K Schärer

Universität Heidelberg, Heidelburg, Baden-Württemberg, Germany

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Publications (279)553.39 Total impact

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    ABSTRACT: A small fraction of patients with initial steroid-sensitive nephrotic syndrome (SSNS) develops late steroid resistance, i.e. a lack of remission after 4 weeks of relapse treatment despite previous response to steroids. The pathophysiological basis of late resistance and the long-term prognosis remain obscure. Fourteen out of 360 patients with SSNS who were seen in our department between 1954 and 2005 developed late resistance. Median age at onset of NS was 4 years and median duration of development of late resistance 4.6 months. Histology showed minimal-change (MC) nephropathy in six patients and focal segmental glomerulosclerosis (FSGS) in three patients on initial biopsy and four patients on repeat biopsies. Late resistance was treated with cyclophosphamide in five patients, cyclosporine A in three, and both drugs in one. Eight of these nine patients went into remission. All 14 patients maintained a stable kidney function during their period of observation. NPHS2 mutation analysis in eight patients revealed no pathogenic mutations, suggesting that late resistance is not typically associated with mutations in the NPHS2 gene. With respect to the clinical course, late resistance appears to resemble SSNS and is characterized by a favorable outcome.
    Pediatric Nephrology 03/2008; 23(2):251-6. DOI:10.1007/s00467-007-0653-5 · 2.88 Impact Factor
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    ABSTRACT: 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 < 2SD, 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.
    Acta Paediatrica 01/2008; 85(4):437 - 445. DOI:10.1111/j.1651-2227.1996.tb14056.x · 1.84 Impact Factor
  • K. SCHÄRER
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    ABSTRACT: Preliminary results from an ongoing multicentre study on pubertal growth and sexual maturation in chronic renal failure are presented. Puberty was delayed by approximately 2.5 years in both sexes in children with chronic renal failure. There was also an irreversible decline in height SDS during puberty. The pulsatile secretion of growth hormone (GH) and luteinizing hormone (LH) were disrupted in patients on conservative treatment or dialysis compared with those in patients with renal transplants; the mean nocturnal GH level and the mean GH peak amplitude were increased, while the number of pulses and peak amplitude of LH were decreased. The biopotency of LH, expressed as the ratio of bioactive to immunoreactive LH, was suppressed in patients with renal transplants.
    Acta Paediatrica 01/2008; 79(s366):90 - 92. DOI:10.1111/j.1651-2227.1990.tb11605.x · 1.84 Impact Factor
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    ABSTRACT: The number of new paediatric patients accepted for treatment by regular dialysis and transplantation increased more slowly than in previous years. Survival in children above 10 years appeared to be better with all modes of therapy than in younger children. The only improvement in survival noted among the different treatments was in patient and graft survival of living donor transplants. A quarter of all children transferred to home dialysis were less than 10 years of age. Nephronophthisis and Henoch-Schönlein nephritis emerged as major primary renal diseases. In 1975 the proportion of retransplants in children rose and living donor grafts from fathers were more common than from mothers. Evening dialysis was practised more frequently in both hospital and home dialysis and rehabilitation in these patients seemed to be better than for those dialysed at other times. Renal osteodystrophy was present in at least half of all children dialysed for more than 1 year. The degree of growth retardation was affected by sex, chronological age and the primary renal disease. Body height on dialysis and after transplantation progressively reduced in the majority of children. Growth seemed to be more impaired in boys than in girls on dialysis. Bone age advanced faster than height age especially in girls. The pubertal growth spurt was usually delayed and depressed on long-term dialysis and the development of genitalia and pubic hair as well as menarche was retarded.
