Heme biosynthesis in uremic patients on CAPD or hemodialysis

Abstract

We have analyzed some parameters of porphyrin metabolism in 60 patients with end-stage renal failure, 20 of them on CAPD and the remaining on HD. In comparison with 56 control subjects, both groups of patients showed the three following findings: low erythrocyte aminolevulinate dehydrase activity, inhibition ability for the activity of this enzyme when their plasma was incubated in vitro with normal erythrocytes, and increased plasma porphyrin levels. Like anemia, these abnormalities were more remarkable in patients on HD who also exhibited increased erythrocyte protoporphyrin levels and compensatory porphobilinogen deaminase activities. Mean weekly porphyrin removal through dialysate was higher in CAPD (90.8 micrograms) than in HD patients (30.4 micrograms). Dialysate and plasma porphyrins were correlated in both circumstances (r = 0.714, P < 0.01 and r = 0.637, P < 0.05, respectively). The less pronounced porphyrin abnormalities found in CAPD patients with respect to HD patients may be due to the more efficient capability of peritoneal dialysis for removing from plasma protein-bound substances, as porphyrins and inhibitors of aminolevulinate dehydrase or other enzymes involved in erythropoiesis. Since no close relationship was found between these abnormalities of porphyrin metabolism and hematocrit values, the anemia of uremia cannot be merely considered as a direct consequence of altered heme biosynthetic pathway.

Inhibition of Erythrocyte Aminolevulinate Dehydratase by a 56.2-kD Peptide from Uremic Plasma

“…This paper shows that plasma from HD patients inhibits the activity of human RBC ALA-D in vitro, in agreement with previous results [1, 3, 4, 5, 17]. Our data also indicate that inhibition occurs in a concentration-dependent manner.…”

“…The activity of aminolevulinate dehydratase (ALA-D) has been shown to be diminished in red blood cells (RBC) from hemodialyzed (HD) patients [1, 2]as well as in experimental CRF [3, 4, 5]. This decreased activity can be attributed to either reduced enzyme synthesis or inhibition.…”

“…Fontanellas et al [1, 3]have suggested the presence of one or more substances inhibiting ALA-D in plasma from patients with CRF as well as in plasma from dogs with experimental nontoxic acute renal failure. Moreover, since the authors had detected the same inhibitory ability in the plasma after dialysis, they hypothesized that the putative toxic molecular species are not dialyzable, either because they are tightly bound to large-size plasma proteins or because of their own molecular size.…”

Hiperpigmentação cutânea em pacientes com insuficiência renal crônica em hemodiálise infectados pelo vírus da hepatite C

“…É caracterizada clinicamente por hiperpigmentação cutânea difusa, fotosensibilidade com lesões vesicobolhosas, erosões ou raramente ulcerações em áreas fotoexpostas, fragilidade da pele, hipertricose e milia. As duas primeiras são as manifestações mais evidentes 7,10,11 . A PCT é causada por alterações na via de síntese de heme levando ao acúmulo de uroporfirinas altamente carboxiladas no plasma e na pele.…”

“…Essas proteínas absorvem a luz solar com subseqüente ativação de melanócitos, além de excitação e liberação de espécies oxigenadas reativas. Esses processos levariam ao surgimento da pigmentação e lesões na pele, como a formação de bolhas [9][10][11] . A expressão clínica da PCT requer a concordância da redução da atividade da enzima uroporfirinogênio decarboxilase (UROD) hepática e um fator ambiental precipitante.…”