RESUMEN
BACKGROUND: Cyanate formed spontaneously from urea carbamoylates non-protonated amino groups of protein, irreversibly altering function, charge and structure. Carbamoylated proteins in renal tissue have not been examined hitherto. OBJECTIVES: To identify homocitrulline (epsilon-amino-carbamoyl-lysine), a result of in vivo carbamoylation by urea-derived cyanate, from patients with renal disease or in newly transplanted kidneys by immunohistochemistry. To evaluate enzymatic activity of carbamoylated and non-carbamoylated matrix metalloproteinase-2 and correlate this with renal tissue carbamoylated in vivo. DESIGN: Anti-homocitrulline antibody is specific for homocitrulline and was used to identify carbamoylation of epsilon-amino-lysine in renal biopsies from patients with elevated BUN, with isolated proteinuria, and as controls, from normal donors at time of transplantation. Enzymatic activity of matrix metalloproteinase-2 carbamoylated in vitro was evaluated. RESULTS: Homocitrulline was present in glomerular basement membrane (8/10), mesangium (8/10), tubular epithelium and cytoplasm (7/10) and Bowman's capsule (1/10) in patients with elevated BUN. The discordant patterns of glomerular and tubular localization of homocitrulline versus immune complexes indicated that the carbamoylated proteins were not a component of immune deposits but were modified proteins in renal tissue. No homocitrulline was found in transplanted kidneys (14/15) or in proteinuric patients (2/2). Enzymatic activity of both human and rat matrix metalloproteinase-2 was strongly inhibited in a dose-dependent fashion when incubated with cyanate. CONCLUSIONS: In situ carbamoylation in proteins occurred in kidneys of patients with renal dysfunction but not in normal newly transplanted kidneys. Decreased enzymatic activity of carbamoylated enzymes may alter specific renal regulatory mechanisms. Carbamoylated proteins with altered function and charge may represent a previously underestimated mechanism in renal pathophysiology.
Asunto(s)
Citrulina/análogos & derivados , Citrulina/metabolismo , Fallo Renal Crónico/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Aminoácidos/metabolismo , Animales , Carbamatos , Cianatos/metabolismo , Cianatos/farmacología , Progresión de la Enfermedad , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica , Fallo Renal Crónico/terapia , Trasplante de Riñón , Microscopía Fluorescente , Proteínas/metabolismo , RatasRESUMEN
Cyanate spontaneously transformed from urea increases as renal function decreased. Acting as a potential toxin, the active form of cyanate, isocyanic acid, carbamoylates amino acids, proteins, and other molecules, changing their structure, charge, and function. The resulting in vivo carbamoylation can modify the molecular activity of enzymes, cofactors, hormones, low-density lipoproteins, antibodies, receptors, and transport proteins. Antibodies specific for epsilon-amino-carbamoyl-lysine (homocitrulline) located carbamoylated proteins in situ in neutrophils, monocytes, and erythrocytes. Carbamoylated proteins were found in renal tissue from uremic patients but not in normal transplanted kidneys. The irreversible reaction with cyanate converts free amino acids (F-AAs) to carbamoyl-amino acids (C-AAs). The Carbamoylation Index (CI), C-AA/F-AA, quantifies the decrease of the F-AA pool for each essential amino acid. C-AAs contribute, in part, to malnutrition of uremia. C-AAs interfered with protein synthesis to lower 14C hemoglobin synthesis in human reticulocytes and osteocalcin synthesis in rat osteosarcoma-derived tissue culture. Insulin-sensitive glucose uptake was decreased 33% in cultured rat adipocytes by alpha-amino-carbamoyl-asparagine. alpha-Amino carbamoylation occurs primarily in F-AA, while epsilon-amino carbamoylation of lysine in protein occurs continuously during the protein life span. Protein catabolism releases epsilon-amino-carbamoyl-lysine. Quantitation of alpha versus epsilon carbamoylation may yield a more sensitive measurement of protein intake versus protein catabolism, and could be useful in decisions concerning the time to initiate dialysis or subsequent changes in dialysis prescription. Carbamoylated molecules can block, enhance, or be excluded from metabolic pathways, thereby influencing the fate of noncarbamoylated molecules. Although not an "all-or-none" phenomenon, urea-derived cyanate and its actions are contributing causes of toxicity in uremia.
