Table 2.

Indicators for which consensus was achieved in PREDICT-FD

Current early indicators of damage
Kidney	Cardiac	PNS	Other	Patient reported
Elevated urine albumin:creatinine ratio*	Markers of early systolic/diastolic dysfunction†‡	Neuropathic pain†§	Pain in extremities/neuropathy¶	Febrile crises
Histological damage (kidney biopsy)*	Elevated serum cardiac troponin†	Painful gastrointestinal symptoms suggestive of gastrointestinal neuropathy related to FD†§	Stroke/transient ischaemic attack**	Patient-reported progression of symptoms/signs††
Microalbuminuria*†	Early indicators of left ventricular hypertrophy		Angiokeratoma	Angiokeratoma
Abnormal glomerular filtration rate	Early indicators of histological damage (heart biopsy)‡‡§§		Organ biopsy¶¶	(Neuro-otological abnormalities)***
Decline in iohexol glomerular filtration rate	Late gadolinium enhancement on cardiac MRI		Non-pain gastrointestinal symptoms (including diarrhoea/frequent diarrhoea) related to FD
Podocyte inclusions	Elevated serum N-terminal probrain natriuretic peptide†		Sweating abnormalities or heat/exercise intolerance
	Reduced myocardial T1 relaxation time on cardiac MRI
	Abnormal ECG‡,‡‡
	Abnormal echocardiogram†‡
	Abnormal wall motion on echocardiography
Early cardiac indicators of FD that may be used in future			Early indicators of FD subject to ongoing research
Reduced myocardial T1 relaxation time on cardiac MRI			Reduced quality of life
Elevated serum cardiac troponin†			High gastrointestinal symptom scores
Elevated serum N-terminal probrain natriuretic peptide†

*It was noted in round 4 that the prognostic significance of this indicator is different in male and female patients.

†It was noted in round 4 that a causal relationship between this indicator and FD is required to justify treatment initiation.

‡Including decreased myocardial strain and strain rate, tissue Doppler abnormalities, enlarged left atrium or pulmonary venous flow abnormalities on echocardiogram.

§Recategorised as PNS in round four because no indicators of CNS damage achieved consensus.

¶Including acroparaesthesias.

**Previously under ‘patient-reported indicators of FD’, recategorised in round 4 under ‘other early indicators of FD’ because such indicators would need to be confirmed clinically.

††Renamed ‘patient-reported progression of symptoms/signs’ from ‘symptom/sign progression’ in round 4.

‡‡Including a shortened PR interval, non-sustained ventricular tachycardia and symptomatic bradycardia.

§§Cardiac histological changes have been reported in FD, but cardiac biopsy is too invasive to be recommended.

¶¶Including skin biopsy for small-fibre neuropathy, and kidney and heart biopsy nominated in other categories.

***This indicator is included because it achieved consensus but was subsequently excluded in round 4. It refers to a cluster of indicators (vertigo, hearing loss and tinnitus) that did not achieve consensus individually.

†††Originally grouped under ‘patient-reported indicators of FD’; combined with ‘non-pain gastrointestinal symptoms’ under ‘other early indicators of FD’ in round 4.

‡‡‡Including bloating, pain, diarrhoea/frequent diarrhoea or constipation, that are causally related to FD.

CNS, central nervous system; PNS, peripheral nervous system; PREDICT-FD, PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease.