A Proven and Probable Case of Pre-Existing IgA Nephropathy Exacerbated By Administration of G-CSF

The Anthony Nolan volunteer hematopoietic stem cell (HSC) donor registry recently encountered two episodes of haematuria following the use of granulocyte colony stimulating factor (G-CSF), highlighting how serious underlying medical conditions may go unnoticed despite rigorous assessment.

A 28-year-old Caucasian male donor had an unremarkable medical history at work-up.� He reported an episode of self-limiting frank haematuria one year previously.� At that time, he was diagnosed with an episode of possible haemorrhagic cystitis. At the pre-donation assessment his creatinine was 95 umol/L. Urinalysis was not performed as per the agreed registry screening policy. He was declared medically fit to donate by G-CSF mobilised PBSC harvest, and commenced a 4-day course of recombinant glycosylated G-CSF at 10�g/kg daily.

Shortly after administration of the third dose, he developed frank haematuria. �The fourth dose was omitted and PBSC harvest occurred the following day. On the day of collection, his creatinine had increased to 148 umol/l and quantitative urinalysis showed frank haematuria and heavy proteinuria (4.1g/day). He was reviewed by a nephrologist and a presumptive diagnosis of IgA nephropathy (IgAN) was made. Renal biopsy features confirmed this. Biochemical indices resolved although proteinuria and microscopic haematuria persisted five months later.�

We encountered a similar case more recently, where a 28-year old Caucasian male donor with an unremarkable medical history developed haematuria after 3 doses of G-CSF. A fourth dose was nevertheless administered as the symptoms were not reported at the time. On the day of collection, his creatinine was 77 umol/l and urinalysis showed heavy haematuria but no proteinuria.� Five days post donation his renal imaging was normal but quantitative urinalysis revealed heavy proteinuria (5 g/day). He was reviewed by a nephrologist two weeks later and his proteinuria had improved to approximately 0.5g/day. A presumptive diagnosis of IgAN was suggested but a renal biopsy was not deemed necessary given the improvement of his laboratory indices.

In summary, these cases illustrate a proven and probable pre-existing IgAN exacerbated by G-CSF. IgAN is a common form of glomerulonephritis seen worldwide. The use of G-CSF has previously been linked to haematuria ^�and 2 case reports of proven IgAN have been reported to date. The Serious Events and Adverse Reactions database held by the World Marrow Donor Association (WMDA) reports 1 episode of unexplained haematuria in G-CSF mobilised donors. This is likely an underestimate particularly when cases present only with asymptomatic proteinuria or microscopic haematuria.� We would urge all donor registries to report any cases to the WMDA.� We would also recommend the introduction of urinalysis as part of the medical work-up in all HSC donors and the follow-up management as shown in Figure 1.

Figure 1.

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