Asunto(s)
Aminoácidos/metabolismo , Proteínas/metabolismo , Uremia/metabolismo , Animales , Carbamatos/metabolismo , Cianatos/metabolismo , Nefropatías Diabéticas/metabolismo , Enzimas/metabolismo , Glucosa/metabolismo , Hormonas/metabolismo , Humanos , Insulina/metabolismo , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/terapia , Lipoproteínas LDL/metabolismo , Diálisis Renal , Toxinas Biológicas/metabolismoRESUMEN
Urea and cyanate, spontaneously transformed from urea, are increased with decreased renal function becoming potential toxins. Isocyanic acid, the active form of cyanate, carbamoylates proteins, amino acids and other molecules, changing molecular structure and function in vivo. Carbamoylation can occur at multiple sites with a cumulative effect over the the life-span of the molecule. Carbamoylation converts free amino acids to carbamoyl-amino acids (C-AA). C-AA interfere with protein synthesis and transamination reactions and contribute, in part, to protein-malnutrition. Insulin-sensitive glucose uptake is decreased by carbamoyl-asparagine. Cyanate inhibits superoxide release from neutrophils to an extent that interferes with microbiocidal activity. Antihomocitrulline antibodies identified homocitrulline (epsilon-amino-carbamoyl lysine) in situ in proteins in neutrophils in end stage renal disease. Also in uremic patients, homocitrulline was located in proteins in renal tissue but was not found in normal transplanted kidneys. Carbamoylated human low density lipoprotein interferes with human receptor binding, has decreased clearance, and is auto-immunogenic in animals. Carbamoylated insulin has decreased biological activity and changed immunological reactivity. Carbamoylation at a site of molecular activity can affect molecular function of enzymes, co-enzymes, antibodies, hormones and receptors. Carbamoyl-molecules can block, enhance, or be excluded from metabolic pathways, and can affect binding and trafficking, thereby influencing the fate of non-carbamoylated molecules. Normal renal function removes C-AA. In uremia, C-AA are removed by residual renal function or dialysis. Toxicity of cyanate is not an "all or none" phenomenon, but the actions of cyanate are a contributing factor in uremia. Removal of urea, cyanate and carbamoyl-molecules partially alleviates the morbidity and mortality of renal disease.
Asunto(s)
Aminoácidos/sangre , Proteínas Sanguíneas/metabolismo , Cianatos/sangre , Toxinas Biológicas/sangre , Urea/sangre , Uremia/fisiopatología , Tasa de Filtración Glomerular , HumanosRESUMEN
Carbamoyl-amino acids (C-AA) are formed by reaction of amino acids with cyanate, which is spontaneously formed from urea at body temperature and pH. In vivo derivatized C-AA are not measured by the usual amino acid analysis methods, which require a free amino group for derivatization. Free-amino acids (F-AA) but no C-AA were found in the postabsorptive plasma of eight normal persons with blood urea nitrogen (BUN) levels ranging from 9 to 16 mg/dl. In a longitudinal study of postprandial plasma (n=43), essential amino acids, both C-AA and F-AA, were isolated and quantified by reverse-phase high-pressure liquid chromatography in six patients with end-stage renal disease who were managed by continuous ambulatory peritoneal dialysis. The mean BUN was 61 mg/dl (range, 36 to 79 mg/dl). In uremia, removal of F-AA from the essential amino acid pool to form C-AA is measured by the ratio of C-AA to F-AA (carbamoylation index (CI)). Using the mean value for each essential amino acid, the CIs were as follows: leucine, 4; valine, 3.3; isoleucine, 11.4; threonine, 9; lysine, 2; methionine, 3.5; histidine, 3.5; phenylalanine, 0.5; and tyrosine, 1.3. Carbamoylation of F-AA may account, in part, for the lower than normal levels of F-AA in patients with uremia. The derivatized amino group of C-AA interferes with formation of a peptide bond in protein synthesis, which requires an underivatized amino acid. A decrease in the F-AA pool available for protein synthesis and anabolism in the presence of C-AA may provide additional contributing factors for the development of malnutrition in uremia.