    Acta Paediatrica 01/2008; 67(1):5 - 10. DOI:10.1111/j.1651-2227.1978.tb16269.x · 1.84 Impact Factor
  • Source
    O. Mehls, R. Waldherr, K. Schärer
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    ABSTRACT: Die wichtigsten und hufigsten Systemerkrankungen, die zu einer Beteiligung der Nieren fhren, sind der systemische Lupus erythematodes und die systemischen Vaskulitiden. Die Niere ist das kritische Organ, an dem sich das Schicksal der Patienten entscheidet. Frhe Diagnose und adquate Therapie knnen die Krankheit rcklufig gestalten und unter Umstnden heilen. Der nachstehende Beitrag beschrnkt sich auf den Lupus erythematodes, die ANCA-assoziierten Vaskulitisformen und die Periarteriitis nodosa. Je nach Gre der beteiligten Gefe kommt es zur Glomerulonephritis oder zu Nekrosen. Alle genannten Krankheiten erfordern im Akutstadium eine aggressive Immunsuppression mit Glukokortikoiden und Cyclophosphamid. Bei der Lupusnephritis ist die Therapie nur beim Vorliegen einer diffus-proliferativen Glomerulonephritis oder sehr schweren Verlaufsformen der fokal-proliferativen Glomerulonephritis und membransen Glomerulonephritis indiziert. Um Nebenwirkungen der Immunsuppression zu vermeiden, sollte die Induktionstherapie mglichst rasch durch eine Erhaltungstherapie ersetzt werden. Dies ist bei den ANCA-assoziierten Vaskulitiden nach 3–6 Monaten mglich. Entsprechende Studien liegen fr den Lupus erythematodes nicht vor.The most important systemic disorders involving the kidney are systemic lupus erythematosus (SLE) and systemic vasculitis. The kidney is a critical organ for the outcome of the diseases. Early diagnosis and adequate therapy may reverse or even heal glomerulonephritis and kidney vasculitis. This contribution is restricted to SLE, the ANCA-associated forms of vasculitis, and the classic Periarteriitis nodosa. Depending on the size of involved vessels, different forms of glomerulonephritis (small vessel disease) or necroses (medium-sized vessel disease) are noted. All diseases mentioned need aggressive immune suppressive therapy (induction with glucocorticoid steroids and cyclophosphamide). In SLE, this is indicated mainly for diffuse proliferative glomerulonephritis (type IV), very severe forms of focal-proliferative glomerulonephritis (type III), and membranous glomerulonephritis (type V). To avoid toxicity, cyclophosphamide should be substituted by azathioprine or mycophenolate mofetil as early as possible. This can be performed for ANCA-associated forms of vasculitis 3–6 months after the start of therapy as was shown in randomized studies, whereas such studies are missing for SLE.
    Monatsschrift Kinderheilkunde 01/2004; 152(3):248-256. DOI:10.1007/s00112-004-0903-6 · 0.28 Impact Factor
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    ABSTRACT: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive tubular disorder that is frequently associated with progressive renal failure. The primary defect is related to impaired tubular reabsorption of magnesium and calcium in the thick ascending limb of Henle's loop. Mutations in PCLN-1, which encodes the renal tight junction protein paracellin-1 (claudin-16), were identified as the underlying genetic defects. Comprehensive clinical data and the results of PCLN-1 mutation analysis of 25 FHHNC families with 33 affected individuals are presented. Patients presented mainly with urinary tract infections, polyuria, and hematuria at a median age of 3.5 yr. At the time of diagnosis, the GFR was already decreased to <60 ml/min per 1.73 m(2) for 11 patients. Twelve patients exhibited progression to end-stage renal disease, at a median age of 14.5 yr. Treatment with magnesium salts and thiazides seemed to have no effect on the progression of the disease. Genotype analysis revealed PCLN-1 mutations in all except three mutant alleles (94%). Fifteen different mutations were observed, including eight novel mutations. The accumulation of mutations affecting the first extracellular loop was striking, with 48% of all mutant alleles exhibiting a Leu151Phe exchange. Haplotype analysis strongly suggested a founder effect among patients with FHHNC who originated from Germany or eastern European countries. In 13 of 23 families, hypercalciuria and/or nephrolithiasis were observed in otherwise unaffected family members, indicating a possible role of heterozygous PCLN-1 mutations in yielding hypercalciuric stone-forming conditions.
