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A high prevalence of chronic kidney disease among children with focal segmental glomerulosclerosis (FSGS) leads to a permanent quest for good predictors of kidney dysfunction. Thus, we carried out a retrospective cohort study in order to examine known clinical and morphological predictors of adverse outcome, as well as to investigate glomerular nestin expression as a potential new early predictor of kidney dysfunction in children with FSGS. Relationships between nestin expression and clinical and morphological findings were also investigated. Among 649 renal biopsy samples, obtained from two children’s hospitals, FSGS was diagnosed in 60 children. Thirty-eight patients, who met the criteria for this study, were followed up for 9.0 ± 5.2 years. Using Kaplan–Meier and Cox’s regression analysis, potential clinical and morphological predictors were applied in two models of prediction: after disease onset and after the biopsy. The present study revealed the following significant predictors of kidney dysfunction: patients’ ages at disease onset, as well as age at biopsy, resistance to corticosteroid treatment, serum creatinine level, urine protein/creatinine ratio, vascular involvement, tubular atrophy, interstitial fibrosis, and decreased glomerular nestin expression. The most important finding of our study is that nestin can be used as a potential new early morphological predictor of kidney dysfunction in childhood onset of FSGS, since nestin has been obviously decreased in both sclerotic and normal glomeruli seen by light microscopy.

Dent disease is an X-linked recessive disorder affecting the proximal tubule and is characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis/nephrolithiasis with a variable number of features of Fanconi syndrome. It is most often associated with mutations in CLCN5, which encodes the endosomal electrogenic chloride/proton exchanger ClC-5. Renal acidification abnormalities are only rarely seen in Dent disease, whereas the hypokalemic metabolic alkalosis associated with hyperreninemic hyperaldosteronism (Bartter-like syndrome) has been reported in only one patient so far. We report on a 5-year-old boy with Dent disease caused by mutation in CLCN5 gene, c.1073G>A, who presented with hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism persisting over the entire follow-up. No mutations were found in NKCC2, ROMK, NCCT, or ClC-Kb genes. In addition, the patient exhibited growth failure associated with partial growth hormone (GH) deficiency. Coexistence of Bartter-like syndrome features with LMWP should prompt a clinician to search for Dent disease. The Bartter syndrome phenotype seen in Dent disease patients may represent a distinct form of Bartter syndrome, the exact mechanism of which has yet to be fully elucidated. Growth delay that persists in spite of appropriate therapy should raise suspicion of other causes, such as GH deficiency.

Eight boys aged 2-12 weeks with urinary tract malformations (UTMs) exhibited features of transient type 1 pseudo-hypoaldosteronism (TPHA1) in the course of urinary tract infection (UTI). Hyponatremia (120.9+/-5.8 mmol/l), hyperkalemia (6.9+/-0.9 mmol/l), metabolic acidosis (plasma bicarbonate 11+/-1.4 mmol/l), and a rise in serum creatinine levels (145+/-101 micromol/l) were associated with high urinary sodium (Na) and low potassium (K) excretion. Tubular resistance to aldosterone was indicated by high plasma aldosterone concentrations (170.4+/-100.5 ng/dl), high levels of the plasma aldosterone to potassium ratio (25.2+/-15.6), and diminished urinary K/Na values (0.31+/-0.19). With appropriate therapy, serum electrolytes, creatinine, and acid-base balance normalized within 2 weeks. A Medline search revealed another 85 cases of TPHA1 reported to date. All of the 93 patients were less than 7 months of age and 90% were less than 3 months of age, 90.3% suffered from UTM, with associated UTI in 89% of them, 11% had UTMin the absence of UTI, and 9.7% showed isolated UTI. These findings indicate that early infancy is the main contributing factor for TPHA1 to occur and that UTI and UTMare additional factors, with at least one being required for its development.

