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Biomedical subjects

J Brodehl

Publications and source records attributed to J Brodehl.

At least 19 recordsLinked to original sources
PubMed1998

Does tacrolimus cause more severe anemia than cyclosporine A in children after renal transplantation?

Initial reports indicated the possibility of severe anemia associated with tacrolimus (TC) therapy. We investigated the degree of anemia under TC treatment in comparison to cyclosporine A (CsA) treatment in children after renal transplantation. A cross-sectional analysis of 95 children successfully transplanted for at least 3 months was performed. Eighty-five children received CsA and 10 TC. TC-treated patients were compared with CsA-treated patients who were matched according to age, gender, creatinine clearance, and time after transplantation. No patient received additional therapy with mycophenolate mofetil or azathioprine. The creatinine clearance of the whole group of transplanted children was 58 ml/min per 1.73 m2. The patients within the matched-pair analysis had a lower creatinine clearance (TC 46 and CsA 48 ml/min per 1.73 m2). The hemoglobin was 10.3 g/dl for the TC-treated children and 10.4 g/dl among the CsA-treated patients. Numerically, EPO was higher and iron lower in the TC group than in the CsA group. Among children with functioning renal grafts, a correlation exists between Hb and creatinine clearance. A significant difference in the degree of anemia between TC- and CsA-treated children could not be found.

Adolescent↗
PubMed1998

End-stage renal failure in children younger than 6 years: renal transplantation is the therapy of choice.

UNLABELLED: Between 1975 and 1994, 46 children under 6 years of age received a total of 52 renal transplants. Obstructive uropathy and dysplasia accounted for most causes of terminal renal failure (17 and 12 cases respectively). Four patients required a second, 1 patient a third transplantation. Cadaveric organs were used on 33 occasions; 19 patients received a living-related donor kidney. Immunosuppression was performed with azathioprine in 5, with cyclosporine A in 21 and combined azathioprine/cyclosporine therapy in 20 cases. After 1 year, graft survival was 81%, and after 5 years 78%. Creatinine clearance declined slightly between 1 and 5 years from 69 to 56 ml/min per 1.73 m2. Main causes of graft failure were thrombotic complications in 6 cases and death with functioning graft in 5 cases. Graft thrombosis occurred only in grafts from young donors under the age of 7 years and after vascular anastomosis to the iliac vessels. Only two transplants were lost in rejection episodes. Patient survival was 94% after 1 and 90% after 5 years. Two patients died due to septiacemia, 1 died of a ruptured aortic aneurysm, 1 of cerebral ischaemia and 1 suddenly of unknown cause. Patient and graft survival was not different compared with 204 patients aged 6-16 years who received a renal transplantation during the same time period at our institution. After transplantation the patients receiving cyclosporine A showed a marked catch-up growth in the 1st year. The median standard deviation score (SDS) of body length improved from -2.63 to -1.39 standard deviations. CONCLUSION: Renal transplantation is the treatment of choice in end-stage renal failure in children under 6 years.

Actuarial Analysis↗
PubMed1998

Reference values for cystatin C serum concentrations in children.

Cystatin C, a low molecular weight protein, is a new endogenous marker of renal function whose serum concentration correlates better with glomerular filtration rate than creatinine. The aim of the present study was to define a reference interval for cystatin C concentrations in children. Cystatin C was measured by an immunoturbidimetric assay in sera obtained from 258 children (93 girls, 165 boys, median age 6.29 years, range 1 day to 18 years) without evidence of kidney disease. The reference interval was calculated non-parametrically using the 2.5th and 97.5th percentiles. For comparison, creatinine was measured in the same samples. The cystatin C concentration was highest on the first days of life (range 1.64-2.59 mg/l) with a rapid decrease during the first 4 months. Beyond the 1st year, the cystatin C concentration was constant, with a reference interval of 0.7-1.38 mg/l. In contrast, serum creatinine concentrations steadily increased with age until adulthood. Compared with creatinine, cystatin C facilitates the recognition of abnormal renal function in children as its reference range is constant beyond the 1st year of life. The higher levels of cystatin C in the 1st year of life probably reflect the low glomerular filtration rate of neonates and infants.

