Christoph Aufricht

Reproducible erythroid aplasia caused by mycophenolate mofetil

Abstract Anemia secondary to mycophenolate mofetil (MMF) was recently described in experimental animals. A clinical association between MMF and anemia has been observed, but there are no proven reports. We describe a girl with chronic graft failure who developed erythroid aplasia under immunosuppression with MMF. She showed prompt resolution when MMF was discontinued and a recurrence of this clinical course when MMF was restarted. As re-challenge with a medication is the most definitive approach for showing a direct relationship between the drug and the side effect, this case clearly demonstrates that MMF can cause erythroid aplasia.

Tubulointerstitial nephritis and uveitis: an immunological disorder?

A 14-year-old boy with tubulointerstitial nephritis and uveitis (TINU syndrome) is described. Nephropathy improved without systemic cortisone treatment, whereas uveitis relapsed and was treated with topical steroids. Blood cell immunological analysis and serum analysis revealed signs of cytotoxic T-cell, macrophage and granulocyte activation, which declined as the clinical symptoms improved. This may be interpreted as an indication of their significance as markers in the pathogenesis of this syndrome or as part of a microbial-triggered immune response.

Oral metronidazole does not improve cyclosporine A-induced gingival hyperplasia

Abstract. Recently, resolution of cyclosporine A (CSA)-induced gingival hyperplasia was reported with antibiotic treatment. We therefore assessed the oral status of 45 children on CSA after renal transplantation and evaluated the effects of metronidazole treatment in children with high-grade gingival hyperplasia. Gingival hyperplasia was absent in 19 (42%), mild in 5 (11%), moderate in 13 (29%), and severe in 8 (18%) children. There was no significantly different incidence in high-grade gingival hyperplasia (moderate and severe) between children with (16 of 30) or without (5 of 15) concomitant treatment with calcium channel blockers. The mean trough level of CSA was not different between children with varying severities of gingival hyperplasia. We treated 13 children with high-grade CSA-induced gingival hyperplasia (9 boys, 4 girls, mean age 14.2±3.4 years) with 750 mg metronidazole in three divided doses (10 – 25 mg/kg) for a total of 7 days. All 13 children were concomitantly treated with calcium channel blockers for hypertension; their mean monoclonal CSA trough level was 246±34 ng/ml. Oral examination and photographic documentation were performed by the same examiner on all patients before and 1 and 3 months after metronidazole treatment. We found no changes in gingival hyperplasia; gingival inflammation improved in 5 children (P = ns). We conclude that synergistic effects of calcium channel blockers and high concentrations of CSA in our population may outweigh beneficial effects of metronidazole treatment of CSA-induced gingival hyperplasia after renal transplantation.

MRI in the diagnosis of a peritoneal leak in continuous ambulatory peritoneal dialysis

Abstract. Mechanical problems in continuous ambulatory peritoneal dialysis (CAPD) can result in ultrafiltration failure and disruption of CAPD therapy. The recently described tool of CT peritoneography with water-soluble contrast medium has the disadvantage of radiation and instillation of nephrotoxic substances. We report a child with a peritoneal leak diagnosed by MRI after instillation of a gadodiamide-dialysate mixture. This method provided good anatomical detail without radiation or nephrotoxic agents.

Erythropoietin, erythropoesis and iron status in children after major surgical stress

The aim of our study was to evaluate bone marrow stimulation and bone marrow response to post-operative anaemia in children after open heart surgery. In 16 children (age 5.7±0.9 years, weight 20.1±3.2 kg) serum erythropoietin, haematocrit, reticulocyte count, ferritin, transferrin saturation and C-reactive protein were assessed perioperatively after cardiopumonary bypass for surgical repair of atrial septal defect. Erythropoietin increased seven fold from 14±6.2 (7–30) to 80±49 (20–171) mU/ml (P<0.05) and the reticulocyte count a 1.7-fold from 11.1±3.1 (6–19) to 18.4±5.9 (10–31) ‰ (P<0.05). Transferrin saturation was inversely correlated to C-reactive protein.ConclusionThese findings suggest adequate bone marrow stimulation but an inadequate bone marrow response during the immediate perioperative period, caused by inhibition of erythropoesis by acute postoperative inflammation in children after open heart surgery.

Transient cerebellopontine demyelinisation revealed by MRI in acute cerebellar ataxia

An eight year old boy was admitted to our ward with a history of abrupt onset of rapidly progressive gait disorder, nausea, vertigo and vomiting. The clinical as well as the labortory findings suggested the diagnosis of acute cerebellar ataxia. Magnetic resonance imaging (MRI), however, showed marked demyelinisation in the cerebellar region and visual evoked potentials were pathologic. After immunosuppression the patient promptly improved clinically and the lesions depicted by MRI disappeared almost completely.