    Journal of the American Society of Nephrology 10/2001; 12(9):1872-81. · 9.47 Impact Factor
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    ABSTRACT: Fifty children with idiopathic membranoproliferative glomerulonephritis (MPGN), aged 2-14 years at apparent onset, were monitored for the presence of C3 nephritic factor (C3 NeF) and signs of complement activation in serum. In addition, C3 allotyping was performed in 32 patients. Observation time ranged from 2 to 20 (median 11) years. C3 NeF activity was detected at least once in 60% of the patients (in 11 of 26 with type I, in 15 of 17 with type II, and in four of seven with type III). C3 NeF-positive patients had significantly reduced levels of CH50 and C3 and elevated levels of C3dg/C3d. During follow-up, C3 levels were persistently normal in 62% of the patients with MPGN type I and in 43% with type III but in only 18% with type II. C3 allotype frequencies differed from those found in healthy controls with a significant shift to the C3F/C3FS variants in C3 NeF-positive patients. C3b(Bb)P as a marker for alternative pathway activation was not increased in C3 NeF-positive patients. Despite the presence of C3 NeF activity, C3 levels remained normal in six patients throughout the observation period. C3 NeF became undetectable in six patients, whereas seven developed C3 NeF activity during follow-up. There was no significant difference in renal survival probability in patients with or without C3 NeF activity. Neither C3 variants nor continuous low C3 or low CH50 levels had any prognostic value for the clinical outcome. No factor H deficiency was detected.
    Pediatric Allergy and Immunology 07/2001; 12(3):166-72. DOI:10.1034/j.1399-3038.2001.012003166.x · 3.86 Impact Factor
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    ABSTRACT: Inhibition of the angiotensin-converting enzyme (ACE) exerts a renoprotective effect in adult patients with chronic kidney disease. We evaluated prospectively changes in blood pressure (BP), protein excretion and renal function after administration of the long-acting ACE inhibitor ramipril as monotherapy during 6 months in 14 moderately hypertensive children aged 5-18 years with various nephropathies. Four patients initially had a decreased glomerular filtration rate (GFR below 60 ml/min/1.73 m2). BP was evaluated by ambulatory 24-h monitoring. After 2 weeks of treatment by oral ramipril (1.5 mg/m2 once daily), mean values of systolic and diastolic 24-h ambulatory BP fell by more than 5 mmHg in nine patients. In eight patients the dose was doubled. At the end of the study systolic BP was below the 95th percentile in 9 and diastolic BP in 13 patients. The initially reduced nocturnal dip increased significantly. Of 11 patients with an increased albumin excretion (median 1.3 g/g creatinine), 6 responded to ramipril by a median reduction of 78% (range 24-83%), whilst in 5 albuminuria increased (median +19%). GFR was well preserved and no other adverse effects from the drug were noted. The study demonstrates that ramipril is an efficacious antihypertensive agent in children with renal hypertension. It is well tolerated, even in mild renal insufficiency. In addition, the drug has a persistent antiproteinuric action in about half of the patients contributing to conserve renal function.
    Pediatric Nephrology 12/2000; 15(1-2):113-8. DOI:10.1007/s004670000422 · 2.88 Impact Factor
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    ABSTRACT: In children with chronic renal failure treated conservatively by dialysis or by transplantation, various alterations of the nutritional, metabolic and fluid homeostasis may occur that may critically affect the patients' acute and chronic well-being. In the past, the assessment of body composition in children was hampered by insufficient precision, standardization and/or availability of appropriate anthropometric tools. Recently, there have been several methodological advances that may facilitate close and precise monitoring of body composition in this population. Specifically, the use of body mass index (BMI) data in children has become possible by the introduction of pediatric reference values processed for the calculation of standard deviation scores accounting for the skewed distribution of BMI. Skewness-adapted reference data have also been provided for percentage fat mass as assessed by multisite skinfold measurements. In addition, bioelectrical impedance analysis has been validated in healthy children as well as in pediatric dialysis and renal transplant populations. This novel auxological technique provides a highly reproducible, non-invasive and inexpensive way of assessing changes in total body water content in dialysed patients, as well as changes in fat and fat-free mass prior to dialysis and after renal transplantation.
