Sexual and gender minority relevant policies in Canadian and United States organ and tissue donation and transplantation systems: An opportunity to improve equity and safety.

Current policies in organ and tissue donation and transplantation (OTDT) systems in Canada and the United States unnecessarily restrict access to donation for sexual and gender minorities (SGMs) and pose safety risks to transplant recipients. We compare SGM-relevant policies between the Canadian and United States systems. Policy domains include the risk assessment of living and deceased organ and tissue donors, physical examination considerations, viral testing recommendations, and informed consent and communication. Identified gaps between current evidence and existing OTDT policies along with differences in SGM-relevant policies between systems, represent an opportunity for improvement. Specific recommendations for OTDT system policy revisions to achieve these goals include the development of behavior-based, gender-neutral risk assessment criteria, a reduction in current SGM no-sexual contact period requirements pending development of inclusive criteria, and destigmatization of sexual contact with people living with human immunodeficiency virus. OTDT systems should avoid rectal examinations to screen for evidence of receptive anal sex without consent and mandate routine nucleic acid amplification test screening for all donors. Transplant recipients must receive enhanced risk-to-benefit discussions regarding decisions to accept or decline an offer of an organ classified as increased risk. These recommendations will expand the donor pool, enhance equity for SGM people, and improve safety and outcomes for transplant recipients.

Association between serum estradiol and cardiovascular health among transgender adults using gender-affirming estrogen therapy.

Gender-affirming estrogen therapy (GAET) is commonly used for feminization in transgender and nonbinary (TNB) individuals, yet the optimal rate of change (ROC) in estradiol levels for cardiovascular health is unclear. We examined the association between serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and Web of Science were systematically searched (inception-April 2023) for original articles reporting serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Data extraction was completed in duplicate following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Stratified random effect meta-analyses using serum estradiol ROC (serum estradiolbaseline - serum estradiolfollow-up/study duration) was used to assess longitudinal studies (low, 0 < ROC ≤ 1 pg/mL/mo; moderate, 1 < ROC ≤ 3 pg/mL/mo; high, ROC ≥ 3 pg/mL/mo). Thirty-five studies (13 cross-sectional, 19 cohort, and 3 trials) were included. Two studies collectively reported 50 cardiovascular-related deaths, and four collectively reported 23 adverse cardiovascular events. Nineteen studies reporting cardiovascular risk factors were meta-analyzed by ROC stratum (low = 5; moderate = 6; high = 8), demonstrating an association between moderate [0.40, 95% confidence interval (CI): 0.22, 0.59 kg/m2, I2 = 28.2%] and high (0.46, 95% CI: 0.15, 0.78 kg/m2; I2 = 0.0%) serum estradiol ROC and increased body mass index. High (-6.67, 95% CI: -10.65, -2.68 mg/dL; I2 = 0.0%) serum estradiol ROC was associated with decreased low-density lipoproteins. Low (-7.05, 95% CI: -10.40, -3.70 mmHg; I2 = 0.0%) and moderate (-3.69, 95% CI: -4.93, -2.45 mmHg; I2 = 0.0%) serum estradiol ROCs were associated with decreases in systolic blood pressure. In TNB adults using GAET, serum estradiol ROC may influence cardiovascular risk factors, which may have implications for clinical cardiovascular outcomes.NEW & NOTEWORTHY In this systematic review and meta-analysis of 35 studies involving 7,745 participants, high rates of serum estradiol change were associated with small increases in body mass index. Moderate to high rates of change were associated with decreases in low-density lipoprotein. Low rates of change were associated with small decreases in systolic blood pressure. Rate of serum estradiol change in adults using gender-affirming estrogen therapy may influence cardiovascular risk factors, though further research is warranted.

A Holistic Framework for the Evaluation of Kidney Function in a Gender-Diverse Landscape.

The most commonly used equations to estimate glomerular filtration rate incorporate a binary male-female sex coefficient, which has important implications for the care of transgender, gender-diverse, and nonbinary (TGD) people. Whether "sex assigned at birth" or a binary "gender identity" is most appropriate for the computation of estimated glomerular filtration rate (eGFR) is unknown. Furthermore, the use of gender-affirming hormone therapy (GAHT) for the development of physical changes to align TGD people with their affirmed gender is increasingly common, and may result in changes in serum creatinine and cystatin C, the biomarkers commonly used to estimate glomerular filtration rate. The paucity of current literature evaluating chronic kidney disease (CKD) prevalence and outcomes in TGD individuals on GAHT makes it difficult to assess any effects of GAHT on kidney function. Whether alterations in serum creatinine reflect changes in glomerular filtration rate or simply changes in muscle mass is unknown. Therefore, we propose a holistic framework to evaluate kidney function in TGD people. The framework focuses on kidney disease prevalence, risk factors, sex hormones, eGFR, other kidney function assessment tools, and the mitigation of health inequities in TGD people.

Heart failure events in randomized controlled trials for adults receiving maintenance dialysis: a meta-epidemiologic study.

BACKGROUND AND HYPOTHESIS: Heart failure is characterized as cardiac dysfunction resulting in elevated cardiac filling pressures with symptoms and signs of congestion. Distinguishing heart failure from other causes of similar presentations in patients with kidney failure is challenging but necessary, and is needed in randomized controlled trials (RCTs) to accurately estimate treatment effects. The objective of this study was to review heart failure events, their diagnostic criteria and adjudication in RCTs of patients with kidney failure treated with dialysis. We hypothesized that heart failure events, diagnostic criteria and adjudication were infrequently reported in RCTs in dialysis. METHODS: We conducted a meta-epidemiologic systematic review of RCTs from high impact medical, nephrology and cardiology journals from 2000 to 2020. RCTs were eligible if they enrolled adults receiving maintenance dialysis for kidney failure and evaluated any intervention. Results. Of 561 RCTs in patients receiving dialysis, 36 (6.4%) reported heart failure events as primary (10, 27.8%) or secondary (31, 86.1%) outcomes. 10 of the 36 (27.8%) RCTs provided heart failure event diagnostic criteria and 5 of these 10 (50%) adjudicated heart failure events. These 10 RCTs included event diagnostic criteria for heart failure or heart failure hospitalizations, and their criteria included dyspnea (5/10), edema (2/10), rales/crackles (4/10), chest x-ray pulmonary edema or vascular redistribution (4/10), treatment in an acute setting (6/10) and ultrafiltration or dialysis (4/10). No study explicitly distinguished heart failure from volume overload secondary to non-adherence or underdialysis. CONCLUSION: Overall, we found that heart failure events are infrequently reported in RCTs in dialysis and are heterogeneously defined. Further research is required to develop standardized diagnostic criteria that are practical and meaningful to patients and clinicians.

Sodium-glucose co-transporter-2 inhibitors are associated with kidney benefits at all degrees of albuminuria: A retrospective cohort study of adults with diabetes.

AIM: To estimate the real-world effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) at reducing loss of kidney function and adverse kidney events in adults with varying levels of albuminuria. MATERIALS AND METHODS: In this retrospective cohort study using administrative data, we matched new SGLT2i users 1:2 to DPP4i users on diabetes therapy, chronic kidney disease (CKD) stage, albuminuria and time-conditional propensity score. Albuminuria was defined by spot urine albumin or equivalent as mild, moderate or severe. Linear regression was used to model the estimated glomerular filtration rate (eGFR), and Poisson regression for a composite kidney outcome (> 40% loss of eGFR, kidney replacement therapy or death from kidney causes) and all-cause mortality. RESULTS: SGLT2i users (n = 19 238, median age 57.9 years, female 40.9%) had mostly nil/mild albuminuria (70.7%). SGLT2is were associated with a 1.36 (95% CI 0.98-1.74) mL/min/1.73m2 (P < .001) acute (≤ 60 days) decline in eGFR, relative to DPP4is. Thereafter, SGLT2is were associated with 1.04 (95% CI 0.93-1.15) mL/min/1.73m2 (P < .001) less annual eGFR loss. SGLT2i users had fewer adverse kidney outcomes (incidence rate ratio [IRR] 0.58 [0.47-0.71]; P < .001), but not all-cause mortality (IRR 0.82 [0.66-1.01]; P = .06). Outcomes were similar considering only those with nil/mild albuminuria. CONCLUSIONS: SGLT2is may prevent eGFR decline and reduce the risk of adverse kidney events in adults with diabetes and nil or non-severe albuminuria.

Inequities in organ and tissue donation and transplantation for sexual orientation and gender identity diverse people: A scoping review.

Sexual orientation and gender identity (SOGI)-diverse populations experience discrimination in organ and tissue donation and transplantation (OTDT) systems globally. We assembled a multidisciplinary group of clinical experts as well as SOGI-diverse patient and public partners and conducted a scoping review including citations on the experiences of SOGI-diverse persons in OTDT systems globally to identify and explore the inequities that exist with regards to living and deceased OTDT. Using scoping review methods, we conducted a systematic literature search of relevant electronic databases from 1970 to 2021 including a grey literature search. We identified and screened 2402 references and included 87 unique publications. Two researchers independently coded data in included publications in duplicate. We conducted a best-fit framework synthesis paired with an inductive thematic analysis to identify synthesized benefits, harms, inequities, justification of inequities, recommendations to mitigate inequities, laws and regulations, as well as knowledge and implementation gaps regarding SOGI-diverse identities in OTDT systems. We identified numerous harms and inequities for SOGI-diverse populations in OTDT systems. There were no published benefits of SOGI-diverse identities in OTDT systems. We summarized recommendations for the promotion of equity for SOGI-diverse populations and identified gaps that can serve as targets for action moving forward.

Improving the inclusion of transgender and nonbinary individuals in the planning, completion, and mobilization of cardiovascular research.

Cardiovascular disease is the leading cause of morbidity and mortality globally. Transgender and nonbinary (TNB) individuals face unclear but potentially significant cardiovascular health inequities, yet no TNB-specific evidence-based interventions for cardiovascular risk reduction currently exist. To address this gap, we propose a road map to improve the inclusion of TNB individuals in the planning, completion, and mobilization of cardiovascular research. In doing so, the adoption of inclusive practices would optimize cardiovascular health surveillance and care for TNB communities.

Management of antineutrophil cytoplasmic antibody-associated vasculitis: a changing tide.

PURPOSE OF REVIEW: Antineutrophil cytoplasmic antibody associated vasculitis (AAV) is a group of autoimmune disorders of small blood vessels. While outcomes in AAV have improved with the use of glucocorticoids (GC) and other immunosuppressants, these treatments are associated with significant toxicities. Infections are the major cause of mortality within the first year of treatment. There is a move towards newer treatments with better safety profiles. This review reflects on recent advances in the treatment of AAV. RECENT FINDINGS: The role of plasma exchange (PLEX) in AAV with kidney involvement has been clarified with new BMJ guideline recommendations following the publication of PEXIVAS and an updated meta-analysis. Lower dose GC regimens are now standard of care. Avacopan (C5a receptor antagonist) was noninferior to a regimen of GC therapy and is a potential steroid-sparing agent. Lastly, rituximab-based regimens were noninferior to cyclophosphamide in two trials for induction of remission and superior to azathioprine in one trial of maintenance of remission. SUMMARY: AAV treatments have changed tremendously over the past decade with a drive towards targeted PLEX use, increased rituximab use and lower GC dosing. Striking a crucial balance between morbidity from relapses and toxicities from immunosuppression remains a challenging path to navigate.

Sex and Gender in Randomized Controlled Trials of Adults Receiving Maintenance Dialysis: A Meta-epidemiologic Study.

