[Pediatric nephrology from the fetal kidney to the kidney graft]. / La néphrologie pédiatrique du rein foetal au rein greffé.

The department of pediatric uro-nephrology was created in 1977 in Brugmann hospital. Since then, various sectors have been developed including: hemodialysis and peritoneal dialysis, kidney transplantation, urological and genital surgery, antenatal screening and rapid management of uronephropathies, treatment of voiding dysfunction and neurogenic bladder, management of tubular and glomerular diseases. The progress in genetics, medical imaging, obstetrics, neonatology and surgery has allowed us to take care of our young patients within a multidisciplinary framework. The most original contributions of the department are related to the performance of combined liver-kidney transplantation in primary hyperoxaluria, to the determination of the natural history of several congenital anomalies of the kidney and urinary tract, to the assessment of the role of genetic mutations on tubular and glomerular diseases, to the usefulness of radioisotopic tracers in the measurement of renal function in infants, and to the study of experimental tolerance of allografts. The transition of young renal patients from pediatric to adult care is actually well organized due to our 30 years experience and the excellent collaboration with the adult nephrologists.

Insulin-dependent diabetes mellitus as long term complication of haemolytic-uraemic syndrome.

Haemolytic-uraemic syndrome (HUS) is a rare cause of insulin-dependent diabetes mellitus during the acute stage. We previously reported the case of a 3-year-old girl having presented with typical HUS with diarrhea, microangiopathic anaemia, thrombocytopenia and acute renal failure (17 days of anuria). Transient hyperglycaemia (highest level: 513 mg/dl) was observed, requiring continuous intravenous insulin infusion for 9 days. Subcutaneous insulin injections were stopped after 24 days. Oral glucose tolerance test performed 4 months after normalization of blood glucose was normal. HLA DQ genotype (DQA1-DQB1.AZH/DQA3-DQB3.1) was not at risk for type 1 diabetes and there were no auto-antibodies (ICA and IAA). The 3-years follow-up was marked by persistent arterial hypertension, proteinuria and slight renal insufficiency despite angiotensin-converting enzyme inhibitor treatment. Ten years after HUS occurred (the patient had been lost to follow-up for 7 years), she came back with complaints of headache but neither polyurodipsia nor weight loss. She was found to have arterial hypertension. Chronic renal impairment had moderately progressed with decreased glomerular filtration rate (63 ml/min/1.73 m2) and proteinuria (2 g/24 hours). Fasting blood glucose was 189 mg/dl and reached 315 mg/dl during an oral glucose tolerance test. HbA1c level was 8.2% (N<6.2%) and diabetes mellitus was diagnosed without any signs of autoimmunity (IAA, ICA, GADA and IA2B were negative). Good glycaemic control was obtained with 0.5 U/kg/day of insulin. In conclusion, transient beta-cell dysfunction complicating HUS acute stage may evolve to overt non-autoimmune diabetes mellitus (microangiopathic process?), even after a long free interval. This case emphasizes the need for a long-term follow-up of patients with HUS.

[Immunosuppressive agents in pediatric renal transplantation]. / Le traitement immunosuppresseur en transplantation renale pédiatrique.

Advances in immunosuppressive therapy over the past decade have led to dramatic improvements of patient and graft survival. The immunosuppression that is used is constantly evolving. The goal remains to find the best combination that will optimize long-term graft survival, while minimizing the adverse effects. It is likely that in the near future the results will even be improved further by the development of new medications with a better therapeutic index and the induction of transplant tolerance.

Early prognostic factors of infants with chronic renal failure caused by renal dysplasia.

