In T2DM with CKD, semaglutide reduced major kidney disease events at 3 y.

SOURCE CITATION: Perkovic V, Tuttle KR, Rossing P, et al; FLOW Trial Committees and Investigators. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391:109-121. 38785209.

The impact of dialysate flow rate on haemodialysis adequacy: a systematic review and meta-analysis.

Background: Patients with kidney failure treated with maintenance haemodialysis (HD) require appropriate small molecule clearance. Historically, a component of measuring 'dialysis adequacy' has been quantified using urea kinetic modelling that is dependent on the HD prescription. However, the impact of dialysate flow rate on urea clearance remains poorly described in vivo and its influence on other patient-important outcomes of adequacy is uncertain. Methods: We searched Embase, MEDLINE and the Cochrane Library from inception until April 2022 for randomized controlled trials and observational trials comparing a higher dialysate flow rate (800 ml/min) and lower dialysate flow rate (300 ml/min) with a standard dialysis flow rate (500 ml/min) in adults (age ≥18 years) treated with maintenance HD (>90 consecutive days). We conducted a random effects meta-analysis to estimate the pooled mean difference in dialysis adequacy as measured by Kt/V or urea reduction ratio (URR). Results: A total of 3118 studies were identified. Of those, nine met eligibility criteria and four were included in the meta-analysis. A higher dialysate flow rate (800 ml/min) increased single-pool Kt/V by 0.08 [95% confidence interval (CI) 0.05-0.10, P < .00001] and URR by 3.38 (95% CI 1.97-4.78, P < .00001) compared with a dialysate flow rate of 500 ml/min. Clinically relevant outcomes including symptoms, cognition, physical function and mortality were lacking and studies were generally at a moderate risk of bias due to issues with randomization sequence generation, allocation concealment and blinding. Conclusion: A higher dialysate flow increased urea-based markers of dialysis adequacy. Additional high-quality research is needed to determine the clinical, economic and environmental impacts of higher dialysate flow rates.

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.

Precision Medicine in Diabetic Kidney Disease: A Narrative Review Framed by Lived Experience.

Purpose of review: Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease (CKD) for which many treatments exist that have been shown to prevent CKD progression and kidney failure. However, DKD is a complex and heterogeneous etiology of CKD with a spectrum of phenotypes and disease trajectories. In this narrative review, we discuss precision medicine approaches to DKD, including genomics, metabolomics, proteomics, and their potential role in the management of diabetes mellitus and DKD. A patient and caregivers of patients with lived experience with CKD were involved in this review. Sources of information: Original research articles were identified from MEDLINE and Google Scholar using the search terms "diabetes," "diabetic kidney disease," "diabetic nephropathy," "chronic kidney disease," "kidney failure," "dialysis," "nephrology," "genomics," "metabolomics," and "proteomics." Methods: A focused review and critical appraisal of existing literature regarding the precision medicine approaches to the diagnosis, prognosis, and treatment of diabetes and DKD framed by a patient partner's/caregiver's lived experience. Key findings: Distinguishing diabetic nephropathy from CKD due to other types of DKD and non-DKD is challenging and typically requires a kidney biopsy for a diagnosis. Biomarkers have been identified to assist with the prediction of the onset and progression of DKD, but they have yet to be incorporated and evaluated relative to clinical standard of care CKD and kidney failure risk prediction tools. Genomics has identified multiple causal genetic variants for neonatal diabetes mellitus and monogenic diabetes of the young that can be used for diagnostic purposes and to specify antiglycemic therapy. Genome-wide-associated studies have identified genes implicated in DKD pathophysiology in the setting of type 1 and 2 diabetes but their translational benefits are lagging beyond polygenetic risk scores. Metabolomics and proteomics have been shown to improve diagnostic accuracy in DKD, have been used to identify novel pathways involved in DKD pathogenesis, and can be used to improve the prediction of CKD progression and kidney failure as well as predict response to DKD therapy. Limitations: There are a limited number of large, high-quality prospective observational studies and no randomized controlled trials that support the use of precision medicine based approaches to improve clinical outcomes in adults with or at risk of diabetes and DKD. It is unclear which patients may benefit from the clinical use of genomics, metabolomics and proteomics along the spectrum of DKD trajectory. Implications: Additional research is needed to evaluate the role of the use of precision medicine for DKD management, including diagnosis, differentiation of diabetic nephropathy from other etiologies of DKD and CKD, short-term and long-term risk prognostication kidney outcomes, and the prediction of response to and safety of disease-modifying therapies.