RATIONALE & OBJECTIVE: How sex and gender concepts are incorporated into randomized controlled trials (RCTs) in adults with kidney failure receiving maintenance dialysis is largely unknown. We describe these practices in published journal articles as well as investigate the proportion of women and female participants in these studies. STUDY DESIGN: Meta-epidemiologic study. SETTING & STUDY POPULATIONS: RCTs in maintenance dialysis. SELECTION CRITERIA FOR STUDIES: Trials published in high-impact journals in 2000-2020. DATA EXTRACTION: Implemented in duplicate with conflicts resolved by a third reviewer. ANALYTICAL APPROACH: Meta-regression was performed to identify trial characteristics independently associated with the proportion of women and female participants. RESULTS: Among 561 included RCTs, 69.7% were parallel and 28.0% were crossover in design; 80.6% were conducted in the hemodialysis population; and 25% of trials compared the treatment of interest with a placebo arm, 25% with a usual care treatment arm, and 50% with an active alternative therapy arm. Of the RCTS, 37.6% were masked. The median size was 60 (IQR, 26-151) participants, and the median follow-up period was 154 (IQR, 42-365) days. The mean proportion of women or female participants was 0.40±0.13 (SD): 39.0% of trials reported sex, and 26.6% reported the gender of the participants. Also, 56.2% referred to participants as females, 25.3% referred to participants as women, and 15.5% referred to both females and women. No trial characteristic other than region (ß of 0.062 [95% CI, 0.007-0.117] for Asia) was associated with the proportion of women or female participants. Considering trial design and conduct, 2.7% of trials used sex and/or gender as an inclusion criterion, 26.6% as an exclusion criterion, 4.5% for randomization, 4.8% for subgroup analyses, and 15.7% for covariate adjustment. LIMITATIONS: Only high-impact journal articles were studied; and the included studies lacked pediatric trials, those addressing chronic kidney disease or kidney transplantation, any trials from Africa and underrepresentation of other regions, and missing data. CONCLUSIONS: RCTs in dialysis are representative of the general dialysis population with regard to sex and gender but they uncommonly report both and often do not include either in their reporting or analysis.

Metabolic acidosis is undertreated and underdiagnosed: a retrospective cohort study.

BACKGROUND: Guidelines recommend treatment of metabolic acidosis (MA) in patients with chronic kidney disease (CKD), but the diagnosis and treatment rates in real-world settings are unknown. We investigated the frequency of MA treatment and diagnosis in patients with CKD. METHODS: In this retrospective cohort study, we examined administrative health data from two US databases [Optum's de-identified Integrated Claims + Clinical Electronic Health Record Database (US EMR cohort; 1 January 2007 to 30 June 2019) and Symphony Health Solutions IDV® (US claims cohort; 1 May 2016 to 30 April 2019)] and population-level databases from Manitoba, Canada (1 April 2006 to 31 March 2018). Patients who met laboratory criteria indicative of CKD and chronic MA were included: two consecutive estimated glomerular filtration results <60 mL/min/1.73 m2 and two serum bicarbonate results 12 to <22 mEq/L over 28-365 days. Outcomes included treatment of MA (defined as a prescription for oral sodium bicarbonate) and a diagnosis of MA (defined using administrative records). Outcomes were assessed over a 3-year period (1 year pre-index, 2 years post-index). RESULTS: A total of 96 184 patients were included: US EMR, 6179; Manitoba, 3223; US Claims, 86 782. Sodium bicarbonate treatment was prescribed for 17.6%, 8.7% and 15.3% of patients, and a diagnosis was found for 44.7%, 20.9% and 20.9% of patients, for the US EMR, Manitoba and US Claims cohorts, respectively. CONCLUSIONS: This analysis of 96 184 patients with laboratory-confirmed MA from three independent cohorts of patients with CKD and MA highlights an important diagnosis and treatment gap for this disease-modifying complication.

Patient views regarding cannabis use in chronic kidney disease and kidney failure: a survey study.

