Plasma Porphyrins in Chronic Renal Failure

Abstract

Using a quantitative sensitive HPLC fluorometric assay for the measurement of plasma and urine porphyrins, we have calculated the renal clearance of uro- and coproporphyrin in normal volunteers and in patients with congenital erythropoietic porphyria and hereditary coproporphyria (HCP). In patients with porphyria cutanea tarda (PCT), only uroporphyrin clearance was calculated. Plasma porphyrin concentrations were measured in patients with chronic renal failure (CRF). All our CRF patients on haemodialysis (10) had raised plasma uroporphyrin, 4 had raised plasma heptacarboxyporphyrins and 2 had raised plasma coproporphyrin, unchanged by haemodialysis. CRF patients with raised uroporphyrins and 7-carboxyporphyrins could be distinguished from PCT in patients with normal renal function, by their higher uro/7-carboxyporphyrin ratio (8.0 vs. 1.7). Renal clearance of coproporphyrin was much greater in HCP than in any of the other groups studied. Since coproporphyrin clearance was less than creatinine clearance in most normal subjects, and because 2 patients with CRF had raised plasma coproporphyrin concentrations, we argue that the kidney is probably not a major source of coproporphyrin, as previously reported. Furthermore, the variability and degree of abnormality in plasma porphyrins in CRF would suggest caution in diagnosing chronic porphyria in patients with renal impairment.

Coproporphyrins in Plasma and Urine Can Be Appropriate Clinical Biomarkers to Recapitulate Drug-Drug Interactions Mediated by Organic Anion Transporting Polypeptide Inhibition

“…At predose, CP-I and CP-III amounts were about the same in human urine, and the ratio of CP-I over total CPs was close to that previously reported (0.29∼0.44) (Koskelo et al, , 1967Gebril et al, 1990) but different from the profiles in monkey, where CP-III was much higher than CP-I (Shen et al, 2016a). Urinary excretion of CP-I increased (3.6-fold) to a similar extent as that of CP-I AUC 0-24h (4.0-fold) after RIF treatment, as compared with RSV alone.…”

“…The result is consistent with the abnormal distribution of CP isomers reported in the urine of patients with Rotor syndrome (Ben-Ezzer et al, 1971;Wolkoff et al, 1976). RIF treatment appeared to decrease CL r of CP-III, suggesting involvement of renal transporters (Koskelo et al, , 1967Gebril et al, 1990). Although CP-III, but not CP-I, appeared to be transported by organic anion transporter 1 (Bednarczyk and Boiselle, 2015), further characterization of the transporter(s) responsible for active renal secretion of CP-III and its association with genetic polymorphism is necessary.…”

Coproporphyrins I and III as Functional Markers of OATP1B Activity: In Vitro and In Vivo Evaluation in Preclinical Species

“…Apparently, transporter-mediated tubular secretion accounts for most of the renal clearance of CP III in monkeys since the ER R value is significantly greater than unity (approximately 10-to 30-fold) (Tables 1 and 2). CP III constitutes the major form of CP excreted in normal urine in monkeys (Table 3), which has also been observed in humans (Koskelo et al, , 1967Gebril et al, 1990). The active tubular secretion was unlikely inhibited by RIF and slightly reduced by CsA in this study.…”

Decreased Uroporphyrinogen Decarboxylase Activity in Patients with End-Stage Renal Disease Undergoing Hemodialysis

“…Our results are in agree ment with those of other workers [2,5], One could, there fore, find the reports demonstrating normal plasma por phyrins in hemodialyzed patients with bullous dermatosis [10,11] contradictory. However, we believe that the dis crepancies are due to the method used for determining porphyrins in plasma.…”

“…The dimethyl sulfoxide (DMSO) method described by Gcbril et al [5] with slight modifica tions was used. Briefly, 1 ml plasma was mixed vigorously for 1 min with 0.36 ml DMSO.…”