Chronic Kidney disease (CKD) describes the gradual loss of kidney function. It is a major public health problem resulting in an important burden for patients and healthcare systems. It affects millions of people with an estimated prevalence ranging from 3 to 17% in Europe. It is one of the 10 leading causes of death in developed countries.
CKD can be due to multiple causes: High blood pressure, diabetes, high cholesterol, kidney infections, glomerulonephritis, polycystic kidney disease, genetic conditions, autoimmune diseases, kidney stones, smoking, age, use of certain medicines etc.
CKD is commonly associated with 2 common debilitating disorders, Iron Deficiency Anaemia (IDA) and Mineral Bone Disorders (MBD). Depending on the stage of the disease, CKD can induce cardiovascular diseases and can progress to end-stage kidney failure, fatal without dialysis or kidney transplant
CKD bears a substantial burden of comorbidities : - Polypharmacy is real and frequent - Suboptimal management of anemia by current therapies - Delay the entry to dialysis or need to transplantation is a key challenge
Iron deficiency leading to Anaemia is a common complication that significantly affects the health-related quality of life (HRQoL) of CKD patients, increased cardiovascular disease, hospitalizations, cognitive impairment and mortality. Prevalence rates in Europe range from 12.8% to 61.5% depending on the stage of CKD.
The cause of iron deficiency and anaemia in patients with CKD is multifactorial. Possible factors include reduced erythropoietin (EPO) production as a result of renal function deterioration, increased levels of hepcidin which inhibits iron absorption, lower levels of ferritin (the main iron storage protein), reduced iron transportation via transferrin, use of Erythropoiesis-stimulating Agents (ESAs), reduced dietary intake of iron, increased blood loss (particularly in patients undergoing dialysis), poor bone marrow responsiveness or suppression, inflammation, and shortened red blood cell survival.
As serum phosphorous levels rise because it cannot be adequately excreted via the impaired kidneys, various compensatory responses occur to maintain phosphorous homeostasis.
The persistent lack of phosphorous excretion via the kidneys leads to detrimental clinical outcomes. The resulting disruption in mineral homeostasis is sometimes termed CKD-mineral and bone disease (CKD-MBD) which is characterised by bone and musculoskeletal abnormalities as well as the extra-skeletal (vascular and soft tissue) calcification implicated in cardiovascular morbidity and mortality CKD-MBD remains a pervasive complication that warrants attention. The severity and prevalence of MBD differ across various CKD stages, with a higher frequency noted in advanced stages
The elevated FGF23 levels seen in patients with CKD contributes towards the multiple complications that often arise in patients.
FGF23 is released primarily from bone osteoblasts/osteocytes; it not only has targets in the kidneys associated with the control of phosphorous, and in other organs such as the parathyroid gland, the heart (increases left ventricular hypertrophy), within bones, and could have targets in other organs such as the liver (resulting in production of inflammatory cytokines).
It has been demonstrated that FGF23 levels are not only impacted by phosphorous levels, but also in conditions where there is iron deficiency and inflammation. Regardless of the cause of elevated levels of FGF23 in CKD patients, increases have been demonstrated to be independently associated with poor clinical outcomes and cardiovascular morbidity/mortality
