|Year : 2019 | Volume
| Issue : 4 | Page : 118-123
Intradialytic complications: a poor prognostic factor among patients with lassa fever with acute kidney injury undergoing hemodialysis
Mojeed O Rafiu1, Samuel A Dada2, Chukwuemeka O Azubike1, Sulaiman D Ahmed1, Alphonsus O Aigbiremolen3, Itohan B Alili4, Peter E Akhideno1, Cyril O Erameh1, Ehinomen C Ifada4, Agnes E Aigbiremolen-Alphonsus4, Esther Omonzokpea4, Kelly O Iraoyah1, Joseph Okoeguale5, Ephraim Ogbaini-Emovon6, Sylvanus A Okogbenin5, George O Akpede7, Peter O Okokhere1
1 Department of Medicine, Irrua Specialist Teaching Hospital (ISTH) Irrua, Ambrose Alli University, Nigeria
2 Nephrology Unit, Department of Medicine, Ekiti State University Teaching Hospital, Ado Ekiti, Nigeria
3 Cedar Centre of Health and Development, Ekpoma, Nigeria
4 Nursing Department, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria
5 Department of Obstetric and Gyneacology, Irrua Specialist Teaching Hospital (ISTH), Irrua, Nigeria
6 Institute of Lassa Fever Research and Control, Nigeria
7 Department of Paediatrics, Irrua Specialist Teaching Hospital (ISTH) Irrua, Ambrose Alli University, Nigeria
|Date of Submission||23-Jul-2019|
|Date of Decision||15-Sep-2019|
|Date of Acceptance||06-Oct-2019|
|Date of Web Publication||25-Nov-2019|
Dr. Samuel A Dada
(MBBS,FWACP) Nephrology Unit, Department of Medicine, Ekiti State University Teaching Hospital, Ado Ekiti, 360261
Source of Support: None, Conflict of Interest: None
Background Acute kidney injury (AKI) is a frequent complication of Lassa fever (LF) that is notably associated with poor outcome. The study aimed at evaluating the relationship between the clinical parameters and outcome of hemodialysis-treated patients with AKI complicating LF and to highlight our experience between 2014 and 2018.
Materials and methods This was a descriptive, observational, and retrospective study involving patients with LF complicated by AKI who had hemodialysis at the dedicated dialysis suite located in our hospital between January 2014 and September 2018. Information were extracted from the clinical and laboratory records of the patients during the period under review.
Results A total of 83 patients had 199 sessions of hemodialysis. Male to female ratio was 2.5 : 1. The mean age was 34.3±13.7 years. The mean number of hemodialysis sessions per patient was 2.4±1.5. The frequency of intradialytic complication was 9.6%, whereas hypotension (62.5%) was the commonest. Occurrence of intradialytic complications was significantly associated with mortality (χ2=5.370, d.f.=1, P=0.020). A high incidence of anemia (65.1%) was observed among the patients. Sixteen (19.3%) of the patients died. There was no significant association between age, sex, number of dialysis session or anemia and outcome of LF. Compared with those who died, patients who recovered had significantly higher mean postdialysis diastolic blood pressure (t=2.382, P=0.020).
Conclusion Intradialytic complication is infrequent in dialysis treated LF patients with AKI, but has significant association with mortality.
Keywords: acute kidney injury, hemodialysis, Lassa fever
|How to cite this article:|
Rafiu MO, Dada SA, Azubike CO, Ahmed SD, Aigbiremolen AO, Alili IB, Akhideno PE, Erameh CO, Ifada EC, Aigbiremolen-Alphonsus AE, Omonzokpea E, Iraoyah KO, Okoeguale J, Ogbaini-Emovon E, Okogbenin SA, Akpede GO, Okokhere PO. Intradialytic complications: a poor prognostic factor among patients with lassa fever with acute kidney injury undergoing hemodialysis. J Egypt Soc Nephrol Transplant 2019;19:118-23
|How to cite this URL:|
Rafiu MO, Dada SA, Azubike CO, Ahmed SD, Aigbiremolen AO, Alili IB, Akhideno PE, Erameh CO, Ifada EC, Aigbiremolen-Alphonsus AE, Omonzokpea E, Iraoyah KO, Okoeguale J, Ogbaini-Emovon E, Okogbenin SA, Akpede GO, Okokhere PO. Intradialytic complications: a poor prognostic factor among patients with lassa fever with acute kidney injury undergoing hemodialysis. J Egypt Soc Nephrol Transplant [serial online] 2019 [cited 2020 Apr 9];19:118-23. Available from: http://www.jesnt.eg.net/text.asp?2019/19/4/118/271562
| Background|| |
Lassa fever (LF) is a viral hemorrhagic fever caused by a single-stranded enveloped RNA virus . The Lassa fever virus (LASV) is the member of Arenaviridae family, which is of most public health importance as a biosafety level 4 pathogen. A multimammate rat (mastomys natalensis) serves as the reservoir host for LASV ,. The virus is transmitted through contact with blood, urine, or excreta of infected rats or the body fluid of infected human . LF is endemic in West African subregions ,. The mortality of LF is 10–20% but can be as high as 65% in hospital outbreaks ,,. Sporadic cases of LF are seen all year round in endemic areas with regular outbreaks in Nigeria, Liberia, Guinea, Sierra Leone, and other countries in the region ,. These outbreaks have devastating health and socioeconomic implications ,. Beyond the endemic region for the disease, LF had been exported outside Africa to USA, Canada, Europe, and Asia, and hence is a potential global menace ,,,.
The clinical spectrum of LF disease ranges from asymptomatic to fulminant multisystemic affectation. The case fatality rate of LF from a retrospective review at lrrua Specialist Teaching Hospital, Edo, State, Nigeria, a dedicated treatment center, for the disease was 24% . Acute kidney injury (AKI) is a known and frequent complication of LF that is specifically associated with poor outcome . A previous study showed that the prevalence of AKI among patients treated for LF in lrrua Specialist Teaching Hospital from January 2011 to December 2015 was 28% whereas the case fatality rate in patients with LF with AKI was reported to be 60% . In that report, elevated serum creatinine among other parameters was found to be an independent predictor of death in LF, whereas the normalization of serum creatinine was beneficial and associated with recovery .
Irrua Specialist Teaching Hospital pioneered the use of hemodialysis to treat patients with LF with AKI in Nigeria in 2010. The observed mortality rate in patients with LF with AKI where hemodialysis was indicated before this period was 100%.
In West Africa, where LF is endemic, very few hospitals have facilities to manage patients with LF. However, in Nigeria, till date, our center manages the largest burden of the disease and dialyzes the largest pool of affected patients. There is scarcity of studies on hemodialysis in patients with LF, specifically, and in viral hemorrhagic fevers, generally. The study was aimed at evaluating the outcome of the patients in relation to the clinical and demographic parameters.
| Materials and methods|| |
This is a retrospective observational study. The study population consists of all consecutive patients who tested positive for LF with polymerase chain reaction (OneStep RT-PCR kit reagents, number 210210 or 210212; Qiagen, Hilden, Germany) , who developed AKI and had hemodialysis at the dedicated Dialysis Suite of Irrua Specialist Teaching Hospital from January 1, 2014 to September 30, 2018. Hemodialysis was done with Nipro Surdial 55 plus (Nipro Europe Goup, Companies Blokhuisstraat Mechelen, Belgium), Fresenius 4008B (Fresenius Medical Care Australia Pty Ltd., Northpoint, North Sydney), and Gambro AK 98 (Gambro Lundia AB, Magistratsvagen, LuN, Sweden) Hemodialysis machines.
Irrua Specialist Teaching Hospital is located in Edo State, the South-South geopolitical region of Nigeria. The hospital has an institute of Lassa fever Research and Control with dedicated treatment facility, comprising isolation ward, laboratory, training center, and dialysis unit. The facility receives referral from all over Nigeria.
After clinical evaluations, blood samples were drawn at presentation to establish diagnosis of LF and determine baselines of other relevant laboratory parameters. Blood samples were taken daily for laboratory analysis to monitor the progress of the patients. Baur, biochemical electronics SP-2000 spectrophotometer was used for electrolyte assays (Baur, Grevenbroich Germany), an Erma PCE-210N automated blood cell counter for hematology (Erma, Tokyo, Japan), and an ELITech Clinical Systems Selectra Pro S chemistry analyzer (ELITechGroup, Dieren, the Netherlands) for other blood chemistry.
The vital signs of the patients were measured and recorded hourly. AKI was diagnosed by nephrologists using Kidney Disease Improving Global Outcome definition, which is increase in serum creatinine by greater than or equal to 0.3 mg/dl (26.5 μmol/1) within 48 h, or an increase in serum creatinine greater than or equal to l.5 of baseline value, which was known or presumed to have occurred within the preceding 7 days, or a urine output of less than 0.5 ml/kg body weight/hour for up to or more than 6 h .
