Diabetes technology in people with diabetes and advanced chronic kidney disease.

Diabetes is the leading cause and a common comorbidity of advanced chronic kidney disease. Glycaemic management in this population is challenging and characterised by frequent excursions of hypoglycaemia and hyperglycaemia. Current glucose monitoring tools, such as HbA1c, fructosamine and glycated albumin, have biases in this population and provide information only on mean glucose exposure. Revolutionary developments in glucose sensing and insulin delivery technology have occurred in the last decade. Newer factory-calibrated continuous glucose monitors provide real-time glucose data, with predictive alarms, allowing improved assessment of glucose excursions and preventive measures, particularly during and between dialysis sessions. Furthermore, integration of continuous glucose monitors and their predictive alerts with automated insulin delivery systems enables insulin administration to be decreased or stopped proactively, leading to improved glycaemic management and diminishing glycaemic fluctuations. While awaiting regulatory approval, emerging studies, expert real-world experience and clinical guidelines support the use of diabetes technology devices in people with diabetes and advanced chronic kidney disease.

Multivariate spatiotemporal functional principal component analysis for modeling hospitalization and mortality rates in the dialysis population.

Dialysis patients experience frequent hospitalizations and a higher mortality rate compared to other Medicare populations, in whom hospitalizations are a major contributor to morbidity, mortality, and healthcare costs. Patients also typically remain on dialysis for the duration of their lives or until kidney transplantation. Hence, there is growing interest in studying the spatiotemporal trends in the correlated outcomes of hospitalization and mortality among dialysis patients as a function of time starting from transition to dialysis across the United States Utilizing national data from the United States Renal Data System (USRDS), we propose a novel multivariate spatiotemporal functional principal component analysis model to study the joint spatiotemporal patterns of hospitalization and mortality rates among dialysis patients. The proposal is based on a multivariate Karhunen-Loéve expansion that describes leading directions of variation across time and induces spatial correlations among region-specific scores. An efficient estimation procedure is proposed using only univariate principal components decompositions and a Markov Chain Monte Carlo framework for targeting the spatial correlations. The finite sample performance of the proposed method is studied through simulations. Novel applications to the USRDS data highlight hot spots across the United States with higher hospitalization and/or mortality rates and time periods of elevated risk.

Racial Disparities in End-Stage Kidney Disease Outcomes among Asians and Native Hawaiians and Other Pacific Islanders across Geographic Residence.

INTRODUCTION: While Asian and Native Hawaiian and other Pacific Islander (NHOPI) patients have a high prevalence of kidney disease risk factors, there are sparse data examining their end-stage kidney disease (ESKD) outcomes. As Hawaii has high representation of Asian and NHOPI individuals, we compared their ESKD outcomes based on residence in the mainland USA versus Hawaii/Pacific Islands (PIs). MATERIALS AND METHODS: Using United States Renal Data System data, we examined the impact of geographic residence in the mainland versus Hawaii/PIs on race-mortality associations among incident ESKD patients transitioning to dialysis over January 1, 2000-December 31, 2016 using Cox regression. We examined likelihood of post-dialysis kidney transplantation using Cox models and cumulative incidence curves. RESULTS: Compared with White patients in the mainland, Asian and NHOPI patients in the mainland had lower mortality: adjusted HRs (95% CIs) 0.67 (0.66-0.67) and 0.72 (0.70-0.73), respectively. When examining Asian and NHOPI patients in Hawaii/PIs, survival benefit was attenuated in Asian and diminished to the null in NHOPI patients (ref: mainland White patients). Cumulative incidence curves comparing Asian, NHOPI, and White patients showed Asian and NHOPI patients in the mainland had the highest likelihood of transplantation, whereas NHOPI and Asian patients in Hawaii/PIs had the lowest likelihood. CONCLUSION: In the mainland, Asian and NHOPI patients had lower mortality versus White patients, whereas in Hawaii/PIs, this survival benefit was diminished in Asian and mitigated in NHOPI patients. NHOPI and Asian patients in Hawaii/PIs had less transplantation versus those in the mainland. Further research is needed to uncover factors contributing to differential ESKD outcomes among Asian and NHOPI patients across geographic residence.

Diabetic Kidney Disease Prevention Care Model Development.

More than one-third of people with diabetes develop diabetic kidney disease (DKD), which substantially increases risks of kidney failure, cardiovascular disease (CVD), hypoglycemia, death, and other adverse health outcomes. A multifaceted approach incorporating self-management education, lifestyle optimization, pharmacological intervention, CVD prevention, and psychosocial support is crucial to mitigate the onset and progression of DKD. The American Diabetes Association convened an expert panel to develop the DKD Prevention Model presented herein. This model addresses prevention and treatment, including screening guidelines, diagnostic tools, and management approaches; comprehensive, holistic interventions; well-defined roles for interdisciplinary health care professionals; community engagement; and future directions for research and policy.

Spatiotemporal multilevel joint modeling of longitudinal and survival outcomes in end-stage kidney disease.

Individuals with end-stage kidney disease (ESKD) on dialysis experience high mortality and excessive burden of hospitalizations over time relative to comparable Medicare patient cohorts without kidney failure. A key interest in this population is to understand the time-dynamic effects of multilevel risk factors that contribute to the correlated outcomes of longitudinal hospitalization and mortality. For this we utilize multilevel data from the United States Renal Data System (USRDS), a national database that includes nearly all patients with ESKD, where repeated measurements/hospitalizations over time are nested in patients and patients are nested within (health service) regions across the contiguous U.S. We develop a novel spatiotemporal multilevel joint model (STM-JM) that accounts for the aforementioned hierarchical structure of the data while considering the spatiotemporal variations in both outcomes across regions. The proposed STM-JM includes time-varying effects of multilevel (patient- and region-level) risk factors on hospitalization trajectories and mortality and incorporates spatial correlations across the spatial regions via a multivariate conditional autoregressive correlation structure. Efficient estimation and inference are performed via a Bayesian framework, where multilevel varying coefficient functions are targeted via thin-plate splines. The finite sample performance of the proposed method is assessed through simulation studies. An application of the proposed method to the USRDS data highlights significant time-varying effects of patient- and region-level risk factors on hospitalization and mortality and identifies specific time periods on dialysis and spatial locations across the U.S. with elevated hospitalization and mortality risks.

New and old approaches to nutritional management of acute and chronic glomerulonephritis.

PURPOSE OF REVIEW: It has been well published that a low protein diet (0.6-0.8 g/kg/day) is optimal for nutritional management of chronic kidney disease and with care be used without inducing protein malnutrition. RECENT FINDINGS: Though care with this approach must be demonstrated in patients with end-stage renal disease and with prominent protein energy wasting, another category of renal patient exists for whom dietary recommendations need more exploration. The Kidney Disease Improving Global Outcomes consortium, actually identifies renal disease as those patients with reduced filtration and those with excessive proteinuria excretion. Proteinuria, indeed, has proven to be a serious marker predisposing renal patients to atherosclerotic heart disease, venous thromboembolism, cerebrovascular accidents, and overall mortality. We discuss what is known about nutritional strategies to curb proteinuria and control inflammation in the setting of glomerulonephritis. SUMMARY: While this area of management of a set of conditions maybe nascent, it has the potential to provide incredible breakthroughs in nutritional management of auto immune diseases of the kidney specifically and the body writ large.

Association of iron therapy with incidence of chronic kidney disease.

OBJECTIVE: We investigated the association of oral iron replacement with the incidence of chronic kidney disease (CKD) in a population with normal kidney function to study the effects of iron replacement on the development of new onset CKD. METHODS: In a national cohort of US Veterans with no pre-existing CKD, we identified 33 894 incident new users of oral iron replacement and a comparable group of 112 780 patients who did not receive any iron replacement during 2004-2018. We examined the association of oral iron replacement versus no iron replacement with the incidence of eGFR <60 mL/min/1.73 m2 and the incidence of urine albumin creatinine ratio (UACR) ≥30 mg/g in competing risk regressions and in Cox models. We used propensity score weighing to account for differences in key baseline characteristics associated with the use of oral iron replacement. RESULTS: In the cohort of 146 674 patients, a total of 18 547 (13%) patients experienced incident eGFR <60 mL/min/1.73 m2 , and 16 117 patients (11%) experienced new onset UACR ≥30 mg/g. Oral iron replacement was associated with significantly higher risk of incident eGFR <60 mL/min/1.73 m2 (subhazard ratio, 95% confidence interval [CI]: 1.3 [1.22-1.38], p < .001) and incident albuminuria (subhazard ratio, 95% CI: 1.14 [1.07-1.22], p < .001). CONCLUSION: Oral iron replacement is associated with higher risk of new onset CKD. The long-term kidney safety of oral iron replacement should be tested in clinical trials.

Hypoglycemia and Mortality Risk in Incident Hemodialysis Patients.

OBJECTIVE: Hypoglycemia is a frequent occurrence in chronic kidney disease patients due to alterations in glucose and insulin metabolism. However, there are sparse data examining the predictors and clinical implications of hypoglycemia including mortality risk among incident hemodialysis patients. DESIGN AND METHODS: Among 58,304 incident hemodialysis patients receiving care from a large national dialysis organization over 2007-2011, we examined clinical characteristics associated with risk of hypoglycemia, defined as a blood glucose concentration <70 mg/dL, in the first year of dialysis using expanded case-mix + laboratory logistic regression models. We then examined the association between hypoglycemia during the first year of dialysis with all-cause mortality using expanded case-mix + laboratory Cox models. RESULTS: In the first year of dialysis, hypoglycemia was observed among 16.8% of diabetic and 6.9% of nondiabetic incident hemodialysis patients. In adjusted logistic regression models, clinical characteristics associated with hypoglycemia included younger age, female sex, African-American race, presence of a central venous catheter, lower residual renal function, and longer dialysis session length. In the overall cohort, patients who experienced hypoglycemia had a higher risk of all-cause mortality risk (reference: absence of hypoglycemia): adjusted hazard ratio (95% confidence interval) 1.08 (1.04, 1.13). In stratified analyses, hypoglycemia was also associated with higher mortality risk in the diabetic and nondiabetic subgroups: adjusted hazard ratios (95% confidence interval's) 1.08 (1.04-1.13), and 1.17 (0.94-1.45), respectively. CONCLUSIONS: Hypoglycemia was a frequent occurrence among both diabetic and nondiabetic hemodialysis patients and was associated with a higher mortality risk. Further studies are needed to identify approaches that reduce hypoglycemia risk in the hemodialysis population.

Nutritional and Dietary Management of Chronic Kidney Disease Under Conservative and Preservative Kidney Care Without Dialysis.

While dialysis has been the prevailing treatment paradigm for patients with advanced chronic kidney disease (CKD), emphasis on conservative and preservative management in which dietary interventions are a major cornerstone have emerged. Based on high-quality evidence, international guidelines support the utilization of low-protein diets as an intervention to reduce CKD progression and mortality risk, although the precise thresholds (if any) for dietary protein intake vary across recommendations. There is also increasing evidence demonstrating that plant-dominant low-protein diets reduce the risk of developing incident CKD, CKD progression, and its related complications including cardiometabolic disease, metabolic acidosis, mineral and bone disorders, and uremic toxin generation. In this review, we discuss the premise for conservative and preservative dietary interventions, specific dietary approaches used in conservative and preservative care, potential benefits of a plant-dominant low-protein diet, and practical implementation of these nutritional strategies without dialysis.

Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO).

People with diabetes and chronic kidney disease (CKD) are at high risk for kidney failure, atherosclerotic cardiovascular disease, heart failure, and premature mortality. Recent clinical trials support new approaches to treat diabetes and CKD. The 2022 American Diabetes Association (ADA) Standards of Medical Care in Diabetes and the Kidney Disease: Improving Global Outcomes (KDIGO) 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease each provide evidence-based recommendations for management. A joint group of ADA and KDIGO representatives reviewed and developed a series of consensus statements to guide clinical care from the ADA and KDIGO guidelines. The published guidelines are aligned in the areas of CKD screening and diagnosis, glycemia monitoring, lifestyle therapies, treatment goals, and pharmacologic management. Recommendations include comprehensive care in which pharmacotherapy that is proven to improve kidney and cardiovascular outcomes is layered on a foundation of healthy lifestyle. Consensus statements provide specific guidance on use of renin-angiotensin system inhibitors, metformin, sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide 1 receptor agonists, and a nonsteroidal mineralocorticoid receptor antagonist. These areas of consensus provide clear direction for implementation of care to improve clinical outcomes of people with diabetes and CKD.

Novel monitoring of renal function and medication levels in saliva and capillary blood of patients with kidney disease.

PURPOSE OF REVIEW: Serum creatinine, urea, and cystatin C are the main biomarkers used to estimate glomerular filtration rates in persons with and without chronic kidney disease (CKD). Frequent measurements of these assays are needed to identify patients with earlier stages of CKD, detect episodes of acute kidney injury (AKI), and monitor for CKD progression. However, the cumbersome, time-consuming nature of conventional laboratory-based kidney function assays limit more frequent monitoring and greater patient self-management. RECENT FINDINGS: Noninvasive salivary assessments of creatinine, cystatin C, and urea make it feasible to conduct frequent monitoring of kidney function in point-of-care settings, as well as in nonclinical-care settings such as at home. Additionally, fingerstick sampling can offer an alternative route of blood testing that is suitable for home-based assessments. In this review, we provide an overview of emerging data on various salivary vs. fingerstick blood assessment methods for kidney function; their accuracy in comparison to 'gold-standard' laboratory-based methods; and their respective strengths and limitations in the clinical setting. SUMMARY: A practical, cost-effective, minimally invasive, multimarker assessment platform has the potential to circumvent the limitation of conventional laboratory blood-based testing approaches, and thereby address a major unmet need in the management of CKD patients.

Novel approaches to hypoglycemia and burnt-out diabetes in chronic kidney disease.

PURPOSE OF REVIEW: Diabetes mellitus is a leading cause of chronic kidney disease (CKD) that confers faster kidney disease progression, higher mortality, and various metabolic derangements including hypoglycemia. RECENT FINDINGS: Even in the absence of diabetes mellitus, growing research demonstrates that CKD patients are at heightened risk for hypoglycemia via multiple pathways. In CKD patients transitioning to end-stage renal disease (ESRD), spontaneous resolution of hyperglycemia and frequent hypoglycemia resulting in reduction and/or cessation of glucose-lowering medications are frequently observed in a phenomenon described as 'burnt-out diabetes'. In non-CKD patients, it is well established that hypoglycemia is causally associated with mortality, with pathways including arrhythmias, sudden cardiac death, stroke, and seizures. Increasing evidence shows that, in CKD and ESRD patients with and without diabetes mellitus, hypoglycemia is associated with cardiovascular complications and mortality risk. SUMMARY: Given the high prevalence of hypoglycemia in CKD patients and the morbidity and mortality associated with this metabolic complication, a multimodal strategy is needed to prevent dysglycemia, including individualization of glycemic targets, selection of glucose-lowering medications less likely to induce hypoglycemia, medical nutrition therapy administered by trained dietitians, and accurate and precise hypoglycemia detection methods, such as self-monitored blood glucose or continuous glucose monitoring including during dialysis treatment.

Current status of the assessment of sarcopenia, frailty, physical performance and functional status in chronic kidney disease patients.

PURPOSE OF REVIEW: Low physical function, frailty, and sarcopenia are common complications of chronic kidney disease (CKD). In this article, we review the epidemiology and pathogenesis of low physical function, as well as its associations with adverse outcomes in CKD patients. Additionally, we present various traditional and novel methods for assessment of physical function in CKD patients. RECENT FINDINGS: In nondialysis dependent (NDD) and dialysis-dependent CKD patients, the prevalence of low physical function, frailty, and sarcopenia are substantially higher than in the general population. The potential mechanisms of low physical function, frailty, and sarcopenia in CKD patients are due to various factors including underlying kidney disease, co-existing comorbidities, and certain therapeutic interventions utilized in CKD. Increasing evidence has also uncovered the ill effects of impaired physical function on clinical outcomes in CKD patients. SUMMARY: Routine assessment of physical function is an under-utilized yet important component in the management of CKD patients. Future studies are needed to determine how prescription of exercise and increased daily physical activity can be tailored to optimize the health and well-being of NDD and dialysis-dependent CKD patients in pursuit of successful aging.

Medical nutrition therapy using plant-focused low-protein meal plans for management of chronic kidney disease in diabetes.

PURPOSE OF REVIEW: Nearly half of all Americans with chronic kidney disease (CKD) also have type-2-diabetes (T2D). Whereas traditional and emerging pharmacotherapies are increasingly frequently used for the management of CKD in diabetes (CKD/DM), the role of integrated or multimodal interventions including the potentially synergistic and additive effect of diet and lifestyle modifications in addition to pharmacotherapy has not been well examined, in sharp contrast to the well-known integrated approaches to heart disease. RECENT FINDINGS: Low-carbohydrate low-fat diets are often recommended in T2D, whereas low-protein diets (LPD) are recommended by guidelines for nondiabetic CKD with increasing emphasis on plant-based protein sources. High-protein diets with greater animal protein lead to glomerular hyperfiltration, especially in patients with T2D, and faster decline in renal function. Guidelines provide differing recommendations regarding the amount (low vs high) and source (plant vs animal) of dietary protein intake (DPI) in CKD/DM. Some such as KDIGO recommend 0.8 g/kg/day based on insufficient evidence for DPI restriction in CKD/DM, whereas KDOQI and ISRNM recommend a DPI of 0.6 to <0.8 g/kg/day. A patient-centered plant-focused LPD for the nutritional management of CKD/DM (PLAFOND), a type of PLADO diet comprising DPI of 0.6 to <0.8 g/kg/day with >50% plant-based sources, high dietary fiber, low glycemic index, and 25-35 Cal/kg/day energy, can be implemented by renal dietitians under Medical Nutrition Therapy. SUMMARY: Potential risks vs benefits of high vs low protein intake in CKD/DM is unknown, for which expert recommendations remain opinion based. Randomized controlled studies are needed to examine safety, acceptability and efficacy of PLAFOND.

Causes of Death in End-Stage Kidney Disease: Comparison between the United States Renal Data System and a Large Integrated Health Care System.

INTRODUCTION: Using a large diverse population of incident end-stage kidney disease (ESKD) patients from an integrated health system, we sought to evaluate the concordance of causes of death (CODs) between the underlying COD from the United States Renal Data System (USRDS) registry and CODs obtained from Kaiser Permanente Southern California (KPSC). METHODS: A retrospective cohort study was performed among incident ESKD patients who had mortality records and CODs reported in both KPSC and USRDS databases between January 1, 2007, and December 31, 2016. Underlying CODs reported by the KPSC were compared to the CODs reported by USRDS. Overall and subcategory-specific COD agreements were assessed using Cohen's weighted kappa statistic (95% CI). Proportions of positive and negative agreement were also determined. RESULTS: Among 4,188 ESKD patient deaths, 4,118 patients had CODs recorded in both KPSC and USRDS. The most common KPSC CODs were circulatory system diseases (35.7%), endocrine/nutritional/metabolic diseases (24.2%), genitourinary diseases (12.9%), and neoplasms (9.6%). Most common USRDS CODs were cardiac disease (46.9%), withdrawal from dialysis (12.6%), and infection (10.1%). Of 2,593 records with causes listed NOT as "Other," 453 (17.4%) had no agreement in CODs between the USRDS and the underlying, secondary, tertiary, or quaternary causes recorded by KPSC. In comparing CODs recorded within KPSC to the USRDS, Cohen's weighted kappa (95% CI) was 0.20 (0.18-0.22) with overall agreement of 36.4%. CONCLUSION: Among an incident ESKD population with mortality records, we found that there was only fair or slight agreement between CODs reported between the USRDS registry and KPSC, a large integrated health care system.

Comparative Effectiveness of Dialysis Modality on Laboratory Parameters of Mineral Metabolism.

INTRODUCTION: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are prevalent in patients undergoing maintenance dialysis. Yet, there are limited and mixed evidence on the effects of different dialysis modalities involving longer treatment times or higher frequencies on CKD-MBD markers. METHODS: This cohort study used data from 132,523 incident dialysis patients treated with any of the following modalities: conventional thrice-weekly in-center hemodialysis, nocturnal in-center hemodialysis (NICHD), home hemodialysis (HHD), or peritoneal dialysis (PD) from 2007 to 2011. We used marginal structural models fitted with inverse probability weights to adjust for fixed and time-varying confounding and informative censoring. We estimated the average effects of treatments with different dialysis modalities on time-varying serum concentrations of CKD-MBD markers: albumin-corrected calcium, phosphate, parathyroid hormone (PTH), and alkaline phosphatase (ALP) using pooled linear regression. RESULTS: Most of the cohort were exclusively treated with conventional in-center hemodialysis, while few were ever treated with NICHD or HHD. At the baseline, PD patients had the lowest mean and median values of PTH, while NICHD patients had the highest median values. During follow-up, compared to hemodialysis patients, patients treated with NICHD had lower mean serum PTH (19.8 pg/mL [95% confidence interval: 2.8, 36.8] lower), whereas PD and HHD patients had higher mean PTH (39.7 pg/mL [31.6, 47.8] and 51.2 pg/mL [33.0, 69.3] higher, respectively). Compared to hemodialysis patients, phosphate levels were lower for patients treated with NICHD (0.44 mg/dL [0.37, 0.52] lower), PD (0.15 mg/dL [0.12, 0.19] lower), or HHD (0.33 mg/dL [0.27, 0.40] lower). There were no clinically meaningful associations between dialysis modalities and concentrations of calcium or ALP. CONCLUSION: In incident dialysis patients, compared to treatment with conventional in-center hemodialysis, treatments with other dialysis modalities with longer treatment times or higher frequency were associated with different patterns of serum phosphate and PTH. Given the recent growth in the use of dialysis modalities other than hemodialysis, the associations between the treatment and the CKD-MBD markers warrant additional study.

Association of pre-ESKD hyponatremia with post-ESKD outcomes among incident ESKD patients.

BACKGROUND: Hyponatremia is one of the most common electrolyte disturbances in advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD) patients, and has been shown to be associated with higher mortality risk. However, the relationship between hyponatremia during late-stage CKD and the risk of poor outcomes after ESKD transition is unknown. METHODS: We conducted a retrospective cohort study including 32 257 US veterans transitioning to ESKD from 1 October 2007 to 30 March 2015. We evaluated adjusted associations between the 3-month averaged pre-transition to ESKD serum sodium and all-cause mortality. Secondary outcomes included cardiovascular (CV) mortality, infection-related mortalities and hospitalization rate. RESULTS: Cohort mean ± standard deviation serum sodium was 139 ± 3 mEq/L, mean age was 67 ± 11 years, 98% were male and 28% were African American. Over a median (interquartile range) follow-up of 702 days (296, 1301) there were 17 162 deaths. Compared with the reference of 135 to <144 mEq/L, the lowest serum sodium group (<130 mEq/L) had a 54% higher all-cause mortality risk [hazard ratio 1.54 (95% confidence interval 1.34-1.76)] in the fully adjusted model. Associations were similar for CV and infection-related mortality, and hospitalization outcomes. CONCLUSIONS: Hyponatremia prior to ESKD transition is associated with higher risk of all-cause, CV and infection-related mortalities, and hospitalization rates after ESKD transition. Future studies evaluating management of pre-ESKD hyponatremia may be indicated to improve patient outcomes for those transitioning to ESKD.

A Bayesian multilevel time-varying framework for joint modeling of hospitalization and survival in patients on dialysis.

Over 782 000 individuals in the United States have end-stage kidney disease with about 72% of patients on dialysis, a life-sustaining treatment. Dialysis patients experience high mortality and frequent hospitalizations, at about twice per year. These poor outcomes are exacerbated at key time periods, such as the fragile period after transition to dialysis. In order to study the time-varying effects of modifiable patient and dialysis facility risk factors on hospitalization and mortality, we propose a novel Bayesian multilevel time-varying joint model. Efficient estimation and inference is achieved within the Bayesian framework using Markov chain Monte Carlo, where multilevel (patient- and dialysis facility-level) varying coefficient functions are targeted via Bayesian P-splines. Applications to the United States Renal Data System, a national database which contains data on nearly all patients on dialysis in the United States, highlight significant time-varying effects of patient- and facility-level risk factors on hospitalization risk and mortality. Finite sample performance of the proposed methodology is studied through simulations.

Intradialytic hypotension: is timing everything?

Intradialytic hypotension (IDH) is a major complication of hemodialysis, leading to myocardial stunning, cerebral hypoperfusion, gut ischemia, loss of residual kidney function, high symptom burden, and death. This study by Keane et al. provides new data on the incidence of IDH over well-defined time intervals during the hemodialysis treatment session, clinical parameters associated with the timing of IDH onset, and whether timing of IDH impacts survival in a nationally representative hemodialysis cohort.