Ear, Nose & Throat Journal2023, Vol. 102(3) 188–192© The Author(s) 2021Article reuse guidelines:sagepub.com/journals-permissionsDOI: 10.1177/0145561321996628journals.sagepub.com/home/ear
Background: Olfactory function of patients with chronic kidney disease (CKD) has been found to be defective, and patients are often unaware of it. This predisposes them to malnutrition with consequence on health recovery and quality of life. Aim: To assess the olfactory function and determine the pattern of olfactory dysfunction in patients with CKD attending the University College Hospital, Ibadan. Materials and Methods: This was a prospective, hospital-based case–control study of adult patients with CKD. The control group were age- and sex-matched individuals without CKD. Olfactory threshold (OT), odor discrimination (OD), and odor identification (OI) tests were carried out in participants using the “Sniffin Sticks.” Results: There were 100 patients with CKD and 100 healthy controls, age ranges between 19 to 86 years (mean ± SD = 46.3 ± 13.9 years) and 20 to 85 years (mean ± SD = 43.4 ± 14.9 years), respectively. There was no statistically significant difference between cases and control gender distribution (P = .57). The mean olfactory scores were significantly lower among the cases than control, OI 11.2 ± 2.3 and 13.1 ± 1.2 (P < .001), OD 8.5 ± 2.4 and 10.9 ± 1.5 (P < .001), OT 6.4 ± 2.5 and 9.6 ± 1.9 (P < .001), and threshold discrimination and identification 26.0 ± 5.7 and 33.6 ± 3.3 (P < .001), respectively. Prevalent olfactory dysfunction among patients with CKD was 77% (hyposmia 72%, anosmia 5%), and the control was 16% (all hyposmia; P <.001). Conclusion: There was high prevalence of olfactory dysfunction among patients with CKD, and the affectation is more at the central olfactory pathway.
Keywordsolfactory function, chronic kidney disease, Sniffin Sticks test, correlation
Chronic kidney disease (CKD) is of global public health importance and it is on the increase.1 Survivors of the disease condition are on the increase because of advancement in health care delivery and availability of specialist man power.1,2 In addition to treating the primary kidney pathology, the management of the associated complications is important for an improved quality of life.2 Olfaction, which is the ability to perceive and recognize odors, has roles to play in our everyday activities, such as in taste appreciation, food intake, and sensation of danger. Olfaction also plays a vital role in our sexuality and emotions. The disorders of olfaction, which has been reported among patients with CKD in previous studies,3,4 adversely affect their well-being and functions, with resultant decrease in quality of life. The pathophysiology of olfactory dysfunction in patients with CKD has largely been attributed to uraemia.4-6 Uremic toxin causes edema of olfactory epithelia mucosa, thereby reducing its sensitivity to odorous substances, it also affects regeneration of olfactory receptor cells, olfactory bulb, and olfactory center, resulting in olfactory dysfunction4,5 Chronic malnutrition, which is common among patients with CKD due to poor appetite7 and repeated removal of amino acids and other nutrients by dialysis,8 may limit the regeneration and continuous renewal of cells in the olfactory epithelium and thus contribute to olfactory dysfunction. Reduced olfactory discrimination may be related to the slow nerve conduction velocities associated in part with vitamin B12 deficiency found in most patients on dialysis.6,9
Exploring the pattern of olfactory dysfunction among patients with CKD will not only give room for holistic evaluation and management of patients with CKD but also enhance systematic and scientifically based intervention to ameliorate the effect on the affected patients. Therefore, this study aimed to assess the olfactory function to determining the prevalence and pattern of olfactory dysfunction among patients with CKD.
This was a hospital-based case–control study conducted at the medical outpatient clinic, medical wards, and ear nose and throat clinic of the University College Hospital, Ibadan.
