Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have olfactory deficits that correlate with markers of malnutrition, and intranasal theophylline may hold promise as a way to improve olfaction, researchers reported.

Sagar U. Nigwekar, MD, of Massachusetts General Hospital in Boston, and colleagues quantified odor identification, odor threshold, and subjective odor perception in a cohort of 161 individuals, including 36 patients CKD, 100 with ESRD, and 25 controls. The mean odor identification score was significantly lower among patients with CKD (75.6%) and ESRD 66.8%) compared with controls (83.6%), the investigators reported online ahead of print in the Journal of the American Society of Nephrology. Patients with ESRD showed higher odor threshold than the other study participants. The 3 groups had similar scores for subjective smell assessment. In multivariate analyses, kidney disease was associated with 4.8-fold increased odds of odor identification deficits.

The investigators assessed the association between olfaction and nutrition using by subjective global assessment (SGA) score—a validated nutritional assessment tool—and serum levels of nutritional markers. A reduction in odor identification score was associated with higher SGA score and lower serum total cholesterol, LDL cholesterol, and albumin concentrations. They found no associations between odor threshold and nutritional parameters.

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“Our results highlight olfactory deficit as a potential novel mechanism to comprehend malnutrition, as patients with odor identification deficits in our study were noted to have a higher SGA score and lower levels of biochemical measures of nutritional status,” they wrote. “Our findings of patients with CKD demonstrating defects in odor identification and patients with ESRD demonstrating defects in odor identification and odor threshold may facilitate the development of interventions tailored to the severity of underlying kidney disease.”

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The study included a 6-week open-label clinical trial in which 5 (71%) of 7 patients who received intranasal theophylline—an epithelial membrane transport and proton secretion activator—experienced an increase in odor identification score. The researchers concluded that the findings from this pilot study “support further testing of nasal theophylline to alleviate olfactory deficits and malnutrition in patients with kidney disease.”

Decreased capacity and impaired regeneration of olfactory epithelial cells in the presence of uremic toxins are among the possible explanations for olfactory deficits in patients with kidney disease, the authors noted.


Nigwekar SU, Weiser JM, Kalim S, et al. Characterization and correction of olfactory deficits in kidney disease. J Am Soc Nephrol 2017;28.   doi: