Kontrastom indukovana nefropatija kao prediktor akutizacije bubrežne insuficijencije, komplikacija i mortaliteta posle kardiohirurških operacija

Abstract

Hronična bolest bubrega (HBB) je zdravstveni problem koji se javlja širom sveta i povezana je sa visokim kardiovaskularnim komorbiditetom i smrtnošću. Veliki porast broja bolesnika koji imaju terminalnu bubrežnu slabošću (TBS) nastaje kao posledica eksponencijalnog porasta broja bolesnika čija je slabost bubrega posledica hipertenzije i dijabetesa, kao i porasta broja starih sa TBS. Zbog toga više od 50% bolesnika sa HBB umire zbog kardiovaskularnih bolesti i pre započinjanja lečenja metodama za zamenu funkcije bubrega. Utvrditi kliničke karakteristike bolesnika sa i bez kontrastom indukovane nefropatije (pre svega varijable bubrežne funkcije definasane pomoću AKIN i RIFLE kriterijuma) podvrgnutih kardiohirurškim operacijama, potom utvrditi postojanje razlike u mortalitetu i postoperativnom morbiditetu između bolesnika sa i bez kontrastom indukovane nefropatije, a koji se podvrgavaju kardiohirurškoj operaciji i takođe utvrditi prediktore mortaliteta i morbiditeta kod bolesnika sa prethodnom kontrastom indukovanom nefropatijom koji se podvrgavaju kardiohirurškoj operaciji. Studija je koncipirana kao retroprospektivna opservaciona studija u ukupnom trajanju od pet godina retrospektivnog perioda i pola godine prospektivnog perioda kojim su obuhvaćene dve grupe bolesnika: I grupa - pacijenti sa kontrastom indukovanom nefropatijom (CIN) i II grupa - pacijenti bez CIN; koji su podvrgnuti kardiohirurškim operacijama (koronarna, valvularna, kombinovana hirurgija i ostale) na Institutu za kardiovaskularne bolesti Vojvodine u Sremskoj Kamenici. Od ukupnog broja operisanih pacijenata u ovom perioda (oko 5000 bolesnika) u ovu studiju je uključeno 1269 bolesnika. U našoj studiji ukupno je analizirano 1269 bolesnika koji su svrstani u dve grupe. Prvu grupu je činilo 59 (4,6%) pacijenata koji su koronarografisani (dijagnostička, terapijska) i razvili CIN te su upućeni u istoj hospitalizaciji po indikaciji konzilijuma na koronarnu, valvularnu i kombinovanu hirurgiju. Drugu grupu je činilo 1210 (95,4%) bolesnika kod kojih nakon koronarografije nije razvijena kontrastom indukovana nefropatija, a takođe su tokom iste hospitalizacije operisani. Kriterijumi za uključivanje pacijenata u studiju su svi punoletni bolesnici koji su upućeni na kardiohirurške operacije (koronarna, valvularna, kombinovana i ostale). CIN je definisan kao porast vrednosti kreatinina unutar pet dana nakon koronarografije za 25% u odnosu na vrednost kreatina pre koronarografije. Praćene su preoperativne, operativne i postoperativne karakteristike bolesnika sa CIN i bolesnika bez CIN. U disertaciji su korišćene mere deskriptivne statistike: aritmetička sredina, standardna devijacija, medijana, kvartili, frekvence i procenti. Za poređenje srednjih vrednosti varijabli dve populacije primenjen je test za nezavisne uzorke i Man-Vitnijev test. Povezanost kategorijskih varijabli ispitana je pomoću Hi-kvadrat testa za tabele kontigencije ili pomoću Fišerovog testa. Određivanje uticaja promenljivih na ishod lečenja izvršen je primenom univarijantne i multivarijantne binarne logističke regresije, koja je poslužila i za pravljenje nove varijable (modela) za procenu ishoda lečenja. Prediktivni kvalitet varijabli na ishod ocenjen je pomoću ROC krivih. Za određivanje dužine preživljavanja primenjena je Kaplan-Meier