Magdalene M. Assimon

Intradialytic Blood Pressure Abnormalities: The Highs, The Lows and All That Lies Between.

Background: Frequent blood pressure (BP) measurements are necessary to ensure patient safety during hemodialysis treatments. Intradialytic BPs are not optimal tools for hypertension diagnosis and cardiovascular risk stratification, but they do have critical clinical and prognostic significance. We present evidence associating intradialytic BP phenomena including fall, rise and variability with adverse clinical outcomes and review related pathophysiologic mechanisms and potential management strategies. Summary: Observational studies demonstrate associations between intradialytic hypotension, hypertension and BP variability and mortality. Lack of consensus regarding diagnostic criteria has hampered data synthesis, and prospective studies investigating optimal management strategies for BP phenomena are lacking. Mechanistic data suggest that cardiac, gut, kidney and brain ischemia may lie on the causal pathway between intradialytic hypotension and mortality, and endothelial cell dysfunction, among other factors, may be an important mediator of intradialytic hypertension and adverse outcomes. These plausible pathophysiologic links present potential therapeutic targets for future inquiry. The phenomenon of intradialytic BP variability has not been adequately studied, and practical clinical measures and treatment strategies are lacking. Key Messages: Intradialytic BP phenomena have important prognostic bearing. Clinical practice guidelines for both intradialytic hypotension and hypertension exist, but their underlying evidence is weak overall. Further research is needed to develop consensus diagnostic criteria for intradialytic hypotension, hypertension and BP variability and to elucidate optimal treatment and prevention strategies for each BP manifestation.

Ultrafiltration Rates and the Quality Incentive Program: Proposed Measure Definitions and Their Potential Dialysis Facility Implications

BACKGROUND AND OBJECTIVES Rapid ultrafiltration rates are associated with adverse outcomes among patients on hemodialysis. The Centers for Medicare and Medicaid Services is considering an ultrafiltration rate quality measure for the ESRD Quality Incentive Program. Two measure developers proposed ultrafiltration rate measures with different selection criteria and specifications. We aimed to compare the proposed ultrafiltration rate measures and quantify dialysis facility operational burden if treatment times were extended to lower ultrafiltration rates. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data were taken from the 2012 database of a large dialysis organization. Analyses of the Centers for Medicare and Medicaid Services measure considered 148,950 patients on hemodialysis, and analyses of the Kidney Care Quality Alliance measure considered 151,937 patients. We described monthly patient and facility ultrafiltration rates and examined differences in patient characteristics across ultrafiltration rate thresholds and differences in facilities across ultrafiltration rate measure scores. We computed the additional treatment time required to lower ultrafiltration rates <13 ml/h per kilogram. RESULTS Ultrafiltration rates peaked in winter and nadired in summer. Patients with higher ultrafiltration rates were younger; more likely to be women, nonblack, Hispanic, and lighter in weight; and more likely to have histories of heart failure compared with patients with lower ultrafiltration rates. Facilities had, on average, 20.8%±10.3% (July) to 22.8%±10.6% (February) of patients with ultrafiltration rates >13 ml/h per kilogram by the Centers for Medicare and Medicaid Services monthly measure. Facilities had, on average, 15.8%±8.2% of patients with ultrafiltration rates ≥13 ml/h per kilogram by the Kidney Care Quality Alliance annual measure. Larger facilities (>100 patients) would require, on average, 33 additional treatment hours per week to lower all facility ultrafiltration rates <13 ml/h per kilogram when total treatment time is capped at 4 hours. CONCLUSIONS Ultrafiltration rates vary seasonally and across clinical subgroups. Extension of treatment time as a strategy to lower ultrafiltration rates may pose facility operational challenges. Prospective studies of ultrafiltration rate threshold implementation are needed.

Rapid ultrafiltration rates and outcomes among hemodialysis patients: re-examining the evidence base.