Hemodialysis was instituted if azotemia or oliguria (urine output <30 ml/h) did not resolve despite conservative management or if patients developed uremic symptoms. Intradialytic hypotension was defined as systolic blood pressure (BP) less than 90 mmHg and or diastolic BP less than 60 mmHg.
Data were extracted from dialysis unit record and entered into statistical package for social sciences version 21 (IBM Corp., Armonk, NY, USA). Mean was used to summarize continuous variable. χ2 was used to test associations between selected variable, whereas paired sample t-test was used to examine the relationship between predialysis and postdialysis continuous variables. Level of significance was set at P less than 0.05. Tables and charts were drawn as appropriate to present data.
| Result|| |
Eighty-three (83) patients with confirmed LF complicated by AKI had 199 sessions of hemodialysis during the period under review. Most patients were adults [78(94.0%)], whereas only two (2.4%) were children, and the age group most affected was 20–39 years (63.9%). Male constitute ∼two-thirds of the patient population [52(62.7%)], as illustrated in [Table 1].
|Table 1 Clinical characteristic and laboratory parameters among the patients|
Click here to view
The median number of hemodialysis session was 2.0, whereas most patients (81.9%) had between one to three treatment sessions (Figure 1).
As illustrated in [Table 2], there was a slight nonstatistically significant decrease in mean systolic post dialysis BP [odds ratio: 0.795; 95% confidence interval: 3.583–8.358, P=0.429], with a marginal increase in the mean diastolic BP.
A large number of patients (65.1%) had anemia [defined operationally as hemoglobin level of <10 g/dl (packed cell volume (PCV) <30%)], whereas the mean PCV of the patients was 30.2%. Compared with the male, the female patients have non-statistically significant lower mean value of PCV (31.5 vs 27.9%, P=0.082).
Few patients had intradialytic complications, as summarized in [Figure 2]; however, the most frequent was hypotension. Sixteen patients died owing to complications unrelated to hemodialysis but as a result of the primary disease.
|Figure 2 Types and frequency of hemodialysis complications among the patients.|
Click here to view
Compared with patients with intradialytic complication, there was a significant difference between patients with and without intradialytic complications who recovered ([Table 3]). Similarly, patients who recovered had a statistically significant higher mean postdialysis diastolic blood compared with those who died ([Table 4] and[Table 5]). Greater proportion of patients without intradialytic complications recovered compared with those who had complications.
|Table 3 Anemia, intradialysis complications, and outcome of Lassa cases with acute kidney injury|
Click here to view
|Table 5 Relationship between peridialysis parameters and outcome of Lassa fever|
Click here to view
However, we did not find any significant association between variables such as age of the patient, sex, number of dialysis sessions, and presence of anemia with outcome of the patient ([Table 3]).
| Discussion|| |
LF is a public health burden in West Africa subregions, where it is endemic with estimated 300 000 cases and 5000 related death occurring yearly . Following the isolation of the virus from a missionary nurse in a town called Lassa in northeastern Nigeria, there have been yearly epidemic outbreaks and sporadic cases in West Africa subregions . LFV is zoonotic, and the natural host is the multimammate rat of the genus Mastomys natalensis. Transmission to man can occur through ingestion of food contaminated with rodent droppings or direct contact with the blood or body fluid of a person infected by the virus ,. After an incubation period of 3–21 days, the spectrum of disease ranges from subclinical to severe clinical disease ,. In severe cases, patients have multisystemic affectations with renal involvement in form of AKI ,. AKI may arise as a result of prerenal insult, renal tubular injury, and/or interstitial nephritis ,. AKI in LF is specifically associated with poor outcome .
There is little experience with hemodialysis in patients with LF, specifically, and viral hemorrhagic fever, generally, from the literature. This index retrospective observational study presents the experience with the largest pool of patients with LF with AKI who underwent hemodialysis in Nigeria from January, 2014 to September 2018.
Fifty-three (63.8%) of the patients in this index study were within the age range 20–39 years old. This observation was similar to an earlier study conducted to determine the outcome of acute renal failure in 33 patients with hemorrhagic fever with renal syndrome from 1983 to 1995 . In that study, the age range of the participants was similar to the present report; however, it included only 19 patients with AKI who required hemodialysis.
The finding of male preponderance in this study is consistent with the observation from previous study. Neugarten et al.  showed that male sex is associated with an increased incidence of AKI requiring hemodialysis in hospitalized patients, whereas female sex was propounded to be protective. Similar observation in sex difference in the susceptibility to AKI was reported by Hodeify et al.  in evaluating endoplasmic reticulum stress-induced AKI in male and female mice. It was concluded that testosterone was found to play a critical role in sexual dimorphism in AKI susceptibility. These previous studies may explain our similar observation on sex difference in this study.
We observed a slight drop in the mean postdialysis systolic BP and a marginal increase in both mean postdialysis diastolic BP and weight in the patients. These observed slight changes may be explained by the resultant effects of ultrafiltration (fluid removal) during dialysis in patients retaining fluid as a result of the kidney injury, fluid administration as indicated, and change in plasma osmolality ,,.
It is not unexpected that most patients were anemic (n=54, 65.1%, mean PCV=30.2%) considering the disease is an hemorrhagic fever. Similar to the findings of Russmann et al. , we found a nonstatistically significant lower mean PCV among the females compared with the males.
The use of ribavirin, the recommended drug for the treatment of LF, which all the patients were on, can cause anemia as adverse effect ,,. Ribavirin induces anemia through inhibition of intracellular energy metabolism and oxidative membrane damage causing extravascular hemolysis by the reticuloendothelial system . The patients in this study were particularly more susceptible to ribavirin-induced anemia because of their established AKI, high-dose treatment regimen, and age . The etiology of anemia in the patients is likely to be multifactorial beyond the effect of ribavirin as similar observation was reported in Ebola virus disease without the use of ribavirin .
Among the eight (9.6%) patients who had intradialytic complications, systemic hypotension was observed to be the commonest. Occurrence of intradialytic complications was found to have a statistically significant association, with fatal outcome (χ2=5.370, d.f.=1, P=0.020).
In the general dialysis population, systemic hypotension has been reported as the most frequent intradialytic complication regardless of cause of AKI ,,,.The observed association of intradialytic complications with fatal outcome in this index study is most likely explained by the documented strong association of absolute nadir systolic BP less than 90 mmHg (intradialytic hypotension) with mortality ,.
There is scarcity of information in the literature on the outcome of hemodialysis in patients with AKI complicating LF or other hemorrhagic fevers. The case fatality (19.3%) observed in this study is slightly lower than the overall case fatality rate of 24% reported in LF from an earlier study from this center . A higher figure (59.6%) was documented by Buba et al. . The observed difference may be the result of remarkable improvement and better experience in the management of AKI in patients with LF compared with when dialysis therapy was unavailable in the center.
In hemorrhagic fever with renal syndrome, Bren et al.  reported that all the patients with acute renal failure recovered, though only 19 of 25 patients required hemodialysis treatment. It is also of note that the mortality for patients with LF with severe AKI requiring renal replacement therapy reported in this study is less than some previously documented mortalities for AKI in critically ill general population requiring replacement therapy ,,.
| Conclusion|| |
Hemodialysis is beneficial in the management of LF patients with AKI. Although intradialytic complication was observed to be infrequent in these category of patients, when it occurs, it is significantly associated with mortality.
The authors thank all the staff of Dialysis Center, Lassa Fever Isolation Ward, and Institute of Lassa Fever Research and Control of Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria, for their cooperation for this study and dedication to the care of patients with Lassa fever.
The manuscript has been read and approved by all the authors. Each author believes that the manuscript represents honest work.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Grant DS, Khan H, Schieffelin J, Bausch DG. Lassa Fever. Amsterdam, Elsevier: Emerging Infectious Diseases; 2014. 37–59.
Bausch DG, Demby AH, Coulibaly M, Kanu J, Goba A, Bah A et al.
Lassa fever in Guinea: I. Epidemiology of human disease and clinical observations. Vector Borne Zoonotic Dis 2001; 14:269–281.
Fisher-Hoch SP, Tomori O, Nasidi A, Perez-Oronoz GI, Fakile Y, Hutwagner L et al.
Review of cases of nosocomial Lassa fever in Nigeria: the high price of poor medical practice. BMJ 1995; 3117009:857–859.
Schmitz H, Kohler B, Laue T, Drosten C, Veldkamp PJ, Gunther S et al.
Monitoring of clinical and laboratory data in two cases of imported Lassa fever. Microbes Infect 2002; 41:43–50.
Kitching A, Addiman S, Cathcart S, Bischop L, Krahe D, Nicholas M, Coakley J et al.
A fatal case of Lassa fever in London, January 2009. Euro Surveill 2009; 14:19117.
Amorosa V, MacNeil A, McConnell R, Patel A, Dillon KE, Hamilton K et al.
Imported Lassa fever, Pennsylvania, USA, 2010. Emerg Infect Dis 2010; 1610:1598–1600.
Mahdy MS, Chiang W, McLaughlin B, Derksen K, Truxton BH, Neg K. Lassa fever: the first confirmed case imported into Canada. Can Dis Wkly Rep 1989; 1539:193–198.
