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 10µg/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.