CKD, Ethics, Nutrition in Sports and HTN

1. CKD, Ethics, Nutrition in Sports and HTN

2. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC recommends a blood pressure (BP) goal of _______ for patients with chronic kidney disease (CKD). A) <140/80 mm Hg B) <135/80 mm Hg C) <130/80 mm Hg D) <125/80 mm Hg

3. Answer • C) <130/80 mm Hg

4. Introduction • reaching blood pressure (BP) goals in patients with chronic kidney disease (CKD) important for preventing rapid loss of kidney function • meta-analysis found patients with systolic BP of 150 mm Hg have glomerular filtration rate (GFR) loss of 8 mL/min per 1.73 m2 per year (4 mL/min per year if BP reduced to 140 mm Hg) • Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends BP goal of <130/80 mm Hg in patients with CKD • systolic BP <130 mm Hg helps stabilize kidney function and prevent development of kidney failure

5. Captopril A) Useful in patients with hyperkalemia and progression to stage 3 CKD  B) Compared to placebo, shown less likely to result in decline in kidney function in patients with type 2 diabetic nephropathy C) Compared to placebo, shown less likely to result in doubling of serum creatinine D) Compared to placebo, shown more effective in reducing BP in patients with type 2 diabetic nephropathy

6. Answer • C) Compared to placebo, shown less likely to result in doubling of serum creatinine

7. Case 1 • woman 63 yr of age with hypertensive nephrosclerosis presents for follow-up • medications include lisinopril (20 mg/day) and amlodipine (5 mg/day) • BP 154/84 mm Hg • creatinine 1.3 mg/dL (stable relative to baseline • stage 3 CKD) • spot protein to creatinine ratio 1.5 g/day • management—increase lisinopril to 40 mg/day and check basic metabolic panel in 1 wk; after 1 wk, electrolytes normal, but creatinine increased to 1.6 mg/dL • What should you do?

8. Answer • Transient increase in creatinine: often seen in patients with proteinuric kidney disease started on angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB), or when dose titrated up • kidney function usually maintained • long-term prognosis better • initial bump in creatinine or decrease in GFR related to ACEIs or ARBs reversible • Prognosis of CKD: greater proteinuria associated with more rapid loss of kidney function over time; as BP increases, relative risk for progression of CKD increases • in patients with CKD, important to decrease proteinuria with ACEIs or ARB

9. Case 2 • man 77 yr of age with hypertensive nephrosclerosis, congestive heart failure (HF), chronic lower extremity edema, and recurrent cellulitis presents for routine follow-up • medications include aspirin, carvedilol (Coreg; 80 mg/day); benazepril (40 mg twice daily), and furosemide (eg, Delone, Furocot, Lasix; 60 mg/day) • BP 179/83 mm Hg • heart rate (HR) 56 bpm • body weight 317 lb • creatinine 1.6 mg/dL (baseline 1.9 mg/dL); electrolytes normal; hemoglobin 9.6 g/dL (baseline 11.2 g/dL) • management—consider that serum creatinine may be falsely assessed as lower due to secondary dilutional effect in setting of severe fluid overload • kidney function unclear; furosemide increased to 100 mg/day; when basic metabolic panel repeated in 1 wk, creatinine increased to 2.3 mg/dL • patient advised to continue current medications, and repeat basic metabolic panel in 1 wk • important to control fluid status, to reduce risk for cellulitis, and to improve mobility

10. Losartan A) Useful in patients with hyperkalemia and progression to stage 3 CKD  B) Compared to placebo, shown less likely to result in decline in kidney function in patients with type 2 diabetic nephropathy C) Compared to placebo, shown less likely to result in doubling of serum creatinine  D) Compared to placebo, shown more effective in reducing BP in patients with type 2 diabetic nephropathy

11. Answer • B) Compared to placebo, shown less likely to result in decline in kidney function in patients with type 2 diabetic nephropathy

12. Case 3 • woman 67 yr of age with poorly controlled diabetes, diabetic retinopathy, and diabetic nephropathy presents for routine follow-up • medications include lisinopril (20 mg/day), insulin, amlodipine (5 mg/day), and simvastatin • BP 165/95 mm Hg; HR 71 bpm • body mass index 36 • has trace edema; • creatinine 1.2 mg/dL (stage 3 CKD) • potassium slightly elevated (5.5 mEq/L) • spot albumin to creatinine ratio >3 g/day • What should you do:?