Motif de la revue: La maladie rénale diabétique (MRD) est une cause majeure d'insuffisance rénale chronique (IRC) pour laquelle il existe de nombreux traitements ayant démontré une capacité à prévenir la progression vers l'insuffisance rénale. Avec son spectre de phénotypes et de trajectoires, la MRD s'avère cependant une étiologie complexe et hétérogène de l'IRC. Dans cette revue narrative, nous discutons des approches de la médecine de précision liées à la MRD­notamment la génomique, la métabolomique et la protéomique­et de leur rôle potentiel dans la prise en charge du diabète et de la MRD. Des soignants et un patient ayant une expérience vécue de l'IRC ont participé à cette revue. Sources: Les articles de recherche pertinents ont été identifiés dans MEDLINE et Google Scholar à l'aide des termes de recherche suivants: « diabète ¼, « insuffisance rénale diabétique ¼, « néphropathie diabétique ¼, « insuffisance rénale chronique ¼, « insuffisance rénale ¼, « dialyse ¼, « néphrologie ¼, « génomique ¼, « métabolomique ¼ et « protéomique ¼. Méthodologie: Revue ciblée et évaluation critique­encadrées par l'expérience vécue d'un partenaire patient et de soignants­de la littérature existante portant sur les approches de la médecine de précision pour le diagnostic, le pronostic et le traitement du diabète et de la MRD. Principales observations: Il est difficile de distinguer la néphropathie diabétique de l'IRC due ou non à d'autres types de MRD; le diagnostic nécessite généralement une biopsie rénale. Des biomarqueurs ont été identifiés pour aider à prédire l'apparition et la progression de la MRD, mais ceux-ci doivent encore être intégrés aux normes cliniques de soins et évalués par rapport aux outils prédictifs du risque d'IRC et d'insuffisance rénale. La génomique a permis d'identifier plusieurs variantes génétiques causales du diabète néonatal et du diabète monogénique chez l'enfant, lesquelles peuvent être utilisées à des fins diagnostiques et de définition du traitement hypoglycémiant. Des études couvrant l'ensemble du génome ont permis d'identifier des gènes impliqués dans la physiopathologie de la MRD en contexte de diabète de type 1 et 2, mais leurs avantages translationnels restent en deçà des scores de risque polygéniques. Il a été démontré que la métabolomique et la protéomique améliorent la précision diagnostique de la MRD, qu'elles ont été utilisées pour identifier de nouvelles voies impliquées dans la pathogenèse de la MRD et qu'elles peuvent être employées pour améliorer la prédiction de la progression de l'insuffisance rénale, ainsi que pour prédire la réponse au traitement de la MRD. Limites: Il existe un nombre limité d'études observationnelles prospectives de qualité et d'envergure, dont aucun essai clinique randomisé, appuyant le recours à des d'approches fondées sur la médecine de précision pour améliorer les résultats cliniques des adultes diabétiques ou atteints de MRD, ou présentant un risque pour ces maladies. On ne sait pas exactement quels patients pourraient bénéficier d'une utilisation clinique de la génomique, de la métabolomique et de la protéomique tout au long de la trajectoire de la MRD. Conclusion: Des recherches supplémentaires sont nécessaires pour mieux évaluer le rôle de la médecine de précision dans la prise en charge de la MRD, notamment pour le diagnostic, la différenciation de la néphropathie diabétique d'autres étiologies de la MRD et de l'IRC, la prédiction des risques à court et à long terme sur le pronostic rénal, et la prédiction de l'innocuité et de la réponse aux traitements pouvant modifier l'évolution de la maladie.

AACC/NKF Guidance Document on Improving Equity in Chronic Kidney Disease Care.

BACKGROUND: Kidney disease (KD) is an important health equity issue with Black, Hispanic, and socioeconomically disadvantaged individuals experiencing a disproportionate disease burden. Prior to 2021, the commonly used estimated glomerular filtration rate (eGFR) equations incorporated coefficients for Black race that conferred higher GFR estimates for Black individuals compared to non-Black individuals of the same sex, age, and blood creatinine concentration. With a recognition that race does not delineate distinct biological categories, a joint task force of the National Kidney Foundation and the American Society of Nephrology recommended the adoption of the CKD-EPI 2021 race-agnostic equations. CONTENT: This document provides guidance on implementation of the CKD-EPI 2021 equations. It describes recommendations for KD biomarker testing, and opportunities for collaboration between clinical laboratories and providers to improve KD detection in high-risk populations. Further, the document provides guidance on the use of cystatin C, and eGFR reporting and interpretation in gender-diverse populations. SUMMARY: Implementation of the CKD-EPI 2021 eGFR equations represents progress toward health equity in the management of KD. Ongoing efforts by multidisciplinary teams, including clinical laboratorians, should focus on improved disease detection in clinically and socially high-risk populations. Routine use of cystatin C is recommended to improve the accuracy of eGFR, particularly in patients whose blood creatinine concentrations are confounded by processes other than glomerular filtration. When managing gender-diverse individuals, eGFR should be calculated and reported with both male and female coefficients. Gender-diverse individuals can benefit from a more holistic management approach, particularly at important clinical decision points.

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.

The Effect of Gender-Affirming Hormone Therapy on Measures of Kidney Function: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Gender-affirming hormone therapy modifies body composition and lean muscle mass in transgender persons. We sought to characterize the change in serum creatinine, other kidney function biomarkers, and GFR in transgender persons initiating masculinizing and feminizing gender-affirming hormone therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We searched PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov from inception to September 16, 2020 for randomized controlled trials, observational studies, and case series that evaluated the change in serum creatinine, other kidney function biomarkers, and GFR before and after the initiation of gender-affirming hormone therapy in adult transgender persons. Two reviewers independently screened and abstracted data, and disagreements were resolved by a third reviewer. A random effects meta-analysis was performed to determine the change in outcomes over follow-up of 3, 6, and 12 months. RESULTS: Of the 4758 eligible studies, 26 met the inclusion criteria, including nine studies that recruited 488 transgender men and 593 women in which data were meta-analyzed. There was heterogeneity in study design, populations, gender-affirming hormone therapy routes, and dosing. At 12 months after initiating gender-affirming hormone therapy, serum creatinine increased by 0.15 mg/dl (95% confidence interval, 0.00 to 0.29) in 370 transgender men and decreased by -0.05 mg/dl (95% confidence interval, -0.16 to 0.05) in 361 transgender women. No study reported the effect of gender-affirming hormone therapy on albuminuria, proteinuria, cystatin C, or measured GFR. CONCLUSIONS: Gender-affirming hormone therapy increases serum creatinine in transgender men and does not affect serum creatinine in transgender women. The effect on gender-affirming hormone therapy on other kidney function biomarkers and measured GFR is unknown. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Change in Kidney Function Biomarkers in Transgender Persons on Gender Affirmation Hormone Therapy-A Systematic Review and Meta-Analysis, CRD42020214248.

Chronic Kidney Disease in the Transgender, Nonbinary, or Gender Diverse Person.

