Conversion from cyclosporin to azathioprine after kidney transplantation.
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Biomedical subjects
Publications and source records attributed to K Lhotta.
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Recent studies have indicated a beneficial effect of one particular low molecular weight heparin preparation (Fragmin) on lipid metabolism in patients on chronic hemodialysis as compared to unfractionated heparin. We conducted a prospective crossover study with paired comparison of two different anticoagulant agents to examine the effects of a recently released new low molecular weight heparin (Sandoparin) on lipid and lipoprotein parameters in 24 patients starting hemodialysis. During the first six months of observation patients received Sandoparin. Then patients were switched to unfractionated heparin and observed for further six months. After switching from Sandoparin to unfractionated heparin we observed significant decreases in total cholesterol (from 168.6 +/- 42.2 to 154.4 +/- 41.9 mg/dl, p < 0.02), LDL cholesterol (from 106.4 +/- 35.2 to 89.9 +/- 32.3 mg/dl, p < 0.005), triglycerides (from 148.7 +/- 85.0 to 121.4 +/- 88.8 mg/dl, p < 0.05) and apolipoprotein B (from 100.0 +/- 35.3 to 89.9 +/- 30.4 mg/dl, p < 0.05) and a significant increase in HDL cholesterol (from 32.8 +/- 12.5 to 37.7 +/- 17.5 mg/dl, p < 0.02). This is in contrast to earlier results and can possibly be explained by a higher percentage of fractions with high M(r) in the investigated Sandoparin, which results in a more pronounced depletion of lipoprotein lipase. Together with the enhanced hepatic clearance of lipoprotein lipase induced by low molecular weight heparins, this may decrease lipoprotein lipase activity with a subsequent increase in plasma triglycerides, total and LDL cholesterol. We conclude from our data that a general recommendation for clinical use of low molecular weight heparin in hemodialysis patients cannot be given.
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1. The genetic background of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis remains largely unknown. Recently a very high prevalence of medium and severe deficiency of alpha 1-antitrypsin was described in a small group of patients with Wegener's granulomatosis and c-ANCA. c-ANCAs are autoantibodies against proteinase 3, and alpha 1-antitrypsin is the main inhibitor of this enzyme. 2. alpha 1-Antitrypsin phenotypic polymorphism was determined by isoelectric focusing in 32 patients with c-ANCA-associated systemic vasculitis. Twenty-nine patients had Wegener's disease, two had microscopic polyarteritis and one suffered from idiopathic rapidly progressive glomerulonephritis. 3. Two patients were homozygous PiZZ and three were heterozygous PiMZ. These phenotype frequencies differed significantly from expected values, assuming Hardy-Weinberg equilibrium (P < 0.01). Compared with a control group of 868 healthy blood donors, these results meant a significant increase in the PiZ allele (0.0138 versus 0.1094, P < 0.001). 4. Furthermore, the serum of 47 patients with severe alpha 1-antitrypsin deficiency (PiZZ) was tested for the presence of ANCA. All sera were negative for c-ANCA and p-ANCA. None of the patients showed clinical signs of systemic vasculitis. 5. In conclusion, these data indicate that alpha 1-antitrypsin deficiency, despite being significantly more common in patients with c-ANCA-associated systemic vasculitis, is only a minor genetic risk factor for the development of this disease.
High lipoprotein(a) [Lp(a)] plasma concentrations are an independent risk factor for atherosclerosis. In the general population, Lp(a) levels are primarily determined by allelic variation at the apolipoprotein(a) [apo(a)] gene locus. Apo(a) isoforms of various sizes are associated with different Lp(a) concentrations. Patients with end-stage renal disease (ESRD) have elevated plasma concentrations of Lp(a), which are not explained by the size variation at the apo(a) gene locus. To further investigate the origin of the elevated Lp(a) plasma concentrations, we examined Lp(a) concentrations and apo(a) phenotypes in 154 ESRD patients undergoing renal transplantation. In a prospective longitudinal study we observed a rapid normalization of Lp(a) levels from an average concentration of 25.9 +/- 28.7 mg/dL before to 17.9 +/- 25.5 mg/dL 3 weeks after renal transplantation (P < .0001). Only patients with high-molecular-weight phenotypes had a significant decrease in Lp(a) plasma concentrations. This study demonstrates the nongenetic origin of elevated Lp(a) concentrations in ESRD patients, which is obviously caused by the disease. It further confirms a phenotype-associated elevation of Lp(a) concentrations in ESRD.
