Biomedical subjects

Joshua A Schwimmer

Publications and source records attributed to Joshua A Schwimmer.

3 recordsLinked to original sources

PubMed2003

C1q nephropathy: a variant of focal segmental glomerulosclerosis.

BACKGROUND: C1q nephropathy is a poorly understood and controversial entity with distinctive immunopathologic features. In order to better define the clinical-pathologic spectrum, we report the largest single-center series. METHODS: Nineteen biopsies with C1q nephropathy were identified from among 8909 native kidney biopsies received from 1994 to 2002 (0.21%). Defining criteria included (1). dominant or co-dominant immunofluorescence staining for C1q, (2). mesangial electron dense deposits, and (3). no clinical or serologic evidence of systemic lupus erythematosus (SLE). RESULTS: The 19 patients were predominantly African American (73.7%), female (73.7%), young adults and children (range, 3 to 42 years; mean, 24.2 years). Presentation included nephrotic range proteinuria (78.9%), nephrotic syndrome (50%), renal insufficiency (27.8%), and hematuria (22.2%). No patient had hypocomplementemia or evidence of underlying autoimmune or infectious disease. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in 17 (including six collapsing and two cellular) and minimal-change disease (MCD) in two. All biopsies displayed co-deposits of immunoglobulin G (IgG), with more variable IgM (84.2%), IgA (31.6%), and C3 (52.6%). Foot process effacement varied from 20% to 100% (mean, 51%). Twelve of 16 patients with available follow-up received immunosuppressive therapy. One patient had complete remission of proteinuria and six had partial remission. Four patients with FSGS pattern had progressive renal insufficiency, including two who reached end-stage renal disease (ESRD). Median time from biopsy to ESRD was 81 months. On multivariate analysis, the best correlate of renal insufficiency at biopsy and at follow-up was the degree of tubular atrophy and interstitial fibrosis (P = 0.0495 and 0.0341, respectively). CONCLUSION: C1q nephropathy falls within the clinical-pathologic spectrum of MCD/FSGS. Although further studies are needed to determine the pathomechanism of C1q deposition, we hypothesize that it may be a non-specific marker of increased mesangial trafficking in the setting of glomerular proteinuria.

Adolescent↗

PubMed2003

Collapsing glomerulopathy.

Collapsing glomerulopathy is a morphologic variant of focal segmental glomerulosclerosis (FSGS) characterized by segmental and global collapse of the glomerular capillaries, marked hypertrophy and hyperplasia of podocytes, and severe tubulointerstitial disease. The cause of this disorder is unknown, but nearly identical pathologic findings are present in idiopathic collapsing glomerulopathy and human immunodeficiency virus (HIV)-associated nephropathy, and collapsing glomerulopathy has been associated with parvovirus B19 infection and treatment with pamidronate. The pathogenesis of collapsing glomerulopathy involves visceral epithelial cell injury leading to cell cycle dysregulation and a proliferative phenotype. Clinically, collapsing glomerulopathy is characterized by black racial predominance, a high incidence of nephrotic syndrome, and rapidly progressive renal failure. Collapsing glomerulopathy also may recur after renal transplantation or present de novo, often leading to loss of the allograft. The optimal treatment for collapsing glomerulopathy is unknown. Treatments may include steroids or cyclosporine in addition to aggressive blood pressure control, angiotensin converting enzyme inhibitors and/or angiotensin II receptor blockers, and lipid lowering agents. The role of other immunosuppressive agents such as mycophenolate mofetil in the treatment of collapsing FSGS remains to be defined. Prospective clinical trials are needed to define optimal therapy of this aggressive form of FSGS.

Capillaries↗

PubMed2002

NPHS2 mutations in late-onset focal segmental glomerulosclerosis: R229Q is a common disease-associated allele.

Mutations in NPHS2, encoding podocin, have been identified in childhood onset focal and segmental glomerulosclerosis (FSGS). The role of NPHS2 in adult disease is less well defined. We studied 30 families with FSGS and apparent autosomal recessive inheritance and 91 individuals with primary FSGS. We screened family members for NPHS2 mutations. NPHS2 mutations appeared to be responsible for disease in nine of these families. In six families, the affected individuals were compound heterozygotes for a nonconservative R229Q amino acid substitution. This R229Q variant has an allele frequency of 3.6% in a control population. In these families, R229Q was the only mutation identified on one of the two disease-associated NPHS2 alleles. We used in vitro-translated podocin and purified nephrin to investigate the effect of R229Q on their interaction and found decreased nephrin binding to the R229Q podocin. These data suggest that this common polymorphism contributes to the development of FSGS. Chromosomes bearing the R229Q mutation share a common haplotype defining an approximately 0.2-Mb region. R229Q appears to enhance susceptibility to FSGS in association with a second mutant NPHS2 allele. Identification of R229Q mutations may be of clinical importance, as NPHS2-associated disease appears to define a subgroup of FSGS patients unresponsive to corticosteroids.

Adolescent↗