IgA nephropathy 2014년 8월 6일 R1 황규환

IgA nephropathy m/c cause of primary GN in Developed countries Peak incidence in Second & Third decades of life Greatest frequency in Asians & Caucasians Rare in Blacks IgA deposits may also be seen in healthy individuals from 3 to 16 percent (renal allograft donors in Japan, non-selected autopsy in Ger many)

Light microscope focal (involving less than 50 percent of glomeruli) or more often diffuse mesangial proliferation and matrix expansion

Immunofluorescence microscope large, globular mesangial IgA deposits that are diagnostic of IgA nephropathy or Henoch-Schönlein purpura

Electron microscope electron-dense deposits that are limited to the mesangial regions (D). The glomerular basement membrane (GBM) is normal, and there are no glomerular capillary wall deposits.

Clinical features IgAN typically present in one ot three ways 40~50% Gross hematuria, following an URI or athletic exertion 30~40% Microscopic hematuria and mild proteinuria Incidentally detected <10% Nephrotic syd. or RPGN Edema, HTN, Renal insufficiency Rarely, Crescentic IgA nephropathy AKI, Increase of dysmorphic RBC

Treatment Non-immunosuppressive Tx. Immunosuppressive Tx. ACEi or ARB : BP control and slow progression of renal dz Statin : Lower cardiovascular risk Fish oil, Tonsillectomy (are Less clear) Immunosuppressive Tx. Glucocorticoid alone Glucocorticoid + Cyclophosphamide followed by azathioprine Glucocorticoid + azathioprine Mycophenolate mofetil(MMF) Calcineurin Inhibitor(Cyclosporine, Tacrolimus)

Treatment Isolated hematuria, no or minimal proteinuria, normal GFR Typically not treated Should be monitored at 6~12 months intervals Persistent proteinuria, normal or nearly normal GFR Non-immunosuppressive Tx. Nephrotic range proteinuria, 6개월이상 치료에도 지속되 는 단백뇨, serum Cr. ↑, severe histologic findings on Bx. Immunosuppresive Tx. in addition to Non-immunosuppressive Tx. Chronically elevated Cr., prominent Glomerulosclerosis, Tubulointerstitial atrophy or fibrosis Not treating with Immunosuppresive Tx.

Non-immunosuppresive tx. ACEi or ARB Lowering both systemic BP and intraglomerular pr. Minimizing proteinuria and slowing rate of progression of renal dz. Greater efficacy compared with other anti-HTN drug Combination of ACEi & ARB (?) Statins Lower cardiovascular risk But No Evidence on slowing the progression of renal dz. Fish oil Maybe act by anti-inflammation Randomized trials : report conflicting results

Immunosuppresive tx. Glucocorticoid alone Significantly reduce incidence of Renal events When ACEi or ARB has failed to lower proteinuria Glucocorticoid + Cyclophosphamide followed by azathioprine with more severe Dz (rapidly progressive clinical course or Crescent formation) PDL(40mg/day, tappered to 10mg/days) 2 years Cyclophosphamide 3 months -> Azathioprine 2yrs Glucocorticoid + azathioprine Severe disease in children Mycophenolate mofetil(MMF) Unclear role, Fetal risk↑ Calcineurin Inhibitor(Cyclosporine, Tacrolimus) No benefit, Relapse

Prognosis Clinical predictors At the time of Dx., a marker for more severe Dz. Elevated serum Cr. HTN (140/90mmHg) Persistent(eg, for more than six months) protein excretion above 1000mg/day Histologic predictors(Oxford classification of IgAN) Mesangial hypercellularity Segmental glomerulosclerosis Endocapillary hypercellularity Tubular atrophy/interstitial fibrosis Serologic predictor High serum levels of “Poorly galactosylatedd IgA1” : Bad prognosis

Recurrence after KT Risk factor Clinical manifestation Use of living-related donor kidney Specific HLA alleles in recipient, including HLA-B35, HLA- DR4, HLA-B8, DR3 Good HLA match between donor and recipient High serum IgA concentration Clinical manifestation persistent microscopic hematuria New or worsening proteinuria Increase in serum creatinine

Recurrence after KT Treatment ACEi or ARB IgAN & HTN : use ACEi or ARB even in absence of evidence of recurr Immunosuppressive Tx. : biopsy-proven recurrence rapidly rising serum Cr nephrotic range proteinuria : high-dose glucocorticoids (PDL 1mg/kg per day) for 2 mo nths : Cyclophosphamide

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