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Background: Chronic kidney disease (CKD) is common, but the longitudinal effects of CKD and associated comorbidities on health care costs in the general population are unknown. Methods: Population-based cohort study of 2,988 subjects in Germany, aged 25–74 years at baseline, who participated both in the baseline and 10-year follow-up examination (1994/95–2004/05). Presence of CKD was based on serum creatinine and defined as an estimated glomerular filtration rate of <60 ml/min/1.73 m². Self-reported health services utilization was used to estimate costs. Results: Health care costs at baseline and follow-up were higher for subjects with CKD. Controlling for socio-economics, lifestyle factors and comorbid conditions, subjects with baseline CKD, in comparison to those without, exhibited 65% higher total costs 10 years after baseline examination, corresponding to a difference in adjusted costs of EUR 743. Incident CKD was related to 38% higher total costs. Costs for inpatient treatment and drug costs were the major costs components, while CKD revealed no effect on outpatient costs. The effect of CKD was strongly modified by angina, myocardial infarction, diabetes, and anemia. Conclusions: The direct effect of CKD on costs is modified by comorbid conditions. Therefore, early treatment of CKD and its precipitous factors may save future health care costs.