Asunto(s)
Aminoácidos/metabolismo , Cianatos/metabolismo , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/terapia , Diálisis Peritoneal Ambulatoria Continua , Adulto , Aminoácidos/sangre , Aminoácidos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Ingestión de Alimentos/fisiología , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Losses of nutrients into dialysate may contribute to malnutrition. Peritoneal dialysis (PD) patients are reported to lose 3-4 g/day of amino acids (AAs) and 4-15 g/day of proteins. The extent to which one exchange with a 1.1% AA dialysis solution (Nutrineal, Baxter, Deerfield, IL, U.S.A.) offsets these losses was investigated in a 3-day inpatient study in 20 PD patients. DESIGN: Simple, open-label, cross-over study on consecutive days in a clinical research unit. On day 1 all patients were given a peritoneal equilibration test (PET). On day 2 they received 1.5% dextrose Dianeal (Baxter) as the first exchange of the day and their usual regimen thereafter. On day 3, the first exchange of the day was the 1.1% AA solution in place of 1.5% Dianeal and the usual PD regimen thereafter. On days 2 and 3 all dialysate effluent was collected and analyzed for AAs and proteins. Patients were maintained on a constant diet. RESULTS: Losses of AAs and total proteins on day 2 were 3.4 +/- 0.9 g and 5.8 +/- 2.4 g, respectively, totaling 9.2 +/- 2.7 g. The net uptake of AAs on day 3 was 17.6 +/- 2.6 g (80 +/- 12% of the 22 g infused). Mean gains of AAs on day 3 exceeded losses of proteins and AAs on day 2, p < 0.001. Losses of total proteins, but not losses of AAs, and the net absorption of AAs from the dialysis solution were correlated directly with peritoneal membrane transport characteristics, obtained from the PET. CONCLUSION: Daily losses of AAs and proteins into dialysate are more than offset by gains of AAs absorbed from one exchange with 1.1% AA-based dialysis solution. Net gains of AAs exceeded losses of proteins and AAs in all patients studied. The difference was relatively constant across a wide range of membrane transport types. Net AA gains were approximately two times the total AA and protein losses.
Asunto(s)
Aminoácidos/uso terapéutico , Soluciones para Diálisis , Diálisis Peritoneal/métodos , Deficiencia de Proteína/tratamiento farmacológico , Adulto , Anciano , Transporte Biológico/efectos de los fármacos , Creatinina/metabolismo , Estudios Cruzados , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Diálisis Peritoneal/efectos adversos , Deficiencia de Proteína/etiologíaRESUMEN
Carbamoylated proteins have been located by using a site-specific polyclonal antihomocitrulline antibody and a fluorescent secondary antibody in leukocytes from patients with end-stage renal disease who were undergoing maintenance continuous ambulatory peritoneal dialysis. A covalent reaction with urea-derived cyanate and the epsilon-amino group of lysine forms homocitrulline residues in carbamoylated proteins. Isocyanic acid, the reactive form of cyanate, is spontaneously formed from urea in aqueous solution at physiologic pH and temperature. In washed, fixed monolayers of cells, an intracellular fluorescent antigen-antibody complex was located throughout the cytoplasm of polymorphonuclear neutrophils (PMNs) and monocytes from 11 patients with blood urea nitrogen (BUN) levels ranging from 32 to 102 mg/dl who were undergoing dialysis for 2 to 135 months. A punctate fluorescence present in the cell surface proteins of living cells demonstrated that lysine residues in the external domain of proteins were carbamoylated, forming homocitrulline. In contrast, we found a perinuclear fluorescence in PMNs in normal subjects with no history of renal insufficiency and BUN levels of 6 to 19 mg/dl. This suggests that homocitrulline is located in carbamoylated proteins within the perinuclear membrane, a structural organelle continuous with the endoplasmic reticulum. It appears that continuous exposure to urea-derived cyanate in low levels results in increasing carbamoylation of stable proteins over the PMN's lifetime. When normal PMNs were exposed to 120 mmol/L cyanate ion in vitro for 10 to 30 minutes, the ability of PMNs to release microbicidal superoxide was strongly inhibited. Thus protein carbamoylation may provide a regulatory mechanism. The altered function of PMNs in renal disease may be due in part to the posttranslational modification of proteins by urea-derived cyanate.
