Hyaluronan is required for the renal medulla to maximally concentrate urine

Abstract

Hyaluronan (HA) is strikingly more concentrated in the kidney's medulla than in its cortex, and so we tested whether renal medullary HA was required for the maximal concentration of urine. Male C57 mice were uninephrectomized, catheters implanted into the medullary interstitium of their remaining kidney, and they were fed a gelled diet with free access to water. Urine was collected daily from the metabolic cages. Saline was infused at 50 μl/hr for 5–6 days and then for a 4 day control period. During the next 48 hours, Streptomyces hyaluronidase (HAase) was infused at 0.1U/min in test animals (n=4) while normal saline was continued in control animals (n=2). Mice were NPO in the final 48 hours period. The mice infused with HAase were unable to fully concentrate urine, as measured on the second NPO day (2,351±120 vs 6,320±335 milliosmoles/liter, p=0.0001). Urine electrolyte concentrations were also less in mice infused with HAase: sodium (75±5 vs. 244±96 mM, p=0.05), potassium (260±27 vs. 679±103 mM, p=0.005) and urea (1.7±0.1 vs. 4.5±0.3 M, P=0.0003). These results indicate that renal medullary hyaluronan is required for maximal urine concentration in mice. (HL-088421, HL-088421-S1 and HL51971)