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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 19  |  Issue : 3  |  Page : 95-100

Epidemiology of acute kidney injury in malignant and benign haematological disorders. A tertiary center experience


1 Nephrology and Renal Transplantation Unit, Department of Internal Medicine, Assiut University, Assiut, Egypt
2 Department of Internal Medicine, Assiut University, Assiut, Egypt

Date of Submission08-Apr-2019
Date of Acceptance25-Jun-2019
Date of Web Publication2-Aug-2019

Correspondence Address:
Phd Nephrology Marwa Kamal A Khairallah
Nephrology and Renal Transplantation Unit, Department of Internal Medicine, Assiut University, Assiut 71515, Arab Republic of Egypt
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jesnt.jesnt_16_19

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  Abstract 


Objective Patients with hematological disorders whether benign or malignant are at high risk for acute kidney injury (AKI), which is associated with high morbidity and mortality. We sought to appraise the frequency, predictors, and outcome of AKI in a large cohort study of patients with hematological disorders.
Patients and methods A prospective, observational database was undertaken at a tertiary referral hematological and oncological center hospital. We collected the medical data of in-hospital patients with AKI and hematological disorder between July 2016 and September 2018 who met the criteria for RIFLE (risk, injury, and failure; loss; and end-stage kidney disease) classification and were followed up by a nephrologist.
Results According to RIFLE criteria, 137 (28.5%) patients had AKI. Overall, 35.8% of patients with hematological disorders and AKI were admitted into the ICU. Moreover, 23.4% of the patients with hematological disorders and AKI died, and only 8.4% of the survivors with AKI received renal replacement therapy. Mortality in patients with AKI in hematological disorders was associated with the presence of malignant hematological diseases (odds ratio: 5.36 and P=0.001), underlying kidney diseases (odds ratio: 1.35 and P=0.001), and occurrence of tumor lysis syndrome (odds ratio: 2.87 and P=0.001).
Conclusions AKI in patients with hematological disorders, both benign and malignant disorders, is not uncommon and is associated with increased rates of ICU admission and mortality.

Keywords: acute kidney injury, benign hematological diseases, malignant hematological diseases, tumor lysis syndrome


How to cite this article:
Khairallah MA, Hossam S, Ibrahiem OA. Epidemiology of acute kidney injury in malignant and benign haematological disorders. A tertiary center experience. J Egypt Soc Nephrol Transplant 2019;19:95-100

How to cite this URL:
Khairallah MA, Hossam S, Ibrahiem OA. Epidemiology of acute kidney injury in malignant and benign haematological disorders. A tertiary center experience. J Egypt Soc Nephrol Transplant [serial online] 2019 [cited 2019 Nov 16];19:95-100. Available from: http://www.jesnt.eg.net/text.asp?2019/19/3/95/263897




  Introduction Top


In the past years, many advances have been made in the field of treatment and supportive care of hematological diseases. However, acute kidney injury (AKI) is still considered a serious and frequent complication in patients with hematological diseases [1]. Usually AKI in these patients occur because of several conditions and multiple factors. In addition to being a population particularly susceptible to renal disease, patients with hematological disorders who develop AKI have worse outcomes [2]. The occurrence of AKI adversely affects the patients’ management and outcomes. It is associated with longer ICU stay and duration of mechanical ventilation, lower complete remission rates, high mortality, and costs [3]. The exact frequency of AKI in patients with hematological disorders has been difficult to ascertain in the past given the absence of a universally accepted definition. The RIFLE (risk, injury, and failure; loss; and end-stage kidney disease) classification for AKI is clinically relevant. RIFLE distinguishes three severity categories (risk, injury, and failure) based on glomerular filtration rate or urine output reduction. However, up to our knowledge, data about the frequency, predictors, and outcome of AKI occurring in patients with hematological disorders including both benign and malignant diseases are scarce. Therefore, our study aims to document the epidemiological data including frequency, predictor, renal outcome, and short-term mortality of AKI in patients with hematological diseases in Upper Egypt.


  Patients and methods Top


This prospective observational study was approved by the ethics committee of the institutional review board of our university hospital in Egypt. Patients or surrogate decision makers were given a specific form explaining the study objectives, the observational design, and the anonymous data collection. No data allowing patient identification were collected. We included consecutive adults admitted to our Hematology Department, ICU, and Oncology Institute in the our university hospital, Egypt, between July 2016 and November 2018, with any benign hematological disorders that were either not treated or being treated and newly diagnosed hematological malignancies that were either not treated or being treated with first-line chemotherapy. Patients were admitted to the ICU either from outside the hospital or from one of the previous mentioned departments in the hospital. AKI was diagnosed when the patients met the RIFLE criteria [4]. Decisions regarding the initiation, discontinuation, of renal replacement therapy were taken by nephrologists based on the guidelines from Bellomo and Ronco [5]. Chemotherapy was prescribed by the hematologist in charge of the patient, according to best standard of care. After ICU discharge, all patients were managed in our hospital, and 6-month follow-up data were available for all of them. Patients were classified as a survivor or nonsurvivor and were classified also according to the outcomes of the AKI, such as both recovery of kidney function, chronic kidney disease, and end-stage renal disease.