Asunto(s)
Proteínas Sanguíneas/metabolismo , Citrulina/análogos & derivados , Fallo Renal Crónico/sangre , Leucocitos/metabolismo , Diálisis Peritoneal , Urea/sangre , Adulto , Anciano , Nitrógeno de la Urea Sanguínea , Citrulina/sangre , Cianatos/farmacología , Femenino , Fluoresceína-5-Isotiocianato , Técnica del Anticuerpo Fluorescente , Colorantes Fluorescentes , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Superóxidos/sangreRESUMEN
In chronic renal failure, the concentration of blood urea increases as the residual function of the kidney decreases, CAPD provides therapy to manage the patient and maintain urea levels at a steady state concentration appropriate for each patient. Although urea is not considered to be a uraemic toxin, cyanate that forms spontaneously from urea reacts with the amino group of amino acids and proteins to form carbamoylated molecules. N-carbamoyl-tyrosine (N-C-Tyr) was measured in a longitudinal study of chronic renal failure and was compared in patients from the U.W.I., Jamaica, managed conservatively with patients from the University of Tennessee, Memphis, managed by CAPD. In post-prandial blood of 5 patients managed by CAPD, the urea mean ñ SD was 22.1ñ4.3 mmol/l and the mean ñ SD for N-C-Tyr was 70 ñ 35 umol/l. The months on CAPD ranged from 7 to 24. The patients managed without dialysis showed a gradual increase in blood urea accompanied by an increase in N-C-Tyr until the time of death. In one patient, the urea level increased from 25 to 82 mmol/l and the N-C-Tyr increased from 51 to 87 umol/l in 10 months. In a second patient, the blood urea level increased from 54 to 77 mmol/l and the N-C-Tyr increased from 59 to 220 in 4 months. In normal individuals, with a blood urea level of 3.6 to 5.7 mmol/l, N-C-Tyr is not found in plasma. This study indicates that CAPD therapy may provide additional benefits by decreasing levels of carbamoylated moieties in patients with chronic renal failure (AU)
Asunto(s)
Humanos , Insuficiencia Renal Crónica/terapia , Diálisis Peritoneal Ambulatoria Continua , JamaicaRESUMEN
The prevalence and incidence of osteonecrosis (ON) of the humeral head in sickle cell disease was determined by a study of 2524 patients who were entered into a prospective study and followed for an average of 5.6 years. At entry, 5.6% had roentgenographic evidence of ON in one or both shoulders. There was little difference in age-adjusted prevalence among genotypes, but there were striking differences in age-specific rates. Observed at ages ranging from five to 24 years, 3.25% of sickle cell anemia (S/S) patients, but only 1.1% of sickle cell disease (S/C) patients, had ON. No S/beta+ thalassemia patients younger than 25 years of age had ON on entry. The highest age-adjusted incidence rate was found in S/S patients with concomitant alpha-thalassemia (4.85 per hundred patient-years), followed by S/beta zero-thalassemia (4.84 per hundred patient-years), S/beta+ thalassemia (2.61 per hundred patient-years), S/S without alpha-thalassemia (2.54 per hundred patient-years), and S/C (1.66 per hundred patient-years). Only 20.9% of patients reported pain or had limited range of movement at the time of diagnosis. Sickle cell disease is a frequent cause of ON of the humeral head, especially in children and young adults.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Enfermedad de la Hemoglobina SC/complicaciones , Húmero , Osteonecrosis/epidemiología , Talasemia alfa/complicaciones , Talasemia beta/complicaciones , Adolescente , Adulto , Factores de Edad , Anemia de Células Falciformes/genética , Niño , Preescolar , Genotipo , Enfermedad de la Hemoglobina SC/genética , Humanos , Incidencia , Persona de Mediana Edad , Osteonecrosis/diagnóstico por imagen , Osteonecrosis/etiología , Prevalencia , Estudios Prospectivos , Radiografía , Rango del Movimiento Articular , Factores de Tiempo , Estados Unidos/epidemiología , Talasemia alfa/genética , Talasemia beta/genéticaRESUMEN
