Influencia de la serología de la hepatitis viral crónica sobre los niveles de eritropoyetina endógena en los pacientes en hemodiálisis / Influence of serology of the chronic viral hepatitis on the levels of endogenous erythropoietin in the patients in hemodialysis

Nos propusimos conocer si la hepatitis viral crónica afecta la concentración sérica de la eritropoyetina endógena en los pacientes con insuficiencia renal crónica terminal sometidos a tratamiento hemodialítico. Estudiamos a 40 pacientes pertenecientes a la Unidad de Hemodiálisis Fresenius Medical Care de Venezuela, con edades entre los 22 a 77 años, sin haber presentado sangramiento activo, ni haber recibido eritropoyetina humana recombinante ni transfusiones de sangre en los últimos tres meses. El análisis de eritropoyetina se efectuó por quimioluminiscencia. Los valores se expresaron en media aritmética ± DE, como sigue: Core: 8,8 ± 2,03 mU/mL; hepatitis B antígeno de superficie positivo y core positivo: 12,45 ± 1,85 mU/mL; hepatitis C: 15,33 ± 2,91 mU/mL; hepatitis B más hepatitis C: 12,55 ± 3,06m U/mL. El grupo control: 12 ± 2,47 mU/mL (no estadísticamente significativo). Concluimos que en los pacientes con insuficiencia renal crónica terminal en tratamiento hemodialítico crónico, la hepatitis crónica por VHB o VHC, no produce modificaciones de los niveles séricos de eritropoyetina endógena

Cuantificación de los niveles de eritropoyetina (EPO) endógena y su relación con variables epidemiológicas en un grupo de pacientes en hemodiálisis / Quantification of the endogenous erythropoie (EPO) levels and its relation with epidemiological varible in a group of patients in hemodialysis

Investigamos los valores de la eritropoyetina (EPO) endógena en pacientes con insuficiencia renal crónica terminal en tratamiento hemodialítico. Este estudio se llevó a cabo en 33 pacientes pertenecientes a la Unidad de Hemodiálisis Fresenius Medical Care de Venezuela, con edades compredidas entre los 22 a 77 años, 40 por ciento de raza caucásica, 22 por ciento de raza negra y 38 por ciento mestizos. Los criterios de inclusión fueron: no haber presentado en los últimos tres meses sangramiento activo, ni haber recibido EPO humana recombinante ni transfusiones de sangre en el mismo período de tiempo. Todos los pacientes recibieron tres sesiones de hemodiálisis por semana. Las muestras de sangre se obtuvieron antes de la primera y antes de la última sesión de hemodiálisis de la semana. El análisis de EPO se efectuó por quimioluminiscencia (Nichols Diagnostics Institute, USA). Los valores se expresaron en media aritmética ñ ES. Los valores de EPO endógena fueron de 10,43 ñ 1,35 mU/mL antes de la primera diálisis de la semana, y de 11,36 ñ 0,31 mU/mL antes de la última diálisis de la semana; los valores fueron menores a los descritos en la literatura para otros países. Los valores de EPO relacionados con la raza fueron 12,59 ñ 1,56 mU/mL para las caucásicos, 7,61 ñ 1,07 mU/mL para los negros y 11,09 ñ 1,62 mU/mL para los mestizos. No hubo diferencia en los valores de EPO en relación al día de la diálisis en que se tomó la muestra, ni en relación con la edad, el sexo y la patología de base, pero el tiempo en diálisis juega con 1 a 30 meses en diálisis con los pacientes que tienen de 1 a 60 meses en tratamiento

Role of persistent amenorrhea in bone mineral metabolism of young hemodialyzed women.

BACKGROUND: Chronic renal failure in women is frequently associated with endocrine disturbances leading to menstrual disorders. However, most studies on renal osteodystrophy have not taken into account the possible role of these hormonal disturbances on the pathogenesis of bone alterations seen in these patients. In the present study, we evaluated bone mineral metabolism in a group of young hemodialyzed women with persistent amenorrhea and compared them with similar women with regular menstruation. METHODS: We studied 74 women who were further subdivided into 43 women with regular menstrual periods and 31 women with persistent amenorrhea, defined as the absence of menstrual bleeding for more than six months. In all patients, we performed a bone mineral density (BMD) analysis and simultaneously evaluated different biochemical parameters, intact parathyroid hormone (iPTH), sexual hormone determinations that included total estradiol, follicle-stimulating (FSH), and luteinizing hormone and markers of bone resorption such as the procollagen type 1 cross-linked carboxy-terminal telopeptide (ICTP). RESULTS: Serum calcium, phosphorus, and iPTH were similar in both groups. Serum alkaline phosphatase was higher in amenorrheic women. Although the total serum estradiol concentration was normal in the amenorrheic women when compared with nonuremic women, the values were significantly lower than those in regularly menstruating women. Serum FSH and ICTP values were significantly higher in the amenorrheic women. Trabecular BMD in the lumbar spine was also significantly lower in the amenorrheic women compared with regularly menstruating dialysis patients. Lumbar spine BMD and total estradiol levels correlated significantly in the amenorrheic group. CONCLUSIONS: These studies show that persistent amenorrheic young women on dialysis have lower trabecular BMD and evidence of increased bone resorption when compared with normal menstruating women on dialysis. The possible impact of these results in the natural history of the uremic osteodystrophy remains to be determined.

Turnover of hepatitis C virus genotypes in hemodialysis patients.

