Oskar H. Oetliker

Persisting Renotubular Sequelae after Cisplatin in Children and Adolescents

UNLABELLED Information on persisting renal sequelae after cisplatin in children and adolescents is limited. Twelve patients aged 4-20 years had been treated with cisplatin and were healthy 4-43 months after stopping chemotherapy. Plasma creatinine, calcium, albumin and hydrogen ion concentration, plasma and urinary sodium, chloride, phosphate and urate, and urinary magnesium and potassium were comparable in patients and controls. However, mean calciuria, magnesemia and potassemia were significantly reduced and bicarbonatemia increased in the patients. Calciuria, magnesemia, potassemia and bicarbonatemia were normal in 3 patients only, calciuria was below -2 SD control in 9 patients, renal magnesium deficiency was demonstrated in 5 patients (all with hypocalciuria as well), and 4 patients presented with hypokalemic metabolic alkalosis (all with magnesium deficiency and hypocalciuria). CONCLUSIONS (1) Renotubular dysfunctions persist very often after cisplatin; (2) hypocalciuria is more frequent than hypomagnesemia; (3) the most severe tubulopathy after cisplatin includes hypocalciuria, renal magnesium deficiency and hypokalemic metabolic alkalosis.

Long-Term Treatment of Infantile Nephropathic Cystinosis with Cysteamine

CYSTINOSIS is a rare autosomal recessive metabolic disorder of children and adults, characterized biochemically by intracellular accumulation of free, nonprotein cystine crystals in the reticuloend...

Acyclovir-induced renal failure: course and risk factors.

Of 19 children treated with high-dose intravenous acyclovir, 7, all of whom had encephalitis, also had a restricted fluid intake. Of these, 3 experienced nonoliguric renal insufficiency (plasma creatinine up to 176, 250 and 351 μmol/l, respectively) which resolved within 1 week of discontinuing acyclovir. Renal function was stable in the remaining 4 patients in this group and in the 12 children treated with acyclovir but without fluid restriction. We suggest the decreased renal function resulted from intratubular acyclovir crystalluria.

Chronic renal magnesium loss, hypocalciuria and mild hypokalaemic metabolic alkalosis after cisplatin

Renotubular handling of sodium, potassium (K) calcium (Ca), phosphate, hydrogen ions and glucose, and urinary concentrating ability were studied in three children (aged 8, 8.5, 11 years) with renal magnesium (Mg) loss, persisting for more than 2 years after discontinuation of cisplatin treatment for neuroblastoma. A group of healthy children served as controls. Besides renal Mg wasting, a clear-cut tendency towards reduced calciuria associated with normal or slightly elevated plasma Ca was observed. Plasma K tended to be low (3.4–3.7 mmol/l), and plasma chloride was normal. Plasma bicarbonate (HCO3) ranged from 24.9 to 27.8 mmol/l, and urinary pH was always less than 6.0, indicating a renal HCO3 threshold exceeding 24 mmol/l. Plasma creatinine levels, glucosuria and phosphaturia, and urinary concentrating capacity were adequate. Comparable features were found in three children (aged 4.5, 9, 13 years) with primary renotubular hypomagnesaemia — hypokalaemia and hypocalciuria. This study complements the picture of chronic cisplatin tubulopathy in childhood demonstrating that, apart from Mg wasting, a reduced Ca excretion, and a tendency to hypokalaemia and metabolic alkalosis exist. Thus cisplatin may induce renal functional damage identical to that found in primary renotubular hypomagnesaemia — hypokalaemia with hypocalciuria.

Differential effect of acetylsalicylic acid and dipyrone on prostaglandin production in human fibroblast cultures

1 Human skin fibroblasts incubated with arachidonic acid in culture show basal release of prostaglandins. They produce the same prostaglandins after stimulation with bradykinin. 2 Basal release of prostaglandins I2 (6‐oxo‐PGF1α), F2α and E2 is inhibited dose‐dependently by both acetylsalicylic acid (ASA) and dipyrone (P < 0.05). The examined dose‐range was 10−7 to 10−4 M for both drugs. During the first 5 min after removal of the drugs from the incubation medium, bradykinin‐stimulated release remains dose‐dependently inhibited (P < 0.001) in ASA‐, but not in dipyrone‐treated cultures. The difference between the effects of ASA and of dipyrone is highly significant (P < 0.0001), whereas the dipyrone‐treated cultures are not different from controls. 3 The findings are consistent with cyclo‐oxygenase inhibition by ASA as well as by dipyrone. However, the data demonstrate rapid reversibility of the effect of dipyrone. This suggests that in contrast to ASA, dipyrone does not inhibit cyclo‐oxygenase by binding covalently to the enzyme.

Cough and converting enzyme inhibitors.

Persisting cough developed in three children treated with converting enzyme inhibitors. The symptoms disappeared within 3–7 days after withdrawing medication. These observations in children complement previous reports in adults and indicate that cough may be induced by treatment with these agents.

Modified urine osmolal gap: an accurate method for estimating the urinary ammonium concentration?

Dr. M.G. Bianchetti, Inselspital, CH3010 Berne (Switzerland) Dear Sir, Since ammonium is the crucial component of renal acid excretion, the measurement of its urinary concentration represents a major diagnostic step in conditions affecting the urinary acid excretion [1-3]. The very cumbersome formaldehyde titration has been traditionally used for the measurement of urinary ammonium [4]. Colorimetric assays are technically simpler [5]. However, in most clinical laboratories, both formaldehyde titration as well as colorimetric assays are unsuitable for a bedside determination of urinary ammonium. An indirect estimate of urinary ammonium, the modified urine osmolal gap, has been more recently suggested [6]. The usefulness of the mentioned estimate was, therefore, evaluated in 34 healthy subjects (25 males and 9 females, age 5-44 years). The urinary ammonium concentration was assessed colorimetrically using a modification of the Berthelot reaction, replacing phenol by sodium salicylate [7]. In addition, the urinary ammonium concentration (mmol/l) was indirectly estimated using the modified urine osmolal gap [6]: Osmolality-[2(sodium+potassium)+urea+glucose] 2 Standard laboratory methods were used for the determination of osmolality (mmol/ kg) and sodium, potassium, glucose, and urea concentrations (mmol/l). The agreement between measured and estimated urinary ammonium was assessed 60 40 40 20 20 0 5 |-20 < B to -40 -20 0 10 20 30 40 50

OUTCOME IN IDIOPATHIC CHILDHOOD NEPHROTIC SYNDROME A 20 Year Experience

112 patients with idiopathic childhood nephrotic syndrome have been referred from 1970 through 1989 at the Department of Pediatrics, University of Berne. One patient remitted spontaneously without medication. Ninety-eight patients responded to prednisone: 15 had a single bout of nephrosis, 47 developed a tendency towards relapses and 36 steroid dependence. In 28 patients with tendency towards relapses cure took place on either prednisone alone or prednisone plus cyclophosphamide. In 18 patients with steroid dependency cure took place on prednisone alone or prednisone plus cyclophosphamide. Thirteen patients failed to respond to steroids. The course of the disease was more benign in 68 patients with minimal change disease as compared with 14 patients with focal and segmental glomerular sclerosis. Immunofluorescence studies demonstrated mesangial IgM deposits in 14 out of 54 patients, but this finding was not a marker for poor steroid response or progression to renal failure. The course of the disease was especially unfavourable in patients with persisting nephrosis on completion of the initial course of steroid therapy. In conclusion it appears appropriate to define the disease in terms of steroid responsiveness as steroid resistant patients sometimes show normal glomeruli, steroid responsive sometimes have focal and segmental glomerular sclerosis or mesangial IgM deposits, and decisions depend more on the steroid responsiveness than on the histological features.

Treatment of recurrent idiopathic nephrotic syndrome after transplantation using plasmaphaeresis and intensified immunosuppression over 2 months.

1. Sanlsbury FT (1993) Corticosteroid therapy does not prevent nephritis in Henoch-Sch6nlein purpura. Pediatr Nephrol 7: 6971 2. Robson WLMR, Lenng AKC (1993) The importance of examining nmltiple urine specimens in patients with glomerulonephritis. Can Faro Physician (in press) 3. Mollica F, LiVolti S, Garozzo R, Russo G (1992) Effectiveness of early prednisone treatment in preventing the development of nepl~opathy in anaphylactoid purpura. Eur J Pediatr 151: 140-144

On the Development of Apoprotein and Lipid Levels throughout Childhood

Epidemiologic and genetic studies on the evolution of cardiovascular disease in man have repeatedly supported the importance of plasma cholesterol levels in the pathogenesis of coronary atherosclerosis (1–4). These studies also emphasize the importance of distinguishing the cholesterol content of the lipoprotein fractions very low density (VLDL), low density (LDL) and high density lipoproteins (HDL). A close correlation between increased levels of LDL known to contain the major part of the transported cholesterol, and the risk of developing coronary atherosclerosis was found (2,5). HDL, on the other hand, appeared to be negatively correlated with the occurrence of coronary heart disease (6–9).