Urea kinetics have been used to measure adequacy of hemodialysis. The role of urea kinetics in CAPD has not been clearly established. Using urea kinetics, we studied 71 hemodialysis and 71 CAPD patients. Age was 53 +/- 12 and 45.8 +/- 12 respectively. Urea kinetics in hemodialysis were studied in the standard manner. CAPD patients collected 24 hr, dialysate fluid to measure urea, creatinine, glucose and protein. Urine was collected for 24 hr. to measure urea and creatinine. Protein catabolic rate (pcr) was calculated from the total amount of urea cleared in 24 h. Both groups of patients had similar body weight. Kt/V in CAPD (0.65 +/- 0.1) was at a level considered underdialysis for hemodialysis. In both groups, pcr increased as Kt/V increased. However, CAPD patients had levels of pcr higher than hemodialysis patients at the same level of Kt/V. BUN, serum albumin and serum potassium were significantly lower in CAPD patients. Patients who dialyze more, eat more. Differences in protein intake may be due to a more liberal diet in CAPD, patient selection, removal of middle molecules, or better control of the acidosis.
Asunto(s)
Fallo Renal Crónico/terapia , Diálisis Peritoneal Ambulatoria Continua , Diálisis Renal , Urea/farmacocinética , Adulto , Nitrógeno de la Urea Sanguínea , Soluciones para Diálisis/análisis , Proteínas en la Dieta/administración & dosificación , Femenino , Humanos , Fallo Renal Crónico/metabolismo , Masculino , Persona de Mediana Edad , Urea/análisisRESUMEN
Lower-than-normal tyrosine concentrations of unexplained pathogenesis in plasma and intracellular body water have been reported in patients with chronic renal failure. We found a derivative of tyrosine that is not measured by the usual methods of amino-acid analysis because its alpha-amino group is blocked and cannot react to form other derivatives. An in vivo covalent reaction with urea-derived cyanate forms alpha-amino-carbamoyl-tyrosine (N-C-Tyr) in patients with end-stage renal disease. A longitudinal study of patients with end-stage renal disease who were treated with continuous ambulatory peritoneal dialysis shows that plasma that is obtained within 4 hours of the morning meal contains 70.1 +/- 6 mumol/L of tyrosine (mean +/- SEM) and 77.2 +/- 12 mumol/L of N-C-Tyr (mean +/- SEM). Thus there is a molecule of N-C-Tyr for each molecule of tyrosine present. The carbamoylation index or ratio of N-C-Tyr to tyrosine, blood urea nitrogen, episodes of peritonitis, and changes in dialysis protocol were compared. A reduction in the number of peritoneal dialysis exchanges resulted in parallel increases in carbamoylation index and blood urea nitrogen. Altering dialysis by increasing the number of exchanges or adding supplemental hemodialysis resulted in a decrease in the carbamoylation index with a delayed decrease in blood urea nitrogen. We found a significant increase of N-C-Tyr (p = 0.005) and of the carbamoylation index (p = 0.004) during six episodes of peritonitis compared with 10 periods of no peritonitis in two patients who had multiple episodes of peritonitis.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Fallo Renal Crónico/sangre , Tirosina/análogos & derivados , Tirosina/sangre , Adulto , Nitrógeno de la Urea Sanguínea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diálisis Peritoneal Ambulatoria Continua , Peritonitis/sangre , Factores de Tiempo , Tirosina/química , Urea/químicaRESUMEN
BACKGROUND AND METHODS: Osteonecrosis of the femoral head is an important complication of sickle cell disease. We studied 2590 patients who were over 5 years of age at entry and followed them for an average of 5.6 years. Patients were examined twice a year, and radiographs of the hips were taken at least twice: at study entry and approximately three years later. RESULTS: At study entry, 9.8 percent of patients were found to have osteonecrosis of one or both femoral heads. On follow-up, patients with the hemoglobin SS genotype and alpha-thalassemia were at the greatest risk for osteonecrosis (age-adjusted incidence rate, 4.5 cases per 100 patient-years, as compared with 2.4 in patients with the hemoglobin SS genotype without alpha-thalassemia and 1.9 in those with the hemoglobin SC genotype). Although the rate of osteonecrosis in patients with the hemoglobin SC genotype did not differ significantly from that in patients with the hemoglobin SS genotype without alpha-thalassemia, osteonecrosis tended to develop in these