Search

IgAN se definira kao autoimuna bolest koju karakterizira taloženje imunokompleksa koji sadrže Gd-IgA1 protutijela u mezangiju glomerula s incidencijom 2.5/100000 u godini. Osnovne patomorfološke promjene IgAN, koje se dio Oxford klasifikacije iz 2016. godine, su: mezangijalna, endokapilarna i ekstrakapilarna proliferacija, segmentalna glomeruloskleroza i tubularna atrofija/intersticijska fibroza. U studiju su uključeni pacijenti čija je vrijednost eGFR-a u trenutku biopsije iznosila >15 ml/min/1.73 m2. Isključeni su pacijenti sa sekundarnim oblikom IgAN. Period opservacije iznosio je 3 godine ili manje ukoliko je došlo do razvoja ESRD-a, dijalize ili smrti. Prethodna tri kriterija ujedno su činila završnu točku studije. Ovom studijom utvrđeno je da skupina s razvojem ESRD-a ima manju vrijednost eGFR-a u trenutku biopsije u odnosu na onu bez razvoja istog (p=0.003). Za skupinu s T1+2 kriterijem dokazana je veća učestalost razvoja ESRD-a u odnosu na skupinu s T0 kriterijem (p=0.025). ROC krivuljom, za vrijednosti eGFR-a u trenutku biopsije, dobiven je AUC u iznosu od 0.844 (95% CI 0.657-0.952) (p0.05). Pacijenti imaju veću vjerojatnost razvoja ESRD-a ako je vrijednost eGFR-a u trenutku biopsije 15 ml/min/1.73 m2. Patients with secondary IgAN were excluded. The observation period was 3 years or less if ESRD development, dialysis or death occurred. The previous three criteria also formed the end point of the study. This study found that the group with the development of ESRD had a lower value of eGFR at the time of biopsy compared to those without the development of the same (p=0.003). For the group with T1+2 criteria, a higher frequency of ESRD development was proven compared to the group with T0 criteria (p=0.025). ROC curve analysis, for eGFR values at the time of biopsy, resultated with an AUC of 0.844 (95% CI 0.657-0.952) (p0.05). Patients are more likely to develop ESRD if the eGFR value, at the time of biopsy, is

Perkutana biopsija bubrega izvodi se u KBC-u Split kontinuirano od 1994. Stroge indikacije za invazivni zahvat obuhvaćaju poznate bubrežne sindrome. Bubrežno tkivo se nakon postavljanja dijagnoze može naknadno analizirati radi novih biljega, važnih u patogenezi bubrežnih bolesti. Bubreg je mjesto aktivacije vitamina D koji ima pleiotropni povoljni učinak na organizam. Zbog bubrežne bolesti kompleksni mehanizam regulacije vitamina D može biti poremećen. Istražili smo izražaj receptora za vitamin D (VDR) te enzima aktivacje (1α-OHaza) i razgradnje (CYP24A1) vitamina D u bioptatima bubrega bolesnika s IgA nefropatijom (IgAN) i usporedili s kontrolnim tkivima. Za epidemiološku analizu prikupljeni su klinički i patološki padaci o 54 bolesnika bioptirana na Klinici za dječje bolesti od 2008. do 2017. Za eksperimentalnu analizu prikupljeni su arhivirani parafinski blokovi bubrežnog tkiva 12 bolesnika s IgAN-om (šestero djece i šestero odraslih). Izrezani su preparati debljine 5 µm, standardno priređeni za indirektno imunohistokemijsko bojenje protutijelima na VDR, 1α-OHazu i CYP24A1, analizirani na imunofluoroscencijskom mikroskopu, fotografirani i kvantificirani uporabom ImageJ računalnog programa. U statističkoj analizi je značajnim smatran P < 0,05. U epidemiološkoj analizi, od 54 ispitanika, 29 je bilo muškog i 25 ženskog spola, srednja dob 9,84 ± 5,4 godine. Polovina indikacija za biopsiju otpada na nefrotski sindrom (NS; 25,93%) i ne-nefrotsku proteinuriju s hematurijom (22,22%). Najčešće je dijagnosticirana IgAN, a potom bolest minimalnih promjena (MCD), Henoch-Schönlein nefritis (HSPN), fokalna segmentalna glomeruloskleroza (FSGS) i Alportov sindrom (AS). Spektar dijagnoza se promijenio u odnosu na prethodno analizirano razdoblje 1995 – 2005. jer je mali postotak prethodno često dijagnosticiranog mezangioproliferativnog glomerulonefritisa (MesPGN). Na promjene u indikacijama i veći broj bioptiranih s IH-om i ne-nefrotskom proteinurijom s hematurijom utjecale su nove klasifikacije i mogućnost boljeg dijagnosticiranja hereditarnih bolesti glomerularne bazalne membrane (GBM). U eksperimentalnoj analizi, izražaj VDR-a u bubrežnom tkivu je značajno veći u bolesnika s IgAN-om nego u kontroli (P = 0,037), a izražaj 1α-OHaze značajno manji nego u kontroli (P < 0,001). Izražaj CYP24A1 i postotak jezgara imunoreaktivnih na CYP24A1 u glomerulima i epitelu distalnih kanalića je značajno veći u bolesnika s IgAN-om nego u kontrolnim tkivima 67 (P < 0,001). Postotak nuklearnog izražaja CYP24A1 u epitelu proksimalnih kanalića pokazuje negativnu korelaciju s eGFR (P = 0,034). Raspodjela indikacija i patoloških nalaza slična je podacima iz većine drugih studija. Razlika u izražaju VDR-a i enzima povezanih s aktivacijom i degradacijom vitamina D upućuje na smanjenu proizvodnju kalcitriola i povećanu razgradnju vitamina D u bubregu bolesnika s IgAN-om., Percutaneous kidney biopsy has been performed at University Hospital of Split continuously since 1994. Strict indications for invasive procedure include well- known renal syndromes. After diagnosis, renal tissue can be subsequently analyzed for new markers, important in the pathogenesis of renal disease. The kidney is the site of activation of vitamin D, which has a pleiotropic beneficial effect on the body. Due to kidney disease, the complex mechanism of vitamin D regulation can be disrupted. We investigated the expression of vitamin D receptor (VDR) and the enzymes of activation (1α-OHase) and degradation (CYP24A1) of vitamin D in kidney biopsies of patients with IgA nephropathy (IgAN) and compared it with control. For epidemiological analysis, clinical and pathological data were collected on 54 patients biopsied in the Clinic for Children´s Diseases from 2008 to 2017. For experimental analysis, archived paraffin blocks of renal tissue of 12 patients with IgAN (6 children and 6 adults) were collected. Five µm thick slides, standardly prepared for indirect immunohistochemical staining with antibodies to VDR, 1α-OHase and CYP24A1, were analyzed on an immunofluorescence microscope, photographed and quantified using an Image J computer program. In the statistical analysis, P < 0.05 was considered significant. In the epidemiological analysis, out of the 54 patients, 29 were male and 25 female; mean age 9.84 ± 5.4 years. Half of the biopsyindications are nephrotic syndrome (NS; 25.93%) and non-nephrotic proteinuria with hematuria, 22.22%. IgAN was most commonly diagnosed, followed by minimal change disease (MCD), Henoch-Schönlein purpura nephritis (HSPN), focal segmental glomerulosclerosis (FSGS), and Alport syndrome (AS). The spectrum of diagnoses changed compared to the previously analyzed period 1995 – 2005 because a small percentage of previously frequently diagnosed mesangioproliferative glomerulonephritis (MesPGN). Changes in indications were influenced by new classifications and the possibility of better diagnosis of hereditary disease of the glomerular basement membrane (GBM). In the experimental analysis, the expression of VDR in renal tissue was higher in patients with IgAN (P = 0.037), and the expression of 1α-OHase was significantly lower than in control (P

