A National Survey of Pregnancy and Parenthood Among Nephrology Trainees: A Focus on Nephrology Fellowship.

BACKGROUND: National and international policies on parental leave for physician trainees are inconsistent. Physician trainees, including nephrology fellows, may be at higher risk of pregnancy complications. Physician trainees face barriers in meeting their breastfeeding goals and in finding childcare due to nontraditional work hours with extended or unpredictable shifts. Here, we examine awareness of current policies in United States (US) nephrology fellowship programs regarding parental leave, pregnancy/breastfeeding accommodations, and fellows' perspectives on family planning. METHODS: An anonymous, on-line survey of US nephrology fellows was undertaken from June 9 to August, 24, 2023. RESULTS: One hundred twenty nephrology fellows submitted the survey. A majority of fellow respondents were unaware of parental leave policies of their training programs (63%), Accreditation Council for Graduate Medical Education (ACGME) (75%), and/or American Board of Medical Specialties(ABMS) (75%). Forty two percent were unaware of the duration of parental leave at their program. Nearly 45% of all respondents were unsure if their program limited night shifts or shifts greater than 24 hours for pregnant trainees. Forty three percent reported they were unsure of lactation accommodations, and 40% were unsure of access to subsidized childcare. When fellows received work accommodations for pregnancy or parenthood, their work obligations were largely covered by co-fellows (60%) or attendings (38%). Over 60% of fellows agreed or strongly agreed that they would avoid a pregnancy in fellowship due to concern they would have to extend their training. Of the 40 fellows who chose to pursue pregnancy or parenthood during medical training, 75% did not change their career plans as a result. CONCLUSIONS: Most nephrology fellows were unaware of parental leave policies and pregnancy/lactation accommodations. While the topic itself has a broad impact to all physician trainees, there is need for improved awareness about national and local program policies among trainees across individual nephrology programs.

Pregnancy and Family Planning in Women With Kidney Disease.

Introduction: Females with kidney disease are at increased risk for pregnancy complications. Few studies have examined pregnancy perspectives of people with kidney disease. Our objective was to examine kidney patients' perspectives on family planning. Methods: We conducted an online survey of female patients with kidney disease from the University of Colorado Hospital between the ages of 18 and 50 years from August to October 2022. The survey asked questions on previous and current pregnancies with kidney disease, family planning, and reproductive health discussions with their nephrologists. Perspectives on how kidney disease influences pregnancies were also explored. Results: A total of 136 participants completed the survey. The majority of participants were White (71.3%) with a mean (SD) age of 37 ± 10 years. The majority of participants self-characterized their kidney disease as moderate (n = 57, 43.5%) with 16 participants (12.2%) receiving dialysis. Fifty-two participants (38.5%) experienced a pregnancy with a diagnosis of kidney disease, which were largely planned (n = 33, 61.1%). The majority of participants were able to conceive within 6 months (64.8%). Nearly half of participants reported that kidney disease influenced their family planning decisions with the majority (n = 91, 66.5%) believing that kidney disease increased their risk for pregnancy complications. More than half of participants never discussed the health risks of a potential pregnancy (54.0%), desire to have children (58.0%), pregnancy prevention (57.0%), and/or optimizing their health prior to pregnancy (68.1%) with their nephrologist. Conclusion: Although kidney disease influenced family planning decisions, few participants had family planning discussions with their nephrologists.

Sodium Zirconium Cyclosilicate in Chronic Kidney Disease, Hyperkalemia, and Metabolic Acidosis: NEUTRALIZE Randomized Study.