patients later in life. Intermediate rates of osteonecrosis were observed among patients with the hemoglobin S-beta zero-thalassemia and the hemoglobin S-beta(+)-thalassemia genotypes (3.6 and 3.3 cases per 100 patient-years, respectively). Osteonecrosis was found in patients as young as five years old (1.8 cases per 100 patient-years for all genotypes). The frequency of painful crises and the hematocrit were positively associated with osteonecrosis. The mean corpuscular volume and serum aspartate aminotransferase level were negatively associated. Twenty-seven patients had hip arthroplasty during the study; 10 were under 25 years of age. Five of the 27 required reoperation 11 to 53 months after the initial operation. CONCLUSIONS: Osteonecrosis of the femoral head is common in patients with sickle cell disease, with an incidence ranging from about 2 to 4.5 cases per 100 patient-years. Patients with the hemoglobin SS genotype and alpha-thalassemia and those with frequent painful crises are at highest risk. The overall prevalence is about 10 percent. The results of hip arthroplasty are poor.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Necrosis de la Cabeza Femoral/etiología , Adolescente , Adulto , Niño , Preescolar , Necrosis de la Cabeza Femoral/epidemiología , Necrosis de la Cabeza Femoral/cirugía , Genotipo , Hemoglobina Falciforme/análisis , Humanos , Persona de Mediana Edad , Talasemia/complicaciones , Estados Unidos/epidemiologíaRESUMEN
Polyclonal antisera to epsilon-amino-carbamoyl-lysine (homocitrulline) on guinea pig carbamoylated low density lipoprotein were used as probes to identify homocitrulline. These antisera detect homocitrulline in the immunogen and on other carbamoylated blood proteins including those from different species. In vivo carbamoylation of intracellular hemoglobin obtained from uremic patients and carbamoyl-proteins, carbamoylated in vitro, located on erythrocyte and lymphocyte cell surface membranes were detected. Solid phase, direct and competitive ELISAs for homocitrulline were used to analyze carbamoylated blood proteins. In uremic patients carbamoylation of protein by endogenous urea-derived cyanate occurs on the epsilon-amino group of lysine residues. Identification of carbamoylated proteins from uremic patients using an immunochemical probe of site specific antibody provides a way to monitor post-translational modification of proteins due to uremia and may give further insight for understanding the pathophysiology of end stage renal disease.
Asunto(s)
Citrulina/análogos & derivados , Hemoglobinas Anormales/análisis , Fallo Renal Crónico/sangre , Uremia/sangre , Animales , Afinidad de Anticuerpos , Carbamatos , Citrulina/inmunología , Ensayo de Inmunoadsorción Enzimática , Cobayas , Lipoproteínas LDL/inmunologíaRESUMEN
Adequacy of CAPD has not been established. The recommendation is a Kt/V (K, total urea clearance in ml/min; t. time in minutes on dialysis; and V, total body water which is the volume of distribution of urea) greater than 1.5/week and/or a creatinine clearance (residual + dialysis) greater than 40 l/week/1.73 m2. We followed 20 CAPD patients for 38.6 +/- 28 mo. We measured blood urea nitrogen, serum creatinine, body weight, residual renal function (Kr), normalized protein catabolic rate (NPCR), Kt/V/week and creatinine clearance (CC) l/w/1.73 m2. We obtained the following values: B Wt 72 +/- 16 kg, BUN 56 +/- 13 mg/dl, s. Cr. 12.6 +/- 5 mg/dl, Kr 0.6 +/- 1 ml/min, NPCR 0.84 +/- 0.3 g/kg/day, Kt/V/week 1.8 +/- 0.3 and CC 50.4 +/- 10 l/w/1.73 m2. Patients dialyzed with a wide range of prescription. There was a good correlation between Kt/V and CC. There was no correlation between the dialysis prescription changes in weight and biochemical determinations. There was a direct correlation between Kt/V and NPCR: patients who were dialyzed more eat more. Of the 20 patients, 10 had 24 hospitalizations, and of these were 12 due to peritonitis. Dialysis prescription and biochemical findings of these patients did not differ significantly from nonhospitalized patients. Larger prospective studies are necessary to determine the adequate range of CAPD prescription and its relationship to morbidity and mortality.
