Single-Center Experience of Pediatric Cystic Kidney Disease and Literature Review.

INTRODUCTION: Pediatric cystic kidney disease (CyKD) includes conditions characterized by renal cysts. Despite extensive research in this field, there are no reliable genetics or other biomarkers to estimate the phenotypic consequences. Therefore, CyKD in children heavily relies on clinical and diagnostic testing to predict the long-term outcomes. AIM: A retrospective study aimed to provide a concise overview of this condition and analyze real-life data from a single-center pediatric CyKD cohort followed during a 12-year period. METHODS AND MATERIALS: Medical records were reviewed for extensive clinical, laboratory, and radiological data, treatment approaches, and long-term outcomes. RESULTS: During the study period, 112 patients received a diagnosis of pediatric CyKD. Male patients were more involved than female (1:0.93). Fifty-six patients had a multicystic dysplastic kidney; twenty-one of them had an autosomal dominant disorder; fifteen had an isolated renal cyst; ten had been diagnosed with autosomal recessive polycystic kidney disease; three had the tuberous sclerosis complex; two patients each had Bardet-Biedl, Joubert syndrome, and nephronophthisis; and one had been diagnosed with the trisomy 13 condition. Genetic testing was performed in 17.9% of the patients, revealing disease-causing mutations in three-quarters (75.0%) of the tested patients. The most commonly presenting symptoms were abdominal distension (21.4%), abdominal pain (15.2%), and oligohydramnios (12.5%). Recurrent urinary tract infections (UTI) were documented in one-quarter of the patients, while 20.5% of them developed hypertension during the long-term follow-up. Antibiotic prophylaxis and antihypertensive treatment were the most employed therapeutic modalities. Seventeen patients progressed to chronic kidney disease (CKD), with thirteen of them eventually reaching end-stage renal disease (ESRD). The time from the initial detection of cysts on an ultrasound (US) to the onset of CKD across the entire cohort was 59.0 (7.0-31124.0) months, whereas the duration from the detection of cysts on an US to the onset of ESRD across the whole cohort was 127.0 (33.0-141.0) months. The median follow-up duration in the cohort was 3.0 (1.0-7.0) years. The patients who progressed to ESRD had clinical symptoms at the time of initial clinical presentation. CONCLUSION: This study is the first large cohort of patients reported from Croatia. The most common CyKD was the multicystic dysplastic kidney disease. The most common clinical presentation was abdominal distention, abdominal pain, and oliguria. The most common long-term complications were recurrent UTIs, hypertension, CKD, and ESRD.

Ultrasound distinction between simple recurrent urinary tract infections and a specific bladder wall inflammatory entity called cystitis cystica.

A specific representative of recurrent urinary tract infections (UTI) called cystitis cystica (CC) was assessed by ultrasound. The aim of the study was to delineate, by means of ultrasound measurement (US) of bladder wall thickness (BWT), the children with mere repeated UTI from those prone to frequent UTI due to CC. Two groups were compared, the control group of 30 with recurrent UTI without US CC BWT changes, and the group of 30 children with characteristic CC bladder wall thickening in whom cystoscopy was performed for verification the diagnosis of CC. BWT of > 3 mm (> 2.8 mm and > 3.3 mm) was found as cut-of value for distinction of CC versus simple recurrent UTI. US BWT measurement is useful in diagnosing CC and therefore valuable in decision about need of UTI prophylaxis.

Genotype-phenotype associations in WT1 glomerulopathy.

