RESUMEN
AIM: End-stage renal disease (ESRD) is often complicated by chronic inflammation and malnutrition. We tested whether serum tartrate-resistant acid phosphatase (TRACP) isoform 5a relates to other markers of inflammation in ESRD. MATERIAL: Predialysis serum was collected from 99 ESRD patients (51 male, 48 female) aged 55 +/- 15 years and a control group of 36 healthy subjects (8 male, 28 female) aged 43.2 +/- 10.5 years. METHODS: Serum TRACP 5a activity and protein, TRACP 5b activity and C-reactive protein (CRP) were estimated by in-house immunoassays. Commercial kits were used for serum bone-specific alkaline phosphatase, Ntelopeptides of Type I collagen, interleukin-6 (IL-6) and fetuin-A. Intact parathyroid hormone was determined by chemiluminescent assay. Albumin, cholesterol, triglycerides, ferritin and hemoglobin were compared to the hospital reference ranges. Bone mineral density (BMD) was measured at the heel in 69 patients and all control subjects and expressed as g/cm2 and age-corrected T-score. RESULTS: Mean (median) levels of all serum markers were significantly elevated in ESRD except fetuin-A, which was significantly reduced. Mean BMD (g/cm2) was not different than control, but mean T-score was significantly reduced. TRACP 5a protein correlated with CRP, triglycerides and ferritin, but not with IL-6 or any other nutritional or bone markers or BMD. TRACP 5b activity correlated with all bone markers and BMD, but not with inflammation or nutritional markers. CONCLUSION: Our findings suggest that TRACP 5a may be a useful marker to estimate the degree of inflammation in ESRD patients on chronic hemodialysis.
Asunto(s)
Fosfatasa Ácida/sangre , Isoenzimas/sangre , Fallo Renal Crónico/sangre , Adulto , Albúminas/metabolismo , Fosfatasa Alcalina/sangre , Biomarcadores/sangre , Densidad Ósea , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Colágeno Tipo I/sangre , Femenino , Humanos , Inflamación/sangre , Interleucina-6/sangre , Fallo Renal Crónico/terapia , Modelos Lineales , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Isoformas de Proteínas/sangre , Diálisis Renal , Estadísticas no Paramétricas , Fosfatasa Ácida Tartratorresistente , alfa-Fetoproteínas/metabolismoRESUMEN
The elderly are the fastest growing segment of the United States population. Age is a key predictor of chronic kidney disease (CKD). A major obstacle in the recognition of CKD in the elderly is the reliance on serum creatinine measurements as an estimation of glomerular filtration rate (GFR). We hypothesized that early stages of CKD would not be recognized by primary care clinicians providing care to elderly men in a highly structured setting. This study was a retrospective study of outpatients 70 years and older seen in VISN 9 at Veterans Administration Medical Centers from 1/1/2001 thru 12/31/2003. GFR was estimated using the MDRD formula. We abstracted demographic and medical data from the electronic medical record. The population consisted primarily of elderly white male (7,289 men; 91% Caucasian). In CKD Stage 2, 3, and 4, men had a diagnosis code reflecting kidney disease in 1.2%, 20%, and 74.6% of the charts. Despite declining kidney function, nephrology consults were requested in fewer than 5%. In summary, we have shown in a large outpatient population of elderly men that CKD is frequently under-recognized, but most pronounced in CKD Stages 2 and 3. Stages 2 and 3 may be the stages in which the most beneficial effects of interventions can be obtained.
Asunto(s)
Enfermedades Renales/diagnóstico , Anciano , Enfermedad Crónica , Humanos , Enfermedades Renales/epidemiología , Masculino , Estudios RetrospectivosRESUMEN
The objective of this study was to identify the isoform, type-5a or type-5b, responsible for increased tartrate-resistant acid phosphatase (TRAP) activity in endstage renal disease (ESRD) and TRAP protein in rheumatoid arthritis (RA). We studied 24 sera each from healthy, ESRD and RA subjects. Type-5 TRAP activity and protein were quantitated by immunoassays. Isoform expression was determined by computerized imaging of non-denaturing polyacrylamide gels (PAGE) stained for TRAP activity. Other biochemical markers included: intact parathyroid hormone (iPTH), total and bone-specific alkaline phosphatase (TAP, BAP), N-telopeptides of type-I collagen (NTx), and free pyridinoline (Pyd). Isoform 5a was normal in both ESRD and RA. Isoform 5b was elevated in ESRD only. Serum TRAP activity correlated with both isoforms 5a and 5b in RA, but only with 5b in ESRD. TRAP protein assays did not correlate with PAGE assays for 5a or 5b. TRAP activity, but not protein, correlated with BAP and NTx in RA sera. Both TRAP activity and protein correlated with iPTH, TAP and Pyd in ESRD sera. Increased TRAP activity in ESRD was due to increased osteoclastic isoform 5b and related to bone turnover. Increased TRAP protein in RA was suspected, but not proven, to be isoform 5a and not related to bone turnover. Heterogeneity of serum TRAP and preferential expression of isoforms has clinical significance in different diseases including ESRD and RA.
