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Biomedical subjects

G Offner

Publications and source records attributed to G Offner.

At least 73 records · Page 4Linked to original sources

Long-term results of cyclosporin A therapy in children.

In order to assess the long-term effectiveness and tolerability of cyclosporin A (CsA) treatment in children with renal transplantation (Tx), the follow-ups of 32 children (17 boys, 15 girls; age at Tx = 12.2 yr; range, 5.1 to 16.9) with a functioning graft of greater than or equal to 5 yr and continuous treatment with CsA and low-dose prednisolone are analyzed retrospectively. For comparison, data of 34 children (19 boys, 15 girls; age at Tx, 11.0; range, 3.2 to 17.1) are collected who had received a graft before the introduction of CsA, had at least 5 yr of graft function, and were continuously treated with azathioprine (AZA) plus high-dose prednisolone. The mean observation period in the CsA group was 6.5 (range, 5.0 to 8.0) yr, and in the AZA group was 10.4 yr (range, 5.7 to 15.8). CsA dosage remained unchanged in the range of 200 mg/m2/day; CsA whole blood trough level was 120 to 130 ng/mL throughout the years. One patient died in each group. Four more grafts were lost in the CsA group by chronic rejection, which was associated with noncompliance in three, and two grafts were lost in the AZA group by chronic rejection. Late acute reversible rejection episodes occurred more frequent in the CsA (six) than in the AZA group (two). The overall survival rates for patients and grafts were significantly better with CsA. The graft function in CsA-treated recipients was significantly lower than that in AZA patients, but there was no progressive loss over the years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Organ transplantation in childhood].

Organ transplantation in children has to consider the development of the children. One limitation is the organ size of orthotopic transplanted organs as liver, heart and lung. The activation of unspecific immune response in the pediatric recipients is a risk of rejection episodes especially in infants. The experiences of the Medical School Hannover with 203 pediatric renal recipients and with 117 pediatric liver recipients are reported. Congenital disorders with chronic organ insufficiency frequently lead to growth retardation and cardiovascular complications already before transplantation and determine the long term outcome especially in renal transplantation.

Adolescent↗

Continuous peritoneal dialysis in children.

During the period from June 1985 to December 1991, 48 children were treated with continuous peritoneal dialysis (CPD) in our centre because of acute renal failure. The median age was 1.8 years (range 0.01-17.1). The most common diagnoses were: hemolytic uremic syndrome (n = 22), anuria after cardiac surgery (n = 7), and septicemia with multiorgan failure (n = 7). Kidney function recovered in 35 (73%); 13 (27%) died of their original disease. One further patient with HUS recovered from dialysis but died of cerebral complications shortly afterwards. One patient remained anuric and requires renal replacement therapy. Hyperkalemia, when present initially, and uremia could be controlled adequately in all cases. However, ultrafiltration posed problems when cardiac output was low. Peritonitis occurred in 11 patients; in 8 children the Tenckhoff catheter had to be revised because of leakage (5), flow problems (2), or bowel perforation (1). CPD proved to be an excellent method to treat acute renal failure in children of all age groups. The rate of complications was acceptable.

Acute Kidney Injury↗

Kidney transplantation in Alport's syndrome: long-term outcome and allograft anti-GBM nephritis.

Anti-glomerular basement membrane (anti-GBM) nephritis occurring in kidneys transplanted in patients with Alport's syndrome (AS) has been reported repeatedly. Therefore, we studied graft survival and course of renal function in all 30 AS patients grafted at Hannover Medical School and compared them with non-diabetic, age and sex matched patients, transplanted on the date closest to the transplantation of the AS patient. Serum creatinine, proteinuria, urinary sediment and anti-GBM antibodies were examined in all AS patients with functioning grafts. Cases of patient or graft loss in the AS group were analyzed retrospectively. One- and five-year patient survival was 100 and 91% in AS and 89 and 78% in controls (p > 0.05, respectively). One- and five-year first graft survival was 79 and 66% in both groups. Graft histology was available in 34 biopsies obtained from 21 kidneys in 15 AS patients. Anti-GBM nephritis was not detected in any of the biopsies. No graft was lost due to anti-GBM nephritis. Anti-GBM antibodies were detectable temporarily only in one AS patient. He also had linear IgG staining in his graft GBM, but no other signs of anti-GBM nephritis. We conclude that patient survival and graft survival in AS patients following kidney transplantation is not different from non-AS patients. Allograft anti-GBM nephritis is a rare complication in patients with Alport's syndrome.

Adult↗

Practical aspects in the use of cyclosporin in paediatric nephrology.