    Pediatric Nephrology 08/2000; 14(7):673-8. DOI:10.1007/s004670000353 · 2.88 Impact Factor
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    ABSTRACT: Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC, MIM 248250) is a complex renal tubular disorder characterised by hypomagnesaemia, hypercalciuria, advanced nephrocalcinosis, hyposthenuria and progressive renal failure. The mode of inheritance is autosomal recessive. A primary defect in the reabsorption of magnesium in the medullary thick ascending limb of the loop of Henle (mTAL) has been proposed to be essential in FHHNC pathophysiology. To identify the underlying genetic defect we performed linkage analysis in eight families, including three with consanguineous marriages. We found linkage to microsatellite markers on chromosome 3q27 with a maximum two-point lod score (Zmax) of 5.208 for D3S3530 without evidence for genetic heterogeneity. Haplotype analysis revealed crucial recombination events reducing the critical interval to 6.6cM. Recently, mutations in the gene PCLN-1, mapping to 3q27 and coding for paracellin-1, were identified by Simon et al (1999) as the underlying genetic defect in FHHNC. Paracellin-1 represents a renal tight junction protein predominantly expressed in the TAL. Mutational analysis in our patient cohort revealed eight different mutations in the PCLN-1 gene, within six novel mutations. In seven of 13 mutant alleles we detected a Leu151 substitution without evidence for a founder effect. Leu151 is a residue of the first extracellular loop of paracellin-1, the part of the protein expected to bridge the intercellular space and to be important for paracellular conductance. This study confirms the implication of paracellin-1 defects in FHHNC and points to a predominant role of this protein in the paracellular reabsorption of divalent cations in the TAL.
    European Journal of HumanGenetics 07/2000; 8(6):414-22. DOI:10.1038/sj.ejhg.5200475 · 4.23 Impact Factor
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    ABSTRACT: Deflazacort (DFZ) has been proposed as an alternative drug for immunosuppression after renal transplantation (TX), with fewer side effects than conventional glucocorticoids. We investigated renal function, body growth, body fat, and bone mineral density (BMD) after switching from oral methylprednisolone (MPR) to equivalent doses of DFZ 1-9 years after TX in 20 patients aged 5-20 years, selected because of severe adverse effects from previous steroid therapy. At conversion the patients received a mean dose of 7.4 +/- 2.4 mg DFZ/m2 per day. The drug was continued for a mean of 3.7 (1.2-5.5) years. Under DFZ, the glomerular filtration rate dropped slightly (NS). A single rejection episode occurred. Growth velocity significantly improved in the 1st year on DFZ treatment and height standard deviation score (SDS) increased steadily after introduction of DFZ (from -2.64 to -1.96 after 4 years, P = 0.06). However, in 10 prepubertal children the height gain (+0.20 SDS in 2 years on DFZ) was not significant and the overall mean annual growth rate after TX was similar to that in 10 matched prepubertal TX children on continued MPR treatment. Relative obesity, estimated from mean body mass index corrected for height, was reduced from +1.11 SDS at the start of DFZ to +0.71 SDS after 2 years (P = 0.03) and to +0.39 SDS after 4 years (NS). BMD-SDS of the lumbar spine (L2-4) increased after 1 year on DFZ (P = 0.005). In conclusion, DFZ is well tolerated and safe in pediatric patients after TX. It improves relative obesity and bone mineralization. However, body growth is not significantly influenced pre puberty.