Perkutana biopsija bubrega izvodi se u KBC Split kontinuirano od 1994. Stroge indikacije za invazivni zahvat obuhvaćaju poznate bubrežne sindrome. Bubrežno tkivo se nakon postavljanja dijagnoze može naknadno analizirati radi novih biljega, važnih u patogenezi bubrežnih bolesti. Bubreg je mjesto aktivacije vitamina D koji ima pleiotropni povoljni učinak na organizam. Zbog bubrežne bolesti kompleksni mehanizam regulacije vitamina D može biti poremećen. Istražili smo izražaj receptora za vitamin D (VDR) te enzima aktivacje (1α-OHaza) i razgradnje (CYP24A1) vitamina D u bioptatima bubrega bolesnika s IgA nefropatijom (IgAN) i usporedili s kontrolnim tkivima. Za epidemiološku analizu prikupljeni su klinički i patološki padaci o 54 bolesnika bioptirana na Klinici za dječje bolesti od 2008. do 2017. Za eksperimentalnu analizu prikupljeni su arhivirani parafinski blokovi bubrežnog tkiva 12 bolesnika s IgAN-om (6 djece i 6 odraslih). Izrezani su preparati debljine 5 µm, standardno priređeni za indirektno imunohistokemijsko bojenje protutijelima na VDR, 1α-OHazu i CYP24A1, analizirani na imunofluoroscencijskom mikroskopu, fotografirani i kvantificirani uporabom ImageJ računalnog programa. U statističkoj analizi je značajnim smatran P < 0, 05. U epidemiološkoj analizi, od 54 ispitanika, 29 je bilo muškog i 25 ženskog spola, srednja dob 9, 84 ± 5, 4 godine. Polovina indikacija za biopsiju otpada na nefrotski sindrom (NS ; 25, 93%) i ne-nefrotsku proteinuriju s hematurijom (22, 22%). Najčešće je dijagnosticirana IgAN, a potom bolest minimalnih promjena (MCD), Henoch-Schönlein nefritis (HSPN), fokalna segmentalna glomeruloskleroza (FSGS) i Alportov sindrom (AS). Spektar dijagnoza se promijenio u odnosu na prethodno analizirano razdoblje 1995 – 2005. jer je mali postotak prethodno često dijagnosticiranog mezangioproliferativnog glomerulonefritisa (MesPGN). Na promjene u indikacijama i veći broj bioptiranih s IH-om i ne-nefrotskom proteinurijom s hematurijom utjecale su nove klasifikacije i mogućnost boljeg dijagnosticiranja hereditarnih bolesti glomerularne bazalne membrane (GBM). U eksperimentalnoj analizi, izražaj VDR-a u bubrežnom tkivu je značajno veći u bolesnika s IgAN-om nego u kontroli (P = 0, 037), a izražaj 1α-OHaze značajno manji nego u kontroli (P < 0, 001). Izražaj CYP24A1 i postotak jezgara imunoreaktivnih na CYP24A1 u glomerulima i epitelu distalnih kanalića je značajno veći u bolesnika s IgAN-om nego u kontrolnim tkivima (P < 0, 001). Postotak nuklearnog izražaja CYP24A1 u epitelu proksimalnih kanalića pokazuje negativnu korelaciju s eGFR (P = 0, 034). Raspodjela indikacija i patoloških nalaza slična je podacima iz većine drugih studija. Razlika u izražaju VDR-a i enzima povezanih s aktivacijom i degradacijom vitamina D upućuje na smanjenu proizvodnju kalcitriola i povećanu razgradnju vitamina D u bubregu bolesnika s IgAN-om.

