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.

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.

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.

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.

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.

Redlining has led to increasing rates of nephrolithiasis in minoritized populations: a hypothesis.

PURPOSE OF REVIEW: The persistent rise in kidney stone prevalence in recent decades has prompted much speculation as to the causes. There has been some discussion about the effect of heat on nephrolithiasis. Here, we review recent data and postulate that heat may play a role in stone formation on a large scale and among African-Americans in particular. RECENT FINDINGS: African-Americans are the race/ancestry group with faster rates of increasing incidence and prevalence of kidney stones. We make the observation that urban heat islands in the United States have resulted in part from the effects of redlining, a practice of systematic segregation and racism in housing that led to the development of neighborhoods with substantial disparities in environmental conditions. SUMMARY: In this thought experiment, we propose that the disproportionate rise in the prevalence of nephrolithiasis in minoritized populations correlates with increased temperatures specifically in neighborhoods adversely affected by the practice of redlining. We discuss phenomena in support of this hypothesis and ongoing work to test this theory.

An Evaluation of Alternative Technology-Supported Counseling Approaches to Promote Multiple Lifestyle Behavior Changes in Patients With Type 2 Diabetes and Chronic Kidney Disease.

OBJECTIVES: Although technology-supported interventions are effective for reducing chronic disease risk, little is known about the relative and combined efficacy of mobile health strategies aimed at multiple lifestyle factors. The purpose of this clinical trial is to evaluate the efficacy of technology-supported behavioral intervention strategies for managing multiple lifestyle-related health outcomes in overweight adults with type 2 diabetes (T2D) and chronic kidney disease (CKD). DESIGN AND METHODS: Using a 2 × 2 factorial design, adults with excess body weight (body mass index ≥27 kg/m2, age ≥40 years), T2D, and CKD stages 2-4 were randomized to an advice control group, or remotely delivered programs consisting of synchronous group-based education (all groups), plus (1) Social Cognitive Theory-based behavioral counseling and/or (2) mobile self-monitoring of diet and physical activity. All programs targeted weight loss, greater physical activity, and lower intakes of sodium and phosphorus-containing food additives. RESULTS: Of 256 randomized participants, 186 (73%) completed 6-month assessments. Compared to the ADVICE group, mHealth interventions did not result in significant changes in weight loss, or urinary sodium and phosphorus excretion. In aggregate analyses, groups receiving mobile self-monitoring had greater weight loss at 3 months (P = .02), but between 3 and 6 months, weight losses plateaued, and by 6 months, the differences were no longer statistically significant. CONCLUSIONS: When engaging patients with T2D and CKD in multiple behavior changes, self-monitoring diet and physical activity demonstrated significantly larger short-term weight losses. Theory-based behavioral counseling alone was no better than baseline advice and demonstrated no interaction effect with self-monitoring.

Hypernatremia in the intensive care unit.

PURPOSE OF REVIEW: Hypernatremia is a relatively frequent electrolyte disorder seen in critically ill patients. As many as 27% of patients in intensive care units (ICUs) develop hypernatremia of variable severity during an ICU stay. Debate among specialists often ensues as to whether to correct hypernatremia or not. Some practitioners, particularly intensivists, believe that correction of hypernatremia with fluids may cause expansion of the extracellular fluid volume (ECFV) thereby worsening ventilation and impeding extubation. Other practitioners, including many nephrologists, do not expect correction of hypernatremia to lead to clinically apparent ECFV expansion, and fear other deleterious effects of hypernatremia. In this review we address the controversy regarding appropriate practice. RECENT FINDINGS: There are no randomized, clinical trials (RCTs) to guide the administration of electrolyte-free fluid administration in hypernatremic patients. However, there are associations, demonstrated in the literature, suggesting that hypernatremia of any severity will increase the mortality and length of stay in these patients. These associations generally support the practice of correction of hypernatremia. In addition, our knowledge of the distribution of total body water influences us towards correcting hypernatremia as an appropriate therapy. We do not expect that adequate RCTs addressing this question will be performed. SUMMARY: Allowing persistence of any degree of hypernatremia is associated with increased mortality, length of stay (LOS) and postdischarge mortality. We expect that proper use of electrolyte-free water intake will avoid adverse outcomes.

Beyond the Urine Anion Gap: In Support of the Direct Measurement of Urinary Ammonium.

Ammonium is a major urinary buffer that is necessary for the normal excretion of the daily acid load. Its urinary rate of excretion (UNH4) may be increased several fold in the presence of extrarenal metabolic acidosis. Therefore, measurement of UNH4 can provide important clues about causes of metabolic acidosis. Because UNH4 is not commonly measured in clinical laboratories, the urinary anion gap (UAG) was proposed as its surrogate about 4 decades ago, and it is still frequently used for that purpose. Several published studies strongly suggest that UAG is not a good index of UNH4 and support the concept that direct measurement of UNH4 is an important parameter to define in clinical nephrology. Low UNH4 levels have recently been found to be associated with a higher risk of metabolic acidosis, loss of kidney function, and death in persons with chronic kidney disease, while surrogates like the UAG do not recapitulate this risk. In order to advance the field it is necessary for the medical community to become more familiar with UNH4 levels in a variety of clinical settings. Herein, we review the literature, searching for available data on UNH4 under normal and various pathological conditions, in an attempt to establish reference values to interpret UNH4 results if and when UNH4 measurements become available as a routine clinical test. In addition, we present original data in 2 large populations that provide further evidence that the UAG is not a good predictor of UNH4. Measurement of urine NH4 holds promise to aid clinicians in the care of patients, and we encourage further research to determine its best diagnostic usage.

Update on Uric Acid and the Kidney.

PURPOSE OF REVIEW: In this review, we report on new findings regarding associations of uric acid with kidney health. We discuss kidney stones, effects of uric acid in chronic kidney disease (CKD), and management of gout in CKD. Recent studies on neuroprotective effects of raising uric acid provide interesting data regarding nephrolithiasis. RECENT FINDINGS: Elevated urate levels have been implicated in the progression of chronic kidney disease (CKD), but the results from PERL and CKD-FIX studies did not demonstrate that allopurinol slowed CKD progression. The SURE-PD3 sought to determine if increasing uric acid would slow the progression of Parkinson's disease. Results ultimately did not support this hypothesis, but high urinary uric acid levels caused uric acid stones, not calcium stones. Low urinary pH remains the key to the formation of uric acid stones. Thiazolidinediones improve insulin resistance, which is associated with an increase in urine pH. The most recent research has not supported the hypothesis that lowering serum uric acid levels will slow the progression of CKD or provide neuroprotection in Parkinson's disease. It is still unclear as to why uric acid stone formers have a high net acid excretion. The STOP-GOUT trial demonstrates that there was a lack of significant adverse events with higher urate-lowering dosages of allopurinol and febuxostat, despite patients' kidney function. This may push other studies to administer higher dosages per ACR guidelines. Future studies could then demonstrate decreased progression of CKD.

Plant-Based Milk Alternatives and Risk Factors for Kidney Stones and Chronic Kidney Disease.

OBJECTIVE: Patients with kidney stones are counseled to eat a diet low in animal protein, sodium, and oxalate and rich in fruits and vegetables, with a modest amount of calcium, usually from dairy products. Restriction of sodium, potassium, and oxalate may also be recommended in patients with chronic kidney disease. Recently, plant-based diets have gained popularity owing to health, environmental, and animal welfare considerations. Our objective was to compare concentrations of ingredients important for kidney stones and chronic kidney disease in popular brands of milk alternatives. DESIGN AND METHODS: Sodium, calcium, and potassium contents were obtained from nutrition labels. The oxalate content was measured by ion chromatography coupled with mass spectrometry. RESULTS: The calcium content is highest in macadamia followed by soy, almond, rice, and dairy milk; it is lowest in cashew, hazelnut, and coconut milk. Almond milk has the highest oxalate concentration, followed by cashew, hazelnut, and soy. Coconut and flax milk have undetectable oxalate levels; coconut milk also has comparatively low sodium, calcium, and potassium, while flax milk has the most sodium. Overall, oat milk has the most similar parameters to dairy milk (moderate calcium, potassium and sodium with low oxalate). Rice, macadamia, and soy milk also have similar parameters to dairy milk. CONCLUSION: As consumption of plant-based dairy substitutes increases, it is important for healthcare providers and patients with renal conditions to be aware of their nutritional composition. Oat, macadamia, rice, and soy milk compare favorably in terms of kidney stone risk factors with dairy milk, whereas almond and cashew milk have more potential stone risk factors. Coconut milk may be a favorable dairy substitute for patients with chronic kidney disease based on low potassium, sodium, and oxalate. Further study is warranted to determine the effect of plant-based milk alternatives on urine chemistry.

Sodium bicarbonate therapy for acute respiratory acidosis.

