|Year : 2017 | Volume
| Issue : 4 | Page : 192-197
Acute kidney injury in patients with liver cirrhosis
Nabil M Lasheen, Abdalla A Elsawy, Nashwa M Nor Eldin, Kamal M Okasha
Department of Internal Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
|Date of Submission||25-Jan-2017|
|Date of Acceptance||02-Jul-2017|
|Date of Web Publication||12-Mar-2018|
Nabil M Lasheen
Birket Elsab, Alminufiya, 31511
Background Acute kidney injury (AKI) is a common complication of cirrhosis and confers a poor prognosis. There are many different causes for the development of AKI among patients with cirrhosis.
Aim The aim was to study the incidence of AKI in cirrhotic patients and the different causes of AKI among them.
Patients and methods Our study was conducted on 900 cirrhotic patients who were investigated in order to detect the incidence and causes of AKI. They were subjected to thorough history taking, complete clinical examination, investigations including: blood urea and serum creatinine, serum albumin, alanine aminotransferase, aspartate aminotransferase, bilirubin, prothrombin time and activity, international normalized ratio, complete blood count, total leukocytic count, C-reactive protein (CRP), hepatitis C virus antibodies, hepatitis B surface antigen, and pelvic-abdominal ultrasonography.
Results AKI was found in 43.6% of the cirrhotic patients studied. The most predominant type was the prerenal AKI. Hepatorenal syndrome was found in 25.2% of patients. Septic causes included (spontaneous bacterial peritonitis in 24.2% of patients, chest infection in 22.6%, and urinary tract infection in 18.6%). Upper gastrointestinal bleeding was reported in 13% of cases. Postrenal causes were reported in 4.3% of cases, while intrinsic renal causes were found in 1% of cases. In 5.3% of cases, the cause of AKI was unidentified. We found that hemoglobin and serum albumin were significantly lower in patients with AKI compared with those without AKI. We found a significant positive correlation between serum creatinine and each of the following laboratory parameters: total leukocytic count, CRP, and international normalized ratio. On the other hand, we found a significant negative correlation between serum creatinine and hemoglobin and serum albumin. The CRP was the most independent risk factor in our patients.
Conclusion AKI incidence in cirrhotic patients is significantly high. Prerenal AKI is the most predominant type. Sepsis was the most important prerenal causes of AKI in our cirrhotic patients. Anemia, hypoalbuminemia, hyperbilirubinemia, gastrointestinal bleeding, and sepsis increase the risk of AKI among cirrhotic patients.
Keywords: AKI, anemia, cirrhosis, hepatorenal, sepsis
|How to cite this article:|
Lasheen NM, Elsawy AA, Nor Eldin NM, Okasha KM. Acute kidney injury in patients with liver cirrhosis. Tanta Med J 2017;45:192-7
| Introduction|| |
Acute kidney injury (AKI) is a frequent and sometimes devastating syndrome, with high costs to patients and health-care systems ,. In developed countries AKI is seen in 13–18% of all patients admitted to hospital ,. The frequency of AKI amongst inpatients means that it has a major patient and economic impact .
In addition to demonstrating a potent, independent effect on mortality, AKI is associated with a significantly increased length of hospital stay and high financial costs .
AKI is common, harmful, and potentially treatable. Even a minor acute reduction in kidney function has an adverse prognosis. Early detection and treatment of AKI may improve outcomes .
AKI is defined as an increase in serum creatinine by greater than or equal to 0.3 mg/dl within 48 h or an increase in serum creatinine to greater than or equal to 1.5 times baseline, which have occurred within the prior 7 days or urine volume output less than 0.5 ml/kg/h for 6 h .
The causes of AKI can be divided into three categories: prerenal (result from decreased renal perfusion), intrinsic renal, and postrenal causes. Acute tubular necrosis is the most common type of intrinsic AKI in hospitalized patients. The cause is usually ischemic (from prolonged hypotension) or nephrotoxic (from an agent that is toxic to the tubular cells). Postrenal causes result from obstruction of the urinary tract mostly due to prostate enlargement .
