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Acute kidney injury (AKI) causes biochemical changes in the brain in animal models and is associated with adverse neurological complications in hospitalized patients. This study tested the association between AKI and incident dementia in a community-based cohort.Prospective cohort study.Adult participants in the Atherosclerosis Risk in Communities (ARIC) study who experienced hospitalized AKI compared with participants hospitalized for other reasons (primary analysis, mean follow-up period 4.3 years) or participants without hospitalized AKI (secondary analysis).Incident AKI, defined by ICD codes from hospital records.Incident dementia, diagnosed based on a combination of neurocognitive testing, informant interviews, ICD codes, and death certificates.In the primary analysis, we estimated the propensity for hospitalized AKI and matched these participants with those hospitalized for another reason to examine the association of AKI with subsequent onset of dementia (N = 1,708). In the secondary analysis, we estimated the association between time-varying hospitalized AKI and subsequent onset of dementia using multivariable Cox proportional hazards regression models, adjusted for age, sex, race/center, education, smoking status, body mass index, baseline estimated glomerular filtration rate, baseline urinary albumin-creatinine ratio, systolic blood pressure, coronary heart disease, diabetes, hypertension, apolipoprotein E (APOE) ε4 allele, and C-reactive protein.The mean age in the propensity-matched cohort was 76.1 ± 6.5 (SD) years, and 53.2% of the participants were women. People who were hospitalized with AKI had a higher risk of dementia (HR, 1.25 [95% CI, 1.02-1.52]; P = 0.03) compared with those without a hospitalization for AKI. The associations were slightly stronger in the time-varying analysis (HR, 1.69 [95% CI, 1.48-1.92]; P 0.001). Other risk factors for dementia included older age, male sex, higher albuminuria, diabetes, current smoker status, and presence of the APOE risk alleles.Observational study, with AKI identified through diagnosis codes.Participants who experienced a hospitalization for AKI were at increased risk of dementia.

Lutetium-177 ( 177 Lu) dotatate has been offered at Fox Chase Cancer Center since 2017 as part of a clinical trial and then in 2018 as a commercially available cancer therapy, and we thought we were prepared for most 177 Lu issues by the fall of 2020. A single phone call identified that the Radiation Safety Department had not been prepared to address extravasations. Fortunately for the patient and Radiation Safety, the 177 Lu therapies are administered by an infusion nurse and Fox Chase Cancer Center has a robust infusion center. The expertise of our infusion center team helped to quickly identify specific mitigation efforts to employ. A team of radiation safety and diagnostic medical physicists worked together to estimate a tissue dose. Research was also started with the aim of identifying therapeutic 177 Lu extravasations as early as possible. The lessons we learned and plans for future early identification of 177 Lu dotatate extravasations are the basis of this paper.

Introduction Metabolic acidosis is associated with cardiovascular events, graft function, and mortality in kidney transplant recipients (KTRs). We examined the effect of alkali therapy on vascular endothelial function in KTRs. Methods We performed an 18-week, randomized, double-blind, placebo-controlled crossover pilot study examining the effect of sodium bicarbonate therapy versus placebo on vascular function in 20 adult KTRs at least 1 year from transplant with an estimated glomerular filtration rate (eGFR) ≥45 ml/min per 1.73 m2 and a serum bicarbonate level of 20 to 26 mEq/L. Each treatment period was 8 weeks in duration with a 2-week washout period between treatments. The primary outcome was change in brachial artery flow-mediated dilation (FMD) between sodium bicarbonate treatment and placebo. Results Twenty patients completed the study and were included in the primary analysis. The mean (SD) baseline eGFR of participants was 75 (22) ml/min per 1.73 m2, respectively. Serum bicarbonate levels did not increase significantly with treatment (0.3 [1.5] mEq/L, P = 0.37). Sodium bicarbonate therapy was not associated with worsening blood pressure, weight gain, or hypokalemia. There was no significant increase in FMD after 8 weeks of sodium bicarbonate therapy compared to placebo (mean change in FMD 2.2%, 95% CI –0.1 to 4.6, P = 0.06). There were no significant changes in high-sensitivity C-reactive protein, interleukin-6, eGFR, or urinary albumin-to-creatinine ratio during treatment. Urinary ammonium excretion decreased by 9 mmol/d (P=0.003), with sodium bicarbonate. Conclusions Sodium bicarbonate therapy is safe and feasible in KTRs, and our results strengthen the need for a larger randomized controlled trial., Graphical abstract

Phosphate binders are among the most common medications prescribed to patients with kidney failure receiving dialysis and are often used in advanced chronic kidney disease (CKD). In patients with CKD glomerular filtration rate category 3a (G3a) or worse, including those with kidney failure who are receiving dialysis, clinical practice guidelines suggest "lowering elevated phosphate levels towards the normal range" with possible strategies including dietary phosphate restriction or use of binders. Additionally, guidelines suggest restricting the use of oral elemental calcium often contained in phosphate binders. Nutrition guidelines in CKD suggest

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.

High dietary acid load may accelerate a decline in kidney function. We prospectively investigated whether dietary acid load is associated with graft outcomes in kidney transplant recipients, and whether venous bicarbonate mediates this association.We used data from 642 kidney transplant recipients with a functioning graft ≥1 year after transplantation. Net endogenous acid production was estimated using food frequency questionnaires and, alternatively, 24-hour urinary urea and potassium excretion to estimate net endogenous acid production. We defined the composite kidney end point as a doubling of plasma creatinine or graft failure. Multivariable Cox regression analyses, adjusted for potential confounders, were used to study the associations of dietary acid load with the kidney end point. We evaluated potential mediation effects of venous bicarbonate, urinary bicarbonate excretion, urinary ammonium excretion, titratable acid excretion, and net acid excretion on the association between net endogenous acid production and the kidney end point.The median net endogenous acid production using food frequency questionnaires and net endogenous acid production using urinary excretion were 40 (interquartile range, 35-45) and 54 (interquartile range, 44-66) mEq/day, respectively. During a median follow-up of 5.3 years (interquartile range, 4.1-6.0), 121 (19%) participants reached the kidney end point. After multivariable adjustment, net endogenous acid production using food frequency questionnaires and net endogenous acid production using urinary excretion (per SD higher) were independently associated with higher risk for kidney end point (hazard ratio, 1.33; 95% confidence interval, 1.12 to 1.57,Higher dietary acid load was associated with a higher risk of doubling of plasma creatinine or graft failure, and this association was partly mediated by venous bicarbonate, urinary ammonium, and net acid excretion.

Youth with type 1 diabetes (T1D) demonstrate insulin resistance, independently of glycaemia, when compared to normoglycaemic peers. Insulin resistance increases the risk of cardiovascular disease and diabetic kidney disease, factors also associated with systemic inflammation. We evaluated the effect of metformin on markers of inflammation and diabetic kidney disease in adolescents with T1D. EMERALD, a double-blind, randomized, placebo-controlled trial of 3 months of metformin in 48 participants aged 12-21 years with T1D, included baseline and follow-up assessments of serum creatinine and cystatin C to estimate glomerular filtration rate (eGFR), aspartate aminotransferase, alanine aminotransferase, high-sensitivity C-reactive protein, white blood count, platelets, adiponectin, leptin, and urine albumin: creatinine ratio (UACR). Metformin was associated with a 13.9 mL/min/1.73 m2 (95% confidence interval 4.7-23.1 mL/min/1.73 m2 ) increase in estimated GFR by serum creatinine versus placebo (P ≤ 0.01), with a significant difference remaining after multivariable adjustments (P = 0.03). Whereas eGFR measured by serum creatinine increased significantly after metformin treatment, no differences were observed in cystatin C, UACR, or systemic inflammatory markers. Additional studies with directly measured GFR in response to metformin in T1D are needed.

Kidney transplantation is the ideal treatment option for patients with end-stage kidney disease (ESKD). Since there is clear mortality benefit to receiving a transplant regardless of comorbidities and age, the gold standard of care should focus on attaining kidney transplantation and minimizing, or better yet eliminating, time on dialysis. Unfortunately, only a small percentage of patients with ESKD receive a kidney transplant. Several barriers to kidney transplantation have been identified. Barriers can largely be grouped into three categories: patient-related, physician/provider-related, and system-related. Several barriers fall into multiple categories and play a role at various levels within the healthcare system. Acknowledging and understanding these barriers will allow transplant centers and dialysis facilities to make the necessary interventions to mitigate these disparities, optimize the transplant evaluation process, and improve patient outcomes. This review will discuss these barriers and potential interventions to increase access to kidney transplantation.

Lower serum bicarbonate levels are associated with an increased risk of kidney disease progression. Whether lower serum bicarbonate levels are associated with an increased risk of developing acute kidney injury (AKI) is unclear. We included 8393 patients from the Systolic Blood Pressure Intervention Trial (SPRINT) that had baseline serum bicarbonate levels and complete data available. AKI was a predetermined adjudicated adverse event that was determined by hospital admission and discharge records with AKI as a recorded diagnosis. Serum bicarbonate was examined in clinically significant cutoffs ≤ 24, 25–28 and > 28 mEq/L, with 25–28 mEq/L as the reference group. Cox proportional hazard models were used to examine the association between serum bicarbonate and development of AKI. The mean (SD) age, estimated glomerular filtration rate (eGFR), and serum bicarbonate level at baseline were 68 (9) years, 77 (23) ml/min/1.73m2 and 26.3 (2.6) mEq/L, respectively. Participants with serum bicarbonate levels ≤ 24 mEq/L were more likely to be male and to have lower baseline eGFR. After a median follow-up time of 3.3 years, 293 participants developed AKI. More patients in the lower bicarbonate group developed AKI (6.1% vs 2.8% in the 25–28 mEq/L and 2.1% in the > 28 mEq/L). A bicarbonate level ≤ 24 mEq/L was associated with a significantly increased risk of AKI compared to those with a bicarbonate level of 25–28 mEq/L after full adjustment (HR 1.42, 95% CI 1.1–1.8). Lower serum bicarbonate levels are an independent risk factor for the development of AKI.