    Pediatric Nephrology 07/2000; 14(6):457-63. DOI:10.1007/s004670050792 · 2.88 Impact Factor
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    ABSTRACT: We studied the long-term outcome of 64 children with biopsy-proven Schönlein-Henoch purpura (SHP) nephritis over 1-23 years of follow-up. Overall renal survival 10 years after onset was 73%. Multivariate logistic regression analysis identified initial renal insufficiency (P=0.004), nephrotic syndrome (P=0.037), and the severity of histological alterations, as defined by the proportion of glomerular crescents (P=0.051), as significant independent predictors of progressive renal failure. Four patients followed for more than 19 years showed glomerular damage after transient recovery. Eight children with crescentic nephritis associated with a rapidly progressive course and/or persistent nephrotic syndrome were treated by at least seven sessions of plasma exchange (PE) within 16 weeks of onset of purpura. During treatment serum creatinine levels dropped in each patient from a mean of 2.3 to 1.1 mg/dl, followed by a rebound increase. Repeated courses of PE in 5 patients produced comparable responses. Four patients undergoing PE reached end-stage renal disease at 1.2.-3.7 years after onset, whilst 3 finally were in preterminal renal failure (creatinine 3.2-6.1 mg/dl after 7-13.5 years), and 1 patient reached a normal glomerular filtration rate. Our experience suggests that initial renal insufficiency is the best single predictor of the further clinical course in children with SHP nephritis. Early PE appears to delay the progression in some patients with severe, rapidly progressive forms of the disease.
    Pediatric Nephrology 12/1999; 13(9):816-23. DOI:10.1007/s004670050707 · 2.88 Impact Factor
  • K Schärer, K G Schmidt, M Soergel
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    ABSTRACT: The long-term consequences of cardiac alterations in children with chronic renal failure (CRF) and after renal transplantation (TX) are largely unknown. Studies in adults with end-stage renal disease (ESRD) assume that the fate of many pediatric patients is determined by a high cardiovascular morbidity and mortality. This review describes clinical manifestations, pathophysiology, cardiac function and structure, and management of heart disease in children with CRF and post transplant. Echocardiography and Doppler ultrasonography allow differentiation of three functional disturbances: hypercirculation, systolic left ventricular (LV) dysfunction, and diastolic LV dysfunction, in addition to analysis of LV size and myocardial mass. From adult studies LV hypertrophy is recognized as an early prognostic marker of cardiovascular disease. It is present in about half of children with ESRD and after TX. It may regress, at least in part, by control of hypertension, hypervolemia, and anemia. Experimental studies have shown that, independent of these hemodynamic complications, uremia is associated with structural abnormalities of the heart, which were also described in adult patients with ESRD. These lesions consist mainly of hypertrophy of cardiomyocytes, interstitial fibrosis, and vascular changes (rarefied capillaries, thickened arteriolar walls). Cardiac complications in children with CRF and after TX deserve regular clinical and echocardiographic monitoring in order to minimize later cardiovascular morbidity by appropriate treatment.
    Pediatric Nephrology 12/1999; 13(9):951-65. DOI:10.1007/s004670050737 · 2.88 Impact Factor
  • K Schärer, H C Essigmann, F Schaefer
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    ABSTRACT: Whilst it is assumed that body growth is retarded in children with steroid-resistant nephrotic syndrome (NS), the degree of growth failure and the pathomechanisms involved are poorly understood. We collected serial growth data in 45 children (24 males) with steroid-resistant NS usually from onset to end-stage renal disease (ESRD) during childhood (n=10) or until final height was attained (n=27). Mean follow-up time was 9 (2-19) years. Mean initial standardized height was -0.3+/-1.2 standard deviation scores (SDS). Mean final height was +0.4 SDS in males and -1.0 SDS in females (sex difference not significant). In 16 patients with serum creatinine levels consistently <1.2 mg/dl, mean final height SDS was 0.3 SDS higher than that obtained within 6 months of onset. In contrast, 9 children who entered ESRD lost an average of 1.3 SDS from the initial record to ESRD (P=0.017). In prepubertal patients without renal insufficiency, mean height SDS decreased during corticosteroid treatment by 0.3 SDS, followed by a partial catch-up after discontinuation of treatment; the change from initial to final height SDS was inversely correlated with the total prednisone dose given (r=-0.50, P=0.03). In 16 prepubertal children with serial height and serum protein measurements who were off steroids and maintained normal creatinine levels, mean individual albumin concentrations correlated with the change in height SDS per year (r=0.65, P=0.0006) and in boys with final height (r=0.73, P=0.03). In conclusion, growth in steroid-resistant NS depends on the preservation of renal function, the cumulative dose of steroids applied, and the severity of hypoproteinemia.