Renal dysplasia (RD) is a common cause of chronic renal failure (CRF) in children. The evolution towards end-stage renal failure is unpredictable due to the paucity of early prognostic factors. In order to identify early prognostic clinical criteria, we have retrospectively analyzed renal function and growth in 11 infants with RD and CRF from birth up to 4 years of age. Children with obstructive RD were not included. Glomerular filtration rate (GFR) was estimated from Schwartz formula. In infants with a GFR below 15 ml/min per 1.73 m2 at 6 months of age (group A, n=5), kidney function did not further improve; 4 reached end-stage renal failure between 8 months and 6 years of age. In contrast, infants with a GFR above 15 ml/min per 1.73 m2 at 6 months of age (group B, n=6) experienced a significant improvement in renal function during follow-up, and none required renal replacement therapy. During the first 3 months of life all infants with RD and CRF developed severe growth retardation. Between 6 months and 4 years of age, children from group B grew significantly better than those from group A. In conclusion, our experience suggests that GFR, estimated from Schwartz formula at 6 months of age, is a useful prognostic factor in infants with RD and CRF. Infants with a GFR below 15 ml/min per 1.73 m2 are at risk of severe growth delay and the need for early renal replacement therapy, whereas those with a GFR above 15 ml/min per 1.73 m2 have a relatively favorable long-term prognosis.

Impact of growth hormone treatment on a Belgian population of short children with renal allografts.

We retrospectively analyzed the effects of recombinant human growth hormone (rhGH) in a Belgian population of 36 short children with renal allografts. Seven children were dropped from the growth study: 1 had skeletal dysplasia and in 6 cases rhGH was given for less than 1 yr (1 died, 1 developed genu valgum, 2 were non-compliant and 2 grafts deteriorated). Final height was reached in 17 patients, and 12 children were still growing at the end of the study. Median height standard deviation score (SDS) in the 29 patients was -2.3 at the time of transplantation, and -2.7 when rhGH therapy was initiated. During rhGH therapy (median duration 3.2 yr, range 0.6-7.7 yr), height SDS increased by a mean of 0.4 per year, and bone maturation was not accelerated. Final height reached was 162.7 (149.0-169.5) cm (median SDS -1.8) in males and 151.0 (130.5-169.5) cm (median SDS -1.9) in females. Final height is significantly greater in males than females compared with a historical control group of untreated patients. Final height is within the parental target height range in 6 out of the 17 patients. The increase in height SDS in patients who were at an advanced stage of puberty (Tanner stages 4-5) when rhGH therapy was initiated exceeded our expectations (mean height gain 14.2 cm in boys and 10 cm in girls). In the cohort of 36 children, 4 patients developed an acute allograft rejection, all of whom had an underlying chronic rejection. This resulted in 3 graft losses within 5 yr. Our results indicate that rhGH treatment has a positive effect in short children with renal allografts, even if it is started in late puberty. In the presence of underlying chronic rejection, rhGH treatment needs careful monitoring to minimize the risk of graft loss.

Cuprophane haemodialysis induces upregulation of LPS receptor (CD14) on monocytes: role of complement activation.

BACKGROUND: The CD14 molecule is a high-affinity receptor for the complex formed by lipopolysaccharide (LPS) and LPS-binding protein. METHODS: We examined by flow cytometry the effect of in vitro and in vivo haemodialysis on cuprophane membrane and recombinant C5a on the expression of CD14 molecules at the surface on monocytes. Monocyte CD14 expression was also studied during in vitro and in vivo haemodialysis on polyacrylonitrile AN69 membrane. RESULTS: In vitro haemodialysis of whole blood from healthy volunteers on cuprophane membrane resulted within 30 min in upregulation of monocyte CD14 expression. The reuse of the cuprophane membrane abolished both complement activation and CD14 upregulation. Moreover, incubation of whole blood with recombinant C5a led to an increased monocyte CD14 expression supporting a role for complement activation in the rapid cuprophane-induced CD14 upregulation. During AN69 dialysis which is not associated with complement activation in the blood phase, monocyte CD14 expression did not change during the first 60 min but was significantly increased after 3 h of in vitro haemodialysis. This late increase might be related to the presence of complement activation products adsorbed on the membrane. In vivo dialysis on cuprophane membrane also resulted in early monocyte CD14 upregulation as indicated by higher CD14 expression found after 60 min on monocytes obtained from the efferent as compared to the afferent line of the dialyser, a phenomenon that was not observed during haemodialysis on AN69 membrane. CONCLUSION: Haemodialysis on the complement-activating cuprophane membrane induces the rapid upregulation of the CD14 LPS-receptor on monocytes.