Purpose of reviewThis review critically summarizes the evidence linking ultrafiltration rates to adverse outcomes among hemodialysis patients and provides research recommendations to address knowledge gaps. Recent findingsGrowing evidence suggests that fluid-related factors play important roles in hemodialysis patient outcomes. Ultrafiltration rate – the rate of fluid removal during hemodialysis – is one such factor. Existing observational data suggest a robust association between greater ultrafiltration rates and adverse cardiovascular outcomes, and such findings are supported by plausible physiologic rationale. Potential mechanistic pathways include ultrafiltration-related ischemia to the heart, brain, and gut, and volume overload-precipitated cardiac stress from reactive measures to ultrafiltration-induced hemodynamic instability. Inter-relationships among ultrafiltration rates and other fluid measures, such as interdialytic weight gain and chronic volume expansion, render the specific role of ultrafiltration rates in adverse outcomes difficult to study. Randomized trials must be conducted to confirm epidemiologic findings and examine the effect of ultrafiltration rate reduction on clinical and patient-centered outcomes. SummaryCompelling observational data demonstrate an association between more rapid ultrafiltration rates and adverse clinical outcomes. Before translating these findings into clinical practice, randomized trials are needed to verify observational data results and to identify effective strategies to mitigate ultrafiltration-related risk.

Intradialytic Hypertension Frequency and Short-Term Clinical Outcomes Among Individuals Receiving Maintenance Hemodialysis

BACKGROUND Intradialytic hypertension occurs in 5-20% of hemodialysis treatments. Observational data support an association between intradialytic hypertension and long-term mortality. However, the short-term consequences of recurrent intradialytic hypertension are unknown. METHODS Data were taken from a cohort of prevalent hemodialysis patients receiving treatment at a large United States dialysis organization on 1 January 2010. A retrospective cohort design with a 180-day baseline, 30-day exposure assessment, and 30-day follow-up period was used to estimate the associations between intradialytic hypertension frequency and 30-day outcomes. Intradialytic hypertension frequency was defined as the proportion of exposure period hemodialysis treatments with a predialysis to postdialysis systolic blood pressure rise >0 mm Hg. Multivariable Cox proportional hazards regression, adjusted for baseline clinical, laboratory, and dialysis treatment covariates, was used to estimate hazard ratios and 95% confidence intervals. RESULTS Of the 37,094 study patients, 5,242 (14.1%), 17,965 (48.4%), 10,821 (29.2%), 3,066 (8.3%) had intradialytic hypertension in 0%, 1-32%, 33-66%, and ≥67% of exposure period treatments, respectively. More frequent intradialytic hypertension was associated with incremental increases in 30-day mortality and hospitalizations. Patients with intradialytic hypertension in ≥67% (vs. 0%) of exposure period treatments had the highest risk of all-cause death, hazard ratio [95% confidence interval]: 2.57 [1.68, 3.94]; cardiovascular (CV) death, 3.68 [1.89, 7.15]; all-cause hospitalizations, 1.42 [1.26, 1.62]; CV hospitalizations, 1.71 [1.36, 2.15]; and volume-related hospitalizations, 2.25 [1.25, 4.04]. CONCLUSIONS Among prevalent hemodialysis patients, more frequent intradialytic hypertension was incrementally associated with increased 30-day morbidity and mortality. Intradialytic hypertension may be an important short-term risk marker in the hemodialysis population.

Definitions of intradialytic hypotension

Intradialytic hypotension (IDH) is a common and often distressful complication of hemodialysis. However, despite its clinical significance, there is no consensus, evidence‐based medical definition for the condition. Over the years, numerous definitions have been implemented in both the clinical and research settings. Definition inconsistencies have hindered data synthesis and the development of evidence‐based guidelines for the prevention and treatment of IDH, as well as prevented accurate estimation of the population burden of IDH and patient risk assessment. Most existing IDH definitions are comprised of one or more of the following components: (1) intradialytic BP criteria (requisite BP declines or minimum BP thresholds), (2) the provision of interventions aimed at restoring effective arterial volume, and/or (3) patient‐reported symptoms. Remarkably, there are insufficient data to inform IDH definition construction, and it remains unknown if a single, universal definition can adequately capture the condition across patient subgroups, and in clinical and research settings.