Data collection

Demographic and baseline data were collected prospectively. AKI stage was assessed based on the worst RIFLE class within 1 week after admission. The clinical, laboratory, and imaging data in each patient were reviewed by the nephrologist, who reached a consensus regarding the diagnosis of AKI. Great care was taken to identify all exposures to nephrotoxic agents. In patients with AKI, hematologist determined the proper drug used in treatment of each individualized case and determine also whether chemotherapy was suboptimal because AKI contraindicated the use of a full-dose regimen and/or the use of one or more classes of chemotherapy agents. Vital signs were obtained 6 months after hospital discharge for all patients. In addition, the kidney status (return back to baseline, become chronic kidney disease, or progress to end-stage renal disease) and serum creatinine at ICU discharge and 6 months after ICU discharge were available.

Statistical analysis

Data were collected and analyzed using Statistical Package for the Social Science (version 20; IBM, Armonk, New York, USA). Continuous data were expressed in the form of mean±SD or median (range), whereas nominal data were expressed in form of frequency (percentage). χ2 test was used to compare the nominal data of different groups in the study, whereas Student t test was used to compare means of different two groups and analysis of variance test for more than two groups in case of normally distributed data, whereas Wilcoxon, Mann–Whitney, and Kruskal–Wallis tests were use in case of not normally distributed data. Multivariate regression analysis was used to determine the independent risk factors for prediction of AKI and outcome in those patients with different hematological diseases. P value was considered significant if less than 0.05.


  Results Top


Analysis of the studied population and patients characteristic

The study included 480 patients with hematological diseases admitted to the Hematology Unit and the Oncology Institute. The patients were divided into 260 (54.2%) patients with benign hematological diseases and 220 (45.8%) patients with malignant hematological diseases. Follow-up data were available during 6 months for all patients. Patient characteristics are reported in [Figure 1] and [Table 1],[Table 2],[Table 3]. The ICU admission among all diseased patients had reached 17.7%, whereas the mortality rate reached 12.9%. The most common hematological malignancy was leukemia, which was found in 25.4%. Overall, 28.5% of the patients fulfilled the AKI criteria. Of the entire studied patients with the disease, 11.7% were in risk stage, 10.4% in injury stage, and 6.5% fulfilled the criteria of the failure stage. Among the patients with AKI, 21.9% had diabetes mellitus, 16.1% had ischemic heart diseases, 21.9% had previous kidney diseases, and 55.5% had been exposed to nephrotoxic agents. Tumor lysis syndrome (TLS) and hypoperfusion, two causes of AKI, accounted for 38% of the cases, and 14.6% of the patients with AKI had hepatitis C virus (HCV) infection. AKI was treated with hemodialysis in eight (5.8%) patients only.
Figure 1 Flow chart of the studied patients.

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Table 1 Classification of the demographic, clinical, laboratory, and outcome data based on presence of acute kidney injury

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Table 2 Renal and clinical outcomes based on stages of acute kidney injury in patients with hematological diseases

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Table 3 Predictors of mortality in patients with acute kidney injury in hematological diseases

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The mortality analysis

Mortality in patients with hematological diseases who developed AKI was associated with increase admission to ICU (35.5%) and with the development of disseminated intravascular coagulation (DIC) (25.8).

Renal and short-term survival analysis based upon the acute kidney injury stages

Short-term survival in patients with hematological diseases was associated with the development of AKI; however, it did not differ in different stages of AKI. Moreover, renal recovery decreased in patients in failure stage (41.9%) than those in the risk stage (85.7%).


