Secondary IgA Nephropathy & HSP
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1 Secondary IgA Nephropathy & HSP Anjali Gupta, MD 1/11/11
2 AKI sec to Hematuria? 65 cases of ARF after an episode of macroscopic hematuria have been reported in the literature in patients with GN. The main histologcal findings was ATN with the presence of red cell casts in the lumen of tubules and edema of the interstitial tissue,changes in the glomeruh were disproportionately mild for the severity of the ARF 57 were suffering from IgA nephropathy, 2 from focal GN, two from postinfectious GN and 1 from HSP Recovery in 2-3 months Renal Failure, 21(1), (1999)
3 Secondary IgA Causes
4 Studied light Mx and immunofloresence of 100 cirrhotic patients. Autopsy done within 24 hours. 90 were sec to alcoholic hepatitis 61 cases had Ig A deposit,58 only mesangial in 3 had subendothelial extension 18 had only Ig A, 43 along with some IgG and IgM. C3 in most cases. Light Mx- focal glomerular changes in 3 cases, rest mesangial widening 3 patients had significant proteinuria, in others clinical correlation not studied
5 Renal Biopsy in 11 patients with cirrhosis 5 had membranoproliferative GN with mainly Ig A deposition- All had nephrotic range proteniuria and hematuria. Renal insufficiency in 3. Others had lobular? GN, mesangial proliferation, glomerulosclerosis In another series of 23 patient, 3 were noted to have h/o microscopic proteinuria and hematuria (Kawaguchi et al) No clinical studies about the course /progression or treatment
6 Secondary IgA In 1950-mesangial expansion seen in cirrhotics was reffered as Cirrhotic gloemrulosclerosis. No specific histological difference between primary n secondary Ig A In 2 case series C3 deposit were absent on 20-40% of pt which is higher than primary Ig A Clinical Presentation- Incidental findings? Most case series are based on autopsy and retrospective review of renal findings Progression to ESRD is not commonly reported as c/w primary Having macroscopic hematuria is uncommon
7 IgA in Cirrhotics Glomerular changes has been reported in more than 50% of cirrhotics approaches 75% in ESLD. Some have suggested its coincidence of 2 common pathology. No consistent evidence that improvement in hepatic disease improves renal disease. One case report of remession following treatment of portal vein thromosis. World J Gastroenterol 2007 November 21; 13(43): Animal models -? No established treatment protocols
8 Pathogenesis (Hypothesis) Increased piga production- dimished mucosal integrity leading to exagerrated response of normal IgA system vs some evidence of intrinsic hyperactivity of IgA system Production of abnormal IgA- did nt come across data referring to glycosylation in heptatic Ig A Decreaed Ig A clearance Fractional catabolism of IgA is reduced. - Alteration in receptor/ receptor distribution. ASGPR is located in canaicular area as c/w sinusoidal area in healthy - Decreased FcR recptor expressions on monocytes Nephrol-dialysis-transp (1999) 14:
9 HSP
10 HSP Association between purpura and arthritis described by Schonlien Henoch recognized GI renal involvement it was known as anaphylactoid purpura 1990 ACR published diagnostic criterion 1)Palpable purpura 2) Age <20 3)Bowel pain 4)Wall granulocytes
11 Clinical Features Systemic vasculits characterized by Ig A dominant immune complex deposits affecting small vessels Mostly affects children <10 yrs, males and commonly caucasian Arthritis and GI symptoms often preceded rash by 2-8 week Frequency of renal involvement in adults is reported as 50-70% as c/w 30-40% in children. Nephritis becomes chronic and mainly results in morbidity
12 Frequency of Histologic Lesions I 8% II 29% III 43% IV 12% V 6% VI 3%
13 Diagnosis Clinical features Increased serum IgA in 20-60% of patients Normal complements in >90% of patients Biopsy with IgA immune complex deposition- edge of fresh purpuric lesions. Can be seen in other disease like IgA, liver disease.
14 Kidney International, Vol. 59 (2001), pp
15 Outcome in children
16 Treatment In Children Role of steroids is controversial. Mainly retrospective data. Aggressive therapy with corticosteroids or cyclophosphamide/azathioprine has not been proven to be beneficial in reversing the renal disease except among patients with crescentic nephritis. Steroid course of 6 months for patients with the nephrotic syndrome and those with a reduced GFR has been used Role of plasamphresis? Rituximab?
17 Corticosteroid treatment and odds of cumulative (transient or persistent ) incidence of renal disease A, Prospective; B, retrospective. The box sizes are proportional to the inverse of the magnitude of the variance. No overall OR is displayed,because of the heterogeneity of the studies.
18 Corticosteroid treatment and odds of persistent renal disease. A, Prospective; B, retrospective. An end point of 1 year was used for the Huber et al and Mollica et al studies and 6 months for the Ronkainen et al study. Early corticosteroid treatment significantly reduced the odds of developing persistent renal disease
19 Retrospective analysis of 250 adults with Biopsy proven HSP. Median follow up 14.8 years Renal involvement in adults varies from 45 to 85% The risk of progression to renal insufficiency, which ranges from 5% to 15% in children, seems to be approximately 30% in adults Palpable purpura was present in 96%, arthritis in 61%, GI in 48% and renal involvement in 32% J Am Soc Nephrol 13: , 2002
20 Renal Manifestations Renal maifestations developed within 2 months of first clinical symptom. The most frequent lesion in renal biopsies was proliferative endocapillary glomerulonephritis (class 3) (61%)
21 Outcomes 64 pt (26%) died. Commonest cause neoplasia(27%) followed by infection( 16%) Median survival 15yrs (11-21) 27 pt (11%) developed ESRD 25 were dialyzed, and 12 received renal transplant None of these lost their graft because of a relapse of HSP. 13% had severe renal failure, and 14% had moderate renal insufficiency. In all 38% had renal insufficency. At the end of the follow-up, only 20% of the patients were in clinical remission.
22 Prognostic factors Age, Class of biopsy or treatment were significant factors in univariate but not in multivariate analysis. High rate of ESRD as c/w other study but it was a longer follow up
23 Retrospective analysis of 37 patients with HUS, single centre UK study Cytotoxics were used in 32%, with no clear effect on outcome. Of the 10 ESRD patients, 60% had received prednisolone and cyclophosphamide. Q J Med 2006; 99:
24 Treatment of HSP in adults Multi-center, prospective, open-label trial intention to treat 54 adults with biopsy-proven HSP with severe visceral manifestations of one organ randomized to steroids alone or steroids plus cytotaxan Average follow up of 5 years. Kidney International (2010) 78,
25 Baseline Renal Characteristics Kidney International (2010) 78,
26 Kidney International (2010) 78,
27 Conclusions Small number of patient. Study does suggest addition of cyclophosphamide may have no clinical benefit. This pt group seemed to have relatively good GFR Ideally an arm with no steroids would have been helpful
28 Thank you
29 Pathogenesis: Characteristics of IgA in IgAN
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A clinical syndrome, composed mainly of:
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