Anemia is one of the major Hematological complications in Chronic Kidney Disease (CKD). As renal function declines, there is a progressive worsening of anemia, which becomes clear once serum creatinine rises above 300 µmol/L or GFR falls below 30 ml/min/1.73m² and its major cause is the loss of cells in the kidney responsible for the synthesis and secretion of erythropoietin.
Click here to know more about Anemia in CKD.
Here is some of the pathogenesis of renal anemia that helps in the management of anemia in CKD
ERYTHROPOIETIN PRODUCTION
It is accepted that insufficient production of erythropoietin is one of the main reason for anemia associated with an end-stage renal disease. Plasma erythropoietin levels are inappropriately low for the severity of anemia, this is majorly seen in anephric patients who tend to have more severe anemia.
Studies showed that severely damaged kidneys can sometimes produce supranormal levels of erythropoietin and that a reversible inhibition of erythropoietin production occurs in acute renal failure and commonly seen in adult polycystic kidney disease. Even in uremia, erythropoietin production can be increased in response to stimuli such as hypoxic hypoxia and suppressed in response to blood transfusion and immunomodulatory cytokines.
UREMIC INHIBITORS OF ERYTHROPOIESIS
The serum culture of uremic individuals shows growth inhibition of erythroid progenitor cells. And there is no evidence to prove that erythropoiesis is blocked by uremic condition, but it is concluded by the fact that renal anemia improves to some extent after starting dialysis and this also supports the theory that a uremic substance removed by dialysis is toxic to the bone marrow.
HYPERPARATHYROIDISM
Hyperparathyroidism might cause renal anemia in two ways, first is by direct inhibition of erythroid progenitor cell growth by parathyroid hormone and second is by its effects in inducing marrow fibrosis and thereby reducing the pool of erythroid progenitor cells in bone marrow. Improvement in anemia is seen after parathyroidectomy and reduction in PTH levels induced by high dose of vitamin D supplementation seen as the improved response to epoetin therapy.
ALUMINUM TOXICITY
Aluminum toxicity associated with microcytic anemia is improved after treated with desferrioxamine chelation therapy. Aluminum toxicity exacerbates anemia may be by interfering with iron transport and/or its utilization, inhibition of heme synthesis, or increased hemolysis due to an increase in red cell fragility. But this has been poorly understood yet. Aluminum toxicity is now less common due to the introduction of water deionizers and reduced use of “aluminum containing” phosphate binders.
IRON AND FOLATE DEFICIENCY
Iron deficiency is commonly seen in most of Hemodialysis patients due to the major loss of iron (about 4-5mg per treatment) partly due to blood loss in dialysis extracorporeal circuit, occult gastrointestinal bleeding and repeated phlebotomy. Excessive loss of hematinic substances is seen in dialysis patients especially Folate as it is readily removed by hemodialysis. Dietary insufficiency may also cause these deficiencies as most of the dialysis patients suffer from poor appetite.
HEMOLYSIS
Uremia in chronic renal failure exacerbates shortened lifespan of red cells due to low-grade hemolysis or hypersplenism this gets corrected after initiation of regular dialysis. Hemodialysis may also exacerbate a more severe hemolysis due to use of several toxins like formaldehyde, copper, chloramines, and nitrates.
CLINICAL CONSEQUENCES OF RENAL ANEMIA
Patients complain of tiredness, lethargy, muscle fatigue, reduced exercise capacity, poor concentration, impaired memory and intellectual ability, breathlessness at rest and on exercise, angina, palpitations, loss of appetite, reduced libido and sensation of feeling cold.
Exercise physiology test shows a decrease in exercise capacity and indicates a reduced maximum oxygen consumption (VO2 max) and anaerobic threshold. Cardiac output increases to compensate for the lowered oxygen capacity of blood, this is achieved by an increase in both stroke volume and heart rate and this in severe case result in high-output cardiac failure. Impaired cognitive function and various abnormities of endocrine functions have been attributed to chronic renal anemia.
Chronic kidney disease is often associated with bleeding tendency, characterized by a prolonged skin bleeding time. This is due to abnormality of platelet function and anemia as a major factor. Correction of anemia by blood transfusion or erythropoietin therapy usually results in the return of bleeding time to normal.
LazyKidney 