The objective of this study was to investigate whether mutations of the renin-angiotensin system genes are involved in primary vesicoureteric reflux (VUR) and VUR-associated renal scarring. The M235T polymorphism of the angiotensinogen ( ATG) gene, the I/D polymorphism of the angiotensin converting enzyme ( ACE) gene, and the A1166C polymorphism of the angiotensin II type 1 receptor ( AT1) gene were identified in 77 patients with primary VUR (aged 6.9+/-3.2 years, mean+/-SD) and 80 healthy controls (aged 33+/-7 years). Thirty-eight of the 77 VUR patients had low-grade VUR (grade I-III) and 39 had high-grade VUR (grade IV and V). Renal scarring was found in 43 VUR patients, while 34 patients had normal kidneys on dimercaptosuccinic acid scan. The ACE gene polymorphism was determined by polymerase chain reaction and the ATG and AT1 gene polymorphisms were determined by single-step LightCycler technology. We found significant over-representation of the DD genotype in patients with renal scarring (44 %) compared with normal controls (23%, P<0.05) and patients with no scar formation (21%, P<0.05). Significantly higher D and significantly lower I allele frequencies were present in VUR patients with scarred kidneys (D allele 0.64 and I allele 0.36) compared with controls (D allele 0.53 and I allele 0.47, P<0.05) and patients with unscarred kidneys (D allele 0.4 and I allele 0.6, P<0.05). No differences in the ATG and AT1 genotype distributions and allele frequencies were observed in VUR patients compared with the normal population. The DD genotype and D allele of ACE may be a genetic susceptibility factor contributing to scar formation in VUR. We detected no linkage of genetic polymorphisms of ATG and AT1 to VUR and VUR-associated renal scarring.

The effects of promethazine were studied in children with frequently recurring pyelonephritis which was not associated with urological abnormalities. The results of three methods of treatment were compared: 10 children were given a combination of gentamycin and promethazine for 7 days (Group 1), 11 received gentamycin treatment alone for 10 days (Group 2), and 19 (Group 3) were on long-term oral antibiotic prophylaxis (5.6 +/- 2.1 years) with episodes of intensive treatment of recurrences. In a 3-year follow-up period, the number of pyelonephritis recurrences was significantly lower in Group 1 than in Groups 2 and 3. Six out of 19 children in Group 3 had renal scarring. The authors suggest a synergistic effect between gentamycin and promethazine therapy. Promethazine increases antibiotic sensitivity, which could contribute to the elimination of recurring urinary tract infections.

A retrospective study was made on 37 children with idiopathic nephrotic syndrome (INS). At the beginning, all patients were steroid sensitive but received more than one steroid course (median 4). Following several relapses, they became steroid dependent or steroid resistant. Group 1 consisted of 22 children [3 focal segmental glomerulosclerosis (FSGS), 19 minimal-change NS (MCNS)] who received cyclophosphamide (CP) orally for 2.5 +/- 0.5 months. Group 2 consisted of 15 children (7 FSGS, 8 MCNS) who received cyclosporine-A (CSA) for 28 +/- 15 months. The level of proteinuria decreased significantly and remained low during the follow-up. The relapse-free period was significantly longer in the CP group (CP 30 +/- 21.5; CSA 26.2 +/- 18 months, p < 0.001). The relapse rate decreased significantly in both groups and remained in this lower level during the follow-up (from 3.4 +/- 2.8 to 0.1 +/- 0.2/year in group 1, and from 3.7 +/- 3.1 to 0.6 +/- 0.8/year in group 2). At the end of the 5-year follow-up, 20/22 patients (90.9%) and 10/15 patients (66.6%) were in remission in groups 1 and 2 respectively, with or without treatment (p < 0.05). In the long term, both CP and CSA is effective second-line therapy following steroid monotherapy in INS patients, but the relapse rate was lower and the relapse free period was significantly longer in the CP-treated group.

The efficacy of combined therapy with recombinant human erythropoietin (rhEPO) and vitamin E versus rhEPO alone in the treatment of anemia was examined in children (n = 10, aged 15.2 +/- 3.2 years) on chronic hemodialysis at the restart of rhEPO therapy after a 4-week interval. The results confirmed that rhEPO induced oxidative stress of the red blood cells as observed during the first rhEPO therapy. Vitamin E (15 mg/kg per day per os) was introduced after 2 weeks of rhEPO monotherapy, when the signs of acute oxidative stress appeared. The level of oxidized glutathione (GSSG) increased from 8.9 +/- 3.1 to 26.7 +/- 5.7 nmol/g hemoglobin (Hb) by that time. After 2 weeks of simultaneous vitamin E treatment, there was a significant difference in GSSG values compared with rhEPO monotherapy (10.1 +/- 3.9 vs. 56.7 +/- 15.8 nmol/g Hb, P < 0.001). A considerable decrease was observed in the previously high ratio of GSSG/reduced glutathione (GSH), an indicator of oxidative stress, and the level of carboxyhemoglobin, indicating hemolysis. A significant increase in Hb and hematocrit (P < 0.01) was achieved within 2 weeks of starting the combined therapy, while similar results occurred only at the 8th and 5th weeks without vitamin E. Antioxidant vitamin E supplementation improved the therapeutic effect of rhEPO in patients with chronic renal failure on hemodialysis.

in obese children an increased platelet aggregation and oxidative insult contribute to the development of hypertension and to the promotion of vascular damage.