Aim: Sexual dimorphisms are evident along the nephron: Females (F) exhibit higher ratios of renal distal to proximal Na + transporters' abundance, greater lithium clearance (C Li ) more rapid natriuresis in response to saline infusion and lower plasma [K + ] vs. males (M). During angiotensin II infusion hypertension (AngII-HTN) M exhibit distal Na + transporter activation, lower proximal and medullary loop transporters, blunted natriuresis in response to saline load, and reduced plasma [K + ]. This study aimed to determine whether responses of F to AngII-HTN mimicked those in M or were impacted by sexual dimorphisms evident at baseline. Methods: Sprague Dawley rats and C57BL/6 mice were AngII infused via osmotic minipumps 2 and 3 weeks, respectively, and assessed by metabolic cage collections, tail-cuff sphygmomanometer, semi-quantitative immunoblotting of kidney and patch-clamp electrophysiology. Results: In F rats, AngII-infusion increased BP to 190 mm Hg, increased phosphorylation of cortical NKCC2, NCC and cleavage of ENaC two to threefold, increased ENaC channel activity threefold and aldosterone 10-fold. K + excretion increased and plasma [K + ] decreased. Evidence of natriuresis in F included increased urine Na + excretion and C Li , and decreased medullary NHE3, NKCC2 and Na,K-ATPase abundance. In C57BL/6 mice, AngII-HTN increased abundance of distal Na + transporters, suppressed proximal-medullary transporters and reduced plasma [K + ] in both F and M. Conclusion: Despite baseline sexual dimorphisms, AngII-HTN provokes similar increases in BP, aldosterone, distal transporters, ENaC channel activation and K + loss accompanied by similar suppression of proximal and loop Na + transporters, natriuresis and diuresis in females and males. K E Y W O R D S angiotensin II, ENaC, female, potassium, proteinuria, sodium transport 2 of 12 | VEIRAS Et Al.

As the most abundant cation in archaeal, bacterial, and eukaryotic cells, potassium (K+) is an essential element for life. While much is known about the machinery of transcellular and paracellular K transport–channels, pumps, co-transporters, and tight-junction proteins—many quantitative aspects of K homeostasis in biological systems remain poorly constrained. Here we present measurements of the stable isotope ratios of potassium (41K/39K) in three biological systems (algae, fish, and mammals). When considered in the context of our current understanding of plausible mechanisms of K isotope fractionation and K+ transport in these biological systems, our results provide evidence that the fractionation of K isotopes depends on transport pathway and transmembrane transport machinery. Specifically, we find that passive transport of K+ down its electrochemical potential through channels and pores in tight-junctions at favors 39K, a result which we attribute to a kinetic isotope effect associated with dehydration and/or size selectivity at the channel/pore entrance. In contrast, we find that transport of K+ against its electrochemical gradient via pumps and co-transporters is associated with less/no isotopic fractionation, a result that we attribute to small equilibrium isotope effects that are expressed in pumps/co-transporters due to their slower turnover rate and the relatively long residence time of K+ in the ion pocket. These results indicate that stable K isotopes may be able to provide quantitative constraints on transporter-specific K+ fluxes (e.g., the fraction of K efflux from a tissue by channels vs. co-transporters) and how these fluxes change in different physiological states. In addition, precise determination of K isotope effects associated with K+ transport via channels, pumps, and co-transporters may provide unique constraints on the mechanisms of K transport that could be tested with steered molecular dynamic simulations.

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With advances in therapeutic interventions, endourology has become standard of care for the treatment of numerous diseases in the field of pediatric urology. However, there remains a lack of agreement and evidence on the optimal approaches and associated complications of endourological treatment of upper urinary tract conditions in children, namely ureteropelvic junction (UPJ) obstruction, primary obstructive megaureter, and nephrolithiasis. While pyeloplasty remains the first-line surgical treatment for pediatric UPJ obstruction, endoscopic retrograde balloon dilatation (ERBD) and endopyelotomy continue to gain traction as less invasive means of treating obstruction, particularly for failed repairs. Studies report success rates ranging from 76–100% although re-stenosis or need for revision surgery is not uncommon. Endourological options for the surgical management of primary obstructive megaureter include ERBD or endoureterotomy, rather than the open option of ureteroneocystotomy with or without tapering. Both have shown long-term success rates ranging from 70–90%, however, there is emerging evidence that these therapies may be associated with a risk of postoperative vesicoureteral reflux. Meanwhile, for stone disease, shock wave lithotripsy (SWL), flexible ureteroscopy (URS), and percutaneous nephrolithotomy (PCNL) are mainstays in the pediatric urologist’s armamentarium. Studies have shown that URS and PCNL have comparable stone-free rates, although PCNL can be associated with increased morbidity. Advancements in technology have led to the use of smaller access sheaths without compromising stone-free rates or increasing long-term complications. The use of mini-PCNL in the adult population holds great potential for use in our pediatric patients. The rise of endourology expertise and improved technology makes it an attractive option that could even be considered as a first-line option for the treatment of various urinary tract conditions. Nevertheless, there is a paucity of evidence on outcomes and complications following its use for treatment of upper urinary tract diseases in children. This review aims to summarize and present results of endourological treatments for pediatric UPJ obstruction, primary obstructive megaureter, and nephrolithiasis, as well as highlight advancements in the field of endourology that may increase its utilization in pediatric urology in the future.