Measuring nephron number in the healthy and diabetic rat kidney in vivo using MRI without contrast agents

We investigated whether physiological oscillations detected by noncontrast resting-state magnetic resonance imaging (rsMRI) can be used to measure functional nephron number, nephron density, or estimated single-nephron glomerular filtration rate (eSNGFR) in vivo. We further investigated whether the observed oscillations below 0.05 Hz reflect tubuloglomerular feedback (TGF). First, we compared features of spectral power of oscillations in rsMRI with total nephron number, nephron density, glomerular filtration rate (GFR), and eSNGFR in healthy Sprague-Dawley rats (n = 20). We then compared features of spectral power to total nephron number in Zucker Diabetic Sprague-Dawley (ZDSD) rats (n = 8) with type-2 diabetes. Finally, we tested the hypothesis that spectral features associated with nephron number reflect TGF by comparing spectra before and after furosemide infusion, which blocks the Na-K-2Cl cotransporter required for TGF and attenuates TGF oscillations. In healthy rats, the median power of rsMRI oscillations below 0.05 Hz in the kidney cortex was significantly correlated (P < 0.05) with nephron number in all animals (R² = 0.68) and within sex groups (R², males = 0.71; R², females = 0.73). Median power in this range was inversely correlated with eSNGFR (P < 0.05, R² = 0.39). No spectral features were correlated with nephron density or GFR. In ZDSD rats with confirmed pathology, total power between 0.015 and 0.045 Hz was significantly correlated with nephron number (R² = 0.59, P < 0.05). In both male and female rats, furosemide caused a significant attenuation of power in rsMRI spectral peaks below 0.05 Hz throughout the cortex (P < 0.05). This work demonstrates the noninvasive, in vivo measurement of nephron number in healthy and diabetic rats using rsMRI, and the potential application of rsMRI to detect TGF-associated physiological fluctuations.NEW & NOTEWORTHY We previously showed that resting-state magnetic resonance imaging (rsMRI) detects spontaneous physiological oscillations in rat and human kidneys, potentially reflecting autoregulation mechanisms. Here, we apply rsMRI and show that the features of these oscillations can be used to measure nephron number in healthy and diabetic rats, and are associated with the tubuloglomerular feedback mechanism. Because the rsMRI scan is short (∼10 min) and noninvasive, it might be rapidly translated to measure nephron number and function in the clinic.