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Intern Seminar : IgA Nephropathy

Intern Seminar : IgA Nephropathy. Teacher : 邱元佑醫師 Presentation : 陳沛吟. Brief history ：. 17-year-old, Boy 民國 85/4 (10 y/o) ： proteinuria was found incidentally in school health examination  Persistent proteinuria  86/11 ： renal biopsy ： IgA nephropathy

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Intern Seminar : IgA Nephropathy

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  1. Intern Seminar :IgA Nephropathy Teacher : 邱元佑醫師 Presentation : 陳沛吟

  2. Brief history： • 17-year-old, Boy • 民國85/4 (10 y/o)：proteinuria was found incidentally in school health examination Persistent proteinuria 86/11：renal biopsy：IgA nephropathy • Lab：IgG:576↓, IgA:142, IgE:<28.3 C3:111, C4:27.8 BUN:13, Crea:0.6, albumin:3.9 DPL:1911 mg/day

  3. Brief history Heavy proteinuria + echo： parenchymal dz. Persistent proteinuria BUN/Cr: 134/15.4 2ndBiopsy： FSGS & TIN Biopsy： IgAN Proteinuria H/D CAPD OPD F/U 85/4 (10 y/o) 86/11 92/1 92/9 (17 y/o) 92/10 1. Captopril→Losartan 2. 89/4 ~ 92/1 Predinisolone + Solumedrol Proteinuria：150~500 mg/dL

  4. BUN / Creatinine： 136 18.8 16 BP：100/70 118/84 138/94 142/98 1.2

  5. Discussion: IgA Nephropathy

  6. Definition: Only by biopsy：IgA immunocomplex deposits in the glomerular mesangium

  7. Mesangial electron dense deposits with ↑mesangial matrix & cellularity in IgAN

  8. Incidence： • Japan, France, Australia：18~40% of all primary glomerular diseases United States, Canada：only 2~10% • male > female • Occur at all ages • predominate：older children and young adults, 20+~30+ y/o：↑

  9. Causes: • IgAN：Primary (idiopathic) or secondary • Cause of primary IgAN：unknown

  10. Genetic factors： • Familial clustering：familial predisposition is a very common finding (9.6% of IgAN pt’s siblings have GN) • ACE gene polymorphism (DD genotype)：correlated to the pathological severity and course of IgAN. • HLA genes：class Ⅱ products – DP, DQ, and DR：susceptibility to IgAN.

  11. Genetic factors： • Platelet-activating factor (PAF) acetylhydrolase gene mutation：degree of proteinuria and the extent of mesangial cell proliferation. • IgA immune system：IgA1 synthesis • Complement factors：homozygous null C4 phenotype↑, C3FF homozygous phenotype↑ (Pediatric Nephrology 2001, 16:446-457)

  12. Causes of Secondary IgAN • Infection：HIV, leprosy • Neoplasia：ca. of the lung, pancreas • Liver diseases：Hepatitis B, cirrhosis, • Skin diseases： Psoriasis • Lung diseases：sarcoidosis • Systemic immunological disorders：SLE, RA, AS, Reiter’s syndrome……

  13. Five Clinical syndromes 1. Gross hematuria (U.S.) 2. Asymptomatic microscopic hematuria with/without proteinuria----62% (Japan, Asia) 3. Acute nephritis with hypertension and/or renal insufficiency 4. Nephrotic syndrome 5. A mixed nephritic-nephrotic syndrome

  14. IgAN In Children： • > 80% children have experience of gross hematuria (in U.S.) • Recurrent gross hematuria is traditionally regarded as the hallmark of childhood IgAN. • Gross hematuria as initial feature: ¼ (asymptomatic child found in school screening) • Gross hematuria is fewer in adults

  15. IgAN In Children： • Gross hematuria often in association with URI. • Proteinuria：often, but severity < nephrotic • Hypertension：mild to moderate • Serum IgA level：8~16%↑in children (30~50%↑ in adults) ※ no diagnostic value

  16. Differential Diagnosis： • Henoch-Schönlein purpura (HSP) • HSP：clinical syndrome • Same：histopathological alterations • Difference：HSP has systemic symptoms：purpuric rash, arthralgias, abdominal pain, acute onset, self-limited. • Variants of the same pathophysiologic process

  17. Outcome： • Used to be thought：benign • Highly variable range of prognosis ： ~ spontaneous remission ~ impaired renal function ~ ESRD • 20~30%,15~20 years ESRD

