Introduction:
Diagnosis of pheochromocytomas/paragangliomas in patients with chronic kidney disease (CKD) is troublesome.
Aims:
Establish optimum pre-analytical procedures for blood sampling for measurements of metanephrines and 3-methoxytyramine in patients receiving hemodialysis and optimized reference intervals for patients with stage III-IV CKD or receiving hemodialysis (HD).
Methods:
Blood was sampled before and after dialysis (including different sampling sites) in 30 patients receiving hemodialysis. Plasma concentrations of metanephrines and 3-methoxytyramine were also measured in 226 patients with CKD (79 stage III, 40 stage IV and 108 stage V) and compared to 173 subjects of an aged-matched reference population.
Results:
Among patients on hemodialysis, plasma normetanephrine concentrations were significant lower (P<0.0001) and metanephrine concentrations significantly higher (P<0.0001) in shunt than in venous blood, with no significant differences for 3-methoxytyramine. Normetanephrine, metanephrine and 3-methoxytyramine concentrations, both in shunt and venous blood, were lower at the end than before dialysis (P<0.0001). Compared with the reference population, upper cut-offs of reference intervals (97.5% percentiles) for normetanephrine, metanephrine and 3-methoxytyramine were respectively 14%, 22% and 41% higher in patients with stage III CKD and 34%, 21% and 75% higher in patients with stage IV CKD or HD. Due to the high concentrations of 3-methoxytyramine in patients with chronic kidney disease, CKD specific cut-offs were assessed only for metanephrines.
Conclusion:
These data establish optimized reference intervals for plasma metanephrines for patients with stage III-IV CKD or HD that are useful for minimizing false-positive results. In particular, using CKD-specific cut offs, it can be expected that the proportion of false positive results would fall from 7.6% to 2.5% for patients with stage III CKD and from 22.9% to 4% for stage IV CKD or HD. We also show that blood sampling in patients receiving hemodialysis is most appropriate at the end of hemodialysis and from the dialysis shunt.