Karl Schärer

Congenital hypokalemia with hypercalciuria in preterm infants: a hyperprostaglandinuric tubular syndrome different from Bartter syndrome.

A congenital hypokalemic tubular disorder is described with many features resembling Bartter syndrome. Additional features include prenatal onset with polyhydramnios and premature labor; failure to thrive; episodes of fever, vomiting, diarrhea, and renal electrolyte and water wastage; hypercalciuria; nephrocalcinosis; and osteopenia. Unlike Bartter syndrome, there is no defect in tubular reabsorption of chloride. Urinary levels of prostaglandin E2 and 7 alpha-hydroxy-5,11-diketotetranorprosta-1,16-dioic acid are selectively elevated, indicating marked stimulation of renal and systemic PGE2 production. Chronic suppression of PGE2 activity by indomethacin corrects most of the abnormalities, and there is an immediate decompensation of the disease on indomethacin withdrawal. We conclude that these preterm infants have a distinct variety of hypokalemic tubular disorders rather than a variant of Bartter syndrome, because renal and systemic hyperprostaglandinism ranks high in the pathogenic chain of events, and the suppression of PGE2 hyperactivity is associated with significant improvement in the development (and probably in the prognosis) of the affected children.

Pubertal Growth in Chronic Renal Failure

ABSTRACT: We evaluated the growth records of 15 boys and 14 girls who developed end-stage renal failure before or during puberty and who were regularly followed from the onset to the end of their pubertal growth spurt. Height data were smoothed by using the kernel estimation method. Mean values for age, height, and height velocity at defined points of the pubertal growth period were compared with those of normal children entering puberty both at an average and late age. The start of the pubertal growth spurt was delayed by 2.5 y in both sexes. Its duration and intensity were significantly reduced. Mean pubertal height gain was 17.3 cm in boys and 13.9 cm in girls, i.e. 58 and 48% of that observed in the late maturing control group. Mean height at the onset of the pubertal spurt in the patients was the same as that in the late maturing healthy girls and 1.0 SD below that of corresponding boys. During the pubertal growth spurt, mean height declined to—2.9 SD in boys and - 2 .3 SD in girls. Although skeletal maturation was increasingly retarded, we did not observe accelerated growth velocity during late puberty. Our data indicate that most patients reaching end-stage renal failure before or during puberty irreversibly lose growth potential during this period. Renal transplantation did not consistently improve pubertal growth.

Progression to end-stage renal disease in children with posterior urethral valves

Abstract. Diagnostic and therapeutic strategies in boys with congenital posterior urethral valves (PUV) have much improved in past decades, but the impact of these changes on the progression to end-stage renal disease (ESRD) has rarely been investigated. We followed renal function in 20 boys with PUV from diagnosis to ESRD. From the first observation period (1969–1978) to the second period (1979–1992) we found a marked drop in age at diagnosis, at valve resection, at first increase of serum creatinine (SCr), and at onset of ESRD. The progression was analyzed by calculating the slope of 1/SCr and the probability of renal survival. In all patients combined, renal survival at the age of 10 years was 35%. In children undergoing valve resection in the 1st year of life, renal survival was worse than in those undergoing later surgery (15% vs. 65% after 10 years, P=0.006). Patients with a SCr>1.2 mg/dl before the age of 12 months progressed more rapidly to ESRD than those attaining this level later. The lower the minimum level of SCr observed after initial surgery, the older the patient at the onset of ESRD. The presence of renal dysplasia or hypoplasia, but not of vesicoureteric reflux, was associated with a more rapid progression. Mean body height at ESRD was −2.3±1.3 standard deviation score compared with controls, and was lower if PUV was diagnosed before the age of 6 months.

The nephronophthisis complex

The clinical and morphological findings are described in 27 children with nephronophthisis. Seventeen children were considered as sporadic cases. In 10 familial cases the presumed mode of inheritance was autosomal recessive. The clinical picture was rather uniform: polyuria-polydipsia, hyposthenuria, anemia, growth retardation, and azotemia with progressive renal failure. Six patients presented with tapeto-retinal degeneration. In a further seven children other ocular changes were detected. Two female siblings showed additional non-renal manifestations: mental retardation, pulmonary emphysema, skeletal anomalies, and congenital hepatic fibrosis. Renal histology displayed a chronic sclerosing tubulo-interstitial nephropathy with extensive tubular atrophy and dedifferentiation. Medullary cysts were frequently found in end-stage kidneys. Immunofluorescence was either non-specific or completely negative. On electron microscopy, the tubular basement membrane changes predominated: thickening, lamellation, splitting, and deposition of microfibrils within the increased basement membrane substance. Detailed light- and electron microscopic findings were non-specific but the overall morphologic picture was characteristic and even diagnostic in conjunction with the clinical presentation. A recurrence of nephronophthisis in transplanted kidneys has not been observed. The pathogenesis of nephronophthisis is obscure but with respect to the morphologic findings a primary or secondary tubular basement membrane defect seems very likely. Our experience suggests that nephronophthisis is a frequent cause of chronic renal failure in children and commonly associated with non-renal abnormalities. To avoid the separation of different syndromes presenting with a uniform renal disease but various non-renal manifestations, we suggest that the term “nephronopthisis complex” be used.

Complement analysis in children with idiopathic membranoproliferative glomerulonephritis: a long-term follow-up.

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 continous low C3 or low CH50 levels had any prognostic value for the clinical outcome. No factor H deficiency was detected.

The paediatric registry of the European Dialysis and Transplant Association: 20 years' experience

The first publication of the paediatric registry of the European Dialysis and Transplant Association appeared in 1971. Since then nearly 50 further articles have appeared and this paper provides a full bibliography as well as tracing the changes in the provision of care, methods and results of treatment of end-stage renal disease in childhood over the last 20 years.

Renal magnesium wasting, incomplete tubular acidosis, hypercalciuria and nephrocalcinosis in siblings

Polyuria, hyposthenuria, hypomagnesemia, hypercalciuria, advanced nephrocalcinosis, low citrate excretion and low glomerular filtration rates were observed in two female siblings who were followed over 10 years. Acid loading revealed incomplete distal tubular acidosis. Hypomagnesemia was due to renal magnesium wasting. It is suggested that the defect in tubular transport of magnesium is an important factor in the pathogenesis of this syndrome.

Weight-/height-related bone mineral density is not reduced after renal transplantation

Abstract. Growth retardation is a frequent finding in patients after renal transplantation (Tx). Areal bone mineral density (BMD) in these patients has usually been reported to be low for age. We investigated the possible influence of height and weight retardation on the measurement of BMD in lumbar spine (BMDL2-4) and total body (BMDbody) using dual-energy X-ray absorptiometry in 44 (13 female) pediatric Tx patients with a median age of 13.1 (range 3.3–23.1) years. Patients were studied at 2.9 (range 1–10) years after Tx. Median body height in female and male patients was –2.10 (–3.6 to -0.3) and –2.35 (–5.3 to +1.0) standard deviation score (SDS), respectively. BMD expressed as grams per square centimeter bone area according to age was below the 5th percentile in 10 of 44 patients, but only 1 patient had low values for BMDL2-4, and none for BMDbody, when the data were corrected for height or weight. BMDbody was closely correlated with height, weight, and body surface area (r=0.88), whereas the correlation for BMDL2-4 was less (r=0.76). In 6 patients who achieved final height, height SDS was –2.27 (–4.3–0.4). Z-scores for BMDbody related to age, height, and weight were –1.0 (–2.6 to –2.3), 1.25 (0.1–3.4), and 0.81 (0.0–2.4), respectively. There was no age-dependent change when areal BMD values (g/cm2) were corrected for vertebral size to obtain bone volumetric density (BMDvol, g/cm3). Independent of height, cumulative methylprednisolone dose correlated negatively with BMDL2-4 only in patients who had received a total dose of more than 6 g/m2 of the drug (r =–0.54, P = 0.045). In conclusion, BMD in pediatric patients after Tx is no longer diminished when the data are corrected for height or weight rather than age, or when the data are expressed as bone volumetric density.

Should liver transplantation be performed before advanced renal insufficiency in primary hyperoxaluria type 1

Primary hyperoxaluria type 1 (PH1) is a rare recessive autosomal inborn error of glyoxylate metabolism leading to oxalate retention, the first target of which is the kidney. The disease is caused by a defect of the liver-specific peroxisomal enzyme alanine: glyoxylate aminotransferase. Patients with pyridoxine-resistant forms of PH1 usually require organ replacement therapy, i.e. liver transplantation to supply the deficient enzyme and/or kidney transplantation to replace the affected organ. The current experience of the management of Ph1 has emphasized two main points: (1) end-stage renal failure must be avoided since it increases dramatically the risk of systemic involvement, (2) the correction of oxalate overproduction and organ overload requires the removal of the host liver. Practical attitudes towards these ideas are difficult to assess and an individualized strategy is therefore required. Isolated kidney transplantation should be limited to adult patients with late-onset and a mild course of the disease. The present experience of combined liver-kidney transplantation was gained mainly in adult patients with severe systemic involvement; the 3-year patient survival rate recently increased to 82%. This figure might be improved if the procedure were performed earlier while the glomerular filtration rate (GFR) is above 25 ml/min per 1.73 m2. Isolated liver transplantation should be considered in carefully selected children with severe forms of pyridoxineresistance (PH1) before GFR has dropped to less than 30 ml/min per 1.73 m2; it seems to be indicated especially in the presence of a rapid decline of GFR in the preceding year. In two young children who underwent isolated liver transplantation in our units 4 years ago, renal function could be stabilized and severe extrarenal involvement prevented.

Assessment of body composition in children with chronic renal failure

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.