13. Answer • management — counsel patient about lifestyle modifications • increase lisinopril to decrease proteinuria add thiazide diuretic; check metabolic panel in 1 w

14.  Furosemide A) Useful in patients with hyperkalemia and progression to stage 3 CKD B) Compared to placebo, shown less likely to result in decline in kidney function in patients with type 2 diabetic nephropathy C) Compared to placebo, shown less likely to result in doubling of serum creatinine  D) Compared to placebo, shown more effective in reducing BP in patients with type 2 diabetic nephropathy

15. Answer • A) Useful in patients with hyperkalemia and progression to stage 3 CKD

16. Lifestyle modifications • weight reduction • sodium restriction (<2400 mg/day can reduce BP by 8 mm Hg) • greater consumption of fresh fruits, vegetables, and meats • prepare meals at home • physical activity • moderate alcohol intake

17. Antihypertensive agents and diabetic nephropathy • Study showed patients with type 1 diabetic nephropathy on ACEI had reduced chance of progressing to kidney disease • other study showed that patients on captopril less likely to have doubling of serum creatinine, compared to patients on placebo (overall BP control same in both groups) • Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study — saw lower likelihood in decline in kidney function in patients with type 2 diabetic nephropathy who received losartan, compared to placebo (BP control same in both arms) • hyperkalemia —diabetes can cause structural changes in kidney tubules, leading to type 4 renal tubular acidosis (hyporeninemic hyperaldosteronism and hyperkalemic state) • monitor patients • inform patients about risk for fatal cardiac arrhythmia • advise patients to follow potassiumrestricted diet (less than 2000-3000 mg/day) • use diuretics (thiazide diuretics typically weaker than loop diuretics) • thiazide diuretics often not effective in patients progressing to advanced stage 3 CKD (switch to, eg, furosemide or bumetanide [Bumex]); • ACEIs and ARBs cannot be used in some patients with diabetic nephropathy and CK

18. Which of the following novel treatment options is approved by the Food and Drug Administration for the treatment ofhypertension in CKD? A) Hypertension vaccine B) Renal denervation C) Vasopeptidase inhibitors D) None of the above

19. Answer •  D) None of the above

20. Antihypertensive therapy in development • Hypertension vaccine —vaccine against angiotensin II • phase II trial showed decreased systolic and diastolic BP after 14 wk on 24-hr ambulatory BP monitoring, compared to placebo (most pronounced during daylight hours) • 2 doses given (higher dose more effective) • renal denervation—radiofrequency applied to sympathetic nerves in kidneys • saw dramatic improvement in systolic and diastolic BP after 6 mo, compared to placebo • Vasopeptidase inhibitors—inhibit ACE and neutral endopeptidase (causes degradation of natriuretic peptides; inhibition results in prolongation of activation of substances, eg, atrial and brain natriuretic peptides) • saw statistically significant improvement in BP, compared to use of ACEI alone

21. Staging of CKD based on revised guidelines considers all the following, except: A) Cause of disease B) Estimated glomerular filtration rate C) Albuminuria D) Hyperkalemia

22. Answer •  D) Hyperkalemia

23. Chronic kidney disease • must be present for 3 mo • defined by reduced kidney function (ie, estimated GFR [eGFR] <60 mL/min per 1.73 m 2) or injury or damage to kidney (through, eg, albuminuria, cysts, stones) • etiology—80% to 90% due to diabetes, hypertension, cardiovascular (CV) disease, or HF • other systemic diseases (eg, lupus, HIV disease, urologic disease) • intrinsic kidney disease (eg, polycystic disease, glomerular disease) • Complications of CKD: end-stage renal disease (ESRD) or kidney failure • increased risk for death • atherosclerotic disease HF • risk for osteoporosis and fracture • cognitive impairment, dementia, and frailty predisposed by CKD • risks associated with medications and treatment procedures • Morbidity: most patients with CKD die before reaching dialysis • 1% to 0.1% of patients with CKD reach kidney failure • data from Northwest Kaiser — 1% of patients with eGFR of 30 to 60 mL/min per 1.73 m2 reached ESRD at 5 yr, and 25% died • 1 in 5 patients with eGFR of 15 to 30 mL/min per 1.73 m 2 had kidney failure at 5 yr, and nearly 50% had die