Thirty-day hospital readmissions in the hemodialysis population: A problem well put, but half-solved

> “A problem well put is half-solved” > > (John Dewey, 1859–1952). In recent years, United States policymakers have made 30-day hospital readmission reduction a centerpiece of efforts to curb Medicare costs. In the general Medicare population, 15% of patients are readmitted to the hospital

Failed Target Weight Achievement Associates with Short-Term Hospital Encounters among Individuals Receiving Maintenance Hemodialysis

Background Hospitalizations and 30-day readmissions are common in the hemodialysis population. Actionable clinical markers for near-term hospital encounters are needed to identify individuals who require swift intervention to avoid hospitalization. Aspects of volume management, such as failed target weight (i.e, estimated dry weight) achievement, are plausible modifiable indicators of impending adverse events. The short-term consequences of failed target weight achievement are not well established.Methods Statistically deidentified data were taken from a cohort of Medicare-enrolled, prevalent hemodialysis patients treated at a large dialysis organization from 2010 to 2012. We used a retrospective cohort design with repeated intervals, each consisting of 180-day baseline, 30-day exposure assessment, and 30-day follow-up period, to estimate the associations between failed target weight achievement and the risk of 30-day emergency department visits and hospitalizations. We estimated adjusted risk differences using inverse probability of exposure weighted Kaplan-Meier methods.Results A total of 113,561 patients on hemodialysis contributed 788,722 study intervals to analyses. Patients who had a postdialysis weight >1.0 kg above the prescribed target weight in ≥30% (versus <30%) of exposure period treatments had a higher absolute risk (risk difference) of 30-day: emergency department visits (2.13%; 95% confidence interval, 2.00% to 2.32%); and all-cause (1.47%; 95% confidence interval, 1.34% to 1.62%), cardiovascular (0.31%; 95% confidence interval, 0.24% to 0.40%), and volume-related (0.15%; 95% confidence interval, 0.11% to 0.21%) hospitalizations.Conclusions In the absence of objective measures of volume status, recurrent failure to achieve target weight is an easily identifiable clinical risk marker for impending hospital encounters among patients on hemodialysis.

Ultrafiltration Rate Scaling in Hemodialysis Patients

To the Editor: Over the last several years, data supporting an association between higher ultrafiltration (UF) rates and increased mortality among individuals receiving maintenance hemodialysis has accumulated (1–4). These observational findings are supported by mechanistic studies showing that intradialytic end-organ ischemic injury may occur in response to aggressive fluid removal (5–7). As a result of these studies and others, there has been heightened interest in improving cliniclevel fluid management across the dialysis community (8), ultimately leading to the approval of an UF rate reporting measure for the 2020 Centers for Medicare and Medicaid (CMS) End Stage Renal Disease (ESRD) Quality Incentive Program (QIP) (9). The CMS measure and its supporting data specify the dialytic UF rate in terms of ml/hour/kg. Said differently, the selected UF rate metric is “scaled” to body weight (body mass). In the January 2017 issue of Seminars in Dialysis, Daugirdas and Schneditz provided commentary on considerations for the appropriate scaling of hemodialysis UF rates (10). In their editorial, they suggested that it may be more appropriate to scale UF rates to body surface area (BSA) rather than to body weight. Relying on data from the Hemodialysis (HEMO) Study, the authors proposed that BSA might better reflect vascular refilling capacity than body weight. They hypothesized that BSA’s correlation with both blood volume and extracellular volume render it more relevant to refilling capacity than body weight on its own (10). Then, citing data from an observational analysis of UF rates (considered scaled to body weight, body mass index and BSA) and all-cause mortality by Assimon et al., they noted that: 1) the rapid UF rate—mortality association may be more pronounced in patients of greater body weight, and 2) the UF rate—mortality association may be more consistent when scaled to BSA than when scaled to body weight (4). Daugirdas and Schneditz appropriately pointed out that the Assimon et al. analyses were not stratified by sex, potentially obscuring important information that could shed light on the optimal approach to UF rate scaling (10). To provide additional insight into the UF rate scaling dilemma, we provide the results of updated UF rate—outcome analyses stratified by both sex and body size. In a previously described cohort of over 118,000 adult individuals who had received center-based hemodialysis for at least 90 days at study start, and using previously described methods (4), we estimated the associations of average delivered UF rates and all-cause mortality across strata of sex and body size (Table 1). When stratified by sex, the association between higher UF rates and increased mortality remained statistically significant across all body size strata. Although we observed some variation in the magnitude of risk across strata of sex and body size, such differences were not sufficiently pronounced to necessitate, in our opinion, stratum-specific UF rate goals. The data suggest that risk from greater UF rates is higher among individuals of larger body sizes; however, the risk from greater UF rates remains significant among individuals of smaller body sizes. Since smaller patients do incur risk from more rapid fluid removal, it is reasonable to counsel either treatment time extension or interdialytic weight gain reduction in this subgroup to mitigate UF-related risk. However, like all clinical recommendations, counseling should be patient specific. Individuals with poor nutritional status who would benefit from enhanced caloric intake should not be counseled to decrease sodium intake to a level that could be detrimental to their nutritional status. Furthermore, the data do not show a consistent rise in UF rate-associated risk across categories of increasing body weight, suggesting that the UF rate—mortality association does not consistently vary by body size, rendering size-specific UF rate recommendations unnecessary based on the current published evidence. Finally, there does not appear to be significant advantages to scaling UF rate to either BSA or body mass index as opposed to body weight. Scaling UF rate to body mass index or BSA (vs. body weight) did not greatly enhance hazard ratio stability across strata of sex and body size. Our findings suggest that the current approach of scaling UF rates to body size as reflected by body weight without weight stratum-specific thresholds is reasonable. When implementing clinical quality measures, population-level and individual-level risks and benefits must be weighed. Generally, ideal quality measures are simple and relevant to diverse subgroups so that they both minimize implementation-associated error and facilitate health of the broader population. We believe the current approach of specifying target UF rate thresholds scaled to body weight achieves these Address correspondence to: Jennifer E. Flythe MD, MPH, University of North Carolina Kidney Center, 7024 BurnettWomack CB #7155, Chapel Hill, NC 27599-7155, Tel.: +1 919-445-2656, Fax: +1 919-966-4251, or e-mail: jflythe@med.unc.edu. Seminars in Dialysis—Vol 30, No 3 (May–June) 2017 pp. 282–283 DOI: 10.1111/sdi.12602

Variability May Be the "Law of Life," but Blood Pressure Variability May Forebode a Shorter Life.

Genetic, phenotypic, and physiologic variability complicate the understanding, diagnosis, and treatment of almost all disease states. Historically, blood pressure (BP) variations across clinic visits were viewed as random fluctuations without clinical or prognostic significance. However, emerging evidence suggests that these long-term fluctuations, termed BP visit-to-visit variability, portend a range of adverse health events in the general and kidney disease populations. 2-4 Higher BP visit-to-visit variability has been associated with acute myocardial infarction (MI), stroke, and left ventricular dysfunction. 5 Such adverse clinical outcomes have proved particularly difficult to modify among patients with chronic kidney disease due to the complex interplay of traditional and kidney disease–specific risk factors involved in cardiovascular disease pathogenesis. The prospect of long-term BP visit-to-visit variability as a novel modifiable cardiovascular risk factor has generated enthusiasm among some because it potentially represents a new therapeutic target through which to improve patient outcomes.