Andrew Wade

Outcomes of kidney transplantation in children with nephronophthisis: An analysis of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Registry

Abstract:  NPHP is an autosomal recessive chronic tubulointerstitial nephropathy that progresses to ESRD. In the 2006 NAPRTCS report, NPHP was the primary diagnosis in 2.8% of all renal transplant patients. At our pediatric center, that covers a population in which the NPHP1 gene is prevalent, 24% of transplant recipients had a primary diagnosis of NPHP. Since no previous literature reports have documented kidney transplant outcomes in patients with NPHP, a review of the 2006 NAPRTCS database was performed. The results of this review illustrate that patients with NPHP as their underlying kidney disease have a significantly better overall graft survival when compared with all other patients registered in the NAPRTCS database. Sub‐analysis demonstrated that this benefit is statistically significant only for LD kidney transplant recipients. CrCl was better in NPHP at all time points from transplant up to five‐yr follow‐up. Moreover, in NPHP LD transplant recipients the decline of CrCl over five yr was slower compared with non‐NPHP LD transplant recipients. Rates of thrombosis, acute, and chronic rejection as well as causes of graft failure were similar in NPHP patients and all other patients. This review demonstrates that NPHP transplant recipients have excellent outcomes that are shown to be better compared with the general pediatric transplant population.

Meckel syndrome in the Hutterite population is actually a Joubert-related cerebello-oculo-renal syndrome.

Meckel syndrome (MKS) is a rare lethal autosomal recessive disorder characterized by the presence of occipital encephalocele, cystic kidneys, fibrotic changes of the liver and polydactyly. Joubert syndrome (JS)‐related disorders (JSRDs) or cerebello‐oculo‐renal syndromes (CORS) are a group of recessively inherited conditions characterized by a molar tooth sign (MTS) on cranial MRI, a set of core clinical features (developmental delay/mental retardation, hypotonia, ataxia, episodic breathing abnormalities, abnormal eye movements) and variable involvement of other systems including renal, ocular, central nervous system, craniofacial, hepatic, and skeletal. A significant clinical overlap between MKS and JSRD/CORS has been recognized in the literature. We describe a group of 10 Hutterite patients, of which 7 had been previously diagnosed with MKS, with a JSRD. Clinical features include variable early mortality, cognitive handicap, a characteristic dysmorphic facial appearance, hypotonia, ataxia, abnormal breathing pattern, nystagmus, and MTS on MRI. Additional features include occipital encephalocele, posterior fossa fluid collections resembling Dandy–Walker malformation, hydrocephalus, coloboma, and renal disease. This JSRD is a recognizable dysmorphic syndrome characterized by hypertelorism, deep‐set eyes, down‐slanting palpebral fissures, ptosis, arched eyebrows with medial sparseness, square nasal tip, short philtrum with tented upper lip, open mouth with down‐turned corners, and posteriorly rotated low‐set ears. Renal disease is present in 70% of patients and is characterized by cystic kidneys, abnormalities in renal function and hypertension. Homozygous deletions of NPHP1 and the known loci for JS/JSRD and MKS were excluded by identity‐by‐descent mapping studies suggesting that this condition in the Hutterites represents yet another locus for a JSRD.

Invasive Streptococcus pneumoniae Infection Causing Hemolytic Uremic Syndrome in Children: Two Recent Cases

INTRODUCTION Streptococcus pneumoniae is an uncommon cause of hemolytic uremic syndrome (HUS) with a unique pathophysiology that differs from Shiga toxin-related HUS. METHODS Case descriptions for each patient are provided. Each strain of S pneumoniae was subjected to a pulsed-field gel electrophoresis (PFGE) analysis, Shiga toxin assay and polymerase chain reaction to detect Shiga toxin genes. A review of the current literature was conducted. CASE PRESENTATIONS Two patients with S pneumoniae-related HUS that presented to the Alberta Childrens Hospital, Calgary, Alberta, within four weeks of each other in 2001 are described. Both presented with pneumonia and empyema with associated HUS. Both patients required dialysis, one patient for 10 days and the other for 18 days. Neither patient demonstrated evidence of Shiga toxin-related disease. S pneumoniae isolated from blood or pleural fluid was penicillin susceptible. One isolate was serotype 3 and the other was serotype 14. The two strains had different PFGE patterns. Both patients recovered well with no persistent renal dysfunction. CONCLUSIONS S pneumoniaecontinues to be an uncommon but important cause of HUS. Most cases can be confirmed or at least considered probable without performing a renal biopsy.

Acute Renal Replacement Therapy in Children with Diarrhea-Associated Hemolytic Uremic Syndrome: A Single Center 16 Years of Experience

Acute kidney injury (AKI) is becoming more prevalent among hospitalized children, its etiologies are shifting, and new treatment modalities are evolving; however, diarrhea-associated hemolytic uremic syndrome (D+HUS) remains the most common primary disease causing AKI in young children. Little has been published about acute renal replacement therapy (ARRT) and its challenges in this population. We describe our single centers experience managing 134 pediatric patients with D+HUS out of whom 58 (43%) required ARRT over the past 16 years. In our cohort, all but one patient were started on peritoneal dialysis (PD). Most patients, 47 (81%), received acute PD on a pediatric inpatient ward. The most common recorded complications in our cohort were peritoneal fluid leaks 13 (22%), peritonitis 11 (20%), and catheter malfunction 5 (9%). Nine patients (16%) needed surgical revision of their PD catheters. There were no bleeding events related to PD despite a mean platelets count of 40.9 (±23.5) × 103/mm3 and rare use of platelets infusions. Despite its methodological limitations, this paper adds to the limited body of evidence supporting the use of acute PD as the primary ARRT modality in children with D+HUS.