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Background: Lipoprotein(a) (Lp(a)) is a causal, genetically determined risk factor for cardiovascular disease (CVD) in the general population. Patients with chronic kidney disease (CKD) have an increased CVD risk and elevated Lp(a) concentrations. Only a few studies on Lp(a) were performed in persons with mild‐to‐moderate CKD; none of them used genetic variants to explore potential causal associations. Objectives: This study aims to investigate the association of measured and genetically predicted Lp(a) concentrations on prevalent and incident CVD events in the German Chronic Kidney Disease (GCKD) study. Methods: The study included 5043 participants of European ancestry with an estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m2 or an eGFR >60 mL/min/1.73 m2 in the presence of overt albuminuria with a follow‐up of 6.5 years. Results: With each 10 mg/dL higher Lp(a) concentration, odds for prevalent CVD (1290 events) increased 1.065‐fold (95%CI: 1.042–1.088, p < 0.001). The risk was significantly higher in patients with Lp(a) ≥50 mg/dL but most pronounced in Lp(a) ≥70 mg/dL (odds ratio = 1.775 [1.409–2.231], p < 0.001) compared to Lp(a) <30 mg/dL. Each 10 mg/dL higher Lp(a) concentration and Lp(a) ≥70 mg/dL increased the risk for incident 3‐point major adverse cardiovascular events (MACEs) (474 events): hazard ratio [HR] = 1.037 [1.009–1.067], p = 0.009 and HR = 1.335 [1.001–1.781], p = 0.050), respectively. Similar results were obtained for 4‐point MACE (653 events). Analyses based on apo(a) isoforms and genetically predicted Lp(a) concentrations led to even stronger associations. Conclusions: In patients with mild‐to‐severe CKD, elevated Lp(a) concentrations and genetic determinants of Lp(a) concentrations are significantly associated with CVD at baseline and during follow‐up, independent of traditional risk factors. [ABSTRACT FROM AUTHOR]

Rationale & Objective: Stratification of chronic kidney disease (CKD) patients at risk for progressing to kidney failure requiring kidney replacement therapy (KFRT) is important for clinical decision-making and trial enrollment., Study Design: Four independent prospective observational cohort studies., Setting & Participants: The development cohort comprised 4,915 CKD patients, and 3 independent validation cohorts comprised a total of 3,063. Patients were observed for approximately 5 years., Exposure: 22 demographic, anthropometric, and laboratory variables commonly assessed in CKD patients., Outcome: Progression to KFRT., Analytical Approach: A least absolute shrinkage and selection operator (LASSO) Cox proportional hazards model was fit to select laboratory variables that best identified patients at high risk for KFRT. Model discrimination and calibration were assessed and compared against the 4-variable Tangri (T4) risk equation both in a resampling approach within the development cohort and in the validation cohorts using cause-specific concordance (C) statistics, net reclassification improvement, and calibration graphs., Results: The newly derived 6-variable risk score (Z6) included serum creatinine, albumin, cystatin C, and urea, as well as hemoglobin and the urinary albumin-creatinine ratio. In the the resampling approach, Z6 achieved a median C statistic of 0.909 (95% CI, 0.868-0.937) at 2 years after the baseline visit, whereas the T4 achieved a median C statistic of 0.855 (95% CI, 0.799-0.915). In the 3 independent validation cohorts, the Z6C statistics were 0.894, 0.921, and 0.891, whereas the T4C statistics were 0.882, 0.913, and 0.862., Limitations: The Z6 was both derived and tested only in White European cohorts., Conclusions: A new risk equation based on 6 routinely available laboratory tests facilitates identification of patients with CKD who are at high risk of progressing to KFRT., (Copyright © 2021 National Kidney Foundation, Inc. All rights reserved.)