Liver cirrhosis is a worldwide medical problem especially in Egypt. It is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue, and regenerative nodules, leading to loss of liver function ,.
AKI is a common complication of cirrhosis and confers a poor prognosis . It occurs in 20% of patients with cirrhosis admitted to hospital . Patients with cirrhosis and renal failure are at high risk for death while waiting transplantation and have an increased frequency of complications and reduced survival after transplantation ,.
Renal impairment in patients with cirrhosis is primarily related to disturbances in circulatory function mainly reduction in systemic vascular resistance due to primary arterial vasodilatation in the splanchnic circulation, triggered by portal hypertension .
In addition, in some patients with cirrhosis, intrinsic renal diseases may be related to the etiologic factors underlying the liver disease. These forms of nephropathy include glomerulonephritis associated with hepatitis B or hepatitis C infection and alcoholic cirrhosis .
Other common causes of renal dysfunction in patients with cirrhosis include hepatorenal syndrome (HRS), infection [especially spontaneous bacterial peritonitis (SBP)], and hypovolemia [mainly due to upper gastrointestinal bleeding (UGIB) and lower gastrointestinal bleeding] .
| Aim|| |
The aim of this work was to study the incidence and causes of AKI in patients with liver cirrhosis.
| Patients and methods|| |
Our study was carried out on 900 cirrhotic patients selected from outpatient clinics, ICU, and wards of Internal Medicine Department of Tanta University Hospitals between September 2015 and February 2015. An informed written consent was obtained from all participants in this research after explanation of the benefits and possible risks of the study. The study carried no risks to the participants as the investigations were non invasive except for the risk of infection during blood sampling that was avoided by complete aseptic technique.
Patients with liver cirrhosis developing AKI (increase in serum creatinine by ≥0.3 mg/dl within 48 h or increase in serum creatinine to ≥1.5 times baseline, which have occurred within the prior 7 days or urine volume <0.5 ml/kg/h for 6 h).
- Patients with known pre-existing chronic kidney disease.
- Patients who underwent renal transplantation.
All patients included in the study were subjected to:
- Thorough history taking.
- Complete clinical examination.
- Investigations including:
- Blood urea and serum creatinine.
- Liver profile: serum albumin, alanine aminotransferase, aspartate aminotransferase, bilirubin, prothrombin time and activity.
- Complete blood count.
- C-reactive protein (CRP).
- Hepatitis C virus antibodies, hepatitis B surface antigen.
- Pelvic-abdominal ultrasonography.
Data analyses were performed using statistical package for the social science (SPSS 10.0; IBM Corp., released 2007, Chicago, USA). Data were fed to the computer and analyzed using IBM SPSS software package, version 20.0. Qualitative data were described using number and percent. Quantitative data were described using the range (minimum and maximum), mean, SD, and median. Significance of the obtained results was judged at the 5% level.
| Results|| |
Our study was conducted on 900 cirrhotic patients 536 (59.6%) men and 364 (40.4%) women, AKI was found in 43.6% of patients. 64.6% of them were men and 35.4% were women. The mean age of the patients who developed AKI was 60.87±7.42 years with a significant increase in the age of AKI patients compared with non-AKI patients as shown in [Table 1].
|Table 1 Comparison between the studied groups according to demographic data|
Click here to view
It was noted that out of the cirrhotic patients, 64 (16.3%) patients who developed AKI were diabetic and 23 (5.9%) patients were hypertensive as shown in [Table 2].
|Table 2 Distribution of acute kidney injury cases according to diabetics mellitus and hypertension|
Click here to view
Prerenal AKI was the most predominant cause. Among our 393 cirrhotic patients who had AKI, 99 (25.2%) patients were diagnosed with HRS. Septic causes of AKI in cirrhotic patients were very important. SBP was found in 24.2%, while chest infection in 22.6%, and urinary tract infection in 18.6%. It is to be noted that some of the cases had mixed infection.
