Molecular and genetic aspects of preeclampsia: state of the art.
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Angiotensinogen↗
Biomedical subjects
S Túri
Publications and source records attributed to S Túri.
Vitamin E alleviates the oxidative stress of erythropoietin in uremic children on hemodialysis.
The efficacy of combined therapy with recombinant human erythropoietin (rhEPO) and vitamin E versus rhEPO alone in the treatment of anemia was examined in children (n = 10, aged 15.2 +/- 3.2 years) on chronic hemodialysis at the restart of rhEPO therapy after a 4-week interval. The results confirmed that rhEPO induced oxidative stress of the red blood cells as observed during the first rhEPO therapy. Vitamin E (15 mg/kg per day per os) was introduced after 2 weeks of rhEPO monotherapy, when the signs of acute oxidative stress appeared. The level of oxidized glutathione (GSSG) increased from 8.9 +/- 3.1 to 26.7 +/- 5.7 nmol/g hemoglobin (Hb) by that time. After 2 weeks of simultaneous vitamin E treatment, there was a significant difference in GSSG values compared with rhEPO monotherapy (10.1 +/- 3.9 vs. 56.7 +/- 15.8 nmol/g Hb, P < 0.001). A considerable decrease was observed in the previously high ratio of GSSG/reduced glutathione (GSH), an indicator of oxidative stress, and the level of carboxyhemoglobin, indicating hemolysis. A significant increase in Hb and hematocrit (P < 0.01) was achieved within 2 weeks of starting the combined therapy, while similar results occurred only at the 8th and 5th weeks without vitamin E. Antioxidant vitamin E supplementation improved the therapeutic effect of rhEPO in patients with chronic renal failure on hemodialysis.
Adolescent↗
Erythropoietin and oxidative stress in haemodialysis: beneficial effects of vitamin E supplementation.
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Child↗
Childhood membranous nephropathy, circulating antibodies to the 58-kD TIN antigen, and anti-tubular basement membrane nephritis: an 11-year follow-up.
Childhood membranous nephropathy (MNP) with anti-tubular basement membrane (anti-TBM) nephritis is a rare disorder that may have extrarenal manifestations. This article describes a new case to be added to the 10 previously reported. A renal biopsy specimen from a 1-year-old white boy with nephrotic syndrome, microhematuria, and hypertension showed MNP (granular global IgG, IgA and C3, and segmental IgM and C1q) associated with hypercellularity and granular deposits of IgM and C1q in the mesangium, arteriolar IgA, and linear TBM IgG, IgA, and C3. A biopsy at age 4 years showed MNP (IgG and C3) and linear IgG and C3 along the TBM. Six months later, temporary glucosuria suggested a mild tubular dysfunction. Biopsy at age 8 years showed sclerosing MNP (IgG and C3), linear TBM IgG and C3, and chronic active tubulointerstitial nephritis (TIN). Indirect immunofluorescence showed circulating anti-TBM antibodies, and the enzyme-linked immunosorbent assay (ELISA) approach verified strong reactivity with the 58-kd TIN antigen. Despite trials with steroids, chlorambucil, azathioprine, and cyclosporine, end-stage renal disease developed by the age of 9 years. At age 10 years, the patient received a cadaveric kidney transplant. With the patient now aged 12 years, the graft is still functioning well, without any clinical evidence of disease recurrence. Neurological, ocular, and abdominal symptoms, including nonbacterial diarrhea, were observed during the follow-up period. The pathophysiology of these extrarenal symptoms remains unclear. Serotyping and genotyping of HLA antigens (A2, A10, B12, B41, DR5 [1101, 1103-4, 1106 or 1108-1113], DR6 [1303, 1312, or 1413], DRB3 [*0101 and 0201-2 or 0301], DQA1 [*0501 homozygous], and DQB1 [*0301 homozygous]) did not indicate any HLA association similar to those described previously in childhood MNP with anti-TBM nephritis (HLA-B7 in four patients, HLA-DR8 in two patients). The presented case is the fifth in the literature that displays reactivity with the 58-kd TIN antigen, and for which data on HLA antigens are reported.
Antibodies↗
Increased platelet thromboxane release in focal segmental glomerulosclerosis.
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Adult↗
[Thin glomerular membrane nephropathy. Clinico-pathological observations].
