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DOI 10.31718/2077-1096.21.3.100 УДК : 616.61-002.3-06:616.36-036.12-004:616.61-008.64 Rusnak I.T., Slyvka N.O., Akentiev S.O., Berezova M.S., Kulachek V.T, Al Salama M.V.O., Rovinskyi O.O.
CHRONIC PYELONEPHRITIS AS A PRECIPITATING FACTOR OF HEPATORENAL SYNDROME IN PATIENTS WITH ALCOHOLIC LIVER CIRRHOSIS
Bukovynian State Medical University, Chernivtsi
Introduction. Most attempts to assess renal failure in alcoholic liver cirrhosis have so far focused on acute kidney injury and on the hepatorenal syndrome in particular. However, there are still limited data on the prevalence and clinical impact of chronic kidney disease in cirrhosis. Objectives. This study aimed to assess the influence of chronic pyelonephritis on the incidence of hepatorenal syndrome in patients with alcoholic liver cirrhosis. Material and methods. 165 patients with decompensated alcoholic liver cirrhosis and concomitant chronic pyelonephritis were enrolled in the study. They were divided into two groups according to the presence or absence of chronic pyelonephritis: group 1 had alcoholic liver cirrhosis only (n=82), group 2 had alcoholic liver cirrhosis + chronic pyelonephritis (n=83). Results. The general bacterial infections were more common in group 1 patients. The spectrum of the most frequent bacterial complications in the examined patients typical for alcoholic liver cirrhosis was as follows: the share of urinary tract infection made up 16.0% (95% confidence interval 14.4-27.9), pneumonia constituted 16.7% (95% confidence interval 10.5-22.7, bacteremia made up 4.0% (95% confidence interval 7.7-38.6), the share of skin infections (erysipelas) was 2.7% (95% confidence interval 0.7-6.6). Other infections including pulmonary tuberculosis, lung abscess, right leg abscess, osteomyelitis, bedsores, were less common (6.7%). Spontaneous bacterial peritonitis, taking into account all options, was found in 6 cases (10.5%, 95% confidence interval 4.0-21.5). As expected, the incidence of hepatorenal syndrome within 14 days of inpatient onset was almost twice higher in group 2 - 22 cases (27%), than in group2 - 13 cases (16%). The group 2 demonstrated a more severe course of alcoholic liver cirrhosis on the Child-Pugh scale compared with group I (class B - 29.9%; class C - 70.1% against class B - 46.4%; class C - 53, 6% ); the differences were statistically significant (x2 = 4.30, p = 0.038). In patients of group 2, the lethal outcome in the hospital occurred in 6 (8.9%) cases. Conclusions: The results of the present study confirm the role of chronic pyelonephritis as one of the major precipitating factors of hepa-torenal syndrome incidence in patients with alcoholic liver cirrhosis. This fact should be considered when making the treatment plan for these patients.
Keywords: chronic pyelonephritis, hepatorenal syndrome, alcoholic liver cirrhosis.
This study is conducted as a part of research project "Risk factors for progression of essential hypertension and metabolic syndrome in comprehensive assessment of hemodynamic, renal function, and circadian structure of blood pressure in the justification of antihypertensive therapy", the Department of Patient Care and Higher Nursing Education, Bukovynian State Medical University, Chernivtsi.
