Is there really an increase in non-minimal change nephrotic syndrome in children?

BACKGROUND: Reports on the worldwide increase in focal segmental glomerulosclerosis (FSGS) in childhood may have been hampered by referral bias. A true increase in FSGS possibly could alter the current practice of withholding renal biopsy in childhood nephrotic syndrome (NS) unless the patient fails to respond to a 28-day course of corticosteroid therapy. METHODS: With these questions in mind, we analyzed a 17-year database covering a 275,000-child population with mandatory referral. The incidence of NS per 100,000 childhood population per year was calculated, charts of 159 patients with NS seen between 1985 and 2002 were reviewed, and a receiver operating characteristic (ROC) plot analysis was performed to analyze the diagnostic performance of remission time. RESULTS: Results show that 115 of 159 patients had minimal change NS, diagnosed either on the basis of corticosteroid response (n = 89), verified by renal biopsy (n = 14), or with minimal change plus mesangial immunoglobulin M on histological examination (n = 12). The remaining 44 patients underwent a renal biopsy showing FSGS (n = 29; 18.2%), diffuse mesangial hypercellularity (n = 8; 5%), membranoproliferative glomerulonephritis (n = 1; 0.6%), membranous nephropathy (n = 3; 1.9%), or other diagnoses (n = 3). The incidence of FSGS increased significantly (P = 0.0253) from 0.37 to 0.94/100,000-child population/y in the two 8(1/2)-year intervals of our study. ROC plot analysis confirmed diagnostic sensitivity and specificity greater than 80% for remission time between 21 and 28 days of therapy. CONCLUSION: We confirm the increasing incidence of FSGS in children with idiopathic NS in a well-defined catchment area and, at the same time, find no reason to change the initial therapy and current indications to perform renal biopsy in childhood NS.

Quantitative tissue polymerase chain reaction for Epstein-Barr virus in pediatric solid organ recipients.

BACKGROUND: Infections caused by herpes virus, in particular, Epstein-Barr virus (EBV), remain a major challenge in solid organ transplantation. Little is known about the significance of tissue EBV load. METHODS: Twenty-three tissue biopsy specimens (19 kidney, 3 gastrointestinal, and 1 tonsil specimen) and 2 bronchoalveolar lavage specimens from 14 pediatric transplant recipients (10 kidney, 3 liver, 1 combined transplant) were subject to tissue EBV polymerase chain reaction (PCR) semiquantitative analysis and enzyme-linked immunosorbent assay (ELISA) methods. Results of biopsies were correlated with clinical data. RESULTS: Five of 14 patients had clinically diagnosed EBV disease: 2 patients presented with a septic picture with multiorgan failure and pneumonitis; 1 patient had mononucleosis; 1 patient had an increase in serum creatinine level, lymphadenopathy, and chronic fatigue; and 1 patient had EBV nephritis. These 5 patients underwent 12 biopsies at the time of clinically active infection; 8 biopsies had positive results (up to 111 copies/10 microL of extracted DNA). Conversely, 1 of the remaining 13 tissue biopsy specimens from asymptomatic patients had positive results on ELISA, but undetectable viral load, whereas 8 patients had a positive EBV immunoglobulin G titer with historic evidence of EBV replication in the blood. No patient without evidence of EBV had positive EBV tissue PCR results. CONCLUSION: Increased EBV load was found in more than 50% of patients, pointing to a previously underrecognized importance of EBV detection in tissues from transplant recipients. The presence of EBV in tissue correlated with the presence of viremia, whereas tissue PCR had 100% specificity. EBV load should be included in biopsy evaluation.

Incidentally detected nephrogenic rests in the setting of congenital obstructive uropathy.

