56 research outputs found
Inherited glomerulopathies of children: a Croatian experience
Bolesti iz spektra Alportovog sindroma (AS-a) nastaju kao posljedica mutacija gena za kolagen tip IV (COL43, COL4A4 i COL4A5). Spektar bolesti obuhvaÄa sve od tzv. benigne obiteljske hematurije na jednom kraju do klasiÄnog AS-a s ranom progresijom bolesti i izvanbubrežnim manifestacijama na drugom kraju spektra. IstraživaÄko iskustvo naÅ”e skupine poÄelo je 2003. godine, kada se prof. dr. sc. Danica GaleÅ”iÄ LjubanoviÄ vratila s edukacije iz nefropatologije od 18 mjeseci u Denveru, SAD i otvorila nefropatoloÅ”ki laboratorij u KB Dubrava. DugogodiÅ”nji rad rezultirao je projektom Hrvatske zaklade za znanost āāGenotip-fenotip korelacija u AS-u i nefropatiji tankih glomerularnih bazalnih membrana (TBMN)āā provedenom u periodu od 2015. do 2019. godine kojeg je profesorica bila voditelj. Glavni cilj istraživanja bio je utvrditi prevalenciju AS-a i TBMN-a u Hrvatskoj i razjasniti AS i TBMN histoloÅ”ki, genetski i kliniÄki s krajnjim ciljem stvaranja registra pacijenta s ovim bolestima. DijagnostiÄki proces poremeÄaja iz spektra AS-a je Äesto zahtijevan. Postoji velika varijabilnost u kliniÄkoj prezentaciji bolesti, ali i u histoloÅ”koj slici. NajtoÄniji test za otkrivanje uzroÄnih patogenih varijanti u genima kolagena tipa IV je opsežno paralelno genetsko testiranje Äitavih kodirajuÄih sekvenci sva tri gena COL4A5, COL4A3 i COL4A4. Biopsija
bubrega je od posebne koristi ako su kliniÄki i podaci o Älanovima obitelji negativni i ne postoji moguÄnost genetskog testiranja. Biopsija daje uvid u stupanj oÅ”teÄenja parenhima bubrega te je u nekim sluÄajevima neizbježna dijagnostiÄka metoda, osobito u pacijenata s neobiÄnim kliniÄkim tijekom bolesti (npr. neoÄekivano poveÄanje proteinurije). Tanke glomerularne bazalne membrane (GBM) su morfoloÅ”ki entitet utvrÄen mjerenjem na elektronskoj mikroskopiji (EM) te su za razumijevanje njihovog znaÄaja neophodni kliniÄki i genetski podaci.Alport spectrum disorders are result of mutations in the type IV collagen genes (COL43, COL4A4 and COL4A5). The spectrum of diseases includes the so-called benign familial hematuria at one end to classic Alport syndrome (AS) with early progression and extrarenal manifestations at the other end of the spectrum. The research experience of our group started in 2003 when professor Danica GaleÅ”iÄ LjubanoviÄ returned to Zagreb after 18 months education in renal pathology (Denver, USA) and started a renal pathology laboratory at Dubrava University Hospital. This long-term work resulted in a project of the Croatian Science Foundation āGenotypephenotype correlations in Alportās syndrome and thin glomerular basement membrane nephropathyā conducted in the period from 2015 to 2019 under the leadership of professor GaleÅ”iÄ LjubanoviÄ. The main goal of the study was to determine the prevalence of AS and thin glomerular basement membrane nephropathy (TBMN) in Croatia and to clarify AS and TBMN histologically, genetically and clinically with the ultimate goal of creating a registry of patients with AS and TBMN. The diagnostic process of AS spectrum disorders is often challenging. There is great variability in the clinical presentation of the disease, but also in the histological findings. The most accurate test for
detecting causative pathogenic variants in type IV collagen genes is extensive parallel genetic testing of the entire coding sequences of all three COL4A5, COL4A3, and COL4A4 genes. A kidney biopsy is especially helpful if there are negative clinical and pedigree data and there is no possibility of genetic testing. The biopsy provides insight into the degree of kidney parenchymal injury and is in some cases an unavoidable diagnostic method, especially in patients with type IV collagen mutations with an unusual clinical course of the disease (such as an unexpected increase in proteinuria). Thin glomerular basement membranes are a morphological entity determined by measurement on electron microscopy, and clinical and genetic data are necessary to understand their significance