Asunto(s)
Diálisis Peritoneal Ambulatoria Continua , Adulto , Nitrógeno de la Urea Sanguínea , Creatinina/metabolismo , Femenino , Humanos , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Diálisis Peritoneal Ambulatoria Continua/métodos , Urea/metabolismoRESUMEN
During the entry examination, leg ulcers were present in 2.5% of 2,075 patients 10 years of age and older with sickle cell disease who entered into the Cooperative Study of Sickle Cell Disease (CSSCD) between 1979 and 1986. Prevalence rates were highest among patients with sickle cell anemia and sickle cell anemia with thalassemia genotypes. Among sickle cell anemia patients free of ulcers at entry, the overall incidence was 5.73 per 100 person years in those having associated alpha-thalassemia and 9.97 for those without. Among sickle cell anemia patients with two alpha genes, the estimated incidence of leg ulcers is 2.38 per 100 person years and 6.12 per 100 person years among sickle cell anemia patients with three alpha genes (P less than .05). In both groups, the incidence was highest among those patients over 20 years of age and considerably higher among males than females (P less than .001). Leg ulcers were nonexistent in patients with sickle beta plus thalassemia and sickle hemoglobin C disease. Low steady-state hemoglobin is associated with a higher incidence of ulcer formation (P less than .0001) in sickle cell anemia patients. The protective effect of hemoglobin F is apparent at all levels of total hemoglobin among sickle cell anemia patients and those with associated alpha-thalassemia.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Úlcera de la Pierna/etiología , Adolescente , Adulto , Factores de Edad , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/fisiopatología , Niño , Empleo , Femenino , Hemoglobina Fetal/análisis , Hemoglobina Falciforme/análisis , Humanos , Úlcera de la Pierna/epidemiología , Úlcera de la Pierna/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estaciones del Año , Factores Sexuales , Talasemia/complicacionesRESUMEN
beta 2-microglobulin (beta 2M) has been implicated in the pathogenesis of amyloidosis in long-term dialysis patients. beta 2M levels were measured in patients with chronic renal failure: before and after conventional hemodialysis in 30, before and after high-flux (HF) hemodialysis in 35, and during the first hemodialysis treatment in five patients, as well as in the serum and peritoneal fluid of 13 patients who were receiving continuous ambulatory peritoneal dialysis (CAPD) and in the serum and urine of three patients who had received kidney transplants. Dialysis patients had markedly elevated beta 2M levels; prehemodialysis values were not significantly different for patients receiving conventional v HF hemodialysis. Most of these patients were functionally anephric, and the beta 2M levels did not correlate with age, sex, or time on dialysis. In patients receiving conventional hemodialysis using cellulose acetate membrane, beta 2M levels increased 25.4% after hemodialysis, whereas in patients receiving HF hemodialysis using polysulfone membrane, beta 2M levels decreased significantly (43.0%) after hemodialysis. End-stage renal disease patients dialyzed for the first time had beta 2M values significantly lower than the other two groups because of residual glomerular filtration rate (GFR). CAPD patients also had lower values because they had an estimated loss of 80.4 mg/d of beta 2M in the dialysate fluid. In patients with chronic renal failure, beta 2M levels paralleled the increase in serum creatinine. Patients who received kidney transplants had a dramatic decrease in beta 2M levels that correlated with improvement in GFR. beta 2M correlated with the residual GFR, and its removal was membrane-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Fallo Renal Crónico/sangre , Microglobulina beta-2/análisis , Adulto , Amiloidosis/sangre , Amiloidosis/etiología , Humanos , Fallo Renal Crónico/terapia , Trasplante de Riñón , Persona de Mediana Edad , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Diálisis Renal/efectos adversos , Diálisis Renal/métodosRESUMEN
Dialysate leakage into subcutaneous tissues occurs not uncommonly in patients on continuous ambulatory peritoneal dialysis. When the leakage site cannot be localized clinically, CT with intraperitoneal contrast medium administration may localize the site. We report our experience with three cases in which this technique did localize the leakage site and thereby determined the type of surgical correction.
Asunto(s)
Medios de Contraste , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Radiografía Abdominal , Tomografía Computarizada por Rayos X , Músculos Abdominales/diagnóstico por imagen , Adulto , Anciano , Femenino , Hernia Ventral/diagnóstico por imagen , Humanos , MasculinoRESUMEN
Peritonitis, a major complication of end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis (CAPD), enhances peritoneal protein losses by increasing protein and energy requirements while simultaneously decreasing appetite, usually causing a negative nitrogen balance. The influence of peritonitis on the nutritional status of CAPD patients was evaluated. Fourteen end-stage renal disease patients being treated with CAPD and presenting with peritonitis were randomized to one group with and one without a nutritional supplement. Four CAPD patients without peritonitis served as controls. Anthropometric measurements, laboratory determinations, dietary protein intake, and protein catabolic rate were obtained. The control group lost an average of 9.6 gm protein per 24 hours in the peritoneal fluid vs. an average of 15.1 gm protein per 24 hours lost by patients with peritonitis (p less than .01). Serum albumin did not decrease except in two diabetic patients in whom it dropped an average of 42% and remained low. Nitrogen balance remained positive in all patients except one with diabetes who had very low daily protein intake and caloric intake. The catabolism produced by short uncomplicated peritonitis did not create a negative nitrogen balance in patients eating at least 1 gm protein per kilogram ideal body weight (IBW) and 25 kcal/kg IBW.
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Trastornos Nutricionales/terapia , Diálisis Peritoneal/efectos adversos , Peritonitis/etiología , Adulto , Anciano , Peso Corporal , Proteínas en la Dieta/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Nutricionales/etiología , Proteínas/metabolismo , Distribución Aleatoria , Albúmina Sérica/análisis , Urea/metabolismoRESUMEN
The chromogenic Limulus amoebocyte lysate test effectively detected 66 (100%) culture-proven gram-negative peritonitis cases among 185 continuous ambulatory peritoneal dialysis patients with clinical evidence of infectious peritonitis.
Asunto(s)
Infecciones Bacterianas/diagnóstico , Prueba de Limulus , Peritonitis/diagnóstico , Infecciones por Enterobacteriaceae/diagnóstico , Bacterias Gramnegativas , Humanos , Diálisis Peritoneal Ambulatoria Continua , Infecciones por Pseudomonas/diagnósticoRESUMEN
Twenty-one microbiologically documented episodes of coagulase-negative staphylococcal peritonitis occurred in 21 continuous ambulatory peritoneal dialysis patients. All strains involved in these infections were tested for antimicrobial susceptibility and in vitro adherence assays. Twenty of the strains were species identified using two commercially available systems. For comparison, 20 saprophytic strains of coagulase-negative staphylococci obtained from the nares and axillae of 10 uninfected, peritoneal dialysis patients were included for in vitro characterization. Staphylococcus epidermidis was the species most often identified for both clinical and saprophytic strains. Eighteen of the 21 (86%) clinical strains were resistant to penicillin G. Methicillin resistance, which was present in five clinical strains, was not found in saprophytic strains. Adherence assay determinations showed marked differences between clinical versus colonization strains, with the clinical isolates significantly more adherent (p less than 0.025) than colonization strains. Electron microscopic examination of silastic catheter segments incubated with a strain of S. epidermidis in used and unused dialysis fluids demonstrated marked differences in attachment of bacteria to catheter material.