|
 
 |
| ORIGINAL ARTICLE |
|
| Year : 2020 | Volume
: 20
| Issue : 2 | Page : 46-50 |
|
Risk factors and outcomes of acute decompensation in patients with chronic kidney disease
Muzamil Olamide Hassan, Bolanle Aderonke Omotoso, Oluyomi O Okunola, Abubakr Abefe Sanusi, Fatiu Abiola Arogundade
Department of Medicine, Renal Unit, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State, Nigeria
| Date of Submission | 12-Jul-2020 |
| Date of Decision | 17-Sep-2020 |
| Date of Acceptance | 18-Feb-2021 |
| Date of Web Publication | 22-Sep-2022 |
Correspondence Address:
Dr. Muzamil Olamide Hassan
Department of Medicine, Renal Unit, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State
Nigeria
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/njhs.njhs_28_20
Introduction: The occurrence of acute decompensation in patients with background chronic kidney disease (CKD) is very common and further worsens the patient's outcome. Because of the limited data on the risk factors and outcomes of acute-on-chronic kidney failure (ACKF), we sought to assess the common causes of acute decompensation in non-dialytic CKD patients necessitating emergency dialysis and to assess the relationship between these risk factors and outcomes.
Materials and Methods: We analysed the data of adults ACKF patients admitted to the Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, between December 2009 and March 2011. One hundred and sixty-three CKD patients with AKI were recruited. Laboratory data, including complete blood count, biochemical and microbiological analyses, were documented. Two-dimensional and Doppler echocardiography was performed where indicated. Multivariable logistic regression analysis was used to analyse the association between the risk factors for ACKF and in-hospital mortality.
Results: The median age was 39 (28–52) years, with male preponderance (76.7%). The common causes of acute decompensation of CKD identified were heart failure (41.7%), malignant hypertension (39.9%), sepsis (35.6%), nephrotoxins (20.9%) and hypovolemia (16. 9.8%). In-hospital mortality was recorded in 34.4% of the patients. Adjusted odds of in-hospital mortality were significantly increased in the presence of heart failure (odds ratio [OR], 2.93 [95%, 1.14–7.55]; P = 0.026) and malignant hypertension (OR, 3.69 [1.15–11.81]; P = 0.028).
Conclusion: The risk factors for ACKF such as heart failure and malignant hypertension are also the independent predictors of in-hospital mortality. Given the high mortality rates, aggressive management of these precipitants could be life-saving.
Keywords: Acute kidney injury, acute-on-chronic kidney failure, chronic kidney disease, in-hospital mortality
How to cite this article:
Hassan MO, Omotoso BA, Okunola OO, Sanusi AA, Arogundade FA. Risk factors and outcomes of acute decompensation in patients with chronic kidney disease. Niger J Health Sci 2020;20:46-50 |
How to cite this URL:
Hassan MO, Omotoso BA, Okunola OO, Sanusi AA, Arogundade FA. Risk factors and outcomes of acute decompensation in patients with chronic kidney disease. Niger J Health Sci [serial online] 2020 [cited 2023 Jun 1];20:46-50. Available from: http://www.https://chs-journal.com//text.asp?2020/20/2/46/356535 |
| Introduction | |  |
Acute-on-chronic kidney failure (ACKF), defined as a rapid decline in kidney function in patients with pre-existing kidney function, represents an important group of acute kidney injury (AKI) and is a major cause of morbidity and mortality.1-5 It often presents acutely with attendant high mortality, so much so that, when severe enough to require urgent dialysis, associated in-hospital mortality could be as high as 30% or even more.[6]
Because ACKF confers greater risk for progression to end-stage renal disease (ESKD) and mortality,6-8 we determined the common risk factors for ACKF and their impacts on the outcomes in chronic kidney disease (CKD) patients requiring dialysis.
| Materials and Methods | | |
Study design and participants
We conducted a single-center, observational, prospective study of adult non-dialytic CKD patients managed at Renal Unit, Obafemi Awolowo University Teaching Hospital Complex (OAUTHC), Ile-Ife, Nigeria, between December 2009 and March 2011. The study participants included all adults CKD patients (≥18 years) admitted consecutively to the medical wards with a need for the emergency dialysis. The following patients were excluded from the study: Patients without baseline creatinine, with pre-existing end-stage kidney disease, those already on maintenance dialysis and those who had received kidney transplantation in the previous 3 months. The study was conducted in accordance with the declaration of Helsinki and conforms to the STROBE statement for reporting observational studies.
Data collection
We collected the information on the date of hospital admission and discharge from Renal Unit, demographics, etiology of CKD, clinical presentation, dialysis requirement and mortality using the case report form. Laboratory data, including packed cell volume (PCV), urinalysis, biochemical parameters and microbiological assays, were performed in the OAUTHC laboratory as part of the routine standard of care. Aetiology of CKD were defined based on our previously published clinical diagnostic criteria used in categorising aetiological factors for CKD.[9],[10] Baseline serum creatinine (SCr) was defined as the lowest value in the 12 months before hospital admission.[11] Estimated creatinine clearance (at baseline, at discharge and 1-year follow-up) was calculated using Cockcroft-Gault equation, which estimates creatinine clearance on the basis of the serum creatinine, weight and gender.[12]
Definitions
AKI was defined according to the KDIGO definition using serum creatinine measurements and urine output criteria.[13] Sepsis was defined according to the American College of Chest Physicians and the Society of Critical Care Medicine consensus.[14],[15] We defined sepsis as a condition in which the patient met the criteria for systemic inflammatory response syndrome (SIRS) and presented with either a documented (culture result) or suspected infection. Hypovolaemia was defined by medical history and physical examination of vital signs, skin turgor and central venous pressure measurement.[16] Heart failure was defined based on all of the following findings: (1) complaint of dyspnoea or presence of orthopnoea, (2) fine crepitation audible in both lungs, (3) radiographic findings consistent with pulmonary oedema and (4) depressed left ventricular ejection fraction on echocardiography. Malignant hypertension was diagnosed in patient with accelerated hypertension with the features of grade 3 or 4 hypertensive retinopathy on fundoscopy or microscopic haematuria. Nephrotoxicity was defined as any decline in baseline kidney function that is secondary to the use of a nephrotoxic agent (including drugs such as non-steroidal anti-inflammatory drugs [NSAIDs], aminoglycosides and herbal medications) and documented by a physician.
Outcomes
The primary outcome was in-hospital mortality from all causes. The secondary outcomes were recovery of kidney function following AKI diagnosis and progression to ESKD, defined as dialysis dependence for ≥3 months. Participants were adjudged to have met the criteria for kidney recovery if the last available creatinine fell within 50% of the baseline value at admission, without requirement of haemodialysis (HD).[17] Participants were followed up for 1 year and follow-up began from the day of hospitalisation and ended at death, when the patient abandon the follow-up in the clinic or 31st March, 2011, which ever came first.
Statistical analysis
We expressed parametric data as mean ± standard deviation and non-parametric data as median (interquartile range). The Chi-square test was used to compare the categorical variables. The t-test and Mann–Whitney test were used to compare the parametric and non-parametric data, respectively. For the assessment of factors that are related to mortality, we performed unadjusted univariate analysis. Multivariable logistic regression analysis was then used to test significant univariate associations with in-hospital mortality by adjusting for age, gender, baseline estimated glomerular filtration rate (eGFR), number of sessions of HD, length of stay and PCV. Statistical analysis was carried out using the Statistical Package for the Social Sciences software, version 16 (SPSS, Inc., Chicago, IL, USA). P < 0.05 (two-tailed) was considered statistically significant.
Ethical approval for this study (Ethical Committee IRB/IEC 00005422) was provided by the Ethical Committee of Obafemi Awolowo University Teaching Hospital Complex, Ile-Ile, Nigeria, on 9th November 2009.
| Results | | |
Patients' characteristics
One hundred and sixty-three previously diagnosed CKD patients were admitted for AKI-requiring HD during the study period. The median age of the study participants was 39 (interquartile range: 28–52 years, 125 (76.7%) were males, median baseline eGFR was 37 (32–45) ml/min/1.73 m[2], 112 (68.7%) had ≥2 proteinuria and 158 (96.9%) had anaemia (PCV <33%). Median systolic blood pressure and diastolic blood pressure were 160 (140–190) and 100 (90–120), respectively. The causes of CKD are outlined in [Table 1]. The majority of patients had chronic glomerulonephritis (52.8%) and hypertension (28.2%) as the cause of CKD while aetiology was unknown in only 3.1%.
Causes of AKI in CKD patients
The common causes of acute decompensation of CKD identified among the study participants were heart failure (68, 41.7%), malignant hypertension (65, 39.9%), sepsis (58, 35.6%) and nephrotoxins (34, 20.9%), of which majority were herbal remedies and hypovolaemia (16. 9.8%). Based on the cause of acute decompensation, patients were categorised into three groups: Group I (94, 57.7%) had only one acute precipitant, Group II had 2 precipitants (62, 38%) while Group III (7, 4.3%) presented with ≥3 causes of acute decompensation of CKD.
[Table 2] showed the common causes of acute decompensation of CKD. Among patients with heart failure who had mandatory echocardiography, median ejection fraction and fractional shortening were 64.2 (59.2–68.3) % and 32.4 (28.3–36.3) %, respectively. The prevalence of systolic dysfunction was 16.6%, whereas diastolic dysfunction was 62.6%. Forty-five (43.3%) had impaired relaxation, whereas 18 (16.3%) had restrictive pattern. There was no evidence of coronary artery disease. Fifty-eight patients had sepsis on admission. The most common foci of sepsis were urinary tract and lower respiratory tract, whereas the common isolates were Escherichia More Details coli (42.9%) and Staph aureus (21.4%), respectively. | Table 2: Common causes of acute decompensation of chronic kidney disease
Click here to view |
Of the patients that had nephrotoxic agents, 22 (64.7%) received herbal medications and drug-related AKI was observed in 12 (35.3%) patients; NSAIDS were the most common culprit agents (n = 10).
Outcomes
Kidney function recovery and progression to end-stage renal disease
Kidney replacement therapy (KRT) offered was HD, and 107 (65.6%) patients were discharged from the hospital after median HD sessions and length of hospital stay of 3 (2–5) sessions and 2.5 (2.0–3.0) weeks, respectively. Of these 107 patients that survived, 95 (88.8%) recovered their kidney functions (median eGFR: 37 [31–43] ml/min/1.73 m[2] while 12 (11.2%) remained dependent on HD (median eGFR: 9.5 [6.5–11.5] ml/min/1.73 m[2]. After 1 year of follow-up, 68 (41.7%) patients had stable kidney function without requiring KRT. Of the remaining patients, 61 (37.4%) deaths were recorded, 16 (9.8%) progressed to ESKD, whereas 18 (11.0%) patients were lost to follow-up.
Mortality
In-hospital mortality was recorded in 56 (34.4%) of the study cohort, of which 30 (53.6%) occurred within the first 2 weeks of hospitalisation. [Table 3] shows the results of multivariable logistic regression analysis to assess the factors that were associated with in-hospital mortality. Adjusted odds of in-hospital mortality were significantly increased when CKD patients presented with heart failure (OR, 2.93 [95%, 1.14–7.55]; P = 0.026) and malignant hypertension (OR, 3.69 [1.15–11.81]; P = 0.028). One-year post-hospitalisation mortality occurred in only five (3.1%) patients, and this precludes further robust analysis of predictors of 1-year all-cause mortality in the present study. | Table 3: Multivariable analysis of factors associated with in-hospital mortality in patients with acute-on-chronic renal failure
Click here to view |
| Discussion | | |
Although most nephrologists are familiar with the term ACKF, there is, however, a paucity of epidemiological data on ACKF because ACKF patients have not been extensively studied. In the present study, we investigated the aetiology and outcome of patients who presented with ACKF at a tertiary centre in South-west Nigeria. The common causes of ACKF in this study were heart failure, malignant hypertension, sepsis and nephrotoxic agents. The findings are consistent with the results of a hospital-based study which revealed that decreased kidney perfusion (probably from heart failure and hypovolaemia) and sepsis were the common precipitating factors for ACKF in CKD patients.[18] Similarly, other studies in the literature showed that sepsis was the leading cause of AKI.[4],[5],[19],[20] In contrast to a study by Prakash et al.[4] which reported that volume depletion was the precipitating factor for ACKF in 17.7% of their patients, hypovolaemia was diagnosed in 9.8% of cases in the present study. Our result corroborated finding by Prakash et al.[4] which showed that NSAIDs are the most common culprits drug precipitating ACKF.
Considering the clinical outcome of patients with ACKF, all our patients required dialysis and we observed dialysis-dependency in 7.4% of patients with ACKF. This is in contrast to the findings of Hsu et al.[18] that showed that more than 60% of patients became dialysis dependent within 30 days of discharge. Ali et al.[5] in their study showed that 12.5% of cases with ACKF needed permanent KRT. The present study observed that only 11.2% had non-recovery of kidney functions among surviving patients. Fifteen percent of our patients progressed to ESKD after the follow-up period, and this is consistent with previous reports suggesting the high rates of progression to ESRD in patients with acute decompensation of CKD.[11],[18],[19],[20],[21],[22] Available evidence suggests that AKI is a risk factor for CKD, progression of CKD and ESKD.[23] Taken together, our findings suggest that AKI patients with pre-existing CKD have considerably higher risk of ESKD, signifying that occurrence of AKI may accelerate progression of CKD. In fact, the high incidence of recovery of kidney functions observed in this study and low post-hospitalisation mortality after 1-year follow-up further confirmed the report of a previous study which showed that kidney recovery after AKI is associated with a lower risk of death.[24] In the context of the 2012 kidney disease improving global outcome guideline for AKI, these data highlight the need to follow-up and evaluate AKI patients 3 months after an episode of AKI to assess for recovery, CKD development or worsening of pre-existing CKD.[13]
The patients with ACKF had 34.4% in-hospital mortality in the present study, and this is similar to the in-hospital mortality rate of 35% reported by the Madrid acute kidney failure study in patients with pre-existing kidney dysfunction but higher than the figure reported by the Nationwide Inpatient Sample study which showed that 22% of patients with ACKF died in the hospital.[25],[26] The representations of the large part of our study cohort by uraemic patients requiring emergency dialysis coupled with late presentation and prolonged waiting time for dialysis may probably be the reason for high in-hospital mortality in this study. These factors have been well documented as the main reasons for high mortality in AKI[27],[28] and chronic kidney failure patients29-31 in the developing countries.
We found that two major risk factors for ACKF – heart failure and malignant hypertension – also were the independent predictors of in-hospital mortality. It was not surprising that heart failure and malignant hypertension were associated with mortality in this study because: First, the most common cause of death among CKD patients is cardiovascular disease, accounting for approximately half of the deaths;[32],[33] second, the presence of congestive heart failure is strongly associated with early mortality in CKD patients, with the risk of cardiovascular death being much higher than the risk of progression to ESKD; 34 and third, malignant hypertension is an important cause of myocardial dysfunction and major adverse cardiovascular events. The West Birmingham Malignant Hypertension Registry revealed that the most common causes of death in patients with malignant hypertension were kidney failure, stroke, myocardial infarction and heart failure.[35] Even though dialysis can prevent death from uraemia, the presence of electrolyte derangement and fluid overload may adversely affect the prognosis in ACKF patients requiring emergency HD. Therefore, the control of fluid balance and hypertension is very crucial in the management of these patients because fluid overload result in persistent extravascular fluid volume expansion, hypertension and potential ventricular dysfunction.
The limitations of this study include the fact this is a single-centre study. While practice may vary across centres, comprehensive data collection from multiple centres increases generalisability. This is an observational study with the limiting ability to control for the confounders. The relatively smaller sample size prevented certain analyses, such as the predictors of long-term survival as well as the impact of CKD aetiology, which larger sample size would have allowed. Finally, Cockcroft–Gault equation was used to estimate creatinine clearance, and this may underestimate true creatinine clearance in earlier stages of CKD.
In summary, the common causes of acute decompensation in CKD were heart failure, malignant hypertension, infections and nephrotoxins. Our findings suggest that some of the risk factors for ACKF – such as heart failure and malignant hypertension – are also the independent predictors of in-hospital mortality, with 2-fold and 3-fold increase in adjusted odds of death in participants with heart failure and malignant hypertension, respectively. Given that ACKF is associated with high mortality rates, aggressive management of these acute precipitants could be life-saving. With appropriate treatment, kidney recovery was achieved in 65% of cases of ACKF suggesting that kidney function could be sustained in these patients after initial salvage dialysis sessions.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Lameire N, Van Biesen W, Vanholder R. Acute renal failure. Lancet 2005;365:417-30.  |
| 2. | Sharfuddin A, Weisbord SD, Palevsky PM, Molitoris BA. Acute kidney injury. In: Taal MW, Chertow GM, Marsden PA, Skorecki K, Yu AS, Brenner BM, editors. Brenner and Rector's the Kidney. 9 th ed. Philadelphia: Elsevier Saunders; 2012. p. 1044-99. |
| 3. | Lameire N, Van Biesen W, Vanholder R. The changing epidemiology of acute renal failure. Nat Clin Pract Nephrol 2006;2:364-77. |
| 4. | Prakash J, Rathore S, Arora P, Ghosh B, Singh T, Gupta T, et al. Comparison of clinical characteristics of acute kidney injury versus acute-on-chronic renal failure: Our experience in a developing country. Hong Kong J Nephrol 2015;17:14-20. |
| 5. | Ali T, Khan I, Simpson W, Prescott G, Townend J, Smith W, et al. Incidence and outcomes in acute kidney injury: A comprehensive population-based study. J Am Soc Nephrol 2007;18:1292-8. |
| 6. | Hsu CY, Ordoñez JD, Chertow GM, Fan D, McCulloch CE, Go AS. The risk of acute renal failure in patients with chronic kidney disease. Kidney Int 2008;74:101-7. |
| 7. | Rimes-Stigare C, Frumento P, Bottai M, Mårtensson J, Martling CR, Bell M. Long-term mortality and risk factors for development of end-stage renal disease in critically ill patients with and without chronic kidney disease. Crit Care 2015;19:383. |
| 8. | Olowu WA, Adefehinti O, Bisiriyu AL. Hospital-acquired acute kidney injury in critically ill children and adolescents. Saudi J Kidney Dis Transpl 2012;23:68-77. [ PUBMED] [Full text] |
| 9. | Arogundade FA, Sanusi AA, Hassan MO, Akinsola A. The pattern, clinical characteristics and outcome of ESRD in Ile-Ife, Nigeria: Is there a change in trend? Afr Health Sci 2011;11:594-601. |
| 10. | Hassan MO, Arogundade FA, Sanusi AA, Akinbodewa AA, Udo AIA, Akinsola A. Causes of Acute Decompensation in Predialytic Chronic Renal Failure Patients - A Prospective Study. Benin: Book of Abstracts 23 rd NAN Congress; 2011. |
| 11. | Siew ED, Ikizler TA, Matheny ME, Shi Y, Schildcrout JS, Danciu I, et al. Estimating baseline kidney function in hospitalized patients with impaired kidney function. Clin J Am Soc Nephrol 2012;7:712-9. |
| 12. | Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41. |
| 13. | Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2:1-138. |
| 14. | American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864-74. |
| 15. | Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992;101:1644-55. |
| 16. | Richards JB, Wilcox SR. Diagnosis and management of shock in the emergency department. Emerg Med Pract 2014;16:1-22. |
