| Sažetak | Imunoglobulin A nefropatija (IgAN) najčešća je glomerularna bolest u svijetu. Jean Berger prvi je opisao ovaj glomerulonefritis 1968. godine te se njemu u čast danas i naziva Bergerova bolest. IgAN zahvaća ljude od najmlađe do najstarije dobi, no ipak se zamjećuje najveća učestalost u drugom i trećem desetljeću života, kao i predominacija muških pacijenata u odnosu na žene u omjeru 2:1. Dijagnoza se postavlja isključivo biopsijom, odnosno patohistološkom analizom i imunohistokemijskim dokazom IgA depozita. Bolest je karakterizirana nastankom i difuznim odlaganjem galaktoza-deficijentnih IgA1 molekula, odnosno imunokompleksa u mezangij s posljedičnom lokalnom upalom, proliferacijom mezangijskih stanica (mezangioproliferativni glomerulonefritis) i lokalnim stvaranjem upalnih citokina (TNF-., IL- 6, IL-1, TGF-ß) što dovodi do oštećenja bubrežne funkcije. Danas su u svrhu adekvatne procjene progresije novodijagnosticirane bolesti u uporabi brojni klinički i patohistološki (negativni) prediktori, od kojih je najvažnije spomenuti bodovanje po MEST-C kriterijima (mezangijska hipercelularnost, endokapilarna hipercelularnost, segmentalna glomeruloskleroza, tubularna atrofija/intersticijska fibroza i polumjeseci (eng. crescents)) prema Oxfordskoj klasifikaciji koje treba sadržavati svaki patohistološki nalaz IgAN. Klinička slika ovih bolesnika izrazito je varijabilna te je u 40-50% bolesnika prvi simptom pojava bezbolne recidivirajuće (makro)hematurije, često uz akutnu infekciju gornjeg respiratornog (ili rjeđe gastrointestinalnog) sustava (sinfaringitička hematurija). U drugih 30-40% slučajeva asimptomatska
hematurija (ili ponekad uz proteinuriju) posve je incidentalan nalaz koji se otkrije tijekom rutinske pretrage urina. Treći tip najrjeđe se uočava, u samo preostalih 10% pacijenata kod kojih se zamjećuje ubrzan razvoj teže kliničke slike praćen nefrotskim sindromom ili brzoprogresivnim nefritičkim sindromom, a može doći i do razvoja akutne bubrežne insuficijencije. Liječenje se uobičajeno započinje s ACEi ili ARB, a u težim slučajevima i kortikosteroidima i/ili drugim oblicima imunosupresivne terapije. Poslije prve epizode, većina bolesnika potpuno će se oporaviti, no kako je bolest kronična i često klinički tiha, do četvrtine bolesnika kroz dvadeset godina razvit će stanje terminalnog zatajenja bubrežne funkcije (stupanj V, odnosno ESRD - end stage renal disease) koje zahtijeva nadomjesnu terapiju hemodijalizom/peritonealnom dijalizom ili liječenje transplantacijom. Nažalost, recidiv IgAN poprilično je čest (ponajprije histološki verificiran, a zatim klinički uočljiv s pojavom kliničkih znakova tipičnih za IgAN), a zamjećuje se s medijanom pojave od 5 godina u jedne trećine svih transplantiranih bolesnika. |
| Sažetak (engleski) | Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is commonly referred to as a Berger’s disease, after a French pathologist Jean Berger who first described it in 1968. Even though people of all age groups are affected, typically, patients are younger and previously healthy, mostly in their second or third decade of life. Usually, there is a slight male predomination over females with a ratio 2:1. Diagnosis is exclusively based on kidney biopsy and pathohistological analysis with immunohistochemical IgA staining. IgAN is characterized by diffuse galactose-deficient (aberrantly glycosylated) IgA1 antibody- immunocomplex formation and deposition in glomerular mesangium with subsequent glomerular inflammation, mesangial cell proliferation and local production of proinflammatory and profibrotic
cytokines (TNF-., IL-6, IL-1, TGF-ß), which all lead to kidney injury. Nowadays, various clinical and pathohistological scoring systems are being developed to predict disease progression and the one most commonly used today is Oxford MEST-C score, based on histological characteristics (mesangial hypercellularity, endocapillary hypercellularity, segmental
glomerulosclerosis, tubular atrophy/interstitial fibrosis, crescents). Clinical presentation of these patients usually varies, but can be divided into three main types. The most common one, seen in up to 40-50% of patients, includes painless, asymptomatic (macro)hematuria with or without proteinuria, which occurs shortly after or during an acute upper respiratory (or gastrointestinal) infection and sometimes may recur. Accordingly, it is commonly referred to as a synpharyngitic hematuria. In another 30-40% of patients, asymptomatic microhematuria (with or without proteinuria) is incidentally discovered during a routine urine analysis. Third pattern is the rarest one and is seen in up to 10% of patients. Usually, these patients may experience rapid decline in kidney function, commonly with clinical signs suggestive of nephrotic syndrome or rapidly progressive nephritic syndrome and sometimes may progress to acute renal failure. Treatment is usually initiated with ACE inhibitors/AT1 blockers (ARB) in milder and asymptomatic cases, whereas patients with moderate to severe disease require immunosuppressive treatment as well. IgAN is a chronic disease that is clinically often completely silent, however up to one fourth of patients will progress to irreversible kidney failure (end stage renal disease, ESRD) in 20 years from diagnosis and will require hemodialysis/peritoneal dialysis as a kidney replacement therapy or a kidney
transplantation as a definitive therapy. Unfortunately, recurrence of IgAN is very common (first verified histologically, then clinically), occurring in approximately one-third of patients in a median period of 5 years. |
