Implications of CKD for Patients With CAD

Peter A. McCullough, M.D., M.P.H., F.A.C.C.

Disclosures

April 15, 2009

Chronic kidney disease (CKD) is present in approximately 20% of patients with a history of coronary artery disease (CAD). Conversely, CAD is present in 50% of patients with CKD by history and probably in 80% of CKD patients who undergo some form of cardiovascular imaging. CKD has a prolonged silent course for years before the development of microalbuminuria and rising blood pressure (Figure 1, Figure 2). We have shown that in younger individuals, the urine albumin:creatinine ratio > 30 mg/g is the highest yield screening test to identify CKD in medical and cardiovascular practice (Figure 3).[1] As the population ages, then the estimated glomerular filtration rate (eGFR) calculated by an equation based on age, gender, race and serum creatinine identifies a greater proportion of those with CKD with an eGFR < 60 ml/min/1.73 m2. There are many mechanisms by which CKD is thought to accelerate calcific atherosclerosis, myocardial disease, valvular abnormalities, and cardiac arrhythmias including sudden death (Figure 4). Appropriately, position papers expand the concept of hazard for CKD beyond that of a "risk factor" to the concept of "risk state". This implies that the CKD-CVD relationship is unique and complicated and goes beyond traditional epidemiology risk factors in terms of contributing to disease and clinical decision making (Figure 5).

Figure 1.

Natural History of Chronic Kidney Disease

Figure 2.

Natural History of Renal Measures Impairment in Diabetic Kidney Disease
Courtesy of Mark E. Molitch, MD. - This slide illustrates the time course of the relationship between diabetic nephropathy and the development of CKD. - In patients with diabetes, a gradual elevation of urinary albumin excretion occurs first. - Urinary albumin ≥ 30 mg/24 h, or 30 mg/g of Cr, is designated microalbuminuria. - Over time, albumin excretion gradually increases to and exceeds ≥ 300 mg/24 h. - At this point, the patient is considered to have albuminuria - After the development of albuminuria, eGFR gradually decreases over time. - The time interval between the development of albuminuria and the development of CKD Stage 5 in most patients ranges between 10 to 20 years. - This time interval provides opportunity for intervention to slow the rate of CKD progression.

Figure 3.

Microalbuminuria and eGFR as CKD Screening Tests by Age

Figure 4.

Chronic Kidney Disease: Illustration

Figure 5.

Chronic Kidney Disease: Implications For Patients With CAD

Recently, the management of acute coronary syndromes (ACS) has been a point of interest in CKD patients as they are less likely to undergo angiography procedures and be selected for an invasive management strategy in the hospital. Because the use of early invasive management depends on hospital facilities, willingness of the physician, and consent from the patient, this component of treatment is particularly susceptible to treatment bias. A prior meta-analysis of seven randomized trials from the general population with unspecified renal function (N = 9212 ACS patients) demonstrated that death or MI was reduced from 14.4% to 12.2% in the routine invasive group (relative 18% risk reduction) with a nonsignificant trend toward fewer deaths (6.0% vs 5.5%).[2] Wong and colleagues have recently demonstrated that patients with stage 4 CKD denoted by an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m² who were selected for an early invasive management approach for ACS enjoyed a 33.7% relative risk reduction in mortality compared to those managed conservatively who ultimately had a 41.5% all-cause mortality (Figure 6).[3] The propensity analysis supported these findings with an adjusted 47% risk reduction, suggesting much more than selection bias accounts for the disparities in outcomes. In the 639 (5.6%) with an eGFR < 30 ml/min/1.73 m2; (serum Cr ~ 2.7 mg/dl) the median age was ~76 years (interquartile range 68-84), ~50% had diabetes, ~75% demonstrated positive biomarkers indicating acute MI, ~55% had a history of previous MI, and ~36% suffered from prior heart failure. Hence, the eGFR < 30 ml/min/1.73 m2; serves as a proxy for a clinical profile characterized by elderly patients with the highest risk for mortality in ACS. The evidence-based risk predictors in the eGFR < 30 ml/min/1.73 m2 suggest clinicians may failing to recognize risk and select these patients for a conservative medical management strategy.[4] It is possible that concern over contrast-induced acute kidney injury, bleeding, and comorbidities account for some of the intentional "therapeutic nihilism" in patients with CKD.

Figure 6.

Mortality in ACS According to eGFR and Use of Early Angiography

Educational efforts should be directed towards understanding how traditional risk predictors including positive biomarkers, age, diabetes, and histories of MI and HF aggregate in patients with significant CKD.[5] If managed conservatively, the studies suggest this ACS population has disastrous outcomes with a nearly 50% case fatality rate at one-year.[3,6] This rate possibly could be reduced with an invasive management approach in appropriate patients. Clearly more evidence is needed concerning the benefits, risks, and selection process of CKD patients for early intervention during hospitalizations for ACS.

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