OBJECTIVES: We examined the incremental cost of CKD over a 66 month period, and the contribution of CKD-related comorbidity to the cost of care. METHODS: Using electronic medical record data at a large HMO, we calculated inpatient, outpatient, pharmacy and total costs for 13,796 cases and 13,796 matched (age and gender) controls. Cases were patients whose glomerular filtration rates (GFR, ml/min/1.72m2) were < 90 on two consecutive measurements (at least 90 days apart) in 1996. Cases were divided into stages 2, 3 and 4 based on new guidelines from the National Kidney Foundation. Patients were followed until death, initiation of renal replacement therapy (RRT), or July 1, 2001. CKD-related comorbidities were identified (diabetes, congestive heart failure, coronary artery disease, anemia and hypertension) based on ICD9 codes. RESULTS: Patients with CKD were 1.9 to 2.5 times more likely (depending on stage) than controls to have been treated with prescription drugs, had more outpatient visits (1.3 to 1.9 times more than controls, across stages), and had 1.8 to 3.1 more inpatient stays than did controls. CKD-related comorbidities almost double the total cost of care for both cases and controls, and cases with no CKD-related comorbidities are about twice as expensive to manage as controls with no CKD-related comorbidities. CONCLUSION: We found that CKD doubles costs to the health care system, and that comorbidities related to CKD contribute more to the cost of managing these patients than does CKD alone. Future research in this area could be usefully directed toward analyzing the clinical and economic consequences of better managing patients with CKD.