Faculty Bibliography

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'.

Popular diets often influence dietary patterns, which have different implications for kidney stone risk. Despite the wide variety of popular diets, some general principles can be gleaned from investigating their potential impact on nephrolithiasis. Plant-based diets, including Dietary Approaches to Stop Hypertension, Mediterranean, flexitarian, and vegetarian diets, may protect against nephrolithiasis when they consist largely of unprocessed plant foods, while carbohydrate-restricted diets (including high-protein diets and the ketogenic diet) may raise kidney stone risk. Patients should be advised to consume a diet rich in whole plants, particularly fruits and vegetables, and minimize their consumption of animal proteins. Accompanying fruits and vegetables that are higher in oxalate content with more water and some dairy intake may also be useful. (We address the oxalate content of fruits and vegetables further below). Calcium consumption is an important component of decreasing the risk of kidney stones, as higher dietary calcium from dairy or nondairy sources is independently associated with lower kidney stone risk. Patients should also be advised to be conscious of fat intake, as fat in the intestinal lumen may complex with calcium and therefore increase urinary oxalate excretion. Finally, patients should avoid consumption of processed foods, which often contain added fructose and high sodium content, two factors that increase kidney stone risk.

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.

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.

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.

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.