UGIB was found in 13% of cases. Postrenal causes of AKI in our study was 17 (4.3%) cases mostly due to obstructive uropathy.
Four (1%) cases were due to intrinsic renal disease whom diagnosis was confirmed by renal biopsy including: IgA nephropathy, membranous nephropathy, and membranoproliferative glomerulonephritis.
We reported 21 (5.3%) patients of the AKI group in whom the cause of AKI was unidentified by clinical, laboratory, or diagnostic imaging and there was a contraindication for renal biopsy as shown in [Table 3].
We found a significant positive correlation between serum creatinine and each of the following laboratory values: total leukocytic count (TLC), CRP, and international normalized ratio (INR). On the other hand, we found a significant negative correlation between serum creatinine and hemoglobin (Hb) and serum albumin as shown in [Table 4].
|Table 4 Correlation between serum creatinine and different laboratory data on acute kidney injury group|
Click here to view
The multivariate regression analysis for AKI in patients with liver cirrhosis with different parameters shows that the Hb, CRP, TLC, and serum albumin were significant risk factors for the development of AKI. The CRP was the most important independent risk factor in our patients (P=0.000) (odds ratio=5.132) as shown in [Table 5].
|Table 5 The multivariate regression analysis for acute kidney injury with different parameters|
Click here to view
| Discussion|| |
AKI is a common complication of liver cirrhosis and confers a poor prognosis .
Among our 900 cirrhotic patients, AKI was found in 43.6%. The mean age of the patients who developed AKI was 60.87±7.42 years. 64.6% of them were men and 35.4% were women.
According to our data, the prerenal causes of AKI were the most predominant. Prerenal causes include HRS, septic AKI, and hypovolemia caused mainly by UGIB.
In our study, septic causes of AKI were significant. We found that SBP was the cause of AKI in 24.2% of cirrhotic patients, chest infections were found in 22.6%, and urinary tract infection were reported in 18.6% of AKI patients. It is to be noted that some of the cases had mixed infection.
Our data were in agreement with Thabut et al. . In their study, systemic inflammatory response syndrome was observed in 41% of patients with cirrhosis and AKI, in 56% of them with infection. Also, Martín et al.  found that 82.4% of patients with cirrhosis had renal failure. The most frequent cause of renal failure was sepsis.
Among our 393 cirrhotic patients who developed AKI, 99 (25.2%) patients were diagnosed with HRS.
In contrast to our study, Martín et al.  have found that HRS occurred only in 13% of cirrhotic patients. While Salerno et al.  concluded that the incidence of HRS were 18 and 39% at 1 and 5 years, respectively.
Our study has shown that hypovolemia was one of the most important causes of AKI among our cirrhotic patients. This was mainly due to UGIB. Fifty-one (13%) of the AKI patients had UGIB. Most of our patients do not follow the medical instructions regarding routine endoscopic follow-up of esophageal varices. This usually results in severe attacks of UGIB which precipitates hypovolemia and prerenal AKI.
Martín and colleagues ,, reported that prerenal AKI due to hypovolemia caused by UGIB was found in 32 and 69% of cirrhotic patients, respectively.
Our study showed that postrenal AKI was found in 17 of AKI patients (4.3%).
On the other hand, Longacre et al.  reported that an obstruction in urine outflow as the cause of renal failure was found in less than 1% of patients with liver cirrhosis.
In our study, we found that 25 AKI patients were undiagnosed by our routine laboratory or imaging studies.
Among the 25 patients, four (1%) patients with AKI were due to intrinsic renal disease whom diagnosis was confirmed by renal biopsy. We reported membranoproliferative glomerulonephritis in two patients, IgA nephropathy in one patient, and membranous nephropathy in one patient.
In contrast to our study, Martín et al.  found that 9% of cirrhotic patients who developed AKI was due to intrinsic renal disease.
In our study, using clinical, laboratory, and diagnostic imaging, the cause of AKI remained unidentified in 21 (5.3%) patients. In those 21 patients there was a contraindication for renal biopsy. However some of them refused the renal biopsy.