Nephrologists are increasingly providing care to transgender, nonbinary, and gender diverse (TNBGD) individuals with chronic kidney disease. This narrative review discusses the care of TNBGD individuals from a nephrology perspective. TNBGD individuals are under-represented in the nephrology literature. TNBGD individuals are at an increased risk of adverse outcomes compared with the cisgender population including mental health, cardiovascular disease, malignancy, sexually transmitted infections, and mortality. Gender-affirming hormone therapy (GAHT) with estradiol in transfeminine individuals potentially increases the risk of venous thromboembolism and cardiovascular disease. GAHT with testosterone in transmasculine individuals potentially increases the risk of erythrocytosis and requires careful monitoring. GAHT modifies body composition and lean muscle mass, which in turn influence creatinine generation and excretion, which may impact the performance of estimated glomerular filtration rate (GFR) equations and the estimation of 24-hour urine values from spot urine albumin/protein to creatinine ratios. There are limited studies regarding TNBGD individuals with chronic kidney disease. Additional research is needed to evaluate the effects of GAHT on GFR and biomarkers of kidney function and the performance of the estimated GFR equation in TNBGD populations.

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.

Providing Care for Transgender Persons With Kidney Disease: A Narrative Review.

PURPOSE OF REVIEW: Nephrologists are increasingly providing care to transgender individuals with chronic kidney disease (CKD). However, they may lack familiarity with this patient population that faces unique challenges. The purpose of this review is to discuss the care of transgender persons and what nephrologists should be aware of when providing care to their transgender patients. SOURCES OF INFORMATION: Original research articles were identified from MEDLINE and Google Scholar using the search terms "transgender," "gender," "sex," "chronic kidney disease," "end stage kidney disease," "dialysis," "transplant," and "nephrology." METHODS: A focused review and critical appraisal of existing literature regarding the provision of care to transgender men and women with CKD including dialysis and transplant to identify specific issues related to gender-affirming therapy and chronic disease management in transgender persons. KEY FINDINGS: Transgender persons are at an increased risk of adverse outcomes compared with the cisgender population including mental health, cardiovascular disease, malignancy, sexually transmitted infections, and mortality. Individuals with CKD have a degree of hypogonadotropic hypogonadism and decreased levels of endogenous sex hormones; therefore, transgender persons with CKD may require reduced exogenous sex hormone dosing. Exogenous estradiol therapy increases the risk of venous thromboembolism and cardiovascular disease which may be further increased in CKD. Exogenous testosterone therapy increases the risk of polycythemia which should be closely monitored. The impact of gender-affirming hormone therapy on glomerular filtration rate (GFR) trajectory in CKD is unclear. Gender-affirming hormone therapy with testosterone, estradiol, and anti-androgen therapies changes body composition and lean body mass which influences creatinine generation and the performance for estimated glomerular filtration rate (eGFR) equations in transgender persons. Confirmation of eGFR with measured GFR is reasonable if an accurate knowledge of GFR is needed for clinical decision-making. LIMITATIONS: There are limited studies regarding the intersection of transgender persons and kidney disease and those that exist are mostly case reports. Randomized controlled trials and observational studies in nephrology do not routinely differentiate between cisgender and transgender participants. IMPLICATIONS: This review highlights important considerations for providing care to transgender persons with kidney disease. Additional research is needed to evaluate the performance of eGFR equations in transgender persons, the effects of gender-affirming hormone therapy, and the impact of being transgender on outcomes in persons with kidney disease.

