Biomedical subjects
Publications and source records attributed to A Drukker.
Twelve dialysis patients received oral pulse therapy with 1-alpha-hydroxyvitamin D3 in a dose of 0.1 microgram/kg body weight twice weekly and daily calcium carbonate (1.5-3.5 g) for a period of 8-12 months. This treatment was very effective in suppressing secondary hyperparathyroidism without causing hypercalcaemia and/or hyperphosphataemia.
Thirty-seven children and adolescents on renal replacement therapy (11 on haemodialysis, 14 on continuous ambulatory peritoneal dialysis and 12 after renal transplantation) were studied by echocardiography, echo-Doppler and phonocardiography. Right and left ventricular (R/L V) diastolic functions were measured by transmitral and transtricuspid flow velocities and by LV isovolumic relaxation time (LVIRT). Thirty-seven age- and sex-matched healthy subjects served as controls. R/L V diastolic dysfunction was only observed in the dialysis patients. In these patients LVIRT was prolonged. LV and RV peak inflow velocities were increased both in early (E) and late (A) diastole with a reduction in the E/A ratios. This pattern of diastolic dysfunction is compatible with the combined effects of a hypercirculatory state (volume overload, anaemia, arteriovenous fistula) and an abnormality of cardiac relaxation. The transplant patients showed no major cardiac abnormalities.
We report an infant with congenital nephrotic syndrome who showed clinical and radiological evidence of cerebral oedema, which resolved during prolonged intravenous albumin therapy. The cerebral oedema in this case can possibly be attributed to the relative immaturity of the blood-brain barrier in early infancy.
Chronic renal failure (CRF) in the young is complicated by, among other conditions, growth retardation, hyperparathyroidism and uremic osteodystrophy. Many children with CRF are now being treated with growth hormone (GH). Since GH has a direct mitogenic effect on osteoblasts in culture, we studied the effects of GH therapy on osteoblastic activity, such as serum alkaline phosphatase (AP), bone GLA-protein (BGP) and bone mass density (BMD) in poorly growing children with and without CRF. Fifteen (4 girls, 11 boys) healthy children with short stature (SS) and 10 (3 girls, 7 boys) children with end-stage renal failure (CRF) 4.5-12.4 years of age were treated with daily subcutaneous injections of GH in a dose of 0.1-0.125 IU/kg/day for 1 year. IGF-I, BGP and BMD of the spine were determined before and after the year of treatment. During GH therapy, a similar increase in height velocity and IGF-I were noted in SS and CRF groups: 3.8 +/- 0.77 to 8.38 +/- 1.25 (p < 0.001) vs. 4.0 +/- 0.6 to 7.14 +/- 1.3 cm/year (p < 0.001) and 7.8 +/- 2.6 to 21.8 +/- 7.5 (p < 0.01) vs. 7.9 +/- 1.3 to 21.5 +/- 5.6 nmol/l (p < 0.01), respectively. AP increased from 205 +/- 27 to 274 +/- 50 IU/l (p < 0.01) in the SS group but not in CRF patients (223 +/- 58 pre- 218 +/- 51 IU/l post-GH therapy).(ABSTRACT TRUNCATED AT 250 WORDS)
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The incidence of hypertension (HT) in renal parenchymal disease of the young is very high, varying from 38 to 78%. This points to the central role of the kidneys in normal blood pressure control. HT in chronic renal failure (CRF) and end-stage renal disease (ESRD) depends on the nature of the underlying disease. The degree of renal failure has a highly variable effect. The clinical signs and symptoms of this form of HT are often superimposed on those of the basic (renal) disorder. The pathogenesis of HT in CRF is dominated by volume- and renin-mediated mechanisms. In addition, a wide variety of humoral and neural factors play a role. The HT seen in patients on renal replacement therapy (RRT) and after renal transplantation (Tx) poses special problems. In this paper these various aspects of HT in CRF are discussed and the principles of treatment are reviewed. It has been shown beyond any doubt that control of HT in young patients with CRF and ESRD, treated conservatively or on RRT and after renal Tx is of utmost importance for their long-term outcome. This is an important challenge for all pediatricians looking after young patients with CRF and ESRD.