BACKGROUND: Metabolic acidosis and hyperkalemia are common in chronic kidney disease (CKD). A potential dual effect of sodium zirconium cyclosilicate (SZC), a selective binder of potassium in the gastrointestinal tract, on serum potassium (sK+) and serum bicarbonate (sHCO3-) was evaluated in patients with hyperkalemia and metabolic acidosis associated with CKD. METHODS: In the NEUTRALIZE study (NCT04727528), non-dialysis patients with stage 3-5 CKD, hyperkalemia (sK+ >5.0 to ≤5.9 mmol/l) and metabolic acidosis (sHCO3- 16-20 mmol/l) received open-label SZC 10 g three times daily for ≤48 hours. Patients achieving normokalemia (sK+ 3.5-5.0 mmol/l) were randomized 1:1 to SZC 10 g or placebo daily for 4 weeks. Primary endpoint was patients (%) maintaining normokalemia at end of treatment (EOT) without rescue. Secondary endpoints included mean change in sHCO3- at EOT (Day 29), and patients (%) normokalemic with a ≥3-mmol/l increase in sHCO3- without rescue. RESULTS: Of 229 patients screened, 37 were randomized (SZC, n = 17; placebo, n = 20). High screen failure led to early study termination. At EOT, 88.2% (SZC) versus 20.0% (placebo) of patients maintained normokalemia (odds ratio 56.2; P = 0.001). Low enrollment rendered secondary endpoint P-values nominal. SZC treatment provided nominally significant increases in sHCO3- versus placebo from Day 15 onwards. Patients who were normokalemic with a ≥3-mmol/l increase in sHCO3- without rescue were 35.3% (SZC) and 5.0% (placebo; P < 0.05). No new safety concerns were reported. CONCLUSIONS: SZC effectively lowered sK+ and maintained normokalemia, with nominally significant increases in sHCO3- observed for SZC versus placebo.

Assessing Cognition in Chronic Kidney Disease Using the NIH Toolbox®.

BACKGROUND: Chronic kidney disease (CKD) is largely an age-related clinical disorder with accelerated cognitive and cardiovascular aging. Cognitive impairment is a well-documented occurrence in midlife and older adults with CKD and affects multiple domains. We examined cognition function and potential sex differences in cognition in adults with CKD. METHODS: We included 105 individuals (49.5% women) with CKD stage 3b-4 (eGFR 15-44 mL/min) from the Bicarbonate Administration in CKD Trial (NCT02915601). We measured cognitive function using the National Institutes of Health (NIH) Toolbox® Cognition Battery, which assesses cognitive and motor measures such as executive function, attention, memory, and dexterity. All study measures were collected and analyzed at the study baseline. RESULTS: The mean (SD) age and eGFR were 61 ± 12 years and 34.9 ± 9.8 mL/min/1.73m2. Overall, when compared to the NIH Toolbox reference population, participants scored, on average, below the 50th percentile across all cognitive domain tests and the dexterity test. Total cognition scores were also below the 50th percentile. Participants with stage 4 CKD had significantly lower fluid cognition scores compared to those with CKD stage 3b (ß-Estimate -5.4 (95% CI-9.8 to -0.9); p=0.03). Female participants with CKD performed significantly better on the episodic memory tests and dexterity tests (dominant and non-dominant pegboard tests), and had higher crystallized cognition scores, on average, compared to males. CONCLUSIONS: Participants with CKD had detectable cognitive deficits in fluid cognition, dexterity, and total cognition. Additionally, sex differences in cognitive measures were found among people with CKD.

Home-Delivered Medically Tailored Meal Engagement Among Hemodialysis Patients and Providers.

OBJECTIVE: Hemodialysis patients face one of the most difficult diets among clinical patient populations. Furthermore, dialysis dietary adherence is generally reported as low with providers generally lacking the time and resources to implement effective behavior change. The purpose of this study was to elucidate measures of patient and provider engagement with home-delivered medically tailored meals (MTMs). METHODS: We surveyed patients and staff at dialysis centers within the Denver metropolitan area. Surveys focused on 1) patient dietary intake, 2) awareness, support, and utilization of meal programs, and 3) nutritional challenges and barriers (including food security). RESULTS: We surveyed 118 patients (mean age 61.0 ± 14.2 year, 58.5% male, and dialysis vintage of 4.6 ± 4.9 years) and 26 staff across the included dialysis facilities. Patients were 20.3% White/Non-Hispanic, 35.6% Hispanic/Latin, and 31.4% Black/African American. Most patients reported eating 2 meals per day (N = 53, 44.9%) and 52.2% reported difficulty with following a kidney diet. The most cited reasons for not following the diet were behavioral or knowledge (38.5%), taste (26.3%), time/convenience (26.9%) and food autonomy (16.9%). Sixty participants (52.2%) reported living in a food desert and 26.3% reported food insecurity. Seventy-one patients (61.2%) were aware of MTMs but only 40.5% had been referred. Most (76.9%) dialysis providers were aware of MTMs but only 15 (57.7%) had actually referred patients to such a service. Black individuals were less likely to be referred for MTMs than White or Hispanics/Latin (29.7% vs 48.1% White and 45.0% Hispanic/Latin) individuals. CONCLUSION: Medically tailored meals (MTMs) represent a potential method to alleviate or bypass some of the many barriers expressed by patients. Our findings reveal a critical need for education around MTMs for both patients and providers. Medically tailored meals (MTMs) could potentially demonstrate health kidney dietary patterns that might translate to altered dietary preferences or toward future behavior change.