Several studies have demonstrated that atherosclerotic complications are the major cause of morbidity and mortality in hemodialysis patients. High lipoprotein(a) [Lp(a)] plasma concentrations are an independent risk factor for atherosclerosis. Patients with end-stage renal disease (ESRD) have elevated plasma concentrations of Lp(a), which are not explained by size variation at the apolipoprotein(a) [apo(a)] gene locus. The aim of our study was to investigate whether Lp(a) concentrations and/or apo(a) phenotypes are predictive of the degree of atherosclerosis in the extracranial carotid arteries in ESRD patients. Of 167 patients, 108 showed atherosclerotic plaques (65%). Univariate analysis showed that the plaque-affected group was significantly older and had a higher frequency of angina pectoris, previous myocardial infarction, or cerebrovascular accident. Furthermore, this group included significantly more patients with low-molecular-weight apo(a) isoforms (26.9% versus 8.5%, P < .005) and had significantly higher mean Lp(a) plasma concentrations (29.3 +/- 31.0 versus 19.7 +/- 25.7 mg/dL, P < .05). Lp(a) plasma concentration increased significantly with the number of affected arterial sites, from 19.7 mg/dL in patients without plaques to 40.1 mg/dL in patients with seven or eight affected sites. In patients with low-molecular-weight phenotypes, significantly more arterial sites were affected (3.62 versus 2.08, P < .001). Multivariate regression analysis showed that age, angina pectoris, and the apo(a) phenotype were the only significant predictors of the degree of atherosclerosis. We conclude that, besides age, the apo(a) phenotype is the best predictor of carotid atherosclerosis in ESRD patients and may be used for assessment of general atherosclerosis risk in this patient group.
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Described here is a family in which the father with partial C4 deficiency had Wegener's granulomatosis and a son with complete C4 deficiency presented with Henoch-Schönlein Purpura. The possible role of C4 deficiency in the pathogenesis of both vasculitic disorders is discussed.
Patients with terminal renal insufficiency suffer from an increased incidence of atherosclerotic diseases. Elevated plasma concentrations of lipoprotein(a) [Lp(a)] have been established as a genetically controlled risk factor for these diseases. Variable alleles at the apo(a) gene locus determine to a large extent the Lp(a) concentration in the general population. In addition, other genetic and nongenetic factors also contribute to the plasma concentrations of Lp(a). We therefore investigated Apo(a) phenotypes and Lp(a) plasma concentrations in a large group of patients with end-stage renal disease (ESRD) and in a control group. Lp(a) concentrations were significantly elevated in ESRD patients (20.1 +/- 20.3 mg/dl) as compared with the controls (12.1 +/- 15.5 mg/dl, P < 0.001). However, no difference was found in apo(a) isoform frequency between the ESRD group and the controls. Interestingly, only patients with large size apo(a) isoforms exhibited two- to fourfold elevated levels of Lp(a), whereas the small-size isoforms had similar concentrations in ESRD patients and controls. Beside elevated Lp(a) concentrations, ESRD patients had lower levels of plasma cholesterol and apolipoprotein B. These results show that elevated Lp(a) plasma levels might significantly contribute to the risk for atherosclerotic diseases in ESRD. They further indicate that nongenetic factors related to renal insufficiency or other genes beside the apo(a) structural gene locus must be responsible for the high Lp(a) levels.
An unusual case of Goodpasture's syndrome in a 26-year-old man with occupational exposure to hard metal dust is described. The patient developed a life-threatening interstitial lung disease that was followed by a rapidly progressive glomerulonephritis two months later. To our knowledge, association of Goodpasture's syndrome and hard metal exposure has not been reported previously.
Hereditary complete C4 deficiency has until now been detected in 18 patients. A disturbed clearance of immune complexes probably predisposes these individuals to systemic lupus erythematosus and other immune complex diseases. Renal involvement of hereditary complete C4 deficiency is described in seven patients from three families. Three patients of one family suffered from SLE and a severe mesangial and endocapillary proliferative glomerulonephritis which required immunosuppressive treatment. In two patients from a second family a mild focal and segmental mesangioproliferative glomerulonephritis was present which, except for an episode of acute renal failure in one patient, did not cause serious clinical problems. One additional child died without renal involvement. The patient from a third family developed Henoch-Schoenlein purpura, mesangioproliferative glomerulonephritis with segmental scarring and terminal renal failure. Immunofluorescence studies showed deposition of immunoglobulins and complement C3 in the glomeruli. Severity of renal disease is probably determined by activation of the alternative pathway of complement in the kidney.
