Measurement of reabsorption by single segments of the human nephron

A widely diffused method to measure the reabsorption by single segments of the nephron in humans is based on water diuresis (WD), assuming that the peak urine flow rate approximates proximal delivery (PD). However, back-diffusion of an unknown volume of solute-free water (CH2O-BD) from lumen to the interstitium even in the absence of antidiuretic hormone (ADH) introduces a significant error in the estimate of PD. We herein describe an improved method that more precisely estimates the rates of segmental reabsorption. It is based on the assumption that the volume back diffusing during WD will not be subtracted when the hypertonicity of the interstitium is dissipated during the action of furosemide (F); hence, it will be estimated by the difference in urine flow rates measured before (V) and at the peak effect of F (Vf), such that CH2O-BD = Vf - V. Therefore, Vf (the urine flow rate during F) is assumed to directly measure PD of filtrate to the distal tubule (DT) during maximal WD. Adding CH2O-BD to the free water excreted during baseline WD (CH2O) yields the total volume (CH2O-T) of solute-free water formed: CH2O-T = CH2O + CH2O-BD. Therefore, the solute-free water generated by the ascending limb of Henle's loop (CH2O-HL) can be separated from that formed by the convoluted DT (CH2O-DT), since the latter is the only free water formed and excreted during F. Therefore CH2O-DT = CH2Of. Subtracting CH2Of from the total yields the free water formed by Henle's loop: CH2O-HL = CH2O-T - CH2Of. A suitable modification of this method allows the estimation of CH2O-HL even during maximal antidiuresis (AD). The present paper describes the theory, discusses its assumptions, the experimental validation by micropuncture experiments in rats, the results in humans, in health and disease, by simple experiments carried out at the bedside. The data show that this new method represents a significant improvement in accuracy with respect to former techniques to estimate segmental reabsorption, and that it can be suitably used to disclose the pathophysiologic derangements of the nephron in a number of diseases.