WT1 mutations cause a wide spectrum of renal and extrarenal manifestations. Here we evaluated disease prevalence, phenotype spectrum, and genotype-phenotype correlations of 61 patients with WT1-related steroid-resistant nephrotic syndrome relative to 700 WT1-negative patients, all with steroid-resistant nephrotic syndrome. WT1 patients more frequently presented with chronic kidney disease and hypertension at diagnosis and exhibited more rapid disease progression. Focal segmental glomerulosclerosis was equally prevalent in both cohorts, but diffuse mesangial sclerosis was largely specific for WT1 disease and was present in 34% of cases. Sex reversal and/or urogenital abnormalities (52%), Wilms tumor (38%), and gonadoblastoma (5%) were almost exclusive to WT1 disease. Missense substitutions affecting DNA-binding residues were associated with diffuse mesangial sclerosis (74%), early steroid-resistant nephrotic syndrome onset, and rapid progression to ESRD. Truncating mutations conferred the highest Wilms tumor risk (78%) but typically late-onset steroid-resistant nephrotic syndrome. Intronic (KTS) mutations were most likely to present as isolated steroid-resistant nephrotic syndrome (37%) with a median onset at an age of 4.5 years, focal segmental glomerulosclerosis on biopsy, and slow progression (median ESRD age 13.6 years). Thus, there is a wide range of expressivity, solid genotype-phenotype associations, and a high risk and significance of extrarenal complications in WT1-associated nephropathy. We suggest that all children with steroid-resistant nephrotic syndrome undergo WT1 gene screening.

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.

The significance of ultrasonography in diagnosing and follow-up of cystic cystitis in children.

Cystic cystitis is a separate form of urinary bladder inflammation, detected by cystoscopy in children with recurrent urinary infections. Cystoscopy is an invasive method, so the aim of this investigation was to determine the ultrasonographic characteristics of cystic cystitis and to assess the reliability of ultrasound in relation to cystoscopy in diagnosing cystic cystitis. The study included 115 girls with repeated urinary infections. Cystoscopy and ultrasonography was performed in all. According to the cystoscopic finding the subjects were divided into 4 groups. Lateral and posterior urinary bladder wall thickness was measured during ultrasonography. A statistically significant difference was found between all 4 groups, the method demonstrated a high degree of sensitivity (0.97) and specificity (0.91). Percentile calculations were determined for wall thickness. Ultrasonography can replace endoscopy in diagnosis and follow-up of cystic cystitis in children, with at least 50% fullness of the urinary bladder as a prerequisite.

[Renal biopsy in children with isolated microhematuria]. / Biopsija bubrega u djece s izoliranom mikrohematurijom.

UNLABELLED: Isolated microscopic hematuria (IMH) in children always raises the question whether, besides other examinations, there is a need of performing a renal biopsy. Many authors consider IMH to be a minor abnormality where pathologic glomerular changes are not likely to be found, however, general agreement has not yet been achieved. The aim of the study was to evaluate the contribution of renal biopsy to the diagnosis of the disease in IMH. PATIENTS AND METHODS: Renal biopsy was performed in 54 children with IMH (22 boys and 32 girls, mean age 8.2 and 8.5 years, respectively) in whom urologic abnormalities, hypercalciuria, systemic diseases, coagulopathy or overt family history of renal disease were excluded. The mean duration of IMH prior to biopsy was 2.8 years. Biopsy specimens were examined by light (LM), immunofluorescent (IF) and electron microscopy (EM). RESULTS: Glomerular abnormalities were found in 43 (79.6%) patients. On LM 18 patients had normal glomeruli (NG), 22 mesangial proliferative glomerulonephritis (MEPGN), 9 focal glomerulosclerosis (FGS), 3 focal glomerulonephritis (FGN) and 2 membranoproliferative glomerulonephritis (MPGN). IF revealed 2 cases of NG, 5 cases of MEPGN, and all 3 cases of FGN as IgA nephropathy. EM detected GBM changes consistent with Alport syndrome in 21 patients, 7 of them with NG, 9 with MEPGN and 5 with FGS on LM. Diffuse thinning of GBM was found in 10 children, 7 with NG and 3 with MEPGN on LM. In 5 cases subepithelial hump-like deposits, which were considered to be the sign of acute postinfectious glomerulonephritis in resolution, were found. One of 2 cases of MPGN showed to be type II (DDD). On follow-up, 6 of 21 children with changes consistent with Alport syndrome developed clinical signs of the syndrome. Further surveillance is needed to confirm the significance of EM findings in others. CONCLUSION: The authors concluded that in children with IMH renal biopsy is justified and should always be analyzed by light, immunofluorescent and electron microscopy.

[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.