BACKGROUND: Cannabis is frequently used recreationally and medicinally, including for symptom management in patients with kidney disease. METHODS: We elicited the views of Canadian adults with kidney disease regarding their cannabis use. Participants were asked whether they would try cannabis for anxiety, depression, restless legs, itchiness, fatigue, chronic pain, decreased appetite, nausea/vomiting, sleep, cramps and other symptoms. The degree to which respondents considered cannabis for each symptom was assessed with a modified Likert scale ranging from 1 to 5 (1, definitely would not; 5, definitely would). Multilevel multivariable linear regression was used to identify respondent characteristics associated with considering cannabis for symptom control. RESULTS: Of 320 respondents, 290 (90.6%) were from in-person recruitment (27.3% response rate) and 30 (9.4%) responses were from online recruitment. A total of 160/320 respondents (50.2%) had previously used cannabis, including smoking [140 (87.5%)], oils [69 (43.1%)] and edibles [92 (57.5%)]. The most common reasons for previous cannabis use were recreation [84/160 (52.5%)], pain alleviation [63/160 (39.4%)] and sleep enhancement [56/160 (35.0%)]. Only 33.8% of previous cannabis users thought their physicians were aware of their cannabis use. More than 50% of respondents probably would or definitely would try cannabis for symptom control for all 10 symptoms. Characteristics independently associated with interest in trying cannabis for symptom control included symptom type (pain, sleep, restless legs), online respondent {ß = 0.7 [95% confidence interval (CI) 0.1-1.4]} and previous cannabis use [ß = 1.2 (95% CI 0.9-1.5)]. CONCLUSIONS: Many patients with kidney disease use cannabis and there is interest in trying cannabis for symptom control.

Gender-affirming estrogen therapy route of administration and cardiovascular risk: a systematic review and narrative synthesis.

Transgender women (individuals assigned male sex at birth who identify as women) and nonbinary and gender-diverse individuals receiving gender-affirming estrogen therapy (GAET) are at increased cardiovascular risk. Nonoral (i.e., patch, injectable) compared with oral estrogen exposure in cisgender women (individuals assigned female sex at birth who identify as women) may be associated with lower cardiovascular risk, though whether this applies to transgender women and/or gender-diverse individuals is unknown. We sought to determine the association between the route of estrogen exposure (nonoral compared with oral) and cardiovascular risk in transgender women and gender diverse individuals. Bibliographic databases (MEDLINE, Embase, PsycINFO) and supporting relevant literature were searched from inception to January 2022. Randomized controlled trials and observational studies reporting cardiovascular outcomes, such as all-cause and cardiovascular mortality, adverse cardiovascular events, and cardiovascular risk factors in individuals using nonoral compared with oral gender-affirming estrogen therapy were included. The search strategy identified 3,113 studies, 5 of which met inclusion criteria (3 prospective cohort studies, 1 retrospective cohort study, and 1 cross-sectional study; n = 259 participants, range of duration of exposure of 2 to 60 mo). One out of five studies reported on all-cause and cardiovascular mortality or adverse cardiovascular events. All five studies reported lipid levels [low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC)], whereas only two studies reported systolic blood pressure (SBP) and diastolic blood pressure (DBP). Limited studies have examined the effect of the route of GAET on all-cause cardiovascular mortality, morbidity, and risk factors. In addition, there is significant heterogeneity in studies examining the cardiovascular effects of GAET.NEW & NOTEWORTHY This study is the first to summarize the potential effect of nonoral versus oral gender-affirming estrogen therapy use on cardiovascular risk factors in transgender women or nonbinary or gender-diverse individuals. Heterogeneity of studies in reporting gender-affirming estrogen therapy formulation, dose, and duration of exposure limits quantification of the effect of gender-affirming estrogen therapy on all-cause and cardiovascular mortality, adverse cardiovascular events, and cardiovascular risk factors. This systematic review highlights the needs for large prospective cohort studies with appropriate stratification of gender-affirming estrogen therapy by dose, formulation, administration route, and sufficient follow-up and analyses to limit selection bias to optimize the cardiovascular care of transgender, nonbinary, and gender-diverse individuals.

Hyperkalemia-Related Discontinuation of Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in CKD: A Population-Based Cohort Study.