In two nephrology centres between 1983 and 1993 among 1545 kidney biopsies 34 cases of thin basement membrane nephropathy have been diagnosed. All patients had a varying degree of microscopic dysmorph haematuria, occasional slight proteinuria--except two nephrotic children; and normal blood pressure with one exception. 5 children and 7 adults experienced repeated bouts of macroscopic haematuria mainly after exercise or upper respiratory tract infection, one child after tonsillectomy. All patients had normal renal function and retained it during the follow-up period (mean 61 months, 3 months to 22 years), except a 46 year old patient, who was found to have the joint occurrence of light chain gammopathy and hypertension. Seven patients had positive family history for microscopic haematuria, in four family members of three patients renal biopsy disclosed mesangioproliferative glomerulonephritis with thin GBM segments. As a cut off value for thin basement membrane nephropathy we considered 264 nm. The morphometric analysis of the electron micrographs revealed a mean thickness of 210 nm. No differences in basement membrane thickness were measured regarding gender, age or the presence of macroscopic haematuria. The thin basement membrane is considered to be the pathological basis and predisposing alteration leading to haematuria.
Adolescent↗
Mitochondrial mutation as a probable causative factor in familial progressive tubulointerstitial nephritis.
Renal biopsy of two children and a maternal relative, diagnosed with severe progressive tubulointerstitial nephritis, has shown the presence of distorted mitochondria. Mitochondrial DNA from the blood of these patients was analysed. No major deletions were found, but an A to G mutation was detected in position 5656. It is proposed that this mutation might play a causative role in the renal disease of the patients.
Adult↗
Oxidative stress and antioxidant defense mechanism in glomerular diseases.
The changes in red blood cell (RBC) lipid peroxidation [measured via the malonyl dialdehyde (MDA) concentration], reduced (GSH), and oxidized glutathione (GSSG) levels, hemoglobin (Hb) oxidation and antioxidant enzyme [catalase (Cat), glutathione peroxidase, and superoxide dismutase (SOD)] activities were studied in 45 pediatric patients with various glomerular diseases [minimal change nephrotic syndrome (MCNS) in relapse or in remission, lupus nephropathy (SLE), poststreptococcal glomerulonephritis (APSGN), IgA nephropathy (IGA gn)], and in 20 adult patients with IGA gn and also in 15 pediatric and 14 adult controls. The in vitro effects of hydrogen peroxide [acetyl phenylhydrazine (APH) test] on the GSH and Hb metabolisms were likewise investigated. There was an increased oxidative stress in MCNS with relapse, IGA gn, SLE gn, and APSGN, which could be detected in the GSH and Hb oxidation and in the lipid peroxidation on the peripheral RBC-s. The RBC SOD and Cat activities were significantly lower in all patients than in the controls. The RBC GSSG level was significantly elevated in all patients, with the exception of MCNS in remission. This stimulated a compensatory GSH production in MCNS with relapse and in IGA gn, but not in SLE or APSGN. The regeneration of GSH from GSSG was reduced in MCNS with relapse, SLE, and IGA gn, but not in APSGN. In remission, the GSH-GSSG redox system normalizes, but in vitro the APH test stimulates an intensive Hb oxidation. In conclusion, there is a correlation between the presence of active glomerular disease and the evidence of oxidative changes in the various parameters measured in peripheral RBCs.
Adolescent↗
Oxidative damage of red blood cells in haemolytic uraemic syndrome.
Changes in red blood cell (RBC) lipid peroxidation [measured by malonyl dialdehyde (MDA) concentration], glutathione (GSH) metabolism, antioxidant enzyme activities (catalase, superoxide dismutase, glutathione peroxidase) and haemoglobin (Hb) metabolites (metHb, carboxy Hb) were studied in six children with post-enteropathic (D+) haemolytic uraemic syndrome (HUS) and ten controls. The in vitro effect of hydrogen peroxide [acetylphenylhydrazine (APH) test] on GSH and Hb metabolism was also investigated. MDA levels were significantly higher and the antioxidant enzyme activities were lower in HUS patients than in the controls (P < 0.01). The oxidised glutathione concentration was significantly higher in the patients than in the control children (26.3 +/- 12.6 vs. 10.9 +/- 1.8 nmol/g Hb. Percentage values of carboxy Hb and metHb were also higher in HUS (P < 0.01). Incubation of RBC with APH induced a more pronounced decrease in the concentration of GSH (P < 0.001) and a significant increase (P < 0.01) in the level of metHb and carboxy Hb in the HUS patients. This suggests that there is reduced RBC GSH stability in HUS. Utilisation of GSH and antioxidant enzymes leads to increased Hb oxidation and haemolysis. The oxidative damage may have an important role in the pathogenesis of haemolytic anaemia in HUS.
Adolescent↗
[Successful treatment of acute tubulointerstitial nephritis associated with infectious mononucleosis and causing severe uremia].
