Abstract
The aim of this study was to determine the iron (Fe) concentration profile within the lumen of the S2 renal proximal convoluted tubule (PCT) and to resolve whether this nephron segment transported Fe. To do this, we performed in vivo renal micropuncture on Wistar rats, collected PCT tubular fluid from superficial nephrons, and measured Fe concentration. The Fe concentration profile along the S2 PCT suggested significant Fe reabsorption. Proximal tubules were also microperfused in vivo with physiological solutions containing Fe and Zn, Cu, Mn, or Cd. PCTs perfused with 12μmol.l−1 55FeCl3 reabsorbed 105.2±12.7 fmol.mm−1.min−1 Fe, 435±52pmol.mm-1.min−1 Na, and 2.7±0.2nl.mm−1.min−1 water (mean ± SEM; n=19). Addition of ascorbate (1mmol.l−1) to the perfusate did not significantly alter Fe, Na, or water reabsorption. Supplementing the control perfusate with 60μmol.l−1 FeSO4 significantly decreased 55Fe uptake. Recalculating for the altered molar activity following addition of unlabeled Fe revealed a three-fold increase in Fe flux. Addition to the perfusate 12μmol.l−1 CuSO4, MnSO4, CdSO4, or ZnSO4 did not affect Fe, Na, or water flux. In conclusion, (1) in vivo, S2 PCTs of rat reabsorb Fe and (2) Fe is reabsorbed along the PCT via a pathway that is insensitive to Cu, Mn, Cd, or Zn. Together, these data demonstrate for the first time the hitherto speculated process of renal Fe filtration and subsequent tubular Fe reabsorption in a living mammal.
Highlights
Iron (Fe) is an essential metal for life
The Fe concentration measured in serum that had been spun through micropartition columns was 4.5 ± 0.4 μmol.−1 (n = 15) for the 30 kDa cutoff filter and 2.5 ± 0.2 μmol.l−1 (n = 23) for the 10 kDa cutoff filter
The aim of the current study was to determine the Fe concentration in ultrafiltrate collected from the lumen of rodent S2 proximal tubule and to determine whether Fe is reabsorbed by the proximal convoluted tubule (PCT)
Summary
Evolution has harnessed its favorable redox potential, and Fe is a key constituent of numerous essential proteins, including hemoglobin, cytochromes, and NADH-coenzyme Q reductase (Ponka, 1999; Williams, 2012). The discovery of Fe transporter proteins expressed in kidney nephron epithelial cells has led to the suggestion that Fe is reabsorbed by the kidney (Gunshin et al, 1997; Kozyraki et al, 2001; Wolff et al, 2011; Smith et al, 2019). A key piece of knowledge is lacking in support of this suggestion, namely, there are no direct measures of Fe in kidney tubular fluid or ultrafiltrate. In the absence of this fundamental piece of information, the prevailing dogma persists that healthy kidneys do not filter Fe because Fe is tightly bound to transferrin and in the absence of pathology transferrin is not filtered
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