RATIONALE & OBJECTIVE: Renin-angiotensin-aldosterone system (RAAS) inhibitors are evidence-based therapies that slow the progression of chronic kidney disease (CKD) but can cause hyperkalemia. We aimed to evaluate the association of discontinuing RAAS inhibitors after an episode of hyperkalemia and clinical outcomes in patients with CKD. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults in Manitoba (7,200) and Ontario (n = 71,290), Canada, with an episode of de novo RAAS inhibitor-related hyperkalemia (serum potassium ≥ 5.5 mmol/L) and CKD. EXPOSURE: RAAS inhibitor prescription. OUTCOME: The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular (CV) mortality, fatal and nonfatal CV events, dialysis initiation, and a negative control outcome (cataract surgery). ANALYTICAL APPROACH: Cox proportional hazards models examined the association of RAAS inhibitor continuation (vs discontinuation) and outcomes using intention to treat approach. Sensitivity analyses included time-dependent, dose-dependent, and propensity-matched analyses. RESULTS: The mean potassium and mean estimated glomerular filtration rate were 5.8 mEq/L and 41 mL/min/1.73 m2, respectively, in Manitoba; and 5.7 mEq/L and 41 mL/min/1.73 m2, respectively, in Ontario. RAAS inhibitor discontinuation was associated with a higher risk of all-cause mortality (Manitoba: HR, 1.32 [95% CI, 1.22-1.41]; Ontario: HR, 1.47 [95% CI, 1.41-1.52]) and CV mortality (Manitoba: HR, 1.28 [95% CI, 1.13-1.44]; and Ontario: HR, 1.32 [95% CI, 1.25-1.39]). RAAS inhibitor discontinuation was associated with an increased risk of dialysis initiation in both cohorts (Manitoba: HR, 1.65 [95% CI, 1.41-1.85]; Ontario: HR, 1.11 [95% CI, 1.08-1.16]). LIMITATIONS: Retrospective study and residual confounding. CONCLUSIONS: RAAS inhibitor discontinuation is associated with higher mortality and CV events compared with continuation among patients with hyperkalemia and CKD. Strategies to maintain RAAS inhibitor treatment after an episode of hyperkalemia may improve clinical outcomes in the CKD population.

Variability in Cardiac Biomarkers during Hemodialysis: A Prospective Cohort Study.

BACKGROUND: The effect of hemodialysis on cardiac biomarkers is unclear. We sought to evaluate the degree and causes of intradialytic variability of high sensitivity troponin I (hs-TnI), galectin-3 (gal-3), and heart-type fatty acid binding protein (hFABP). METHODS: hs-TnI, gal-3, and hFABP were prospectively measured pre-dialysis and post-dialysis for 1 week every month for 6 months in 178 prevalent adult hemodialysis patients at a single center in Hamilton, Canada. The degree of change from pre-dialysis to post-dialysis for each cardiac biomarker was estimated with multilevel linear regression models. RESULTS: The median change in the concentration of hs-TnI during hemodialysis was -1 ng/L (interquartile range [IQR] -1 to 2 ng/L) while gal-3 and hFABP changed by -36.3 ng/mL (IQR -27.7 to -46.8 ng/mL) and -19.41 ng/mL (IQR -13.61 to -26.87 ng/mL), respectively. The median (IQR) percentage intradialytic changes for hs-TnI, gal-3, and hFABP were 2.6% (-4.4% to 12.5%), -59.8% (-54.7% to -64.8%) and -35.3% (-28.4% to -42.1%), respectively. Ultrafiltration was associated with an increase in concentration of hs-TnI, gal-3, and hFABP (mean 0.99 ng/L, 1.05 ng/mL, and 1.9 ng/mL per L ultrafiltration, respectively, P < 0.001). Both gal-3 and hFABP concentrations decreased in association with the volume of blood processed (P < 0.001) and with hemodialysis treatment time (P = 0.02 and P = 0.04) while hs-TnI concentration decreased only in association with hemodialysis treatment time (P < 0.001). CONCLUSIONS: Ultrafiltration volume and hemodialysis treatment time influenced hs-TnI, gal-3, and hFABP concentrations during hemodialysis and should be considered when interpreting their measurement.