analiza preživljavanja. Uticaj varijabli na preživljavanje izvršen je na osnovu Coxove regresione analize. Za statistički značajnu testa uzeta je vrednost p<0,05. Statistička obrada podataka izvedena je primenom statističkog paketa SPSS 17. Dokazana je statistička značajnost u ispitivanim grupama u pogledu akutizacije bubrežne insuficijencije (p=0,007). Broj bolesnika sa akutizacijom bubrežne insuficijencije u grupi CIN je bio 3 (5,1%), a u grupi bez CIN je 6 (0,5%). Dokazana je statistička značajnost u ispitivanim grupama na osnovu perikardnog izliva (p=0,046). Statističku značajnost treba uslovno prihvatiti jer je broj bolesnika sa perikardnim izlivom u grupi sa CIN bio samo 1 (1,7%). Dokazana je statistička značajnost u ispitivanim grupama na osnovu mortaliteta (p<0,0005). Broj umrlih u grupi pacijenata sa CIN je 8 (13,6%), a u grupi pacijenata bez CIN je 23 (1,9%). Dokazana je statistička značajnost u ispitivanim grupama na osnovu AKIN kriterijuma (p<0,0005). Broj bolesnika bez AKIN kriterijuma u grupi sa CIN bio je 29 (49,2%), a u grupi pacijenata bez CIN je 1210 (100,0%). U Stadijumu 1 AKIN kriterijuma broj bolesnika u grupi sa CIN bio je 26 (44,1%), a u grupi bolesnika bez CIN je 0 (0,0%). U Stadijumu 2 AKIN kriterijuma broj bolesnika u grupi sa CIN bio je 1 (1,7%), a u grupi bolesnika bez CIN bio je 0 (0,0%). U Stadijumu 3 AKIN kriterijuma broj bolesnika u grupi sa CIN bio je 3 (5,1%), a u grupi bolesnika bez CIN bio je 0 (0,0%). Dokazana je statistička značajnost u ispitivanim grupama na osnovu RIFLE kriterijuma (p<0,0005). Broj bolesnika bez RIFLE kriterijuma u grupi sa CIN bio je 0 (0,0%), a u grupi pacijenata bez CIN bio je 1169 (96,6%). U riziku (Risc) RIFLE kriterijuma broj bolesnika u grupi sa CIN bio je 51 (86,4%), a u grupi bolesnika bez CIN bio je 41 (3,4%). U oštećenju (Injury) RIFLE kriterijuma broj bolesnika u grupi sa CIN bio je 5 (8,5%), a u grupi bolesnika bez CIN bio je 0 (0,0%). U stabost (Failure) RIFLE kriterijuma broj bolesnika u grupi sa CIN bio je 3 (5,1%), a u grupi bolesnika bez CIN bio je 0 (0,0%). Dokazana je statistička značajnost u ispitivanim grupama na osnovu broja komplikacija (p<0,0005). Broj bolesnika bez komplijacija u grupi sa CIN bio je 39 (66,1%), a u grupi pacijenata bez CIN bio je 1027 (84,9%). Broj bolesnika sa 1 komplijacijom u grupi sa CIN bio je 12 (20,3%), a u grupi pacijenata bez CIN bio je 146 (12,1%). Broj bolesnika sa 2 komplijacije u grupi sa CIN bio je 6 (10,2%), a u grupi pacijenata bez CIN bio je 20 (1,7%). Broj bolesnika sa 3 komplijacije u grupi sa CIN bio je 1 (1,7%), a u grupi pacijenata bez CIN bio je 11 (0,9%). Broj bolesnika sa 4 komplijacije u grupi sa CIN bio je 1 (1,7%), a u grupi pacijenata bez kontrastom indukovane nefropatije bio je 6 (0,5%). Dokazana je statistička značajnost u ispitivanim grupama na osnovu MACE komplikacija (p<0,0005). Broj bolesnika sa MACE komplikacijama u grupi sa CIN bio je 20 (33,9%), a u grupi pacijenata bez CIN bio je 183 (15,1%). Akutna bubrežna slabost je relativno česta komplikacija kardiohirurških operacija. Posebno su ugroženi bolesnici sa visokim preoperativnim rizikom, u našoj studiji pacijenti sa prethodnim CIN-om, kod kojih je akutizacija bubrežne slabosti znatno učestalija. Kardiohirurški bolesnici kod kojih nastane akutna bubrežna slabost imaju, kao i u našoj studiji, više postoperativnih komplikacija, produžen boravak u jednici intenzivne nege, kao i rizik za nastanak hronične bubrežne bolesti.