In our study, we found that the presence of anemia, hypoalbuminemia, high INR, leukocytosis, high CRP, and hyperbilirubinemia increase the risk of AKI in cirrhotic patients.
In our study, we found that the Hb level was significantly lower in AKI patients than non-AKI (P=0.012). We also found that there was a significant negative correlation between Hb level and creatinine (P<0.001).
In accordance with our study, Michael et al.  found that anemia was an independent risk factor for AKI (P=0.018).
On the other hand, a retrospective analysis by Powell-Tuck et al.  found that in critically ill patients with AKI stage 1, anemia was not associated with an increased risk of progression to more severe AKI. In this study, they could not find a precise explanation to their results.
According to our data, serum albumin was significantly lower in cirrhotic patients who developed AKI than non-AKI patients (P=0.030). Moreover, there was a significant negative correlation between serum albumin and serum creatinine (P=0.002).
In accordance with our study, Levey et al.  found that hypoalbuminemia was a very important risk factor for the development of renal failure and low GFR is usually associated with low serum albumin (P<0.001).
In our study, we found that INR was significantly higher in our AKI patients (P<0.001). Besides, there was a significant positive correlation between INR and serum creatinine (P=0.001).
In accordance with our study, Schepke et al.  reported that INR was a very important prognostic factor for the development of AKI in cirrhotic patients (P<0.001).
In our study, we found that TLC and CRP as markers of sepsis were significantly higher in cirrhotic patients who developed AKI than those without AKI (P<0.001). There was also a significant positive correlation between CRP and TLC with serum creatinine (P<0.001).
Our data were in agreement with Thabut et al. . In this study CRP and TLC show a significant positive correlation between CRP and TLC with serum creatinine (P<0.001).
In our study, we found that serum bilirubin was significantly higher among AKI patients than those without AKI (P<0.001).
Our data were in agreement with the study of Ravindra et al.  who found that median total bilirubin was statistically higher among ICU patients who developed AKI.
In contrast to our study, Shin et al.  found that total serum bilirubin was positively correlated with estimated glomerular filtration rate and negatively correlated with proteinuria.
In our study, multivariate regression analysis for AKI with different laboratory data shows that the Hb level, CRP, TLC, and serum albumin were significant independent risk factors for the development of AKI. Our results show that CRP was the most significant independent risk factor in our patients (P<0.001).
In contrast to our study, a meta-analysis made by Christian et al.  found that low serum albumin was the most significant independent predictor of AKI development.
| Conclusion|| |
AKI incidence in cirrhotic patients is significantly high. Prerenal AKI is the most predominant type. Septic causes, followed by HRS, and then gastrointestinal bleeding were the most important prerenal causes of AKI in our cirrhotic patients. Anemia, hypoalbuminemia, hyperbilirubinemia, and sepsis increase the risk of AKI among cirrhotic patients. CRP was the most significant independent risk factor for AKI in our cirrhotic patients.
Early detection and management of risk factors for AKI in cirrhotic patients by prompt treatment of infection to avoid septic causes of AKI and routine endoscopic follow-up for cirrhotic patients with esophageal varices to prevent variceal bleeding are recommended.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Li P, Burdmann E, Mehta R. Acute kidney injury: global health alert. Kidney Int 2013; 83:372–376.
National Clinical Guideline Centre. Acute kidney injury: prevention, detection and management of acute kidney injury up to the point of renal replacement therapy. Clinical guidelines (CG169) UK: National Clinical Guideline Centre; 2013.
Kerr M. Insight health economics economics of acute kidney injury. Edinburgh, Scotland: Royal College of Physicians of Edinburgh consensus conference on AKI; 2012.
Pannu N, James M, Hemmelgarn BR, Dong J, Tonelli M, Klarenbach S et al.
Modification of outcomes after acute kidney injury by the presence of CKD. Am J Kidney Dis 2011; 58:206–213.