Many factors must be considered for the effective and safe use of cyclosporin A (CsA) in paediatric nephrology. Detailed knowledge of the variable bioavailability, tissue distribution, and metabolism, as well as causes which lead to their alteration are necessary. Factors which affect the activity of the mixed function oxidase system cytochrome P-450 must be considered, i.e. liver dysfunction and many drugs. Precise knowledge of the CsA determination method and the spectrum of metabolites is essential. In children with renal transplants, a body surface area-related dose will better meet the dose requirements than a body weight related-dose. For drug level monitoring whole blood rather than plasma should be used, and the parent drug level should be the main determinant; elevated metabolite levels may be important in suspected nephrotoxicity or liver dysfunction. Pharmacokinetic profiles are necessary to discover absorption problems or increased CsA clearance rates which necessitate shorter dosing intervals. In children with steroid-dependent minimal change nephrotic syndrome, remission without steroids is maintained as long as CsA is given. The appropriate starting dosage is 150 mg/m2 per day; trough level monitoring is mandatory to prevent nephrotoxicity and to confirm adequate immunosuppressive drug levels which should be 80-160 ng/ml (parent drug level). Although the benefit of CsA has been reported in some cases of lupus erythematosus, its use should be restricted to severe cases only until its efficacy and safety has been confirmed in controlled trials.

Child↗

Renal transplantation in 22 children with nephropathic cystinosis.

In 1989, 22 children (11 boys, 11 girls aged 8-23 years) with nephropathic cystinosis, who had received a total of 28 renal allografts over the previous 14 years, were reviewed. Nineteen were alive, of whom 17 had functioning grafts 5 months to 13 years after transplantation. The mean serum creatinine level in these 17 was 135 mumol/l. Patient and graft survival did not differ from non-cystinotic children. Persistent hypothyroidism was found in 3 patients, transient diabetes mellitus in 1, severely disturbed vision in 1 and brain atrophy in 11. Arterial hypertension was present in 16 patients. Growth retardation was universal, although in 4 patients on cyclosporin A post-transplant catch-up growth occurred. Five patients over 15 years completed puberty. Readjustment in terms of school performance was good but was less good for psychosocial development. None of the patients had ever been treated with cystine-depleting agents; the data will therefore provide a historical control group with which to compare the results from a group treated with these agents.

Adolescent↗

Growth after renal transplantation: an update.

Several factors influencing post-transplant growth were analysed in a total of 163 children receiving transplants at the Medical School Hannover. Statural height at the time of transplantation depended on the length of the pre-transplant period of chronic renal failure, and was more retarded in children with congenital renal diseases than in those with acquired diseases. The retardation of bone age correlated significantly with the degree of growth retardation. The immunosuppressive regimen of cyclosporine A (CyA) and low-dose prednisolone was followed by significantly better growth rates than azathioprine (Aza) plus high-dose prednisolone. In 22 prepubertal children receiving CyA, poor graft function with a glomerular filtration rate below 40 ml/min per 1.73 m2 inhibited catch-up growth. The final height of 20 grown-up transplant recipients was found to be in the lower range of normal. A comparison of conventional and CyA treatment showed that adult height in the CyA group was higher than in the Aza group due to a significantly higher growth velocity.

Adolescent↗

Adult height achieved in children after kidney transplantation.

We evaluated posttransplantation growth, bone maturation, and adult height in 20 adolescents who had received kidney transplants at the age of 10.5 to 17 years. Nine patients (five male, four female) were treated with cyclosporine and low-dose prednisolone, and 11 children (six male, five female) were treated with azathioprine and high-dose prednisolone. The cumulative dose of steroids after transplantation was significantly lower in the cyclosporine-treated group. Bone age, according to the radius-ulna-short bones method of Tanner and Whitehouse, was almost the same in both groups at the time of transplantation (15.0 and 14.6 years for male subjects, 13.3 and 13.1 years for female subjects). Predicted adult height (Tanner-Whitehouse Mark II-method of Tanner et al) and target height were estimated at transplantation. Adult height was defined as achieved when bone age in male subjects had reached 18 years and, in female subjects, 16 years. Bone maturation of the cyclosporine-treated patients occurred at a normal rate (0.92 bone-age years per chronologic year), whereas the azathioprine-treated group exhibited a significantly slower rate (0.56 bone-age years per chronologic year). The growth rate per year for the cyclosporine-treated group was more than double that of the azathioprine-treated group (3.0 cm vs 1.4 cm). The adult height of the cyclosporine-treated group exceeded the predicted adult height by a mean of 1.3 cm, but the azathioprine-treated group missed it by 3.9 cm. Target heights could not be achieved in any group. Kidney function was significantly lower in the cyclosporine- vs the azathioprine-treated group, but no patients suffered from severe renal insufficiency. We conclude that cyclosporine and low-dose prednisolone are associated with normal bone maturation and a better prognosis for final height in children with renal transplants.

