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Biomedical subjects

G Offner

Publications and source records attributed to G Offner.

At least 91 records · Page 5Linked to original sources

[Cystic kidneys in children].

From 1976-1987 a total of 26 infants and children with polycystic kidney disease were treated at the Children's Hospital of the Medical School Hannover. 13 of them suffered from infantile recessive polycystic kidney disease (IRPKD), and 13 from adult dominant polycystic kidney disease (ADPKD). IRPKD was diagnosed at a median age of 0.33 years (range 1 day-13 years), ADPKD at 6.0 years (3 days-14 years). Of those with IRPKD two infants died from bacterial infection and two others developed terminal renal insufficiency at the age of 8 years, while the others are living and 1-20 years old. All those suffer from severe arterial hypertension and have reduced renal function, but only 5 developed signs of liver fibrosis. Of those with ADPKD one infant died from sepsis and renal insufficiency, while the others are well and now 2-17 years old. Only one child needs an antihypertensive treatment. The most important criteria to differentiate IRKPD and ADKPD in children are the genetic transmission, age of first manifestation, hypertension and renal function. The prognosis is much more severe in IRPKD than in ADPKD, but is not as infaust in IRPKD as often assumed.

Adolescent↗

Renal handling of magnesium in transplanted children under cyclosporin A treatment.

We investigated the renal handling of magnesium in 12 transplanted children under cyclosporin A treatment during the early period after transplantation. We also studied 30 children treated with cyclosporin A 2 years after renal transplantation and compared the results with those of 22 children treated with azathioprine and prednisolone 2-4 years after transplantation. Twenty-two children with chronic renal failure and 10 healthy children served as controls. During the 1st week after transplantation, the mean serum magnesium level dropped to 0.54 +/- 0.14 mmol/l and was accompanied by a high fractional magnesium clearance. During this period two patients showed generalized convulsions. After magnesium substitution, serum levels increased gradually and normalized 4 months later. Fractional magnesium clearance remained slightly elevated due to lower glomerular filtration rates. One to four years after transplantation there were no statistically significant differences in serum levels, clearance, excretion and fractional clearance of magnesium between patients treated with cyclosporin A and those receiving azathioprine. There was a linear regression between magnesium clearance and creatinine clearance and an inverse exponential correlation between fractional magnesium clearance and creatinine clearance. We conclude that cyclosporin A treatment after transplantation has no major effect on the renal handling of magnesium in kidney transplants. The observed changes in serum magnesium levels and fractional clearance are probably due to tubular cell damage early after transplantation and to high doses of furosemide.

Adolescent↗

Renal handling of uric acid under cyclosporin A treatment.

The renal handling of uric acid during cyclosporin A (CyA) treatment was investigated by clearance studies using 24-h urine collections in 28 paediatric renal transplant recipients (CyA group), and the results were compared with those of 19 renal transplanted children treated with azathioprine and prednisolone (AZA group), 35 children with chronic renal failure (CRF) and 10 children with normal renal function (N group). Serum uric acid levels were significantly higher in the CyA group (567 +/- 156 mumol/l) compared with the AZA group (378 +/- 98), the CRF group (415 +/- 119) and the N group (290 +/- 68). Mean uric acid clearances in each group measured 3.9 +/- 2.8 ml/min per 1.73 m2 (CyA), 5.6 +/- 3.4 (AZA), 4.0 +/- 2.2 (CRF) and 8.4 +/- 3.7 (N). Calculation of the net tubular uric acid reabsorption per millilitre glomerular filtration rate revealed a significantly increased value of 0.53 +/- 0.15 mumol/ml in the CyA group (P less than 0.01) compared with 0.34 +/- 0.08, 0.29 +/- 0.15 and 0.27 +/- 0.07 mumol/l for the AZA, CRF and N groups respectively. We therefore conclude that CyA treatment is associated with an increased net tubular reabsorption of uric acid, which may lead to hyperuricaemia.

Azathioprine↗

Effect of cyclosporine on the renal tubular amino acid handling after kidney transplantation.

The renal tubular handling of free amino acids was studied 5-6 weeks after successful renal transplantation (tx) in 20 children treated with CsA and in 10 children treated with azathioprine (Aza). The results were compared with those of 34 control children. The amino-acid clearance studies were performed in combination with short-term inulin clearance. The CsA group revealed a mean inulin clearance of 49 +/- 16.8 ml/min/1.73 m2, the Aza group of 76.9 +/- 18.2, and the controls of 114 +/- 15.6. The plasma amino-acid concentrations were not different between CsA- and Aza-treated groups; however, most of the essential amino acids were lower in transplanted children than in controls. The decrease was correlated with the GFR. The amino-acid-clearance rates were statistically not different between both transplanted groups, but lower values than in controls were found for alanine, glycine, histidine, lysine, and phenylalanine, and significantly higher values for methionine. The fractional clearance rates of most amino acids were significantly elevated in transplanted children compared to controls. In CsA-treated patients, the fractional clearance rates of arginine, glycine, and serine were higher than in Aza-treated patients. No influence of CsA blood levels or rejection episodes on the amino-acid handling were detectable. We conclude that CsA has no specific influence on the renal handling of amino acids. Most disturbances observed depend on the graft function or may be caused by injuries to the graft following the tx procedure.

