The humanistic burden of immunoglobulin A nephropathy on patients and care-partners in the United States.

PURPOSE: This cross-sectional survey study quantified the humanistic burden of immunoglobulin A nephropathy (IgAN), in terms of physical and mental health-related quality of life (HRQoL) and work productivity, among adults with primary IgAN and their care-partners. METHODS: HRQoL was assessed (01/31/22 - 05/31/23) with validated tools including the KDQoL-36 (with SF-12), GAD-7 (anxiety), PHQ-9 (depression), and WPAI: SHP (work productivity). Participant characteristics and total/domain scores were summarized; selected outcomes were compared to an external, kidney disease-free cohort. RESULTS: 117 adults with IgAN and their care-partner pairs, and one adult without a care-partner, were included. The mean ages of patients and care-partners were 38.0 (SD: 8.6) and 40.2 (11.8) years, respectively; 55.9% and 43.6% were female. Mean physical and mental SF-12 scores for patients were 46.7 (SD: 8.0) and 41.9 (9.2), respectively, and 50.7 (7.3) and 43.7 (10.24) for care-partners. Both SF-12 components for patients, and the mental component for care-givers, were significantly worse compared to the US general population. Among patients, 27.1% had moderate/severe anxiety and 49.2% reported at least moderate depression. Compared to external controls, patients experienced significantly higher severity of anxiety (6.6 vs. 5.4) and depression (8.1 vs. 6.6; both p < 0.0001). Among care-partners, 13.7% experienced moderate anxiety and 37.8% experienced moderate/moderately-severe depression. Among employed individuals, both groups reported IgAN-related absenteeism (8.8-9.4%), presenteeism (25.1-25.9%), and overall work impairment (30.4-30.5%). CONCLUSION: US adults with IgAN and their care partners experience impairments to mental and physical HRQoL and heightened levels of depression and anxiety, underscoring the need for effective IgAN therapies and care-partner support.

Chronic kidney disease-associated pruritus and quality of life with difelikefalin treatment: a post hoc analysis of phase 3 data using the Skindex-10 questionnaire.

Background: Pruritus is a common condition in chronic kidney disease (CKD), especially for patients receiving haemodialysis. CKD-associated pruritus (CKD-aP) can be distressing and have a negative impact on quality of life (QoL). This post hoc analysis aimed to assess the relationship between pruritus relief and QoL. Methods: Data from phase 3 trials [(NCT03422653, NCT03636269 grouped), and NCT03998163] of the novel antipruritic difelikefalin (N = 914) were used to assess the relationship between reductions in pruritus intensity at Week 12 (24-h Worst Itching Intensity Numeric Rating Scale; WI-NRS), perceived improvement in itch (Patient Global Impression of Change, PGI-C) and pruritus-related QoL (Skindex-10 questionnaire). Results: Patients receiving difelikefalin had greater improvements in Skindex-10 total scores than those receiving placebo [LS mean treatment difference -3.4; 95% confidence interval (CI) -5.5, -1.3; P = .002] and greater improvements across Skindex-10 domains (disease, mood and social functioning) at Week 12. In patients receiving difelikefalin, those with clinically meaningful improvements in pruritus (≥3-point reduction in WI-NRS score) at Week 12 had a greater improvement in Skindex-10 total score (mean difference 14.2; 95% CI 11.0, 17.3; P < .001) and Skindex-10 domains than those with a <3-point reduction in WI-NRS score. Improvements in Skindex-10 total scores correlated with PGI-C. Conclusions: Improvements in pruritus intensity following 12 weeks of treatment with difelikefalin were associated with improvements in QoL. Larger improvements in Skindex-10 scores were seen in patients with a greater reduction in pruritus intensity, indicating that improvements in pruritus are associated with a range of factors, such as mood and social functioning, that affect pruritus-related QoL.

The lived experience of renal cachexia: An interpretive phenomenological analysis.