Uchino S, Bellomo R, Goldsmith D, Bates S, Ronco C. An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Crit Care Med 2006; 34:1913–1917.
Coca SG, Yusuf B, Shlipak MG, Garg AX, Parikh CR. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis 2009; 53:961–973.
Mehta RL, Cerdá J, Burdmann E, Tonelli M, García-García G, Jha V et al.
International society of nephrology’s 0 by 25 initiative for acute kidney injury (zero preventable deaths by 2025): a human rights case for nephrology. Lancet 2015; 385:2616–2643.
Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int 2012; 2:1–138.
Kellum A, Mark U, Unruh ML. Acute kidney injury. BMJ Clin Evid 2011; 2011:pii.
Lehman EM, Wilson ML. Epidemic of HCV infection in Egypt, estimation of past incidence & future morbidity & mortality. J Viral Hepat 2009; 16:650–658.
Roguin A. Rene TheophileHyacintheLaënnec (1781-1826): the man behind the stethoscope. Clin Med Res 2006; 3:230–235.
Du Cheyron D, Bouchet B, Parienti J, Ramakers M, Charbonneau P. The attributable mortality of acute renal failure in critically ill patients with liver cirrhosis. Intensive Care Med 2005; 31:1693–1699.
Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology 2008; 48:2064–2077.
Lassnigg A, Schmidlin D, Mouhieddine M, Bachmann LM, Druml W, Bauer P et al.
Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol 2004; 15:1597–1605.
Chertow GM, Burdick E, Honour M, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 2005; 16:3365–3370.
Ginès P, Schrier R. Renal failure in cirrhosis. N Engl J Med 2009; 361:1279–1290.
Fasolato S, Angeli P, Dallagnase L, Maresio G, Zola E, Mazza E et al.
Renal failure and bacterial infections in patients with cirrhosis: epidemiology and clinical features. Hepatology 2007; 45:223–229.
Thabut D, Massard J, Gangloff A, Carbonelli N, Francoz C, Nguyen-Khac E 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. Hepatology 2007; 46:1872–1882.
Martín M, Guevara M, Torre A, Fagundes C, Restuccia T, Gilabert R et al.
Prognostic importance of the cause of renal failure in patients with cirrhosis. Gastroenterology 2011; 140:488–496.
Salerno F, Gerbes A, Ginès P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Postgrad Med J 2008; 84:662–670.
Nafisseh S, Jennifer A, Rafia B, Wong D, Arroyo F, Gines P et al.
Acute kidney injury and chronic kidney disease in hospitalized patients with cirrhosis. J Investig Med 2011; 59:1244–1250.
Longacre AM, Alsauskas ZC, Ranganna K. Renal failure in patients with cirrhosis. Med Clin N Am 2009; 93:855–869.
Michael H, Rinaldo B, David S, Letis A, Klemz K, Matalanis G et al.
Effect of mean arterial pressure, haemoglobin and blood transfusion during cardiopulmonary bypass on post-operative acute kidney injury. Nephrol Dial Transplant 2012; 27:153–160.
Powell-Tuck J, Crichton S, Raimundo M. Anaemia is not a risk factor for progression of acute kidney injury: a retrospective analysis. Crit Care 2016; 52:1231–1237.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI et al.
A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150:604–612.
Schepke M, Appenrodt B, Heller J, Zielinski J, Sauerbruch T. Prognostic factors for patients with cirrhosis and kidney dysfunction in the era of MELD: results of a prospective study. Liver Int 2006; 26:834–839.
Mehta RL, Maria T, Savage BR, Himmelfarb J, Ikizler TA, Paganini EP et al.
Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int 2004; 66:1613–1621.
Shin H, Yeon S, Rim H. Relationship of serum bilirubin concentration to kidney function and 24-hour urine protein in Korean adults. BMC Nephrol 2011; 12:29.
Christian J, Wolfgang W, Michael J. Hypoalbuminemia and acute kidney injury: a meta-analysis of observational clinical studies. Intensive Care Med 2010; 36:1657–1665.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]