  18. Pool prognostic Factors： • Clinical presentation： 1. Persistent hypertension 2. ↑Serum cr., ↓renal function when onset 3. Prolonged or heavy proteinuria (>1g/day) • Pathological expression： 1. Diffuse mesangial proliferation 2. Extensive glomerular crescents 3. Glomerulosclerosis and tubulointerstitial change

  19. Treatment

  20. Treatment: • Goal: prevent progression of disease and protect renal function • ACE Inhibitors • Corticosteroids • Immunosuppressants • Fish-oil supplement • Tonsillectomy

  21. Corticosteroid： • Corticosteroid：antiinflammatory & immunosuppressive • Floege et al：for proteinuria <1.5g/day and normal GFR：can↓proteinuria • High risk or renal function worsen： steroid + cyclophosphamide/cytotoxic • No effect on renal function was observed • On-going：corticoteroid + azathioprine

  22. AngiotensinⅡ AⅡ Receptor O2- Renin-Angiotensin System Angiotensinogen Renin Inactive peptides AngiotensinⅠ ACE Angiotensin II Bradykinin ATI Receptor Endothelium

  23. ACEI & AngiotensinⅡReceptor Blocker： • Angiotensin is a central factor in the progression of glomerular sclerosis. • hypothesis：↓BP has protective renal effects in cases of mild insufficiency with hypertension in IgAN. • ACEI for preserve renal function：? But,↓BP,↓proteinuria：proven

  24. ACE inhibitor： • Probability of renal survival (<50% increase of baseline serum creatinine) in enalapril-treated group and control group.(Roland et al) P < 0.05

  25. Fish Oil Supplements： • n-3 polyunsaturated fatty acids (DHA, EPA) • Depress eicosanoid and cytokine production  may ↓renal inflammation and glomerulosclerosis  may prevent renal injury • Review： ＊ 2 studies：benefits on renal function ＊ 2 studies：no difference

  26. Fish Oil Supplements： • Danadio et al：in persistent proteinuria (>1g/day) & SCr <3 mg/dL ： ↓82% risk in SCr↑ and ↓67% risk of death or ESRD. • High-dose: 3.76g EPA+2.94g DHA (8#) v.s. Low-dose: 1.88g EPA+1.47g DHA (4#)： no difference

  27. Fish Oil Supplements：

  28. Tonsillectomy： • IgA：mucosa defense • Popular in Japan and France. • Indication：chronic infections (dental abscess, sinusitis) • In pediatric：tonsillectomy：↓ gross hematuria episodes. • No evidence for affect the progression to CRI or ESRD. • Recommended：controversial

  29. Renal Transplantation： • When ESRD: It is best to transplantation • In U.S.：IgAN -- 10% of primary GN with renal transplantation • Survival：excellent • Recurrence：20~60% in 5 years • Equal rates over cadaveric, living, or related donor.

  30. Conclusion： • In low risk (proteinuria < 1.5g/day) 1. Steroid for ↓proteinuria (grade B) 2. ACEI (grade C) • In higher risk： immunosuppressive therapy (grade A)  proteinuria 1~3.5g/day steroid x 6 months  progressive renal failure： steroid + cytotoxic treatment

  31. About This Case： • No gross hematuria • Serum IgA level：normal • Poor predictors：persistent heavy proteinuria, hypertension • Onset~ESRD：only 7 years Poor drug compliance? Unknown herbs? Hypertension?

  32. Summary： • Primary IgAN：the most common primary GN • Diagnosis：biopsy：IgA deposition • Prognosis：variable, 20~30%ESRD • Treatment：Immunosuppressive therapy (steroid/ cyclophophamide/ AZT) ACEI Fish-oil Tonsillectomy Renal transplantation

  33. References: • JV Donadio, IgA Nephropathy. N Engl J Med 2003;347(10):738-48. • Yoshikawa N. Tanaka R. Iijima K. Pathophysiology and treatment of IgA nephropathy in children. Pediatr Nephrol 2001;16(5):446-57. • Wyatt RJ. Hogg RJ. Evidence-based assessment of treatment options for children with IgA nephropathies. Pediatr Nephrol 2001;16(2):156-67. • D'Amico G. Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors. Am J Kidney Dis 2000;36(2):227-37.

  34. References: • Donadio JV Jr. Use of fish oil to treat patients with immunoglobulin A nephropathy. Am J Clin Nutr 2000;71(1 Suppl):373S-5S. • Julian BA. Treatment of IgA nephropathy. Semin Nephrol 2000;20(3):277-85. • Jurgen Floege. Evidence-based recommendations for immunosuppression in IgA nephropathy: handle with caution. Nephrol Dial Transplantation2003;18:241-5. • Testbook of Pediatrics, Nelson 17th Edition

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