24. Prognosis • must consider kidney function (ie, eGFR) and proteinuria • recent meta-analysis— patients classified by albumin to creatinine ratio (ACR; eg, <10 mg/g, 10-30 mg/g, 30-300 mg/g, >300 mg/g) • ACR >30 mg/g or eGFR <60 mL/min per 1.73 m 2 • associated with 2-fold increase in risk for death (risk higher when combined)patients with eGFR of 45 to 60 mL/min per 1.73 m 2 and no albuminuria at low increased risk of dying, but risk for death doubles with ACR of 30 to 300 mg/g (triples with ACR >300 mg/g) • CKD staging: stage 1 — eGFR >90 mL/min per 1.73 m 2 with proteinuria or other manifestation of kidney disease • stage 2 — eGFR 60 to 90 mL/min per 1.73 m 2 with proteinuria or other manifestation of kidney disease • stage 3 — eGFR 30 to 60 mL/min per 1.73 m 2 • stage 4 — eGFR 15 to 30 mL/min per 1.73 m2 • stage 5 — eGFR <15 mL/min per 1.73 m 2 • , or on dialysis • problems — difficult to distinguish between stages 1 and 2 • eGFR range for stage 3 too broad; albuminuria addressed only in stages 1 and 2 • disease etiology not addressed • Revised staging — due in early 2012 • 3-dimensional staging (cause, eGFR, and albuminuria) to replace 5-stage schema • descriptive staging (eg, hypertensive patient with eGFR of 50 mL/min per 1.73 m2 and ACR of 10 mg/g [not at high risk of developing need for dialysis] • diabetic patient with preserved eGFR and high ACR [at high risk for progressive CKD]

25. For primary prevention of CKD, patients with diabetes should undergo albumin to creatinine ratio screening every: A) 6 mo B) 1 yr C) 2 yr D) 3 yr

26. Answer • B) 1 yr

27. Screening for CKD • hypertension and CV disease guidelines advise screening for creatinine • diabetes guidelines advise measuring creatinine and albuminuria • begin checking creatinine at 40 yr of age in lower-risk populations • in higher-risk populations (eg, blacks, American Indians) start at 30 yr of age • any patient with hypertension, diabetes, CV disease, or HF should have known creatinine • no evidence about frequency of screening • in patients with no risk other than ethnicity, screening every 3 to 5 yr reasonable; reasonable to screen patients with risk factors or strong positive family history every 1 to 2 y

28. Estimating GFR from creatinine • eGFR <60 mL/min per 1.73 m 2 concerning for kidney disease, but clearly not diagnostic (25% of patients do not have low eGFR when confirmed by second test) • eGFR measurements >60 mL/min per 1.7 m 2 highly inaccurate • Cockroft-Gault equation— easily calculated, but antiquated • never been tested in women • not highly effective • used by Food and Drug Administration and pharmacies • Modification of Diet in Renal Disease (MDRD) Study equation — used in most laboratories • Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation — used mostly by researchers • interpretation of serum level of creatinine must be indexed for varying muscle mass based on demographic characteristics (eg, age, sex, ethnicity) • advantages —beneficial to consider both GFR and creatinine levels • disadvantages — equations mostly validated in younger patients with kidney disease • assumes demographic characteristics alone can define muscle mass • equations developed only in whites and blacks • provides estimated value only

29. Screening with ACR • for primary prevention —screen patients with diabetes annually • screen patients with hypertension • screen elderly patients • for CKD staging —screen all patients with CKD • Screen patients with diabetes annually • (nondiabetics every 2 yr) • ACR <30 mg/g —normal or mildly elevated • ACR 30 to 300 mg/g—moderately elevated • ACR >300 mg/g—severely elevated • Urine dipstick—“trace” indicates abnormal level (quantify with ACR

