Kidney News February 2017 9#2 : Page 1

February 2017 | Vol. 9, Number 2 Depression Undertreated in Patients Receiving Chronic Dialysis By Tracy Hampton Journal of the American Society of Neph-rology , also found that when patients are willing to accept treatment for depression, renal providers commonly do not pre-scribe it. Depression affects nearly one-quarter of people receiving chronic hemodialysis, compared with an average population lifetime risk of between 8.3% and 9%. These high rates likely reflect the various physiological and psychosocial con-sequences of living with impaired kidney function—from the adverse ef-fects of frequent treatment to the poten-tial loss of social support and vocational capacity. Depression in dialysis patients affects not only their mental health and quality of life but has also been linked to missed and abbreviated dialysis treatments, more frequent emergency department visits and hospitalizations, and an increased risk of premature death. To address the negative effects that depression can have on dialysis patients’ health and survival, the Centers for Medicare & Medicaid Services Quality Improvement Program (QIP) for end stage renal disease recently mandated that all dialysis facilities report individual patient screening and treat-ment plans for depression for payment year 2018. Little information, however, is available on the effectiveness of anti-depressant therapy in patients on chronic hemodialysis or the acceptance of treat-ment by patients and clinicians. To investigate, a team led by Steven Weisbord, MD, MSc, and Julio Pena-Po-lanco, MD, of the VA Pittsburgh Health-care System and University of Pittsburgh School of Medicine, asked 101 patients on hemodialysis who were participating in the Symptom Management Involv-ing ESRD (SMILE) trial to complete the Patient Health Questionnaire 9 (PHQ-9) each month. The prospective, multi-center, cluster-randomized SMILE trial compared 2 strategies for the manage-ment of 3 common symptoms in cog-nitively intact adults receiving chronic, Inside Report: Kidney Disease Research Underfunded US government spends more on the Medicare ESRD program (nearly $32 billion) than it invests in the entire NIH budget (approximately $31 billion) Kidney Workforce Trends to watch in 2017 include shifts in nephrology GME, new training offerings, and the changing healthcare landscape N Fellows Corner A fellow looks at the clinical implications of low health literacy ew research indicates that many patients who are receiving chron-ic hemodialysis have depressive symptoms but do not wish to receive ag-gressive treatment to alleviate them. The study, which is published in the Clinical Findings Mortality differs acccording to reason for starting dialysis Continued on page 2 Why Is Low Blood Pressure Related to Increased Cardiovascular Risk in CKD? Practice Pointers Pregnancy and kidney failure M Study Suggests “Reverse Causality” from Subclinical Cardiac Disease “Confounding by disease is the chief explanation for the apparent weakening and reversal of the association between systolic BP and cardiovascular risk in mod-erate-to-advanced CKD,” said William G. Herrington, MD, MRCP(UK) of the Clinical Trial Service Unit & Epidemio-logical Studies Unit (CTSU), University of Oxford. “Such confounding masks a causal association between blood pressure and risk in patients with CKD with established cardiovascular disease.” Together with other recent evidence, these results add weight to the hypothesis that more-intensive BP reductions might reduce cardiovascular risk in patients with CKD, including those on dialysis. any studies have noted a U-shaped association between blood pressure and cardiovas-cular risk in patients with chronic kidney disease (CKD). A report in Hypertension suggests a possible explanation for this par-adoxical relationship: a confounding effect by subclinical cardiac disease. U-shaped association between BP and mortality in CKD The researchers analyzed data from The Study of Heart and Renal Protection Continued on page 2

Depression Undertreated In Patients Receiving Chronic Dialysis

Tracy Hampton

New research indicates that many patients who are receiving chronic hemodialysis have depressive symptoms but do not wish to receive aggressive treatment to alleviate them. The study, which is published in the Clinical Journal of the American Society of Nephrology, also found that when patients are willing to accept treatment for depression, renal providers commonly do not prescribe it.

Depression affects nearly onequarter of people receiving chronic hemodialysis, compared with an average population lifetime risk of between 8.3% and 9%. These high rates likely reflect the various physiological and psychosocial consequences of living with impaired kidney function—from the adverse effects of frequent treatment to the potential loss of social support and vocational capacity.

