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 b2, 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 b2 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.

Background Systemic Lupus Erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE (pSLE) on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa (SA). Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serologic characteristics was extracted from medical records. Results were compared to a well-described North American pSLE cohort. Results Seventy-two SA patients were enrolled in the study; mean age 11.5 years, 82% female. The racial distribution was 68% Coloured, 24% Black, 5% White, and 3% Asian/Indian. Most patients presented with severe lupus nephritis (LN) documented by renal biopsy (61%). Of patients with LN, 63% presented with International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate, and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K [SLEDAI-2K] 20.6). The SLEDAI-2K at enrollment in the PULSE cohort (5.0) did not differ from the North American pSLE cohort (4.8). Sixty three % of PULSE cohort had end organ damage with System Lupus International Collaborating Clinic-Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, 9 (13%) developed ESRD with 6 (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrollment in the SA registry. SA patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study reveals a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population.

SummaryBackground 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 m 2 per minute) was maintained with an adapted continuous venovenous hemofiltration machine. Ultrafiltration flow rate was set at 2.5 ml/1.73 m 2 per minute. Results ConclusionsIn 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 .

Peritonitis is a frequent complication of peritoneal dialysis (PD) in children as well in adults. Data on PD and peritonitis in pediatric patients are very scarce in developing countries. A retrospective cohort study was performed between 2000 and 2008 with the aim to evaluate PD treatment and peritonitis epidemiology in pediatric patients in South Africa and identify risk factors for peritonitis. Baseline characteristics and potential risk factors of peritonitis were recorded, including housing, socio-economic circumstances, distance to PD center, type of PD, mode of catheter placement, race, presence of gastrostomy tube, weight, and height. Outcome indices for peritonitis were peritonitis rate, time to first peritonitis, and number of peritonitis-free patients. The patient cohort comprised 67 patients who were on PD for a total of 544 months. The total number of peritonitis episodes was 129. Median peritonitis rate was one episode every 4.3 patient months (2.8 episodes/patient-year, range 0–21.2). Median time to first infection was 2.03 months (range 0.1–21.5 months), and 28.4% of patients remained free from peritonitis. Patients with good housing and good socio-economic circumstances had a significantly lower peritonitis rate and a longer time to first peritonitis episode. Peritonitis rate was high in this cohort, compared to numbers reported for the developed world; the characteristics of causative organisms are comparable. The most important risk factors for the development of peritonitis were poor housing and poor socio-economic circumstances. More intensive counseling may be beneficial, but improvement of general socio-economic circumstances will have the greatest influence on PD success.

The aim of this study was to determine the proportion of children who develop urinary tract infection (UTI) after kidney transplantation (KTx) and to identify the factors associated with UTI and its impact on graft function. To this end, we undertook a chart review of children who underwent KTx at Red Cross Children's Hospital between January 2003 and December 2009 and were followed-up for at least 6 months after transplantation. Sixty-two children (53.2% males) were followed-up for a mean (standard deviation) period of 36.9 (19.7) months. Mean age at transplantation was 10.0 (4.6) years. Twenty-five (40.3%) children had 89 UTI episodes during the study period, equivalent to 0.94 UTI episodes per one patient-year of follow-up. Acute pyelonephritis occurred in 17 (27.4%) children; another 17 (27.4%) had multiple post-KTx UTI. Klebsiella (40.0%) and Escherichia (28.0%) were the commonest organisms. Those with post-KTx UTI were, at transplantation, younger (8.3 vs. 11.2 years; p = 0.017), had lower urinary tract abnormality (LUTA) (13 vs. 1; p = 0.000) and had pre-KTx UTI (13 vs. 5; p = 0.001). Multivariate analysis revealed that only age <5 years at transplantation and LUTA remained significant and that UTI KTx was not associated with worsening graft function. UTI is common after post-KTx. Among our patient cohort, younger age and LUTA were risk factors, but UTI did not affect graft function.

Continuous flow peritoneal dialysis improves UF in fluid overloaded infants who are not achieving adequate UF on conventional PD.

Revascularization was beneficial to the management of blood pressure control in about half of our RVH patients.

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