Urea and maximum water conservation

Urea is said to play a pivotal role in maximal renal water conservation. One must bear in mind, however, that ADH increases the permeability for water and urea in the inner medullary collecting duct (IMCD). Since particles that are permeable do not have a direct influence on water distribution, we reasoned that urea would not be an effective osmole in the IMCD and could only decrease water excretion if it raised the IM tonicity and/or decreased the number of effective osmoles that were excreted. Two series of experiments were performed in 16 hr water-deprived humans: first controls (n=l 1) (urea excretion 226±21 nmol/min, Um 1114 ±24) were compared to chronic fasted subjects (n=4, urea excretion 71±7 Hmol/min, Uosm 745+ 53); second subjects were studied before and after 6 mmol urea po/kg (n=6) (urea excretion 257 ±52 vs 565±57 junol/min). The urine flow rate was similar (0.5±0.01 vs 0.4±0.03 ml/min) as was the non-urea Uosm (587125 vs 590+.25) and non-urea osmole excretion (281±33 vs 253±24 nmol/min), but the urine [urea] was much lower during fasting ( 158⁺29 vs 524⁺23 mM). In the second protocol, the urine flow rate rose (<>.6±(). 1 to 1.1±().()1, p<0.01), the non-urea Un(tm) declined (448±45 to 311±34 mosm/L, p<0.01) and the non-urea osmole excretion rate rose (261±57 vs 337±6() |imol/min, p<0.01) when urea was ingested; there was little change in the urine [urea] (534±21, 439±49 mM). We conclude that variations in urea excretion between 70 and 225 umol/min had no influence on IM tonicity whereas higher (and still physiologic) urea excretion rates led to a fall in IM tonicity.