Prognosis of AKI in malignant diseases with and without sepsis
© Heeg et al.; licensee BioMed Central Ltd. 2013
Received: 5 August 2013
Accepted: 14 October 2013
Published: 29 October 2013
AKI significantly worsens prognosis of hospitalized patients. This is particularly the case in patients with sepsis. The risk for aquiring sepsis is significantly increased in malignant diseases. Aim of the present retrospective study was to analyze outcomes of tumor patients with sepsis and AKI.
One-thousand and seventeen patients, treated at the ICU of the Department of Nephrology and Rheumatology of the University Hospital Göttingen from 2009 to 2011 were retrospectively analyzed for mortality, sepsis, AKI, need for renal replacement therapy (dialysis) and malignancies.
AKI occurred significantly more frequent in septic than in non-septic patients and in tumor as oposed to non-tumor patients. Mortaliy rates were higher in the respective latter groups. Mortality increased even further if patients suffered from a malignant disease with sepsis and AKI. Mortality rates peaked if dialysis treatment became mandatory. In non-solid tumors 100% of the patients died if they suffered drom sepsis and AKI. This was not the case in solid malignancies (mortality rate 56%).
We conclude that prognosis of tumor patients with AKI and sepsis is very poor. Mortality increases to almost 70% if diaylsis therapy is initiated. Non-solid tumors are associated with a 100% mortality if sepsis and AKI conincide.
KeywordsAKI Sepsis Malignancies Mortality
Acute kidney injury is one of the major problems in today’s clinical medicine. Approximately 1-5% of all hospitalized patients develop AKI during the course of the treatment [1, 2]. Prognosis has not substantially been improved during the last 20–30 years since mortality rates still vary between 30-50% . The poor prognosis is not exclusively induced by AKI per se but does also result from the underlying causes / diseases leading to the decline in kidney function . This is particularly the case with conditions that compromize oxygen and nutrient supply of the whole organism. Among those are heart failure and sepsis. Especially the latter has been identified as one of the most potent risk factors for AKI during intensive care treatment [5, 6]. According to newer data, about 50% of all sepsis patients treated at the ICU suffer from AKI of various severity. The average mortality in sepsis-associated AKI is 50%, even if dialysis treatment has been initiated . The risk for sepsis is being increased by circumstances that affect the immunological response of the host. This typically occurs in malignant diseases. The risk for infectious complications in tumor patients is dramatically increased by bone marrow-toxic chemotherapeutics. Cytotoxic treatment on the other hand can also induce AKI, depending on the type of drugs used for therapy. Maccariello and colleagues analyzed the outcome of ICU patients requiring renal replacement therapy in a prospective manner . The study failed to show an association between mortality and cancer. Nevertheless, mortality was higher if patients suffered from sepsis. The authors did not separately analyze sepsis patients with a malignant disease.
Aim of the this retrospective observational single center study was to analyze outcomes of ICU patients with AKI. Thereby, our particular interest focused on mortality of AKI in malignancies with versus without sepsis.
Patients and setting
The present investigation was a retrospective single-centre analysis. All patients treated at the medical intensive care unit of the department of nephrology and rheumatology (University Hospital of Göttingen, Germany) between 2009 and 2011 were included into the study. It was formally approved by the local ethics committee. Acute kidney injury was defined using the AKIN criteria . Patients with pre-existing ESRD (end stage renal disease) were also included into the study. In these patients, any further acute aggravation of renal dysfunction was defined as AKI if the AKIN criteria were applicable and / or if, for other reasons, dialysis treatment was initiated. Indications for dialysis were the presence of one or more of the following criteria: refractory hyperkalemia, increases of serum creatinine >3 mg/dl and / or of blood urea nitrogen >100 mg/dl at any given time point, and signs / symptoms of fluid overload due to dimished urine output, respectively. As in earlier studies , sepsis was defined as systemic inflammatory response syndrome (SIRS) of infectious origin . Thus, beside fulfilling the criteria of SIRS , all patients showed at least once positive blood cultures for either Gram-positive or Gram-negative bacteria and/or clinical symptoms of an infectous disease. The term malignancy was used in any case of tumor manifestation at the time of treatment at the ICU, regardless of the respective stage of the disease. Thereby, we differentiated between solid and non-solid (hemato-oncological) malignancies. For further clinical characterization a number of different parameters, such as c-reactive protein and the SAPS (Simplified Acute Physiology Score) II scores were documented on a daily basis. All data analyzed in this study were extracted from a database, belonging to the department of Nephrology & Rheumatology of the University Hospital of Göttingen.
All results are expressed as percentages. Differences between 3 or more groups were analyzed by ANOVA. Differences between two groups were analyzed by chi-square test. Significance was considered at p<0.05.
64.3 ±16.6 years
69.5 ±13.5 years
7.4 ±8.1 days
7.4 ±8.4 days
Serum creatinine concentrations in AKI patients before onset of AKI
[Creatinine]Sbefore onset of AKI (mg/dl)
AKI in sepsis
AKI in malignancies
AKI in malignancies with sepsis
Mortality and dialysis
A total number of 341 patients required dialysis treatment. Subgroup analysis revealed the following frequencies of renal replacement therapy in patients with versus without malignant diseases: patients without tumor and without sepsis (28%) 94/341, mortality was 15% (14/94), patients without tumor but with sepsis (28%) 95/341, mortality was 46% (44/95), patients with tumor and without sepsis 6% (20/341), mortality was 20% (4/20), patients with tumor plus sepsis 11% (36/341), mortality was 66% (24/36). The following differences in mortality rates were statistically significant between the groups: no tumor, no sepsis versus no tumor, sepsis p<0.001, tumor, no sepsis versus tumor, sepsis p<0.001, no tumor, sepsis versus tumor, sepsis p=0.037.
Aim of this study was to retrospectively analyze epidemiology and outcome of ICU patients with AKI. Our particular interest focused on AKI mortality rates in malignancies and sepsis.
AKI significantly worsens the prognosis of hospitalized patients [2, 4]. This is particularly the case in the ICU setting in which mortality can increase to 60% . Meanwhile, sepsis / septic shock have been emerged as the most frequent causes of AKI at the intensive care unit . The pathogenesis of sepsis-associated AKI is complex and includes severe hemodynamic alterations with subsequent renal hypoperfusion on one hand, but also systemic activation of the innate and aquired immune response leading to inflammation of the kidney on the other hand [6, 13]. The processes involved shall not be reviewed more in detail at the moment. However, regarding the widespread host-initiated defense mechanisms it becomes understandable that mortality rates gradually increase with progressive severity of the septic syndrome . The prognosis of sepsis-associated AKI also depends on the severity of renal dysfunction per se: Bagshaw and colleagues showed higher AKI mortality rates in septic shock with progressive deterioration of renal function . Interestingely, the authors did not find higher incidences of AKI if the diagnosis of metastatic solid organ cancer was made . Patients with non-solid hematologic malignacies on the other hand developed AKI more frequently. Finally, Plataki and colleagues identified numerous AKI risk factors in septic shock, including delayed initiation antibiotic therapy, intra-abdominal sepsis, and blood product transfusion . A detailed metaanalysis about AKI risk factors in sepsis was published by Cartin-Ceba et al. in 2012 .
As oposed to sepsis, there are generally less data available about epidemiology and outcome of AKI in tumor patients. A recently published cross-sectional analysis of prospectively collected data revealed an AKI incidence of 12% in the latter group of patients . In this study AKI risk was significantly correlated with pre-existing diabetes, hyponatremia, intravenous contrast media administration, chemotherapy, and antibiotics. Sepsis in contrast was not identified as risk factor. Another study evaluated predictors of hospital mortality in critically ill cancer patients according to the severity of renal dysfunction. AKI, as defined by the RIFLE criteria , occurred in 54.2% and mortality increased with progression from ‘R’ to ‘F’ . The results from our study are more or less in line with data from the literature: incidences of AKI were higher in sepsis than in non-septic patients, survival in sepis-associated AKI was lower than in AKI without sepsis or in sepsis without AKI. Frequencies / survival of AKI were higher / lower if a malignant disease was present. Somehow surprising was the observation of comparable mortality rates in non-tumor, non-septic patients with versus without AKI (15%). One might argue that due to the absence of sepsis, the overall morbidity of these patients was lower than in septic individuals.
The first new aspect in our study is related to the conincidence of tumor and sepsis and to survival rates of these patients if dialysis therapy became mandatory. In the latter group, mortality increased to almost 70% (66%) which once had been reported as the average mortality of AKI patients in the 1970s . A second new aspect is related to mortality in tumor patients with sepsis and AKI, regarding the respective nature of the malignant disease. If a non-solid tumor was diagnosed, mortality was 100% as compared to patients with non-solid malignant disease. In those patients mortality was significantly lower (56%). To our knowledge, this observation has never been reported before and we can only speculate whether non-solid tumors affect the outcome by mechanism related to the disease per se or if the poor outcome results from more aggressive therapeutic interventions. In summary, we conclude that prognosis of tumor patients with AKI and sepsis is very poor. We are well aware of the fact that due to the retrospective and single center-based character of our study, conclusions must be drawn with caution. Thus, further prospective analyses are urgently needed.
We conclude that prognosis of tumor patients with AKI and sepsis is very poor, with a mortality of approximately 70% if diaylsis therapy becomes mandatory. Mortality increases even further if patients suffer from a non-solid malignant disease, in this particular group almost 100% of the patients die.
Sepsis and AKI significantly worsen prognosis of tumor patients.
Dialysis treatment in this group is associated with an average mortality of 70%.
Non-solid tumors are associated with mortality rates of 100% if patients suffer from sepsis and AKI.
Acute kidney injury
End-stage renal disease
Intensice care unit
Risk injury failure loss end-stage renal disease
Renal replacement therapy
Sequential organ failure assessment.