Marcel Kornfeld ā Forgotten Pathologist and Respected Teacher
Autori su u radu prikazali život i rad Marcela Kornfelda (1886. ā 1937.), patologa i sveuÄiliÅ”nog nastavnika. U radu je kronoloÅ”ki prikazan Kornfeldov život, od njegovih poÄetaka u Donjoj Tuzli do njegove smrti u Zagrebu. Istaknuti su najvažniji detalji iz njegova života i bogate karijere koju je prekinula smrt u 51. godini života. Uz literaturu, pri nastanku rada veliku važnost su imali arhivski izvori pohranjeni na Medicinskom fakultetu SveuÄiliÅ”ta u Zagrebu i u Državnom arhivu u Zagrebu.The authors present the life and work of Marcel Kornfeld (1886 ā 1937), a pathologist and a university teacher. The paper chronologically describes Kornfeldās life, from his beginnings in Donja Tuzla to his death in Zagreb. The most important details from his life and rich career, which was interrupted by his death at the age of 51, are highlighted. The paper was written based on extensive literature and archival research
The Banff classification of renal allograft pathology
Do ranih 1990-ih nije postojala standardizirana meÄunarodna klasifikacija biopsija bubrežnih presadaka. To je rezultiralo znaÄajnom heterogenoÅ”Äu patohistoloÅ”kih nalaza izmeÄu razliÄitih centara. Skupina nefropatologa, nefrologa i transplantacijskih kirurga napravila je u Banffu (Alberta, Kanada) 1991. prvi klasifikacijski sustav histoloÅ”kih promjena u transplantiranom bubregu koji je pružio smjernice za patohistoloÅ”ku i kliniÄku dijagnozu te omoguÄio usporedbu izmeÄu istraživaÄkih i kliniÄkih studija za dijagnozu, lijeÄenje i ishod transplantiranih bubrega. Bio je to poÄetak danas opÄeprihvaÄene Banff klasifikacije. Navedeni eksperti nastavili su se sastajati svakih nekoliko godina te su Banff klasifikaciju prilagoÄavali i mijenjali u skladu s najnovijim spoznajama. Cilj rada je prikazati Banff klasifikaciju bubrežnih presadaka kroz njenu povijest od poÄetaka do posljednjeg izvjeÅ”taja. DijagnostiÄka procjena patologije bubrežnih presadaka uvelike je poboljÅ”ana, kvantificirana i kliniÄki dokazana, ali mnoga pitanja joÅ” treba prouÄiti. Trenutne preporuke se i dalje kliniÄki vrednuju, a izvjeÅ”taj o tome i nove teme bit Äe raspravljeni na jubilarnom sastanku o tridesetoj godiÅ”njici Banff susreta 2021. godine u gradu Banffu iz kojega je klasifikacija i potekla.Until the early 1990s, there was no standardized international classification of the renal allograft biopsies resulting in significant heterogeneity of biopsy findings between different centres. A group of nephropathologists, nephrologists and surgeons developed in Banff (Alberta, Canada) in 1991 the first classification system (the so-called Banff classification) which provided guidelines for the pathohistological and clinical diagnosis and enabled meaningful comparisons between research and clinical studies for diagnosis, treatment and outcome of the renal allograft pathology. The aim of this article is to present the Banff classification through its history from the beginnings to the recent reports. The diagnostic assessment of the kidney allograft pathology has been greatly improved, quantified, and clinically proven but many issues remain to be studied. Current recommendations are further clinically validated and the report and new topics will be discussed at the jubilee meeting in 2021 in Banff, the city from which the Banff classification originates
Tiopronin i/ili NSAR? Nefrotski sindrom i akutni intersticijski nefritis u mlade žene s cistinurijom - prikaz sluÄaja
Cystinuria is an autosomal recessive disease that leads to recurrent stone formation.
Tiopronin, a glycine derivative with a free thiol similar to penicillamine, prevents stone formation
and facilitates their dissolution. Nephrotic-range proteinuria is a serious and relatively uncommon
adverse effect, reported in 6-10% of patients, most frequently during the first year of tiopronin use.