Background: Chronic kidney disease is common, affecting up to 13 % of the global population, and is predicted to become the fifth leading cause of 'life years lost' by 2040. Individuals with end-stage kidney disease commonly develop complications such as protein-energy wasting and cachexia which further worsens their prognosis. The syndrome of 'renal cachexia' is poorly understood, under-diagnosed and even if recognised has limited treatment options. Objective: To explore the lived experience of renal cachexia for individuals with end-stage kidney disease and the interrelated experiences of their carers. Design: This interpretive phenomenological study was designed to facilitate an in-depth exploration of how patients and carers experience of renal cachexia. To improve and document the quality, transparency, and consistency of patient and public involvement in this study the Guidance for Reporting Involvement of Patients and the Public-Short Format was followed. Setting: The study was conducted across two nephrology directorates, within two healthcare trusts in the United Kingdom. Participants: Seven participants who met the inclusion criteria were recruited for this study, four patients (three female, one male) and three carers (two male, one female). Methods: We employed a purposive sampling strategy. Data collection was conducted between July 2022 and December 2023. Interviews were semi-structured, audio-recorded, transcribed verbatim and analysed in six steps by two researchers using interpretive phenomenological analysis. Ethical approval was approved by the Office for Research Ethics Committees Northern Ireland (Reference: 22/NI/0107). Results: Analysis generated six group experiential themes: the lived experience of appetite loss, functional decline and temporal coping, weight loss a visual metaphor of concern, social withdrawal and vulnerability, the emotional toll of eating challenges and psychological strain amidst a lack of information about cachexia. Conclusion: This is the first qualitative study exploring the lived experience of renal cachexia for patients and carers. Our study highlights that psycho-social and educational support is urgently needed. Additionally, healthcare professionals need better information provision to help them to recognise and respond to the needs of this population. Further research is required to develop models of holistic support which could help patients and carers cope with the impact of renal cachexia and optimally manage this syndrome within the family unit. Registration: N/A.

Dietary burden of phosphorus and aluminum in ready-to-eat wheat flour tortillas exceed that of corn tortillas: Implications for patients with renal or cardiovascular disease.

Ready-to-eat, shelf-stable tortillas contain several phosphorus- and aluminum-containing additives that may increase the risk of adverse events in patients with chronic kidney disease (CKD). The present study analyzes and compares the elemental content of wheat flour and corn tortillas with special reference to dietary aluminum and phosphorus burden. Twenty-one elements were quantified by ICP-MS and ICP-OES in 14 corn and 13 wheat flour tortilla brands purchased from local supermarkets in Southern California. The aluminum and phosphorus concentrations of many ready-to-eat tortilla brands can present a daily dietary load of up to approximately 100 mg aluminum and 700 mg phosphorus based on an average daily tortilla intake of 330 grams. Ready-to-eat wheat flour tortillas generally had more phosphorus than corn tortillas. Tortillas with aluminum listed as a food additive contained a higher aluminum content than those without such listing, exceeding the tolerable weekly intake. Despite conventional wisdom that CKD patients should avoid phosphorus-rich corn tortillas, ready-to-eat wheat flour tortillas consistently had a higher aluminum and phosphorus content due to additives. CKD patients and healthcare providers should pay attention to food labels, and regulatory authorities should monitor the use of approved food additives and mandate food label warnings for patients at risk.

Accuracy of Continuous Glucose Monitoring in Hemodialysis Patients With Diabetes.

OBJECTIVE: In the general population, continuous glucose monitoring (CGM) provides convenient and less-invasive glucose measurements than conventional self-monitored blood glucose and results in reduced hypoglycemia and hyperglycemia and increased time in target glucose range. However, accuracy of CGM versus blood glucose is not well established in hemodialysis patients. RESEARCH DESIGN AND METHODS: Among 31 maintenance hemodialysis patients with diabetes hospitalized from October 2020 to May 2021, we conducted protocolized glucose measurements using Dexcom G6 CGM versus blood glucose, with the latter measured before each meal and at night, plus every 30-min during hemodialysis. We examined CGM-blood glucose correlations and agreement between CGM versus blood glucose using Bland-Altman plots, percentage of agreement, mean and median absolute relative differences (ARDs), and consensus error grids. RESULTS: Pearson and Spearman correlations for averaged CGM versus blood glucose levels were 0.84 and 0.79, respectively; Bland-Altman showed the mean difference between CGM and blood glucose was ∼+15 mg/dL. Agreement rates using %20/20 criteria were 48.7%, 47.2%, and 50.2% during the overall, hemodialysis, and nonhemodialysis periods, respectively. Mean ARD (MARD) was ∼20% across all time periods; median ARD was 19.4% during the overall period and was slightly lower during nonhemodialysis (18.2%) versus hemodialysis periods (22.0%). Consensus error grids showed nearly all CGM values were in clinically acceptable zones A (no harm) and B (unlikely to cause significant harm). CONCLUSIONS: In hemodialysis patients with diabetes, although MARD values were higher than traditional optimal analytic performance thresholds, error grids showed nearly all CGM values were in clinically acceptable zones. Further studies are needed to determine whether CGM improves outcomes in hemodialysis patients.