Ievads. Imūnglobulīna A nefropātija (IgAN) ir biežākais glomerulonefrīta veids pasaulē. Slimība visbiežāk skar pacientus otrajā, trešajā dzīves dekādē un ir viens no hroniskas nieru mazspējas cēloņiem. Darba mērķis. Apkopot un analizēt IgAN klīniskās manifestācijas, noteikt nieru piecu gadu dzīvildzi un to ietekmējošos faktorus, validēt starptautisko IgAN prognozes kalkulatoru (PK) Latvijas populācijā. Materiāli un metodes. Retrospektīvs kohortas pētījums tika veikts Paula Stradiņa Klīniskās universitātes slimnīcas Nefroloģijas centrā, pētījumā tika iekļauti vismaz 18 gadus veci pacienti ar histoloģiski apstiprinātu IgAN diagnozi laika posmā no 2013.gada 1.janvāra līdz 2019.gada 11.novembrim. No stacionāra kartēm tika iegūti dati: vecums, GFĀ pēc CKD-EPI formulas, arteriālais asinsspiediens, diennakts proteīnūrija, AKEI/ARB grupas medikamentu un imūnsupresijas medikamentu lietošana iepriekš vai biopsijas brīdī, nieru biopsijas rezultāti pēc MEST rādītājiem. Datu statistiskajai analīzei tika izmantots Spīrmena korelācijas koeficients, Kaplana-Meiera metode un Koksa regresijas analīze. Rezultāti. Tika iekļauti 105 pacienti (59 vīrieši, vecuma mediāna 37 gadi (vecumā 18-72 gadiem)). Visvairāk pacientu (38%) bija 30-39 gadus veci, biežākā glomerulārā manifestācija bija nefrītiskais sindroms (72,8%). Nieru dzīvildzes mediāna bija 49 mēneši (95% TI 26,81-71,19). Statistiski ticami nieru dzīvildzi ietekmēja proteīnūrijas smagums (χ2(2)=7,115; p=0,029), MEST E (χ2(1)=3,892; p=0,049) un T (χ2(2)=32,06; p=0,001) punktu skaits. Pacientiem ar proteīnūriju 3,5g/dn, attiecīgi 40 mēneši (95% TI 7,63-72,37) un 18 mēneši (95% TI 5,81-30,19). Pacientiem ar MEST E0 mediānā nieru izdzīvotība bija 49 mēneši, tas ir, garāka nekā pacientiem ar E1 - 11 mēneši (95% TI 0,00-23,88). Pacientiem ar MEST T0 nieru izdzīvošanas mediāna bija ilgāka par 5 gadu periodu, tas bija ilgāk nekā pacientiem ar T1 un T2, attiecīgi 40 mēneši (95% TI 0,00-81,85) un 5 mēneši (95% TI 0,00-13,22). Koksa regresijas analīzei tika iekļauti 69 pacienti (37 vīrieši, vecuma mediāna 38 gadi (vecumā 18-72 gadiem)). Salīdzinot PK un Koksa regresijas aprēķinātos datus tika iegūta vidēji cieša pozitīva korelācija pēc viena (rs=0,618; p=0,001) un pieciem (rs=0,693; p= 0,001) gadiem. Kopīgie risku ietekmējošie faktori pēc viena un pieciem gadiem, kas uzrādīja lielāko atšķirību starp PK un Koksa regresijas aprēķinātajiem datiem bija vecums (18-29 gadi), vīriešu dzimums, AKEI/ARB lietošana, MEST M1. Secinājumi. IgAN skar jaunus cilvēkus un samazina nieru izdzīvotību. Nozīmīgi nieru dzīvildzi ietekmējošie faktori ir proteīnūrijas smagums, MEST E un T punktu skaits. Daļai pacientu PK piešķīra augstāku risku par aprēķinos iegūto. Ņemot vērā statistiski ticamo korelāciju starp PK un iegūtajiem datiem, PK varētu tikt izmantots nefrologu klīniskajā praksē Latvijā., Introduction. Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. The disease is one of chronic kidney disease causes and most often affects patients in second and third decade of life. Aim. The study aimed to collect and analyze IgAN patients’ clinical manifestations; to determine kidney survival and its affecting risks factors; to validate new International IgAN Prediction Tool (PT) in Latvian population. Materials and methods. A retrospective cohort study at Pauls Stradins Clinical University Hospital Nephrology center included at least 18 years old patients with a histologically confirmed diagnosis of IgAN from 1st January 2013 till 1st November 2019. Data were collected from medical records: age, glomerular filtration rate calculated by CKD-EPI formula, blood pressure, daily proteinuria, use of ACEI/ARBs and immunosuppression before or at the time of renal biopsy and MEST scores. Spearman’s Correlation, Kaplan-Meier method and Cox regression model were used for statistical data analysis. Results. 