Hepatitis C virus (HCV) genotypes were determined in hemodialysis patients with a high prevalence and incidence of infection. A change of HCV genotype was observed in 6/14 follow-up samples analyzed 13 and 21 months later. The appearance and disappearance of HCV genotypes may be due to either genotype-specific intermittent viremic status or viral interference.

Hepatitis G virus infection in Amerindians and other Venezuelan high-risk groups.

Recently, a new virus related to flaviviruses, the hepatitis G virus (HGV), or GBV-C virus, was discovered as a putative blood-borne human pathogen. HGV RNA (NS5 region) was amplified by reverse transcription-nested PCR in the sera of 6 of 64 (9%) hemodialysis patients; 2 of 80 (2.5%) West Yukpa Amerindians, a population with a high rate of HBV infection but negative for HCV infection; and 1 patient with an acute episode of non-A, non-B, non-C hepatitis (NABCH). The patterns of single-strand conformation polymorphism of the amplified products were unique among different specimens and similar on follow-up for hemodialysis patients. All patients tested remained HGV RNA positive 1 and 2 years later, without major sequence variation, except for the NABCH patient, for whom a double infection and an apparent clearance of the original dominant variant was observed after 2 years. The sequences of the NS5 amplified products demonstrated 85 to 90% identity with other reported HGV sequences.

Reduced antibody reactivity to hepatitis C virus antigens in hemodialysis patients coinfected with hepatitis B virus.

Antibody reactivities to hepatitis C virus (HCV) antigens and to synthetic peptides derived from different parts of the HCV genome (core, NS4, and NS5) were evaluated in HCV-infected hemodialysis patients. In the RIBA 3 assay, NS5 was significantly less recognizable by sera of hemodialysis patients compared to other HCV-infected subjects. Among hemodialysis patients, those coinfected with hepatitis B virus (HBV) (positive for hepatitis B surface antigen [HBsAg+]) showed a reduction in reactivity to C33 and C100. Sera of only 23% of the hemodialysis patients (37 of 161) reacted with more than three of eight peptides tested, significantly fewer than the 60% (12 of 20) of the sera of other HCV-infected patients tested (P = 0.001). This immunosuppression was also manifested by a reduced frequency of recognition of additional peptides on follow-up. An even more reduced reactivity was observed among the HBV-coinfected patients (HBsAg+). The low-responder hemodialysis patients were not infected with any particular genotype of HCV, and the same HCV genotypes observed in the whole group of hemodialysis patients (1a, 1b, 2a, and 3a) were found circulating in the low-responder group. Even in this low-responder population, the good performance of two peptides (peptide 716, corresponding to a portion of the core, and peptide 59, corresponding to a portion of NS4) corroborates the immunodominance of the conserved epitopes within these peptides.

High incidence of hepatitis C virus infection in hemodialysis patients in units with high prevalence.

The prevalence of hepatitis C virus (HCV) infection was evaluated in 227 hemodialysis patients from four units in Caracas, Venezuela, by using different second- and third-generation enzyme immunoassays (EIAs) and immunoblot assays. HCV antibodies were detected in 162 patients (71%) by the recombinant-based second-generation assays (Abbott and Ortho) and in 161 patients by the synthetic peptide-based EIA (UBI). Of the 162 HCV antibody-positive serum samples, 161 were confirmed to be positive by RIBA 3. HCV RNA was detected in 49 of 68 (72%) of the seropositive patients and in 5 of 21 (24%) of the seronegative ones. HCV RNA was not always correlated with an increase in alanine aminotransferase (ALT) levels. Among 20 patients positive for HCV RNA and for HCV antibodies (without any hepatitis B virus [HBV] marker), only 10 had elevated ALT levels. The possible interference of HBV for HCV replication was evaluated. No significant difference was found between the presence of HCV RNA and the presence of any HBV serological markers. The possible routes of transmission of HCV in hemodialysis patients are multiple, and some of them are still controversial. Of the HCV-positive patients, 30% received a blood transfusion, significantly more than the 15% found for the HCV-negative group. However, blood transfusions alone could not account for the high incidence observed in this group of patients (38% from 1994 to 1995). In conclusion, about one-quarter of the apparently non-HCV-infected patients were probably seroconverting, ALT may not be a useful indicator of HCV infection in hemodialysis patients, and nosocomial transmission of HCV may play a role in the spread of HCV in this group.

Risk factors for dialysis-associated hepatitis C in Venezuela.

Utilizing the first and second generation of enzyme immunoassays which detect antibodies to the C virus we investigated the frequency of anti-HCV antibodies in 315 patients undergoing hemodialysis. Other subpopulations at risk were used as reference groups. One hundred and twenty-three samples (39%) from the hemodialysis group repeatedly showed anti-HCV positive antibodies while only 19% and 1% were positive in the reference groups. The rate of anti-HCV reactive patients correlated with time on hemodialysis (less than 1 year, 17%; 1 to 5 years 43%; greater than 5 years, 64%; r = 0.94, P less than 0.001) and with the number of blood transfusions (1 to 10, 40%; greater than 10, 76%; r = 0.97; P less than 0.001). Length of time on hemodialysis was shown to be the major risk factor in thirty-three anti-HCV positive patients who had no previous record of blood transfusions. Co-infection with HBV was demonstrated in 41% out of 123 anti-HCV reactive patients, and increased alanine aminotransferase (ALT) activity was documented in this co-infected group. Our results further extend the observations on the predisposing factors to HCV spread in hemodialysis units, and suggest that in these renal patients co-infection with C and B viruses is a major cause of rising ALT activity.