56 research outputs found
Segmental infantile hemangioma and concomitant hypertension in three African American neonates
We present three African American infants with segmental, ulcerated infantile hemangiomas and concomitant, persistent hypertension. When treated with beta-blocker therapy, the hemangiomas decreased in size and the ulcerations resolved, but there was no impact on the elevated blood pressure in one of our patients. We failed to identify any associations between infantile hemangioma and hypertension in the literature
Women and Alport syndrome
X-linked Alport syndrome (XLAS) is caused by mutations in type IV collagen causing sensorineural hearing loss, eye abnormalities, and progressive kidney dysfunction that results in near universal end-stage renal disease (ESRD) and the need for kidney transplantation in affected males. Until recent decades, the disease burden in heterozygous âcarrierâ females was largely minimized or ignored. Heterozygous females have widely variable disease outcomes, with some affected females exhibiting normal urinalysis and kidney function, while others develop ESRD and deafness. While the determinants of disease severity in females with XLAS are uncertain, skewing of X-chromosome inactivation has recently been found to play a role. This review will explore the natural history of heterozygous XLAS females, the determinants of disease severity, and the utility of using XLAS females as kidney donors
The importance of clinician, patient and researcher collaborations in Alport syndrome
This is a post-peer-review, pre-copyedit version of an article published in Pediatric Nephrology. The final authenticated version is available online at: https://doi.org/10.1007/s00467-019-04241-7Alport syndrome (AS) is caused by mutations in the genes COL4A3, COL4A4 or COL4A5 and
is characterised by progressive glomerular disease, sensorineural hearing loss and ocular
defects. Occurring in less than 1:5000, AS is rare genetic disorder but still accounts for >1%
of the prevalent population receiving renal replacement therapy. There is also increasing
awareness about the risk of chronic kidney disease in individuals with heterozygous mutations
in AS genes. The mainstay of current therapy is the use of angiotensin converting enzyme
inhibitors and angiotensin receptor blockers, yet potential new therapies are now entering
clinical trials. The 2017 International Workshop on Alport Syndrome in Glasgow was a preconference workshop ahead of the 50th anniversary meeting of the European Society for
Pediatric Nephrology. It focussed on updates in clinical practice, genetics, basic science and
also incorporated patient perspectives. More than 80 international experts including clinicians,
geneticists, researchers from academia and industry, and patient representatives took part in
panel discussions and breakout groups. This report summarises the workshop proceedings
and the relevant contemporary literature. It highlights the unique clinician, patient and
researcher collaborations achieved by regular engagement between the groups
Renal Survival in Children with Glomerulonephritis with Crescents: A Pediatric Nephrology Research Consortium Cohort Study
There is no evidence-based definition for diagnosing crescentic glomerulonephritis. The prognostic implications of crescentic lesions on kidney biopsy have not been quantified. Our objective was to determine risk factors for end-stage kidney disease (ESKD) in patients with glomerulonephritis and crescents on kidney biopsy. A query of the Pediatric Nephrology Research Consortiumâs Pediatric Glomerulonephritis with Crescents registry identified 305 patients from 15 centers. A retrospective cohort study was performed with ESKD as the primary outcome. Median age at biopsy was 11 years (range 1â21). The percentage of crescents was 3â100% (median 20%). Etiologies included IgA nephropathy (23%), lupus (21%), IgA vasculitis (19%) and ANCA-associated GN (13%), post-infectious GN (5%), and anti-glomerular basement membrane disease (3%). The prevalence of ESKD was 12% at one year and 16% at last follow-up (median = 3 years, range 1â11). Median time to ESKD was 100 days. Risk factors for ESKD included %crescents, presence of fibrous crescents, estimated GFR, and hypertension at biopsy. For each 1% increase in %crescents, there was a 3% decrease in log odds of 1-year renal survival (p = 0.003) and a 2% decrease in log odds of renal survival at last follow-up (p \u3c 0.001). These findings provide an evidence base for enrollment criteria for crescentic glomerulonephritis in future clinical trials
Advances and unmet needs in genetic, basic and clinical science in Alport syndrome::report from the 2015 International Workshop on Alport Syndrome
Alport syndrome (AS) is a genetic disease characterized by haematuric glomerulopathy variably associated with hearing loss and anterior lenticonus. It is caused by mutations in the COL4A3, COL4A4 or COL4A5 genes encoding the α3α4α5(IV) collagen heterotrimer. AS is rare, but it accounts for >1% of patients receiving renal replacement therapy. Angiotensin-converting enzyme inhibition slows, but does not stop, the progression to renal failure; therefore, there is an urgent requirement to expand and intensify research towards discovering new therapeutic targets and new therapies. The 2015 International Workshop on Alport Syndrome targeted unmet needs in basic science, genetics and diagnosis, clinical research and current clinical care. In three intensive days, more than 100 international experts including physicians, geneticists, researchers from academia and industry, and patient representatives from all over the world participated in panel discussions and breakout groups. This report summarizes the most important priority areas including (i) understanding the crucial role of podocyte protection and regeneration, (ii) targeting mutations by new molecular techniques for new animal models and potential gene therapy, (iii) creating optimal interaction between nephrologists and geneticists for early diagnosis, (iv) establishing standards for mutation screening and databases, (v) improving widespread accessibility to current standards of clinical care, (vi) improving collaboration with the pharmaceutical/biotech industry to investigate new therapies, (vii) research in hearing loss as a huge unmet need in Alport patients and (viii) the need to evaluate the risk and benefit of novel (including 'repurposing') therapies on an international basis
Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study
Introduction:
The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients.
Methods:
Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment.
Results:
A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001).
Conclusion:
This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies
Recommended from our members
Alport Syndrome
Alport syndrome (AS) is characterized by progressive kidney failure, hematuria, sensorineural hearing loss, and ocular abnormalities. Pathogenic variants in the COL4A3-5 genes result in a defective deposition of the collagen IV α3α4α5 protomers in the basement membranes of the glomerulus in the kidney, the cochlea in the ear and the cornea, lens capsule and retina in the eye. The presence of a large variety of COL4A3-5 gene(s) pathogenetic variants irrespective of the mode of inheritance (X-linked, autosomal recessive, autosomal dominant, or digenic) with and without syndromic features is better defined as the âAlport spectrum disorderâ, and represents the most common cause of genetic kidney disease and the second most common cause of genetic kidney failure. The clinical course and prognosis of individuals with AS is highly variable. It is influenced by gender, mode of inheritance, affected gene(s), type of genetic mutation, and genetic modifiers. This review article will discuss the epidemiology, classification, pathogenesis, diagnosis, clinical course with genotype-phenotype correlations, and current and upcoming treatment of patients with AS. It will also review current recommendations with respect to when to evaluate for hearing loss or ophthalmologic abnormalities
- âŠ