Intravenous immunoglobulins: in-depth review of excipients and acute kidney injury risk.
BACKGROUND
Used in a variety of approved and off-label indications, there are several intravenous immunoglobulin (IVIG) preparations available which differ in the excipients (e.g. sucrose, glucose, maltose, D-sorbitol, glycine or L-proline) used to stabilize the protein in the solution. A very rare, but severe adverse drug reaction (ADR) reported with sucrose-stabilized IVIGs, acute renal failure, is well established, but the relative risks with sucrose-free IVIGs are unknown.


METHODS
Medline and Embase were searched for published data on ADRs involving the kidney, and DrugCite, a public database of >4,000,000 ADRs from the USA, was also searched. Renal impairment-associated ADRs and categories were summarized.


RESULTS
Compared with sucrose-containing IVIGs, reports of ADRs involving the kidney were relatively rare with sucrose-free IVIGs: 12 cases were published prior to February 28, 2012; incidences reported in DrugCite were also relatively low and similar among sucrose-free preparations. The incidence of hemolysis-related ADRs, a potential cause of secondary acute renal impairment, was higher with glycine- and L-proline-stabilized IVIGs. Reported incidences of renal impairment with sucrose-free IVIGs are similar between products and much lower than with sucrose-stabilized IVIGs.


CONCLUSIONS
It is recommended that the choice of IVIG should be guided by the patient's medical history, present comorbidities and concomitant medications. Prospective studies with inclusion of creatinine values, as well as rigorous reporting of cases in the literature and/or via pharmacovigilance systems, are imperative to better define patient profiles.
Institut de Transplantation Urologie Néphrologie (ITUN) and INSERM U643, CHU Hôtel Dieu, Nantes, France.
Jacques
J
Dantal
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000453:epidemiology; D015897:Comorbidity; D064420:Drug-Related Side Effects and Adverse Reactions; D005079:Excipients / Q000009:adverse effects*; D005998:Glycine / Q000009:adverse effects; D006461:Hemolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects* / Q000627:therapeutic use*; D015994:Incidence; D007668:Kidney / Q000187:drug effects; D008320:Maltose / Q000009:adverse effects; D011392:Proline / Q000009:adverse effects; D013012:Sorbitol / Q000009:adverse effects; D013395:Sucrose / Q000009:adverse effects
D005079:Excipients; D016756:Immunoglobulins, Intravenous; D013012:Sorbitol; D013395:Sucrose; D008320:Maltose; D011392:Proline; D005998:Glycine