Angiotensin-converting enzyme genotype is not a significant genetic risk factor for idiopathic nephrotic syndrome in Croatian children.

AIM: The association of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with idiopathic nephrotic syndrome (INS) is controversial. Only scarce information on European populations is available. The aim of the study was to investigate the distribution of the ACE gene I/D polymorphism and its impact on INS in children from Croatia. MATERIALS AND METHODS: Ninety-five children with INS were investigated: 30 with minimal change disease (MCD), 35 with mesangial proliferative glomerulonephritis (MesPGN) and 30 with focal segmental glomerulosclerosis (FSGS). The control group consisted of 73 healthy adults. ACE gene was analyzed using the PCR method. The results were correlated with clinical features, renal morphology and response to immunosuppresive therapy. RESULTS: There was no correlation of ACE genotype with gender, age of the disease onset, level of proteinuria, presence of hematuria or hypertension, and GFR at onset of the disease. No statistically significant differences in ACE genotype or allele frequencies between the controls and whole group of patients, MCD group, MesPGN group, FSGS group, steroid sensitive (SS) patients, steroid resistant (SR) patients, as well as each other, were found, although DD genotype tended to be more frequent in FSGS patients, SR patients, and frequent relapsers. Among 11 children treated with cyclophosphamide the D allele was significantly higher among non-responders (p = 0.003). CONCLUSION: DD genotype is not a genetic risk factor for acquiring INS nor significant phenotype modifier regarding to clinical and pathohistological picture and response to steroids in Croatian children. The potential application of ACE genotyping in predicting cyclophosphamide response deserves further investigation.

Demographic characteristics and metabolic risk factors in Croatian children with urolithiasis.

The aim of this study was to assess demographic data, clinical presentation, metabolic features, and treatment in 76 children with urolithiasis presented from 2002 to 2011. Urolithiasis is responsible for 2.5/1,000 pediatric hospitalizations, with new cases diagnosed in 1.1/1,000 admissions. From the observed period, two-fold rise of incidence rate was observed. Compiling the data from other pediatric institutions in our country, we estimated present overall incidence rate in Croatia as 6.5/100,000 children under 18 years. There were 41 boys and 35 girls (ratio 1.17:1). The mean age at diagnosis was 9.7 (range 0.8-16) years and follow-up duration was 5.3 (range 1.8-10) years. Renal colic (75.0 %) and hematuria (57.89 %) were the main symptoms. In 65.78 % of children, stones were unilateral. Stones were located in kidney in 52.63 %, in the ureter in 26.32 %, and in bladder in 6.58 % cases. Stone analysis showed calcium oxalate in 75.0 % of the cases. Associated urinary tract abnormalities were found in 19.73 % children. Most common metabolic disturbances were hypercalciuria (47.37 %) and idiopathic or mild hyperoxaluria (18.42 %). Urine saturation (EQUIL2) was elevated in 61.84 % cases. Spontaneous stone evacuation occurred in 51.21 % children. Extracorporeal shock wave lithotripsy, surgical evacuation, and endoscopic removal of calculi were performed in 21.0, 6.58, and 5.26 % of cases, respectively. Follow-up conservative therapy, consisting of fluid/diet recommendations and additional potassium citrate and/or chlorothiazide in children with increased risk, was sufficient for stone recurrence prevention in 92.1 % of children. In conclusion, the study gave insight in epidemiology and metabolic disturbances of urinary stone disease in Croatian children.

Vesicoureteral reflux and urodynamic dysfunction.

INTRODUCTION: The concept of vesicoureteral reflux (VUR) as a consequence of congenital anomaly of vesicoureteral junction has undergone changes owing to the finding that such children may have lower urinary tract dysfunction, which produces high intravesical pressure and consequently a predisposition for VUR. PATIENTS AND METHODS: The urodynamics was investigated by pressure-flow-EMG study in 132 children with VUR and 162 refluxing units. RESULTS: Only 33 (25.0%) patients had normal urodynamic finding. The most frequent pathological finding was overactive bladder (OAB), found in 59 (44.7%) children, followed by dysfunctional voiding (DV) in 25 (18.9%) children. Children with VUR grades I and II had a higher percentage of pathological urodynamic findings than children with VUR grades III and IV. OAB was more frequent in children under 5 years of age with unilateral and lower grade VUR. It was found equally in children with and without uroinfections. DV was more frequent in children older than 5 years, with bilateral VUR, higher grade VUR and uroinfections. CONCLUSIONS: Children with VUR have a high incidence of urodynamic disorders. The results of the study indicate the possible role of urodynamic dysfunction in the pathogenesis of VUR, especially mild one.

Positive feedback loop for cystitis cystica: the effect of recurrent urinary tract infection on the number of bladder wall mucosa nodules.

The main purpose of this study was to demonstrate positive feedback loop between bladder wall nodules (nodules being one of the key diagnostic factors), bladder wall thickness, and recurrent urinary tract infections. Cystitis cystica was diagnosed in 115 prepubertal girls (mean age 7.79 +/- 3.05 years) by optic examination of bladder mucosal nodules and by ultrasonographic measurement of bladder wall thickness. Bladder wall thickness increased with the frequency of recurrent urinary tract infections as well as with the number of nodules on bladder wall mucosa (3.52 +/- 0.522 mm < or = 5 nodules vs. 4.42 +/- 0.429 mm 6-10 nodules vs. 5.20 +/- 0.610 mm > 10 nodules, respectively). Study results suggested that early control of urinary tract infections by chemoprophylaxis could prevent higher grades of bladder wall mucosal changes and consequently shorten the length of chemoprophylaxis.

Idiopathic nephrotic syndrome in children: review of 282 Croatian cases.