Various patterns of morphologic kidney injury have been associated with tiopronin use, including
MCD, MN, and MPGN. Acute interstitial nephritis can be caused virtually by any drug. Non-steroidal
anti-inflammatory drugs (NSAID s) may cause AIN , with or without nephrotic syndrome due to
minimal change disease or membranous nephropathy.Cistinurija je autosomno recesivna bolest koja dovodi do recidivirajuÄeg stvaranja kamenaca. Tiopronin, derivat glicina sa
slobodnim tiolom, sliÄan penicilaminu, sprjeÄava stvaranje kamenaca i Äini ih topljivima. Proteinurija nefrotskog raspona
ozbiljan je i relativno rijedak neželjeni uÄinak, zabilježen u 6-10% bolesnika, najÄeÅ”Äe tijekom prve godine upotrebe tiopronina.
Razni obrasci morfoloÅ”ke ozljede bubrega povezani su s upotrebom tiopronina, ukljuÄujuÄi MCD, MN i MPGN.
Akutni intersticijski nefritis može biti uzrokovan gotovo bilo kojim lijekom. Nesteroidni protuupalni lijekovi (NSAR) mogu
uzrokovati AIN , s nefrotskim sindormom ili bez njega uzrokovanog boleÅ”Äu minimalnih promjena ili membranskom nefropatijom
DRUG INDUCED ALLERGIC INTERSTITIAL NEPHRITIS
Alergijski intersticijski nefritis (AIN) uzrokovan lijekovima rijedak je oblik bubrežne bolesti koji se kliniÄki primarno manifestira akutnom bubrežnom insuficijencijom. NajÄeÅ”Äa etiopatogeneza AIN-a reakcija je preosjetljivosti na lijekove meÄu kojima su najzastupljeniji antibiotici. Najvažnija dijagnostiÄka metoda u bolesnika sa sumnjom na AIN jest biopsija bubrega. Uz ukidanje uzroÄnog lijeka, u lijeÄenju AIN preporuÄuje se primjena glukokortikoida, u dozi od 1 mg/kg/dan s postepenim snižavanjem doze, u trajanju do 3 mjeseca. U ovom radu, prikazali smo 10 bolesnika kod kojih je nakon pregleda bubrežnog bioptata s nalazom AIN-a, retrospektivno uÄinjena analiza kliniÄkih i biokemijskih podataka. Definirane su Äetiri razliÄite uzroÄne skupine lijekova AIN-a, a najÄeÅ”Äi su bili antibiotici. U kliniÄkoj prezentaciji dominirala je akutna bubrežna insuficijencija s medijanom serumskog kreatinina od 497,5 Āµmol/L. Svi bolesnici osim jednoga lijeÄeni su preporuÄenim dozama glukokortikoida. Troje bolesnika lijeÄeno je i hemodijalizom. U svih bolesnika doÅ”lo je do oporavka bubrežne funkcije, uz medijan serumskog kreatinina nakon tromjeseÄnoga glukokortikoidnog lijeÄenja (u sedmero bolesnika) od 152 Āµmol/L (p=0,018).The allergic interstitial nephritis (AIN) is a rare renal disorder which is commonly clinically presented with an acute renal failure. AIN is the most frequent result of the hypersensitivity related to drugs (most often antibiotics). In the patients with clinical suspicion to a drug related AIN, kidney biopsy is the most important diagnostic procedure. Except of causative drug discontinuation, AIN therapy is based on high dose glucocorticoids 1 mg/kg/day with dose tapering during consecutive 3 months. In the present work, we have shown 10 patients with drug induced AIN. We identified 4 causative drug groups among which most frequent were antibiotics. In clinical presentation of our patients acute renal failure was dominant and median of baseline serum creatinine was 497.5 Āµmol/L. In all patients the kidney biopsy was performed and nine patients (90%) have been treated with recommended glucocorticoid regimen, additionally, in 3 patients hemodialysis was introduced. In all patients, reduction in serum creatinine value was achieved with serum creatinine median of 152 Āµmol/L after a three-month glucocorticoid treatment (p=0.018)
Goodpastureov sindrom ā prikazi bolesnika [Goodpasture's syndrome - case reports]
Goodpasture's syndrome is a rare clinical entity characterized by rapidly progressive glomerulonephritis, diffuse pulmonary hemorrhage and the presence of circulating autoantibodies to the glomerular basement membrane (GBM). Autoantibodies bind to reactive epitopes of noncollagenous domain of the collagen type IV alpha-3 chain in glomerular and alveolar basement membranes. Autoantibodies activate the complement cascade resulting in tissue injury by the type II hypersensitivity reaction according to the Coombs and Gell classification of antigen-antibody reactions. Prognostic factors include the renal excretory function and the degree of renal and lung damage at the time of