Amino Acids↗

End stage renal failure: 14 years' experience of dialysis and renal transplantation.

One hundred and thirteen children (59 boys and 54 girls aged from 2 to 16 years) with end stage renal failure entered the renal dialysis and transplantation programme between 1972 and 1983. They were followed up until December 1985. Ninety eight children were initially treated by haemodialysis in hospital and 15 by renal transplantation. The average wait on dialysis was seven months (range 0.1-43 months). One hundred and six children were given 129 renal transplants, 32 of which were from living related donors. At the end of 1985 94 of the 113 patients (83%) were alive, 81 (72%) with functioning grafts, 11 (10%) were receiving haemodialysis in hospital, two (1%) were being treated by continuous ambulatory peritoneal dialysis, and three had been lost to follow up. The 14 years actuarial survival was 81%. Four patients receiving dialysis and 12 who had received transplants died, a mortality of 14%. The main complications of treatment were retardation of growth in 49 (43%), hypertension in 75 (66%), and osteopathy in 36 (32%). Retardation of growth could not be reversed by successful renal transplantation. Seventy two patients (88%) assessed their health as good to excellent, and 9 (12%) as poor. Patients with a functioning graft did much better than those receiving dialysis. Treatment of end stage renal failure led to full rehabilitation in most patients, and renal transplantation was more effective than dialysis.

Adolescent↗

Somatic growth after kidney transplantation. Beneficial effect of cyclosporine in comparison with conventional immunosuppression.

Growth performance was evaluated in 69 children, aged 3 to 16 years, who had undergone kidney transplantation between 1974 and 1984. Forty children (21 boys, 19 girls) who received transplants before September 1982 were treated conventionally with azathioprine and high-dose prednisolone; 29 children (13 boys, 16 girls) who received transplants after September 1982 were treated with cyclosporine and low-dose prednisolone. The mean (+/- SD) survival times of grafts in the azathioprine and cyclosporine groups were 6.0 +/- 2.1 years and 1.4 +/- 0.5 years, respectively. Height and bone age were evaluated at the time of transplantation, one year after transplantation, and at reevaluation in December 1985. Growth rates expressed by standard deviation scores (SDS) declined in the azathioprine group for boys (mean, -2.2 at transplantation, -2.5 after one year, and -2.8 in December 1985) and girls (-2.1, -2.4, and -2.7) and improved in the cyclosporine group for boys (-2.5, -2.2, and -2.1) and girls (-2.2, -1.9, and -1.8). The difference between both groups one year after transplantation was significant. This trend continued beyond the first year after transplantation. Graft function was better in the azathioprine group than in the cyclosporine group. Bone age in December 1985 was less retarded in the cyclosporine group, but this could have been related to the shorter observation time. We conclude that somatic growth after kidney transplantation is below expected rates under azathioprine-prednisolone immunosuppression but is significantly better under cyclosporine-prednisolone immunosuppression.

Adolescent↗

Acute rejection episodes after renal transplantation in children under cyclosporin A treatment.

Thirty-two pediatric renal transplant patients receiving cyclosporin and 34 receiving azathioprine treatment (historical controls) were investigated for the occurrence of rejection episodes; their clinical symptoms and findings, time of onset, influence of donorship, relation to cyclosporin blood levels and graft function outcome were also studied. In the cyclosporin group, four grafts were lost in the 2nd year, while in the azathioprine group five grafts were lost within the first 5 weeks after transplantation due to acute irreversible rejection. Clinical signs of rejection episodes under cyclosporin were mild and usually presented a silent increase of serum creatinine. First rejection episodes occurred later in patients treated with cyclosporin than in azathioprine-treated patients (50% probability after 7 weeks as opposed to 2 weeks). The percentage of patients receiving cyclosporin who had experienced no rejection episodes was 18.8% as opposed to 11.8% of patients receiving azathioprine. The lowest incidence of rejection episodes was observed in patients with living related grafts receiving cyclosporin treatment, 75% of whom were free of rejection episodes after 2 years. Cyclosporin blood levels below 400 ng/ml were observed in 74% of rejection episodes. Biopsies were often used to differentiate between cyclosporin nephrotoxicity and rejection when the cyclosporin levels were above 400 ng/ml. Both treatment groups exhibited a parallel decline in graft function, which correlated with the number of rejection episodes.

Adolescent↗

Cyclosporin A in paediatric kidney transplantation.