PURPOSE OF REVIEW: Respiratory acidosis is commonly present in patients with respiratory failure. The usual treatment of hypercapnia is to increase ventilation. During the recent surge of COVID-19, respiratory acidosis unresponsive to increased mechanical ventilatory support was common. Increasing mechanical ventilation comes at the expense of barotrauma and hemodynamic compromise from increasing positive end-expiratory pressures or minute ventilation. Treating acute respiratory acidemia with sodium bicarbonate remains controversial. RECENT FINDINGS: There are no randomized controlled trials of administration of sodium bicarbonate for respiratory acidemia. A recent review concluded that alkali therapy for mixed respiratory and metabolic acidosis might be useful but was based on the conflicting and not conclusive literature regarding metabolic acidosis. This strategy should not be extrapolated to treatment of respiratory acidemia. Low tidal volume ventilation in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) has beneficial effects associated with permissive hypercapnia. Whether the putative benefits will be negated by administration of alkali is not known. Hypercapnic acidosis is well tolerated, with few adverse effects as long as tissue perfusion and oxygenation are maintained. SUMMARY: There is a lack of clinical evidence that administration of sodium bicarbonate for respiratory acidosis has a net benefit; in fact, there are potential risks associated with it.

Challenging patient phenotypes in the management of anaemia of chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is often complicated by anaemia, which is associated with disease progression and increased hospital visits, decreased quality of life, and increased mortality. METHODS: A comprehensive literature search of English language peer-reviewed articles in PubMed/MedLine published between 1998 and 2020 related to the treatment of anaemia of CKD was conducted. The United States Renal Database System and Dialysis Outcomes and Practice Patterns Study (DOPPS) data reports, the Centers for Disease Control and Prevention and the US Food and Drug Administration websites, and published congress abstracts in 2020 were surveyed for relevant information. RESULTS: Subgroups of patients with anaemia of CKD present a clinical challenge throughout the disease spectrum, including those with end-stage kidney disease, advanced age or resistance to or ineligibility for current standards of care (ie, oral or intravenous iron supplementation, erythropoietin-stimulating agents and red blood cell transfusions). In addition, those with an increased risk of adverse events because of comorbid conditions, such as cardiovascular diseases or diabetes, comprise special populations of patients with an unmet need for interventions to improve clinical outcomes. These comorbidities must be managed in parallel and may have a synergistic effect on overall disease severity. CONCLUSIONS: Several therapies provide promising opportunities to address gaps with a standard of care, including hypoxia-inducible factor prolyl hydroxylase inhibitors, which stimulate haematopoiesis through promoting modest increases in serum erythropoietin and improved iron homeostasis. The critical issues in the management of anaemia of CKD in these challenging phenotypes and the clinical utility of new therapeutic agents in development for the treatment of anaemia of CKD should be assessed and the information should be made available to healthcare providers.

Feasibility and Acceptability of mHealth Interventions for Managing Hyperphosphatemia in Patients Undergoing Hemodialysis.

OBJECTIVE: The objective of the study was to evaluate the feasibility and acceptability of mobile health (mHealth) phosphorus management programs in hemodialysis (HD) patients. METHODS: Patients receiving thrice-weekly HD who had 3-month average serum phosphorus of >5.5 mg/dL were randomized to one of the three self-directed phosphorus management programs delivered using tablet PCs: (1) educational videos and handouts (Education), (2) education intervention plus mobile self-monitoring with email feedback (Monitoring), or (3) education and monitoring interventions plus social cognitive theory-based behavioral videos (Combined). Feasibility and acceptability were assessed based on enrollment and retention and training needs (feasibility) and adherence to self-monitoring and reported satisfaction (acceptability). RESULTS: Of 312 patients, 56 expressed interest, and 40 were enrolled. The majority of participants (80%) completed the 6-month study; none withdrew for intervention-related reasons. The Monitoring and Combined groups received 44 ± 15 minutes of technology training, which was considered adequate by most (75%). Self-monitoring rates were initially high, with 78% and 71% of the participants recording at least one meal and phosphate binder in week 1, respectively, but decreased over time to 15% and 9% in the final week. Most participants reported that self-monitoring helped them stay motivated (64%), track nutrients (80%), and understand how to change diet (76%), and nearly two-thirds of participants (64%) stated that they would like to continue using the tablet PC to manage their health. However, few participants (16%) indicated that self-monitoring was worth the effort. The Monitoring and Combined groups did not differ from the Education group in study outcomes. CONCLUSION: Although the mHealth programs were generally well received, self-monitoring rates decreased substantially over time and were unaffected by social cognitive theory-based videos. Self-directed mHealth programs may be a useful adjunct to standard care but should be compared to more resource intensive programs (e.g., involving more "live" contact with a dietitian) to determine overall cost-effectiveness and role in HD care.

Nephrolithiasis in women: how different from men?