Introduction Material and methods
Most attempts to assess renal failure in alco- 165 patients with decompensated ALC and
holic liver cirrhosis (ALC) have so far focused on concomitant CP were enrolled in the study. They
acute kidney injury (AK|), and as a result detailed were divided into two groups according to the
kn°wledge( of hepatorenal syndroT (HRS) as a presence or absence of CP: group 1 - ALC only
part of AKI in cirrhosis is now available [1]. How- (n=82) group 2 -ALC+CP (n=83)
ever, there are still limited data on the prevalence ( -rh)e Xxclupsion criteria w(ere: I).-IV CKD stages
and clinical impact of chronic kidney disease (CKD) h5?riudiiaiysS'steprrio wtSrt5he^I|LidVniss^Dr.i5 taegeis-
in cirrhosis. ALC patients are susceptible to HRS стгопю hem°chalysis ртогю tne admission, hepa
development due to circulato ry disorders , neuro- tocellular carcinoma outside ^ ,Milan c"teria and
hormonal changes, and other precipitating factors, other malignancies, viral aetiology of cirrhosis,
such as bacterial infection, gastrointestinal bleed- and'5ck innformed consent °f the patient: л ч
ing, medication, and paracentesis [1-8]. Depending . AKK was diagnosed. accordin,g torthf [pA
on the severity, duration, and frequency, CKD ria [2], the ALC severity was classified ьУ meld
might increase the risk of accidental HRS due to and Child-Pugh scales [7]. decreased renal mass and number of nephrons, CL|F-C-ACLF score organ/system failure crite-
vascular insufficiency, and maladaptive recovery ria were: liver - bilirubin, kidney - creatinine, brain
mechanisms [8]. There is another condition, acute- - liver encephalopathy, coagulation - international
on-chronic liver failure (ACLF) that can contribute normalized ratio (INR), blood circulation - use of
to the HRS development and cause a sharp dete- vasopressors (dopamine), lungs - SpO2/FiO2 [8]. rioration of the liver function in patients with cirrho- Comparison of normally distributed continuous
sis. This condition is becoming more often recog- variables was performed by Student's t-test or
nized fulminant hepatitis caused by secondary or ANOVA. Comparison of non-normally distributed
extra hepatic causative factors, precipitating factors continuous variables was made by Mann-Whitney
(PF), such as infections that lead to dysfunction of (U) or Kruskal-Wallis tests. Categorical variables
the target organs. The number of studies in this area were expressed as numbers and percentages and
is rather limited, but this gap has to be filled. were compared with each other using the chi-
square test (x2) or Fisher's exact test. All statisti-
cal studies were processed by the statistical package SPSS, version 23.0. A p-value of less than 0.05 for all studies was found to be statistically significant.
Results and discussion
The baseline clinical characteristics of the par-
ticipants with decompensated ALC are shown in Table 1. The general bacterial infections were more common in group 1 patients. As expected, the incidence of HRS was almost twice higher in group 2 than in group 1 that confirms the important role of CP as an HRS precipitator.
Table 1.
Clinical and laboratory data of ALC patients
Group 1, ALC (n=82) Ggroup 2, ALC+CP (n=83)
Age, years 42,34±12,57 44,28±11,82
Gender, male/female, n (%) 56/26 (68%/32%) 57/26 (68%/32%)
Asscites, n (%) 43 (52%) 56 (67%)*
Hepatic encephalopathy , n (%) 6 (7%) 16 (19%)*
Bacterial infections , n (%) 27 (32%) 41 (50%)*
Creatinine, (mg / dL) 0,85 ±0,44 2,68±0,68*
Bilirubin (mg / dL) 2,52±0,94 2,61 ±0,95
INR 1,57±0,57 1,55±0,63
Na serum, (mmol/l) 131,54±6,42 139,68±3,54*
Platelets, (*109/L) 85,18±19,25 77,26±21,18*
MELD score 14,32±2,24 19,21 ±3,17*
Child-Pugh scale 7,52±1,93 8,47±1,92*
Incidence of HRS within 14 days of inpatient onset, n (%) 13 (16%) 22 (27%)*
Note: *-the difference is statistically significant compared to group 1
Table. 2.
The structure of precipitating factors in examined ALC patients
Infectious complications Share in the structure infectious complications,n=67 Share in the general ALC cohort, n = 165 (%; 95 % CI)
Absolute no %
Spontaneous bacterial peritonitis 6 8,9 4,0 (4,0-21,5)
Urinary tract infections 24 35,8 16,0 (14,4-27,9)
Pneumonia 16 23,9 10,7 (10,5-22,7)
Sepsis 1 1,5 0,7 (0-3,6)
Bacteremia 6 8,9 4,0 (7,7-38,6)
Erysipelas 4 5,9 2,7 (0,7-6,6)
Other 10 14,9 6,7 (3,7-12,7)
The structure of infectious complications established as precipitating factors in the patients is shown in the Table 2.