MOTIF DE LA REVUE: Dans leur pratique, les néphrologues sont de plus en plus appelés à traiter des personnes transgenres atteintes d'insuffisance rénale chronique (IRC). Une population de patients qui fait face à des défis particuliers et avec laquelle les spécialistes ne sont pas toujours familiers. L'objectif de cette revue est de discuter des soins prodigués aux personnes transgenres et des enjeux auxquels les néphrologues qui soignent ces patients devraient être sensibilisés. SOURCES: Les articles de recherche originaux ont été répertoriés sur MEDLINE et Google Scholar à l'aide des termes transgender (transgenre), gender (genre), sex (sexe), chronic kidney disease (insuffisance rénale chronique), end stage kidney disease (insuffisance rénale terminale), dialysis (dialyse), transplant (transplantation) et nephrology (néphrologie). MÉTHODOLOGIE: On a procédé à un examen ciblé et une évaluation critique de la documentation portant sur les soins aux personnes transgenres atteintes d'IRC, notamment la dialyse et la transplantation, afin de cerner les enjeux liés spécifiquement aux thérapies d'affirmation du genre et à la prise en charge de la néphropathie chronique chez les personnes transgenres. PRINCIPAUX RÉSULTATS: Les personnes transgenres courent un risque accru d'événements défavorables comparativement à la population cisgenre, notamment en matière de santé mentale, de maladies cardiovasculaires, de tumeurs malignes, d'infections transmissibles sexuellement et de mortalité. Les individus atteints d'IRC présentent un certain degré d'hypogonadisme hypogonadotrope et des taux réduits d'hormones sexuelles endogènes; les personnes transgenres atteintes d'IRC pourraient ainsi nécessiter un dosage réduit d'hormones sexuelles exogènes. L'estradiol exogène augmente le risque de thrombo-embolie veineuse et de maladies cardiovasculaires, un risque pouvant être augmenté davantage en contexte d'IRC. La testostérone exogène augmente le risque de polycythémie et doit être surveillée étroitement. L'impact de l'hormonothérapie d'affirmation du genre sur la trajectoire du débit de filtration glomérulaire (DFG) en IRC est encore mal connu. L'hormonothérapie d'affirmation du genre avec testostérone, estradiol et anti-androgène altère la composition corporelle et la masse maigre, ce qui influe sur la production de créatinine et la performance des équations calculant le DFG estimé (DFGe) chez les personnes transgenres. La confirmation du DFGe à l'aide du DFG mesuré est raisonnable si connaître la valeur précise du DFG est nécessaire pour la prise de décision clinique. LIMITES: Peu d'études se sont penchées sur l'intersection des personnes transgenres et de la néphropathie, et les études existantes consistent principalement en des rapports de cas. Les essais contrôlés randomisés et les études observationnelles en néphrologie ne font pas systématiquement de distinction entre les participants cisgenres et transgenres. CONCLUSION: Cette revue met en lumière des considérations importantes pour la prise en charge des personnes transgenres atteintes de néphropathies. D'autres recherches sont nécessaires pour évaluer la performance des équations calculant le DFGe, les effets de l'hormonothérapie d'affirmation du genre et l'incidence d'être transgenre sur les résultats des personnes atteintes de néphropathies.

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.

Safety of Intravenous Iron in Dialysis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: The safety of intravenous iron dosing in dialysis is uncertain. Higher-dose intravenous iron may be associated with a higher risk of infections, cardiovascular events, hospitalizations, and mortality. This systematic review aimed to determine the safety of higher-dose versus lower-dose intravenous iron, oral iron, or no iron supplementation in adult patients treated with dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We searched Medline, EMBASE, Cochrane library, and CINAHL from inception to January 6, 2017 for randomized, controlled trials and observational studies comparing higher-dose intravenous iron with lower-dose intravenous iron, oral iron, or no iron in patients treated with dialysis that had all-cause mortality, infection, cardiovascular events, or hospitalizations as outcomes. RESULTS: Of the 2231 eligible studies, seven randomized, controlled trials and 15 observational studies met inclusion criteria. The randomized, controlled trials showed no association between higher-dose intravenous iron (>400 mg/mo for most studies) and mortality (six studies; n=970; pooled relative risk, 0.93; 95% confidence interval, 0.47 to 1.84; follow-up ranging from 35 days to 26 months) or infection (four studies; n=743; relative risk, 1.02; 95% confidence interval, 0.74 to 1.41). The observational studies showed no association between higher-dose intravenous iron (>200 mg/mo for most studies) and mortality (eight studies; n=241,408; hazard ratio, 1.09; 95% confidence interval, 0.98 to 1.21; follow-up ranging from 3 to 24 months), infection (eight studies; n=135,532; pooled hazard ratio, 1.13; 95% confidence interval, 0.99 to 1.28), cardiovascular events (seven studies; n=135,675; hazard ratio, 1.18; 95% confidence interval, 0.90 to 1.56), or hospitalizations (five studies; n=134,324; hazard ratio, 1.08; 95% confidence interval, 0.97 to 1.19). CONCLUSIONS: Higher-dose intravenous iron does not seem to be associated with higher risk of mortality, infection, cardiovascular events, or hospitalizations in adult patients on dialysis. Strength of this finding is limited by small numbers of participants and events in the randomized, controlled trials and statistical heterogeneity in observational studies.