    Pediatric Nephrology 11/1999; 13(9):828-34. DOI:10.1007/s004670050709 · 2.88 Impact Factor
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    ABSTRACT: The variable response of patients with idiopathic nephrotic syndrome (NS) to glucocorticoid (GC) treatment has not been explained. Earlier studies indicated that the response is limited by cellular GC receptors. We investigated these receptors in mononuclear leukocytes of 28 pediatric patients with NS divided into three groups: steroid-sensitive in relapse, steroid-sensitive in remission, and steroid-resistant. Density and binding affinity of GC receptors were determined by a dexamethasone binding assay; no significant differences were found between the three patient groups and between these and healthy controls, although a few patient values fell outside the range of controls. Total and free plasma concentrations of cortisol were low in all three patient groups. A weak positive correlation was found between the number of GC receptors and total plasma cortisol (r=0.36, P=0.03). The results suggest that factors other than GC receptors that mediate the cellular effects of GC are involved in the variable response of NS patients to GC.
    Pediatric Nephrology 11/1999; 13(8):653-6. DOI:10.1007/s004670050675 · 2.88 Impact Factor
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    ABSTRACT: Autosomal dominant polycystic kidney disease is one of the most common inherited disorders with a prevalence of 1:1000 and is responsible for cca 10% of end-stage renal disease in adult patients. Renal insufficiency is a rare symptom of ADPKD in children, however, there are some symptoms, which can occur already in childhood. The aim of this study was to detect early signs of renal damage and to reveal the blood pressure profile in children with ADPKD using ABPM (ambulatory blood pressure monitoring). 32 children (aged 3.4-19.4 years, mean age 12.3)-carriers of PKD-gene with normal GFR, diagnosed on the basis of a positive family history and characteristic ultrasound features, and in 21 cases also indirect DNA analysis revealed positive results. 11/32 children (34%) presented arterial hypertension detected by ABPM (values higher than 95th centile of normal individuals). The mean of ABPM values of all patients was significantly higher than normal children (p < 0.01), 76% patients had values above the 50th centile. Signs of renal damage (proteinuria, microalbuminuria, decreased renal concentrating capacity, pathological excretion of tubular markers) were found in 22-64% of investigated children. Significantly higher renal volume and renal length were found in more than 1/3 of the children, renal volume and length higher than the mean of healthy children in about 90% of patients and a significant correlation between ABPM parameters and renal length and volume (p < 0.05). The results of this study show, that the signs of renal damage and arterial hypertension occur relatively often in children with ADPKD despite still normal GFR. This justifies the early diagnosis of ADPKD especially as it reveals the most important treatable complication of ADPKD-arterial hypertension. These findings emphasise the importance of early diagnosis in children from families with ADPKD. Probably, early treatment of hypertension could even postpone the otherwise common end-stage renal damage in adult patients with ADPKD. Careful follow up of all children with ADPKD is strongly recommended, above all the blood pressure should be controlled.
    Casopís lékar̆ů c̆eských 04/1999; 138(6):178-84.