Okokhere P, Colubri A, Azubike C, Iruolagbe C, Osazuwa O, Tabrizi S et al.
Clinical and laboratory predictors of Lassa fever outcome in a dedicated treatment facility in Nigeria: a retrospective, observational cohort study. Lancet Infect Dis 2018; 186:684–695.
Asogun DA, Adomeh DI, Ehimuan J, Odia I, Hass M, Gabriel M et al.
Molecular diagnostics for lassa fever at Irrua specialist teaching hospital, Nigeria: lessons learnt from two years of laboratory operation. PLoS Negl Trop Dis 2012; 69:e1839.
Kellum JA, Lameire N, Aspelin P, Barsoum RS, Burdmann EA, Goldstein SL et al.
Kidney disease: improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012; 21:1–138.
McCormick JB, Webb PA, Krebs JW, Johnson KM, Smith ES. A prospective study of the epidemiology and ecology of Lassa fever. J Infect Dis 1987; 1553:437–444.
Walker DH, McCormick JB, Johnson KM, Webb PA, Komba-Kono G, Elliott LH et al.
Pathologic and virologic study of fatal Lassa fever in man. Am J Pathol 1982; 1073:349–356.
Bren AF, Pavlovcic SK, Koselj M, Kovac J, Kandus A, Kveder R. Acute renal failure due to hemorrhagic fever with renal syndrome. Ren Fail 1996; 184:635–638.
Neugarten J, Golestaneh L, Kolhe NV. Sex differences in acute kidney injury requiring dialysis. BMC Nephrol 2018; 191:131.
Hodeify R, Megyesi J, Tarcsafalvi A, Mustafa HI, Hti Lar Seng NS, Price PM. Gender differences control the susceptibility to ER stress-induced acute kidney injury. Am J Physiol Renal Physiol 2013; 3047:F875–F882.
Kovacic V, Roguljic L, Kovacic V, Bacic B, Bosnjak T. Ultrafiltration volume is associated with changes in blood pressure in chronically hemodialyzed patients. Ren Fail 2003; 256:945–951.
Testa A, Plou A. Clinical determinants of interdialytic weight gain. J Ren Nutr 2001; 113:155–160.
Bergstrom J, Asaba H, Furst P, Oules R. Dialysis, ultrafiltration, and blood pressure. 1976. Blood Purif 2006; 242:222–226. discussion 26–31
Russmann S, Grattagliano I, Portincasa P, Palmieri VO, Palasciano G. Ribavirin-induced anemia: mechanisms, risk factors and related targets for future research. Curr Med Chem 2006; 1327:3351–3357.
Rendón AL, Núñez M, Romero M, Barreiro P, Martín-Carbonero L, García-Samaniego J et al.
Early monitoring of ribavirin plasma concentrations may predict anemia and early virologic response in HIV/hepatitis C virus-coinfected patients. J Acquir Immune Defic Syndr 2005; 394:401–405.
Afdhal NH. Role of epoetin alfa in maintaining ribavirin dose. Gastroenterol Clin 2004; 331:25–35.
Joob B, Wiwanitkit V. Anemia during hospitalization in the patients with ebola virus disease. Iran J Pathol 2016; 112:189–190.
Sulowicz W, Radziszewski A. Pathogenesis and treatment of dialysis hypotension. Kidney Int 2006; 70:S36–S39.
Palevsky PM, Zhang JH, O’Connor TZ, Chertow GM, Crowley ST, Choudhury D et al.
Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008; 3591:7–20.
Shoji T, Tsubakihara Y, Fujii M, Imai E. Hemodialysis-associated hypotension as an independent risk factor for two-year mortality in hemodialysis patients. Kidney Int 2004; 663:1212–1220.
Islam F, Siddiqui FA, Sabir S, Butt B, Qayyum M, Kiani IG et al.
Frequencies of acute intra-dialytic complications: a single centre experience. Pak Armed Forces Medl 2017; 67:253–258.
Flythe JE, Xue H, Lynch KE, Curhan GC, Brunelli SM. Association of mortality risk with various definitions of intradialytic hypotension. J Am Soc Nephrol 2015; 263:724–734.
Buba MI, Dalhat MM, Nguku PM, Waziri N, Mohammad JO, Bomoi IM et al.
Mortality among confirmed lassa fever cases during the 2015-2016 outbreak in Nigeria. Am J Public Health 2018; 1082:262–264.
Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S et al.
Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005; 2947:813–818.
Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S et al.
Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med 2009; 36117:1627–1638.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]