Depression in dialysis patients affects not only their mental health and quality of life but has also been linked to missed and abbreviated dialysis treatments, more frequent emergency department visits and hospitalizations, and an increased risk of premature death. To address the negative effects that depression can have on dialysis patients’ health and survival, the Centers for Medicare & Medicaid Services Quality Improvement Program (QIP) for end stage renal disease recently mandated that all dialysis facilities report individual patient screening and treatment plans for depression for payment year 2018. Little information, however, is available on the effectiveness of antidepressant therapy in patients on chronic hemodialysis or the acceptance of treatment by patients and clinicians.

To investigate, a team led by Steven Weisbord, MD, MSc, and Julio Pena-Polanco, MD, of the VA Pittsburgh Healthcare System and University of Pittsburgh School of Medicine, asked 101 patients on hemodialysis who were participating in the Symptom Management Involving ESRD (SMILE) trial to complete the Patient Health Questionnaire 9 (PHQ- 9) each month. The prospective, multicenter, cluster-randomized SMILE trial compared 2 strategies for the management of 3 common symptoms in cognitively intact adults receiving chronic, thrice-weekly outpatient hemodialysis at 9 dialysis units in western Pennsylvania.

For depressed patients (PHQ-9 score ≥10), trained nurses generated treatment recommendations and helped implement therapy if patients and renal providers accepted the recommendations.

Of the 101 patients who were followed for at least 1 year, 39 met criteria for depression based on their PHQ-9 scores. These 39 patients had depression on 147 of 373 (39%) monthly assessments. At 70% of these 147 assessments, patients were receiving anti-depressant therapy. and at 51 of 70 (70%) assessments, patients did not accept nurses’ recommendations to intensify treatment. At 44 assessments, patients with depression were not receiving anti-depressant therapy and in 40 instances (91%) did not accept recommendations to start treatment.

In most cases, patients refused the recommendations because they felt their depression was attributable to an acute event, chronic illness, or dialysis. Factors associated with refusal of treatment recommendations were older age, being married, and African American race, although only the association of older age with treatment refusal was statistically significant.

In 11 of 18 instances (61%) in which patients accepted the recommendation related to treatment for depression, renal providers were unwilling to provide treatment. In 8 of these 11 instances, the renal provider offered no explanation for not accepting the recommendation; in 2 instances, the provider deferred treatment recommendations to the patients’ primary care provider; and in 1 instance, the provider did not accept the recommendation because the patient was hospitalized.

“We discovered that some patients are on anti-depressant treatment that does not appear to be effective, and most who are not on treatment do not wish to be treated,” Weisbord said. “We also noted that when patients do request treatment, renal providers commonly do not prescribe treatment.”

Weisbord and his colleagues pointed to past research indicating that 90% of nephrologists provide primary care to their patients who are on dialysis and that as few as 20% of patients on chronic dialysis have a separate primary care provider.

“The apparent unwillingness of renal providers to consider implementing treatment for depression, particularly in the absence of primary providers who might assume this responsibility, represents a major obstacle to the systematic provision of therapy,” they wrote.

Considering Medicare’s recently released criteria for the end stage renal disease QIP, the authors noted that the implementation of a performance measure based on screening and treatment is logically based on the assumption that patients wish to have the condition treated. Therefore, the results of this study suggest that the requirement to universally document and provide care for depression in dialysis patients may be premature.

In an accompanying editorial, Maree Hackett, PhD, and Meg Jardine, PhD, of the University of Sydney, in Australia, noted that there are many challenges to the detection and treatment of depression in people on dialysis. “The importance of the inner experience may get lost by patients, carers and clinicians in a setting of intensive medical intervention, intercurrent comorbidities, and high rates of unwelcome events,” they wrote. They argued that a safe, effective, low-cost treatment for managing depression could help patients live well, rather than just survive, while on dialysis.

