P0878INDEPENDENT EFFECTS OF SECONDARY HYPERPARATHYROIDISM ON CHRONIC KIDNEY DISEASE PROGRESSION AND CARDIOVASCULAR EVENTS IN THE NEFRONA COHORT
Authors: Bermudez-Lopez Marcelino , Forne Izquierdo Carles , Cambray Serafí , Bozic Milica , Valdivielso Jose Manuel 
Published: June 2020

Abstract

Background and Aims
Secondary hyperparathyroidism (sHPT) is a common complication in patients with chronic kidney disease, and is associated with mortality in non-dialysis and CKD patients. However, it is not clear whether negative outcomes linked to sHPT are confounded by other factors associated to the disease. Furthermore, potential effects of sHPT on CKD progression are not entirely clear. Therefore, the present study was designed to identify the effect of sHPT (defined as patients treated with cinacalcet or phosphate binders, active vitamin D, or with PTH blood levels over the KDOQI recommended values (&gt;70 in CKD3; &gt;110 in CKD4; &gt;300 in CKD5 or 5D)) on risk of CKD progression and cardiovascular incidence in a cohort of CKD patients (NEFRONA cohort) and whether hypercalcemia and/or hyperphosphatemia act as effect modifiers.

Method
We used the 2445 patients with CKD of the NEFRONA cohort (950 stage 3, 807 stage 4-5 and 688 on dialysis) followed for 2 years for the CKD progression outcome (defined as a 30% decrease of GFR or entering in renal replacement therapy) and for 4 years for cardiovascular events. Follow up periods were defined in the original NEFRONA protocol.

Results
After excluding 244 patients with missing values in PTH levels, 1693 (76.9%) patients presented with sHPT, 433 (57.4%) on stage 3, 625 (82.1%) on stage 4-5 and 635 (92.7%) on dialysis. From the 1283 patients with data on CKD progression, 301 (23.5%) fulfilled the criterion of CKD progression after 2 years. During the 4 years follow-up, 203 CVE were recorded in the whole cohort. Bivariate analysis showed that factors associated with the disease progression were male gender, higher age, lower BMI, present with hypertension, albuminuria, hyperphosphatemia or sHPT, being in a more advanced CKD stage, lower levels of glucose, LDL cholesterol or 25(OH)D. Multivariate logistic regression analysis adjusted by possible confounding factors showed that sHPT was still associated with higher odds of CKD progression (OR: 2.75; 95%CI: 1.55-4.88). Hyperphosphatemia also showed an effect on CKD progression (OR: 6.13; 95%CI: 1.48-25.3) and no statistically significant interaction with sHPT was detected. Factors showing statistical significance with the CVE outcome in the crude analysis were male gender, higher age, being diabetic or smoker, hyperphosphatemia, a more advanced CKD stage, presence of sHPT, higher levels of glucose or hsCRP and lower levels of HDL cholesterol or 25(OH)D. Multivariate Fine and Gray regression model showed that patients with sHPT showed higher hazards of presenting cardiovascular events (HR: 1.61; 95%CI: 1.07-2.43). Hyperphosphatemia maintained its independent effect on mortality (HR: 1.64; 95%CI: 1.20-2.23) and again no significant interaction was found with sHPT. A sensitivity analysis was performed eliminating treatment with phosphate binders from the definition of sHPT, yielding similar results.

Conclusion
We conclude that sHPT and hyperphosphatemia independently influence CKD progression and the incidence of cardiovascular events.