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    ABSTRACT: An increasing number of children with hereditary tubular disorders (HTD) reach adult life due to diagnostic and therapeutic advances which results in growing need to manage these patients by adult centres. Data on the prevalence and the late clinical problems of these patients are limited. Methods: We observed 177 paediatric patients with isolated or complex HTD between 1969 and 1994. The median age at the time of diagnosis was 3 (range 0-18) years and the median observation period 10 (range 1-43) years. The long-term outcomes with respect to renal function, bone disease, and body growth were analyzed. The prevalence of HTD was 3.2% of all patients observed in our renal unit and 14% of those patients with chronic renal failure and/ or end-stage renal disease. The three most frequent disorders observed were nephropathic cystinosis (n = 34), X-linked hypophosphataemic rickets (n = 26), and idiopathic hypercalciuria (n = 17). At the last observation, 12% of the patients with isolated HTD and 30% of those with complex HTD had developed preterminal chronic renal failure; end-stage renal disease was observed in 5 and 25%, respectively (p < 0.001). Progressive disease occurred mainly in patients having cystinosis, primary hyperoxaluria, the syndrome of hypomagnesaemia/hypercalciuria, primary Fanconi syndrome, Fanconi-Bickel syndrome, and methylmalonic aciduria. Nephrocalcinosis was found in 42%, urolithiasis in 14%, bone deformities and/or fractures in 28%, and other extrarenal alterations in 29% of all patients. The median body height at last observation was 2.0 SD below the normal mean (range from -10.4 to +2. 6), and the adult height was subnormal in 48% of 67 grown-up patients. Growth retardation was more severe in complex than in isolated HTD. The mortality decreased from 17% in 1969-1981 to 12% in 1982-1994. Although HTD are rare nephropathies, their frequently progressive course associated with extrarenal complications requires the attention of nephrologists beyond the paediatric age.
    Nephron 02/1999; 83(3):250-60. DOI:10.1159/000045518 · 13.26 Impact Factor
  • M J Koch, R Bührer, T Pioch, K Schärer
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    ABSTRACT: Chronic renal failure (CRF) in the first years of life is associated with developmental defects of enamel in the permanent dentition. We investigated if CRF also affects the primary (deciduous) dentition. Thirty-one children with CRF on conservative treatment (n = 12) or on renal replacement therapy (n = 19) underwent dental inspection. In addition, 18 CRF children provided an exfoliated deciduous tooth for microscopic examination. Enamel defects were detected in a total of 12 children (31%), either clinically or microscopically. Of the 7 children affected clinically, 6 (19% of all examined) presented localized hypoplasia of the primary canines, which was found only in 3% of healthy control children: 1 patient had generalized pitted enamel hypoplasia. By microscopy, 5 of 10 primary canines examined showed enamel hypoplasia localized exclusively in enamel formed after birth. The "birth line," a visible structure within the primary enamel, was always present, which excludes a prenatal onset of the defects. Of the 12 patients with an enamel defect, 9 had a documented onset of CRF within the first 7 weeks of life. We conclude that renal disease leading to CRF may affect enamel formation of primary teeth in early postnatal life, resulting in lesions different from those observed in the secondary dentition.
    Pediatric Nephrology 02/1999; 13(1):68-72. DOI:10.1007/s004670050566 · 2.88 Impact Factor
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    ABSTRACT: In a prospective, uncontrolled multicenter study, we have evaluated the effects of probucol on hyperlipidemia, proteinuria, and glomerular filtration rate (GFR) in hyperlipidemic children with persistent nephrotic syndrome. Probucol was started for a total of 12 weeks in 8 children and for 24 weeks in 14 children. Lipoprotein profiles, serum malondialdehyde (MDA) levels, proteinuria, renal function, and electrocardiogram were monitored every 4 weeks. Side effects were recorded by questionnaire. Treatment was completed by 7 of 8 patients for 12 weeks and by 7 of 14 children for 24 weeks. After 12 weeks, the mean serum concentrations of triglycerides (-15%), total cholesterol (-25%), very low-density lipoprotein-cholesterol (-27%), low-density lipoprotein-cholesterol (-23%), and high-density lipoprotein-cholesterol (-24%), as well as apolipoprotein (apo) A-I (-19%), apo B (-21%), and MDA (-32%) were reduced. The positive effects of probucol on the lipoprotein profile persisted over 24 weeks; however, there was no significant effect on either proteinuria or GFR. In conclusion, probucol had beneficial effects on lipoproteins and lipid peroxidation, but improved neither proteinuria nor GFR. The drug was generally tolerated well, but had to be discontinued because of a prolonged QT interval in 4 of 22 patients.