Consenting adult patients (≥18years) with clinical and laboratory diagnosis of CKD defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 with or without albuminuria, while the controls were healthy volunteers, who were age- and gender-matched individuals with no clinical or laboratory evidence of CKD. Excluded from the study were individuals having upper respiratory tract infection, symptoms of nasal allergy, congenital olfactory dysfunction, previous nasal surgery/trauma, previous head injury, and smokers or those who smoked and stopped and those who sniff tobacco. Written informed consent was obtained, and interviewer’s assisted questionnaire was administered on all participants. Blood samples were collected to determine serum creatinine, which was used to calculate the eGFR of each participant, and olfactory function test was carried out on the participants with the pen-like odor dispensing devices called “Sniffin Sticks,” which were in 3 test kits for odor identification (OI), odor discrimination (OD), and odor threshold (OT). Three-minute breaks were observed in between the 3 test components.3 Each of these 3 different tests allows for a maximum score of 16 points and together, a total maximum score of 48 points. The sum of OI, OD, and OT values was referred to as threshold discrimination and identification (TDI) score. It ranges from 1 to 48.
Data obtained were analyzed using statistical package (IBM- SPSS statistic, version 20). Demographic variables were represented using tables, while summary statistics were done using means and proportions. The comparison of mean olfactory scores between patients with CKD and healthy controls was carried out using the independent-samples t test. The eGFR were graded as stage 1 CKD ≥ 90, stage 2 CKD 60 to 89, stage 3 CKD 30 to 59, stage 4 CKD 15 to 29, and stage 5 CKD (endstage kidney disease or ESKD) <15. Olfaction was graded as TDI score >30 normosmia, 16 to 30 hyposmia, and ≤15 anosmia, while normal OI, OD, and OT were defined as scores of equal to or greater than 12, 11, and 6, respectively.10,11
There were 100 patients with CKD and 100 age- and gendermatched healthy controls. The age ranged between 19 to 86 and 20 to 85 years, respectively, while the mean age (SD) were 46.3 ± 13.9 and 43.4 ± 14.9 years, respectively (Table 1). There were 56 males and 44 females among the cases, while the control had 52 males and 48 females. There was no statistically significant difference between cases and control gender distribution (P = .57).
The cases consisted of 4 (4.0%) stage 1 CKD, 8 (8.0%) stage 2 CKD, 19 (19.0%) stage 3 CKD, 22 (22.0%) stage 4 CKD, and 47 (47%) stage 5, while all the control had eGFR ≥ 90 (normal), as shown in Figure 1.
The prevalence of olfactory dysfunction (TDI × 30) was 77% in patients with CKD and 16% among the controls (P = .001; Table 1). The distribution of olfactory dysfunction amongpatientswithCKDwere72.0% with hyposmia (TDI score16-30), while 5.0% had anosmia (TDI score ×15; Figure 2). The prevalence of olfactory dysfunction among the control was 16.0% and all were hyposmic. The mean scores for OI, OD, OT, and TDI were significantly lower among the patients with CKD compared to the control (Table 2), while there was no significant difference in the mean scores for OI, OD, OT, and TDI stratified by gender in both cases and controls (Tables 3 and 4).
The study showed high prevalence of olfactory dysfunction among patients with CKD, and it increases with worsening severity of kidney disease. The pattern of olfactory distribution is similar to the report by Sagar et al,12 where 74% of cases with ESKD had olfactory dysfunction, and Griep et al6 who reported 81% of olfactory dysfunction among patients with ESKD who were on renal replacement therapy. Furthermore, Veronika et al13 observed olfactory dysfunction in 64.4% of Indonesia patients with stage 5 CKD. This finding may be explained by the fact that majority of patients with early stages of CKD will be asymptomatic and often may not present in the hospital. Those with early stages of CKD included in this study were those receiving care for other primary illness but were found to have early CKD on routine screening.