30. The combination of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) is recommended for most patients with proteinuria and CKD. A) True B) False

31. Answer •  B) False

32. Treatment of CKD • goals —prevent progression to ESRD (rare) • prevent complications (eg, CV disease, HF) • ACEIs and ARBs — diabetic patients with CKD nearly always have albuminuria • Many patients have hypertension and diabetes (if ACR <30 mg/g, CKD likely due to hypertension) • ACEIs and ARBs essential for type 1 or type 2 diabetes with moderate or severe albuminuria (ACR >30 mg/g) • studies show ACEIs and ARBs do not appear to prevent onset of albuminuria in patients with diabetes and ACR <30 mg/g • In nondiabetic CKD, benefits of ACEIs and ARBs vary depending on patient’s proteinuria status • Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) —compared lisinopril, amlodipine, and chlorthalidone • subgroup analysis of patients with CKD (eGFR <60 mL/min per 1.73 m 2 most patients did not have proteinuria) found no difference between ACEIs, thiazides, and calcium channel blockers in effect on decline in kidney function or development of ESRD • advanced CKD—trial found significant benefit associated with benazepril, compared to placebo (43% reduction in combined outcome of doubling of creatinine, ESRD, and death • 52% reduction in proteinuria • effects independent of BP) • adverse events rare • speaker’s recommendations— if creatinine high, continue ACEI for as long as potassium at tolerable level (ie, 5.5 mEq/L • consider diuretics to balance potassium • increased creatinine often occurs due to hemodynamics (does not indicate discontinuation of ACEI

33. All the following treatment options slow the progression of kidney disease, except: A) Statins B) ACEIs C) ARBs D) Glucose control

34. Answer • A) Statins

35. Combination of ACEIs and ARBs • ACEIs or ARBs alone have similar effects on reducing proteinuria, and thought to have similar efficacy in CKD • combination of ACEI and ARB results in additional reductions in proteinuria, but risk for adverse events high (combined therapy not recommended) • BP targets in CKD: systolic BP control important • often requires 3 to 4 medications at full dose • meta-analysis found ideal systolic BP 110 to 130 mm Hg • progressive antihypertensive agents often reduce diastolic BP disproportionately to systolic BP (may increase risk for adverse events) • Diastolic BP has little effect on risk for CKD • new CKD hypertension guidelines suggest systolic BP target of <130 mm Hg, but recommend <140 mm Hg

36. Glycemic control and Statins • type 1 diabetes— tight glucose control slows progression of kidney disease • odds ratio of progression, 0.34 (two-thirds reduction in risk) • onset of disease earlier, with resulting higher lifetime risk for kidney failure • type 2 diabetes — Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial showed tight glucose control lowers risk for new or worsening nephropathy (ie, progression of albuminuria or lowered eGFR) by 20% • however, absolute difference in risk small (individualized therapy needed) • Statins: do not prevent progression of kidney disease • Associated with good outcomes in CKD patients • meta-analysis found that statins reduced all-cause mortality and CV mortality by 20%, compared to placebo in patients with CKD • Study of Heart and Renal Protection (SHARP) trial showed 17% reduction in risk for CV disease with combination of simvastatin and ezetimibe, compared to placebo • no change seen in kidney function • reasonable to place CKD patients at high CV risk on statins, but not those at low CV risk • statins appear ineffective in patients on dialysis

37.  Choose the correct statement about renal artery stenosis. A) Usually seen in older patients with multiple vascular risk factors B) Commonly due to fibromuscular dysplasia C) Stenting more effective treatment than medical therapy D) Imaging recommended for all patients