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.

ANCA Associated Vasculitis Secondary to Levamisole-Adultered Cocaine with Associated Membranous Nephropathy: A Case Series.

BACKGROUND: Cocaine is a risk factor for acute kidney injury and chronic kidney disease with progression to end-stage renal disease. Levamisole is an adulterant that is added to cocaine to enhance its euphoric effects. Levamisole-adulterated cocaine (LAC) is associated with the distinct clinical syndromes of agranulocytosis, leukocytoclastic vasculitis, cocaine-induced midline destructive lesions (CIMDL), and ANCA-associated vasculitis (AAV) with pauci-immune necrotizing glomerulonephritis. METHODS: We reviewed all cases of AAV secondary to LAC at our institution. RESULTS: We report 3 cases of AAV secondary to LAC and associated membranous nephropathy (MN). The first and second cases are concurrent AAV secondary to LAC and associated MN while the third case involves the development of MN after AAV secondary to LAC. CONCLUSIONS: Clinicians should be aware of this novel association of LAC with MN.

The Patterns, Risk Factors, and Prediction of Progression in Chronic Kidney Disease: A Narrative Review.

Chronic kidney disease (CKD) is a global public health problem that is associated with excess morbidity, mortality, and health resource utilization. The progression of CKD is defined by a decrease in glomerular filtration rate and leads to a variety of metabolic abnormalities including acidosis, hypertension, anemia, and mineral bone disorder. Lower glomerular filtration rate also bears a strong relationship with an increased risk of cardiovascular events, end-stage renal disease, and death. Patterns of CKD progression include linear and nonlinear trajectories, but kidney function can remain stable for years in some individuals. Addressing modifiable risk factors for the progression of CKD is needed to attenuate its associated morbidity and mortality. Developing effective risk prediction models for CKD progression is critical to identify patients who are more likely to benefit from interventions and more intensive monitoring. Accurate risk-prediction algorithms permit systems to best align health care resources with risk to maximize their effects and efficiency while guiding overall decision making.

The Effect of Erythropoietin-Stimulating Agents on Health-Related Quality of Life in Anemia of Chronic Kidney Disease: A Systematic Review and Meta-analysis.

BACKGROUND: The efficacy of erythropoietin-stimulating agents (ESAs) for improving health-related quality of life (HRQOL) in anemia of chronic kidney disease (CKD) is unclear. PURPOSE: To determine the effect of ESAs on HRQOL at different hemoglobin targets in adults with CKD who were receiving or not receiving dialysis. DATA SOURCES: Searches of PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov from inception to 1 November 2015, supplemented with manual screening. STUDY SELECTION: Randomized, controlled trials that evaluated the treatment of anemia with ESAs, including erythropoietin and darbepoetin, targeted higher versus lower hemoglobin levels, and used validated HRQOL metrics. DATA EXTRACTION: Study characteristics, quality, and data were assessed independently by 2 reviewers. Outcome measures were scores on the Short Form-36 Health Survey (SF-36), Kidney Dialysis Questionnaire (KDQ), and other tools. DATA SYNTHESIS: Of 17 eligible studies, 13 reported SF-36 outcomes and 4 reported KDQ outcomes. Study populations consisted of patients not undergoing dialysis (n = 12), those undergoing dialysis (n = 4), or a mixed sample (n = 1). Only 4 studies had low risk of bias. Pooled analyses showed that higher hemoglobin targets resulted in no statistically or clinically significant differences in SF-36 or KDQ domains. Differences in HRQOL were further attenuated in studies at low risk of bias and in subgroups of dialysis recipients. LIMITATION: Statistically significant heterogeneity among studies, few good-quality studies, and possible publication bias. CONCLUSION: ESA treatment of anemia to obtain higher hemoglobin targets does not result in important differences in HRQOL in patients with CKD. PRIMARY FUNDING SOURCE: KRESCENT and Manitoba Health Research Council Establishment.