presentation. Prompt diagnosis and early and adequate medical treatment is vital for patients. Clinical treatment must be aggressive in order of achieving better outcome. This article describes three patients who clinically presented with renopulmonary syndrome, renal failure, hematuria, proteinuria and hemoptysis. Kidney biopsy diagnosis was crescentic glomerulonephritis due to antibodies against GBM. In all three patients we started therapy with glucocorticoids and cyclophosphamide combined with plasma exchange therapy. In two patients who initially had severe impairment of renal function and high percentage of crescents in the renal biopsy, kidney function recovery was not achieved. In one patient, who at the time of clinical presentation showed milder renal failure and lower percentage of crescents in renal biopsy, the full recovery of renal function was obtained
GOODPASTUREāS SYNDROME ā CASE REPORTS
Goodpastureov sindrom rijedak je kliniÄki entitet karakteriziran brzoprogresivnim glomerulonefritisom (BPGN), difuznim pluÄnim hemoragijama i prisutnoÅ”Äu cirkulirajuÄih autoprotutijela na glomerularnu bazalnu membranu (GBM). Autoprotutijela se vežu na reaktivne epitope nekolagene domene a-3 lanca kolagena tipa IV, sastavnog dijela alveolarne i glomerularne bazalne membrane, te aktiviraju kaskadu komplementa, Å”to rezultira oÅ”teÄenjem tkiva po tipu II reakcije preosjetljivosti prema Coombsu i Gellu. PrognostiÄki faktori ukljuÄuju patohistoloÅ”ke promjene i promjene ekskrecijske funkcije bubrega te stupanj pluÄnog oÅ”teÄenja u trenutku oÄitovanja bolesti. Brzo postavljena dijagnoza i Å”to ranije provedeno adekvatno lijeÄenje osobito su važni za bolesnike. Agresivno lijeÄenje kombinacijom imunosupresivne terapije i plazmafereze ima najbolje izglede za uspjeh. U ovom radu prikazano je troje bolesnika koji su se kliniÄki oÄitovali renopulmonalnim sindromom: bubrežnim zatajenjem, hematurijom, proteinurijom i hemoptizama. HistoloÅ”ki u tkivu bubrega dobivenom biopsijom u svih bolesnika radilo se o glomerulonefritisu s polumjesecima uzrokovanom protutijelima na GBM. U sve troje bolesnika provedeno je lijeÄenje glukokortikoidima, ciklofosfamidom i plazmaferezom. Svi bolesnici preživjeli su uz remisiju pluÄne bolesti. U dva bolesnika koja su u trenutku kliniÄke prezentacije imala znatno sniženu ekskrecijsku bubrežnu funkciju i visok postotak polumjeseca u tkivu bubrega dobivenog biopsijom doÅ”lo je do trajnoga gubitka bubrežne funkcije. U jednog bolesnika koji je u trenutku oÄitovanja bolesti pokazivao lakÅ”e bubrežno oÅ”teÄenje te manji postotak polumjeseca doÅ”lo je do potpunog oporavka bubrežne funkcije.Goodpastureās syndrome is a rare clinical entity characterized by rapidly progressive glomerulonephritis, diffuse pulmonary hemorrhage and the presence of circulating autoantibodies to the glomerular basement membrane (GBM). Autoantibodies bind to reactive epitopes of noncollagenous domain of the collagen type IV a-3 chain in glomerular and alveolar basement membranes. Autoantibodies activate the complement cascade resulting in tissue injury by the type II hypersensitivity reaction according to the Coombs and Gell classification of antigen-antibody reactions. Prognostic factors include the renal excretory function and the degree of renal and lung damage at the time of presentation. Prompt diagnosis and early and adequate medical treatment is vital for patients. Clinical treatment must be aggressive in order of achieving better outcome. This article describes three patients who clinically presented with renopulmonary syndrome, renal failure, hematuria, proteinuria and hemoptysis. Kidney biopsy diagnosis was crescentic glomerulonephritis due to antibodies against GBM. In all three patients we started therapy with glucocorticoids and cyclophosphamide combined with plasma exchange therapy. In two patients who initially had severe impairment of renal function and high percentage of crescents in the renal biopsy, kidney function recovery was not achieved. In one patient, who at the time of clinical presentation showed milder renal failure and lower percentage of crescents in renal biopsy, the full recovery of renal function was obtaine
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