A ten years old boy with severe acute renal failure was presented. The development of acute uremia was proceeded by infectious mononucleosis. Renal biopsy revealed acute tubulointerstitial nephritis. Peritoneal- and haemodialysis was completed by steroid therapy and cytostatic treatment when glomerular proteinuria was observed. Following a 2 months uremic period the patient cured completely.
Acute Disease↗
Hereditary nephritis, platelet disorders and deafness-Epstein's syndrome.
A 14-year-old boy with persistent proteinuria (1.6-4.0 g/day), microscopic haematuria, moderate hypertension, macrothrombocytopenia (giant platelets, platelet number 30 x 10(9)/l) and a familial sensorineural hearing loss (the father and the brother were also affected) was studied. Kidney biopsy revealed a diffuse mesangial proliferation, and a focal thickening of the glomerular basement membrane was seen on electron microscopy. A normal number of megakaryocytes was observed in bone marrow aspirates. The aggregation response of the platelets to collagen, epinephrine and adenosine diphosphate (ADP) was decreased. The platelet number was slightly diminished, platelets were of normal size in both parents and the brother, and showed a decreased aggregability in response to collagen, epinephrine and ADP in the brother and mother. No functional abnormality of the platelets was observed in the father. Urinalysis and kidney function were normal in the family members. This boy with nephritis, platelet disorders and hearing loss corresponds to Epstein's syndrome.
Adolescent↗
The effect of erythropoietin on the cellular defence mechanism of red blood cells in children with chronic renal failure.
The glutathione redox system, haemoglobin (Hb) oxidation, the activity of antioxidant enzymes and the lipid peroxidation product malonyl dialdehyde (MDA) were studied in red blood cells (RBCs) during administration of recombinant human erythropoietin (rhEPO) over 12 weeks in ten children maintained on haemodialysis. A rapid increase in the reticulocyte count was accompanied by a slower rise in total Hb concentration. The mean level of oxidized glutathione (GSSG) increased from 13.2 +/- 5.3 nmol/g Hb to 56.7 +/- 15.8 nmol/g Hb 4 weeks after the start of rhEPO (P < 0.001), followed by a fall to the basal value. Reduced glutathione (GSH) levels showed a smaller though constant elevation during rhEPO therapy (P < 0.001). Before rhEPO treatment, incubation of RBCs for 1 h with acetylphenylhydrazine induced a decrease in GSH concentration compared with controls (P < 0.001), which became more pronounced in the first few weeks of rhEPO therapy (P < 0.001). In addition, the percentage of Hb derivatives (metHb and haemichrome) increased in the first 4 weeks of rhEPO therapy (P < 0.001). Although there was no significant difference between the values obtained preEPO and during EPO treatment, MDA levels were continuously higher and superoxide dismutase, catalase and glutathione peroxidase concentrations were lower than in the controls (P < 0.001). These results are compatible with oxidative damage to the RBCs in the early period of rhEPO therapy in children with end-stage renal failure. The GSH-GSSG system, as an important cellular defence mechanism of the RBCs, appears to be severely affected.
Adolescent↗
[Macrothrombopenia, nephritis and hearing loss--a new case of Epstein syndrome].
A 14 years old boy with persistent proteinuria (1.6-4.0 g/day), microscopic haematuria, macrothrombocytopenia (giant platelets, platelet number 30 G/l), and a familial sensorineural hearing loss (the father and the brother were also affected) was studied. Kidney biopsy presented a diffuse mesangial proliferation, and a focal thickening of the glomerular basement membrane was seen on electron microscopy. With bone marrow aspiration normal number of megacaryocytes was observed. The aggregation response of the platelets was decreased on collagen, epinephrine and ADP but it was normal on aggristin. The presented case with nephritis, platelet disorders and hearing loss corresponds to Epstein syndrome, a variant of Alport's syndrome.
Adult↗
[Comparative study of acetate and bicarbonate hemodialysis in children with chronic uremia].
Comparative studies on 5 children suffering from chronic uremia were performed regarding the efficacy of acetate and bicarbonate hemodialysis. Clinical symptoms, acid-base and blood gas analysis, serum osmolality, blood pressure and EEG were examined. On authors experience the patients tolerated better the bicarbonate dialysis. Laboratory data and blood pressure were found to be closer to the normal values too. The abnormality of EEG made after bicarbonate dialysis were not so expressed than that of acetate dialysis. On the basis of this examinations the authors suggest the bicarbonate hemodialysis in uremic patients with severe cardiovascular and/or neurological complications.
Acetates↗
The effects of vitamin E on tissue oxidation in nephrotoxic (anti-glomerular basement membrane) nephritis.