The prevalence of olfactory dysfunction among patients with CKD in this study was 77.0%. Majority of the patients with CKD with olfactory dysfunction had hyposmia (72.0%) while 5.0% had anosmia. The pattern of olfactory dysfunction was consistent with that observed by Koseoglu et al3 in Turkey where the prevalence of olfactory dysfunction among patients with CKD was 83.1%, with 74.7% hyposmia and 8.4% anosmia. Veronika et al13 reported a prevalence of olfactory dysfunction among patients with CKD to be 64.4%, while 60.0% were hyposmia and 4.4% were anosmia. The difference in prevalence of olfactory dysfunction in these studies may be due to differences in their sample sizes and the proportion of advanced stages of CKD in the studies. However, all the studies have shown higher prevalence of olfactory dysfunction in patients with CKD than general population.
The prevalence of olfactory dysfunction among the control was 16.0%, and all of them were hyposmic. The relatively high proportion of controls with olfactory dysfunction (16%) suggests that other causes of olfactory dysfunction apart from CKD may be prevalent in the study population. The prevalence of olfactory dysfunction in the control was 16.0%, this was similar to the prevalence of 25% and 19% reported by Murphy et al14 and Bramerson et al15 among the general population in Sweden and United States, respectively.
This study did not only establish that there was higher prevalence of olfactory dysfunction among patients with CKD compared to the control group (about 5-fold), but also that the olfactory dysfunction was more severe in patients with CKD than in the healthy controls. Specifically, there was significantly higher proportion of patients with CKD with hyposmia and anosmia than the healthy controls. Anosmia was more among participants with severe disease (ESKD) than participants with the milder disease, although ESKD represents the largest proportion of patients with CKD, but the prevalence of anosmia was very small compared to their population size and this was similar to the report by Sagar et al.12
The mean score of the test components follows the same pattern in both patients with CKD and controls, with OI being the highest and followed by OD and the least was OT. This pattern was similar to other reports from previous studies.10,11,16 The parts of the olfactory function being assessed also have a direct correlation with pattern of dysfunction, OT assesses the peripheral part of olfactory system, while the OI and OD assess the central olfactory pathway. It is, therefore, obvious that the CKD effect on olfaction is predominantly at central olfactory pathways. Some studies have also reported abnormal OI and OD score without OT affectation among patients with CKD,5,12,17 further confirming central olfactory pathway affectation predominance.
Furthermore, the index study observed that the olfactory functions of females in the control group were better than those of males in the same group. This was similar to the observations by Murphy et al,14 Bramerson et al,15 and Oleszkiewicz et al.18 However, olfactory functions of females with CKD tend to be worse compared to their male counterpart in this study. This may imply that female patients with CKD have worse olfactory dysfunction than do male patients with CKD, although the differences in their mean olfactory test scores were not statistically significant.
The limitations of the study include the inability to recruit equal proportion of CKD stages because most of patients seen at the hospital were those in advanced stages of CKD. This limited the ease of analysis and comparability of data between groups in different stages of CKD. Also, the olfactory test is very subjective; hence, patients’ mood or perception may affect the reliability or validity of the findings. In addition, future work should consider study of gustatory function in patients with CKD, as this has not been well described in literature; similarly, comparing the difference of TDI score before and after dialysis will further strengthen the role of dialysis in olfactory function among patients with CKD.
The study has demonstrated that patients with CKD have prevalence of olfactory dysfunction, and it appears that the affectation was more at the central olfactory pathway. The severity of olfactory dysfunction increases with worsening severity of kidney disease. This finding will serve as basis to ensure olfactory function assessment is included as parts of routine evaluation of patients with CKD, with the aim of improving their overall well-being and quality of life.
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
The author(s) received no financial support for the research, authorship, and/or publication of this article.
O. A. Lasisi https://orcid.org/0000-0003-4439-653X
1 Department of Otorhinolaryngology, University College Hospital, Ibadan, Oyo State, Nigeria
2 Nephrology Unit, Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria
3 Department of Otorhinolaryngology, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria
4 Department of Chemical Pathology, University College Hospital, Ibadan, Oyo State, Nigeria
Received: January 19, 2021; revised: January 19, 2021; accepted: February 1, 2021
Corresponding Author:O.A. Lasisi, MBChB, FWACS, FMCORL, MD, Department of Otorhinolaryngology, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria.Email: akeemlasisi@gmail.com