Asunto(s)
Fosfatasa Ácida/sangre , Artritis Reumatoide/sangre , Isoenzimas/sangre , Fallo Renal Crónico/sangre , Huesos/metabolismo , Electroforesis en Gel de Poliacrilamida , Humanos , Fosfatasa Ácida TartratorresistenteRESUMEN
The purpose of the present study was to determine the effect of protein kinase A and protein kinase C activation on the membrane expression of NaPi-4, the type II sodium-phosphate cotransporter in OK cells. NaPi-4 expression was measured using polyclonal antisera produced in rabbits against a peptide identical to the carboxy-terminal 12-amino acid sequence of NaPi-4. The antisera identified an apically localized protein by confocal imaging of intact OK cells and a broad band of 110-140 kDa by immunoblot analysis of OK cell membranes. Treatment of OK cells with parathyroid hormone (PTH) decreased the intensity of the 110- to 140-kDa band, which was detectable by 2 h, maximal by 4 h at 62%, and sustained for 24 h. 8-Bromo-cAMP (8-BrcAMP) inhibited NaPi-4 expression for up to 24 h by over 90%. However, phorbol 12-myristate 13-acetate inhibited NaPi-4 expression by less than 10%. PTH-(3-34), a fragment which stimulates only protein kinase C, inhibited phosphate transport but also had no effect on NaPi-4 expression. We conclude that protein kinase A but not protein kinase C inhibits sodium-phosphate uptake in OK cells by downregulation of NaPi-4 expression.
Asunto(s)
Proteínas Portadoras/genética , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Regulación de la Expresión Génica , Riñón/metabolismo , Proteína Relacionada con la Hormona Paratiroidea , Proteína Quinasa C/metabolismo , Simportadores , 8-Bromo Monofosfato de Adenosina Cíclica/farmacología , Secuencia de Aminoácidos , Animales , Anticuerpos , Proteínas Portadoras/biosíntesis , Línea Celular , Membrana Celular/fisiología , Proteína Quinasa Tipo II Dependiente de AMP Cíclico , Activación Enzimática , Regulación de la Expresión Génica/efectos de los fármacos , Immunoblotting , Cinética , Zarigüeyas , Hormona Paratiroidea/farmacología , Hormona Paratiroidea/fisiología , Fragmentos de Péptidos/química , Fragmentos de Péptidos/inmunología , Fragmentos de Péptidos/farmacología , Fosfatos/metabolismo , Proteínas/farmacología , Conejos , Proteínas Cotransportadoras de Sodio-Fosfato , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo II , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
The purpose of this study was to determine the mechanisms of dopamine regulation of phosphate uptake in opossum kidney (OK) cells, a model of proximal renal tubules. Dopamine stimulated cAMP generation and inhibited radiolabeled phosphate uptake into OK cell monolayers by 14.4 +/- 1.8%. The effect of dopamine was transient, as phosphate uptake returned toward control level by 3 h despite the continued presence of dopamine. Pretreatment with pertussis toxin increased dopamine inhibition of phosphate uptake to 25 +/- 3%, increased the duration of the dopamine effect to at least 3 h, and enhanced cAMP generation. In an OK cell clone that overexpressed cAMP phosphodiesterase, dopamine did not inhibit phosphate uptake, but pharmacologic inhibition of protein kinase A activation did not prevent dopamine inhibition of phosphate uptake. A DA1 receptor agonist inhibited phosphate uptake more potently than dopamine (29.5 +/- 1.1%) or a DA2 receptor agonist (7.9 +/- 2%). However, both DA1 and DA2 receptor antagonists completely blocked dopamine inhibition of phosphate uptake. DA1, but not the DA2, antagonists blocked dopamine-stimulated cAMP generation. Treatment with alpha-adrenergic receptor antagonists potentiated dopamine inhibition of phosphate uptake to the same extent as pertussis toxin and was not additive with pertussis toxin. It is concluded that dopamine inhibits phosphate uptake through DA1 and DA2 receptor stimulation by cAMP-dependent and -independent pathways and activates a pertussis toxin-sensitive counter-regulatory pathway that attenuates this response through alpha-adrenergic receptor stimulation.
