Renal anaemia

Navarro JF. In the erythropoietin era, can we forget alternative or adjunctive therapies for renal anaemia management Nephrol Dial Transplant 2003 18 2222-6. 

What concomitant therapy might Mrs HK require to treat her renal anaemia ... 

Sexton J (2008) Renal Anaemia. In Ashley C, Morlidge C (eds) Introduction to Renal Therapeutics. London Pharmaceutical Press, 45-56. 

Renal anaemia is generally treated with erythropoiesis-stimulating agents (ESAs), of which three are currently in general use the erythropoietins, namely epoetin alfa (Eprex), epoetin beta (NeoRecormon) and darbepoetin alfa (Aranesp). 

Treatment for renal anaemia is divided into two stages - correction and maintenance phase - and the dosage regimens vary according to the preparation used. 

Macdougall IC, Hutton RD, CavUl I, Coles GA, Williams JD. Treating renal anaemia with recombinant human erythropoietin practical guidehnes and a clinical algorithm. BMJ 1990 300(6725) 655-9. 

Silberberg J. Total correction of renal anaemia does not lead to adversely high blood viscosity. Erythropoiesis New Dimens Treat Anaemia 2001 11 25-6. 

Ruiz PG, Balcke P, Martinez JM, Harris K. Tolerability of the epoetin-beta multidose formulation (Reco-Pen) in patients with renal anaemia. Chn Drug Invest 2000 20 151-8. 

Silverberg D, Wexler D, Blum M, et al. The cardio-renal anaemia syndrome does it exist Nephrol Dial Transplant 2003 18(Suppl 8) viii7-12. 

Van Wyck DB. Management of early renal anaemia Diagnostic workup, iron therapy, epoetin therapy. Nephrol Dial Transplant 2000 15(Suppl 3) 36-39. 

Carrera F, Lok CE, de Francisco A, Locatelli F, Mann JF, Canaud B, Kerr PG, Macdougall IC, Besarab A, Villa G, Kazes I, Van Vlem B, Jolly S, Beyer U, Dougherty FC. Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly a randomized comparative trial. Nephrol Dial Transplant 2010 25(12) 4009-17. 

Neorecormon (tradename, also known as epoetin beta) is a recombinant human EPO first approved for medical use in the EU in 1997. It is indicated for the treatment of anaemia associated with various medical conditions, most commonly chronic renal failure and cancer patients receiving chemotherapy. Neorecormon is produced by recombinant DNA technology in a CHO cell line and is manufactured as outlined in Figure 10.5. It is presented in lyophilized format at various strengths (500-10 000 IU/vial) and contains phosphate buffer, sodium chloride, calcium chloride, urea, polysorbate and various amino acids as excipients. 

Erythropoeitins are used to treat symptomatic anaemia associated with erythropoietin deficiency in chronic renal failure and to shorten the period of symptomatic anaemia in patients receiving cytotoxic chemotherapy. It is not recommended for use in cancer patients who are not receiving chemotherapy. In cancer patients, the risk of thrombosis and related complications might be increased. The haemoglobin concentration should be maintained within the range of 10-12 g/100 ml - higher concentrations should be avoided to reduce risk of complications of therapy. 

Rifampicin Shock, haemolytic anaemia, renal failure... 

Although manifest hemolytic anaemia is rare a positive Coomb s test may develop in about 3% of patients. As with the penicillins neurotoxicity manifested by hallucinations, confusion and convulsions may occur with high doses or in patients with renal impairment. 

Pathophysiologically normochromic and normo-cytic anaemia, as occurs in many clinical syndromes exemplified by renal failure, a number of cancers, rheumatoid arthritis and systemic lupus erythematosus, is typical. Initially erythrocytes are of normal size and degree of haemoglobinization. However, persistent impairment of iron supply, especially from mitochondria to globin in the cytoplasm, leads to them becoming hypochromic and microcytic. 

Adverse effects include nausea, vomiting, diarrhoea, abdominal pain, neuropathy, myopathy especially in patients with decreased renal function. Prolonged therapy may lead to aplastic anaemia, agranulocytosis, alopecia and myopathy. 

Plasma expanders are not used in severe anaemia, cardiac failure, pulmonary edema and renal failure. 

It is produced primarily by peritubular cells in the proximal tubule of the kidney. In anaemia renal secretion of erythropoietin increases rapidly manifold. Erythropoietin levels are always detectable in plasma. 

It is used in the treatment of anaemia of chronic renal failure, in anaemia of patients with AIDS who are being treated with zidovudine and anaemia associated with cancer chemotherapy. 

