Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:Initiation of hemodialysis treatment with a thrice-weekly prescription is currently the standard of care irrespective of patients' residual kidney function (RKF), comorbidities, and preferences. RECENT FINDINGS/RESULTS:Each year ∼12 000 Veterans with advanced kidney disease progress to end-stage kidney disease (ESKD) requiring dialysis and comprise greater than 10% of the US incident ESKD population. Dialysis is costly and is associated with impaired health-related quality of life (HRQOL) and high mortality risk, especially in the first year of treatment. Evidence suggests an incremental dialysis transition using twice-weekly hemodialysis provides various benefits, including more dialysis-free time, longer RKF preservation, less vascular access damage, and lower patient burden. Pragmatic studies are needed to inform the efficacy and safety of incremental hemodialysis as a personalized dialysis regimen, and could inform its consideration as a conservation strategy during times of supply shortages. Broadly implementing twice-weekly hemodialysis could also potentially allow more Veterans to receive care within VA-based dialysis units. The VA IncHVets Trial is a pragmatic, multicenter, randomized controlled trial comparing the efficacy and safety of twice-weekly incremental vs. thrice-weekly hemodialysis among Veterans transitioning to ESKD. SUMMARY/CONCLUSIONS:Further research is needed to determine whether incremental hemodialysis is well tolerated, effective, and facilitates a more favorable transition to dialysis.

PURPOSE OF REVIEW/OBJECTIVE:Extremes of weather as a result of climate change are affecting social, economic and health systems. Kidney health is being threatened by global warming while treatment of kidney disease is contributing to increasing resource utilization and leaving a substantial carbon footprint. Improved physician awareness and patient education are needed to mitigate the risk. RECENT FINDINGS/RESULTS:Rising temperatures are changing kidney disease patterns, with increasing prevalence of acute kidney injury, chronic kidney disease and kidney stones. These issues disproportionately affect people suffering from social inequality and limited access to resources. SUMMARY/CONCLUSIONS:In this article, we review the effects of climate change on kidney stones, and acute and chronic kidney injury. Finally, we discuss the impact of renal replacement therapies on the environment and proposed ways to mitigate it.

OBJECTIVE:In people with chronic kidney disease (CKD), hyperphosphatemia is a risk factor for mortality. Though unproven, dietary phosphorus control is considered essential in CKD. Although dietary and serum phosphorus are correlated, phosphorus from plant foods rich in phytate is less bioavailable than from animal and processed foods. Yogurt, valued for its low phosphorus and high protein, may be detrimental in CKD due to animal protein content. Plant-based yogurts (PBYs) might offer similar benefits without the downsides of animal protein, but little is known about their phosphorus content. DESIGN AND METHODS/METHODS:Protein contents and phosphorus additives were gathered from nutrition labels of several PBYs, including almond, cashew, oat, coconut, and soy substrates. Phosphorus content was measured via emission spectrometry by Eurofins (Madison, WI), and the phosphorus-to-protein ratio (PPR) was calculated for each PBY. RESULTS:Phosphorus content was highest in Silk Soy Strawberry, Silk Almond Strawberry, and Siggi's Coconut Mixed Berries, while it was lowest in So Delicious Coconut Strawberry, Oatly Oat Strawberry, Forager Cashew Strawberry, and Kite Hill Almond Strawberry. Ingredient labels revealed that Silk Soy Strawberry, Silk Almond Strawberry, and Oatly Oat Strawberry contained phosphorus additives, and Siggi's Coconut Mixed Berries contained pea protein additives. Though from the same substrate class, So Delicious Coconut Strawberry and Siggi's Coconut Mixed Berries showed significant differences in phosphorus and protein contents. All seven PBYs had higher PPR ratios than dairy yogurts like Stonyfield Organic Oikos Strawberry, Chobani Nonfat Strawberry, and Yoplait Greek Strawberry. CONCLUSION/CONCLUSIONS:Low-PPR foods are important for CKD patients. Siggi's Coconut Mixed Berries had the lowest PPR, making it potentially the most desirable for CKD patients. However, there is high variability in PPR among PBYs with the same substrate; therefore, Delicious Coconut Strawberry had the highest PPR, highlighting the importance of product selection for patients with CKD.

INTRODUCTION/UNASSIGNED:Hyperoxaluria is a risk factor for kidney stone formation and chronic kidney disease progression. The microbiome is an important protective factor against oxalate accumulation through the activity of its oxalate-degrading enzymes (ODEs). In this cross-sectional study, we leverage multiomics to characterize the microbial community of participants with primary and enteric hyperoxaluria, as well as idiopathic calcium oxalate kidney stone (CKS) formers, focusing on the relationship between oxalate degrading functions of the microbiome. METHODS/UNASSIGNED:Patients diagnosed with type 1 primary hyperoxaluria (PH), enteric hyperoxaluria (EH), and CKS were screened for inclusion in the study. Participants completed a food frequency questionnaire recording their dietary oxalate content while fecal oxalate levels were ascertained. DNA and RNA were extracted from stool samples and sequenced. Metagenomic (MTG) and metatranscriptomic (MTT) data were processed through our bioinformatics pipelines, and microbiome diversity, differential abundance, and networks were subject to statistical analysis in relationship with oxalate levels. RESULTS/UNASSIGNED:A total of 38 subjects were recruited, including 13 healthy participants, 12 patients with recurrent CKS, 8 with PH, and 5 with EH. Urinary and fecal oxalate were significantly higher in the PH and the EH population compared to healthy controls. At the community level, alpha-diversity and beta-diversity indices were similar across all populations. The respective contributions of single bacterial species to the total oxalate degradative potential were similar in healthy and PH subjects. MTT-based network analysis identified the most interactive bacterial network in patients with PH. Patients with EH had a decreased abundance of multiple major oxalate degraders. CONCLUSION/UNASSIGNED:The composition and inferred activity of oxalate-degrading microbiota were differentially associated with host clinical conditions. Identifying these changes improves our understanding of the relationships between dietary constituents, microbiota, and oxalate homeostasis, and suggests new therapeutic approaches protecting against hyperoxaluria.