Subcutaneous recombinant human erythropoietin in chronic renal allograft dysfunction

Abstract. We investigated the efficacy and safety of subcutaneous recombinant human erythropoietin (rHuEpo) in 25 children with chronic renal allograft dysfunction (13 girls, 12 boys, mean age 15.8±4.2 years) for a treatment period of 9 – 162 (median 43) weeks. rHuEpo was started once weekly at a dose of 105±25 U/kg per week in 16 children, twice weekly at a dose of 175±70 U/kg per week in 6 children, and three times weekly at a dose of 270±28 U/kg per week in 3 children. The hematocrit increased in 21 children from 23.2%±3.1% to 33%±3.1% within 7.2±4.9 weeks at a mean rate of 1.98%/week. The hematocrit increase and rHuEpo starting dose were linearly related (delta hematocrit/week = 0.8+0.08 U/kg per week, r = 0.44, P <0.05). The maintenance dose was 74±23 (43 – 114) U/kg per week. Four children failed to reach the target hematocrit, most likely due to noncompliance. Seventeen recurrences of anemia (“anemic episodes”) during rHuEpo therapy were identified in 12 children, mostly associated with acute or insidious deteriorations in graft function. There was no acceleration of progression of graft dysfunction with rHuEpo treatment. We conclude that subcutaneous rHuEpo at a single weekly dose of 100 IU/kg per week is highly effective in children with chronic graft dysfunction. Children who appear to be rHuEpo resistant or experience rHuEpo-resistant episodes should be assessed for noncompliance, changes in graft function since the last dosage adjustment, and blood loss, such as seen in dysfunctional uterine bleeding in adolescent girls.

Angiotensin converting enzyme inhibitor does not reduce proteinuria in an infant with congenital nephrotic syndrome of the Finnish type

Intractable proteinuria in the congenital nephrotic syndrome which is resistant to aggressive conservative treatment leads to malnutrition and increases the risk of lifethreatening infections, severe hypovolaemia and thromboembolic complications. Only bilateral nephrectomy followed by dialysis and ultimately a renal transplant have improved the outcome. Recently unilateral nephrectomy was suggested as an alternative for markedly reducing proteinuria. Based on reports of reduction of proteinuria in both animal models [1, 2] and patients with various renal diseases [3 -7] , we treated a female infant aged 2 months, weight 4,006 g, with congenital nephrotic syndrome with the angiotensin converting enzyme inhibitor (ACEI) captopril. Renal biopsy had indicated the Finnish type of congenital nephrotic syndrome, and two siblings had died of the congenital nephrotic syndrome. Captopril was started at a daily dose of 0.15 mg/kg in three doses and was increased as tolerated to 2.5 mg/kg daily for an 8-week period. Daily spot urine and 24-h urine was collected for measurement of 24-h protein excretion the day before the first captopril dose, after maximum captopril dosage and 10 days after the last dose. We observed no change in urinary protein excretion as determined from the protein/creatinine ratio and the albumin/creatinine ratio of daily spot urine samples or the 24-h urine protein excretion. Serum protein and albumin remained stable. Renal function remained stable during ACEI therapy. The clinical and biochemical effects of captopril are summarized in Table 1. The failure to detect even a small decrease in urinary protein excretion with ACEI was surprising. ACEI causes vasodilatation of the efferent arteriole by inhibiting the conversion of angiotensin I to angiotensin II, increasing circulating bradykinin levels and directly stimulating renal prostaglandin synthesis [1 -7] . This vasodilatation increases renal blood flow and decreases transcapillary hydraulic pressure, reducing axial protein concentration and transglomerular protein filtration, respectively. Young infants have a high renal resistance, and the finding that neonates are especially prone to ACEI-induced renal failure indicates that this is not only due to preglomerular capillaries. One explanation of our findings might be that the acute anti-proteinuric effect of ACE inhibition is more directly related to bradykinin, as reported recently [8]. Bradykinin corrects the sieving defect in proteinuria by reducing glomerular pressure and the stretch force imposed upon the capillary wall; this reduces the number of large non-selective pores. In conclusion, we report a patient with congenital nephrotic syndrome who did not respond to ACE inhibition. However, more data are necessary before Table 1. Clinical and biochemical effects of captopril therapya

Use of prostaglandin I2 in three small children at high risk of early renal graft thrombosis

We report the use of prostaglandin I2 (PGI2) in three small children weighing less than 15 kg at high risk of graft thrombosis after cadaveric renal transplantation complicated by acute tubular necrosis. PGI2 was started at a dose of 5 ng/kg per min within the first 6 h after transplantation, and was continued for 12–15 days. Before and during PGI2 infusion, color-coded and pulsed Doppler sonography was performed. We found immediate restoration of diastolic flow, consistent with a decrease in vascular resistance. During the subsequent days, the sonographically assessed flow pattern and clinical graft function improved gradually. None of the three consecutively treated children developed graft thrombosis or lost his graft; no clinically relevant bleeding or adverse hemodynamic or pulmonary effects were seen.

Iron supplementation in children after cardiopulmonary bypass for surgical repair of congenital heart disease

SummaryA controlled study was carried out to evaluate the effects of postoperative iron therapy on iron status in anemic children after cardiopulmonary bypass. The patients were 8 boys and 9 girls (mean age 6.5 years) who underwent elective closure of atrial septal defect, secundum type. On postoperative day 9, patients were randomly assigned to either iron supplementation with iron sulfate 5mg/kg until day 56 or to a control group. Hemoglobin, reticulocytes, transferrin saturation, free erythrocyte protoporphyrin, and ferritin were measured, the final outcome measure being postoperative iron status on day 56. The treatment group showed higher transferrin saturations (33.5% versus 18.0%), smaller decreases in ferritin level (+3.0 versus −13.7ng/ml), and a lower incidence of depleted iron stores (0/8 versus 5/9) than the control group (all data:P<0.05). Anemic children after cardiopulmonary bypass for surgical repair of congenital heart disease thus benefit from iron supplementation within the first postoperative weeks.