Horseshoe Kidney and Membranous Glomerulonephritis with Cold Activation of Complement.

Fujimoto, Shouichi; Hirayama, Naoteru; Uchida, Toshihiro; Iemura, Fumio; Yamamoto, Yoshitaka; Eto, Tanenao; Washimine, Hisanori; Sumiyoshi, Akinobu

doi:10.2169/internalmedicine.31.625

Cited by 12 publications

(13 citation statements)

References 9 publications

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“…It is frequently associated with anomalies of other systems in which genetic factors may play a common etiological role, including musculoskeletal, cardiovascular, and gastrointestinal systems, as well as in certain neurological conditions (23). The occurrence of glomerulonephritis in horseshoe kidney has already been reported (24)(25)(26)(27), with focal and segmental glomerulosclerosis described in two cases (25,27).…”

Section: Discussionmentioning

confidence: 99%

Frasier syndrome: four new cases with unusual presentations

Guaragna

Lutaif

Bittencourt

et al. 2012

Arq Bras Endocrinol Metab

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SUMMARYFrasier syndrome (FS) is characterized by gonadal dysgenesis and nephropathy. It is caused by specific mutations in the Wilms' tumor suppressor gene (WT1) located in 11p23. Patients with the 46,XY karyotype present normal female genitalia with streak gonads, and have higher risk of gonadal tumor, mainly, gonadoblastoma. Therefore, elective bilateral gonadectomy is indicated. Nephropathy in FS consists in nephrotic syndrome (NS) with proteinuria that begins early in childhood and progressively increases with age, mainly due to nonspecific focal and segmental glomerular sclerosis (FSGS). Patients are generally unresponsive to steroid and immunosuppressive therapies, and will develop end-stage renal failure (ESRF) during the second or third decade of life. We report here four cases of FS diagnosis after identification of WT1 mutations. Case 1 was part of a large cohort of patients diagnosed with steroid-resistant nephrotic syndrome, in whom the screening for mutations within WT1 8-9 hotspot fragment identified the IVS9+5G>A mutation. Beside FS, this patient showed unusual characteristics, such as urinary malformation (horseshoe kidney), and bilateral dysgerminoma. Cases 2 and 3, also bearing the IVS9+5G>A mutation, and case 4, with IVS9+1G>A mutation, were studied due to FSGS and/or delayed puberty; additionally, patients 2 and 4 developed bilateral gonadal tumors. Since the great majority of FS patients have normal female external genitalia, sex reversal is not suspected before they present delayed puberty and/or primary amenorrhea. Therefore, molecular screening of WT1 gene is very important to confirm the FS diagnosis. Arq Bras Endocrinol Metab. 2012;56(8):525-32 SUMÁRIO A síndrome de Frasier (SF), caracterizada por disgenesia gonadal e nefropatia, é causada por mutações específicas no gene supressor do tumor de Wilms (WT1) localizado em 11p23. Pacientes com cariótipo 46,XY apresentam genitália feminina normal com gônadas disgenéticas e alto risco de tumor gonadal, principalmente o gonadoblastoma. Por isso, a gonadectomia bilateral eletiva está indicada. A nefropatia na SF consiste de síndrome nefrótica com proteinúria que se inicia na infância e aumenta progressivamente com a idade, principalmente devido à glomeruloesclerose focal e segmentar (GESF). Esses pacientes não respondem ao tratamento com esteroides e imunossupressores e desenvolverão insuficiência renal crônica durante a segunda ou terceira década de vida. Neste trabalho, são relatados quatro casos de SF cujo diagnóstico foi definido após o rastreamento molecular do gene WT1. O caso 1 faz parte de um grande grupo de pacientes que tiveram diagnóstico de síndrome nefrótica corticorresistente e no qual o rastreamento de mutações no fragmento 8-9 do gene WT1 identificou a mutação IVS9+5G>A. Além da SF, essa paciente apresentou características incomuns, tais como malformação urinária (rins em ferradura) e disgerminoma bilateral. Os casos 2 e 3 também apresentaram a mutação IVS9+5G>A, e, no caso 4, foi identificada a mutação IVS9+1G>A, sendo que esse...

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Section: Discussionmentioning

confidence: 99%

Frasier syndrome: four new cases with unusual presentations

Guaragna

Lutaif

Bittencourt

et al. 2012

Arq Bras Endocrinol Metab

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“…Accordingly, temperature dependence seemed to explain the persistent, marked drops in haemolytic complement activity in our patients, while their clinical manifestations and laboratory parameters showed no evidence of active dysfunction. In addition, the fact that complement component C3 and C4 protein levels remained normal suggested that CDAC did not occur in vivo due to decreased synthesis and/or increased consumption, but did occur in vitro when sera were exposed to low temperatures [8][9][10][11][12][13][14]29,30]. CDAC was inhibited by EDTA because the latter acted as an anticoagulant agent as well as an inhibitor of the classical complement pathway by chelating such metal ions as Ca and Mg [7][8][9][10][11][12][13][14].…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C virus (HCV)-induced IgG-IgM rheumatoid factor (RF) complex may be the main causal factor for cold-dependent activation of complement in patients with rheumatic disease

Wei

Yano

Kuroiwa

et al. 1997

Clinical and Experimental Immunology

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SUMMARYA low serum complement level is commonly found in patients with rheumatic diseases. We evaluated 170 patients with such diseases to determine their serum levels of CH 50 , C3 and C4 protein. Persistent hypocomplementaemia was found in 19 of those patients, particularly in those with systemic lupus erythematosus (SLE). Cold-dependent activation of complement (CDAC) was demonstrated in nine of the 19 (47 . 4%), and six of the nine patients demonstrated infection with HCV (66 . 7%). The nine patients that exhibited CDAC had nearly normal haemolytic complement activity when the sera were separated either at 378C or in EDTA-treated plasma. Conversely, it markedly decreased, even to the point of being immeasurable, when the sera were separated at 4-218C. No significant deficiency in C3 and C4 protein levels was found in these patients. Clinical parameters other than levels of anti-HCV antibody, transaminase, and RF were not influenced by CDAC. In an attempt to isolate the causal factor for CDAC, we isolated IgG fractions from the CDAC patients by using a protein G column, in which case precipitates were collected from the eluates. The precipitates were mixed with normal serum and incubated at 4-218C for 18 h. A decrease in the level of CH 50 in normal serum was observed, which predominated (P < 0 . 001) when precipitates from HCV-infected patients were used. This indicated CDAC was possibly interrelated to the precipitates of such patients. This precipitate was proved to contain IgM besides IgG. It is therefore possible that an HCV-related IgG complex or an IgG-IgM RF complex may be formed at low temperature and be involved in activating the complement system in vitro.

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“…found five cases regarding horseshoe kidney in association with glomerulonephritis: membranoproliferative glomerulonephritis, [4] membranous glomerulonephritis, [5][6][7] and focal and segmental glomerulosclerosis. [8] The case with membranoproliferative glomerulonephritis was associated with cryoglobulinemic hepatitis C virus infection.…”

Section: Kayatas and Y üRünmentioning

confidence: 99%

“…One of the cases with membranous glomerulonephritis was associated with the cold activation of complement. [5] The remaining three cases were two patients with membranous glomerulonephritis, and one patient with FSGS was reported as idiopathic. [6][7][8] Vesicoureteral reflux, which can lead to focal segmental glomerulosclerosis, is a clinical condition commonly associated with horseshoe kidney.…”

Section: Kayatas and Y üRünmentioning

confidence: 99%