The Relevance of Phytate for the Treatment of Chronic Kidney Disease.

Diets high in plant-based foods are commonly recommended for people with CKD. One putative advantage of these diets is reduced intestinal phosphate absorption. This effect has been ascribed to phytic acid (myoinositol hexaphosphoric acid) and its anion, phytate, that are present in many plant foods, particularly in the seeds, nuts, grains, and fruits of plants. This article reviews the structure and many actions of phytate with particular reference to its potential effects on people with CKD. Phytate binds avidly to and can reduce gastrointestinal absorption of the phosphate anion and many macrominerals and trace elements including iron, zinc, calcium, and magnesium. This has led some opinion leaders to label phytate as an anti-nutrient. The human intestine lacks phytase; hence, phytate is essentially not degraded in the small intestine. A small amount of phytate is absorbed from the small intestine, although phytate bound to phosphate is poorly absorbed. Clinical trials in maintenance hemodialysis patients indicate that intravenously administered phytate may decrease hydroxyapatite formation, vascular calcification, and calciphylaxis. Orally administered phytate or in vitro studies indicate that phytate may also reduce osteoporosis, urinary calcium calculi formation, and dental plaque formation. Phytate seems to have anti-inflammatory and antioxidant effects, at least partly because of its ability to chelate iron. Other potential therapeutic roles for phytate, not definitively established, include suppression of cancer formation, reduction in cognitive decline that occurs with aging, and amelioration of certain neurodegenerative diseases and several gastrointestinal and metabolic disorders. These latter potential benefits of phytate are supported by cell or animal research or observational studies in humans. Many of the above disorders are particularly common in patients with CKD. Definitive clinical trials to identify potential therapeutic benefits of phytate in patients with CKD are clearly warranted.

Safety of SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor agonists in US veterans with and without chronic kidney disease: a population-based study.

Background: We examined the real-world comparative safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs. other newer anti-glycemic medications (dipeptidyl peptidase-4 inhibitors [DPP4i], glucagon-like peptide-1 receptor agonists [GLP1a]) in patients with and without chronic kidney disease (CKD). Methods: Among US Veterans with diabetes receiving care from the Veterans Affairs (VA) healthcare system over 2004-19, we identified incident users of SGLT2i vs. DPP4i vs. GLP1a monotherapy. In analyses stratified by CKD status, defined by estimated glomerular filtration rate and albuminuria, we examined associations of SGLT2i vs. DPP4i vs. GLP1a use with risk of infection-related (primary outcome) and genitourinary infection hospitalizations (secondary outcome) using multivariable Cox models. Findings: Among 92,269 patients who met eligibility criteria, 52% did not have CKD, whereas 48% had CKD. In the overall and non-CKD cohorts, compared to DPP4i use, SGLT2i use was associated with lower infection-related hospitalization risk (HRs [95% CIs] 0.74 [0.67-0.81] and 0.77 [0.67, 0.88], respectively), whereas GLP1a use demonstrated comparable risk. However, in the CKD cohort SGLT2i and GLP1a use were each associated with lower risk (HRs [95% CIs] 0.70 [0.61, 0.81] and 0.91 [0.84, 0.99], respectively). Propensity score-matched analyses showed similar findings in the non-CKD and CKD cohorts. In the overall, non-CKD, and CKD cohorts, SGLT2i use was associated with lower genitourinary infection hospitalization risk whereas GLP1a use showed comparable risk vs. DPP4i use. Interpretation: In a national cohort of Veterans with diabetes, compared with DPP4i use, SGLT2i use was associated with lower infection-related and genitourinary infection hospitalization risk. Funding: VA Health Services Research and Development, USA.

BRD4 plays an antiaging role in the senescence of renal tubular epithelial cells.

Background: Age-related kidney failure is often induced by a decrease in the bioavailability of tubular epithelial cells in elderly chronic kidney disease (CKD) patients. BRD4, an epigenetic regulator and a member of the bromodomain and extraterminal (BET) protein family, acts as a super-enhancer (SE) organizing and regulating genes expression during embryogenesis and cancer development. But the physiological function of BRD4 in normal cells has been less studied. This study aimed to research certain biological roles of BRD4 in the process of normal cell aging and discuss the potential mechanisms. Methods: In this study, we investigated the biological functions of BRD4 proteins in the aging of renal tubular cells. At first, we used a D-galactose (D-gal) and BRD4 inhibitor (Abbv-075) to replicate kidney senescence in vivo. D-gal and Abbv-075 were then used to measure the aging-related changes, such as changes in cell cycle, ß-galactosidase activity, cell migration, and p16 protein expression in vitro. At last, we knocked down and over-expressed BRD4 to investigate the aging-related physiological phenomena in renal tubular cells. Results: In vitro, D-gal treatment induced noticeable aging-related changes such as inducing cell apoptosis and cell cycle arrest, increasing ß-galactosidase activity as well as up-regulating p16 protein expression in primary human tubular epithelial cells. In the aging mice model, D-gal significantly induced renal function impairment and attenuated BRD4 protein expression. At the same time, the BRD4 inhibitor (Abbv-075) was able to mimic D-gal-induced cell senescence. In vivo, Abbv-075 also decreased kidney function and up-regulated p21 protein expression. When we knocked down the expression of BRD4, the senescence-associated ß-galactosidase (SA-ß-gal) activity increased dramatically, cell migration was inhibited, and the proportion of cells in the G0/G1 phase increased. Additionally, the knockdown also promoted the expression of the senescence-related proteins p16. When the renal tubular cells were overexpressed with BRD4, cell aging-related indicators were reversed in the D-gal-induced cell aging model. Conclusions: BRD4 appears to have an active role in the aging of renal tubular cells in vivo and in vitro. The findings also suggest that BRD4 inhibitors have potential nephrotoxic effects for oncology treatment. BRD4 may be a potential therapeutic biomarker and drug target for aging-related kidney diseases, which warrants additional studies.

Residual Kidney Function in Hemodialysis: Its Importance and Contribution to Improved Patient Outcomes.

Individuals afflicted with advanced kidney dysfunction who require dialysis for medical management exhibit different degrees of native kidney function, called residual kidney function (RKF), ranging from nil to appreciable levels. The primary focus of this manuscript is to delve into the concept of RKF, a pivotal yet under-represented topic in nephrology. To begin, we unpack the definition and intrinsic nature of RKF. We then juxtapose the efficiency of RKF against that of hemodialysis in preserving homeostatic equilibrium and facilitating physiological functions. Given the complex interplay of RKF and overall patient health, we shed light on the extent of its influence on patient outcomes, particularly in those living with advanced kidney dysfunction and on dialysis. This manuscript subsequently presents methodologies and measures to assess RKF, concluding with the potential benefits of targeted interventions aimed at preserving RKF.

Management of serum phosphorus over a 1-year follow-up in patients on peritoneal dialysis prescribed sucroferric oxyhydroxide as part of routine care: a retrospective analysis.

BACKGROUND: Hyperphosphatemia is associated with increased morbidity and mortality in patients with end-stage kidney disease (ESKD). Whereas clinical and observational studies have demonstrated the effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus (sP) in ESKD, data on the real-world impact of switching to SO in patients on peritoneal dialysis (PD) are limited. In this retrospective database analysis, we examine the impact of SO on sP management over a 1-year period among PD patients prescribed SO as part of routine clinical care. METHODS: We analyzed de-identified data from adults on PD in Fresenius Kidney Care clinics who were prescribed SO monotherapy between May 2018 and December 2019 as part of routine clinical management. Changes from baseline in sP levels, phosphate binder (PB) pill burden, and laboratory parameters were evaluated during the four consecutive 91-day intervals of SO treatment. RESULTS: The mean age of the 402 patients who completed 1 year of SO was 55.2 years at baseline, and they had been on PD for an average of 19.9 months. SO was initiated with no baseline PB recorded in 36.1% of patients, whereas the remaining 257 patients were switched to SO from sevelamer (39.7%), calcium acetate (30.4%), lanthanum (1.2%), ferric citrate (14.0%), or more than one PB (14.8%). Mean sP at baseline was 6.26 mg/dL. After being prescribed SO, the percentage of patients achieving sP ≤ 5.5 mg/dL increased from 32.1% (baseline) to 46.5-54.0% during the 1-year follow-up, whereas the mean number of PB pills taken per day decreased from 7.7 at baseline (among patients on a baseline PB) to 4.6 to 5.4. Serum phosphorus and PB pill burden decreased regardless of changes in residual kidney function over the 12-month period. Similar results were observed for the full cohort (976 patients who either completed or discontinued SO during the 1-year follow-up). CONCLUSIONS: Patients on PD who were prescribed SO as part of routine care for phosphorus management experienced significant reductions in SP and PB pills per day and improvements in sP target achievement, suggesting the effectiveness of SO on SP management with a concurrent reduction in pill burden.

The Relationship Between Sarcopenia And Proteinuria, What Do We Know?

Sarcopenia is one of the most common geriatric syndromes in the elderly. It is defined as a decrease in muscle mass and function, and it can lead to physical disability, falls, poor quality of life, impaired immune system, and death. It is known that, the frequency of sarcopenia increases in the kidney patient population compared to healthy individuals. Although it is known that kidney disease can lead to sarcopenia; our knowledge of whether sarcopenia causes kidney disease is limited. Prior studies have suggested that protein energy wasting may be a risk of de novo CKD. Proteinuria is an important manifestation of kidney disease and there is a relationship between sarcopenia and proteinuria in diabetes, geriatric population, kidney transplant, and nephrotic syndrome. Does proteinuria cause sarcopenia or vice versa? Are they both the results of common mechanisms? This issue is not clearly known. In this review, we examined the relationship between sarcopenia and proteinuria in the light of other studies.

Hyperkalemia Recurrence and Its Association With Race and Ethnicity in United States Veterans: A Retrospective Cohort Study.

INTRODUCTION: Information on whether race and ethnicity are associated with a greater risk of recurrent hyperkalemia is limited. The aim of this study was to examine the association between race or ethnicity and recurrent hyperkalemia in a population of US veterans. METHODS: This retrospective study used the US Veterans Affairs database to identify adults (aged ≥18 years) with at least one serum potassium measurement during the study period who ever experienced hyperkalemia (serum potassium > 5.0 mmol/L). The proportion of patients with hyperkalemia recurrence (≥1 subsequent event) within one year was determined for different race and ethnicity groups. The association between patient race and ethnicity and the risk of hyperkalemia recurrence within one year after the index hyperkalemia event was analyzed using competing risk regression. RESULTS: Among a total of 1,493,539 veterans with incident hyperkalemia (median age (interquartile range): 61.0 years (54.0, 71.0)), recurrence within one year occurred in 19.1% of Black, 16.0% of Native Hawaiian/other Pacific Islander, 15.1% of White, 14.9% of American Indian/Alaska Native, and 13.1% of Asian patient groups. Recurrent hyperkalemia occurred in 18.1% of Hispanic and 15.6% of non-Hispanic patient groups. In a fully-adjusted regression model, recurrent hyperkalemia risk was significantly higher in Black versus White patient groups (subhazard ratio (sHR), 1.17; 95% confidence interval (CI), 1.16-1.19; p< 0.0001) and in Hispanic versus non-Hispanic patient groups (sHR, 1.30; 95% CI, 1.28-1.33; p< 0.0001). DISCUSSION/CONCLUSION: Among US veterans with incident hyperkalemia, the risk of recurrent hyperkalemia was higher in Black and Hispanic patient groups. This information may be useful for health system screenings to risk stratify patient groups and both guide the frequency of serum potassium monitoring and better understand the root causes of group differences.

Frailty in patients on dialysis.

Frailty is a condition that is frequently observed among patients undergoing dialysis. Frailty is characterized by a decline in both physiological state and cognitive state, leading to a combination of symptoms, such as weight loss, exhaustion, low physical activity level, weakness, and slow walking speed. Frail patients not only experience a poor quality of life, but also are at higher risk of hospitalization, infection, cardiovascular events, dialysis-associated complications, and death. Frailty occurs as a result of a combination and interaction of various medical issues in patients who are on dialysis. Unfortunately, frailty has no cure. To address frailty, a multifaceted approach is necessary, involving coordinated efforts from nephrologists, geriatricians, nurses, allied health practitioners, and family members. Strategies such as optimizing nutrition and chronic kidney disease-related complications, reducing polypharmacy by deprescription, personalizing dialysis prescription, and considering home-based or assisted dialysis may help slow the decline of physical function over time in subjects with frailty. This review discusses the underlying causes of frailty in patients on dialysis and examines the methods and difficulties involved in managing frailty among this group.