Metabolic acidosis is associated with increased risk of adverse kidney outcomes and mortality in patients with non-dialysis dependent chronic kidney disease: an observational cohort study.

BACKGROUND: Management of chronic kidney disease (CKD) requires the management of risk factors, such as hypertension and albuminuria, that affect CKD progression. Identification of additional modifiable risk factors is necessary to develop new treatment strategies for CKD. We sought to quantify the association of metabolic acidosis with CKD progression and mortality in a large U.S. community-based cohort. METHODS: In this longitudinal, retrospective cohort study we identified non-dialysis-dependent patients with stage 3‒5 CKD from Optum's de-identified integrated electronic health records. We selected cohorts of patients with confirmed metabolic acidosis or normal serum bicarbonate levels based on 2 consecutive serum bicarbonate values: 12 to < 22 mEq/L or 22-29 mEq/L, respectively, 28‒365 days apart. The primary composite outcome was ≥ 40 % decline in estimated glomerular filtration rate (eGFR), renal replacement therapy (chronic dialysis or kidney transplant), or all-cause mortality (DD40). Secondary outcomes included each component of the composite outcome. Cox proportional hazards models were used for the DD40 outcome and secondary outcomes, while logistic regression models were used for the DD40 outcome at 2 years. RESULTS: A total of 51,558 patients qualified for the study. The unadjusted 2-year incidence of adverse renal and fatal outcomes was significantly worse among patients in the metabolic acidosis group vs. those who had normal serum bicarbonate levels: 48 % vs. 17 % for DD40, 10 % vs. 4 % for ≥ 40 % decline in eGFR, 20 % vs. 6 % for renal replacement therapy, and 31 % vs. 10 % for all-cause mortality (all P < 0.001). Over a ≤ 10-year period, for each 1-mEq/L increase in serum bicarbonate, the adjusted hazard ratio for DD40 was 0.926 (95 % confidence interval [CI], 0.922-0.930; P < 0.001); over a ≤ 2-year period, the adjusted odds ratio for DD40 was 0.873 (95 % CI, 0.866-0.879; P < 0.001). CONCLUSIONS: In this large community cohort of patients with stage 3‒5 CKD, the presence of metabolic acidosis was a significant, independent risk factor for the composite adverse outcome of CKD progression, renal replacement therapy, and all-cause mortality (DD40).

Recent advances in the treatment of uremic pruritus.

PURPOSE OF REVIEW: This article provides a focused update on uremic pruritus, highlighting the latest evidence concerning the epidemiology, pathophysiology, and treatment options for this common and bothersome condition. RECENT FINDINGS: Half of dialysis patients and a quarter of those with nondialysis chronic kidney disease experience bothersome itch that reduces quality of life and is increasingly recognized to be associated with poor outcomes including mortality. The KALM-1 trial, which reported effective symptomatic relief with difelikefalin, has bolstered support for the role of an imbalance of µ and κ-opioid receptor activity in pruritogenesis. The role of a chronic inflammatory state, increased cytokine levels and altered immune signaling in pruritogenic nerve activation continues to be elucidated with basic science, which paves the wave for future novel therapeutics. In the meantime, gabapentin appears to be the most evidence-based widely available uremic pruritus treatment, as long as care is taken with dosing and monitoring of side-effects. SUMMARY: Uremic pruritus remains a top research priority. Patients with uremic pruritus may be able to look forward to a new decade of understanding, knowledge, and novel treatment options for this burdensome condition. As difelikefalin and other potential agents come to market, cost-effectiveness assessments of these interventions will help determine if the widespread use of them is feasible amongst renal programs.

The Fracture Risk Assessment Tool (FRAX®) predicts fracture risk in patients with chronic kidney disease.