Recent data suggests increased incidence of focal segmental glomerulosclerosis (FSGS) among children with idiopathic nephrotic syndrome (INS). To determine the causes and possible longitudinal changes in the etiology of INS, 282 Croatian children diagnosed with INS between 1990 and 2009 were evaluated. In total, 122 children were assessed as having minimal change nephrotic syndrome (MCNS) based on their initial presentation, laboratory findings and clinical course. Kidney biopsy was performed in the remaining 160 children. MCNS was present in 18.1% of all biopsies performed. Total incidence of MCNS (assessed + biopsy proven) was only 53.5%. In contrast, FSGS was found in 40.6% of all biopsies and accounted for 23.1% of all cases. Mesangial proliferative glomerulonephritis (MesPGN) was the third most common diagnosis, present in 26.9% of the biopsies, and accounted for 15.2% of all cases. There were no significant longitudinal differences in the incidence of different causes of INS. The overall response to steroids at presentation was 71.6%. A higher proportion of initial steroid responders among children with FSGS (43.1%) and MesPGN (67.4%) than previously reported was noted. A longitudinal tendency of increasing steroid resistance in FSGS and MesPGN groups was observed.

[Clinical and histopathological characteristics of biopsy-proven renal diseases in Croatia]. / Klinicke i patohistoloske karakteristike biopsijom dokazanih bubreznih bolesti djece u Hrvatskoj.

There is little data on the spectrum of renal diseases in children in Croatia. The Croatian Society for Pediatric Nephrology has established the Registry of Biopsy-Proven Renal Diseases in an attempt to address this issue nationwide. Here we report preliminary results of a retrospective analysis of clinical and histopathological data of 565 children aged < or =17 years presenting to 9 hospitals in Croatia from 1991 to 2004, in whom kidney biopsy was performed. The most common indication for renal biopsy was nephrotic syndrome (39.1%), followed by asymptomatic proteinuria/hematuria (22.0%) and acute nephritic syndrome (17.0%). All biopsies were analysed by light-, immunofluorescent and electron microscopy. The majority of children, 552 out of 565 (92.4%), had glomerulonephritis (GN). Tubulointerstitial nephritis was found in 16 (2.8%), congenital renal parenchyma anomalies in 14 (2.5%) and vascular disease in 11 (1.9%) cases. One (0.2%) child had sarcoidosis with nephrocalcinosis. The sample was non-diagnostic in 1 (0.2%) case. Among children with GN, primary GN accounted for 70.9%, secondary GN for 16.1% and hereditary GN for 13.0% cases. The most frequent primary GN forms were focal segmental glomerulosclerosis (FSGS) (24.6%), mesangial proliferative glomerulonephritis (MEPGN) (19.2%) and IgA nephropathy (18.1%). Acute GN in resolution was found in 11.1% and minimal changes GN in 6.8% of cases. Most children with secondary GN had nephritis of Henoch-Schönlein purpura (HSP) (54.7%) and nephritis of systemic lupus erythematosus (SLE) (40.5%), while among hereditary GN Alport syndrome was most common (80.9%). In the group of children with primary GN who presented with nephrotic syndrome, most common forms were FSGS (38.5%) and MEPGN (24.0%). Minimal changes GN accounted for only 10.9% of cases. IgA nephropathy, primary or related to HSP (20.0%), FSGS (16.1%), MEPGN (12.6%) and Alport syndrome (9.7%) were the most common biopsy-proven renal diseases in Croatian children. The analysis provided data on the frequency of histological renal lesions in children in Croatia. The higher frequency of FSGS and MEPGN among Croatian children in comparison with other countries deserves further evaluation.

Analysis of calcium, oxalate, and citrate interaction in idiopathic calcium urolithiasis in children.

The majority of urinary stones in children are composed of calcium oxalate. To investigate the interaction between urinary calcium, oxalate, and citrate as major risk factors for calcium stones formation, their 24-h urinary excretion was determined in 30 children with urolithiasis and 15 normal healthy children. The cutoff points between children with urolithiasis and healthy children, accuracy, sensitivity, and specificity for each risk factor alone as well as for all three taken together were determined. OneR and J4.8 classifiers as parts of the larger data mining software Weka, based on machine learning algorithms, were used for the determination of the cutoff points for differentiation of the children. The decision tree based on J4.8 classifier analysis of all three risk factors together proved to be the best for differentiating stone formers from normal children. In comparison to the accuracy of the differentiation after calcium and oxalate of 80% and 75.6%, respectively, the decision tree showed an accuracy of 97.8%. Even when its stability was tested by the leave-one-out cross-validation procedure, the accuracy remained at a very acceptable percentage of 93.2% correctly classified patients. J4.8 classifier analysis gave a look inside urinary calcium, oxalate, and citrate interaction. Urinary calcium excretion was shown as the most informative in discrimination of the children with urolithiasis from healthy children. However, it was shown that oxalate and citrate excretions might influence the stone formation in a subpopulation of the stone formers. In patients with low urinary calcium, a major role in lithogenesis belongs to oxalate, in some of them alone and in others in conjunction with citrate. Decreased urinary citrate excretion in the presence of increased oxalate excretion may lead to stone formation.

[Cystic cystitis in children]. / Cisticni cistitis u djece.

Cystic cystitis is a common urinary bladder disease with a histologic picture of nodular lesions of the bladder mucosa. Intralesional lymphoid proliferation due to recurrent urinary tract infection play a major role in the occurrence of cystic cystitis. It is often found together with vesicoureteral reflux and other urinary tract anomalies and urodynamic disturbances. Examination of 116 children with cystic cystitis revealed it to be associated with urinary tract anomalies, especially vesicoureteral reflux. The average age at diagnosis is 7 years. The disease often needs longterm prophylaxis for urinary tract infections, and has favorable prognosis.