The effect of 8 weeks of daily oral fish oil supplementation in a dose of 3 to 8 g/d on serum lipid levels was studied in 16 patients, 7 to 8 years of age, who had end-stage renal disease and were receiving renal replacement therapy. Fasting serum cholesterol (CHOL), triglyceride (TG) levels, and lipoprotein profiles were measured before therapy, 8 weeks after fish oil supplementation, and 4 weeks after its cessation. During 8 weeks of treatment the mean serum CHOL level did not change. The mean serum TG level, however, decreased significantly (P less than .01) from 236 +/- 31 mg/dL to 171 +/- 21 mg/dL (27.5%). Four weeks after treatment was stopped, the mean serum TG level returned to a value not significantly different from the pretreatment level (208 +/- 30 mg/dL). In a subgroup of 11 excessively hyperlipidemic patients, with serum CHOL and TG levels greater than or equal to 50% of the 90th percentile for age and sex, the mean serum TG level decreased even more (30.8%), from 286 +/- 35 mg/dL to 198 +/- 24 mg/dL (P less than .01), and the mean CHOL/high-density lipoprotein CHOL ratio decreased from 8.4 +/- 1.2 to 7.4 +/- 1.3 (P less than .05). Blood pressure and platelet counts remained stable during the entire study period. Side effects of the treatment were minimal. These results show that dietary fish oil supplementation reduces serum TG levels in young patients receiving renal replacement therapy and improves their "atherogenic" serum lipoprotein profile.
Rats made uremic by 2-stage 5/6 nephrectomy and sham-operated control animals were fed either a normal laboratory chow, a high-sucrose (60%) or a high-fat (10% cholesterol; 20% olive oil) diet, all containing 21% protein and identical amounts of electrolytes, vitamins and trace elements. Serum creatinine levels remained unchanged in the control animals but rose in the 5/6 nephrectomised uremic animals by a factor of 2.7 from a mean of 0.44 +/- 0.05 mg/dl to 1.20 +/- 0.11 mg/dl at 8 weeks, without differences between the dietary groups. During 8 weeks of dietary regimen the high-sucrose and high-fat diets induced significant hypertriglyceridemia, generally similar in control and uremic rats. The uremic animals on a high-sucrose and high-fat diet had the most pronounced rise in serum triglycerides, 331.5 +/- 89.0 and 298.0 +/- 45.0 mg/dl, respectively (control: 159.9 +/- 14.0 mg/dl). After 4 and 8 weeks, only the animals on the high-fat diet had significant hypercholesterolemia, most pronounced in the uremic animals (356 +/- 56.3 mg/dl; control: 71.6 +/- 12.9 mg/dl). The animals in the latter group also had significant proteinuria and renal histologic abnormalities consisting of xanthoma-like glomerular lesions, infiltrates and fibrosis not seen in the other groups of animals. These data indicate that dietary-induced hyperlipidemia of short duration causes or aggravates renal damage in the rat with mild-moderate uremia, induced by ablation.
In adults with chronic renal failure (CRF) and/or renal replacement therapy (RRT) various immunological abnormalities have been described, but few data are available for the paediatric age group. We performed basic in vitro immunological studies in 26 patients 10 months-19 years of age with advanced renal failure, 11 with CRF (creatinine clearance 16.8 +/- 5.2 ml/min per 1.73 m2), 15 on RRT with haemodialysis (HD; n = 9) and continuous ambulatory peritoneal dialysis (CAPD; n = 6) as well as in 16 healthy controls. None had clinical evidence of deranged immune function. No significant differences were found in the percentages of B- and T-cells, T-cell subsets CD3, CD4, CD8 and mitogenic responses to phytohaemagglutinin and concanavalin A (Con A) between RRT patients (HD = CAPD) and control children. Most parameters in CRF patients were also normal, although they had a low percentage of B-cells (12.1 +/- 4.1; RRT: 19.7 +/- 6.5; controls: 18.5 +/- 7.1; P less than 0.01), relatively low levels of serum immunoglobulin G (948.4 +/- 209.4 mg/dl; HD: 1374.7 +/- 235.2 mg/dl; P less than 0.01; CAPD: 966.3 +/- 430.2 mg/dl, NS) and a high normal response to Con A (34.3 +/- 13.6 cpm x 10(-3); RRT: 24.5 +/- 11.3 cpm x 10(-3); controls: 23.4 +/- 9.9 cpm x 10(-3), P less than 0.01). All these values were, however, well within the normal accepted range. These data indicate that children/adolescents with CRF and/or RRT have no significant basic in vitro immunological defects. This study did not test the functional immune status of the young uraemic patients.
