RESUMEN
BACKGROUND: Calcific uremic arteriolopathy (CUA) is a rare complication in end stage renal disease with high mortality. Numerous case reports and one case series of 3 patients report the benefit of sodium thiosulfate (STS) for treatment of CUA. The purpose of this evaluation was to examine the response to a STS-based treatment approach in patients with CUA with 1 year follow up. METHODS: A retrospective case series of 6 consecutive patients from Manitoba, Canada who met predefined diagnostic criteria for CUA and received STS between 2006 and 2008 were included. STS responders were defined as improvement in at least one of the following three parameters: pain severity, wound size and diagnostic imaging/radiography. Mortality, STS dose, duration, adverse events and cost were also collected. RESULTS: Four patients were classified as responders. The 2 responders who survived at 1 year of follow-up demonstrated an improvement in all 3 parameters examined including an improvement in their follow-up diagnostic imaging results within the first 4 - 6 weeks of STS treatment. At 1 year of follow-up, 3 patients died. CONCLUSION: Using an STS-based multifaceted treatment approach for CUA, 4 patients responded but 3 of 6 patients died within 1 year. Further larger prospective studies are needed to delineate STS responders from non-responders.
Asunto(s)
Arteriopatías Oclusivas/tratamiento farmacológico , Calcifilaxia/tratamiento farmacológico , Fallo Renal Crónico/complicaciones , Tiosulfatos/uso terapéutico , Uremia/tratamiento farmacológico , Adulto , Arteriopatías Oclusivas/diagnóstico , Arteriopatías Oclusivas/etiología , Arteriopatías Oclusivas/mortalidad , Calcifilaxia/diagnóstico , Calcifilaxia/etiología , Calcifilaxia/mortalidad , Femenino , Humanos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Masculino , Manitoba , Persona de Mediana Edad , Dolor/etiología , Dolor/prevención & control , Diálisis Peritoneal , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Uremia/diagnóstico , Uremia/etiología , Uremia/mortalidad , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Calcitonin gene-related peptide (CGRP) is a potent vasodilator that is suggested to act via ATP-sensitive K channels (KATP). In the present study, we examined the actions of CGRP on pressure- and angiotensin II-induced vasoconstriction, using the in vitro perfused hydronephrotic rat kidney. Elevated pressure (from 80 to 180 mmHg) and 0.1 nM angiotensin II elicited similar decreases in afferent diameter in this model. CGRP inhibited myogenic reactivity in a concentration-dependent manner, completely preventing pressure-induced constriction at 10 nM (95 +/- 10% inhibition). These effects were partially attenuated by 10 microM glibenclamide (62 +/- 16% inhibition, P = 0.025), indicating both KATP-dependent and -independent actions of CGRP. In contrast, 10 nM CGRP inhibited angiotensin II-induced vasoconstriction by only 54 +/- 11%, and this action was not affected by glibenclamide (41 +/- 11%, P = 0.31). CGRP also inhibited the efferent arteriolar response to angiotensin II in the absence and presence of glibenclamide. Pinacidil (1.0 microM), a KATP opener also preferentially inhibited pressure- vs. angiotensin II-induced vasoconstriction (97 +/- 5 and 59 +/- 13% inhibition, respectively; P = 0.034). We conclude that the renal vasodilatory mechanisms of CGRP are pleiotropic and involve both KATP-dependent and -independent pathways. The effectiveness of CGRP in opposing renal vasoconstriction and the role of KATP in this action appear to depend on the nature the underlying vasoconstriction. We suggest that this phenomenon reflects an inhibition of KATP activation by angiotensin II.
Asunto(s)
Péptido Relacionado con Gen de Calcitonina/farmacología , Gliburida/farmacología , Riñón/irrigación sanguínea , Canales de Potasio/efectos de los fármacos , Vasoconstricción/efectos de los fármacos , Angiotensina II/antagonistas & inhibidores , Angiotensina II/farmacología , Animales , Arteriolas/efectos de los fármacos , Presión Sanguínea , Péptido Relacionado con Gen de Calcitonina/antagonistas & inhibidores , Hidronefrosis/fisiopatología , Masculino , Microcirculación/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , VasodilataciónRESUMEN
K+ channel openers (PCOs), such as pinacidil, elicit vasodilation primarily by hyperpolarization-induced inhibition of L-type Ca2+ channel activation. The physiological role of other mechanisms suggested to contribute to PCO-induced vasodilation is not well established. In the renal microcirculation, L-type Ca2+ channels play a prominent role in vasoconstriction of the afferent arteriole (AA) but are absent or physiologically silent in the efferent arteriole (EA). Thus, L-type Ca2+ channel-dependent and -independent mechanisms can readily be distinguished in this model. In the present study, we found that pinacidil potently inhibited Bay K 8644-induced AA vasoconstriction. Pinacidil also preferentially inhibited angiotensin II-induced AA vasoconstriction (approximately ninefold greater potency than EA). These results are consistent with an AA effect of pinacidil on L-type Ca2+ channel activation. Unexpectedly, 10 mumol/L pinacidil inhibited AA and EA responses to similar extents (84 +/- 10% and 71 +/- 9%, respectively). In both AAs and EAs, glibenclamide restored normal reactivity, indicating an involvement of the ATP-sensitive K+ channels. In the EA, however, pretreatment with diltiazem did not alter the effects of pinacidil. Nevertheless, 45 mmol/L KCl reversed the EA actions of pinacidil, indicating an essential requirement for a normal K+ gradient. These findings suggest that the EA actions of pinacidil involve alterations in membrane potential but not changes in L-type Ca2+ channel activity. Overall, our findings do support the premise that L-type Ca2+ channel modulation is involved in PCO-induced vasodilation in the renal microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS)