneity in dialysed patients with chronic renal failure and patients with coronary artery stenosis.

Serum cholesterol, triglyceride, apolipoprotein B (apo B) and the cholesterol and phospholipid content of apo-B-containing particles was determined in 41 male patients on dialysis for chronic renal failure, in 41 male patients with coronary artery disease selected on the basis of a total cholesterol level below 6.72 mmol/l and in 41 male control subjects of similar age. Apo B was assessed as total B protein determined using polyclonal antibodies and also by measuring the expression of epitopes recognized by three different monoclonal antibodies (BL3, BL5 and BL7). Triglyceride was increased (p less than 0.01) and cholesterol was decreased (p less than 0.01) in the dialysed patients with chronic renal failure. Total apo B was similar in the three tested groups while the expression of the BL7 epitope was increased in the group of dialysed patients with chronic renal failure (p less than 0.001). The expression of BL3 and BL5 epitopes was increased in patients with coronary artery disease (BL3: p less than 0.05; BL5: p less than 0.02) but not in dialysed patients with chronic renal failure. These results suggest an abnormal composition and an immunological heterogeneity of apo-B-containing lipoprotein particles in patients with coronary artery stenosis and in dialysed patients with chronic renal failure.