Priya Gajjar

Mutations in the Human Laminin β2 (LAMB2) Gene and the Associated Phenotypic Spectrum

Mutations of LAMB2 typically cause autosomal recessive Pierson syndrome, a disorder characterized by congenital nephrotic syndrome, ocular and neurologic abnormalities, but may occasionally be associated with milder or oligosymptomatic disease variants. LAMB2 encodes the basement membrane protein laminin β2, which is incorporated in specific heterotrimeric laminin isoforms and has an expression pattern corresponding to the pattern of organ manifestations in Pierson syndrome. Herein we review all previously reported and several novel LAMB2 mutations in relation to the associated phenotype in patients from 39 unrelated families. The majority of disease‐causing LAMB2 mutations are truncating, consistent with the hypothesis that loss of laminin β2 function is the molecular basis of Pierson syndrome. Although truncating mutations are distributed across the entire gene, missense mutations are clearly clustered in the N‐terminal LN domain, which is important for intermolecular interactions. There is an association of missense mutations and small in frame deletions with a higher mean age at onset of renal disease and with absence of neurologic abnormalities, thus suggesting that at least some of these may represent hypomorphic alleles. Nevertheless, genotype alone does not appear to explain the full range of clinical variability, and therefore hitherto unidentified modifiers are likely to exist. Hum Mutat 31:992–1002, 2010.

Continuous flow peritoneal dialysis: first experience in children with acute renal failure

BACKGROUND AND OBJECTIVES Acute renal failure can be treated with different dialysis modalities, depending on patient characteristics and hospital resources. Peritoneal dialysis (PD) can be first choice in situations like hypotension, disturbed coagulation, or difficult venous access. The main disadvantage of PD is the relatively limited efficacy. The aim of this study was to investigate whether continuous flow peritoneal dialysis (CFPD) is a more effective treatment than conventional PD in acute renal failure. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A pilot study was performed at The Red Cross University Hospital in Cape Town in six patients. Patients were treated with both CFPD and conventional PD for 8 to 16 hours. CFPD was performed with two bedside-placed catheters. After initial filling, dialysate flow rate (100 ml/1.73 m2 per minute) was maintained with an adapted continuous venovenous hemofiltration machine. Ultrafiltration flow rate was set at 2.5 ml/1.73 m2 per minute. RESULTS Mean ultrafiltration was 0.20 ml/1.73 m2 per minute with conventional PD versus 1.8 ml/1.73 m2 per minute with CFPD. Mean clearances of urea and creatinine were 5.0 and 7.6 ml/1.73 m2 per minute with conventional PD versus 15.0 and 28.8 ml/1.73 m2 per minute with CFPD, respectively. No complications occurred. CONCLUSIONS In this first report of CFPD in six pediatric patients with acute renal failure, CFPD was on average three to five times more effective for urea and creatinine clearance and ultrafiltration than conventional PD, without any complications observed. CFPD has the ability to improve therapy for acute renal failure.

Microsporidiosis in pediatric renal transplant patients in Cape Town, South Africa: Two case reports

Microsporidia are an emerging group of pathogens associated with life‐threatening opportunistic infections in immunocompromised hosts, particularly human immunodeficiency virus (HIV)‐infected individuals. There have, however, been recent reports of infection in adult solid organ transplant recipients. We report two cases in children, to our knowledge the first in the paediatric literature. Two 13‐yr‐old, HIV‐seronegative females received deceased donor renal transplants from the same donor. Both patients suffered acute cell‐mediated rejection and CMV infection reactivation, managed with intensified immunosuppression and ganciclovir. Pyrexia of unknown origin and intermittent diarrhea in both prompted extensive investigations. In both patients, numerous spores of a microsporidial species were demonstrated in renal tissue on biopsy and in the urine, using modified trichrome and quick‐hot Gram‐chromotrope staining. Electron microscopy and PCR confirmed Encephalitozoon cuniculi infections. Both patients were successfully treated with 400 mg twice daily of albendazole, with sustained clinical improvement. We recommend that microsporidiosis be considered in the differential diagnosis of pyrexia of unknown origin in severely immunocompromised pediatric solid organ transplant recipients, particularly when associated with diarrhea.

Neonatal Urinary Ascites: A Report of Three Cases

Urinary ascites in neonates is not a common condition. Three cases of urinary ascites are presented and each of them has a different aetiology. Neonates with urinary ascites usually present as clinical emergency, requiring resuscitation, ventilator support, and subsequent drainage of urine. The ultimate management depends on the site of extravasation and the underlying cause.

Urological complications following unstented pediatric renal transplantation

Urological complications which develop post‐renal transplantation can be associated with significant morbidity especially in children. We evaluated the occurrence and management of all urological complications in a series of unstented pediatric renal transplants in a tertiary pediatric hospital. We reviewed the medical records of children who underwent unstented renal transplant between January 1996 and December 2014. Postoperative urological complications and the outcomes of their management were analyzed. A total of 160 unstented renal transplants were performed, and 32 urological complications were noted in 29 transplants (18%). There were 20 boys and nine girls with an age range of 2.5 years to 18.4 years. Nine (31%) of these patients had LUTD. The most common complication was VUR occurring in 17 patients (10.6%). Urine leaks occurred in six patients (3.8%) and ureteric obstruction in six patients (3.8%), and three patients (1.9%) had unexplained hydronephrosis. Loss of graft occurred in three patients (1.9%), and one patient died from sepsis post‐uretero‐ureterostomy. Patients with LUTD had more urological complications (P = .037). Unstenting is feasible in most pediatric renal transplants. LUTD is associated with a higher incidence of urological complications, especially VUR.