The spectrum of the most frequent bacterial complications in the examined patients was typical for ALC and included urinary tract infection (CP) in 16.0% of cases (95% CI 14.4-27.9), pneumonia in 16.7% of cases (95% CI 10.522.7), bacteremia in 4.0% of cases (95% CI 7.738.6), and skin infections (erysipelas) in 2.7% of cases (95% CI 0.7-6.6). Other infections were less common (6.7%): pulmonary tuberculosis, lung abscess, right leg abscess, osteomyelitis, bedsores. SBP, taking into account all options, was found in 6 cases (10.5%, 95% CI 4.0-21.5). In group 2 there was a more severe course of ALC on the
Comparison of markers of systemic inflammation and cyt
Child-Pugh scale compared with group I (class B -29.9%; class C - 70.1% against class B - 46.4%; class C - 53, 6%), the differences were statistically significant (x2 = 4.30, p = 0.038). In the group 2, the lethal outcome in the hospital occurred in 6 (8.9%) cases. In the group 1 (n = 83) 1 (1.2%) patient died, the differences were statistically significant (p = 0.030).
Because many patients with HRS-1 meet ACLF criteria, we investigated whether elevated levels of inflammatory cytokines detected in HRS-1 were potentially associated with concomitant ACLF or with CP only. We classified patients with HRS -1 according to the presence or absence of ACLF. We found out that cytokine levels correlated with the severity of ACLF (Table 3).
Table 3.
in plasma and urine in patients with HRS-1 associated with ACLF
CLIF-C-ACLF l-ll (n=82) CLIF-C-ACLF ll-lV (n=83) P value
CRP (mg/dl) 3,52±1,23 3,78±1,24 0,855
Leucocites (x109/L) 6,52±1,84 7,56±1,89 0,400
Systemic inflammatory response 7 (32%) 7 (33%) 0,993
INF - y (pg/ml) 35,81±6,17 19,08±5,14 0,582
IL - 6 (pg/ml) 45,36±5,78 56,44±7,21 0,207
IL - 8 (pg/ml) 44,52±6,37 91,62±7,93 0,006*
TNF - a (pg/ml) 46,41±5,67 49,35±5,84 0,749
VEGF (pg/ml) 169,72±2,51 144,57±9,76 0,936
uMCP - 1 (pg/ml) 1624,32±8,39 1250,63±7,42 0,274
Tom 21, BunycK 3 (75)
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The results of our study show that patients with HRS-1 have systemic inflammation with an altered cytokine profile compared with patients with ALC without HRS and, most interestingly, with HRS-2. The study also demonstrates that the systemic inflammatory response in HRS-1 is not associated with the presence of bacterial infections, concomitant ACLF or the intensity of renal dysfunction and is not normalized by improving renal function through pharmacological therapy. Interestingly, the intensity of the inflammatory response correlates with renal function and patients who have elevated levels of some inflammatory markers, especially VEGF, are associated with lack of HRS resolution and mortality.
In this study, a large number of patients with cirrhosis and HRS-1 were examined for the presence of a systemic inflammatory response assessed by a large number of inflammatory and anti-inflammatory cytokines using multiplex technology. For comparison, a control group of patients with ALC without HRS was included. A group of patients with ALC+HRS-2 was also studied. This type of HRS was chosen as a comparison group for HRS-1, because in both conditions AKI has a prerenal origin, but the main pathogenetic cause is very different. While the decrease in blood flow is the cause of renal hypoperfusion in the hypovolemic variant of HRS-2, renal dysfunction in HRS-1 is associated with opposite features of blood circulation, and namely with pronounced vasodilation, especially in splanchnic circulation [2 , 4]. The results of this study clearly show that with the development of decompensated cirrhosis to HRS, there is a progressive increase in inflammatory status with significantly elevated levels of some potent inflammatory cytokines. Previous studies have shown that plasma levels of inflammatory cytokines increase significantly in decom-pensated cirrhosis compared with compensated [8]. It is not known whether this inflammatory driving force is the cause or consequence of liver disease progression. Our data confirm that this inflammatory status due to decompensated cirrhosis increases even more as the disease progresses to HRS, which is considered one of the last stages of cirrhosis due to its high mortality. Our data are thus consistent with the recently
Реферат
ХРОН1ЧНИЙ ПЮЛОНЕФРИТ ЯК ПРЕЦИП1ТУЮЧИЙ ФАКТОР ГЕПАТОРЕНАЛЬНОГО СИНДРОМУ У ХВОРИХ НА АЛКОГОЛЬНИЙ ЦИРОЗ ПЕЧ1НКИ
Руснак 1.Т., Сливка Н.О., Акентьев С.О., Аль Салама М.В.О., Ровшський О.О.
