Characterization and Correction of Olfactory Deficits in Kidney Disease

Abstract

Patients with CKD suffer from food aversion, anorexia, and malnutrition. Although olfaction has a significant role in determining food flavor, our understanding of olfactory impairment and of the olfaction-nutrition axis in patients with kidney disease is limited. We quantified odor identification, odor threshold, and subjective odor perception in a cohort (n=161) comprising 36 participants with CKD, 100 participants with ESRD, and 25 controls. We investigated olfaction-nutrition associations in these participants and examined a novel intervention to improve olfaction in ESRD. The mean odor identification score was lower in patients with CKD (75.6%±13.1%; P=0.02) and ESRD (66.8%±15.1%; P<0.001) than in controls (83.6%±11.4%). Patients with ESRD exhibited higher odor threshold than the remaining participants exhibited. All groups had similar scores for subjective smell assessment. In multivariable adjusted analyses, kidney disease associated with increased odds of odor identification deficits (odds ratio, 4.80; 95% confidence interval, 1.94 to 11.89). A reduction in odor identification score was associated with higher subjective global assessment score and lower serum total cholesterol, LDL cholesterol, and albumin concentrations. We found no associations between odor threshold and nutritional parameters. In a proof of concept, 6-week, open-label clinical trial, intranasal theophylline (an epithelial membrane transport and proton secretion activator) increased odor identification score in five out of seven (71%) patients with ESRD. In conclusion, patients with kidney disease have olfactory deficits that may influence their nutritional status. Our preliminary results regarding olfactory improvement using intranasal theophylline warrant confirmation in a randomized controlled trial.

Keywords: chronic kidney disease; end-stage renal disease; malnutrition; olfaction; theophylline.

Figure 1.

Distribution of study participants among olfactory identification functional categories. On the basis of the results of the UPSIT, controls with normal kidney function and patients with CKD and ESRD are categorized as normosmic (Normal, green), mildly hyposmic (Mild, yellow), moderately hyposmic (Moderate, orange), severely hyposmic (Severe, red), or anosmic (black). Shown are the percentages of study participants from each of these cohorts that were assigned to the five functional olfactory categories.

Figure 2.

Kidney disease is a predictor of odor identification defects in univariate and multivariable ordinal logistic regression models. Multivariable 1 denotes a model adjusted for age, race, and sex; multivariable 2 denotes a model adjusted for age, race, sex, current tobacco use, education, and presence of diabetes; multivariable 3 denotes a model adjusted for age, race, sex, education, presence of diabetes, current tobacco use, and for the use of the following medications: aspirin, statin, β blocker, angiotensin inhibitor, vitamin D (nutritional and/or active vitamin D), and cinacalcet; and multivariable 4 denotes a model adjusted for age, race, sex, education, presence of diabetes, current tobacco use, and prior stroke. Shown are the odds ratios (circle for univariate model, triangle for multivariable 1, square for multivariable 2, diamond for multivariable 3, and hexagon for multivariable 4) and 95% confidence intervals. Dotted line marks an odds ratio of 1.

Figure 3.

Percentages of correct answers for food-related and nonfood-related odorants on the odor identification test are higher in the control than in the CKD and ESRD groups.

Figure 4.

Box plots of nutritional markers across the olfactory functional categories in all study participants indicate a worsening of the nutritional status associated with olfactory identification impairment.