Phosphorus Content of Several Plant-Based Yogurts.

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: 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: 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.

Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions.

Introduction: 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: 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: 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: 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.

Climate change and its implications for kidney health.

PURPOSE OF REVIEW: 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: 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: 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.

New use of thiazide diuretics vs. nonthiazide antihypertensive drugs was linked to hyponatremia over 2 y.

SOURCE CITATION: 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.

Predictors of Acute Kidney Injury (AKI) among COVID-19 Patients at the US Department of Veterans Affairs: The Important Role of COVID-19 Vaccinations.

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: 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.

Let's stop talking about 'citrate toxicity'.

PURPOSE OF REVIEW: 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: 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: 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'.

Climate change and kidney stones.

PURPOSE OF REVIEW: 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: 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: 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.

Thiazides do not affect mortality but may reduce CV events vs. nondiuretic antihypertensive drugs at up to 5 y.

SOURCE CITATION: Reinhart M, Puil L, Salzwedel DM, et al. First-line diuretics versus other classes of antihypertensive drugs for hypertension. Cochrane Database Syst Rev. 2023;7:CD008161. 37439548.

Role of Climate Change in Urologic Health: Kidney Stone Disease.

Kidney stones are rising in incidence and prevalence worldwide. Given the temperature dependence of kidney stone presentations, climate change is projected to further increase the burden of disease for individuals and society. PATIENT SUMMARY: This mini-review reports current knowledge on climate change in relation to kidney stone disease. Kidney stones are more common in patients living in parts of the world that are hotter and more humid. Kidney stone problems are also more common after periods of high heat, which have a greater impact on men than on women. As temperatures rise with climate change, it is likely that the occurrence of kidney stones and the costs associated with their diagnosis and treatment will increase as well.

Effect of a high-citrate beverage on urine chemistry in patients with calcium kidney stones.

A well-accepted strategy to prevent kidney stones is to increase urine volume by increasing oral intake of fluids, especially water, to lower supersaturation of the relevant, relatively insoluble salts, and thereby lower the risk of precipitation. Randomized controlled trials have shown that this strategy works. It is inexpensive, safe, and intuitively attractive to patients. However, although any beverage can increase urine volume, and citrus juices can increase urine citrate content and pH, no beverage other than water has been clearly shown by randomized controlled trial to prevent kidney stones. We designed an innovative, palatable, low-calorie, high alkali citrate beverage to prevent kidney stones, called Moonstone. One packet of Moonstone powder, mixed in 500 ml of water, contains 24.5 meq of alkali citrate. We administered one packet twice a day to ten calcium stone formers. Moonstone resulted in an increase in mean 24-h urine citrate and urine pH, and a decrease in supersaturation of calcium oxalate in calcium stone formers compared to an equal volume of water. These changes, comparable to those seen in a prior study of a similar amount of (potassium-magnesium) citrate, will likely be associated with a clinically meaningful reduction in kidney stone burden in patients with calcium stones. The effect to increase urine pH would also be expected to benefit patients with uric acid and cystine stones, groups that we hope to study in a subsequent study. The study preparation was well tolerated and was selected as a preferred preventative strategy by about half the participants. Moonstone is an alternative, over-the-counter therapy for kidney stone prevention.

Healthcare utilization, quality of life, and work productivity associated with primary hyperoxaluria: a cross-sectional web-based US survey.

Primary hyperoxaluria (PH) is a family of ultra-rare, autosomal recessive, metabolic disorders associated with frequent kidney stones, chronic kidney disease and kidney failure, and serious complications due to systemic oxalosis, resulting in significant morbidity. We investigated the burden of PH among affected patients and caregivers. This cross-sectional, web-based survey was used to quantify the burden of PH, in terms of healthcare resource utilization, health-related quality of life, and work productivity and activity impairment among adults (≥ 18 years) with PH and caregivers of children (≤ 17 years) with PH in the US. Among the 20 respondents, there were 7 adults with PH and 13 caregivers of children with PH. Adherence to hyperhydration was noted as the most, or one of the most, difficult aspects of PH by 56% of respondents. Most patients (95%) had experienced painful kidney stone events, one-third had visited the emergency room, and 29% were hospitalized for complications due to PH. Of the 24% of patients on dialysis, all found the procedure burdensome. Adult patients' quality of life was negatively affected across several domains. Most respondents (81%) reported that PH had a negative effect on their finances. Employed adult patients and caregivers, and children with PH, had moderate impairment in work productivity, school attendance, and activity. Anxiety about future PH-related sequelae was moderate to high. These findings highlight the need for improvements in PH medical management. A plain language summary is available in the supplementary information.

