Urea transporters and sweat response to uremia

Abstract

In humans, urea is excreted in sweat, largely through the eccrine sweat gland. The urea concentration in human sweat is elevated when compared to blood urea nitrogen. The sweat urea nitrogen (UN) of patients with end‐stage kidney disease (ESRD) is increased when compared with healthy humans. The ability to produce sweat is maintained in the overwhelming majority of ESRD patients. A comprehensive literature review found no reports of sweat UN neither in healthy rodents nor in rodent models of chronic kidney disease (CKD). Therefore, this study measured sweat UN concentrations in healthy and uremic rats. Uninephrectomy followed by renal artery ligation was used to remove 5/6 of renal function. Rats were then fed a high‐protein diet to induce uremia. Pilocarpine was used to induce sweating. Sweat droplets were collected under oil. Sweat UN was measured with a urease assay. Serum UN was measured using a fluorescent ortho‐pthalaldehyde reaction. Immunohistochemistry (IHC) was accomplished with a horseradish peroxidase and diaminobenzidine technique. Sweat UN in uremic rats was elevated greater than two times compared to healthy pair‐fed controls (220 ± 17 and 91 ± 15 mmol/L, respectively). Post hoc analysis showed a significant difference between male and female uremic sweat UN (279 ± 38 and 177 ± 11 mmol/L, respectively.) IHC shows, for the first time, the presence of the urea transporters UT‐B and UT‐A2 in both healthy and uremic rat cutaneous structures. Future studies will use this model to elucidate how rat sweat UN and other solute excretion is altered by commonly prescribed diuretics.

Physiological mechanisms determining eccrine sweat composition

“…While urea is a small molecule able to diffuse through and/or between cell walls, recent literature suggests that eccrine glands may express localized urea transporter subtypes (Keller et al 2016;Na et al 2019;Xie et al 2017). The expression of urea transporter 1 isoform 1 (UT-1) at the transcriptome and proteome level suggests the facilitation of transmembrane urea movement (Keller et al 2016;Xie et al 2017).…”

“…While urea is a small molecule able to diffuse through and/or between cell walls, recent literature suggests that eccrine glands may express localized urea transporter subtypes (Keller et al 2016;Na et al 2019;Xie et al 2017). The expression of urea transporter 1 isoform 1 (UT-1) at the transcriptome and proteome level suggests the facilitation of transmembrane urea movement (Keller et al 2016;Xie et al 2017). UT-A1 and UT-B1 protein expression and localization have been found in cells of both the secretory coil (clear cells) and duct (Keller et al 2016), with significantly higher mRNA expression in uremic patients compared with normal controls (Xie et al 2017).…”

“…The expression of urea transporter 1 isoform 1 (UT-1) at the transcriptome and proteome level suggests the facilitation of transmembrane urea movement (Keller et al 2016;Xie et al 2017). UT-A1 and UT-B1 protein expression and localization have been found in cells of both the secretory coil (clear cells) and duct (Keller et al 2016), with significantly higher mRNA expression in uremic patients compared with normal controls (Xie et al 2017). These findings suggest that with excess urea production, there may be an active mechanism of urea excretion through sweat.…”

The Expression of AQP5 and UTs in the Sweat Glands of Uremic Patients

“…The structure of human sweat glands has some similarity with the convoluted tubules of the kidney and the composition of sweat is very similar with urine, also containing potassium, sodium, urea nitrogen, creatinine, uric acid, and other metabolic waste [ 1 ]. According to the fact that urea concentration in the sweat fluid was much higher than the serum level and the sweat urea concentration of CKD patients was dramatically increased [ 4 ], there must have been some mechanism to excrete urea out of the skin. The change of UTs in sweat glands of uremic patients is unclear.…”

“…In addition, urea concentration in the sweat was much higher than the serum, which indicated that sweat is another way of expelling water and metabolic wastes besides urine. In particular, it was found that urea concentration was much higher in the sweat of chronic kidney disease (CKD) patients than that in normal people [ 3 , 4 ], indicating that the sweat glands play an important role in the water and metabolic wastes excretion in CKD patients.…”