Ein akutes dialysepflichtiges Nierenversagen im Kindesalter wird in etwa 6% der Fälle durch Glomerulopathien verursacht. Häufig ist eine intensivmedizinische Behandlung erforderlich, insbesondere wenn sekundäre Organkomplikationen aufgetreten sind. Diese zeigen oft eine vorwiegend neurologische Symptomatik und erfordern eine dringliche Diagnostik und Therapie. Neben dem relativ häufigen hämolytisch-urämischen Syndrom kann eine Vielfalt von Glomerulopathien zum akuten Nierenversagen führen. Bei einigen dieser Erkrankungen kann bei frühzeitiger Diagnosestellung durch aggressive Therapie zumindest die Langzeitprognose verbessert werden. Beim Krankheitsbild der rapid progressiven Glomerulonephritis sind dazu in letzter Zeit bei erwachsenen Patienten therapeutische Fortschritte erzielt worden, die auch für die Pädiatrie relevant sein könnten. Der Einsatz spezieller Blutreinigungsverfahren wie Plasmapherese oder Immunadsorption bei Kindern wird in dieser Arbeit ebenfalls diskutiert.

Hämaturie und Proteinurie sind häufige Befunde im Kindesalter. Die Aufgabe des Kinderarztes ist es, beim Auftreten dieser Symptome die Dringlichkeit weiterer Untersuchungen abzuschätzen und diese evtl. durchzuführen, um die zugrunde liegenden Erkrankungen aufzudecken. Algorithmen zu Hämaturie und Proteinurie, die in dieser Mitteilung vorgestellt und diskutiert werden, sollen eine gezielte Diagnostik ermöglichen und überflüssige Untersuchungen vermeiden.

Copper can induce acute and chronic intoxications in humans. Copper in tap water has caused a series of severe systemic diseases in Germany in recent years (chronic copper poisoning, CCuP). From the clinical point of view it has been difficult to establish the diagnosis on the basis of clinical and laboratory methods. In a retrospective study, we therefore looked for essential clinical signs as well as laboratory findings which might be typical and essential for the diagnosis of CCuP. - We observed that in patients with severe systemic CCuP not only the liver but also several other organs have been the target of copper. As a proof copper overload has been measured. The latter results are presented here. - During or shortly after exposure "free" serum copper (= non-ceruloplasmin-bound copper) was significantly elevated in all patients (range 5.1 to 47.1 micromol/l, or 25.7 to 56.2 % of total serum copper). The normal upper limits in infants according to Salmenperä (8) are: 0.3 micromol/l, or 1.6 % of total serum copper. - Total serum copper was elevated in 14/16 patients: 13.7 to 30.1 micromol/l in sick infants (normal upper level: 12.6 micromol/l), and 17.0 to 27.2 in sick children (normal upper level for children and adults: 21.4 micromol/l). - Urine copper excretion was found elevated in 9/10 patients, with a range of 11 to 456 microg/dl (normal upper level in adults: 15 microg/dl). - Our results show that patients with systemic CCuP are in a "hypercupric" state. The data thus firstly prove that indeed the putative agent copper is found in excess in the patients and secondly show that the estimation of "free" copper in serum and the measurement of copper in urine are reliable diagnostic methods. Elevation of total serum copper (even though not specific) can give a first hint to the diagnosis. - The hypercupric state of systemic CCuP can be differentiated from that of Wilson's disease by (1) normal levels of ceruloplasmin and (2) the observation that values for free copper in serum or urinary copper normalize in an environment without copper in tap water, for instance in a hospital.

In ten cystic fibrosis patients and nine age-matched controls, renal function was determined before and after infusion of secretin. Under baseline conditions creatinine excretion and clearance were significantly elevated, exclusively due to those patients who were homozygous for the DF508 mutation (153 vs 132 ml/min*1.73m2), whereas the glomerular filtration rate, measured by inulin clearance showed no difference. Renal plasma flow and the fractional reabsorption rates of electrolytes were similar in patients and controls. During secretin infusion renal plasma flow increased and the fractional reabsorption rates of electrolytes decreased in both groups. The patients had a increased metabolic clearance (2900 vs 1660 ml/min*m2) and endogenous production rate (9,9 vs 2,5 pmol/min*m2) of of secretin. In conclusion global renal function and electrolyte handling, in particular chloride permeability, are unchanged in cystic fibrosis. Individuals expressing the DF508 genotype showed a selective elevation of creatinine excretion and clearance. The secretion and metabolic clearance of secretin are increased in cystic fibrosis.

Zusammenfassung Das Hyper-IgD-Syndrom ist eine erstmals von Van der Meer et al. im Jahre 1984 beschriebene sehr seltene Erkrankung. Typischerweise präsentiert sie sich mit einer über Jahre verlaufenden Anamnese von rezidivierenden Fieberattacken, vergesellschaftet mit abdominalen Beschwerden, Arthralgien, Hauterscheinungen, Schüttelfrost und Kopfschmerzen. Beweisend für die Diagnose ist die polyklonale Erhöhung des Serum-IgD. Derzeitige therapeutische Optionen sind nur supportiver Art. Bisher kommen nahezu alle dokumentierten Krankheitsfälle aus Europa. In Deutschland ist kein Fall beschrieben. Wir berichten über einen 8 jährigen Jungen, der seit seinem 3. Lebensmonat an rezidivierenden mehrtägigen Fieberschüben in 2- bis 3 wöchigen Abständen leidet. Weitere Kardinalsymptome sind die heftigen, den Patienten schwer beeinträchtigenden Brechattacken sowie Kopfschmerzen und ein flüchtiges Exanthem. Eine erhöhte Blutsenkungsgeschwindigkeit, eine Leukozytose mit Linksverschiebung sowie erhöhte Werte für IgA, IgE und IgD können im Schub festgestellt werden. Diskussion: Das Hyper-IgD-Syndrom muß in die Differentialdiagnose des „Fieber unklarer Genese“ einbezogen werden. So können einzelnen Patienten über Jahre sich wiederholende Krankenhausaufenthalte und z. T. invasive diagnostische Maßnahmen erspart werden.

Recombinant human growth hormone (rhGH) has become a new treatment modality for short children with chronic renal failure (CRF) and after renal transplantation. The rationale for high-dose rhGH treatment is the insensitivity of the uremic organism to GH. As the insensitivity to GH is expressed more in end-stage renal failure than in earlier stages of CRF, patients on dialysis respond less to rhGH. In transplanted children, rhGH can counterbalance the growth-depressing effects of corticosteroids, In prepubertal children, rhGH improves the height standard deviation score by a mean of +2 within 5 years. The effect of rhGH treatment on final height remains to be studied.

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.

The effects of the diuretic furosemide (CAS 54-31-9) 1 mg/kg bw i.v., of the angiotensin converting enzyme (ACE) inhibitor captopril (CAS 62571-86-2) 1 mg/kg bw p.o. and the prostaglandin synthesis inhibitor indometacin (CAS 53-86-1) 2 mg/kg bw p.o. on kidney function, salt and water excretion, the excretion of renal prostaglandins PGE2, PGF2a, 6-keto-PGF1a, thromboxane B2 (TXB2) and the plasma renin activity (PRA) were investigated on 29 neonatal piglets. Within 1 h, fuorsemide led to pronounced diuresis and natriuresis, to a rise of the glomerular filtration rate (GFR) (which ist low in neonatal pigs) by 1.8 times, increased the excretion of renal prostaglandins (especially the vasoconstrictor, thromboxane B2 (TXB2 and PGF2a) and raised the PRA significantly. Under captopril, the PRA rose significantly, whereas there was no unequivocal change in the excretion of renal prostaglandins. There was a pronounced decline of the sodium and potassium excretion in the urine with a fall in the concentrations of electrolytes in serum and of the hematocrit. Under indometacin, the excretion of all prostaglandins in the urine declined (this decline was most pronounced for PGE2). There was also a decrease in sodium excretion, whereas there was no significant change in PRA. It can be concluded from the results that the effects of the investigated drugs on the pig neonate kidney is at least partially attributable to an influence on hormonal factors.

A 13-year-old Turkish girl was admitted because of recurrent episodes of muscle pain and weakness since the age of 5 years. As an outpatient she developed severe acute rhabdomyolysis (myoglobinuria and increased serum creatine kinase level of 19,000 units/l). The acute rhabdomyolysis and the preceding episodes of muscle pain and weakness had been induced by exercise. There was no increase in plasma ammonia level during ischaemic forearm exercise test and bicycle ergometry. Myoadenylate deaminase deficiency was proven both histochemically and biochemically. The girl was found to be homozygous for the C 34-T mutation of the AMPD1 gene causing primary myoadenylate deaminase deficiency in skeletal muscle. Both parents and her brother were heterozygous for that mutation. Myoadenylate deaminase deficiency has to be considered as a cause of severe rhabdomyolysis.

Bromism, the chronic intoxication with bromide is rare and has been almost forgotten. In the recent past bromide is rediscovered as an anticonvulsive drug. The increasing frequency of bromism in children coming to admission induced this report. We describe the cause, the symptoms and the pseudohyperchloremia associated with bromism. If unclarified neurological or psychiatric symptoms are associated with the determination of an elevated serum chloride concentration and a diminished anion gap chronic intoxication with bromide has to be excluded.

: Bromism, the chronic intoxication with bromide is rare and has been almost forgotten. In the recent past bromide is rediscovered as an anticonvulsive drug. The increasing frequency of bromism in children coming to admission induced this report. We describe the cause, the symptoms and the pseudohyperchloremia associated with bromism. If unclarified neurological or psychiatric symptoms are associated with the determination of an elevated serum chloride concentration and a diminished anion gap chronic intoxication with bromide has to be excluded.