Implantation of a single-chamber pacemaker was planned in an 83-year-old woman with sick-sinus syndrome causing dizziness, bradycardia and tachycardia. After puncture of the right subclavian vein it proved impossible to advance a guide-wire into the superior vena cava, under fluoroscopy the wire always being seen to coil in the left subclavian vein and hence passing into a caudally directed vein. This vessel proved to be a persistent left superior vena cava (PLSVC) which connected to a markedly dilated coronary sinus (2 cm diameter) opening into the right atrium. An 85-cm electrode was then passed via the PLSVC and right atrium into the right ventricle without difficulty and was anchored in its apex. Echocardiography failed to reveal any further anomaly. Three-dimensional computed tomographic reconstruction established atresia or agenesis of the (right) superior vena cava. Normal pacemaker function freed the patient of all symptoms postoperatively.
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Whether extensive ablation of renal mass in humans leads to progressive glomerulosclerosis, proteinuria, and hypertension, as it does in animal models, is a matter of controversy. We have studied kidney function in six patients who underwent enucleation of a renal cell carcinoma in a solitary kidney. Four patients had previously had a nephrectomy. The two others each had one atrophic, nonfunctioning kidney. Serum creatinine levels before surgery were within the normal range (mean, 99.9 mumol/L [1.13 mg/dL]). Two weeks after tumor enucleation, creatinine levels were significantly higher than the preoperative values (mean, 124.6 mumol/L [1.41 mg/dL]). The follow-up period varied from 10 to 23 months. In all patients, kidney function improved during the following months. Serum creatinine levels nearly reached preoperative values in all patients (mean, 105.2 mumol/L [1.19 mg/dL]). None of the patients showed a progressive deterioration in renal function or proteinuria. We found a modest increase in blood pressure in two patients who had been normotensive before surgery. In conclusion, tumor enucleation in a solitary kidney did not cause significant renal injury to the remnant kidneys in our patients, at least in the short term.
1. Expression of intercellular adhesion molecule-1 was investigated in five normal kidneys and 47 renal biopsies with the use of monoclonal antibody 7F7 and immunoperoxidase staining. 2. In the normal kidney, intercellular adhesion molecule-1 was expressed on endothelial cells of glomerular and peritubular capillaries, on Bowman's capsule, on some interstitial cells and weakly in the mesangium. 3. Increased glomerular staining was detected in early cases of rapidly progressing glomerulonephritis (5/8) and in some cases of non-IgA mesangioproliferative glomerulonephritis (5/9), IgA nephropathy (3/5), Henoch-Schoenlein purpura (2/2), lupus nephritis (5/6) and focal segmental glomerulosclerosis (1/3). A decrease in intercellular adhesion molecule-1 expression was noted in advanced rapidly progressive glomerulonephritis (3/8), two cases of membraneous nephropathy, one severe mesangioproliferative glomerulonephritis biopsy, the two membranoproliferative glomerulonephritis biopsies and in sclerotic loops in focal segmental glomerulosclerosis. 4. Expression de novo on tubular epithelial cells occurred in rapidly progressive glomerulonephritis, in membranoproliferative glomerulonephritis, and to a lesser extent in some cases of membraneous nephropathy, minimal change disease, IgA nephropathy, focal segmental glomerulosclerosis, a severe case of mesangioproliferative glomerulonephritis and in the mixed essential cryoglobulinaemia case. In 63% of positive tubuli, intraluminal cells which expressed CD18, the common beta-chain of leucocyte-function-associated antigen-1, Mac-1 and p150,95, were present. 5. Intercellular adhesion molecule-1 was also found on the majority (59%) of infiltrating mononuclear cells in all forms of glomerulonephritis.
Difficulties may arise in the diagnosis of patients with clinical features suggestive of plasma cell dyscrasia-related amyloidosis (amyloidosis L), but without evidence of a paraprotein. We have employed gene rearrangement methodology to demonstrate the clonality of bone marrow cells not only in a patient with myeloma-associated systemic amyloidosis, but also in a patient with "primary" systemic amyloidosis without overt myeloma or a detectable paraprotein. Furthermore, we have shown the clonality of the amyloid-producing plasma cells within a skin nodule of a patient with primary localized cutaneous amyloidosis; by contrast, clonal rearrangement was not detected in bone marrow cells from this patient. This finding provides definitive proof that organ-limited nodular primary localized cutaneous amyloid deposits arise in relation to cutaneous plasmacytomas. Gene rearrangement studies may enable early diagnosis and initiation of treatment in patients with systemic amyloidosis L, as well as their differentiation from patients with organ-limited nodular cutaneous amyloidosis, who do not require aggressive therapy.
A 27-year-old patient on CAPD presented with febrile illness and abdominal pain suggestive of peritonitis. Dialysis fluid culture yielded Enterococcus. Response to treatment was slow, with pain persisting. Laparotomy revealed a toothpick, which was causing peritoneal irritation. It was unclear how the foreign object entered the peritoneum.