Abstract Background and Aims Although guidelines recommend opportunistic screening for chronic kidney disease (CKD) in individuals with established risk factors, such as diabetes, hypertension, or cardiovascular disease, screening for CKD in these individuals remains suboptimal. This study aimed to evaluate the effectiveness of an additional systematic home-based albuminuria screening program in patients at risk for CKD in a primary care setting. Method A cross-sectional screening study was performed in 10 general practices and 5 pharmacies in the Netherlands between Nov 2021-Nov 2023. A random selection of patients aged 45-80 years with risk factors for CKD progression was invited for home-based albuminuria screening. These patients were registered at their general practitioner (GP) or at the pharmacy. Patients in the GP-group were identified based on the following risk factors: diabetes, cardiovascular disease, hypertension, hypercholesterolemia, or obesity. Patients were excluded in case of a normal albuminuria status (ACR (albumin-creatinine ratio) <3.0 mg/mmol) within 18 months prior to the screening. Patients in the pharmacy-group were identified based on drug prescriptions for the aforementioned risk factors in the last 6 months. Home-based albuminuria screening was performed using a urine collection device that was sent by post to a central laboratory for ACR measurement. If the test result was positive upon confirmation (i.e. ≥two tests ACR ≥3 mg/mmol), patients were invited for an elaborate visit in the general practice or pharmacy, to assess presence of CKD and cardiovascular risk factors. Main outcomes were participation rate and yield of the home-based albuminuria screening in the total study population and in both screening groups separately. Secondary outcomes were the yield of persistent albuminuria despite treatment with RAS-inhibition in both screening groups and the yield of previously undiagnosed albuminuria in the GP-group. Results We invited 6 380 patients (2 578 via pharmacy registries and 3 802 via GP registries), of whom 2 147 completed the home-based screening, corresponding to a participation rate of 33.7%. The participation rate among GP patients was 41.4% (1 575/3 802), compared to 22.2% (572/2 578) among pharmacy patients (P < .001). Albuminuria was confirmed in 8.5% (134/3 802) and 5.6% (32/2 578) of the participants in the GP- and pharmacy-group, respectively. Among participants in the GP-group, 59.7% (80/134) had a positive albuminuria test within one year prior to the screening; the remaining 40.3% either had no albuminuria test (or a normal albuminuria test within one year prior to the screening. Of those with increased albuminuria in the GP- and pharmacy-group, 85.8% (115/134) and 81.3% (26/32) attended the elaborate screening visit, respectively. In the GP-group, 72.2% (83/115) had an eGFR >60 and only 19.1% (22/115) an adequate blood pressure (<130/80 mmHg), compared to 69.2% (18/26) and 19.2% (5/26) in the pharmacy-group. Of the albuminuric participants in the GP- and pharmacy-group, respectively, 44.3% (51/115) and 23.1% (6/26) were not treated with RAS inhibition, and 94.8% (109/115) and 96.2% (25/26), respectively, were not treated with an SGLT2 inhibitor. Many patients were not aware of having albuminuria before participating in the systematic home-based screening program 42.6% (109/115) in the GP-group vs. 61.5% (16/26) in the pharmacy-group). Conclusion In conclusion, systematic albuminuria screening in the primary care setting when added to regular opportunistic screening has an acceptable participation rate and yield when performed via GPs, but is less effective when performed via pharmacies. It identifies patients with yet unknown albuminuria and most of the identified patients may benefit of initiation or optimization of albuminuria-lowering treatment. The introduction of such systematic albuminuria screening programs via GPs merits further study.