38. Answer •  A) Usually seen in older patients with multiple vascular risk factors

39. Renal artery stenosis • typical clinical profile—older patient with multiple vascular risk factors and known coexisting vascular disease • etiology usually atherosclerosis (fibromuscular dysplasia rare) • patients at extremely high risk for CV disease • have poor prognosis and low physiologic tolerance for procedures • Imaging studies —controversial • ultrasonography does not provide adequate visualization of vasculature • concern for nephrogenic systemic sclerosis with magnetic resonance imaging and gadolinium • Risk for contrast nephropathy with computed tomography angiography • direct angiography provides best images, but invasive and uses greater amount of contrast • use imaging if diagnosis challenging, or if patient has frequent flash pulmonary edema (patients often have acute episodes of HF) • medical therapy—cornerstone of treatment • ACEIs ideal if tolerated (hypotension uncommon • hyperkalemia common [monitor carefully]); creatinine expected to rise by 50% (may double; returns to baseline over time) • BP control in patients unable to tolerate ACEIs may require multiple antihypertensive agents (minoxidil or hydralazine often used as fourth or fifth agent) • procedures —surgery; angioplasty • most centers favor stenting • recent trials indicate no benefit to BP or kidney function with stenting, compared to medical therapy

40. Indications for referral to nephrologist • combined hematuria and proteinuria (concern for glomerulonephritis) • eGFR <30 mL/min per 1.73 m 2 • (plan for dialysis) • nephrotic proteinuria (3 g/day; potential for treatable condition) • need for mineral metabolism management (eg, high phosphorus or parathyroid hormone) • anemia of CKD

41. The _______ was the first set of guidelines primarily concerned with research ethics. A) Nuremberg Code B) Declaration of Helsinki C) Belmont Report D) Council for International Organizations of Medical Sciences Ethical Guidelines

42. Answer • A) Nuremberg Code

43. Medical oaths • Hippocratic Oath (Greek) • Oath of Maimonides (named for Jewish scholar) • Oath of Hindu Physician • Absolute Sincerity of Great Physicians (Chinese form of physician’s oath) • nearly all cultures and societies place high value on medical ethics • Principles, codes, and books of medical ethics: Adab alTabib (“Practical Ethics of the Physician” • first known book on medical ethics) • Thomas Percival's Code of Medical Ethics • American Medical Association (AMA) code of medical ethics (1847 • similar to and released shortly after Percival’s code) • AMA Principles of Medical Ethics (extremely long, with annotations) • Physician’s Charter of Professionalism

44. Codes, declarations, and reports on research ethics • primarily begins with Nuremberg Code (response to discoveries of World War II atrocities conducted under pretext of medical research) • Declaration of Helsinki (follows on Nuremberg Code) • Belmont Report (created in United States after revelation of unethical Tuskegee Institute experiments with syphilis) • International Committee on Harmonization's Good Clinical Practice guidelines • Council for International Organizations of Medical Sciences’ ethical guideline

45. Which of the following statements about the Hippocratic Oath is not true? A) It includes the concept of maintenance of confidentiality B) It includes admonitions against the administration of lethal drugs and abortion C) It is the source of the phrase "primum non nocere" D) It is strongly religious

46. Answer • C) It is the source of the phrase "primum non nocere"

47. Hippocratic Oath (original version) • exists in 3 forms (original version from Byzantine texts, classic version used during 17th and 18th centuries, and current version [updated for modern world]) • original oath — strong religious oath • begins with emphasizing respect for teachers • includes statements related to avoiding harm (with controversial language forbidding administration of lethal drugs and abortion), acting only in patient’s best interest, and maintenance of confidentiality • not typically used by modern medical schools (due to cultural specificities associated with ancient Greece

48. Declaration of Geneva (1948) • originally developed by World Medical Association • eligible for and subjected to multiple amendments and revisions • updated to address controversies related to “respect for life” (eg, abortion, euthanasia) • emphasizes “service to humanity,” respect and gratitude for teachers • practicing with conscience and dignity • prioritization of patient concerns • maintenance of confidentiality • protection of medical profession • nondiscriminatory practices, and respect for human life • internationally relevant • contains clause forbidding physicians from using medical knowledge “to violate human rights and civil liberties” (supports physicians in resisting pressure to commit atrocities [as seen during World War II]) • secular oath (unlike Hippocratic Oath)

49. The American Medical Association's (AMA) Principles of Medical Ethics includes: A) The obligation to report fellow physicians deficient in character or competence B) The obligation to respect established laws C) The obligation to seek change in laws contrary to patient interests D) All the above

50. Answer •  D) All the above