BACKGROUND: Children who are critically ill with AKI suffer from high morbidity and mortality rates, and lack treatment options. Emerging evidence implicates the role of complement activation in AKI pathogenesis, which could potentially be treated with complement inhibitors. The purpose of this study is to evaluate the association between complement activation fragments and severity of AKI in children who are critically ill. METHODS: A biorepository of samples from children who are critically ill from a prior multisite study was leveraged to identify children with stage 3 AKI and matched to patients without AKI on the basis of PELOD-2 (illness severity) scores. Specimens were analyzed for plasma and urine complement activation fragments of factor B, C3a, C4a, and sC5b-9. The primary outcomes were MAKE30 and severe AKI rates. RESULTS: In total, 14 patients with stage 3 AKI (five requiring RRT) were matched to 14 patients without AKI. Urine factor Ba and plasma C4a levels increased stepwise as severity of AKI increased, from no AKI to stage 3 AKI, to stage 3 AKI with RRT need. Plasma C4a levels were independently associated with increased risk of MAKE30 outcomes (OR, 3.2; IQR, 1.1–8.9), and urine Ba (OR, 1.9; IQR, 1.1–3.1), plasma Bb (OR, 2.7; IQR, 1.1–6.8), C4a (OR, 13.0; IQR, 1.6–106.6), and C3a (OR, 3.3; IQR, 1.3–8.4) were independently associated with risk of severe stage 2–3 AKI on day 3 of admission. CONCLUSIONS: Multiple complement fragments increase as magnitude of AKI severity increases. Very high levels of urine Ba or plasma C4a may identify patients at risk for severe AKI, hemodialysis, and MAKE30 outcomes. The fragments may be useful as a functional biomarker of complement activation and may identify those patients to study complement inhibition to treat or prevent AKI in children who are critically ill. These findings suggest the need for further specific investigations of the role of complement activation in children who are critically ill and at risk of AKI.

RATIONALE AND OBJECTIVE: The safety of intensive blood pressure (BP) targets is controversial for persons with chronic kidney disease (CKD). We studied the effects of hypertension treatment on cerebral perfusion and structure in those with and without CKD. STUDY DESIGN: Neuroimaging substudy of a randomized trial. SETTING & PARTICIPANTS: A subset of participants in the Systolic Blood Pressure Intervention Trial who underwent brain MRI studies. Presence of baseline CKD was assessed by estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR). INTERVENTION: Participants were randomly assigned to intensive (systolic BP 30 mg/g (N=151), the effects of intensive versus standard BP treatment on change in global cerebral blood flow, WMLs and total brain volume were 1.91 ml/100g/min (95% CI −3.01, 6.82), 0.003 cm(3) (asinh transformed, 95% CI −0.13, 0.13), and −7.0 cm(3) (95% CI −13.3, −0.3), respectively. The overall treatment effects on cerebral blood flow and total brain volume were not modified by baseline eGFR or UACR; however the effect on WMLs was attenuated in participants with albuminuria (interaction p-value 0.04). LIMITATIONS: Measurement variability due to multi-site design. CONCLUSIONS: Among hypertensive adults with primarily early kidney disease, intensive versus standard blood pressure treatment did not appear to have a detrimental effect on brain perfusion or structure. The findings support the safety of intensive blood pressure treatment targets on brain health in persons with early kidney disease. FUNDING: The Systolic Blood Pressure Intervention Trial was funded by the National Institutes of Health (including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke), and this substudy was funded by the National Institutes of Diabetes and Digestive and Kidney Diseases. TRIAL REGISTRATION: SPRINT was registered at ClinicalTrials.gov with the study number NCT01206062.

Rationale & Objective: Data suggest that exercise is beneficial for patients with chronic kidney disease (CKD) to reduce cardiovascular disease and the progression of CKD. Despite these benefits, the majority of patients with CKD remain sedentary. The purpose of this study was to identify attitudes, motivators, and barriers to exercise among individuals with CKD. Study Design: Qualitative study. Setting & Participants: 10 focus groups (41 adult participants with CKD stages 3-4 who were not currently exercising) from the Denver Metro Area. Analytical Approach: Thematic analysis. Clinics were purposively sampled. Focus groups were recorded and transcribed. Results: We identified 7 themes reflecting perceptions of exercise of patients with CKD: improvement in health and quality of life; motivation from family, friends, or peers; limitations due to comorbid conditions; challenges due to environmental factors (safety, weather, and cost concerns); lack of time; family as a barrier; and lack of provider counseling on type of exercise and the benefits. Participants recognized the benefits of exercise on health, but exercise was not viewed to have a significant impact on CKD. Having a friend, family member, or group to exercise with was viewed as a significant motivator. However, particularly in Spanish-speaking participants, family was often seen as a barrier if they were not willing to exercise with the patients. Most participants expressed receiving limited information from their kidney provider regarding how exercise affected their kidney health. Spanish-speaking participants in particular expressed frustration with their nephrologist's lack of advice regarding exercise. Limitations: Potential selection bias and inclusion of only sedentary patients with CKD. Conclusions: Barriers and motivators to exercise were similar among participating men and women with CKD. Lack of advice from kidney providers regarding exercise was a significant barrier. Exercise interventions in patients with CKD should include not only increased patient self-efficacy and social support, but also counseling and prescribing of exercise by nephrologists. Index Words: Exercise, chronic kidney disease, focus group, qualitative study, patient perspective

Background and Aims The 2017 Kidney Disease Improving Global Outcomes (KDIGO) Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) guidelines inform clinical practice for the management of secondary hyperparathyroidism (SHPT) internationally; however, many recommendations lacked high or moderate clinical evidence as defined by KDIGO. An expert panel was convened to establish clinical consensus for the current management of SHPT in the United States (US). Method The panel comprised 10 US healthcare providers (HCPs; [6 nephrologists, 1 surgeon, 1 nurse practitioner, 1 pharmacist, 1 dietician]) and 1 patient. HCP panelists participated in a modified Delphi process over 3 phases, addressing 126 questions based on a review of the literature and published guidelines. The threshold for consensus was 66%. In phases 1 and 2, panelists anonymously completed electronic surveys considering a ‘typical’ patient with SHPT unless otherwise specified. In phase 1, panelists answered 126 questions based on their own knowledge and experiences. In phase 2, panelists were reminded of their answers to closed-ended questions that did not achieve consensus in phase 1 and were asked if they would change their responses in light of the most common response. For open-ended questions, they were asked if they agreed with summary statements that captured the most common answers. Phase 3 was an unblinded virtual meeting where panelists reviewed the consensus reached in phases 1 and 2, and through active discussion, resolved those questions that had not reached consensus. The patient completed a separate electronic survey, which complemented key points in the HCP survey, and provided perspective during the virtual meeting. Results All 11 panelists completed the entire modified Delphi process. Sixty-three out of 126 (50%) and 116/126 (92.1%) questions reached consensus or addressed practice-specific information not requiring consensus by the end of phase 1 and 2, respectively; all questions reached consensus by the end of phase 3, including modification of 2 questions and the addition of 1 question. The panel unanimously agreed that SHPT treatment is often started too late and suggested additional markers for early identification of patients requiring treatment are needed. Serum levels of calcium, phosphate, and parathyroid hormone (PTH) should be monitored starting at CKD stage G3a at intervals of every 6 months, 3–6 months for CKD G3b, and at least every 3 months at CKD G4 and above. Thresholds for interventions could not be defined in absolute terms for all patients due to patient-and practice-specific factors. However, in patients on dialysis, serum levels of phosphate > 5.5 mg/dL (1.8 mmol/L) and calcium > 9.5 mg/dL (2.4 mmol/L), warrant increased monitoring and consideration of therapeutic interventions. Serum intact PTH > 300 pg/mL (32 pmol/L) typically indicates a need for SHPT treatment, with a consensus preferred target of 150–300 pg/mL (16–32 pmol/L); patients on dialysis were considered out of PTH target at ≥ 8 times the upper limit of normal (> 520 pg/mL [55 pmol/L] intact PTH). HCPs were concerned about vascular calcification in all patients with CKD 3a–G5D. The panel reached consensus on the use of several SHPT interventions, including a consensus preference for the intravenous calcimimetic etelcalcetide over the oral calcimimetic cinacalcet in appropriate in-center dialysis patients requiring PTH-lowering therapy; cinacalcet was agreed to be first-line therapy in appropriate patients on home dialysis (Table 1). Factors such as formularies and dialysis center protocols were recognized to influence therapeutic choices. Conclusion Ten US HCPs reached consensus on many aspects of SHPT management, further defining therapeutic strategies and highlighting the need to be proactive. While the panel expressed evidenced-based preferences for certain therapies, factors such as cost and dialysis center protocols may affect decision making.

Background Interest in nephrology as a career has declined dramatically over the past several years. Only 62% of nephrology fellowship positions are filled for the upcoming 2020 appointment year. The purpose of this study was to identify perceptions, attitudes, motivators, and barriers to a career in nephrology among internal medicine residents. Methods We recruited focus groups of internal medicine residents (N=25) from the University of Colorado, and asked questions aimed at exploring perceptions, attitudes, and barriers to a career in nephrology, and ways to increase interest in nephrology. All focus groups were conducted on the University of Colorado Denver Anschutz Medical Campus. Focus group sessions were recorded and transcribed. Thematic analysis was used to identify key concepts and themes. Results Residents described many barriers to a career in nephrology, including lack of exposure, lack of advances in the field, low monetary compensation, high complexity, lack of role models/mentors, and low-prestige/noncompetitive nature of the field. Most residents had no exposure to outpatient nephrology. Lack of new therapeutics was a significant deterrent to nephrology. Nephrology teaching in medical school was described as not clinically relevant and too complicated. Several residents felt they were not smart enough for nephrology. Only three residents had a role model within nephrology. Residents used the word “stigmatized” to describe nephrology, and discussed how low prestige decreased their interest in a field. Participants expressed suggestions to increase interest in nephrology through earlier and more outpatient nephrology exposure, enhanced interactions with nephrologists, and research and advancements in the field. Conclusions Residents identified several modifiable barriers to a career in nephrology. Changing how nephrology is taught in medical school, enhancing interactions with nephrologists through increased exposure, and highlighting research and advancements in nephrology may change the perception of nephrology and increase the number of residents entering the field.

Vascular dysfunction plays an important role in the etiology of chronic kidney disease (CKD) and is associated with cardiovascular diseases. Sex differences in vascular function are common in clinical and nonclinical populations. However, no data exist in individuals with CKD. The present study tested the hypothesis that sex and/or aging differences exist in vascular function in patients with CKD. Endothelium-dependent dilation (EDD; measured via brachial artery flow-mediated dilation) and endothelium-independent dilation (EID; measured via nitroglycerin-mediated dilation) were assessed. Analyses were adjusted for several variables that could influence vascular function (diabetes, cardiovascular disease, and blood pressure). Women, in general, had higher EDD values than men (6.5 ± 4.9% vs. 4.4 ± 3.4%); however, EID did not differ among these groups. In younger men and women (

Lower serum bicarbonate levels are associated with an increased risk of kidney disease progression. Whether lower serum bicarbonate levels are associated with an increased risk of developing acute kidney injury (AKI) is unclear.We included 8393 patients from the Systolic Blood Pressure Intervention Trial (SPRINT) that had baseline serum bicarbonate levels and complete data available. AKI was a predetermined adjudicated adverse event that was determined by hospital admission and discharge records with AKI as a recorded diagnosis. Serum bicarbonate was examined in clinically significant cutoffs ≤ 24, 25-28 and 28 mEq/L, with 25-28 mEq/L as the reference group. Cox proportional hazard models were used to examine the association between serum bicarbonate and development of AKI.The mean (SD) age, estimated glomerular filtration rate (eGFR), and serum bicarbonate level at baseline were 68 (9) years, 77 (23) ml/min/1.73mLower serum bicarbonate levels are an independent risk factor for the development of AKI.

Deficiency of 25-hydroxyvitamin D (25[OH]D) is common in patients with chronic kidney disease stages 3 and 4 and is associated with poor outcomes. However, the evaluation and management of vitamin D deficiency in nephrology remains controversial. This article reports on the proceedings from a “controversies conference” on vitamin D in chronic kidney disease that was sponsored by the National Kidney Foundation. The report outlines the deliberations of the 3 work groups that participated in the conference. Until newer measurement methods are widely used, the panel agreed that clinicians should classify 25(OH)D “adequacy” as concentrations > 20 ng/mL without evidence of counter-regulatory hormone activity (ie, elevated parathyroid hormone). The panel also agreed that 25(OH)D concentrations < 15 ng/mL should be treated irrespective of parathyroid hormone level. Patients with 25(OH)D concentrations between 15 and 20 ng/mL may not require treatment if there is no evidence of counter-regulatory hormone activity. The panel agreed that nutritional vitamin D (cholecalciferol, ergocalciferol, or calcifediol) should be supplemented before giving activated vitamin D compounds. The compounds need further study evaluating important outcomes that observational studies have linked to low 25(OH)D levels, such as progression to end-stage kidney disease, infections, fracture rates, hospitalizations, and all-cause mortality. We urge further research funding in this field.

Background and objectives We examined the effect of alkali replacement for metabolic acidosis on vascular endothelial function in patients with CKD. Methods We performed a pilot, prospective, open-label 14-week crossover study examining the effect of oral sodium bicarbonate treatment on vascular function in 20 patients with an eGFR of 15–44 ml/min per 1.73 m 2 with low serum bicarbonate levels (16–21 mEq/L). Each period was 6 weeks in duration with a 2-week washout period in between. Patients were treated to goal serum bicarbonate of ≥23 mEq/L. The primary end point was change in brachial artery flow-mediated dilation (FMD) between treatment and control conditions. Secondary end points included changes in markers of inflammation, bone turnover, mineral metabolism, and calcification. Results Eighteen patients completed the study and were included in the primary efficacy analysis. The mean (SD) age and eGFR were 59 (12) years and 26 (8) ml/min per 1.73 m 2 , respectively. Serum bicarbonate increased significantly with sodium bicarbonate treatment (+2.7±2.9 mEq/L, P ≤0.001), whereas there was no change in bicarbonate levels in the control group. FMD significantly improved after sodium bicarbonate therapy (mean±SD, FMD baseline: 4.1%±4.1%; 6 weeks: 5.2%±2.9%; P =0.04) There was no significant change in FMD in the control group (mean±SD, FMD baseline: 4.6%±3.1%; 6 weeks: 4.1%±3.4%; P =0.20). Compared with control, sodium bicarbonate treatment resulted in a significant increase in FMD (mean, 1.8%; 95% confidence interval, 0.3 to 3.3; P =0.02). There was no significant change in bone markers or serum calcification propensity with treatment. Serum phosphorus and intact fibroblast growth factor 23 increased significantly during treatment. Conclusions Treatment of metabolic acidosis with sodium bicarbonate significantly improved vascular endothelial function in patients with stages 3b and 4 CKD.