Chronic kidney disease (CKD) is a healthcare problem that occurs worldwide and is associated with high cardiovascular comorbidity and mortality. A large increase in the number of patients with terminal renal failure (TRF) occurs as a result of an exponential increase in the number of patients whose renal failure is due to hypertension and diabetes, as well as an increase in the number of elderly with TRF. As a result, more than 50% of patients with CKD die from cardiovascular disease even before starting treatment with kidney replacement therapy. To determine the clinical characteristics of patients with and without contrast-induced nephropathy (CIN) (renal function parameters defined by AKIN and RIFLE criteria) undergoing cardiac surgery, to determine the difference in mortality and postoperative morbidity between patients with and without CIN who are submitted to cardiac surgery and also to determine predictors of mortality and morbidity in patients with CIN undergoing cardiac surgery. The study was conceived as a retroprospective observational study with a total duration of five years of retrospective period and half a year of prospective period which included two groups of patients: Group I - patients with contrast-induced nephropathy (CIN) and Group II - patients without CIN; who underwent cardiac surgery (coronary, valvular, combined surgery and other) at the Institute for Cardiovascular Diseases of Vojvodina in Sremska Kamenica. Out of the total number of operated patients in this period (about 5000 patients), 1269 patients were included in this study. In our study, a total of 1269 patients were analyzed, which were classified into two groups. The first group consisted of 59 (4.6%) patients who underwent coronary angiography (diagnostic, therapeutic) and developed CIN and were submitted to surgery in the same hospitalization as indicated by heart team. The second group consisted of 1210 (95.4%) patients who did not develop CIN after coronary angiography but were also operated on during the same hospitalization. Criteria for inclusion of patients in the study are: all adult patients who are referred for cardiac surgery (coronary, valvular, combined and other). CIN was defined as a at least 25% increase in creatinine value within five days after coronary angiography compared to creatine value before coronary angiography. Preoperative, operative and postoperative characteristics of patients with CIN and patients without CIN were analyzed. Statistical analyses included measures of descriptive statistics: arithmetic mean, standard deviation, median, quartiles, frequencies and percentages. To compare the mean values of the variables of the two populations, t-test for independent samples and the Mann-Whitney test were applied. The correlation of categorical variables was examined using the Chi-square test for contingency tables or using the Fisher test. The influence of variables on the treatment outcome was determined by applying univariate and multivariate binary logistic regression, which also served to create a new variable (model) for assessing the treatment outcome. The predictive quality of outcome variables was assessed using ROC curves. Kaplan-Meier survival analysis was used to determine survival length. The influence of variables on survival was performed based on Cox regression analysis. For a statistically significant test, the value of p <0.05 was taken. Statistical data processing was performed using the statistical package SPSS 17. Statistical significance was observed in the examined groups regarding the acutization of renal failure (p = 0.007). The number of patients with acute renal failure in the CIN group was 3 (5.1%), and in the group without CIN it was 6 (0.5%). Statistical significance was observed between the examined groups based on pericardial effusion (p = 0.046). Statistical significance should be conditionally accepted because the number of patients with pericardial effusion in the group with CIN was only 1 (1.7%). Statistical significance was demonstrated in the examined groups based on mortality (p <0.0005). The number of deaths in the group of patients with CIN was 8 (13.6%), and in the group of patients without CIN it was 23 (1.9%). Statistical significance was demonstrated in the examined groups based on the AKIN criteria (p <0.0005). The number of patients without AKIN criteria in the group with CIN was 29 (49.2%), and in the group of patients without CIN it was 1210 (100.0%). In Stage 1 of the AKIN criterion, the number of patients in the group with CIN was 26 (44.1%), and in the group of patients without CIN it was 0 (0.0%). In Stage 2 of the AKIN criterion, the number of patients in the group with CIN was 1 (1.7%), and in the group of patients without CIN it was 0 (0.0%). In Stage 3 of the AKIN criterion, the number of patients in the group with CIN was 3 (5.1%), and in the group of patients without CIN it was 0 (0.0%). Statistical significance was demonstrated between the examined groups based on the RIFLE criteria (p <0.0005). The number of patients without RIFLE criteria in the group with CIN was 0 (0.0%), and in the group of patients without CIN it was 1169 (96.6%). In the Risk of the RIFLE criterion, the number of patients in the group with CIN was 51 (86.4%), and in the group of patients without CIN it was 41 (3.4%). In the Injury of the RIFLE criterion, the number of patients in the group with CIN was 5 (8.5%), and in the group of patients without CIN it was 0 (0.0%). In the Failure of the RIFLE criterion, the number of patients in the group with CIN was 3 (5.1%), and in the group of patients without CIN it was 0 (0.0%). Statistical significance was demonstrated in the examined groups based on the number of complications (p <0.0005). The number of patients without complications in the group with CIN was 39 (66.1%), and in the group of patients without CIN it was 1027 (84.9%). The number of patients with 1 complication in the group with CIN was 12 (20.3%), and in the group of patients without CIN it was 146 (12.1%). The number of patients with 2 complications in the group with CIN was 6 (10.2%), and in the group of patients without CIN it was 20 (1.7%). The number of patients with 3 complications in the group with CIN was 1 (1.7%), and in the group of patients without CIN it was 11 (0.9%). The number of patients with 4 complications in the group with CIN was 1 (1.7%), and in the group of patients without contrast-induced nephropathy it was 6 (0.5%). Statistical significance was demonstrated between the examined groups based on MACE complications (p <0.0005). The number of patients with MACE complications in the group with CIN was 20 (33.9%), and in the group of patients without CIN it was 183 (15.1%). Acute renal failure is a relatively common complication of cardiac surgery. Vulnerable patients are particularly at risk, in our study patients with previous CIN, in whom the acutazation of renal failure is significantly more frequent. Cardiac surgery patients who develop acute renal failure have, as demonstrated in our study, more postoperative complications, prolonged stay in the intensive care unit, as well as the risk of developing chronic kidney disease.