PURPOSE: Nephrogenic rests (NR) are clusters of cells similar to renal blastema. NR are frequently seen in kidneys with Wilms' tumor (WT) and are seen with higher frequency in nephrectomy specimens from obstructed and/or multicystic dysplastic kidneys (MCDK) compared to autopsy series of normal kidneys. The significance of NR and their role in tumorigenesis is largely unknown. We report the findings of two cases with NR associated with ureteral ectopy/obstruction and review the relevant literature. MATERIALS AND METHODS: Two cases of upper pole heminephrectomy associated with ectopic upper pole ureter and resultant hydronephrosis were found to have nephrogenic rests present on pathologic examination. A literature search was done to review recent developments in the understanding of NR and their significance, primarily to guide patient recommendations regarding follow-up. RESULTS: Recent developments in the understanding of NR include the description of intralobar versus perilobar nephrogenic rests and prognostic considerations associated with each. However, the implications of finding nephrogenic rests in upper pole hemi-nephrectomy specimens associated with ureteral ectopy is not well delineated. CONCLUSIONS: The role of NR in tumorigenesis is still poorly understood. Because of the still undefined relationship with WT we recommend patients with incidentally detected NR be followed with serial abdominal ultrasounds for the first 5 years of life.

Osteofibrous dysplasia: a review of the literature and presentation of an additional 3 cases.

Osteofibrous dysplasia is a rare fibro-osseous lesion of uncertain etiology that occurs exclusively in the pediatric population. Diagnosis and treatment are complicated by the fact that osteofibrous dysplasia can resemble monostotic fibrous dysplasia and adamantinoma of long bones grossly and microscopically and that it tends to recur if surgical intervention is performed before skeletal maturity is reached. We present 3 cases of this lesion seen at our institution and provide a review of all previous cases reported in the literature.

Treatment and outcome of vertebral Langerhans cell histiocytosis at the Children's Hospital of Eastern Ontario.

BACKGROUND: We wished to evaluate the treatment methods for vertebral Langerhans cell histiocytosis (LCH) (a rare reticuloendothelial disorder) at a tertiary care pediatric centre and compare treatment and outcomes with those reported in the recent literature. METHODS: A total of 55 charts were retrieved between 1980 and 2003 for children with LCH. Only those children who were under 18 years of age, had a diagnosis of LCH, histiocytosis X or eosinophilic granuloma and had documented vertebral involvement were included. The data collected were compared with data in the literature with respect to epidemiologic features, symptoms, investigations and procedures done, treatment, outcome and follow-up. RESULTS: Of the 8 children who met the inclusion criteria for vertebral LCH, the most common presenting complaint was back or neck pain. The thoracic vertebrae were most commonly affected followed equally by cervical and lumbar spines. Most children underwent a complete diagnostic work-up. A single solitary lesion was found in only 1 child. Biopsies were attempted in all cases with 6 positive results. Treatment varied depending on the severity of the presenting complaint; however, none of the tumours was completely resected. Follow-up averaged 3.4 years, and only 1 child has had a recurrence. CONCLUSION: A multidisciplinary investigation is recommended for children with suspected vertebral LCH. Treatment depends on the severity of the disease.

Tissue viral DNA is associated with chronic allograft nephropathy.

Viral infections post-renal transplant (Tx) impact on outcome. Increased rejection rates and decreased renal function secondary to acute CMV, EBV and HHV-6 infections are well described. However, the clinical significance of a mere presence of these viruses on kidney tissue biopsy remains questionable. Thirty-six kidney biopsies obtained from 17 renal transplants (five females) and two combined liver-kidney recipients (one female) were retrospectively evaluated. Age at Tx ranged from 1.7 to 17.2 yr (median = 7.4). Biopsies were performed as protocol biopsies or when renal function deteriorated, between 6 weeks and 11 yr post-Tx (median = 1.2 yr). Immunosuppression included steroids and combination of tacrolimus/cyclosporin, mycophenolate mofetil/azathioprin and induction therapy. Fourteen patients received antiviral prophylaxis (ganciclovir/valganciclovir/acyclovir). Renal tissue was classified according to Banff '97 criteria. Tissue CMV, EBV, HHV-6 and HHV-7 was analyzed by PCR. We used an estimation of GFR from average plasma Cystatin C (CysC) and slopes of 1/CysC to assess renal function. The 16/36 biopsies were positive for one virus; 5/36 biopsies were positive for two viruses. In the infected group, Banff '97 scores for interstitial fibrosis (ci) and tubular degeneration/atrophy (ct) were significantly higher (p < 0.03 vs. the non-infected group for both). The slope of 1/CysC, or the proportion of patients on antiviral prophylaxis, did not differ significantly between both groups. In conclusion, a significant number of kidney biopsies showed PCR positivity for CMV, EBV, HHV-6 and HHV-7. This was associated with a significantly higher Banff score for ci and ct; while renal function was not affected. Further controlled studies are required.