Background: Only a small percentage of dialysis patients receive a transplant and this is particularly the case for racial/ethnic minorities. Our objective was to identify barriers to initial transplant evaluation in our dialysis centers. Methods: We conducted a survey of adult hemodialysis patients from 4 dialysis units in the Denver Metro area in 2016. Participants completed an 11-item survey with demographic information and questions regarding time on dialysis, if a provider ever spoke to them about transplant, and whether they had been evaluated for a transplant. Reasons for not having an evaluation were explored. Descriptive statistics, chi-square analyses, and multivariate analyses were used to examine the responses. Results: A total of 167 patients completed the survey (response rate 63.9%). The majority of participants were male and were Hispanic (49%) or Non-Hispanic black (31.7%). Of these, 140 patients (84.0%) reported discussing kidney transplantation with their doctor but only 53% reported having a transplant evaluation. After adjustment for age, gender, and time on dialysis, significantly fewer blacks reported having an evaluation than Non-Hispanic whites or Hispanics (43.4 vs. 57.7% [whites] and 59.7% [Hispanics], p = 0.03). The most frequent responses of the patients who had not been evaluated were the following: not referred by their provider (46%), did not know how to proceed (43.4%), or did not understand the benefits (39.5%) or transplant process (38.2%). Compared to Non-Hispanic whites, blacks and Hispanics reported less understanding of the benefits and process of transplant. Conclusion: Timely referral by providers and improved kidney transplantation education may reduce disparities in access to kidney transplantation.

Background Data regarding the effect of a solitary kidney during pregnancy have come from studies of living kidney donors. We evaluated the risk for adverse pregnancy outcomes in women with a single kidney from renal agenesis. Study Design Matched cohort study. Setting & Participants Using data from 7,079 childbirths from an integrated health care delivery system from 1996 through 2015, we identified births from women with renal agenesis. Only first pregnancies and singleton births were included. After excluding those with diabetes and kidney disease, 200 women with renal agenesis were matched 1:4 by age (within 2 years), race, and history of hypertension to women with 2 kidneys. Predictor Renal agenesis defined by International Classification of Diseases, Ninth Revision ( ICD-9 ) codes prior to pregnancy. Outcomes The primary outcome was adverse maternal outcomes, including preterm delivery, delivery by cesarean section, preeclampsia/eclampsia, and hospital length of stay. Adverse neonatal end points were considered as a secondary outcome and included low birth weight ( Results Mean gestational age at delivery was 37.9±2.1 weeks for women with renal agenesis compared to 38.6±1.8 weeks for women with 2 kidneys. Compared with women with 2 kidneys, those with renal agenesis had increased risk for preterm delivery (OR, 2.88; 95% CI, 1.86-4.45), delivery by cesarean section (OR, 2.11; 95% CI, 1.49-2.99), preeclampsia/eclampsia (OR, 2.41; 95% CI, 1.23-4.72), and length of stay longer than 3 days (OR, 1.81; 95% CI, 1.18-2.78). Renal agenesis was not significantly associated with increased risk for infant death/transfer to acute facility (OR, 2.60; 95% CI, 0.57-11.89) or low birth weight after accounting for preterm delivery (OR, 2.11; 95% CI, 0.76-5.88). Limitations Renal agenesis was identified by ICD-9 code, not by imaging of the abdomen. Conclusion Women with unilateral renal agenesis have a higher risk for adverse outcomes in pregnancy.

Background Few quantitative nephrology-specific simulations assess fellow competency. We describe the development and initial validation of a formative objective structured clinical examination (OSCE) assessing fellow competence in ordering acute dialysis. Methods The three test scenarios were acute continuous renal replacement therapy, chronic dialysis initiation in moderate uremia and acute dialysis in end-stage renal disease-associated hyperkalemia. The test committee included five academic nephrologists and four clinically practicing nephrologists outside of academia. There were 49 test items (58 points). A passing score was 46/58 points. No item had median relevance less than ‘important’. The content validity index was 0.91. Ninety-five percent of positive-point items were easy–medium difficulty. Preliminary validation was by 10 board-certified volunteers, not test committee members, a median of 3.5 years from graduation. The mean score was 49 [95% confidence interval (CI) 46–51], κ = 0.68 (95% CI 0.59–0.77), Cronbach’s α = 0.84. Results We subsequently administered the test to 25 fellows. The mean score was 44 (95% CI 43–45); 36% passed the test. Fellows scored significantly less than validators (P

OBJECTIVE:The high pill burden of many phosphate binders (PBs) may contribute to increased prevalence of hyperphosphatemia and poor nutritional status observed among patients undergoing maintenance hemodialysis therapy. We examined the real-world effectiveness of sucroferric oxyhydroxide (SO), a PB with low pill burden, in managing serum phosphorus in patients with prevalent hemodialysis over a 1-year period. DESIGN:Historical cohort analyses of de-identified electronic medical records. SUBJECTS:In-center hemodialysis patients switched from another PB to SO therapy as part of routine care with 12months of uninterrupted SO prescriptions recorded, and documented serum phosphorus levels were eligible for inclusion. Clinical data were extracted from a pharmacy service, FreseniusRx, database and Fresenius Kidney Care clinical data warehouse. MAIN OUTCOME MEASURES:Comparisons were made between the 91-day period before SO initiation (i.e., baseline) and the 4 consecutive 91-day intervals of SO treatment (Q1-Q4). Clinical measures included achievement of target phosphorus levels (≤5.5mg/dL) and mean number of PB pills/day. RESULTS:Among 530 analyzed patients, the proportion achieving target serum phosphorus levels increased by >100% 1year after switching to SO therapy, that is, from 17.7% at baseline to 24.5%, 30.5%, 36.4%, and 36.0% at Q1 through Q4, respectively (P&nbsp