Nedosiran in primary hyperoxaluria subtype 3: results from a phase I, single-dose study (PHYOX4).

Nedosiran is an N-acetyl-D-galactosamine (GalNAc)-conjugated RNA interference agent targeting hepatic lactate dehydrogenase (encoded by the LDHA gene), the putative enzyme mediating the final step of oxalate production in all three genetic subtypes of primary hyperoxaluria (PH). This phase I study assessed the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneous nedosiran in patients with PH subtype 3 (PH3) and an estimated glomerular filtration rate  ≥ 30 mL/min/1.73 m2. Single-dose nedosiran 3 mg/kg or placebo was administered in a randomized (2:1), double-blinded manner. Safety/tolerability, 24-h urinary oxalate (Uox) concentrations, and plasma nedosiran concentrations were assessed. The main PD endpoint was the proportion of participants achieving a > 30% decrease from baseline in 24-h Uox at two consecutive visits. Six participants enrolled in and completed the study (nedosiran, n = 4; placebo, n = 2). Nedosiran was well-tolerated and lacked safety concerns. Although the PD response was not met, 24-h Uox excretion declined 24.5% in the nedosiran group and increased 10.5% in the placebo group at Day 85. Three of four nedosiran recipients had a > 30% reduction in 24-h Uox excretion during at least one visit, and one attained near-normal (i.e., ≥ 0.46 to < 0.60 mmol/24 h; ≥ 1.0 to < 1.3 × upper limit of the normal reference range) 24-h Uox excretion from Day 29 to Day 85. Nedosiran displayed predictable plasma PK. The acceptable safety and trend toward Uox-lowering after single-dose nedosiran treatment enables further clinical development of nedosiran in patients with PH3 who currently have no viable therapeutic options. A plain language summary is available in the supplementary information.

A Summary of Current Guidelines and Future Directions for Medical Management and Monitoring of Patients with Cystinuria.

Cystinuria is the most common genetic cause of recurrent kidney stones. As the result of a genetic defect in proximal tubular reabsorption of filtered cystine, increased urine levels of the poorly soluble amino acid result in recurrent cystine nephrolithiasis. Recurrent cystine stones not only adversely affect the quality of patients suffering from cystinuria but also may result in chronic kidney disease (CKD) from recurrent renal injury. Thus, the mainstay of medical management revolves around prevention of stones. Recently published consensus statements on guidelines for managing cystinuria were released from both the United States and Europe. The purpose of this review is to summarize guidelines for medical management of patients with cystinuria, to provide new insight into the utility and clinical significance of cystine capacity-an assay for monitoring cystinuria, and to discuss future directions for research on treatment of cystinuria. We discuss future directions, including the potential use of cystine mimetics, gene therapy, V2-receptor blockers, and SGLT2 inhibitors, topics which have not appeared in more recent reviews. It is notable that in the absence of randomized, controlled trials, the recommendations cited here and in the guidelines are based on our best understanding of the disorder's pathophysiology, observational studies, and clinical experience.

Epidemiology of Kidney Stones.

In the past two decades, major breakthroughs that improve our understanding of the pathophysiology and therapy of kidney stones (KS) have been lacking. The disease continues to be challenging for patients, physicians, and healthcare systems alike. In this context, epidemiological studies are striving to elucidate the worldwide changes in the patterns and the burden of the disease and identify modifiable risk factors that contribute to the development of kidney stones. Our expanding knowledge of the epidemiology of kidney stones is of paramount importance and largely upgrades the modern management of the disease. In this paper, we review the variables affecting prevalence and incidence, including age, gender, race, ethnicity, occupation, climate, geography, systemic diseases, diabetes, vascular disease, chronic kidney disease, and dietary risk factors relevant to kidney stones.