Adolescent↗
PubMed1998

Cystatin C--a new marker of glomerular filtration rate in children independent of age and height.

OBJECTIVES: Serum creatinine is the most common endogenous marker of renal function. The proportionality between creatinine production and muscle mass requires adjustment for height and body composition. The low molecular weight protein cystatin C is produced by all nucleated cells and eliminated by glomerular filtration. Therefore, cystatin C was studied as an alternative marker of glomerular filtration rate (GFR) in children. METHODS: Cystatin C and creatinine were measured in sera from inulin clearance (CIn) examinations performed in 184 children aged 0.24 to 17.96 years. CIn ranged from 7 to 209 mL/min/1.73 m (median, 77). RESULTS: The reciprocal of cystatin C correlated better with CIn (r = 0.88) than the reciprocal of creatinine (r = 0.72). Stepwise regression analysis identified no covariates for the correlation between cystatin C and CIn, whereas height was a covariate for creatinine. Using an estimate of GFR from serum creatinine and height, correlation with CIn was similar to cystatin C, but female gender and dystrophy were associated with an overestimation of GFR. Diagnostic accuracy in the identification of reduced GFR measured as area under the receiver-operating characteristic plot was 0.970 +/- 0.135 (mean +/- SE) for cystatin C and 0.894 +/- 0.131 for creatinine (NS). A cutoff cystatin C concentration of 1.39 mg/L had 90% sensitivity and 86% specificity for detecting abnormal GFR. CONCLUSION: Unlike creatinine, serum cystatin C reflects renal function in children independent of age, gender, height, and body composition.

Adolescent↗
PubMed1998

Recurrence of renal disease after kidney transplantation in children: 24 years of experience in a single center.

The aim of this study was to assess the frequency and clinical implications of a recurrence of the original renal disease in children after kidney transplantation. Thus, the records of patients with immunological and metabolic diseases transplanted between 1970 and 1994 were retrospectively analyzed. There were 113 renal transplantations in 99 patients, who had the following original diseases: focal segmental glomerulosclerosis (FSGS), membrano-proliferative glomerulonephritis type I and type II (MPGN I, II), Henoch-Schoenlein nephritis, IgA-nephropathy, hemolytic uremic syndrome (HUS) and hyperoxaluria type I (PH I) and other rare diseases. Recurrences were observed in FSGS, MPGN II, HUS and PH I but not in the other diseases. In FSGS, the recurrence rate was 20% with graft failure in 5 of 6 grafts. No specific risk factors for recurrent FSGS could be determined. In MPGN II, the recurrence was 60% but the loss of grafts occurred at the same rate as in the non-recurrence group. In HUS, recurrence was seen in 4 out of 24 renal grafts (16.6%) with subsequent graft loss in all cases. All cases had suffered from an atypical HUS. PH I recurred in 4 of 5 allografts with graft loss in all patients. The remaining graft was transplanted after a liver transplantation and graft function was well preserved for 4 years. We confirm that the risk of recurrence with loss of the graft is high in a certain group of renal diseases. In these the indication for transplantation, particularly with living related donor kidneys, needs special evaluation. A better understanding of the pathomechanism of the diseases should lead to prevention of recurrence, as in PH I in which a liver transplant is now the primary option.

Adolescent↗
PubMed1997

Response to diphtheria and tetanus booster vaccination in pediatric renal transplant recipients.

BACKGROUND: Although inactivated vaccines are recommended for immunocompromized patients, efficacy and safety of diphtheria and tetanus immunization in renal transplant recipients have received little attention so far. The aim of the study was to investigate the response to a standard diphtheria and tetanus booster vaccination in pediatric renal transplant recipients. METHODS: Forty-two children, median age 13.2 years (range, 7.8-18.9 years) with complete primary immunization 9.2 years (0.9-15.4 years) before transplantation were enrolled. Immunosuppression consisted of cyclosporine plus prednisolone in 15 (36%), cyclosporine, azathioprine, and prednisolone in 24 (57%), and tacrolimus plus prednisolone in 3 (7%). Antibodies were measured by enzyme-linked immunosorbent assay before and 1, 6, and 12 months after vaccination. RESULTS: Before vaccination, protective antibody concentrations exceeding 0.1 IU/ml against diphtheria were found in 16 children (38%). Thirty-eight (90%) had protective antibody concentrations against tetanus. After booster immunization, the protection rate against diphtheria rose to 95% at 1 month with a decline to 93% at 6 and 76% at 12 months. Protection against tetanus was complete after vaccination and persisted over the observation. Antibody concentrations were comparable to those reported for healthy children. Statistical analysis showed no influence of allograft function, immunosuppressive regimen, previous cytotoxic therapy, or time between primary immunization and end-stage renal failure on antibody response. Immunization was well tolerated and kidney function remained unaffected in patients with stable allograft function. CONCLUSIONS: Diphtheria and tetanus vaccination can be performed effectively and safely in renal transplant recipients as generally recommended.

Adolescent↗
PubMed1997

Pharmacokinetics of cyclosporine in pediatric long-term liver transplant recipients converted from Sandimmun to Neoral.

Absorption of cyclosporin from the microemulsion formulation Neoral is less variable than from Sandimmun. Because of a lack of data in pediatric liver transplant recipients, the pharmacokinetic profiles with Sandimmun and Neoral were compared in a conversion study. Thirty-eight children with stable graft function were converted 2-12.3 years post-transplant at a 1:1 ratio. The trough-level (Cmin) with Neoral was 123 +/- 39 ng/ml versus 134 +/- 29 ng/ml with Sandimmun (P = NS), the area under the time-concentration curve (AUC) was 3325 +/- 1125 ng.h/ml versus 2423 +/- 846 ng.h/ml (P < 0.001), the peak concentration (Cmax) was 650 +/- 280 ng/ml versus 337 +/- 142 ng/ ml (P < 0.001), and the median time to Cmax was 2 h (range 0.5-3 h) versus 4 h (range 1-8 h; P < 0.05). The weak correlation between Cmin and AUC with Sandimmun (r = 0.5; P = NS) was improved by using Neoral (r = 0.7; P < 0.001). The best predictor of AUC was the 2-h concentration (C2h) of Neoral (r = 0.9; P < 0.001). Increased absorption and a more predictable pharmacokinetic profile with Neoral permit safer therapeutic monitoring in children. The exclusive measurement of Neoral-C2h allows one to estimate drug exposure with high precision (> 90%).

Administration, Oral↗
PubMed1997

Etiologic classification of severe hypospadias: implications for prognosis and management.

OBJECTIVE: Classification of severe hypospadias employing a broad array of diagnostic tools. Standardization of a diagnostic approach to children with hypospadias. Indentification of patients at risk of having malignancies and endocrine problems. DESIGN: Retrospective analysis of patients in a single-center study. SUBJECTS: Thirty-three patients with severe (scrotal or penoscrotal) hypospadias, aged 1 to 18 years. METHODS: Clinical assessment, ultrasonography, karyotyping, endocrine evaluation including adrenal steroid concentrations, sex hormone-binding globulin test for androgen sensitivity, human chorionic gonadotropin stimulation with determination of testosterone and dihydrotestosterone concentrations to exclude 5 alpha-reductase deficiency, and molecular genetic analysis of the androgen receptor gene and the 5 alpha-reductase gene. RESULTS: In 12 patients the cause was clarified. Diagnoses included Drash syndrome with Wilms tumor in infancy (3 patients), partial androgen insensitivity resulting from androgen receptor mutations (2), true hermaphroditism (2), chromosomal aberration (1), deficiency of antimüllerian hormone (1), gonadal dysgenesis (1), partial 5 alpha-reductase deficiency caused by a novel point mutation (1), and XX-male syndrome (1). Twelve patients had associated findings such as cardiac malformations (3 patients), rectal atresia (1), dilation of urinary tract (2), cystinuria (1), and others. CONCLUSIONS: Patients with severe hypospadias should be submitted to a standardized set of diagnostic procedures in infancy. A stepwise diagnostic study avoids unnecessary, invasive, and expensive testing. A high proportion of classified causes can be expected. Patients at risk of having malignancies or hormonal disorders must remain under close surveillance.