Article: “Acceptance of Anti-Depressant Treatment by Patients on Hemodialysis and their Renal Providers.” doi: 10.2215/ CJN.07720716

Editorial: “We Need to Talk about Depression and Dialysis: But What Questions Should We Ask and Does Anyone Know the Answers?”

Read the full article at http://onlinedigeditions.com/article/Depression+Undertreated+In+Patients+Receiving+Chronic+Dialysis/2700345/380295/article.html.

Why Is Low Blood Pressure Related To Increased Cardiovascular Risk In CKD?

Study Suggests “Reverse Causality” from Subclinical Cardiac Disease

Many studies have noted a Ushaped association between blood pressure and cardiovascular risk in patients with chronic kidney disease (CKD). A report in Hypertension suggests a possible explanation for this paradoxical relationship: a confounding effect by subclinical cardiac disease.

“Confounding by disease is the chief explanation for the apparent weakening and reversal of the association between systolic BP and cardiovascular risk in moderate- to-advanced CKD,” said William G. Herrington, MD, MRCP(UK) of the Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), University of Oxford. “Such confounding masks a causal association between blood pressure and risk in patients with CKD with established cardiovascular disease.”

Together with other recent evidence, these results add weight to the hypothesis that more-intensive BP reductions might reduce cardiovascular risk in patients with CKD, including those on dialysis.

U-shaped association between BP and mortality in CKD

The researchers analyzed data from The Study of Heart and Renal Protection (SHARP)—a seminal trial in which 9270 patients with CKD were randomly assigned to ezetimibe/simvastatin versus placebo. The principal investigators of the SHARP Study (www.sharpinfo.org) were Colin Baigent, FRCP, FFPH, and Martin J. Landray, PhD, FRCP, also of CTSU.

The main SHARP results—published in The Lancet in 2011—showed that cholesterol-lowering therapy can substantially reduce the risk of major atherosclerotic events in CKD. Subsequent analyses of the SHARP data have yielded further insights on the outcomes and prognostic factors among people with CKD. In this new analysis, the SHARP investigators explored the paradoxical relationship between BP and cardiovascular risk in patients with CKD.

In apparently healthy adults, as BP increases so does the risk of death from ischemic heart disease, stroke, or heart failure. Risk is approximately doubled for each 20 mm Hg increase in “usual” systolic BP and each 10 mm Hg increase in diastolic BP—there is no threshold below which lower SBP is not associated with lower risk.

However, in CKD, the association curve is often U-shaped—cardiovascular risk is increased at both higher and lower BP values, including low-normal BP. One suggested reason is reverse causality: longstanding hypertension may lead to changes in cardiac structure and function, thus lowering BP while at the same time increasing cardiovascular risk.

Previous studies have found that at least half of patients with stage 4 to 5 CKD show cardiac structural abnormalities, often without signs or symptoms. In the Chronic Renal Insufficiency Cohort (CRIC) study, 75% of patients with an estimated glomerular filtration rate less than 30 mL/min per 1.73 m2 had left ventricular hypertrophy on echocardiography.

Herrington and colleagues tested the hypothesis that the association between BP and cardiovascular risk might be confounded by the presence of such cardiac damage—patients who have CKD but have not yet developed cardiac disease might exhibit a positive loglinear association similar to that observed in apparently healthy adults.

To do this, the researchers needed a marker of cardiovascular risk. “The investigative trick was to use blood troponin to identify those at lowest risk of subclinical heart disease,” Herrington explained. “This was based on several previous studies showing that troponin-I is positively correlated with left ventricular mass and negatively correlated with cardiac function.”

In the SHARP cohort, higher baseline troponin-I was associated with male sex, older age, higher systolic BP, a higher prevalence of diabetes, and worse renal function. During a median follow- up of nearly five years, 2188 subjects had one or more cardiovascular events—a rate of 6.7% per year.

On adjusted analysis, higher baseline troponin-I was a strong predictor of future cardiovascular events. Risk was increased 61% for CKD patients with baseline troponin- I over 0.01 ng/mL and 182% for those over 0.03 ng/mL (compared to the reference value of 0.01 ng/mL or less). This association was apparent in both dialysis and non-dialysis CKD patients.

In the full cohort, the association between systolic BP and cardiovascular risk was U-shaped. However, among the 7278 patients without previous cardiovascular disease, there was a positive loglinear association. On adjusted analysis, each 10 mm Hg increment in usual systolic BP was associated with a 16% increase in cardiovascular risk. This risk increased to 27% per 10 mm Hg when analyses were further restricted to those patients without evidence of subclinical cardiac disease—i.e., baseline troponin of 0.01 ng/mL or less. The association was little affected by adjustment for baseline albumin:creatinine ratio, was about the same for atherosclerotic and nonatherosclerotic events, in dialysis and nondialysis patients, and among patients younger than 62 (the study median age) and those 62 years or older.

In the full cohort, however, there were also U-shaped associations for diastolic BP (but not pulse pressure). Associations with diastolic BP remained U-shaped among patients with a low troponin-I.

Support for studies of lower BP targets in CKD

The findings add to previous data on the complex relationship between BP and cardiovascular risk in CKD. Herrington and coauthors write: “The presence of a clear positive loglinear relationship between SBP (or pulse pressure) and cardiovascular events in patients with CKD at lowest risk of cardiac disease in SHARP suggests that reverse causality is a plausible explanation for previously observed U-shaped associations among patients with moderate-to-advanced CKD.”

Herrington commented: “This suggests that guidelines should not be using observational analyses of BP to define optimum BP targets in diseased populations, as such analyses may wrongly conclude that lower BP is dangerous, when the opposite may be the case.”

Randomized trials, which control for such confounding, have supported the effectiveness of lowering BP in other population groups where U-shaped associations between BP and cardiovascular risk have been observed, including patients with prior cardiovascular disease and older adults (e.g., the Systolic Blood Pressure Intervention Trial, or SPRINT). The same may therefore be true in CKD.

In the absence of sufficiently large trials, the optimal BP target in CKD remains unknown, and current recommendations vary widely. Recent studies, including SPRINT, “taken together with the evidence of reverse causality in the present analysis in the SHARP trial, suggest that trials of lower BP targets in patients with CKD are indicated,” the researchers write. Such studies would also address the potential harms as well as benefits of lower BP targets; in SPRINT, more intensive BP control was associated with an increased risk of acute kidney injury.

“The findings in this paper probably are most applicable to people with CKD not on dialysis,” commented Rajiv Agarwal, MBBS, of Indiana University School of Medicine, Indianapolis. In a 2004 review in Hemodialysis International, Agarwal hypothesized that reverse causality might account for the U-shaped association between blood pressure and cardiovascular risk in CKD.

To understand the association between BP and cardiovascular risk would require home or ambulatory BP recordings— which weren’t available in the SHARP data.

“Nonetheless, observational studies show that low BP associates with higher mortality in dialysis, while meta-analyses of randomized trials suggest the opposite,” Agarwal said. ”While we don’t have a definitive trial on BP level and outcomes in dialysis, I believe that the meta-analyses trump the observational data. Clearly there is room for research in this important area.”

Baigent noted: “The observational data in SHARP only appear to show that lower BP associates with higher risk of cardiovascular events. We argue that, if correctly analyzed with due regard to the presence of confounding by subclinical cardiac disease, the true association between BP and risk of major cardiovascular events is positive throughout the range studied.”

Suggested Reading

1. Herrington W, et al. Evidence for reverse causality in the association between blood pressure and cardiovascular risk in patients with chronic kidney disease. Hypertension 2017; 69:314– 322.

2. Agarwal R. Exploring the paradoxical relationship of hypertension with mortality in chronic hemodialysis. Hemodial Int 2004; 8:207–213.

3. Baigent C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011; 377:2181–2192.

4. Park M, et al. Associations between kidney function and subclinical cardiac abnormalities in CKD. J Am Soc Nephrol 2012; 23:1725–1734.

5. The SPRINT Research Group: A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015; 373:2103–2116.

Read the full article at http://onlinedigeditions.com/article/Why+Is+Low+Blood+Pressure+Related+To+Increased+Cardiovascular+Risk+In+CKD%3F/2700346/380295/article.html.

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