- Feldkamp T, Bienholz A, Kribben A: Acute kidney injury. Dtsch Med Wochenschr. 2011, 136: 194-197. 10.1055/s-0031-1272508.View ArticlePubMedGoogle Scholar
- Kribben A, Herget-Rosenthal S, Pietruck F, Philipp T: Acute renal failure–an review. Dtsch Med Wochenschr. 2003, 128: 1231-1236.View ArticlePubMedGoogle Scholar
- Devarajan P: Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol. 2006, 17: 1503-1520. 10.1681/ASN.2006010017.View ArticlePubMedGoogle Scholar
- Singbartl K, Kellum JA: AKI in the ICU: definition, epidemiology, risk stratification, and outcomes. Kidney Int. 2012, 81: 819-825. 10.1038/ki.2011.339.View ArticlePubMedGoogle Scholar
- Murugan R, Kellum JA: Acute kidney injury: what’s the prognosis?. Nat Rev Nephrol. 2011, 7: 209-217. 10.1038/nrneph.2011.13.View ArticlePubMedPubMed CentralGoogle Scholar
- Zarjou A, Agarwal A: Sepsis and acute kidney injury. J Am Soc Nephrol. 2011, 22: 999-1006. 10.1681/ASN.2010050484.View ArticlePubMedGoogle Scholar
- Ricci Z, Ronco C: Pathogenesis of acute kidney injury during sepsis. Curr Drug Targets. 2009, 10: 1179-1183. 10.2174/138945009789753192.View ArticlePubMedGoogle Scholar
- Maccariello E, Valente C, Nogueira L, et al: Outcomes of cancer and non-cancer patients with acute kidney injury and need of renal replacement therapy admitted to general intensive care units. Nephrol Dial Transplant. 2011, 26: 537-543. 10.1093/ndt/gfq441.View ArticlePubMedGoogle Scholar
- Cruz DN, Ricci Z, Ronco C: Clinical review: RIFLE and AKIN–time for reappraisal. Crit Care. 2009, 13: 211-10.1186/cc7759.View ArticlePubMedPubMed CentralGoogle Scholar
- Patschan SA, Patschan D, Temme J, et al: Endothelial progenitor cells (EPC) in sepsis with acute renal dysfunction (ARD). Crit Care. 2011, 15: R94-10.1186/cc10100.View ArticlePubMedPubMed CentralGoogle Scholar
- Marshall JC: Endotoxin in the pathogenesis of sepsis. Contrib Nephrol. 2010, 167: 1-13.View ArticlePubMedGoogle Scholar
- Levy MM, Fink MP, Marshall JC, et al: SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Intensive Care Med. 2001, 2003 (29): 530-538.Google Scholar
- Wan L, Bagshaw SM, Langenberg C, Saotome T, May C, Bellomo R: Pathophysiology of septic acute kidney injury: what do we really know?. Crit Care Med. 2008, 36: S198-S203. 10.1097/CCM.0b013e318168ccd5.View ArticlePubMedGoogle Scholar
- Uchino S, Kellum JA, Bellomo R, et al: Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005, 294: 813-818. 10.1001/jama.294.7.813.View ArticlePubMedGoogle Scholar
- Bagshaw SM, Lapinsky S, Dial S, et al: Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med. 2009, 35: 871-881. 10.1007/s00134-008-1367-2.View ArticlePubMedGoogle Scholar
- Plataki M, Kashani K, Cabello-Garza J, et al: Predictors of acute kidney injury in septic shock patients: an observational cohort study. Clin J Am Soc Nephrol. 2011, 6: 1744-1751. 10.2215/CJN.05480610.View ArticlePubMedGoogle Scholar
- Cartin-Ceba R, Kashiouris M, Plataki M, Kor DJ, Gajic O, Casey ET: Risk factors for development of acute kidney injury in critically ill patients: a systematic review and meta-analysis of observational studies. Crit Care Res Pract. 2012, 2012: 691013-PubMedPubMed CentralGoogle Scholar
- Salahudeen AK, Doshi SM, Pawar T, Nowshad G, Lahoti A, Shah P: Incidence rate, clinical correlates, and outcomes of AKI in patients admitted to a comprehensive cancer center. Clin J Am Soc Nephrol. 2013, 8: 347-354. 10.2215/CJN.03530412.View ArticlePubMedGoogle Scholar
- Bentley W: Towards evidence-based emergency medicine: best BETs from the manchester royal infirmary: BET 3: RIFLE criteria versus acute kidney injury network (AKIN) criteria for prognosis of acute renal failure. Emerg Med J. 2011, 28: 900-901.View ArticlePubMedGoogle Scholar
- Liborio AB, Abreu KL, Silva GBJ, et al: Predicting hospital mortality in critically ill cancer patients according to acute kidney injury severity. Oncology. 2011, 80: 160-166. 10.1159/000329042.View ArticlePubMedGoogle Scholar
- Minuth AN, Terrell JBJ, Suki WN: Acute renal failure: a study of the course and prognosis of 104 patients and of the role of furosemide. Am J Med Sci. 1976, 271: 317-324. 10.1097/00000441-197605000-00007.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2253/13/36/prepub
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