Adolescent↗
PubMed1996

Liver transplantation in children with chronic end stage liver disease: factors influencing survival after transplantation.

To identify pretransplant factors that are influencing survival after orthotopic liver transplantation a Cox proportional hazards regression model was applied to 118 children with chronic terminal liver failure transplanted at Medical School Hannover during the period of 1978 to 1994. The response variable was survival, as covariates a total of 19 pretransplant variables were entered--i.e. age, diagnosis (biliary cirrhosis, metabolic cirrhosis, postnecrotic cirrhosis, cryptogenetic cirrhosis) sex, laparotomy prior to OLT, height, weight, standard deviation scores for height and weight, date of first OLT, serum alanine aminotransferase, asparagine aminotransferase, albumin, total bilirubin, cholinesterase activity, glomerular filtration rate, and prothrombin time. Significant independent predictors of survival after OLT were bilirubin (P=0.0024), SDS for weight (P=0.034), and albumin (P=0.039). In a subsequent discriminant analysis cut off points for these variables could be identified--i.e., bilirubin >340 micromol/L, SDS for weight <-2.2 and albumin < 33 g/L. Patients with one or more of these risk factors were grouped as urgent indication group (n=76) and those with no risk factor as elective indication group (n=42). Comparing the posttransplantation survival in these groups there is a statistically significant difference at 1 year (57% vs. 90.5%) and 4 years (49% vs. 90.5%) after OLT (P=0.0001, log rank test). It is concluded that the risk of OLT is much higher if liver function is very poor. Optimal nutritional support prior to transplantation is mandatory to optimise the clinical status of the children and to improve the results of OLT.

Adolescent↗
PubMed1996

Oxalate elimination via hemodialysis or peritoneal dialysis in children with chronic renal failure.

Oxalate elimination and oxalate dialysance via hemodialysis (HD) or peritoneal dialysis (CAPD) has not been studied in detail in pediatric patients. We studied plasma oxalate, oxalate elimination, and oxalate dialysance in 15 infants and children undergoing CAPD (9 female, 6 male, aged 9 months to 18 years) and in 10 children on HD (4 female, 6 male, aged 7-18 years). Two children in each group had primary hyperoxaluria (PH). The mean duration of dialysis prior to examination was 12 +/- 11 months in CAPD and 31 +/- 23 months in HD patients. Bicarbonate HD was performed 5 h three times a week, CAPD consisted of five daily exchanges in 5 patients and four changes in the remaining 10 children (dwell volume 40 ml/kg body weight, 2.3 g/l glucose). Although oxalate dialysance was significantly higher in HD (mean 115.6 ml/ min per 1.73 m2 in HD versus 7.14 ml/min in CAPD), mean oxalate elimination per week was not different between both renal replacement therapies (3,478 mumol/1.73 m2 surface area/week in CAPD versus 3,915 mumol/1.73 m2 per week in HD). Oxalate elimination in patients with PH was between 6,650 and 9,900 mumol/week. Plasma oxalate remained elevated in both procedures [28-84 mumol/l in CAPD (92/148 in PH) and 33-101 mumol/l in HD (70/93 in PH)]. Oxalate elimination can be increased by a more frequent hemodialysis regimen.

Adolescent↗
PubMed1996

Autosomal recessive polycystic kidney disease in 115 children: clinical presentation, course and influence of gender. Arbeitsgemeinschaft für Pädiatrische, Nephrologie.

