Pathogenesis (disease development)
Chronic renal failure or other renal diseases result in impaired renal (“kidney-related”) erythropoietin formation (synonyms: erythropoietin, EPO), which stimulates erythropoiesis (blood formation). Furthermore, there is a disturbed iron incorporation, a shortened life span of erythrocytes (red blood cells), hemolysis (dissolution of red blood cells) and an inhibition of erythropoiesis (process of formation and development of erythrocytes/red blood cells) by “uremic toxins” (mostly nitrogenous substances, which are responsible for the symptoms of uremia (increased occurrence of urinary substances in the blood) and nephropathy (kidney disease), among others. Aggravating agents:
- Deficiency of iron / folic acid / vitamin B12.
- Secondary hyperparathyroidism (sHPT; parathyroid hyperfunction)/bone marrow fibrosis.
- Chronic inflammation (chronic inflammation).
- Blood loss (blood collection, hemodialysis/blood purification procedure called, which is used as a replacement procedure in renal failure).
- Bone marrow damage due to aluminum overload
- Inhibition of EPO production or erythropoiesis by drugs:
- ACE(“angiotensin-converting enzyme”) inhibitors decrease EPO production.
- Immunosuppressants (e.g., azathioprine, mycophenolic acid) and cytostatic drugs inhibit erythropoiesis (see below).
Etiology (causes)
Biographical causes
- Genetic burden from parents, grandparents
- Genetic diseases/misformations
- Polycystic kidney disease – kidney disease due to multiple cysts (fluid-filled cavities) in the kidneys
- Partly with autosomal dominant as well as autosomal recessive inheritance (see below Cystic Kidney Disease).
- Polycystic kidney disease – kidney disease due to multiple cysts (fluid-filled cavities) in the kidneys
- Genetic diseases/misformations
Causes due to disease
- Acute renal failure (ANV)
- Chronic renal failure
- Diabetic nephropathy – kidney disease due to vascular disease in the presence of diabetes mellitus (diabetes).
- Hemolytic uremic syndrome (HUS) – triad of microangiopathic hemolytic anemia (MAHA; form of anemia in which erythrocytes (red blood cells) are destroyed), thrombocytopenia (abnormal reduction in platelets/platelets), and acute kidney injury (AKI); Mostly occurring in children in the context of infections; most common cause of acute renal failure requiring dialysis in childhood.
Medications
Anemia
- Antiprotozoal drugs
- Analogue of the azo dye trypan blue (suramin).
- Pentamidine
- Alpha-methyldopa (antihypertensive).
- Antimalarials, such as primaquine or dapsone.
- Chelating agents (D-penicillamine, trieethylenetetramine dihydrochloride (Trien), tetrathiomolybdenum).
- Quinidine
- Direct Factor Xa inhibitor (rivaroxaban).
- Immunosuppressants (thalidomide).
- Janus kinase inhibitors (ruxolitinib).
- Monoclonal antibodies – pertuzumab
- MTOR inhibitors (everolimus, temsirolimus).
- Neomycin
- P-aminosalicylic acid (mesalazine)
- Phenytoin [megaoblastic anemia]
- Thrombin inhibitor (dabigatran)
- Tuberculostatics (isoniazid, INH; rifampicin, RMF).
- Antivirals
- Nucleoside analogues (ribavirin) [hemolytic anemia.]
- NS5A inhibitors (daclatasvir).
- Protease inhibitors (boceprevir, telaprevir).
Aplastic anemia
- Allopurinol*
- Alpha-methyldopa*
- Antibiotics – drugs such as streptomycin* , tetracycline* or methicillin* .
- Antidiabetic drugs – tolbutamide and chlorpropamide.
- Antihistamines – cimetidine
- Anticonvulsants – carbomazepine
- Carboanhydrase inhibitors (CAH, CAI) – acetazolamide, dichlorophenamide, methazolamide.
- Quinidine*
- Chloramphenicol
- Colchicine
- D-penicillamine – drug used in the therapy of rheumatoid arthritis.
- Lithium*
- Medicines for protozoan infections such as chloroquine or mepacrine.
- Non-steroidal anti-inflammatory drugs (NSAIDs) – phenylbutazone, ibuprofen, or acetylsalicylic acid (ASA).
- Estrogens
- Sedatives – such as chlorpromazine* or meprobamate* .
- Sulfonamides
- Tuberculostatics (isoniazid, INH)
- Thyrostatic drugs – such as methylthiouracil or carbimazole.
- Cytostatics
- Alkylants such as chlorambucil or cyclophosphamide.
- Antimetabolites such as mercaptopurine, fluorouracil or methotrexate.
- Mitosis inhibitors such as vincristine or paclitaxel.
Note: For drugs marked with an asterisk (* ), the association with aplastic anemia is poorly established.