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August 20, 2013 Issue

Clinical Practice Points

Blood Pressure and Mortality in U.S. Veterans With Chronic Kidney Disease. A Cohort Study

The ideal blood pressure for adults with chronic kidney disease (CKD) is unclear. This large study involving U.S. veterans with non–dialysis-dependent CKD found that systolic BP (SBP) of 130 to 159 mm Hg and diastolic BP (DBP) of 70 to 89 mm Hg were associated with the lowest mortality rates. But veterans with moderately elevated SBP combined with DBP no less than 70 mm Hg had lower mortality rates than those with ideal SBP and DBP less than 70 mm Hg, suggesting that achieving ideal SBP at the expense of lower-than-ideal DBP could be harmful in patients with CKD.

Use this study to:

  • Start a teaching session with a multiple-choice question about hypertension. We’ve provided one below.
  • Ask your residents what target blood pressure they aim to achieve in their patients. How should the target be adjusted according to the presence of comorbidities?
  • Discuss the limitations of observational studies and of residual confounding. These are explained in an accompanying editorial.
  • Review the choices of therapy for hypertension. Use the tables and text in the Physicians Information and Education Resource.

Tofacitinib in Combination With Nonbiologic Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis. A Randomized Trial

This randomized trial of patients with active rheumatoid arthritis despite the use of various disease-modifying regimens found that the addition of tofacitinib, an inhibitor of a kinase normally active in immune and inflammatory signaling, improved disease activity compared with placebo.

Use this paper to:

  • Review the clinical manifestations of rheumatoid arthritis (RA). Don’t forget to discuss the extra-articular complications of RA. Use the In the Clinic review of RA to identify key teaching points.
  • Discuss the approach to drug therapy for RA. Methotrexate is considered the "anchor drug"—how is it used? How is therapy monitored?
  • Should your residents prescribe methotrexate to their patients or should they consult rheumatology?

ACP Journal Club

Use these concise summaries and commentaries of recent studies, chosen for their clinical relevance, to review important clinical pearls. Topics in this month’s edition include studies of pneumatic compression to reduce DVT and stroke, therapeutic options for asymptomatic carotid stenosis, anticoagulation during pacemaker or ICD surgery, and more.


Business and Ethics in Medical Research

Are Human Genes Patentable?

This commentary reviews the events leading toward the Supreme Court decision regarding Myriad Genetics patents on the BRCA1 and BRCA2 genes. Those developing molecular diagnostics will have to comport with a new rule for U.S. patent jurisprudence: Yes, complementary DNA can be patented, but not genomic DNA.

Use this article to:

  • Invite a patent lawyer (or someone else knowledgeable about science and patents) to join resident report for a change! Chances are your institution has a patent office where you might find the right person. Or invite a medical ethicist—or both.
  • Ask your residents if they think genes should be patentable.
  • Why should they be? Could it help promote research and development that would otherwise be too costly?
  • Why shouldn’t they be? Can someone really “own” a human gene? If they do, how might that affect access to tests and treatments for some patients?

Humanism and Professionalism

Black and White

Take time to discuss how our interactions with patients and their families can make us pause, or even jar us. Play the audio recording of this issue’s On Being a Doctor essay. Dr. Epner describes the “business-like” manner of a patient’s son as he discussed his mother’s end-of-life care.

Use this essay to:

  • Ask your residents whether they have had notable experiences discussing death and dying with patients and their families.
  • How did they feel when they heard about Sam’s plan regarding his mother’s burial request? How might they have responded? Do they think Sam’s plan to do differently than what he tells his mother is the doctor’s concern?

mksap16

A 51-year-old man is evaluated for a 1-year history of uncontrolled hypertension. He has not responded to treatment with metoprolol and clonidine. He has no family history of hypertension. He has never smoked cigarettes and has no other medical problems. Current medications are maximum doses of chlorthalidone, lisinopril, and amlodipine.

On physical examination, seated blood pressure is 160/94 mm Hg, and pulse rate is 76/min. The remainder of the examination is unremarkable. Laboratory studies reveal a serum creatinine level of 1.1 mg/dL (97.2 μmol/L), a potassium level of 4.1 meq/L (4.1 mmol/L), and an estimated glomerular filtration rate of >60 mL/min/1.73 m2.

Which of the following is the most appropriate next step in management?

A. Discontinue chlorthalidone; begin furosemide
B. Discontinue lisinopril; begin aliskiren
C. Obtain kidney Doppler ultrasonography
D. Obtain a plasma aldosterone-plasma renin activity ratio

Answer: D. Obtain a plasma aldosterone-plasma renin activity ratio

Key Point: A high proportion of patients with resistant hypertension have secondary hypertension due to primary hyperaldosteronism or renovascular hypertension.

Educational Objective: Diagnose aldosterone excess in a patient with resistant hypertension.

Obtaining a plasma aldosterone-plasma renin activity ratio (ARR) is indicated for this patient. He has resistant hypertension, which is defined as blood pressure that remains above goal despite the administration of three antihypertensive drugs, one of which is a diuretic. A high proportion of patients with resistant hypertension have secondary hypertension due to primary hyperaldosteronism or renovascular hypertension; therefore, these conditions should be excluded in patients with resistant hypertension. Primary hyperaldosteronism is inconsistently associated with hypokalemia, and its absence in a patient with resistant hypertension should not influence the decision to screen for this condition. The ARR is a screening test for primary hyperaldosteronism. The normal range varies among institutions because renin and aldosterone assays may differ, but an ARR above 25 is generally considered abnormal. An elevated ARR alone is not diagnostic of primary hyperaldosteronism unless nonsuppressible or autonomous aldosterone excess is demonstrated by the presence of a urine aldosterone excretion of 12 micrograms/24 h (33.2 nmol/24 h) or higher obtained after correction of hypokalemia and adherence to a high-sodium diet for 3 days. In some patients, administering an intravenous saline infusion also may demonstrate nonsuppressible serum aldosterone levels. Both medical and surgical management have proved effective in the treatment of aldosterone excess.

The substitution of a loop diuretic such as furosemide for a thiazide diuretic is recommended in patients with difficult to control hypertension and chronic kidney disease or hypervolemic states. This patient has normal kidney function and no evidence of hypervolemia; therefore, the substitution is unlikely to affect his blood pressure.

Aliskiren is not a more effective antihypertensive agent than lisinopril. More importantly, evaluating for potential secondary causes of resistant hypertension is a more effective long-term strategy to control this patient's blood pressure than is switching to a new drug. Atherosclerotic renovascular disease is usually associated with widespread atherosclerosis, peripheral vascular disease, cardiovascular disease, and ischemic target organ damage. This patient has no risk factors for renovascular hypertension; therefore, kidney Doppler ultrasonography is not warranted at this time.

Bibliography
Rossi GP. Diagnosis and treatment of primary aldosteronism. Rev Endocr Metab Disord. 2011;12(1):27-36. PMID: 21369868

This question was derived from MKSAP® 16, the latest edition of the Medical Knowledge Self-Assessment Program.

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