Asunto(s)
Dopamina/fisiología , Riñón/metabolismo , Fosfatos/farmacocinética , Receptores Adrenérgicos alfa/fisiología , Receptores de Dopamina D1/fisiología , Receptores de Dopamina D2/fisiología , 3',5'-AMP Cíclico Fosfodiesterasas/metabolismo , Antagonistas Adrenérgicos alfa/farmacología , Animales , Células Cultivadas , AMP Cíclico/biosíntesis , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Dopamina/farmacología , Antagonistas de Dopamina/farmacología , Inhibidores Enzimáticos/farmacología , Riñón/citología , Riñón/efectos de los fármacos , Zarigüeyas , Toxina del Pertussis , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D2/agonistas , Factores de Virulencia de Bordetella/farmacologíaRESUMEN
Hypoxemia can be an early life-threatening complication of orthotopic heart transplantation. Commonly, hypoxemia after orthotopic heart transplantation is due to pulmonary hypertension or pulmonary complications. Rarely, structural defects either in the donor or recipient heart can lead to life-threatening hypoxemia. This case illustrates hypoxemia after orthotopic heart transplantation caused by the development of a right-to-left shunt through a patent foramen ovale in the recipient which had preoperatively been hemodynamically insignificant. The refractory hypoxemia required emergency surgical correction of the patent foramen ovale within the first postoperative week. In addition, this case illustrates the unique application of different methods of echocardiograms providing noninvasive diagnosis of structural defects in orthotopic heart transplantation.
Asunto(s)
Ecocardiografía Transesofágica , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interatrial/diagnóstico por imagen , Trasplante de Corazón/efectos adversos , Hipoxia/etiología , Adulto , Femenino , Defectos del Tabique Interatrial/cirugía , HumanosRESUMEN
The oxidative burst of neutrophils from azotemic patients (AzoPMNs) is primed for an enhanced response compared to neutrophils from normal subjects (NorPMNs). The mechanism for this priming is unknown, although TNF alpha does not further prime AzoPMNs. The present study examines the hypothesis that azotemia and TNF alpha prime neutrophils by the same mechanism. Formyl peptide receptor expression and degranulation were not primed in AzoPMNs, but were primed by both LPS and TNF alpha. LPS was also able to prime the AzoPMN oxidative burst. Guanine nucleotide exchange by multiple guanine nucleotide binding proteins, including heterotrimeric G-proteins and low molecular weight GTP-binding proteins (LMWGs), was increased in AzoPMNs, as demonstrated by GTP gamma S binding and azidoanilide GTP photoaffinity labeling. The plasma membrane density of G-protein alpha i2, alpha i3, and alpha s subunits and the density in the cytosol of the LMWG, Rap1A, was present in significantly greater amounts on plasma membranes from AzoPMNs. FMet-Leu-Phe-stimulated phospholipase D activity, but not basal activity, was significantly greater in AzoPMNs. Finally, incubation of NorPMNs in plasma from azotemic patients resulted in a significant increase in basal GTP gamma S binding. These results demonstrate that priming of AzoPMNs is restricted to oxidative burst activity and that it occurs by a mechanism distinct from that utilized by TNF alpha and LPS. While the exact mechanism remains unknown, it appears to involve a plasma factor and changes in LMWG expression or activity.