    Pediatric Nephrology 02/1999; 13(1):7-12. DOI:10.1007/s004670050554 · 2.88 Impact Factor
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    R E Port, R W Ding, T Fies, K Schärer
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    ABSTRACT: To establish a pharmacodynamic model that allows one to predict the haemoglobin (Hb) response to EPO in children as a function of dose and time, and to derive recommendations for initial dosing and subsequent dose adjustment. Haemoglobin was monitored in eight children aged 8-15 years with anaemia due to renal failure during treatment with EPO. All patients were free of conditions known to impair the response to EPO. Pretreatment Hb was 4.9-9.0 g dl(-1). The drug was administered once weekly by subcutaneous injection; doses ranged from 1700 to 6800 U week (-1). Hb was monitored for 4-38 months. The Hb-time data were analysed by applying a population pharmacodynamic model proposed for EPO in adult haemodialysis patients. Internal model validation was carried out by using a bootstrap procedure. The increase of Hb during treatment with EPO was linear until steady state was reached after 103+/-33 days (mean +/- interindividual s.d.). The weekly gain in Hb from the onset of therapy to steady state was 0.0805+/-0.026 g dl(-1) (mean +/- interindividual s.d.) for every 1000 U EPO week (-1); it did not exhibit a dependence on body weight. Estimated mean prediction errors are +/-1.53 g dl(-1) for predictions that are based on the mean population parameters and +/-0.83 g dl(-1) for predictions that take into account the complete individual Hb-time data up to and including steady state. The model describes the time course of the Hb response to EPO in children with renal anaemia. The required weekly EPO dose should initially be calculated from the individual pretreatment Hb and the desired Hb at steady state by using the mean population estimates of the weekly gain in Hb per dose unit before steady state (beta) and the time needed to reach steady state (tau). A reduction of the initial dose according to body weight is not justified by the available evidence. beta should be re-estimated individually after 6 weeks of treatment and dose should be adjusted accordingly. A final dose adjustment should be made when steady state has been reached based on individual estimates of beta and tau.
    British Journal of Clinical Pharmacology 12/1998; 46(5):461-6. DOI:10.1046/j.1365-2125.1998.00797.x · 3.69 Impact Factor

Publication Stats

3k Citations
553.39 Total Impact Points

Institutions

  • 1973–2008
    • Universität Heidelberg
      • • Department of Pediatric Neurology
      • • Institute of Immunology and Serology
      • • Institute of Pathology (Mannheim)
      Heidelburg, Baden-Württemberg, Germany
  • 2000
    • Philipps University of Marburg
      Marburg, Hesse, Germany
  • 1977–1999
    • University of Iowa Children's Hospital
      Iowa City, Iowa, United States
  • 1996
    • University of Bonn
      • Institute of Human Genetics
      Bonn, North Rhine-Westphalia, Germany
  • 1995
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France
  • 1993–1994
    • Gesellschaft für Pädiatrische Nephrologie
      Heidelburg, Baden-Württemberg, Germany
    • The University of Manchester
      • School of Biomedicine
      Manchester, England, United Kingdom
  • 1987
    • Heidelberg University
      Tiffin, Ohio, United States
  • 1976
    • Orthopädische Universitätsklinik Friedrichsheim
      Frankfurt, Hesse, Germany