a 34-year-old Chinese man (Case 1)
Fabry disease, an inherited (X-linked) disorder from a GLA gene mutation (c.493G>T) that damages the kidneys; he had proteinuria and severe kidney impairment
He was given enzyme replacement therapy with agalsidase beta (brand name Fabrazyme, made by Sanofi) at 1 mg per kilogram of body weight every two weeks. He received this therapy for 21 months before having a kidney transplant at about age 32. The doctors say the kidney recovery was mainly due to the transplant, while the enzyme therapy helped control the disease throughout his body. His blood marker Lyso-Gb3 dropped 70.6%, from 93.33 to 27.38 ng/mL, and the protein in his urine resolved.
In one man with Fabry disease and failing kidneys, a kidney transplant restored stable kidney function while enzyme therapy lowered a key disease marker in his blood by 70.6%.
- This man's kidney function became stable (creatinine under 115 micromol/L) and his urine protein went away only after a kidney transplant at about age 32.
- The doctors credit the kidney recovery mainly to the transplant, not to the enzyme therapy.
- Enzyme replacement therapy with agalsidase beta (1 mg/kg every two weeks) worked on the disease throughout his body, dropping his plasma Lyso-Gb3 from 93.33 to 27.38 ng/mL, a 70.6% fall.
- He took the enzyme therapy for 21 months before the transplant, so the two treatments played different roles rather than one replacing the other.
- Fabry disease comes from a GLA gene change (here c.493G>T) and causes protein in the urine and kidney damage over time, which is why his problems started young, at age 23.
Why it might work
Fabry disease is caused by a gene change that leaves the body short of an enzyme called alpha-galactosidase A. Without enough of it, a fatty substance builds up in cells, including in the kidneys, and slowly damages them. Enzyme replacement therapy gives the body a lab-made version of the missing enzyme, which helps clear that buildup across the body. In this case you can see that effect in the blood: the Lyso-Gb3 marker fell by 70.6%. But by the time he was treated, his kidneys were already badly harmed, so a new, healthy kidney from a transplant is what actually gave him stable kidney function again, while the enzyme therapy kept the underlying disease in check.
The honest limits
- This is a single person (Case 1 of a two-patient report), so it cannot tell you how often this result happens.
- The kidney improvement came from a transplant, not from a treatment most kidney patients could take, so it does not apply to people with stage 3 kidney disease who still have their own kidneys.
- Lyso-Gb3 is a blood marker of the disease, not a direct measure of kidney function, so its 70.6% drop does not by itself mean the kidneys got better.
- Kidney function was reported only as creatinine under 115 micromol/L, with no eGFR given, and follow-up stopped at age 34, so long-term results are unknown; the abstract also names the drug maker (Sanofi) but does not state its funding or conflict-of-interest details.
- I have my own kidneys and stage 3 kidney disease, so does a case built around a kidney transplant apply to me at all?
- Is there any reason to test me for Fabry disease or another genetic cause, given how this patient's kidney problems started young?
- If a treatment lowers a blood marker like Lyso-Gb3, how would we actually check whether my kidney function is improving?