Asunto(s)
Lipopolisacáridos/farmacología , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Estallido Respiratorio/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Uremia/metabolismo , Adulto , Anciano , Degranulación de la Célula/efectos de los fármacos , Proteínas de Unión al GTP/metabolismo , Humanos , Técnicas In Vitro , Persona de Mediana Edad , N-Formilmetionina Leucil-Fenilalanina/farmacología , Fagocitosis/efectos de los fármacosRESUMEN
Purinergic P2 receptors are present on proximal renal tubules, but their function is unknown. Because P2 agonists antagonize vasopressin-stimulated water transport in the distal tubule by inhibiting activation of adenylyl cyclase, we postulated that P2 receptor activation blocks parathyroid hormone (PTH) inhibition of phosphate uptake in proximal tubule by preventing PTH-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation. PTH inhibition of sodium-dependent phosphate uptake was attenuated by alpha,beta-methylene-ATP (AMP-CPP), a P2x receptor agonist, but not by 2-methyl-thio-ATP, a P2y receptor agonist, in a dose-dependent manner. AMP-CPP did not attenuate inhibition of phosphate uptake produced by direct activation of adenylyl cyclase with forskolin, by addition of the cAMP analogue 8-bromo-cAMP, or by inhibition of cAMP phosphodiesterase with RO-20-1724. Additionally, AMP-CPP had no effect on basal or PTH-stimulated cAMP production. As PTH also stimulates protein kinase C activation, the effect of AMP-CPP on inhibition of phosphate uptake stimulated by phorbol 12-myristate 13-acetate (PMA) was tested. AMP-CPP had no effect on PMA-induced inhibition of phosphate uptake. Pretreatment with pertussis toxin abolished the attenuating effect of AMP-CPP on PTH inhibition of sodium-dependent phosphate uptake. We conclude that activation of purinergic P2 receptors attenuates the inhibitory effect of PTH on sodium-dependent phosphate uptake by a G protein-dependent mechanism that is independent of cAMP generation protein kinase A activation, or protein kinase C activation.
Asunto(s)
Proteínas de Unión al GTP/fisiología , Riñón/metabolismo , Hormona Paratiroidea/farmacología , Fosfatos/antagonistas & inhibidores , Receptores Purinérgicos/fisiología , Adenosina Trifosfato/análogos & derivados , Adenosina Trifosfato/farmacología , Toxina de Adenilato Ciclasa , Animales , AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Activación Enzimática , Riñón/citología , Zarigüeyas , Toxina del Pertussis , Fosfatos/farmacocinética , Proteína Quinasa C/metabolismo , Agonistas Purinérgicos , Sodio/fisiología , Factores de Virulencia de Bordetella/farmacologíaRESUMEN
The hypothesis that carboxylmethylation of gamma subunits plays a role in G protein activation was tested by examining the ability of N-acetyl-S-farnesyl-L-cysteine (AFC) and its methyl ester (AFC-ME) to inhibit G protein-mediated signalling in intact HL-60 granulocytes and isolated HL-60 plasma membranes. Incubation of HL-60 granulocytes with AFC or AFC-ME inhibited superoxide release stimulated by fMet-Leu-Phe, but not by opsonized bacteria. AFC-ME, but not AFC, inhibited NaF- and PMA-stimulated superoxide release. Addition of AFC to HL-60 membranes inhibited fMet-Leu-Phe-, leukotriene B4- (LTB4) and C5a-stimulated GTP gamma S binding and GTP hydrolysis more potently than it inhibited basal guanine nucleotide exchange. AFC-ME inhibited basal- and ligand-stimulated G protein activation with equal potency, but less potently than AFC. AFC also inhibited mastoparan-stimulated GTP gamma S binding. Binding of fMet-Leu-Phe and LTB4 to HL-60 membranes was completely inhibited by AFC, while AFC-ME inhibited ligand binding by less than 50%. Neither AFC nor AFC-ME inhibited pertussis toxin or cholera toxin-catalysed ADP-ribosylation of alpha i. It was concluded that AFC interrupts signal propagation in G protein-dependent pathways by multiple mechanisms, including inhibition of ligand-receptor interactions, of receptor-G protein coupling and of guanine nucleotide binding to G proteins. Carboxylmethylation alters the specificity of AFC interruption of signal propagation in intact cells and isolated membranes.
Asunto(s)
Acetilcisteína/análogos & derivados , Células Quimiorreceptoras/metabolismo , Proteínas de Unión al GTP/metabolismo , Granulocitos/metabolismo , Acetilcisteína/farmacología , Proteínas Bacterianas , Línea Celular , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Células Cultivadas , Ésteres , Granulocitos/efectos de los fármacos , Guanosina 5'-O-(3-Tiotrifosfato)/antagonistas & inhibidores , Guanosina 5'-O-(3-Tiotrifosfato)/metabolismo , Guanosina Trifosfato/antagonistas & inhibidores , Guanosina Trifosfato/metabolismo , Humanos , Leucotrieno B4/antagonistas & inhibidores , Leucotrieno B4/metabolismo , N-Formilmetionina Leucil-Fenilalanina/antagonistas & inhibidores , N-Formilmetionina Leucil-Fenilalanina/metabolismo , Transducción de Señal/efectos de los fármacos , Superóxidos/metabolismoRESUMEN
The role of G protein gamma subunit carboxylmethylation was examined in HL-60 granulocytes using an inhibitor of S-adenosylmethionine-dependent methylation, periodate-oxidized adenosine (Adox). A 40-60% reduction in gamma subunit carboxyl-methylation was associated with attenuation of fMet-Leu-Phe-stimulated GTP gamma S binding and GTP hydrolysis, while plasma membrane density of formyl peptide receptors, alpha i2, alpha i3, beta, gamma 5, and gamma 7 were not reduced. Reduced pertussis toxin-catalyzed ADP-ribosylation was re-established by in vitro methylation or addition of transducin beta gamma subunits. Superoxide release and inositol phosphate generation stimulated by fMet-Leu-Phe were significantly inhibited by Adox treatment. Carboxylmethylation contributes to transmembrane signalling and functional responses by enhancing association of alpha and beta gamma subunits.
Asunto(s)
Proteínas de Unión al GTP/metabolismo , Receptores Inmunológicos/metabolismo , Receptores de Péptidos/metabolismo , S-Adenosilmetionina/metabolismo , Adenosina/química , Adenosina Difosfato Ribosa/metabolismo , Guanosina Trifosfato/metabolismo , Humanos , Técnicas In Vitro , N-Formilmetionina Leucil-Fenilalanina/metabolismo , Oxidación-Reducción , Ácido Peryódico/química , Toxina del Pertussis , Receptores de Formil Péptido , Transducción de Señal , Superóxidos/metabolismo , Células Tumorales Cultivadas , Factores de Virulencia de Bordetella/farmacologíaRESUMEN
The role of isoprenylation in formyl peptide receptor-mediated G protein activation was studied using plasma membranes isolated from normal HL-60 granulocytes and from cells in which isoprenylation was inhibited with mevastatin. Plasma membrane expression of formyl peptide receptors and G protein beta subunits, but not alpha i2 and alpha i3, was significantly reduced by inhibition of isoprenylation. This reduced expression resulted in impaired basal and fMet-Leu-Phe-stimulated G protein activation.
Asunto(s)
Proteínas de Unión al GTP/metabolismo , Granulocitos/metabolismo , N-Formilmetionina Leucil-Fenilalanina/farmacología , Receptores Inmunológicos/metabolismo , Receptores de Péptidos/metabolismo , Adenosina Difosfato Ribosa/metabolismo , Anticolesterolemiantes/farmacología , Membrana Celular/metabolismo , Toxina del Cólera/metabolismo , Toxina del Cólera/farmacología , Proteínas de Unión al GTP/aislamiento & purificación , Guanosina 5'-O-(3-Tiotrifosfato)/metabolismo , Guanosina 5'-O-(3-Tiotrifosfato)/farmacología , Guanosina Trifosfato/metabolismo , Humanos , Cinética , Lovastatina/análogos & derivados , Lovastatina/farmacología , Sustancias Macromoleculares , NAD/metabolismo , Receptores de Formil Péptido , Receptores Inmunológicos/efectos de los fármacos , Receptores de Péptidos/efectos de los fármacos , Células Tumorales Cultivadas , Factores de Virulencia de Bordetella/metabolismo , Factores de Virulencia de Bordetella/farmacologíaRESUMEN
The hypothesis that protein kinase C (PKC) participates in agonist-mediated desensitization of formyl peptide receptors in HL-60 granulocytes was tested. fMet-Leu-Phe and leukotriene B4(LTB4) produced homologous desensitization of agonist-stimulated intracellular calcium transients. Pre-treatment with the PKC activator, phorbol myristate acetate (PMA; 10 nM), abolished both fMet-Leu-Phe and LTB4-stimulated calcium transients. Membranes prepared from control HL-60 granulocytes (NM) or cells treated with 10 nM PMA (PMA-M) demonstrated increased formyl peptide receptor and G protein density, as determined by radioligand binding and pertussis toxin- and cholera toxin-catalysed ADP ribosylation. fMet-Leu-Phe stimulation of guanosine 5'-[gamma-thio]-triphosphate (GTP gamma S) binding and GTP hydrolysis and GDP inhibition of fMet-Leu-Phe binding were not different between NM and PMA-M. Pre-treatment with 10 nM PMA did not inhibit subsequent fMet-Leu-Phe-stimulated superoxide generation or phospholipase D activation. We conclude that PKC desensitizes fMet-Leu-Phe-stimulated phospholipase C, but not phospholipase D, responses and that PKC activation does not mediate agonist-induced desensitization of formyl peptide receptors.
Asunto(s)
Calcio/metabolismo , Proteínas de Unión al GTP/metabolismo , Proteínas de la Membrana/metabolismo , Fosfolipasa D/fisiología , Proteína Quinasa C/metabolismo , Receptores Inmunológicos/metabolismo , Receptores de Péptidos/metabolismo , Autorradiografía , Línea Celular , Activación Enzimática/fisiología , Proteínas de Unión al GTP/genética , Granulocitos/metabolismo , Leucotrieno B4/farmacología , N-Formilmetionina Leucil-Fenilalanina/análogos & derivados , N-Formilmetionina Leucil-Fenilalanina/farmacología , Fosforilación , Receptores de Formil Péptido , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
Despite the large number of organ transplants performed yearly, to date there have been no reports of candidal splenic abscess. We describe here the first case of candidal splenic abscess in a renal transplant recipient treated successfully by splenectomy and amphotericin B. Despite a lengthy illness, the patient recovered with preservation of renal function.
Asunto(s)
Absceso/etiología , Candidiasis/etiología , Trasplante de Riñón , Enfermedades del Bazo/etiología , Absceso/patología , Absceso/cirugía , Anfotericina B/uso terapéutico , Candidiasis/patología , Candidiasis/cirugía , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Enfermedades del Bazo/patología , Enfermedades del Bazo/cirugíaRESUMEN
Hyperlipidemia, particularly hypercholesterolemia, occurs in cardiac transplant recipients both as a preexisting condition and as a consequence of immunosuppressive therapy. Lovastatin (Mevacor) has emerged as an agent that may effectively manage this condition. Few serious side effects of this drug have been observed. We describe two cardiac transplant recipients treated with lovastatin in conjunction with their other medications, including cyclosporine, who developed acute renal failure and rhabdomyolysis. Resolution of muscle damage followed discontinuation of cyclosporine and lovastatin therapy. We postulate that hepatic dysfunction secondary to cyclosporine predisposed these patients to lovastatin-induced muscle damage. Use of this drug in cardiac and other organ transplant recipients should be accompanied by close surveillance of creatine kinase, hepatic transaminases, and cyclosporine levels.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , Hipercolesterolemia/tratamiento farmacológico , Lovastatina/efectos adversos , Rabdomiólisis/inducido químicamente , Lesión Renal Aguda/complicaciones , Adulto , Creatina Quinasa/sangre , Trasplante de Corazón , Humanos , Legionelosis/complicaciones , Lovastatina/uso terapéutico , Masculino , Persona de Mediana Edad , Rabdomiólisis/complicacionesRESUMEN
The classic proposal of intracellular K+ for extracellular H+ exchange as responsible for the hyperkalemia of diabetic ketoacidosis (DKA) has been questioned because experimentally induced organic anion acidosis fails to produce hyperkalemia. It has been suggested, instead, that the elevated serum [K+] of DKA might be the result of the compromised renal function, secondary to volume depletion, that usually accompanies DKA. However, several metabolic derangements other than volume depletion and acidosis, which are known to alter potassium metabolism, also develop in DKA. This study of 142 admissions for DKA examines the possible role of alterations in plasma pH, bicarbonate, glucose (G), osmolality, blood urea nitrogen (BUN) and plasma anion gap (AG) on the levels of [K+]p on admission. Significant (p less than 0.01) correlations of [K+]p with each of these parameters were found that could individually account for 8 to 15 percent of the observed variance in the plasma potassium levels; however, the effects of some or all of these parameters on the [K+]p could be independent and therefore physiologically additive. Since the parameters under study are themselves interrelated, having statistically significant correlations with each other, their possible independent role on [K+]p was evaluated by multiple regression analysis. Only plasma pH, glucose and AG emerged as having a definite independent effect on [K+]p, with no independent role found for bicarbonate, BUN and osmolality. The equation that best describes [K+]p on admission for DKA was: [K+]p = 25.4 - 3.02 pH + 0.001 G + 0.028 AG, (r = 0.515). These results indicate that the endogenous ketoacidemia and hyperglycemia observed in DKA, which result primarily from insulin deficit, are the main determinants of increased [K+]p. Since exogenous ketoacidemia and hyperglycemia in the otherwise normal experimental animal do not increase [K+]p, it is postulated that insulin deficit itself may be the major initiating cause of the hyperkalemia that develops in DKA. Renal dysfunction by enhancing hyperglycemia and reducing potassium excretion also contributes to hyperkalemia.