P0758THE CORRELATION BETWEEN THE MANAGEMENT OF COMORBIDITIES AND THE PROGRESSION OF THE RENAL DYSFUNCTION OR ADVERSE EVENTS OF CHRONIC KIDNEY DISEASE
Authors: Takahiro Kuragano , Kida Aritoshi , Yahiro Mana , Nanami Yoshimasa , Nagasawa Yasuyuki , Nakanishi Takeshi 
Published: June 2020

Abstract

Background and Aims
Several factors, such as anemia, hypertension, hyperuricemia, metabolic acidosis, and chronic kidney disease (CKD)-mineral and bone disorder (MBD), are associated with the progression of CKD or adverse events in CKD patients. However, the significant factors associated with the progression of CKD or adverse events in patients under the condition of appropriate control according to guidelines have not been clarified.

Method
The study was a 3-year observational study conducted in a single center. In 88 patients with various stages of CKD (not on renal replacement therapy (RRT)) who were treated by nephrologists, blood levels of Hb, ferritin, iron, total iron-binding capacity, and albumin were measured every 3 months, and high-sensitivity C reactive protein (hCRP), β2-microglobulin (MG), HCO3-, and intact-parathyroid hormone (int-PTH), in addition to urinary sodium, potassium, calcium, phosphorus, protein, and β2-MG levels, were measured every 6 months. We also evaluated the doses of iron, erythropoiesis-stimulating agent (ESA), vitamin D, phosphate binder, anti-hypertensive agents, and anti-hyperuricemic agents. All patients were treated according to the clinical practice guidelines for CKD (Japanese Society of Nephrology 2013). A time-dependent Cox hazard model was applied to evaluate the associations between clinical parameters and adverse events (initiation of RRT and hospitalization resulting in cardiovascular disease or infection).

Results
Unexpectedly, under the condition of appropriate control by nephrologists, hypertension, hyperuricemia, metabolic acidosis, iron metabolism, and inflammation were not selected as significant predictors of the progression of renal dysfunction or adverse events. (Factors associated with the progression of renal dysfunction) In multiple regression analysis, lower baseline blood levels of Hb (β=0.497, P&lt;0.001) and vitamin D 125 (β=0.258, P=0.006) and higher baseline blood levels of int-PTH (β=-0.334, P=0.001), urinary phosphorus (β=0.328, P=0.001), urinary β2-MG (β=-0.225, P=0.031) and urinary protein (β=0.280, P=0.02) were selected as significant predictors of reduced estimated glomerular filtration rate (eGFR) or 1/creatinine (Cr) at the end of the study. (Factors associated with the initiation of RRT and adverse events) In the Cox hazard model, low calcium (HR: 0.37, P=0.026), high phosphate (HR: 5.90, P&lt;0.001), low 1,25-vitamin D (HR: 0.94, P=0.013), high int-PTH (HR: 1.02, P&lt;0.001), use of a phosphate binder (HR: 4.95, P=0.012), and use of vitamin D analogs (HR: 3.75, P=0.014) were selected as risks for adverse events, including the initiation of RRT.

Conclusion
In this study, we found that among several factors, anemia and CKD-MBD-related factors (phosphate, calcium, vitamin D, int-PTH) were selected as significant predictors of the progression of renal dysfunction. Furthermore, although phosphate binders or vitamin D analogs were administered appropriately, CKD-MBD-related factors (phosphate, calcium, vitamin D, and int-PTH) were associated with RRT initiation or adverse events in these patients. From these results, we presumed that early intervention or strict control of CKD-MBD factors might attenuate the risk for adverse events in CKD patients.