Insulin Secretion, Sensitivity, and Kidney Function in Young Individuals With Type 2 Diabetes.

OBJECTIVE: ß-Cell dysfunction and insulin resistance magnify the risk of kidney injury in type 2 diabetes. The relationship between these factors and intraglomerular hemodynamics and kidney oxygen availability in youth with type 2 diabetes remains incompletely explored. RESEARCH DESIGN AND METHODS: Fifty youth with type 2 diabetes (mean age ± SD 16 ± 2 years; diabetes duration 2.3 ± 1.8 years; 60% female; median HbA1c 6.4% [25th, 75th percentiles 5.9, 7.6%]; BMI 36.4 ± 7.4 kg/m2; urine albumin-to-creatinine ratio [UACR] 10.3 [5.9, 58.0] mg/g) 21 control participants with obesity (OCs; age 16 ± 2 years; 29% female; BMI 37.6 ± 7.4 kg/m2), and 20 control participants in the normal weight category (NWCs; age 17 ± 3 years; 70% female; BMI 22.5 ± 3.6 kg/m2) underwent iohexol and p-aminohippurate clearance to assess glomerular filtration rate (GFR) and renal plasma flow, kidney MRI for oxygenation, hyperglycemic clamp for insulin secretion (acute C-peptide response to glucose [ACPRg]) and disposition index (DI; ×103 mg/kg lean/min), and DXA for body composition. RESULTS: Youth with type 2 diabetes exhibited lower DI (0.6 [0.0, 1.6] vs. 3.8 [2.4, 4.5] × 103 mg/kg lean/min; P < 0.0001) and ACPRg (0.6 [0.3, 1.4] vs. 5.3 [4.3, 6.9] nmol/L; P < 0.001) and higher UACR (10.3 [5.9, 58.0] vs. 5.3 [3.4, 14.3] mg/g; P = 0.003) and intraglomerular pressure (77.8 ± 11.5 vs. 64.8 ± 5.0 mmHg; P < 0.001) compared with OCs. Youth with type 2 diabetes and OCs had higher GFR and kidney oxygen availability (relative hyperoxia) than NWCs. DI was associated inversely with intraglomerular pressure and kidney hyperoxia. CONCLUSIONS: Youth with type 2 diabetes demonstrated severe ß-cell dysfunction that was associated with intraglomerular hypertension and kidney hyperoxia. Similar but attenuated findings were found in OCs.

Sodium Bicarbonate Treatment and Vascular Function in CKD: A Randomized, Double-Blind, Placebo-Controlled Trial.

SIGNIFICANCE STATEMENT: Lower serum bicarbonate levels, even within the normal range, are strongly linked to risks of cardiovascular disease in CKD, possibly by modifying vascular function. In this randomized, controlled trial, treatment with sodium bicarbonate (NaHCO 3 ) did not improve vascular endothelial function or reduce arterial stiffness in participants with CKD stage 3b-4 with normal serum bicarbonate levels. In addition, NaHCO 3 treatment did not reduce left ventricular mass index. NaHCO 3 did increase plasma bicarbonate levels and urinary citrate excretion and reduce urinary ammonium excretion, indicating that the intervention was indeed effective. NaHCO 3 therapy was safe with no significant changes in BP, weight, or edema. These results do not support the use of NaHCO 3 for vascular dysfunction in participants with CKD. BACKGROUND: Lower serum bicarbonate levels, even within the normal range, are strongly linked to risks of cardiovascular disease in CKD, possibly by modifying vascular function. Prospective interventional trials with sodium bicarbonate (NaHCO 3 ) are lacking. METHODS: We conducted a randomized, double-blind, placebo-controlled trial examining the effect of NaHCO 3 on vascular function in 109 patients with CKD stage 3b-4 (eGFR 15-44 ml/min per 1.73 m 2 ) with normal serum bicarbonate levels (22-27 mEq/L). Participants were randomized 1:1 to NaHCO 3 or placebo at a dose of 0.5 mEq/lean body weight-kg per day for 12 months. The coprimary end points were change in brachial artery flow-mediated dilation (FMD) and change in aortic pulse wave velocity over 12 months. RESULTS: Ninety patients completed this study. After 12 months, plasma bicarbonate levels increased significantly in the NaHCO 3 group compared with placebo (mean [SD] difference between groups 1.35±2.1, P = 0.003). NaHCO 3 treatment did not result in a significant improvement in aortic pulse wave velocity from baseline. NaHCO 3 did result in a significant increase in flow-mediated dilation after 1 month; however, this effect disappeared at 6 and 12 months. NaHCO 3 resulted in a significant increase in 24-hour urine citrate and pH and a significant decrease in 24-hour urine ammonia. There was no significant change in left ventricular mass index, ejection fraction, or eGFR with NaHCO 3 . NaHCO 3 treatment was safe and well-tolerated with no significant changes in BP, antihypertensive medication, weight, plasma calcium, or potassium levels. CONCLUSION: Our results do not support the use of NaHCO 3 for vascular dysfunction in participants with CKD and normal serum bicarbonate levels.