105 patients (59 men, median age 37 years (age range 18-72)) were included. Most of all (38 %) patients were in the age group of 30-39 years and most often patients had nephritic syndrome (72,8 %). Overall median kidney survival time was 49 (95% CI 26,81 - 71,19) months. Factors that statistically significantly affected renal survival were daily proteinuria (χ2(2) = 7,115; p = 0,029), MEST E (χ2(1) = 3,892; p = 0,049) un T (χ2(2) = 32,06; p = 0,001) scores. Participants with proteinuria 3,5g/24-hour urine, which was 40 (95% CI 7,63 - 72,37) and 18 (95% CI 5,81 - 30,19) months, respectively. Participants with MEST E0 median kidney survival was 49 months, that was longer then in patients with E1- 11 months (95% CI 0,00 - 23,88). Participants with MEST T0 median kidney survival time was longer than the follow-up period, that was longer than in patients with T1 and T2, which was 40 (95% CI 0,00 - 81,85) and 5 months (95% CI 0,00 - 13,22), respectively. For Cox regression analysis were included 69 patients (37 men, median age 38 years (age range 18-72)) due to missing data. A moderate positive correlation was observed between PT and our data in analysis after one (rs = 0,618; p = 0,001) and five years (rs = 0,693; p = 0,001). Common factors affecting differences between PT and our data were: age (18-29 years), male gender, use of ACEI/ARBs, MEST M1. Conclusions. IgAN is more common in young adults and affects kidney survival. Significant factors affecting renal survival were daily proteinuria, MEST E un T scores. For majority of patients’ PT calculated higher risk than our estimated. Since there was a statically significant correlation between PT and our data, we concluded that this calculator could be applied to use in Latvian population.

Izmještaj referelanog centra za glomerularen bolesti za IgA nefropatiju

Preemptivna transplantacija bubrega je vrsta transplantacije koja se radi prije početka dijalitičkog liječenja. Ona omogućuje bolju kvalitetu života i značajno smanjenje troškova liječenja u odnosu na dijalizu, a također je uz nju vezano bolje preživljenje, kako presatka, tako i bolesnika. Prikazali smo 26-godišnjeg bolesnika koji ima kroničnu bubrežnu bolest (KBB) uzrokovanu IgA nefropatijom. Bubrežna funkcija bolesnika je unatoč primijenjenoj imunosupresivnoj terapiji postupno slabila tijekom vremena, ali je jedan napadaj akutnog enterokolitisa doveo do značajnog i trajnog slabljenja bubrežne funkcije. Kod bolesnika se tada počelo razmišljati o nadomještanju bubrežne funkcije. Bolesnikova majka je prihvaćena kao živi darivatelj. Lijevi bubreg majke je transplantiran u desnu ilijačnu jamu. Operacija i rani postoperacijski tijek prošli su bez komplikacija. Postoperacijski, a kao indukcijska terapija, koristila su se monoklonska protutijela protiv interleukina 2 sa standardnom trojnom imunosupresivnom terapijom koja se sastojala od kortikosteroida, mikofenolat-mofetila i takrolimusa. Godinu dana nakon transplantacije bolesnik ima dobro funkcionirajući presadak bez ikakvih kirurških ili imunoloških komplikacija. Zaključno može se reći da je preemptivna transplantacija bubrega efikasna metoda liječenja pacijenta s kroničnim bubrežnim zatajenjem i treba biti preporučena u svih bolesnika u kojih se može učiniti transplantacija., Pre-emptive kidney transplantation is the type of transplantation that is performed before starting dialysis. It allows a better quality of life to the patient and significant reduction of costs in comparison with dialysis, and also is connected with higher survival rate of graft and patient. We present a 26-year-old patient diagnosed with chronic kidney disease (CKD) due to IgA nephropathy. His kidney function, despite of immunosuppressive therapy, gradually