PURPOSE OF REVIEW: Men have more kidney stones compared with women; however, the difference is progressively decreasing. The reasons for higher prevalence of stones in men, as well as increasing prevalence in women, is a subject of ongoing speculation. In this review, we summarize the evidence of differences between men and women and expand on the speculative causes. RECENT FINDINGS: Stone incidence is rising in women and adolescent girls. Stone disease is more heritable among men than women, and women demonstrate greater influence of the unique environment. Women under the age of 50 years who have been pregnant, have more than double the odds of kidney stones compared with those who have never been pregnant. Women are more burdened with obesity, bariatric surgery and dieting, all associated with increased stones. Women have higher urinary pH because of greater absorption of dietary organic anions leading to increased urinary citrate, compared with men, and they differ in tubular calcium handling. SUMMARY: It is obvious that the cause of stones in men and women is complex and requires further study. Potential clues offered are in the change of the female environment, influencing increasing incidence in stones, particularly of younger women and female adolescents.

Occupational kidney stones.

PURPOSE OF REVIEW: Kidney stones are a common and preventable disorder. Certain occupations may increase risk for stone disease which will be discussed in this review. Few observational studies have examined this association. RECENT FINDINGS: Some occupations prevent individuals from drinking enough fluids to maintain a dilute urine or to void when they need to. People may have poor access to fluids or to bathroom facilities. These issues pose a risk for stone disease and are exacerbated by those who work in warmer climates. Individuals who do more activity while working, especially outdoors, perspire more, leading to more concentrated urine. In more sedentary jobs, individuals are at a higher risk of metabolic syndrome and therefore have a higher risk for stones. Astronauts, who work in environments without gravity, mobilize calcium from bone, leading to a higher risk of stone disease. SUMMARY: Proper fluid intake, more access to restrooms and increased use of potassium citrate may be the best options for those who encounter greater risk for stones because of their occupation.

Prevalence of low molecular weight proteinuria and Dent disease 1 CLCN5 mutations in proteinuric cohorts.

BACKGROUND: Dent disease type 1 (DD1) is a rare X-linked disorder caused mainly by CLCN5 mutations. Patients may present with nephrotic-range proteinuria leading to erroneous diagnosis of focal segmental glomerulosclerosis (FSGS) and unnecessary immunosuppressive treatments. METHODS: The following cohorts were screened for CLCN5 mutations: Chronic Kidney Disease in Children (CKiD; n = 112); Multicenter FSGS-Clinical Trial (FSGS-CT) (n = 96), and Novel Therapies for Resistant FSGS Trial (FONT) (n = 30). Urinary α1-microglobulin (α1M), albumin (A), total protein (TP), and creatinine (Cr) were assessed from CKiD subjects (n = 104); DD1 patients (n = 14); and DD1 carriers (DC; n = 8). TP/Cr, α1M/Cr, α1M/TP, and A/TP from the CKiD cohort were compared with DD1 and DC. RESULTS: No CLCN5 mutations were detected. TP/Cr was lower in DC and CKiD with tubulointerstitial disease than in DD1 and CKiD with glomerular disease (p < 0.002). α1M/Cr was higher in DD1 than in CKiD and DC (p < 0.001). A/TP was lower in DD1, DC, and CKiD with tubulointerstitial disease and higher in CKiD with glomerular disease (p < 0.001). Thresholds for A/TP of ≤ 0.21 and α1M/Cr of ≥ 120 mg/g (> 13.6 mg/mmol) creatinine were good screens for Dent disease. CONCLUSIONS: CLCN5 mutations were not seen in screened CKiD/FSGS cohorts. In our study, a cutoff of TP/Cr > 600 mg/g (> 68 mg/mmol) and A/TP of < 0.3 had a high sensitivity and specificity to distinguish DD1 from both CKiD glomerular and tubulointerstitial cohorts. α1M/Cr ≥ 120 mg/g (> 13.6 mg/mmol) had the highest sensitivity and specificity when differentiating DD1 and studied CKiD populations.

Managing Hyperkalemia: Another Benefit of Exercise in People With Chronic Kidney Disease?

People with chronic kidney disease (CKD) are at increased risk of hyperkalemia, an electrolyte abnormality that can cause serious, sometimes fatal, cardiac arrhythmias. Muscle contraction causes potassium to be released from cells, increasing serum potassium concentrations. However, these effects are transient, and the long-term impact of exercise training on hyperkalemia risk in CKD patients is largely unknown. In this review, we examine the effects of exercise on factors affecting potassium balance in people with CKD, highlighting the potential benefits of regular exercise on hyperkalemia risk in this population. Although regular exercise is already recommended for people with CKD, research examining this hypothesis may lead to novel therapeutic treatments for this life-threatening condition.