Ключовi слова: хрожчний телонефрит, гепаторенальний синдром, алкогольний цироз печЫки.
Вступ. Бтьшють спроб оцшити ниркову недостатнють при алкогольному цироз1 печшки дос були зосереджеш на гострому ураженш нирок, та гепаторенальному синдром! зокрема. Однак, дос1 е обме-женими дан1 про поширенють та кл1н1чний вплив хрошчноТ хвороби нирок при цирозк Завдання. Це до-слщження мало на мет1 оцшити вплив хрошчного шелонефриту на частоту виникнення гепатореналь-ного синдрому у пац1ент1в з алкогольним цирозом печшки. Матер1ал i методи. У дослщження було включено 165 па^ен^в з некомпенсованим алкогольним цирозом печшки та супутшм хрошчним тело-нефритом. Вони були роздтеш на двi групи за наявнютю або вщсутнютю хрошчного шелонефриту: група 1 - лише алкогольний цироз печшки (n = 82), група 2 - алкогольний цироз печшки + хрошчний шелонефрит (n = 83). Результати. Загальш бактерiальнi шфекци були бтьш поширеними у па^ен^в
proposed theory of systemic inflammation, which causes complications of cirrhosis [6]. Two pieces of evidence suggest that elevated inflammatory status is not associated with ACLF but with CP. First, plasma cytokine levels in patients with HRS but without ACLF did not differ significantly from those in patients with HRS and ACLF. Moreover, cytokine levels were largely unrelated to the ACLF class. On the other hand, the cytokine profile in patients with HRS was markedly different from the profile of patients with ACLF and HRS-2, suggesting that the cytokine profile is mainly associated with HRS and not with ACLF. However, these findings should be taken with caution due to the relatively low number of patients included in our work. Further research is needed to try to determine whether systemic inflammation is caused by hepatorenal syndrome "per se" or ACLF, or both.
Conclusions
The results of the present study confirm the role of chronic pyelonephritis as one of the major precipitating factors of hepatorenal syndrome incidence in patients with alcoholic liver cirrhosis. This fact should be considered while choosing the treatment plan for these patients.
References
1. Bunchorntavakul C. Bacterial infections in cirrhosis: A critical review and practical guidance. World J Hepatol. 2016;8(6):307-321.
2. Angeli P, Ginès P, Wong F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol. 2015;62(4):968 - 974.
3. Angeli P, Bernardi M, Villanueva C, et al. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2): 406 - 460.
4. Ginès P, Solà E, Angeli P, Wong F, et al. Hepatorenal syndrome. Nat Rev Dis Prim. 2018;4(1):23.
5. Thabut D, Massard J, Gangloff A, et al. Model for end - stage liver disease score and systemic inflammatory response are major prognostic factors in patients with cirrhosis and acute functional renal failure. Hepatol. 2007;46(6):1872 - 1882.
6. Clària J, Stauber R, Coenraad M, et al. Systemic inflammation in decompensated cirrhosis: characterization and role in acute - on - chronic liver failure. Hepatol. 2016;64(4):1249 - 1264.
7. Moreau R, Jalan R, Gines P, et al. Acute - on - chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterol. 2013;144(7):1426 - 1437.