  Discussion Top


This is a large prospective study assessing frequency, predictors, and short-term renal outcomes in patients with hematological diseases, both malignant and benign, according to presence or absence of AKI. Based on RIFLE criteria, AKI was present in 28.5% of the patients with hematological disease. AKI required dialysis in 5.3% of cases. Overall, 23.4% of the patients who developed AKI died within 6 months of follow-up. Up to our knowledge, our study is the first to demonstrate the frequency of AKI and renal outcomes in both benign and malignant hematological diseases in Arab world; in addition, previous foreign studies may have underestimated the occurrence of AKI owing to the low sensitivity of other markers of renal insufficiency. In keeping with this possibility, the rate of AKI in malignant hematological diseases (58.2%) ([Figure 2]) in our study was higher than previously published cohort studies of AKI in patients with hematological diseases[6]; however, in both benign and malignant diseases, the frequency of AKI was 28.5%. Patients with hematological diseases often develop AKI owing to several mechanisms including dehydration owing to gastrointestinal toxicity, TLS, and direct nephrotoxicity. In our study, 55.5% of the patients who developed AKI were exposed to nephrotoxic drugs, and the total leukocytic count had a statistically significant higher values in those who developed AKI than in those who did not, which indicated a higher frequency of sepsis in the AKI group. As for the renal outcomes, the full renal recovery occurred in 85.7% in the risk stage, 60% in the injury stage, and 41.9% in the failure stage. The overall renal recovery had reached 79% in the survivors and 25% in the nonsurvivors. Therefore, the overall renal recovery in all patients who developed AKI reached 66.4%. These results were smaller than those reported in other studies, which had reported that the renal recovery occurred in more than 90% of survivors [7]. This could be explained by the presence of some patients who developed chronic kidney disease and did not reach full renal recovery. Our patients were managed jointly by intensivists, nephrologists, and hematologists. This multidisciplinary approach allowed us to evaluate the etiologies of AKI. In agreement with earlier works, the main causes of AKI were nephrotoxicity (55%) and acute tubular necrosis [8],[9],[10]. The next most common etiologies were TLS and hypoperfusion, which contributed to the development of AKI in 38% of our patients. Our study found that high levels of white blood cells were associated with the development of AKI (P<0.001). This high level either reflects high tumor burden in the cases of malignant hematological diseases or severe sepsis as in the cases of benign hematological diseases. These results are similar to others. Another interesting finding in our study was the statistically significant association between HCV and the development of AKI in those patients (P<0.001). Actually, it is well known that HCV is associated with development of various types of glomerulonephritis, and it is also associated with the progression of chronic kidney diseases [11]. In addition to the already known previous data, our results showed that HCV was associated also with the development of AKI without apparent manifestations of glomerulonephritis. This important finding needs further research to identify its reason. Identification of suspected etiologies and associations of AKI is very important to ensure appropriate treatment, such as adequate hydration and urate oxidase therapy to prevent uric acid nephropathy [12]. Another major finding in our study was that dialysis in patients with AKI was associated with improvement in the renal outcome and was associated with increasing survival rate, where 8.5% of the AKI surviving patients had dialysis; however, no one in the AKI nonsurviving group had dialysis sessions. Based upon these findings, we recommend early dialysis in patients with hematological diseases who develop AKI. Unfortunately, we only had one type of renal replacement modality in our hospital, which is the intermittent hemodialysis. Therefore, there were several cases that were unfit for dialysis by this modality owing to severe hypotension.One of the important finding in this study was the increased development of disseminated intravascular coagulation in the patients who developed AKI; however, these findings were not associated with increased short-term mortality, where odds ratio was 2.67, and the P value was 0.03. However, it was associated with increased ICU admission. To the best of our knowledge, this association with AKI has not been reported previously. Previous works focused on short mortality to assess the effect of AKI in patients with hematological malignancies [8],[13],[14],[15]. All studies consistently showed higher mortality rates in the patients with AKI compared with those without AKI. We found that AKI was associated with mortality, even with the recovery of the renal failure and return of the kidney function to its baseline. This effect was evident in patients who did not survive even though the kidney function had returned to its normal levels or just left some renal impairment, which gave the effect of AKI even after its improvement on the mortality. Possible explanation is owing to the lack of knowledge of pharmacokinetics of the drugs in patients with acute renal dysfunction which will decrease the effectiveness of the drugs and chemotherapeutic agents even when full doses and regimens are given. From the aforementioned findings and explanations, we could consider the development of AKI in patients with hematological diseases as a predictor of mortality in those patients. Importantly, our research showed that the etiology influences the prognostic effect of AKI, where TLS was found to increase the risk of mortality in the patients who developed AKI. Moreover, mortality increased in patients with AKI in hematological malignant diseases. These findings could be explained with several explanations. The most important is that the AKI will negatively influence the chemotherapeutic agents’ doses and regimens, which will increase the mortality. Another explanation is that TLS refers to high tumor burden; therefore, early recognition and management of high-risk patients for clinical TLS might improve outcome. Finally, an interesting finding was that despite being increased by the development of AKI, the mortality rates were increased by the deterioration of AKI from the risk stage to failure stage. Therefore, once there is AKI, the mortality rate will increase even if the AKI was just in the risk stage. However, the best renal outcome is with the risk stage. Our study has several limitations. First, it was conducted at a single institution (including the hematology ward nephrology dialysis unit and oncology institution). Our admission policy and patient recruitment patterns may have influenced the findings; in addition, the dialysis decision was taken based upon emergency situations only. Therefore, we recommend early dialysis in patients who develop AKI in hematological diseases especially those who are old, hypertension and had previous kidney diseases, those with TLS, and those with high leukocyte count. Second, renal biopsies were not performed, either because of a high risk of bleeding or because the renal disorder was not severe, which may affect our estimation to some causes of AKI as infiltration of the kidney by malignancy. Third, as various causes of benign and malignant hematological disorders are included in this study we were unable to individualize prognostic factors of each disorder; thus, we could not exclude that AKI was a poor risk in some hematological disorders. The strengths of our study include the gathering of all hematological disorders including both the benign and the malignant disorders which is considered to be an important part in AKI epidemiology leading to improvement in the ongoing practices in those patients.
Figure 2 Frequency of AKI in malignant hematological diseases. AKI, acute kidney injury.

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Acknowledgements

The work was carried out in Assiut University Hospital: Hematology Ward, Renal Dialysis Unit, Intensive Care Unit, and Assiut Oncology Institution.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/ her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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