Management of children with congenital nephrotic syndrome (CNS) is challenging. Bilateral nephrectomies followed by dialysis and transplantation are practiced in most centres, but conservative ...treatment may also be effective.
We conducted a 6-year review across members of the European Society for Paediatric Nephrology Dialysis Working Group to compare management strategies and their outcomes in children with CNS.
Eighty children (50% male) across 17 tertiary nephrology units in Europe were included (mutations in NPHS1, n = 55; NPHS2, n = 1; WT1, n = 9; others, n = 15). Excluding patients with mutations in WT1, antiproteinuric treatment was given in 42 (59%) with an increase in S-albumin in 70% by median 6 (interquartile range: 3-8) g/L (P < 0.001). Following unilateral nephrectomy, S-albumin increased by 4 (1-8) g/L (P = 0.03) with a reduction in albumin infusion dose by 5 (2-9) g/kg/week (P = 0.02). Median age at bilateral nephrectomies (n = 29) was 9 (7-16) months. Outcomes were compared between two groups of NPHS1 patients: those who underwent bilateral nephrectomies (n = 25) versus those on conservative management (n = 17). The number of septic or thrombotic episodes and growth were comparable between the groups. The response to antiproteinuric treatment, as well as renal and patient survival, was independent of NPHS1 mutation type. At final follow-up (median age 34 months) 20 (80%) children in the nephrectomy group were transplanted and 1 died. In the conservative group, 9 (53%) remained without dialysis, 4 (24%; P < 0.001) were transplanted and 2 died.
An individualized, stepwise approach with prolonged conservative management may be a reasonable alternative to early bilateral nephrectomies and dialysis in children with CNS and NPHS1 mutations. Further prospective studies are needed to define indications for unilateral nephrectomy.
Background
Children with congenital nephrotic syndrome (CNS) commonly develop end stage renal failure in infancy and require dialysis, but little is known about the complications and outcomes of ...dialysis in these children.
Methods
We conducted a retrospective case note review across members of the European Society for Pediatric Nephrology Dialysis Working Group to evaluate dialysis management, complications of dialysis, and outcomes in children with CNS.
Results
Eighty children (50% male) with CNS were identified form 17 centers over a 6-year period. Chronic dialysis was started in 44 (55%) children at a median age of 8 (interquartile range 4–14) months. Of these, 17 (39%) were on dialysis by the age of 6 months, 30 (68%) by 1 year, and 40 (91%) by 2 years. Peritoneal dialysis (PD) was the modality of choice in 93%, but 34% switched to hemodialysis (HD), largely due to catheter malfunction (
n
= 5) or peritonitis (
n
= 4). The peritonitis rate was 0.77 per patient-year. Weight and height SDS remained static after 6 months on dialysis. In the overall cohort, at final follow-up, 29 children were transplanted, 18 were still on dialysis (15 PD, 3 HD), 19 were in pre-dialysis chronic kidney disease (CKD), and there were 14 deaths (8 on dialysis). Median time on chronic dialysis until transplantation was 9 (6–18) months, and the median age at transplantation was 22 (14–28) months.
Conclusions
Infants with CNS on dialysis have a comparable mortality, peritonitis rate, growth, and time to transplantation as infants with other primary renal diseases reported in international registry data.
Typically associated with a staghorn calculus, the kidney shows loss of the normal cortex with multiple low attenuation areas that represent areas of renal tissue replaced with lipid-laden ...macrophages. 2 Percutaneous drainage and adjunctive antibiotic therapy prior to nephrectomy are recommended to avoid complications. 3 Nephrectomy is usually curative and confirms the diagnosis histologically.
Background
The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked multi-systemic disorder, almost always characterized by the triad of congenital cataract, cognitive and behavioral ...impairment and a proximal tubulopathy.
Methods
Twenty-eight novel patients with suspected Lowe syndrome were studied.
Results
All patients carried
OCRL
gene defects with mutational hot spots at CpG dinucleotides. Mutations previously unknown in Lowe syndrome were observed in ten of the 28 patients, and carriership was identified in 30.4 % of the mothers investigated. Mapping the exact breakpoints of a complete
OCRL
gene deletion revealed involvement of several flanking repeat elements. We noted a similar pattern of documented clinically relevant symptoms, and even though the patient cohort comprised relatively young patients, 32 % of these patients already showed advanced chronic kidney disease. Thrombocytopenia was seen in several patients, and hyperosmia and/or hyperacusis were reported recurrently. A p.Asp523Asn mutation in a Polish patient, associated with the typical cerebrorenal spectrum but with late cataract (10 year), was also evident in two milder affected Italian brothers with ocular involvement of similar progression.
Conclusions
We have identified clinical features in 28 patients with suspected Lowe syndrome that had not been recognized in Lowe syndrome prior to our study. We also provide further evidence that
OCRL
mutations cause a phenotypic continuum with selective and/or time-dependent organ involvement. At least some of these mutants might exhibit a genotype–phenotype correlation.
Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman ...syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies.
Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN).
A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs -0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate-standard deviation score < -2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting.
Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.
Lowe syndrome (LS) and Dent-2 disease (DD2) are disorders associated with mutations in the OCRL gene and characterized by progressive chronic kidney disease (CKD). Here, we aimed to investigate the ...long-term renal outcome and identify potential determinants of CKD and its progression in children with these tubulopathies.
Retrospective analyses were conducted of clinical and genetic data in a cohort of 106 boys (LS: 88 and DD2: 18). For genotype-phenotype analysis, we grouped mutations according to their type and localization. To investigate progression of CKD we used survival analysis by Kaplan-Meier method using stage 3 CKD as the end-point.
Median estimated glomerular filtration rate (eGFR) was lower in the LS group compared with DD2 (58.8 versus 87.4 mL/min/1.73 m2, P < 0.01). CKD stage II-V was found in 82% of patients, of these 58% and 28% had moderate-to-severe CKD in LS and DD2, respectively. Three patients (3%), all with LS, developed stage 5 of CKD. Survival analysis showed that LS was also associated with a faster CKD progression than DD2 (P < 0.01). On multivariate analysis, eGFR was dependent only on age (b = -0.46, P < 0.001). Localization, but not type of mutations, tended to correlate with eGFR. There was also no significant association between presence of nephrocalcinosis, hypercalciuria, proteinuria and number of adverse clinical events and CKD.
CKD is commonly found in children with OCRL mutations. CKD progression was strongly related to the underlying diagnosis but did not associate with clinical parameters, such as nephrocalcinosis or proteinuria.
Background
Primary central nervous system (PCNS) post-transplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation and is typically an Epstein–Barr virus ...(EBV)-induced B-cell CD20+ lymphoma. The modalities of treatment include reduction in immunosuppression, cranial radiotherapy (CRT), intravenous and intrathecal rituximab when CD20 is expressed on B-lymphocytes and PTLD cells, and chemotherapy.
Case-Diagnosis/Treatment
We report the successful treatment of EBV-driven PCNS PTLD by reduction in immunosuppression (RI), CRT, and intravenous rituximab. Our patient was an 11-year-old boy with a living-related renal transplant for end-stage renal failure (ESRF) secondary to posterior urethral valves (PUV) and bilateral renal dysplasia (BRD) and on triple immunosuppression with prednisolone, tacrolimus, and azathioprine who had a rising EBV load, which was managed with reduction in tacrolimus dose, withdrawal of azathioprine, and introduction of mycophenolate mofetil (MMF).
Conclusions
The patient presented 7 years post-transplant with a seizure and abnormal neurology secondary to polymorphous hyperplastic lesions in the brain, which responded to rituximab and CRT.
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