8. Karakike E. Infections in severe alcoholic hepatitis. Ann Gastroenterol. 2017;30(2):152-160.
групи 1. Спектр найчаспших бактерiальних ускладнень у обстежених хворих був традицшним для алкогольного цирозу печшки - шфек^я сечовивiдних шляхiв 16,0% (95% довiрчий iнтервал 14,4-27,9), пневмошя 16,7% (95% довiрчий iнтервал 10,5-22,7), бактерieмiя 4,0% (95 % довiрчий iнтервал 7,738,6), шкiрнi шфекци (бешиха) 2,7% (95% довiрчий штервал 0,7-6,6). Iншi шфекци зустрiчалися рщше (6,7%): туберкульоз легень, абсцес легеш, абсцес право! нижньо! кiнцiвки, остеомieлiт, пролежнi. Спо-нтанний бактерiальний перитонгг, враховуючи всi варiанти, був виявлений у 6 випадках (10,5%, 95% довiрчий штервал 4,0-21,5). Як i очкувалось, частота гепаторенального синдрому протягом 14 дшв вiд початку стацюнарного лiкування була майже вдвiчi вищою у групi 2 - 22 випадки (27%), шж у груш 2 -13 випадш (16%). У 2 груш спостер^ався бтьш важкий перебiг АЦП за шкалою Чайлд-Пью порiвняно з групою I (клас В - 29,9%; клас С - 70,1% проти класу В - 46,4%; клас С - 53, 6%), рiзницi були статис-тично значущими (х2 = 4,30, р = 0,038). У па^енлв 2 групи летальний результат у лшарш стався у 6 (8,9%) випадках. Висновки: Результати цього дослщження пщтверджують роль хрошчного шелонеф-риту як одного з основних факторiв, що спричиняють поширенiсть гепаторенального синдрому у пац^ ентiв з алкогольним цирозом печшки. Цей факт слщ враховувати пщ час вибору плану лкування для цих па^ен^в.
Реферат
ХРОНИЧЕСКИЙ ПИЕЛОНЕФРИТ КАК ПРЕЦИПИТИРУЮЩИЙ ФАКТОР ГЕПАТОРЕНАЛЬНОГО СИНДРОМА У БОЛЬНЫХ С АЛКОГОЛЬНЫМ ЦИРРОЗОМ ПЕЧЕНИ
Руснак И.Т., Сливка Н.А., Акентьев С.А., Аль Салама М.В.О., Ровинский А.А.
Ключевые слова: хронический пиелонефрит, гепаторенальный синдром, алкогольный цирроз печени.
Введение. Большинство попыток оценить почечную недостаточность при алкогольном циррозе печени до сих пор были сосредоточены на остром повреждении почек и гепаторенальном синдроме в частности. Однако, до сих пор ограничены данные о распространенности и клиническом влиянии хронической болезни почек при циррозе. Целью этого исследования было оценить влияние хронического пиелонефрита на частоту возникновения гепаторенального синдрома у пациентов с алкогольным циррозом печени. Материал и методы. В исследование было включено 165 пациентов с декомпенси-рованным алкогольным циррозом печени и сопутствующим хроническим пиелонефритом. Они были разделены на две группы по наличию или отсутствию хронического пиелонефрита: группа 1 - только алкогольный цирроз печени (п = 82), группа 2 - алкогольный цирроз печени + хронический пиелонефрит (п = 83). Результаты. Общие бактериальные инфекции были более распространенными у пациентов группы 1. Спектр частых бактериальных осложнений у обследованных больных был традиционным для алкогольного цирроза печени - инфекция мочевыводящих путей 16,0% (95% доверительный интервал 14,4-27,9), пневмония 16,7 % (95% доверительный интервал 10,5-22,7), бактериемия 4,0% (95% ДИ 7,7-38,6), кожные инфекции (рожа) 2,7% (95% доверительный интервал 0,7-6 6). Другие инфекции встречались реже (6,7%): туберкулез легких, абсцесс легкого, абсцесс правой нижней конечности, остеомиелит, пролежни. Спонтанный бактериальный перитонит, учитывая все варианты, был обнаружен в 6 случаях (10,5%, 95% доверительный интервал 4,0-21,5). Как и ожидалось, частота ге-паторенального синдрома в течение 14 дней от начала стационарного лечения была почти вдвое выше в группе 2 - 22 случая (27%), чем в группе 2 - 13 случаев (16%). Во 2 группе наблюдался более тяжелое течение алкогольного цирроза печени по шкале Чайлд-Пью по сравнению с группой I (класс В - 29,9%; класс С - 70,1% против класса В - 46,4%; класс С - 53, 6%) , разницы были статистически значимыми (х2 = 4,30, р = 0,038). У пациентов 2 группы летальный исход в больнице произошел в 6 (8,9%) случаях. Выводы: Результаты этого исследования подтверждают роль хронического пиелонефрита как одного из основных факторов, вызывающих распространенность гепаторенального синдрома у пациентов с алкогольным циррозом печени. Этот факт следует учитывать при выборе плана лечения для этих пациентов.
Том 21, Випуск 3 (75)
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