decreased in time but an onset of acute enterocolitis has lead to significant and permanent deterioration of kidney function with the forthcoming need for renal replacement therapy. His mother was accepted as a living kidney donor. The left kidney of the mother was transplanted to the right iliac fossa of the patient. The operation went without any complications. The postoperative course was uneventful with induction therapy with monoclonal antibody against interleukin 2 receptor and standard triple immunosuppressive therapy consisting of corticosteroid, mycophenolat mofetil and tacrolimus. One year after the transplantation, the patient has a good functioning kidney transplant without any surgical or immunological complications. Conclusively, pre-emptive kidney transplantation is an effective treatment for patients with end-stage renal disease and it should be recommended to all patients where this type of treatment is possible.

Preemptivna transplantacija bubrega je vrsta transplantacije koja se radi prije početka dijalitičkog liječenja. Ona omogućuje bolju kvalitetu života i značajno smanjenje troškova liječenja u odnosu na dijalizu, a također je uz nju vezano bolje preživljenje, kako presatka, tako i bolesnika. Prikazali smo 26-godišnjeg bolesnika koji ima kroničnu bubrežnu bolest (KBB) uzrokovanu IgA nefropatijom. Bubrežna funkcija bolesnika je unatoč primijenjenoj imunosupresivnoj terapiji postupno slabila tijekom vremena, ali je jedan napadaj akutnog enterokolitisa doveo do značajnog i trajnog slabljenja bubrežne funkcije. Kod bolesnika se tada počelo razmišljati o nadomještanju bubrežne funkcije. Bolesnikova majka je prihvaćena kao živi darivatelj. Lijevi bubreg majke je transplantiran u desnu ilijačnu jamu. Operacija i rani postoperacijski tijek prošli su bez komplikacija. Postoperacijski, a kao indukcijska terapija, koristila su se monoklonska protutijela protiv interleukina 2 sa standardnom trojnom imunosupresivnom terapijom koja se sastojala od kortikosteroida, mikofenolat-mofetila i takrolimusa. Godinu dana nakon transplantacije bolesnik ima dobro funkcionirajući presadak bez ikakvih kirurških ili imunoloških komplikacija. Zaključno može se reći da je preemptivna transplantacija bubrega efikasna metoda liječenja pacijenta s kroničnim bubrežnim zatajenjem i treba biti preporučena u svih bolesnika u kojih se može učiniti transplantacija., Pre-emptive kidney transplantation is the type of transplantation that is performed before starting dialysis. It allows a better quality of life to the patient and significant reduction of costs in comparison with dialysis, and also is connected with higher survival rate of graft and patient. We present a 26-year-old patient diagnosed with chronic kidney disease (CKD) due to IgA nephropathy. His kidney function, despite of immunosuppressive therapy, gradually decreased in time but an onset of acute enterocolitis has lead to significant and permanent deterioration of kidney function with the forthcoming need for renal replacement therapy. His mother was accepted as a living kidney donor. The left kidney of the mother was transplanted to the right iliac fossa of the patient. The operation went without any complications. The postoperative course was uneventful with induction therapy with monoclonal antibody against interleukin 2 receptor and standard triple immunosuppressive therapy consisting of corticosteroid, mycophenolat mofetil and tacrolimus. One year after the transplantation, the patient has a good functioning kidney transplant without any surgical or immunological complications. Conclusively, pre-emptive kidney transplantation is an effective treatment for patients with end-stage renal disease and it should be recommended to all patients where this type of treatment is possible.