Andersson NW, Wohlfahrt J, Feenstra B, et al. Cumulative incidence of thiazide-induced hyponatremia: a population-based cohort study. Ann Intern Med. 2024;177:1-11. 38109740.

PURPOSE OF REVIEW/OBJECTIVE:Continuous renal replacement therapy (CRRT) is a vital medical intervention used in critically ill patients with acute kidney injury (AKI). One of the key components of adequate clearance with CRRT is the use of anticoagulants to prevent clotting of the extracorporeal circuit. Regional citrate anticoagulation is the most often recommended modality. The term 'citrate toxicity' is used to describe potential adverse effects of accumulation of citrate and subsequent hypocalcemia. However, citrate is itself not inherently toxic. The term and diagnosis of citrate toxicity are questioned in this review. RECENT FINDINGS/RESULTS:Citrate is being increasingly used for regional anticoagulation of the CRRT circuit. Citrate accumulation is infrequent and can cause hypocalcemia and metabolic alkalosis, which are potential adverse effects. Citrate itself, however, is not a toxic molecule. The term 'citrate toxicity' has been used to denote hypocalcemia and metabolic acidosis. However, citrate administration is well known to cause systemic and urinary alkalinization and under certain circumstances, metabolic alkalosis, but is not associated itself with any 'toxic' effects.We review the existing literature and debunk the perceived toxicity of citrate. We delve into the metabolism and clearance of citrate and question current data suggesting metabolic acidosis occurs as the result of citrate accumulation. SUMMARY/CONCLUSIONS:In conclusion, this article calls into question prevailing concerns about 'citrate toxicity'. We emphasize the need for a more nuanced understanding of its safety profile. We recommend discarding the term 'citrate toxicity' in favor of another frequently used, but more meaningful term: 'citrate accumulation'.

BACKGROUND:There are knowledge gaps about factors associated with acute kidney injury (AKI) among COVID-19 patients. To examine AKI predictors among COVID-19 patients, a retrospective longitudinal cohort study was conducted between January 2020 and December 2022. Logistic regression models were used to examine predictors of AKI, and survival analysis was performed to examine mortality in COVID-19 patients. RESULTS:A total of 742,799 veterans diagnosed with COVID-19 were included and 95,573 were hospitalized within 60 days following COVID-19 diagnosis. A total of 45,754 developed AKI and 28,573 AKI patients were hospitalized. Use of vasopressors (OR = 14.73; 95% CL 13.96-15.53), history of AKI (OR = 2.22; CL 2.15-2.29), male gender (OR = 1.90; CL 1.75-2.05), Black race (OR = 1.62; CL 1.57-1.65), and age 65+ (OR = 1.57; CL 1.50-1.63) were associated with AKI. Patients who were vaccinated twice and boosted were least likely to develop AKI (OR = 0.51; CL 0.49-0.53) compared to unvaccinated COVID-19 patients. Patients receiving two doses (OR = 0.77; CL = 0.72-0.81), or a single dose (OR = 0.88; CL = 0.81-0.95) were also less likely to develop AKI compared to the unvaccinated. AKI patients exhibited four times higher mortality compared to those without AKI (HR = 4.35; CL 4.23-4.50). Vaccinated and boosted patients had the lowest mortality risk compared to the unvaccinated (HR = 0.30; CL 0.28-0.31). CONCLUSION/CONCLUSIONS:Use of vasopressors, being unvaccinated, older age, male gender, and Black race were associated with post COVID-19 AKI. Whether COVID-19 vaccination, including boosters, decreases the risk of developing AKI warrants additional studies.

PURPOSE OF REVIEW/OBJECTIVE:Kidney stones affect an increasing proportion of the population. We suggest that these trends are in part influenced by exposure to higher temperatures as a result of climate change and urbanization. The changing epidemiology of kidney stones is a topic worthy of discussion due to the economic and healthcare burden the condition poses as well as the quality-of-life disruption faced by individuals with kidney stones. RECENT FINDINGS/RESULTS:The relationship between heat and kidney stones is well supported. Exposure to high temperatures has been shown to increase risk for stone development within a short time frame. Effects are modified by factors such as sex, comorbid conditions, and population vulnerability and adaptability. Urban heat islands (UHIs) likely exaggerate the effect of increasing global surface temperature. The concentration of UHIs often coincides with historic redlining practices in the United States, potentially contributing to observed disparities in kidney health among minoritized populations. As global surface temperature increases and urbanization trends continue, a greater proportion of the world's population is exposed to significant temperature extremes each year, leading to the expectation that kidney stone prevalence will continue to increase. SUMMARY/CONCLUSIONS:This work describes the effect of increasing global surface temperature as a result of climate change on kidney stone disease and kidney health. These effects may result in further perpetuation of significant kidney stone related social disparities. We suggest strategies to mitigate the effects of heat exposure on stone formation.