A 5.5-month-old male infant with hypokalaemia and gall bladder dilatation is reported. The child was shown to have Bartter syndrome. After oral treatment with potassium and indomethacin, serum potassium levels became low normal and the gall bladder enlargement resolved. This entity should be included in the clinical spectrum of neuromuscular disturbances resulting from hypokalaemia and should be considered in a hypokalaemic infant with a right-sided abdominal mass.
Twenty-one children and adolescent patients, 2-19 years of age, on renal replacement therapy were immunised at monthly intervals with three doses of 20 micrograms hepatitis B vaccine (Heptavax B, Merck Sharp & Dohme). In the absence of seroconversion, vaccination was continued with monthly doses of 40 micrograms hepatitis B vaccine until antibody to hepatitis B surface antigen became positive. The rate of seroconversion increased from 33.3% (7 of 21) to 76.1% (16 of 21) and 85.6% (18 of 21) with three, four and five vaccine injections respectively. Three patients had no immune response despite six to seven vaccine dosages; they had previously received immunosuppressive therapy. Antibody titres measured 1 year after seroconversion were found to be within the protective range (85-2500 mIU/ml). These results show that the impaired immune response to hepatitis B vaccination in young dialysis patients can be overcome by increasing the number of injections and the dose of the vaccine. Protective antibody titres are maintained for at least 1 year after vaccination. Immunosuppressive therapy may interfere with the vaccine response.
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A 16-year-old boy developed bullous lesions on fingers, ears, tongue, and buccal mucosa as well as cauliflower-like growths on the epiglottis and vocal cords 1 1/2 years after a second renal transplantation and exposure to sunlight while receiving cyclosporin A (CsA). Withdrawal of CsA was followed by complete resolution of skin and mucosal lesions. A predisposition for adverse reactions to CsA is suggested, as additional side effects of CsA therapy were also present.
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The immunological and clinical effects of levamisole were studied in 10 children with frequently relapsing steroid responsive nephrotic syndrome (SRNS). The efficacy of the drug was tested during remission of the disease with all patients on alternate day steroid therapy. The lymphocyte proliferative response to phytohemagglutinin (PHA), concanavalin-A (Con-A) and pokeweed mitogen (PWM) were normal. The Con-A induced suppressor T-lymphocyte activity of 7 patients was low before treatment with levamisole 8 +/- 3.7% and increased to normal values during therapy 34 +/- 6%; p less than 0.001 (control 32 +/- 5%). In these 7 children prednisolone dosage could be decreased significantly or discontinued altogether (44.1 +/- 5.3%). Patients without immunoregulatory abnormalities did not respond to levamisole. In 3 out of 4 children tested the percentage of OKT8+ cells rose during levamisole therapy from 19.7 +/- 2.1 to 37 +/- 2.3 (p less than 0.001), thus correcting the elevated pre-treatment OKT4+/OKT8+ ratio from 3.1 +/- 0.2 to 1.5 +/- 0.2; p less than 0.001 (control 1.47 +/- 0.2). These data support the hypothesis that abnormal immunoregulation may play a role in the pathogenesis of SRNS. Treatment with levamisole can be useful in some patients with the frequently relapsing form of the disease.
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Late graft histology after renal transplantation for Fabry's disease has only once been previously reported. Clinical data and kidney biopsy findings in a case of Fabry's disease before and eight years after successful kidney transplantation are presented. The graft maintains normal function. Graft histology in light microscopy showed no abnormalities reminiscent of the diseased native kidney. Electron microscopy revealed occasional small myelin figures which were present only in the vascular endothelium. Their significance and a review of conflicting reports and opinions from the literature are discussed.