The effects of vitamin E on tissue oxidation, kidney function and morphology were studied in rats with nephrotoxic nephritis (NTN). Thirty-six nephritic animals received no treatment (group 1), while 36 were treated with vitamin E (group 2). Twenty-four hours after the administration of anti-glomerular basement membrane antibody, sulfhydryl-containing renal protein was significantly lower in group 1 than in group 2 (0.70 +/- 0.16 and 1.08 +/- 0.06 mmol/100 g kidney tissue, respectively), suggesting a free oxygen radical scavenging effect of vitamin E in group 2. The difference was similar on day 14. The creatinine clearance was significantly lower in group 1 than in group 2 on day 1 (40 +/- 30 and 204 +/- 60 microliter/min per 100 g body weight, respectively). The protein excretion was initially high in both groups, but a significant decrease was detected in group 2 relative to group 1 on day 14 (25 +/- 18 and 92 +/- 38 mg/24 h, respectively). The morphological changes were less severe in group 2. Vitamin E treatment did not alter any of the above values significantly in healthy animals. The release of oxygen free radicals in NTN might play an important role in the pathogenesis, which can be influenced by free radical scavengers through changes in kidney function and morphology.
Animals↗
The effects of bicarbonate and acetate haemodialysis on platelet cyclic AMP concentration, thromboxane B2 release and aggregation.
The effects of chronic uraemia and serial acetate (HDA) or bicarbonate (HDB) haemodialysis on the aggregation, thromboxane B2 (TXB2) release and cyclic AMP (cAMP) concentration of platelets from arterial blood were studied in 14 uraemic patients (6 dialysed and 8 conservatively treated) and 10 controls. Platelets from uraemic patients, either dialysed or treated conservatively, exhibited a significantly higher cAMP level (P less than 0.005), a lower TXB2 level (P less than 0.01), and a lower aggregability (P less than 0.001) than the controls. The platelet cAMP level was more markedly decreased after HDB than after HDA (P less than 0.05). Greater increases in platelet aggregation (P less than 0.05) and TXB2 formation were observed after HDB than after HDA. The concentration of platelet cAMP and aggregability, and also the platelet cAMP and the TXB2 level showed a significantly negative correlation (r = -0.7, P less than 0.05 and r = -0.60, P less than 0.05, respectively). There was a positive correlation between the platelet-derived TXB2 and the aggregability (r = 0.67, P less than 0.05). Although most patients had secondary hyperparathyroidism, the serum parathyroid hormone level did not correlate closely with the cAMP, TXB2 or aggregation results. The dysfunction of uraemic platelets accompanied by a reduced TXB2 release may be explained by an increased cAMP and a decreased arachidonic acid availability. HDB improves the platelet function to a greater degree than does HDA.
Acetates↗
Erythrocyte defense mechanisms against free oxygen radicals in haemodialysed uraemic children.
Changes in erythrocyte lipid peroxidation (measured as the concentration of malonyl dialdehyde), glutathione metabolism, antioxidant enzyme activities (glutathione peroxidase, catalase, and superoxide dismutase), the oxidized products of haemoglobin (Hb), and hydrogen peroxide (H2O2)-induced haemolysis were studied in six children with chronic renal failure treated with serial acetate and bicarbonate haemodialysis (HD). Ten age- and sex-matched children acted as controls. Malonyl dialdehyde levels were significantly higher and antioxidant enzyme activities lower in uraemic red blood cells (RBCs) compared with controls (P less than 0.05). Incubation of RBCs for 1 h with acetylphenylhydrazine induced a decrease in the concentration of reduced glutathione (P less than 0.001) and an increase in the level of oxidized products of Hb (P less than 0.001), but only in the uraemic patients. The H2O2 haemolysis test revealed a mild (n = 3) to increased (n = 3) haemolysis in the uraemic RBCs. Oxidative haemolysis is probably a multifactorial process in uraemic patients, and may be an important risk factor in HD therapy.
Adolescent↗
[Prostacyclin-like activity modifying plasma factors in diabetic microangiopathy].
The plasma factors influencing PGI2-like activity in 19 patients with diabetes mellitus (Dm) and 17 control subjects were studied by comparing the signs of retinal versus glomerular angiopathy. The plasma PGI2-supporting activity (PSA) was lower in 15 Dm cases than in the controls. Inhibitory activity against PGI2 production was detected in 6 patients. When more serious retinopathy was associated with glomerulopathy, a significantly lower level of PSA was observed than in patients with mild retinopathy without glomerular disease. The plasma concentrations of total and LDL cholesterol were significantly higher, while the level of HDL cholesterol was lower than in the controls. There was a positive correlation between PSA and HDL cholesterol values and a negative correlation between PSA and LDL cholesterol levels, which is related to the inhibitory effect of LDL and the protective role of HDL in PGI2 synthesis.
Cholesterol↗