The clinical course of 66 boys and 49 girls with autosomal recessive polycystic kidney disease recruited from departments of paediatric nephrology was investigated over a mean observation period of 4.92 years. This is a selected study group of children from departments of paediatric nephrology who in most cases survived the neonatal period, since birth clinics did not participate. The median age at diagnosis was 29 days (prenatal to 14.5 years). We observed decreased glomerular filtration rates (GFRs) in 72% (median age at onset of decrease of GFR < 2 SD, 0.6 years; range, 0-18.7 years), and 11 patients developed end-stage renal disease. Hypertension requiring drug treatment was found in 70% (median age at start of medication, 0.5 years; range, 0-16.7 years). Kidney length was above the 97th centile in 68% of patients, and kidney length did not increase with age or deterioration of renal function. Urinary tract infections occurred in 30%, growth retardation in 25%, and clinical signs of hepatic fibrosis were detected in 46%. Thirteen patients (11%) died during the observation period, 10 of them in the first year of life. There was a statistically significant sex difference in terms of a more pronounced progression in girls. The survival probability at 1 year was 94% for male patients and 82% for female patients (p < 0.05) in this study. Urinary tract infections occurred more frequently in girls (p < 0.025) and were observed earlier. In addition, more girls had impaired renal function, developed end-stage renal disease and showed growth retardation; these differences, however, were not significant. For the children in this study, however, our results indicate that the long-term prognosis in the majority of cases is better throughout childhood and youth than often stated.

Adolescent↗
PubMed1996

Clinical course of hypophosphatemic rickets in 23 adults.

Twenty-three adult patients (19 females, 4 males) with x-linked hypophosphatemic rickets (HPR) underwent a retrospective evaluation of the clinical course and a clinical examination by a nephrologist, orthopedic surgeon and dentist. Blood and urine analysis, bone density measurements with QCT and DEXA, ultrasonic examination of the kidneys were performed and the patients were asked to fill in a standardized questionnaire on pain and psychosocial rehabilitation. Mean final height was 152.4 cm +/- 8.5 SD in females and 157.3 cm +/- 8.9 SD in males. Decreased joint mobility was seen in all patients, deviations of the normal leg axis in 18/23 patients in spite of 69 correcting osteotomies in the past. Dental (n = 14) and psychosocial problems were associated with inability to work (n = 8). There was a trend that patients with a very low Tp/GFR had a more severe course of the disease. Early therapy with vitamin D metabolites and phosphate had a beneficial effect on growth, bone density and deformations. Eight patients had nephrocalcinosis due to vitamin D and phosphate therapy and had normal kidney function. Four patients had urinary tract abnormalities. We conclude that patients with HPR should receive continuous interdisciplinary care given by nephrologists, orthopedic surgeons, physiotherapists and dentists not only during childhood but also as adults.

Adult↗
PubMed1995

Improved absorption of cyclosporin A from a new microemulsion formulation: implications for dosage and monitoring.

Recently, a new oral microemulsion formulation of cyclosporin A (CsA)--Neoral (Sandoz, Basle, Switzerland)--with a higher bioavailability has become available. Ten stable paediatric renal transplant recipients with excessive variations in CsA trough levels with the original Sandimmun (Sandoz, Basle, Switzerland) preparation were switched to Neoral on a 1:1 basis. Pharmacokinetic studies revealed impaired absorption of Sandimmun in six patients. Compared with equal doses of Sandimmun, the 8-h area under the concentration-time curve increased from 1,422 to 2,657 ng x h/ml and the peak concentration rose from 319 to 824 ng/ml (P < 0.01). In six patients with Sandimmun malabsorption, conversion on a 1:1 basis led to a reduction in creatinine clearance which was reversible after dose reduction by 9%-25%. With trough levels at the lower end of the present target range, creatinine clearance stabilised around pre-conversion values.

Adolescent↗
PubMed1995

Steroid resistant nephrotic syndrome associated with spondyloepiphyseal dysplasia, transient ischemic attacks and lymphopenia.

Focal segmental glomerulosclerosis, nephrotic syndrome and chronic renal failure were associated with spondyloepiphyseal dysplasia, growth failure, lymphopenia and transient ischemic attacks leading to severe neurological symptoms in three children. Two boys and one girl developed the full syndrome at the age of 5, 6 and 10 years. Positron emission tomography revealed perfusion defects of both cerebral and cerebellar arteries. A variant of the disease was found in two other children who had a nephrotic syndrome and terminal renal failure with only mild spondyloepiphyseal dysplasia, impaired growth and a normal cerebral function. It is concluded that there may be a close association between focal segmental glomerulosclerosis and spondyloepiphyseal dysplasias.

Brain↗