Effects of ultrapure and non-sterile dialysate on the inflammatory response during in vitro hemodialysis.

Several studies support the hypothesis that bacterial contamination of the dialysate stimulates the inflammatory response to hemodialysis (HD) and increases the long-term morbidity of HD patients; this phenomenon could also be modulated by the nature of the HD membrane. Therefore, this study was designed to compare the effects of non-sterile (NSBD, mean endotoxin content +/- SEM 97 +/- 22 EU/ml) and ultrapure bicarbonate dialysate (UPBD, sterile and pyrogen-free, obtained by ultrafiltration through polyamide) on several aspects of the inflammatory reaction during in vitro HD. The HD sessions (7 in each experimental group) were performed using miniaturized new cuprophane (CU) and polyacrylonitrile (PAN) hollow fiber dialyzers, and closed dialysate and blood circuits (the latter filled with heparinized blood from healthy donors). Plasma C3aDesarg levels were significantly increased after 15 minutes (t1) and increased further after three hours (t2) of CU HD, while during PAN dialysis they decreased from t0 to t1 and t2; however, no difference appeared between experiments with NSBD and UPBD. Granulocyte (PMN) and monocyte (MNC) expression of LFA-1, Mac-1, and CD45 at the start (t0), t1 and t2 was quantitated by flow cytometry analysis, after staining of the cells with specific fluorescinated monoclonal antibodies. In contrast with published data of in vivo HD, LFA-1 was overexpressed at t1 and peaked at t2, which suggests that the leukocytes expressing more LFA-1 leave the systemic circulation during in vivo HD. During CU HD, Mac-1 and CD45 on PMN and MNC were significantly increased at t1, and still more at t2. During PAN HD, Mac-1 and CD45 remained unchanged at t1, but increased significantly at t2 on PMN as on MNC. Again, no significant difference was found between NSBD and UPBD in LFA-1, Mac-1 and CD45 expression on PMN and MNC, during both CU and PAN HD. AFter three hours of dialysis, plasma levels of TNF-alpha, but not of IL-6, were significantly increased with CU and PAN. Again, no difference appeared when NSBD and UPBD were compared. Moreover, the lack of influence of bacterial contamination of the dialysate on TNF-alpha production was confirmed when MNC were cultured up to 24 hours after the end of the HD session. We conclude that complement activation products, either in plasma (CU) of those adsorbed on the HD membrane (CU and PAN) play the major role in the overexpression of beta 2-integrins and CD45 by PMN and MNC during HD. Also, bacterial products (at the levels that can be found in clinical conditions) do not influence either beta 2-integrin overexpression or TNF-alpha production induced by the dialysis membrane.

Combined liver-kidney transplantation in primary hyperoxaluria type 1. Bone histopathology and oxalate body content.

In three patients with end-stage renal failure due to primary hyperoxaluria type 1, successful combined liver-kidney transplantation enabled us to assess the insoluble oxalate pool, which was compared with the histopathological changes observed in iliac crest biopsy specimens. Good correlation was observed between the histopathological grade of bone oxalosis and the estimated oxalate content of the body. In the end-stage of oxalate bone disease, hyperparathyroidism does not play a significant role in bone resorption, which appears to be the consequence of the granulomatous reaction induced by oxalate deposition. Combined liver-kidney transplantation should be performed long before this stage. Early hepatorenal grafting in uremia secondary to primary hyperoxaluria type 1 would avoid the deleterious clinical consequences of systemic oxalosis and shorten the duration of postransplant hyperoxaluria, which may compromise the course of kidney graft.

MRI evaluation and follow-up of bone necrosis after meningococcal infection and disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a serious complication of meningococcal septicaemia. It often results in infarction of various tissues namely the skin, adrenal glands, kidneys, brain and, much less commonly, bones. We describe a patient who presented bone lesions after meningococcal septicaemia. In addition to plain radiography and scintigraphy the lesions were evaluated with MRI and have proved to be extensive and still progressive, approximately 18 months after the onset of the disease.