The complement system in pediatric acute kidney injury.

The complement cascade is an important part of the innate immune system. In addition to helping the body to eliminate pathogens, however, complement activation also contributes to the pathogenesis of a wide range of kidney diseases. Recent work has revealed that uncontrolled complement activation is the key driver of several rare kidney diseases in children, including atypical hemolytic uremic syndrome and C3 glomerulopathy. In addition, a growing body of literature has implicated complement in the pathogenesis of more common kidney diseases, including acute kidney injury (AKI). Complement-targeted therapeutics are in use for a variety of diseases, and an increasing number of therapeutic agents are under development. With the implication of complement in the pathogenesis of AKI, complement-targeted therapeutics could be trialed to prevent or treat this condition. In this review, we discuss the evidence that the complement system is activated in pediatric patients with AKI, and we review the role of complement proteins as biomarkers and therapeutic targets in patients with AKI.

Electrolyte derangements in critically ill children receiving balanced versus unbalanced crystalloid fluid resuscitation.

BACKGROUND: Adult studies have demonstrated potential harm from resuscitation with 0.9% sodium chloride (0.9%NaCl), resulting in increased utilization of balanced crystalloids like lactated ringers (LR). The sodium and potassium content of LR has resulted in theoretical safety concerns, although limited data exists in pediatrics. We hypothesized that use of LR for resuscitation would not be associated with increased electrolyte derangements compared to 0.9%NaCl. METHODS: A prospective, observational cohort study of critically ill children who received ≥ 20 ml/kg of fluid resuscitation and were admitted to two pediatric intensive care units from November 2017 to February 2020. Fluid groups included patients who received > 75% of fluids from 0.9%NaCl, > 75% of fluids from LR, and a mixed group. The primary outcome was incidence of electrolyte derangements (sodium, chloride, potassium) and acidosis. RESULTS: Among 559 patients, 297 (53%) received predominantly 0.9%NaCl, 74 (13%) received predominantly LR, and 188 (34%) received a mixture. Extreme hyperkalemia (potassium ≥ 6 mmol/L) was more common in 0.9%NaCl group (5.8%) compared to LR group (0%), p 0.05. Extreme acidosis (pH > 7.1) was more common in 0.9%NaCl group (11%) compared to LR group (1.6%), p 0.016. CONCLUSIONS: LR is associated with fewer electrolyte derangements compared to 0.9%NaCl. Prospective interventional trials are needed to validate these findings.

Youth versus adult-onset type 2 diabetic kidney disease: Insights into currently known structural differences and the potential underlying mechanisms.

Type 2 diabetes (T2D) is a global health pandemic with significant humanitarian, economic, and societal implications, particularly for youth and young adults who are experiencing an exponential rise in incident disease. Youth-onset T2D has a more aggressive phenotype than adult-onset T2D, and this translates to important differences in rates of progression of diabetic kidney disease (DKD). We hypothesize that youth-onset DKD due to T2D may exhibit morphometric, metabolic, and molecular characteristics that are distinct from adult-onset T2D and develop secondary to inherent differences in renal energy expenditure and substrate metabolism, resulting in a central metabolic imbalance. Kidney structural changes that are evident at the onset of puberty also serve to exacerbate the organ's baseline high rates of energy expenditure. Additionally, the physiologic state of insulin resistance seen during puberty increases the risk for kidney disease and is exacerbated by both concurrent diabetes and obesity. A metabolic mismatch in renal energetics may represent a novel target for pharmacologic intervention, both for prevention and treatment of DKD. Further investigation into the underlying molecular mechanisms resulting in DKD in youth-onset T2D using metabolomics and RNA sequencing of kidney tissue obtained at biopsy is necessary to expand our understanding of early DKD and potential targets for therapeutic intervention. Furthermore, large-scale clinical trials evaluating the duration of kidney protective effects of pharmacologic interventions that target a metabolic mismatch in kidney energy expenditure are needed to help mitigate the risk of DKD in youth-onset T2D.