We retrospectively evaluated the clinical and histopathological features, treatment modalities, and outcome of 53 children and adolescents with biopsy-proven lupus nephritis (LN), followed between September 1983 and September 2001. The mean age (+/-SD) at the time of diagnosis of systemic lupus erythematosus (SLE) was 12.9+/-2.6 years and the mean follow-up from the time of biopsy was 4.8+/-3.4 years. At the time of biopsy, all 53 patients had proteinuria, 21 (40%) had nephrotic syndrome, and 14 (26%) had impaired renal function. Class IV nephritis, observed in 34 (64%) patients, was the most frequent histopathology on initial renal biopsy. The patients with class IV LN had a significant tendency to develop hypertension ( P=0.04) and nephrotic syndrome ( P=0.027), and a lower mean glomerular filtration rate ( P=0.000). Based on the renal histopathology and clinical presentation, patients were treated with corticosteroids alone or combined with azathioprine or with intravenous cyclophosphamide. Plasmapheresis or cyclosporine was used in 4 and 1 patient, respectively. Follow-up biopsies, performed in 13 patients, showed no change in 6 patients, were progressive in 4, and regressive in 3. On final clinical evaluation, renal disease was in complete or partial remission in 42 of 53 patients (80%), 4 had clinically active disease but with normal renal function, and 7 (13%), all with WHO class IV LN, were classified as having an adverse outcome, i.e., either preterminal (2) or terminal (4) renal failure or death (1). Five-year kidney and patient survival rates from the time of biopsy to the endpoints of terminal renal failure or death were 88.6% and 98.1%, respectively, in the whole group, and 82.4% and 97.1%, respectively, in the WHO class IV group. Nephrotic syndrome and class IV nephritis at initial biopsy were the only parameters significantly associated with adverse outcome in our study group. There was no association with gender, age, hypertension, impaired renal function, anemia, increased morphological index scores, and treatment modalities. We conclude that clinical and histopathological features of LN and treatment regimens in our study do not differ markedly from those in most pediatric series. However, the 5-year kidney and patient survival rates are among the best reported in recent pediatric series. The prognosis of LN is primarily dependent on the histopathological lesions.

There is evidence of a genetic basis in some cases of idiopathic membranoproliferative glomerulonephritis (MPGN) types I and III, particularly those occurring in families. The clinical and morphological features and disease course in two siblings with MPGN are described. In the male sibling, both clinical and morphological features as well as serum complement profile suggested type I MPGN; electron microscopy appearance in the female sibling was consistent with type III MPGN. Both patients had treatment-resistant nephrotic syndrome which evolved into renal insufficiency in the girl. No hereditary complement deficiencies were found in siblings or their parents. Both children exhibited HLA-A24; -B27, w4; -DR11, 52; -DQ3 antigens. Between 1981 and 1996, 18 patients from eight families with unequivocal diagnosis of MPGN I or III had been described. The mode of inheritance appeared to be autosomal dominant or X-linked in four of these families. In 11 patients, including our 2, in whom HLA typing was performed, eight had the HLA-A2 antigen. Similarities and discrepancies regarding clinical and morphological features and outcomes were evident in these intrafamilial cases, suggesting either a similar genetic background or a multigenic origin of MPGN. The familial occurrence of the MPGN, highlighted by our report, supports the concept that genetically determined factors may be involved in the pathogenesis of the disease.

During an outbreak of haemorrhagic fever with renal syndrome (HFRS) in 1989, five children (3 girls, 2 boys, aged 6.8-16 years) with severe clinical form of the disease, were treated at the Institute of Mother and Child Health of Serbia; four of them were followed-up 22-28 months thereafter. The main clinical features were: fever, headache, myalgia, abdominal and back pains, and vomiting in all, and haemorrhagic syndrome in three; renal syndrome with severe acute renal failure in all five patients. All the patients recovered. Serological confirmation by an indirect immunofluorescence assay, enzyme immunoassay for IgM antibodies, and by plaque reduction neutralization test revealed that the infection was caused by Belgrade virus in three, and by Hantaan virus in two patients. It was not possible to differentiate these two serogroups on the basis of clinical features. This finding gave further evidence of circulation of different hantaviruses causing severe HFRS in Serbia.

A boy who developed haemolytic-uraemic syndrome (HUS) at 8 years 6 months of age had four further episodes of the disease during the next 3 years. No renal abnormalities were detected between the attacks nor in the 2.5 years after the last recurrence. Reduced levels of serum complement were found during four of the episodes and in two intervening periods.