Optimal biopsy techniques in the diagnosis of primary ciliary dyskinesia.

OBJECTIVE: Adequate biopsy specimens that clearly demonstrate cilia, and therefore enable the determination of the presence or absence of primary cilia dyskinesia, may be difficult to obtain. This study is an attempt to identify the optimal sampling technique to best examine respiratory tract cilia. DESIGN: A prospective comparison of the four sampling techniques was carried out: nasal brushing, nasal biopsy, bronchial brushing, and tracheal biopsy. SETTING: Tertiary care pediatric hospital: Children's Hospital of Eastern Ontario. METHODS: Ten consecutive patients booked for bronchoscopy and tracheal biopsy underwent all four procedures. Specimens were examined under light microscopy for an assessment of quality. RESULTS: The nasal brushing and tracheal biopsy specimens provide superior quality (p = .22); however, nasal brushing is more cost efficient. Nasal biopsy samples frequently are metaplastic and therefore are inferior to nasal brushing samples (p = .02). CONCLUSION: With equal efficiency demonstrated, the reduction in potential morbidity and health care costs suggests nasal brushings to be the optimal initial investigation for primary ciliary dyskinesia.

Combination of ceftriaxone and acyclovir - an underestimated nephrotoxic potential?

Management of meningo-encephalitis often involves the need for antibiotic and antiviral treatment. We report a retrospective analysis over a 6-month period of 17 patients (age range 1-14 years) who were treated with combination therapy of ceftriaxone and acyclovir. Mean acyclovir and ceftriaxone doses were 1,222+/-304 and 2,315+/-509 mg/m(2) per day, respectively. Three patients developed acute renal failure with a peak creatinine of up to 865% above baseline, occurring 2-3 days after starting combination therapy. Patients revealed a tubular proteinuria pattern. Renal biopsy of 1 patient showed a tubulotoxic picture but no evidence of crystals. In 12 of 17 patients (70%) there was a significant increase in serum creatinine. This was significantly greater than literature reports of 16% with acyclovir monotherapy. The degree of renal impairment in our patients correlated significantly with the acyclovir dose, while no correlation was found with the ceftriaxone dose. We conclude that the addition of a second nephrotoxic drug aggravated the extent of renal injury in our patients. The mechanism is tubulotoxicity. Caution should be exercised when using this potentially nephrotoxic cocktail, with clear criteria established for the initiation of combination therapy and close monitoring of serum creatinine.

Cilia ultrastructure in children with Down syndrome.

Chronic sinusitis, otitis media with effusion, and upper respiratory tract infections are commonly found in patients with Down syndrome. These diseases are generally felt to be secondary to depressed immune function and altered craniofacial dimensions. Recently, a cilia ultrastructure abnormality was found in a child with Down syndrome. This study is the first to be carried out to determine if cilia ultrastructure abnormalities are prevalent in the population with Down syndrome. Four of 10 patients had documented cilia abnormalities, but these were present in the background of normal cilia, suggesting that they were the result rather than the cause of chronic sinusitis. Similarly, nasal epithelium metaplasia was detected in 50% of the patients. Chronic sinusitis, otitis media with effusion, and recurrent upper respiratory tract infections in children with Down syndrome cannot generally be attributed to primary cilia ultrastructure abnormalities.