It is indicated in renal transplantation, severe active rheumatoid arthritis unresponsive to other therapy, certain autoimmune diseases, chronic active hepatitis, idiopathic thrombocytopenic purpura and acquired haemolytic anaemia. 

Long-term feeding of hydroquinone to rats led to aplastic anaemia, liver cord-cell atrophy and ulceration of the gastric mucosa. A single high dose was reported to induce renal tubule necrosis in rats (lARC, 1977). 

Case study level 3 - Pre-dialysis patient with anaemia 359 Case study level Ma - Diabetes and renal impairment 361 Case study level Mb - Hypertension-associated kidney disease 363... 

In chronic arsenic poisoning anorexia, anaemia, disturbances in renal and hepatic function, dermatitis, skin hardening (hyperkeratosis) and pigmentation can occur. Arsine gas is a powerful haemolytic agent and symptoms of poisoning are due to its action on the blood. 

The anaemia of chronic renal disease is due to the reduced secretion of EP by the kidney, and in renal failure red cell count and haemoglobin concentration fall considerably. 

In anaemia of chronic disease, anaemia associated with chemotherapy or anaemia associated with renal disease, recombinant erythropoietin can stimulate red cell production. 

ACE INHIBITORS AZATHIOPRINE Risk of anaemia with captopril and enalapril and leukopenia with captopril The exact mechanism is uncertain. Azathioprine-induced impairment of haematopoiesis and ACE inhibitor-induced l in erythropoietin may cause additive effects. Enalapril has been used to treat post-renal transplant erythrocytosis Monitor blood counts regularly... 

MITOMYCIN HORMONES AND HORMONE ANTAGONISTS -TAMOXIFEN t incidence of anaemia and thrombocytopenia and risk of haemolytic-uraemic syndrome Mitomycin causes subdinical endothelial damage in addition to the thrombotic effect on platelets caused by tamoxifen, which leads to haemolytic-uraemic syndrome Monitor renal function at least twice weekly during concurrent therapy and watch clinically for bleeding episodes, e.g. nose bleeds, bleeding from the gums, skin bruising... 

Adverse effects include hyperuricaemia and arthralgia, which is relatively frequent with daily but less so with intermittent dosing and, unlike gout, affects both large and small joints. Pyrazinoic acid, the principal metabolite of pyrazinamide, inhibits renal tubular secretion of urate. Symptomatic treatment with an NSAID is usually sufficient and it is rarely necessary to discontinue pyrazinamide because of arthralgia. Hepatitis, which was particularly associated with high doses, is not a problem with modern short-course schedules. Sideroblastic anaemia and urticaria also occur. 

Fenamic acid. The principal adverse effects of mefenamic acid are diarrhoea, upper abdominal discomfort, peptic ulcer and haemolytic anaemia. Elderly patients who take mefenamic acid may develop nonoliguric renal failure especially if they become dehydrated, e.g. by diarrhoea the drug should be avoided or used with close supervision in the elderly. 

First the patient is given a small dose of radioactive vitamin Bj2 orally, with a simultaneous large dose of nonradioactive vitamin B intramuscularly. The large injected dose saturates binding sites so that any of the oral radioactive dose that is absorbed cannot bind and will be eliminated in the urine where it can easily be measured (normally > 10% of the administered dose appears in urine collected for 24 h, if renal function is normal). In pernicious anaemia and in malabsorption, gut absorption and therefore subsequent appearance of radioactivity in the plasma (measured 8-12 h later) and urine are negligible. 

The initial dose in cobalamin deficiency anaemias, including uncomplicated pernicious anaemia, is hydroxocobalamin 1 mg i.m. every 2-3 days for 5 doses to induce remission and to replenish stores. Maintenance may be 1 mg every 3 months higher doses will not find binding sites and will be eliminated in the urine. Higher doses are justified during renal or peritoneal dialysis where hydroxy-cobalamin clearance is increased, and resultant raised plasma methylmalonic acid and homocysteine represent an independent risk factor for vascular events in these patients (see later). 

Erythropoietin is a glycoprotein hormone encoded by a gene on the long arm of chromosome 7 (7q) and 90% is produced in the kidney (the remainder in the liver and other sites) in response to hypoxia. The anaemia of chronic renal failure is largely due to failure of the diseased kidneys to make enough erythropoietin. The principal action of the hormone is to stimulate the proliferation, survival and differentiation of erythrocyte precursors. The manufacture of erythropoietin for clinical use became possible when the human gene was successfully inserted into cultured hamster ovary cells. 

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