We report a disease entity which occured in certain areas of West Germany and which was not diagnosed correctly in the past. At present, we are aware of 21 patients (pts) in 15 unrelated families with a total of 45 children. 11 pts died between 8 and 13 months of age, and 6 survived with liver cirrhosis. In the remaining 4 transaminases were initially elevated and turned to normal with correction of drinking water. All families lived in rural areas known for acid ground water. Drinking water was obtained from the own farm's wells with low pH (5.0 - 6.2) and was highly contaminated after passage through copper pipes. All pts were exposed to copper beginning shortly after birth; none of them was breast fed and all received milk formula prepared with the tap water. None of the 24 healthy siblings were exposed during the first three months of life. All pts developed a micronodular liver cirrhosis which resembled the “Indian Childhood Cirrhosis” and which was accompanied by significant copper accumulation in the liver. Common clinical symptoms included: enlargement of liver and spleen, anemia, bleeding disorders, muscular hypotonia. We believe that this disease might occur in other parts of the world if the environmental conditions are similar (acid drinking water and copper piping).

(1989). Natural Killer Cell Function and Interferon Production in Familial Hemophagocyticlymphohistiocytosis. Pediatric Hematology and Oncology: Vol. 6, No. 3, pp. 265-272.

The validity of ultrasound in the diagnosis of pyonephrosis in infants and children was retrospectively investigated in 14 patients. The disease was unilateral in 13 patients and bilateral in one. The diagnosis was proven by percutaneous nephrostomy in 7 and by operation in 7 patients. Ultrasound was true positive in 9 patients (10 kidneys) and false negative in 5. Large staghorn calculi were present in 2 of the 5 false negative cases. A group of 20 patients with simple hydronephrosis, investigated by percutaneous punctures, served as a control group. There were two false positive cases in this group. The sensitivity of sonography for the diagnosis of pyonephrosis was only 66.7%, which is considerably lower than in previous reports. We therefore recommend early sonographically guided percutaneous puncture of the renal pelvis whenever pyonephrosis is suspected.

A diagnostic schedule in pyonephrosis was followed in thirteen infants and children. Obstruction of the urinary tract could be demonstrated in 12 patients, non-obstructive pyonephrosis was present in one case. Congenital obstructive malformation of the urinary tract was found in 7 patients, obstruction was acquired in 5. Sonographically, pyonephrosis could be diagnosed in 8 patients (64.3%). Excretory urography (10/13) was helpful in no actual case. Sonographical-guided percutaneous nephrostomies were performed in 5 patients and operative nephrostomies in 4. Emergency-nephrectomies were done in 4 patients. A tap of the renal pelvis is the best way for early diagnosis whenever pyonephrosis is clinically suspected.

A severe copper storage disease of the liver with micronodular cirrhosis resembling Indian childhood cirrhosis (ICC) was found in two siblings of a German family leading to death in one infant at the age of 13 months. The fatal outcome correlated with severe ballooning of hepatocytes and excessive formation of Mallory bodies. The copper content of the liver was 698 micrograms per gramme wet weight (control 5 micrograms) in the living patient and 2154 micrograms per gramme dry weight (controls 39, 54 micrograms) in the dead infant. In both cases copper was stored not only in hepatocytes but also to a high degree in mesenchymal cells. Chronic contamination of drinking water supplied from a well via copper pipes could be verified as the cause of copper intoxication, lending further support to ICC as an environmental, acquired disorder. Accumulation of exogenic copper already very early in infancy appears most important for the development of the disease, as both the parents and one child not exposed to copper intoxication during the first 9 months of its life are clinically healthy.

Three of the four children of two unrelated German families fell ill in the first year of life with severe hepatopathy leading to death in two of the children so far, after a progressive clinical course and severe hepatic failure. Laboratory and morphological investigations revealed a high concentration of copper in the liver and to a lesser degree in the kidneys and other organs. The liver architecture was severely altered by micronodular cirrhosis with toxic liver cell damage similar to that found in Indian childhood cirrhosis. Epidemiologically, copper intoxication of the drinking water was verified. The drinking water was obtained from wells via copper pipes. The copper content of the drinking water went as high as 3400 micrograms/l in the two families while water taken directly from the well showed normal content but had lowered pH (6.2). Both parents were clinically healthy, as was an older son who had not been exposed to copper intoxication during the first nine months of his life. Therefore, copper intoxication during the perinatal period appears to be a prerequisite for manifestation of the disease.

TNF is a cytokine released by activated monocytes exerting a number of reactions that may occur during HD (fever, neutropenia, monocytopenia, vascular endothelial lesions). We measured serum levels of TNF in 6 adolescents aged 14-21 years undergoing regular HD 5 min before and 15 min after start of the procedure with cuprophane membranes. Before HD TNF could not be detected in measurable amounts. In contrast, 5 of 6 sera taken after start of the HD session we found significant amounts of TNF (1045-7000 pg/ml serum). Our results suggest that TNF is released by HD. Therefore the above mentioned side effects of HD may be related to the action of TNF. The high TNF levels may also contribute to the development of autoantibodies or the persistance of cytotoxic antibodies in HD pts. Supported by BMFT, Bonn, FRG, PTB#03 8397