Personalized nutritional management in the transition from non-dialysis dependent chronic kidney disease to dialysis.

Dialysis has been the dominant treatment regimen in end-stage kidney disease as a means to remove uremic waste products and to maintain electrolyte, acid base, and fluid balance. However, given that dialysis may not always provide a survival benefit nor improved quality of life in certain subpopulations, there is growing recognition of the need for conservative and preservative management as an alternative treatment strategy for advanced chronic kidney disease (CKD). Personalized nutritional management tailored to patient's sociodemographics, social needs, psychological status, health literacy level, and preferences is a key component of conservative and preservative care, as well as in the management of patients transitioning from non-dialysis dependent CKD to dialysis. In this review, we discuss the nutritional and metabolic alterations that ensue in CKD; the rationale for low-protein diets in the conservative and preservative management of advanced CKD; the role of plant-based diets in kidney health; emerging data on dietary potassium and sodium intake on CKD outcomes; and the practical implementation of dietary interventions in advanced kidney disease.

A new era in the science and care of kidney diseases.

Notable progress in basic, translational and clinical nephrology research has been made over the past five decades. Nonetheless, many challenges remain, including obstacles to the early detection of kidney disease, disparities in access to care and variability in responses to existing and emerging therapies. Innovations in drug development, research technologies, tissue engineering and regenerative medicine have the potential to improve patient outcomes. Exciting prospects include the availability of new drugs to slow or halt the progression of chronic kidney disease, the development of bioartificial kidneys that mimic healthy kidney functions, and tissue engineering techniques that could enable transplantable kidneys to be created from the cells of the recipient, removing the risk of rejection. Cell and gene therapies have the potential to be applied for kidney tissue regeneration and repair. In addition, about 30% of kidney disease cases are monogenic and could potentially be treated using these genetic medicine approaches. Systemic diseases that involve the kidney, such as diabetes mellitus and hypertension, might also be amenable to these treatments. Continued investment, communication, collaboration and translation of innovations are crucial to realize their full potential. In addition, increasing sophistication in exploring large datasets, implementation science, and qualitative methodologies will improve the ability to deliver transformational kidney health strategies.

Incident Diuretic Use and Subsequent Risk of Bone Fractures: A Large Nationwide Observational Study of US Veterans.

OBJECTIVE: To investigate the association of incident use of diuretics with subsequent risk of incident bone fractures. PATIENTS AND METHODS: In a nationwide cohort of 863,339 US veterans receiving care from the VA health care system between October 1, 2004, and September 30, 2006, with follow-up through June 30, 2018, we examined the association of incident diuretic use (overall, and separately by thiazide, loop, and potassium-sparing diuretics) with subsequent risk of incident bone fractures using multivariable Cox regression models while minimizing confounding by indication using a target trial emulation approach. RESULTS: Patients were 63.3±12.9 years old; 93.5% (n=807,180) were male; and 27.1% (n=233,996) were diabetic. Their baseline estimated glomerular filtration rate was 84.4±16.5 mL/min per 1.73 m2. Among 863,339 patients, 424,386 (49.2%) newly initiated diuretics, of which 77.4% (n=328,524), 22.5% (n=95,457), and 0.1% (n=405) were thiazide, loop, and potassium-sparing diuretic users, respectively. After multivariable adjustments, incident diuretic use (vs non-use) was significantly associated with higher risk of incident fracture (adjusted HR [aHR], 1.14; 95% CI, 1.11 to 1.16). The association was most pronounced for loop diuretics (aHR, 1.39; 95% CI, 1.35 to 1.44) but less evident for thiazide diuretics (aHR, 1.08; 95% CI, 1.06 to 1.10) and was not significant for potassium-sparing diuretics (aHR, 0.97; 95% CI, 0.62 to 1.52). The diuretic-fracture association was more evident in younger (vs older) patients, those with (vs without) corticosteroid use, and those with lower (vs higher) serum sodium levels. CONCLUSION: Incident use of diuretics, particularly loop diuretics, was independently associated with higher risk of incident bone fractures. Our findings suggest distinct pathophysiologic contributions of diuretics to bone metabolism and the need for careful attention to skeletal outcomes when initiating diuretics.

Anti-Tumor Necrosis Factor Therapy and Risk of Kidney Function Decline and Mortality in Inflammatory Bowel Disease.

Importance: Inflammatory bowel disease (IBD) is associated with adverse clinical outcomes, including chronic kidney disease and mortality, due in part to chronic inflammation. Little is known about the effects of anti-tumor necrosis factor (TNF) therapy on kidney disease progression and mortality among patients with new-onset IBD. Objective: To examine the association of incident use of TNF inhibitors with subsequent decline in kidney function and risk of all-cause mortality. Design, Setting, and Participants: This retrospective cohort study used data from the US Department of Veterans Affairs health care system. Participants were US veterans with new-onset IBD enrolled from October 1, 2004, through September 30, 2019. Data were analyzed from December 2022 to February 2024. Exposures: Incident use of TNF inhibitors. Main Outcomes and Measures: The main outcomes were at least 30% decline in estimated glomerular filtration rate (eGFR) and all-cause mortality. Results: Among 10 689 patients (mean [SD] age, 67.4 [12.3] years; 9999 [93.5%] male) with incident IBD, 3353 (31.4%) had diabetes, the mean (SD) baseline eGFR was 77.2 (19.2) mL/min/1.73 m2, and 1515 (14.2%) were newly initiated on anti-TNF therapy. During a median (IQR) follow-up of 4.1 (1.9-7.0) years, 3367 patients experienced at least 30% decline in eGFR, and over a median (IQR) follow-up of 5.0 (2.5-8.0) years, 2502 patients died. After multivariable adjustments, incident use (vs nonuse) of TNF inhibitors was significantly associated with higher risk of decline in eGFR (adjusted hazard ratio [HR], 1.34 [95% CI, 1.18-1.52]) but was not associated with risk of all-cause mortality (adjusted HR, 1.02 [95% CI, 0.86-1.21]). Similar results were observed in sensitivity analyses. Conclusions and Relevance: In this cohort study of US veterans with incident IBD, incident use (vs nonuse) of TNF inhibitors was independently associated with higher risk of progressive eGFR decline but was not associated with risk of all-cause mortality. Further studies are needed to elucidate potentially distinct pathophysiologic contributions of TNF inhibitor use to kidney and nonkidney outcomes in patients with IBD.

Change Over Time in Pre-End-Stage Renal Disease 24-Hour Urine Creatinine as Muscle Mass Surrogate and Post-End-Stage Renal Disease Mortality.

OBJECTIVE: Loss of muscle mass and sarcopenia are common in chronic kidney disease (CKD) and end-stage renal disease (ESRD), and sarcopenia can worsen insidiously in patients with advancing CKD. The temporal dynamics of sarcopenia in patients with progressive loss of kidney function, and its association with future outcomes, is unclear. METHODS: In a contemporary national cohort of incident ESRD US veterans, we selected 661 patients who had at least 2 24-hour urine creatinine (24hrUC) measurements, a surrogate of muscle mass, performed during the 3-year prelude period prior to ESRD transition. We estimated 24hrUC slopes in mixed effects models. To assess the temporal dynamics of pre-ESRD changes in 24hrUC and its association with changing eGFR, we separately fitted in mixed effects models a penalized spline regression of 24hrUC on time and on eGFR. We examined the association of 24hrUC slopes with postdialysis all-cause mortality using Cox models adjusted for confounders. RESULTS: The mean slope of 24hrUC versus time was -78 mg/year (95% confidence interval: -102 to -54), with a steeper decline noted in the last year prior to ESRD. More severe decreases in 24hrUC were associated with higher all-cause mortality: a 100 mg/year decrease in 24hrUC was associated with a multivariable adjusted death hazard ratio of 1.41 (95% confidence interval: 1.00-1.98, P = .05). CONCLUSION: Patients with advanced CKD lose a substantial proportion of their muscle mass each year during pre-ESRD prelude. Loss of muscle mass accelerates near ESRD transition, and more loss of muscle mass is associated with higher mortality after ESRD transition.