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Table 1 Renal signs: guideline stipulations and PREDICT-FD consensus [11]

From: Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease?

 

Histological damage (kidney biopsy)

Podocyte inclusions

Proteinuria

Elevated urine ACR (including microalbuminuria)

Abnormal GFRa

Decline in iohexol GFR

Renal dialysis or transplant

PREDICT-FDb [11]

 + 

 + 

–

 + 

 + 

 + 

–

EFWGc [1]

No consensus

No consensus

M, I; F, IIB

M, I; F, IIB

CKD stage 2: cM, I; ncM, IIA; cF, IIA; ncF, IIB

CKD stage 3: cM, I; ncM, IIB; cF, IIB; ncF, IIB

–

Dialysis, do not withhold treatment

Transplant, NA

Australia [24]

Alld

–

M, > 150 mg/d

F, > 300 mg/d

Me,f > ULN

–

–

–

Canadag [21]

M, Fh

Renal pathology:

M, major criterion

F, minor criterion

All, ≥ 500 mg/di

All, ≥ 300 mg/di

–

All, CKD stage ≥ 2j

Decline in mGFR

All (considered CKD stage 5)

Catalonia (Spain)

–

–

All, > 300 mg/d

All

All, CKD stage ≥ 2k

–

All

Francel [23, 25]

F

–

F, > 1 g/d

–

F, moderate-to-severe

–

All

Portugal [22]

Confirmatory biopsy if needed, all asymptomatic

Confirmatory biopsy if needed, all asymptomatic

All

All

All, CKD stage ≥ 2

–

–

Slovenia (FCGHSG)

Confirmatory biopsy if needed in cF and in late-onset adultsm

–

All

All

All CKD

–

–

Switzerlandn

Fo

Fn

F, > 300 mg/dp

–

–

–

Alln

UKq [26]

–

–

All, > 300 mg/dr

–

All, CKD stage 2 and 3s

–

–

  1. Unpublished guidelines are summarized in Additional file 1: Table S1
  2. aCKD: stage 2, 60–90 mL/min/1.73 m2; stage 3, 45–60 mL/min/1.73 m2
  3. bConsensus was reached that FD-specific treatment should be initiated at diagnosis in male patients aged 16 years or older who are asymptomatic for organ involvement, in boys younger than 16 years old with early indicators of organ involvement, and in all patients with guideline indicators of organ involvement
  4. cRecommendations are based on class of evidence assigned: class I, treatment recommended or indicated; class IIA, treatment should be considered; class IIB, treatment may be considered; class III, treatment not recommended
  5. dIncluding disease due to long-term renal accumulation of glycosphingolipids
  6. eIn two samples separated by at least 1 day
  7. fIn male patients, guideline abnormal albumin threshold of > 20 µg/minute is approximately equivalent to the threshold for microalbuminuria (> 30 mg/d)
  8. gTreatment initiated based on one major or two minor criteria. Minor criteria not shown are renal tubular dysfunction and hypertension for at least 1 year
  9. hIf biopsy is indicated, glomerular sclerosis, tubulointerstitial atrophy, fibrosis, or vascular sclerosis constitute a major criterion in male patients and a minor criterion in female patients; biopsy not required for treatment initiation
  10. iMajor criterion: persistently ≥ 500 mg/d/1.73m2; minor criterion: ≥ 300 mg/d/1.73m2 in isolation or > normal and persisting for at least 1 year
  11. jMajor criterion: CKD stage 2 based on three consistent eGFRs over at least 4 months or stages 3–5 based on two consistent eGFRs over at least 2 months using CKD-EPI formula [27] in adults and the Counahan–Barrett formula [28] in children; also ≥ 15% decrease in GFR or slope greater than the age-related normal among those with hyperfiltration (GFR ≥ 135 mL/min/1.73 m2) determined by nuclear medicine techniques. Minor criterion: hyperfiltration in two measurements at least 1 month apart
  12. kReduced rate in at least three determinations by CKD-EPI equation [27]
  13. lAll male patients with a confirmed FD diagnosis should be offered ERT from age 18 years; ERT may be considered in children (6–18 years) with organic renal involvement
  14. mAlso if necessary in asymptomatic boys with a classical mutation
  15. nERT is practically always indicated in men, even those with mild symptoms and low organ involvement, and in patients undergoing hemodialysis or with a kidney transplant
  16. oRelevant, histologically proven Gb3 deposits in kidney or heart biopsies
  17. pRegardless of CKD stage
  18. qFD-specific therapy should be considered in male patients with classical mutations at diagnosis; tabulated additional considerations apply to male and female patients with later-onset disease
  19. rPersistent proteinuria > 300 mg/d in male patients; use anti-proteinuria medication for at least 12 months if proteinuria is the only presentation in female patients
  20. sCKD stage 2 based on three or more consistent GFR estimates over at least 12 months and GFR slope greater than the age-related normal; CKD stage 3 based on two or more consistent GFR estimates over at least 6 months
  21.  + , achieved consensus in PREDICT-FD; ACR, albumin–creatinine ratio; cF, female patient(s) with classical disease; cM, male patient(s) with classical disease; CKD, chronic kidney disease; CKD-EPI, CKD-Epidemiology Collaboration; d, day; EFWG, European Fabry Working Group; eGFR, estimated GFR; F, female patient(s); FCGHSG, Fabry Center, General Hospital Slovenj Gradec; FD, Fabry disease; Gb3, globotriaosylceramide; GFR, glomerular filtration rate; M, male patient(s); mGFR, measured GFR; ncF, female patient(s) with non-classical disease; ncM, male patient(s) with non-classical disease; NA, not available; ULN, upper limit of normal
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Orphanet Journal of Rare Diseases

ISSN: 1750-1172