Risk of acute kidney injury after lower urinary tract reconstruction with early NSAID therapy: A propensity matched retrospective analysis.

INTRODUCTION: The opioid epidemic response led to increased use of postoperative, non-opioid analgesia. Some pediatric urologists do not routinely use non-steroidal anti-inflammatory drugs (NSAIDs) for fear of causing acute kidney injury (AKI). While previous studies have demonstrated the safety and efficacy of NSAIDs in children, safety after lower urinary tract reconstruction has not been well characterized. OBJECTIVE: ptUsing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for AKI (increase in creatinine ≥0.3 mg/dL or increase in creatinine ≥1.5x baseline or urine output <0.5 mL/kg/hr for 6 h), we hypothesized there would be a difference in the incidence of postoperative AKI between patients who did and did not receive NSAIDs following surgery. STUDY DESIGN: Patients 2-18 years old who underwent lower urinary tract reconstruction (i.e., bladder augmentation and/or creation of a catheterizable channel) from 2009 to 2021 and had documented urine output were retrospectively reviewed. Chronic kidney disease (CKD) stage was calculated from creatinine and cystatin C within 6 months of surgery using the CKiD U25 equations. Patients who received NSAIDs were propensity matched on 11 characteristics with patients undergoing similar surgeries who did not receive NSAIDs. The primary outcome was incidence of AKI within 48 h of surgery. RESULTS: The unmatched cohorts included 243 patients. Propensity matching identified 166 patients in the NSAID arm and 41 in the no NSAID arm. 26 patients with CKD stage 2-3 were included. There was no significant difference in the incidence of postoperative AKI based on any KDIGO criteria (17.1% no NSAID versus 16.3% NSAID, p = 0.87). Median postoperative opioids fell from 0.88 mg/kg in the no NSAID arm to 0.37 mg/kg morphine equivalents in the NSAID arm, although this was not statistically significant. Log-rank testing by Kaplan-Meier analysis demonstrated no difference in time to incidence of low urine output between the groups (p = 0.32). In the whole population not stratified by NSAID use, no differences were seen in AKI between those with and without CKD (16.7% with versus 17.9% without CKD). DISCUSSION: There was no difference in the incidence of postoperative AKI among patients who did and did not receive NSAIDs after lower urinary tract reconstruction, excluding those with advanced CKD. CONCLUSION: These results support that postoperative NSAIDs were an unlikely source of AKI. However, AKI remained a risk following these surgeries, regardless of NSAID use, likely owing to underlying disease, longer operations, and fluid shifts.

Stable potassium isotopes (41K/39K) track transcellular and paracellular potassium transport in biological systems.

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.

Electrolyte and transporter responses to angiotensin II induced hypertension in female and male rats and mice.

AIM: Sexual dimorphisms are evident along the nephron: Females (F) exhibit higher ratios of renal distal to proximal Na+ transporters' abundance, greater lithium clearance (CLi ) 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 CLi , 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.