Androgens for the anaemia of chronic kidney disease in adults

Anaemia, which occurs when red blood cell and haemoglobin levels fall below normal, is a common problem among adults with chronic kidney disease (CKD). Anaemia can cause breathlessness, dizziness and chest pain (angina); reduce ability to think clearly; limits ability to exercise; and contributes to sexual problems, poor appetite and reduced quality of life. Anaemia may also cause longer hospital stays, and sometimes death.

There are several approaches to correct anaemia in people with CKD, including drugs to stimulate red blood cell production, dialysis to remove waste and excess water from the blood, blood transfusions, dietary management, and supplementary iron and folate agents.

Other drugs, such as androgens - which are male steroid hormones - may be given in some settings to help reduce undesirable effects of treatments. Another possible benefit of androgen therapy for people with CKD, especially in regions with limited health resources, is that these drugs have lower costs than some other treatments.

We assessed eight small studies that presented data from 181 adults with CKD-related anaemia that investigated use of androgen therapy. Limitations and flaws in the evidence lead to our conclusion that androgen therapy for adults with CKD-related anaemia was not associated with substantial benefits.

Authors' conclusions: 

We found insufficient evidence to confirm that use of androgens for adults with CKD-related anaemia is beneficial.

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Background: 

Anaemia occurs when blood contains fewer red blood cells and lower haemoglobin levels than normal, and is a common complication among adults with chronic kidney disease (CKD). Although a number of approaches are applied to correct anaemia in adults with CKD, the use of androgen therapy is controversial.

Objectives: 

The aim of this review was to determine the benefits and harms of androgens for the treatment of anaemia in adult patients with CKD.

Search strategy: 

We searched CENTRAL, the Cochrane Renal Group's Specialised Register, the Chinese Biomedicine Database (CBM), CNKI, VIP and reference lists of articles without language restriction. The most recent search was conducted in August 2014.

Selection criteria: 

All randomised controlled trials (RCTs) that assessed the use of androgens for treating anaemia of CKD in adults were eligible for inclusion.

Data collection and analysis: 

Two authors independently extracted data and assessed risk of bias in the included studies. Meta-analyses were performed using relative risk (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI).

Main results: 

We included eight studies that reported data from 181 participants. Study quality was assessed as moderate in six studies, one was low quality, and one was high quality. The small number of included studies, and low participant numbers adversely influenced evidence quality overall.

We found limited evidence (1 study, 24 participants) to indicate that oxymetholone can increase haemoglobin (Hb) (MD 1.90 g/dL, 95% CI 1.66 to 2.14), haematocrit (HCT) (MD 27.10%, 95% CI 26.49 to 27.71), change in albumin (MD 4.91 g/L, 95% CI 3.69 to 6.13), alanine aminotransferase (ALT) (MD 54.50 U/L, 95% CI 43.94 to 65.06), and aspartate aminotransferase (AST) (MD 47.33 U/L, 95% CI 37.69 to 56.97); and decrease high-density lipoprotein (HDL) (MD -15.66 mg/dL, 95% CI -24.84 to -6.48). We also found that compared with erythropoietin alone, nandrolone decanoate plus erythropoietin may increase HCT (3 studies, 73 participants: MD 2.54%, 95% Cl 0.96 to 4.12). Compared with erythropoietin (1 study, 27 participants), limited evidence was found to suggest that nandrolone decanoate can increase plasma total protein (MD 0.40 g/L, 95% CI 0.13 to 0.67), albumin (MD 0.20 g/L, 95% CI 0.01 to 0.39), and transferrin (MD 45.00 mg/dL, 95% CI 12.61 to 77.39) levels. Compared with no therapy (remnant kidney), evidence was found to suggest that nandrolone decanoate can increase Hb (2 studies, 33 participants: MD 1.04 g/dL, 95% Cl 0.66 to 1.41) and HCT (1 study, 24 participants: MD 3.70%, 95% Cl 0.68 to 6.72). Compared with no therapy (anephric), evidence was found (1 study, 5 participants) to suggest that nandrolone decanoate can increase Hb (MD 1.30 g/dL, 95% Cl 0.57 to 2.03), but nandrolone decanoate did not increase HCT (MD 2.00%, 95% Cl -0.85 to 4.85).

However, oxymetholone was not found to reduce blood urea nitrogen (BUN), serum creatinine (SCr), cholesterol, or triglycerides; or increase plasma total protein, prealbumin, or transferrin. No evidence was found to indicate that nandrolone decanoate increased prealbumin or decreased BUN, SCr, AST, ALT, cholesterol, triglycerides, HDL or low-density lipoprotein (LDL). Adverse events associated with androgen therapy were reported infrequently.

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