Background: Latinos with end-stage renal disease (ESRD) have worse mental and kidney composite health-related quality of life (HRQOL) scores compared to non-Latino ESRD patients. Latino ESRD patients uniquely report that social factors (e.g., lack of care coordination, food insecurity, and low health literacy) and mental health influence their HRQOL. We developed a culturally tailored peer navigator (PN) intervention to improve the HRQOL of Latinos on hemodialysis. Objective: To determine the feasibility of the PN intervention. Design: Single-arm prospective study. The PN provided individualized support with advance care planning, care coordination, and counseling about the importance of diet and mental health. Setting and Participants: Latino with ESRD receiving scheduled outpatient thrice-weekly hemodialysis or reliant on emergency-only hemodialysis in Denver. Main measures: Recruitment, retention rates, data completeness, intervention dose, patient- and staff-reported satisfaction with the intervention. Results: Of 49 eligible patients, 40 (82%) agreed to participate. The majority of participants received scheduled outpatient hemodialysis (75%), 20 were women (50%), with a mean (standard deviation [SD]) age of 56 (13) years. No participants withdrew from the intervention. One participant died. The mean (SD) number of PN visits per participant was 7 (2) and the mean (SD) length of the visits was 97 minutes (49). The majority of visits took place at the hemodialysis facility (59%) and home (27%). The vast majority of participants reported that the PN improved their quality of life as a patient on hemodialysis (95%). Conclusions: The PN intervention achieved feasibility goals and was well received by participants.

Maintenance of calcium levels within a narrow physiological range is essential to life. Calcium homeostasis is complex and tightly regulated and depends on regulation of calcium fluxes within the intestine, kidney, and bones. Calcium metabolism is controlled by calcium itself through a calcium receptor and several hormones, the major ones of which are parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH)2D). PTH and 1,25(OH)2D exert their effects on the gastrointestinal tract, kidney, and bone in order to maintain normal levels of calcium. Hypercalcemia and hypocalcemia indicate critical disruptions of calcium homeostasis. This chapter reviews the regulation of calcium homeostasis and the diagnosis and management of disorders of calcium metabolism.

Background: Low serum bicarbonate concentrations are associated with mortality and kidney disease progression. Data regarding associations between bicarbonate and cardiovascular disease (CVD) are scarce. Methods: We performed a cohort study of 6,229 adult participants from the Multi-Ethnic Study of Atherosclerosis, a community-based cohort free of CVD at baseline. Serum bicarbonate was measured at baseline. Cardiovascular outcomes were defined as: (1) subclinical CVD (left ventricular mass [LVM] and aortic pulse pressure [PP] measured at baseline), (2) incident atherosclerotic cardiovascular events (CVE; composite of myocardial infarction, resuscitated cardiac arrest, stroke, coronary heart disease death, and stroke death), and (3) incident heart failure. Results: During a median (interquartile range) follow-up of 8.5 (7.7-8.6) years, 331 (5.3%) participants had an incident CVE and 174 (2.8%) developed incident heart failure. We stratified analyses by use of diuretics because we observed a significant interaction between diuretic use and bicarbonate with study outcomes. Among diuretic nonusers, with adjustment, bicarbonate ≥25 mEq/L was associated with an estimated 3.0 g greater LVM (95% CI 0.5-5.0) and 1.0 mm Hg higher aortic PP (95% CI 0.4-2.0) compared to bicarbonate 23-24 mEq/L. Each 1 mEq/L of bicarbonate increase was associated with a 13% higher risk of incident heart failure (hazards ratio 1.13, 95% CI 1.01-2.11). Among diuretic users, higher bicarbonate was not associated with CVD. Bicarbonate was not associated with incident atherosclerotic CVE irrespective of diuretic use. Conclusion: Among nonusers of diuretics in a large community-based study, higher serum bicarbonate concentrations are associated with subclinical CVD and new heart failure.

Background: Long-term patterns of fibroblast growth factor 23 (FGF23) are poorly characterized among dialysis patients. Objectives: To identify different FGF23 trajectories and determine clinical factors that predict distinct FGF23 trajectories and whether FGF23 trajectories differ in regard to their associations with all-cause mortality among prevalent hemodialysis patients. Methods: The HEMO study was a randomized multicenter study evaluating the effects of high-dose vs. standard-dose and high-flux vs. low-flux hemodialysis on mortality. We measured intact FGF23 levels in stored serum samples at baseline and annually among 919 HEMO participants and identified FGF23 trajectories using group-based modeling. Logistic regression determined predictors of trajectories. Cox regression models evaluated the association between trajectory and all-cause mortality. Results: We identified 5 distinct FGF23 trajectory groups during the initial 24 months: low stable, low increasing, elevated increasing, elevated decreasing, and elevated stable. In multivariable models, diabetes, high dose dialysis, no venous catheter, low serum calcium, phosphorus, and interleukin-6, no vitamin D analog use, and greater residual kidney function were associated with the low stable trajectory group compared to the elevated stable group. High flux dialysis, no venous catheter, and low serum phosphorus and 25-hydroxyvitamin D were associated with the elevated decreasing trajectory group compared to the elevated stable group. After full adjustment, the low stable trajectory group was associated with reduced mortality (hazard ratio [HR] 0.61; 95% CI ­0.41–0.91) compared to the elevated stable trajectory group. Conclusions: We identified 5 distinct FGF23 trajectories over 24 months among HEMO study participants including a decreasing trajectory. The low stable FGF23 trajectory was associated with a reduced HR of all-cause mortality.