Cyclosporin A (CyA) is an immunosuppressive agent which has been used in children following kidney transplantation since 1982. The paediatric experience made with CyA in a single centre is reported here. Forty-seven children, ranging in age from 2 to 16 years, were given transplants between September 1982 and May 1986 and received CyA with low-dose prednisolone for immunosuppression. The mean cold ischaemia time of the grafts was 20.9 h. Under routine volume expansion during and 24 h posttransplantation, 40 grafts (85%) functioned immediately. Acute rejection episodes occurred with the highest frequency during the 1st month (0.6 rejection/patient). The actuarial survival rate for patients was 98% after 3 years. Graft survival was 92% after 1 year, 87% after 2 years and 78% after 3 years. The side-effects observed with CyA were hypertrichosis (38%), neurological complications (21%), and infections (17%). One girl of 16 years developed benign mammary fibroadenomas. Hypertension was common (60%), but less so than seen with conventional therapy (83%). Graft function was reduced. The mean creatinine clearance at 6 weeks after transplantation was 60 ml/min per 1.73 m2, after 1 year was 46.4 ml/min per 1.73 m2 and after 2 years it was 42.5 ml/min per 1.73 m2. Twenty-nine children with functioning grafts of at least 1 year could be evaluated for growth performance and normal or even catch-up growth could be demonstrated for the whole group. The individual annual growth rates expressed by standard deviation score (SDS) remained stable or even improved 3 years after kidney transplantation. Longer periods of follow-up are necessary to confirm whether the advantages concerning survival rates and growth rates persist over time and will outweigh the side-effects of CyA treatment.

Adolescent↗

Renal function after kidney transplantation in children. A comparison of conventional immunosuppression with cyclosporine.

Clearance studies were performed in 32 transplanted children treated with CsA in combination with low-dose prednisolone (CsA group), and the results were compared with those of 29 children transplanted earlier and treated with azathioprine and prednisolone (CIS group). Serum creatinine and urea levels 6 weeks and 1 year after transplantation (Tx) were significantly higher in the CsA than in the CIS group. Clearance studies 6 weeks after Tx exhibited significantly lower rates in the CsA group: Cin = 47 +/- 16.5 versus 83 +/- 25 ml/min/1.73 sqm, CPAH = 271 +/- 110 versus 503 +/- 181 ml/min/1.73 sqm (P less than 0.001). The filtration fractions were not different (19.1 versus 17.1%). The tubular phosphate reabsorption per ml GFR (Tp/Cin) was only slightly lower in the CsA group (0.76 +/- 0.23 mumol/ml versus 0.93 +/- 0.29; P = 0.09). The endogenous glucose clearance rates were equally elevated in both groups and returned to normal after 1 year. The creatinine clearance (Ccr) had dropped in both groups by a mean for 13 ml/min/1.73 sqm between 6 weeks and 1 year after Tx. No correlation was found between the Ccr and the CsA blood levels, but Ccr was inversely correlated with the number of rejection episodes (r = -0.72, P = 0.001). In conclusion, renal allografts in CsA-treated children exhibited a significantly lower function than in CIS-treated children. The effect was related to the global kidney function without any signs of additional tubular toxicity and was apparent within the first weeks after Tx. Thereafter, the decline in graft function was comparable in both groups and could not be related to CsA treatment.

Adolescent↗

Cyclosporine in pediatric kidney transplantation.

The immunosuppressive treatment with cyclosporin A plus low-dose prednisolone in 33 children after kidney transplantation was compared with conventional treatment with azathioprine plus regular prednisolone dosage in 34 children. The results showed the following: Graft survival in the CyA group is significantly better than in the conventional group (97% vs. 68% at one year). Patient survival is the same in both groups (97% vs. 94%). Kidney function six weeks and one year after successful renal transplantation is significantly lower in the CyA group than in the conventional group. The major nephrotoxic effect of CyA seems to be related to the first period after kidney transplantation, since later the decline in renal function is the same in both treatment groups. Other side effects of CyA are not severe and are well manageable. A major benefit of CyA treatment is the growth after transplantation, which is significantly better than in the conventional group. Almost all transplanted children show normal or even catch-up growth rates.

Adolescent↗

Acute renal failure in children: prognostic features after treatment with acute dialysis.

A 12-year review (1972-1983) is presented of 76 children who were dialysed because of acute renal failure. The causes of acute renal failure were mainly the haemolytic-uraemic syndrome (53%), trauma (16%) and operation (13%). Fifty-eight children (76%) survived, 18 children (24%) died. Fifty-two children, the majority suffering from haemolytic-uraemic syndrome, regained complete or partial renal function after a period of dialysis lasting between 1 and 57 days. One to 7.7 years after dialysis, clearance studies with inulin (CIn), p-aminohippuric acid (CPAH) and phosphate (Tp/CIn) for staging renal function were carried out. The results of this investigation show a significant inverse correlation between the glomerular function regained and the duration of intermittent dialysis.

Acute Kidney Injury↗