| 17. | Chawla LS, Bellomo R, Bihorac A, Goldstein SL, Siew ED, Bagshaw SM, et al. Acute kidney disease and renal recovery: Consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup. Nat Rev Nephrol 2017;13:241-57. |
| 18. | Hsu CY, Chertow GM, McCulloch CE, Fan D, Ordoñez JD, Go AS. Nonrecovery of kidney function and death after acute on chronic renal failure. Clin J Am Soc Nephrol 2009;4:891-8. |
| 19. | Esezobor CI, Ladapo TA, Lesi FE. Clinical profile and hospital outcome of children with severe acute kidney injury in a developing country. J Trop Pediatr 2015;61:54-60. |
| 20. | Bosan I, Ibrahim A, Oguche S, Tuko M, Abdulrasheed M. Characteristics of acute kidney injury in adult patients in a tertiary health facility in northern Nigeria. J Curr Res Sci Med 2016;2:102-8. [Full text] |
| 21. | Wu VC, Huang TM, Lai CF, Shiao CC, Lin YF, Chu TS, et al. Acute-on-chronic kidney injury at hospital discharge is associated with long-term dialysis and mortality. Kidney Int 2011;80:1222-30. |
| 22. | Prescott GJ, Metcalfe W, Baharani J, Khan IH, Simpson K, Smith WC, et al. A prospective national study of acute renal failure treated with RRT: Incidence, an etiology and outcome. Nephrol Dial Transplant 2007;22:2513-9. |
| 23. | Leung KC, Tonelli M, James MT. Chronic kidney diseases following acute kidney injury-risk and outcome. Nat Rev Nephrol 2013;9:77-85. |
| 24. | Pannu N, James M, Hemmelgarn B, Klarenbach S, Alberta Kidney Disease Network. Association between AKI, recovery of renal function, and long-term outcomes after hospital discharge. Clin J Am Soc Nephrol 2013;8:194-202. |
| 25. | Liaño F, Pascual J. Epidemiology of acute renal failure: A prospective, multicenter, community-based study. Madrid Acute Renal Failure Study Group. Kidney Int 1996;50:811-8. |
| 26. | Waikar SS, Liu KD, Chertow GM. Diagnosis, epidemiology and outcomes of acute kidney injury. Clin J Am Soc Nephrol 2008;3:844-61. |
| 27. | Chijioke A, Makusidi AM, Rafiu MO. Factors influencing hemodialysis and outcome in severe acute renal failure from Ilorin, Nigeria. Saudi J Kidney Dis Transpl 2012;23:391-6. [ PUBMED] [Full text] |
| 28. | Naicker S, Aboud O, Gharbi MB. Epidemiology of acute kidney injury in Africa. Semin Nephrol 2008;28:348-53. |
| 29. | Adejumo OA, Akinbodewa AA, Okaka EI, Alli OE, Ibukun IF. Chronic kidney disease in Nigeria: Late presentation is still the norm. Niger Med J 2016;57:185-9. [ PUBMED] [Full text] |
| 30. | Madala ND, Thusi GP, Assounga AG, Naicker S. Characteristics of South African patients presenting with kidney disease in rural KwaZulu-Natal: A cross sectional study. BMC Nephrol 2014;15:61. |
| 31. | Sylvanus E, Sawe HR, Muhanuzi B, Mulesi E, Mfinanga JA, Weber EJ, et al. Profile and outcome of patients with emergency complications of renal failure presenting to an urban emergency department of a tertiary hospital in Tanzania. BMC Emerg Med 2019;19:11. |
| 32. | Cozzolino M, Mangano M, Stucchi A, Ciceri P, Conte F, Galassi A. Cardiovascular disease in dialysis patients. Nephrol Dial Transplant 2018;33 Suppl 3:iii28-34. |
| 33. | Go AS. Cardiovascular disease consequences of CKD. Semin Nephrol 2016;36:293-304. |
| 34. | Daly C. Is early chronic kidney disease an important risk factor for cardiovascular disease? A background paper prepared for the UK Consensus Conference on early chronic kidney disease. Nephrol Dial Transplant 2007;22 Suppl 9:ix19-25. |
| 35. | Lip GY, Beevers M, Beevers DG. Complications and survival of 315 patients with malignant-phase hypertension. J Hypertens 1995;13:915-24. |
[Table 1], [Table 2], [Table 3]
|
Search Pubmed for