Summary: Chronic kidney disease mineral bone disorder (CKD-MBD) is common in end-stage renal disease and is associated with an increased risk of cardiovascular morbidity and mortality. Mainstays of treatment include decreasing serum phosphorus level toward the normal range with dietary interventions and phosphate binders and treating increased parathyroid hormone levels with activated vitamin D and/or calcimimetics. There is significant variation in serum levels of mineral metabolism markers, intestinal absorption of phosphorus, and therapeutic response among individual patients and subgroups of patients with end-stage renal disease. This variation may be partly explained by polymorphisms in genes associated with calcium and phosphorus homeostasis such as the calcium-sensing receptor gene, the vitamin D–binding receptor gene, and genes associated with vascular calcification. In this review, we discuss how personalized medicine may be used for the management of CKD-MBD and how it ultimately may lead to improved clinical outcomes. Although genetic variants may seem attractive targets to tailor CKD-MBD therapy, complete understanding of how these polymorphisms function and their clinical utility and applicability to personalized medicine need to be determined.

CKD mineral and bone disorder (CKD-MBD) is characterized by several inter-related abnormalities in circulating vitamin D metabolites and related regulatory hormones ([1][1]). Reduced kidney function leads to reduced circulating concentrations of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active

Abnormalities in mineral metabolism are a universal complication in dialysis patients and are associated with an increased risk of cardiovascular disease and mortality. Hyperphosphatemia, increased fibroblast growth factor 23 levels and secondary hyperparathyroidism are all strongly associated with adverse outcomes in end stage renal disease (ESRD) and most treatment strategies target these parameters. Over the past few years, new therapies have emerged for the treatment of abnormalities of mineral metabolism in ESRD and many are promising. This article will review these new therapeutic options including the potential advantages and disadvantages compared to existing therapies.

Background Pregnancy in kidney disease is considered high risk, but the degree of this risk is unclear. We tested the hypothesis that kidney disease in pregnancy is associated with adverse maternal and fetal outcomes. Study Design Retrospective study comparing pregnant women with and without kidney disease. Setting & Participants Using data from an integrated health care delivery system from 2000 through 2013, a total of 778 women met the criteria for kidney disease. Using a pool of 74,105 women without kidney disease, we selected 778 women to use for matches for the women with kidney disease. These women were matched 1:1 by age, race, and history of diabetes, chronic hypertension, liver disease, and connective tissue disease. Predictor Kidney disease was defined using the NKF-KDOQI definition for chronic kidney disease or International Classification of Diseases, Ninth Revision codes prior to pregnancy or serum creatinine level > 1.2mg/dL and/or proteinuria in the first trimester. Outcomes & Measurements Maternal outcomes included preterm delivery, delivery by cesarean section, preeclampsia/eclampsia, length of stay at hospital (>3 days), and maternal death. Fetal outcomes included low birth weight (weight Results Compared with women without kidney disease, those with kidney disease had 52% increased odds of preterm delivery (OR, 1.52; 95% CI, 1.16-1.99) and 33% increased odds of delivery by cesarean section (OR, 1.33; 95% CI, 1.06-1.66). Infants born to women with kidney disease had 71% increased odds of admission to the neonatal intensive care unit or infant death compared with infants born to women without kidney disease (OR, 1.71; 95% CI, 1.17-2.51). Kidney disease also was associated with 2-fold increased odds of low birth weight (OR, 2.38; 95% CI, 1.64-3.44). Kidney disease was not associated with increased risk of maternal death. Limitations Data for level of kidney function and cause of death not available. Conclusions Kidney disease in pregnancy is associated independently with adverse maternal and fetal outcomes when other comorbid conditions are controlled by matching.

African Americans are at increased risk for cardiovascular and metabolic diseases, including obesity, high BP, diabetes, CKD, myocardial infarction, and stroke. Here we summarize the current risks and provide an overview of the underlying risk factors that may account for these associations. By reviewing the relationship between cardiovascular and renal diseases and the African-American population during the early 20th century, the historic and recent associations of African heritage with cardiovascular disease, and modern population genetics, it is possible to assemble strong hypotheses for the primary underlying mechanisms driving the increased frequency of disease in African Americans. Our studies suggest that underlying genetic mechanisms may be responsible for the increased frequency of high BP and kidney disease in African Americans, with particular emphasis on the role of APOL1 polymorphisms in causing kidney disease. In contrast, the Western diet, particularly the relatively high intake of fructose-containing sugars and sweetened beverages, appears to be the dominant force driving the increased risk of diabetes, obesity, and downstream complications. Given that intake of added sugars is a remediable risk factor, we recommend clinical trials to examine the reduction of sweetened beverages as a primary means for reducing cardiovascular risk in African Americans.