A 6-Month clinical practice pilot study of sucroferric oxyhydroxide on nutritional status in patients on peritoneal dialysis.

BACKGROUND: Hyperphosphatemia is common in patients on peritoneal dialysis (PD). Restricting dietary phosphorus often leads to a decrease in protein intake, which may result in hypoalbuminemia. The high pill burden of phosphate binders may also contribute to compromised appetite and dietary intake. Hypoalbuminemia is associated with an increased risk of morbidity and mortality in PD patients. The goal of this study was to determine if sucroferric oxyhydroxide improves albumin and self-reported measures of appetite in PD patients. METHODS: We performed a prospective, open-label, 6-month, pilot study of 17 adult PD patients from the Denver Metro Area. Patients had to use automated peritoneal dialysis for ≥ 3 months, have a serum albumin ≤ 3.8 g/dL, and have serum phosphate ≥ 5.5 mg/dL or ≤ 5.5 mg/dL on a binder other than SO. SO was titrated to a goal serum phosphate of < 5.5 mg/dL. The primary outcome was change in serum phosphate, albumin, and phosphorus-attuned albumin (defined as albumin divided by phosphorus) over 6 months. RESULTS: The mean (SD) age and dialysis vintage was 55 ± 13 years and 3.8 ± 2.7 years, respectively. Participants' serum phosphate significantly decreased with fewer phosphate binder pills/day after switching to SO. There was no change in serum albumin, appetite, or dietary intake. However, participants had significant improvements in phosphorus-attuned albumin. CONCLUSION: The transition to SO improved phosphorus control, phosphorus-attuned albumin, and pill burden. There were no significant changes in self-reported appetite or dietary intake during the study. These findings suggest that PD patients maintained nutritional status with SO therapy. TRIAL REGISTRATION: First registered at ClinicalTrials.gov ( NCT04046263 ) on 06/08/2019.

Reducing disparities in kidney transplantation for Spanish-speaking patients through creation of a dedicated center.

INTRODUCTION: Hispanic Americans receive disproportionately fewer organ transplants than non-Hispanic whites. In 2018, the Hispanic Kidney Transplant Program (HKTP) was established as at the University of Colorado Hospital (UCH). The purpose of this quality improvement study was to examine the effect of this culturally sensitive program in reducing disparities in kidney transplantation. METHODS: We performed a mixed-methods analysis of data from 436 Spanish-speaking patients referred for transplant to UCH between 2015 and 2020. We compared outcomes for patients referred between 2015-2017 (n = 156) to those referred between 2018-2020 (n = 280). Semi-structured phone interviews were conducted with 6 patients per time period and with 6 nephrology providers in the Denver Metro Area. Patients and providers were asked to evaluate communication, transplant education, and overall experience. RESULTS: When comparing the two time periods, there was a significant increase in the percentage of patients being referred (79.5% increase, p-0.008) and evaluated for transplant (82.4% increase, p = 0.02) during 2018-2020. While the number of committee reviews and number waitlisted increased during 2018-2020, it did not reach statistical significance (82.9% increase, p = 0.37 and 79.5% increase, p = 0.75, respectively. During patient and provider interviews, we identified 4 themes reflecting participation in the HKTP: improved communication, enhanced patient education, improved experience and areas for advancement. Overall, patients and providers reported a positive experience with the HKTP and noted improved patient understanding of the transplantation process. CONCLUSIONS: The establishment of the HKTP is associated with a significant increase in Spanish-speaking Hispanic patients being referred and evaluated for kidney transplantation.

College students' motivations for using fitness related technology.

Objective: The purpose was to understand college students' motivations for the use and discontinued use of fitness related technology (FRT) in relation to their physical activity behaviors. Participants: Participants were undergraduate students (n = 22) who were eligible if they were between 18-24 years of age (emerging adulthood) and current or previous users of FRT. Methods: Qualitative descriptive design was used with semi-structured interviews conducted virtually. Thematic analysis was used to analyze the data. Results: Participants discussed four themes; (1) Motivations for physical activity, (2) Motivations for using FRT, (3) Social connection improves accountability for physical activity, and (4) The ups and downs of FRT goal setting and data display. Conclusions: Best practice guidelines need to be established for the use of FRT along with approaches to promote physical activity among this population. Additional research is needed to identify reasons for discontinuation of use and to develop potential interventions to promote sustained engagement with FRT.

