Is Chronic Kidney Disease Also an Affair of the Heart?
What effects do therapies for cardiovascular disease have on chronic kidney disease?
The 1990s were an exciting decade for the treatment of chronic kidney disease (CKD). The addition of angiotensin-converting enzyme inhibitors (ACEIs) and then angiotensin receptor blockers to the antihypertensive armamentarium helped preserve renal function and decrease proteinuria in patients with CKD. For the first time, tight control of glucose was determined to have a positive impact on diabetes-related small-vessel disease—including that portion associated with glomerular damage. But it seems that some of the promise of the 1990s, at least in terms of continuing therapeutic innovations in CKD, may have reached a plateau.
TIME TO REFRAME OUR PRESENT APPROACH?
Is the critical issue in CKD also a problem of the heart and not just of the kidney? A meta-analysis of 31 studies focused on postoperative outcome in patients with CKD who underwent elective, noncardiac surgery.1 The worse the CKD, the greater the risk of postoperative death—a scenario similar to that seen in persons with cardiovascular disease. In fact, CKD was just as strongly and independently associated with death after surgery as diabetes, stroke, or coronary disease.
It appears that the course of CKD, like that of diabetes, is complicated by heart disease. If CKD is associated with cardiac disease, might some traditional treatments for heart disease improve survival in patients with CKD?
Updated guidelines (eg, the National Cholesterol Education Program) suggest that low-density lipoprotein (LDL) cholesterol levels be reduced to 70 mg/dL or lower in patients who require secondary prevention, such as those who have diabetes or who already have coronary or vascular disease.2 In the Treating to New Targets (TNT) study—which looked at optimum statin dosing and LDL levels—of 9656 subjects for whom renal function data were available, 3107 had CKD at baseline. The CKD cohort exhibited greater cardiovascular morbidity than those without CKD.3
When specific treatment was taken into account— either a high (80 mg/d) or a typical (10 mg/d) dosage of atorvastatin—cardiovascular events were shown to decrease by 32% in patients with CKD who received high-dose therapy and by 15% in those who received the lower dosage. The complications associated with highdose atorvastatin were minimal: 1.1% of patients experienced myalgias and 1.5% had elevated liver enzyme levels.
IMPLICATIONS FOR CLINICAL PRACTICE
How will this affect the approach to the patient with CKD? First, every at-risk patient should have a calculated glomerular filtration rate (GFR)—preferably by the Modification of Diet in Renal Disease (MDRD) Study equation—in addition to a serum creatinine measurement. Those with CKD should be categorized (stage 1 CKD, GFR greater than or equal to 90 cc/min [some laboratories report GFR in mL/min/1.73 m2]; stage 2 CKD, 60 to 89; stage 3 CKD, 30 to 59; stage 4 CKD, 15 to 29; and stage 5 CKD, less than 15) and treated appropriately for their renal disease (eg, control of hypertension to target blood pressure with an ACEI).
Then the patient should be viewed as someone who probably already has cardiovascular disease and approached accordingly. Secondary prevention targets and attention to higher risks in the perioperative period will go a long way in preventing a prohibitive cardiovascular mortality that is a critical part of CKD.
1. Mathew A, Devereaux PJ, O’Hare A, et al. Chronic kidney disease and postoperative mortality: a systematic review and meta-analysis. Kidney Int. 2008;73:1069-1081.
2. Grundy SM, Cleeman JI, Merz CN, et al; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines [published correction appears in Circulation. 2004;110:763]. Circulation. 2004;110:227-239.
3. Shepherd J, Kastelein JJ, Bittner V, et al; TNT (Treating to New Targets) Investigators. Intensive lipid lowering with atorvastatin in patients with coronary heart disease and chronic kidney disease: the TNT (Treating to New Targets) study. J Am Coll Cardiol. 2008;51:1448-1454.