The Fracture Risk Assessment Tool (FRAX®) was developed to predict fracture risk in the general population, but its applicability to patients with chronic kidney disease (CKD) is unknown. Using the Manitoba Bone Mineral Density (BMD) Database, we identified adults not receiving dialysis with available serum creatinine measurements and bone densitometry within 1 year. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Incident major osteoporotic fractures and hip fractures were ascertained from population-based health care databases. The performance of FRAX, derived without and with BMD, was studied in relation to CKD stage. Among 10,099 subjects (mean age 64 ± 13 years, 13.0% male), 2,154 had eGFR 30-60 mL/min/1.73 m2 (CKD stage 3) and 590 had eGFR <30 mL/min/1.73 m2 (CKD stages 4-5). During a 5-year observation period, 772 individuals experienced a major osteoporotic fracture and 226 had a hip fracture. FRAX predicted risk for major osteoporotic fracture and hip fracture in all eGFR strata. For every standard deviation increase in FRAX score derived with BMD, the hazard ratio (HR) for hip fracture was 4.54 (95% confidence interval [CI] 3.57-5.77) in individuals with eGFR ≥ 60 mL/min/1.73m2, 4.52 (95% CI 3.15-6.49) in individuals with eGFR 30-60 mL/min/1.73m2, and 3.10 (95% CI 1.80-5.33) in individuals with eGFR <30 mL/min/1.73m2. The relationship between FRAX and major osteoporotic fracture was stronger in those with CKD compared to those with preserved eGFR. These findings support the use of FRAX to risk stratify patients with non-dialysis CKD for major osteoporotic fractures and hip fractures.

Fracture risk and treatment in chronic kidney disease.

PURPOSE OF REVIEW: Chronic kidney disease (CKD) is associated with the development of mineral bone disorder (MBD), osteoporosis, and fragility fractures. The purpose of this review is to provide an update on recent findings in the diagnosis and treatment of osteoporosis in patients with CKD. RECENT FINDINGS: Multiple observational studies have shown that bone mineral density measurement using DEXA is equally predictive in CKD stages 1-3, as in the general population. Post hoc analyses from randomized trials of bisphosphonates, SERM, RANKL inhibitors and PTH agonists all suggest equal efficacy in mild-moderate CKD. A recent systematic review also found evidence for efficacy of bisphosphonates in patients with a kidney transplant. SUMMARY: Bone mineral density measurement using DEXA is accurate in patients with CKD stages 1-3 and should be considered to guide treatment of osteoporosis. Current treatments are unaffected by mild-to-moderate decline in kidney function, and physicians should use bisphosphonates and other osteoporosis treatments in this population, whenever indicated. Studies evaluating the optimal diagnostic and management strategy in patients with CKD stages (G4-5D) are needed.

Anemia management in chronic kidney disease and dialysis: a narrative review.

PURPOSE OF REVIEW: This review describes the current state of anemia management with erythropoietin (EPO)-stimulating agents and iron supplementation in both chronic kidney disease and dialysis patients, with a focus on novel therapies. RECENT FINDINGS: We review the benefits and risks of EPO-stimulating agents, focusing on health-related quality of life and the uncertainties regarding optimal iron utilization in patients with kidney disease. We discuss novel therapies for iron supplementation including iron-based phosphate binders and dialysate iron delivery as well as alternatives to EPO-stimulating agents including hypoxia-inducible factor prolyl hydroxylase inhibitors. SUMMARY: Individualization of hemoglobin targets using EPO-stimulating agents and iron supplementation may be considered in younger, healthier patients with kidney disease to improve health-related quality of life. Optimal iron utilization in kidney disease patients is unclear, but novel iron base phosphate binders and dialysate iron delivery may play a role in intravenous iron avoidance and its potential complications. Phase 3 randomized controlled trials of hypoxia-inducible factor prolyl hydroxylase inhibitors are ongoing and are promising new alternatives to EPO-stimulating agents and their known adverse effects.

A Methanol Intoxication Outbreak From Recreational Ingestion of Fracking Fluid.

Single-patient methanol intoxications are a common clinical presentation, but outbreaks are rare and usually occur in settings in which there is limited access to ethanol and methanol is consumed as a substitute. In this case report, we describe an outbreak of methanol intoxications that was challenging from a public health perspective and discuss strategies for managing such an outbreak.