Adolescent↗

Efficacy of calcium carbonate and low-dose vitamin D/1,25(OH)2D3 in reducing the risk of developing renal osteodystrophy in children on continuous ambulatory peritoneal dialysis.

Eight children with terminal renal insufficiency on continuous ambulatory peritoneal dialysis were followed for 12 months to evaluate laboratory parameters of mineral ion and bone metabolism. Calcium carbonate (range 47-295 mg/kg body weight per day) was given in combination with low doses of either vitamin D or 1,25(OH2D3. Blood urea nitrogen and serum phosphate concentrations remained well controlled throughout the observation period. A significant increase in serum calcium levels from 2.35 +/- 0.18 to 2.61 +/- 0.22 mmol/l (mean +/- SD) was observed during the first 6 months. Alkaline phosphatase activity and mid-C-regional parathyroid hormone, both indirect parameters of bone metabolism, revealed no evidence of severe secondary hyperparathyroidism. Our data indicate that calcium carbonate may be sufficient to induce relative hypercalcaemia in uraemic children, and thus reduce the risk of developing renal osteodystrophy. Unwanted side-effects of vitamin D preparations, i.e. increased intestinal phosphate absorption and hypercalcaemia after successful renal transplantation, may thus be avoided.

Administration, Oral↗

Association of spondylo-epiphyseal dysplasia with nephrotic syndrome.

The association of a spondylo-epiphyseal dysplasia and growth failure with the nephrotic syndrome was found in three boys. Renal biopsy performed on two revealed focal and segmental glomerulosclerosis. The nephrotic syndrome occurred at the age of 3-7 years, leading to end-stage renal failure in all patients. Growth failure persisted after successful renal transplantation. This association may represent a distinct disease entity.

Child↗

One year's experience with recombinant erythropoietin in children undergoing continuous ambulatory or cycling peritoneal dialysis.

Fourteen patients (aged 5.9-22.1 years) undergoing continuous ambulatory or cycling peritoneal dialysis were treated with recombinant human erythropoietin (rhEPO), which was given intravenously once a week at a dosage of 300 units/kg. The mean haematocrit level increased from 18.5% to 27.5% and the reticulocyte count from 19% to 62% within 1 month. After an average time of 3.1 months rhEPO dosage could be adjusted to 100 units/kg per week to keep the haematocrit level at 30%. Only 1 patient had an exacerbation of hypertension, which required a dosage reduction; other side-effects were not noted.

Adolescent↗

Hypertension after renal transplantation in patients treated with cyclosporin and azathioprine.

The incidence of hypertension was sought in 102 children who had undergone renal transplantation. Fifty five were being treated with cyclosporin and 47 with azathioprine, and they were followed up for a maximum of five years. After one year 35 of those receiving cyclosporin (64%) and 34 of those receiving azathioprine (72%) were hypertensive; after five years the figures were 5/6 (83%) and 25/35 (71%), respectively. Recipients of grafts from living related donors had a lower incidence of hypertension than recipients of cadaveric grafts. The incidence of hypertension was higher in patients with acquired original kidney disease than in children with congenital or familial diseases. In both groups creatinine clearance and the frequency of acute rejection episodes did not differ between normotensive and hypertensive patients. When the lowest concentrations of cyclosporin in whole blood were more than 400 ng/ml the incidence of hypertension one year after transplantation was higher. The incidence of hypertension after renal transplantation in children is higher than that reported in adults. Acquired original disease, transplantation of cadaveric grafts, and nephrotoxicity of cyclosporin are all contributory factors.

Azathioprine↗

[Multicystic kidney dysplasia].

The clinical course of 48 children (27 boys and 21 girls) with multicystic kidney dysplasia was analysed retrospectively. The patients were seen and treated at the Children's Hospital of Medical School Hannover between 1976 to 1989. There was no familial occurrence of the disease, yet in eight families various other renal diseases could be observed. In 20 patients the diagnosis of multicystic renal dysplasia was presumed by prenatal sonographic examination, in the other patients the diagnosis was established at the age between 1 day to 12 years. The first manifestations were palpable abdominal mass (n = 16), urinary tract infection (n = 4), casually because of a sonographic evaluation for other reasons (n = 4) and vomiting (n = 2). Associated malformations were found in 18 patients: cardiac malformations (n = 6), dysplasia of the other kidney (n = 5), ureter obstruction of the other kidney (n = 3), horseshoe kidney (n = 1) and others (n = 3). There was no hypertension and serum creatinine levels were normal in those children, who did not suffer from associated malformations of the other kidney. The multicystic kidney was removed operatively in 42 patients at the age of 3 days to 9.5 years (median 4 weeks). The prognosis of multicystic kidney dysplasia depends on associated renal and other malformations.

Child↗