Serum Phosphorus and Pill Burden Among Hemodialysis Patients Prescribed Sucroferric Oxyhydroxide: One-Year Follow-Up on a Contemporary Cohort.

Purpose: In prior analyses of real-world cohorts of hemodialysis patients switched from one phosphate binder (PB) to sucroferric oxyhydroxide (SO), SO therapy has been associated with improvements in serum phosphorus (sP) and reductions in daily PB pill burden. To characterize how SO initiation patterns have changed over time, we examined the long-term effectiveness of SO in a contemporary (2018-2019) cohort. Patients and Methods: Adult Fresenius Kidney Care hemodialysis patients first prescribed SO monotherapy as part of routine care between May 2018 and May 2019 (N = 1792) were followed for 1 year. All patients received a non-SO PB during a 91-day baseline period before SO prescription. Mean PB pills/day and laboratory parameters were compared before and during SO treatment. Results were divided into consecutive 91-day intervals (Q1-Q4) and analyzed using linear mixed-effects regression and Cochran's Q test. These results were contrasted with findings from a historical (2014-2015) cohort (N = 530). Results: The proportion of patients achieving sP ≤5.5 mg/dl increased after switching to SO (from 27.0% at baseline to 37.8%, 45.1%, 44.7%, and 44.0% at Q1, Q2, Q3, and Q4, respectively; P < 0.0001 for all). The mean daily PB pill burden decreased from a baseline of 7.7 to 4.4, 4.6, 4.8, and 4.9, respectively, across quarters (P < 0.0001 for all). Patients in the contemporary cohort had improved sP control (27.0% achieving sP ≤5.5 mg/dl vs 17.7%) and lower daily PB pill burden (mean 7.7 vs 8.5 pills/day) at baseline than those in the historical cohort. Overall use of active vitamin D was similar between cohorts, although higher use of oral active vitamin D (63.9% vs 15.7%) and lower use of IV active vitamin D lower (23.4% vs 74.2%) was observed in the contemporary cohort. Conclusion: Despite evolving treatment patterns, switching to SO resulted in improved sP control with fewer pills per day in this contemporary hemodialysis cohort.

Effect of Sodium Zirconium Cyclosilicate on Serum Potassium and Bicarbonate in Patients with Hyperkalemia and Metabolic Acidosis Associated with Chronic Kidney Disease: Rationale and Design of the NEUTRALIZE Study.

INTRODUCTION: Sodium zirconium cyclosilicate (SZC) is a selective potassium (K+) binder for hyperkalemia management that provides rapid and sustained correction of hyperkalemia. The NEUTRALIZE study is investigating whether SZC, in addition to correcting hyperkalemia and maintaining normal serum K+, can provide sustained increases in serum bicarbonate (HCO3-) in patients with hyperkalemia and metabolic acidosis associated with chronic kidney disease (CKD). METHODS: This is a prospective, randomized, double-blind, placebo-controlled phase 3b study of US adults with stage 3-5 CKD not on dialysis with hyperkalemia (K+ >5.0-≤5.9 mmol/L) and low-serum HCO3- (16-20 mmol/L). In the open-label correction phase, all eligible patients receive SZC 10 g three times daily for up to 48 h. Patients who achieve normokalemia (K+ ≥3.5-≤5.0 mmol/L) are then randomized 1:1 to once-daily SZC 10 g or placebo for a 4-week, double-blind, placebo-controlled maintenance phase. The primary endpoint is the proportion of patients with normokalemia at the end of treatment (EOT) without rescue therapy for hyperkalemia. Key secondary endpoints include mean change in serum HCO3-, the proportion of patients with an increase in serum HCO3- of ≥2 or ≥3 mmol/L without rescue therapy for metabolic acidosis, and the proportion of patients with serum HCO3- ≥22 mmol/L at EOT. CONCLUSIONS: NEUTRALIZE will establish whether SZC can provide sustained increases in serum HCO3- while lowering serum K+ in patients with hyperkalemia and CKD-associated metabolic acidosis and may provide insights on the mechanism(s) underlying the increased serum HCO3- with SZC treatment.