Acetazolamide and N-acetylcysteine in the treatment of chronic mountain sickness (Monge's disease).

Patients suffering from chronic mountain sickness (CMS) have excessive erythrocytosis. Low -level cobalt toxicity as a likely contributor has been demonstrated in some subjects. We performed a randomized, placebo controlled clinical trial in Cerro de Pasco, Peru (4380m), where 84 participants with a hematocrit (HCT) ≥65% and CMS score>6, were assigned to four treatment groups of placebo, acetazolamide (ACZ, which stimulates respiration), N-acetylcysteine (NAC, an antioxidant that chelates cobalt) and combination of ACZ and NAC for 6 weeks. The primary outcome was change in hematocrit and secondary outcomes were changes in PaO2, PaCO2, CMS score, and serum and urine cobalt concentrations. The mean (±SD) hematocrit, CMS score and serum cobalt concentrations were 69±4%, 9.8±2.4 and 0.24±0.15µg/l, respectively for the 66 participants. The ACZ arm had a relative reduction in HCT of 6.6% vs. 2.7% (p=0.048) and the CMS score fell by 34.9% vs. 14.8% (p=0.014) compared to placebo, while the reduction in PaCO2 was 10.5% vs. an increase of 0.6% (p=0.003), with a relative increase in PaO2 of 13.6% vs. 3.0%. NAC reduced CMS score compared to placebo (relative reduction of 34.0% vs. 14.8%, p=0.017), while changes in other parameters failed to reach statistical significance. The combination of ACZ and NAC was no better than ACZ alone. No changes in serum and urine cobalt concentrations were seen within any treatment arms. ACZ reduced polycythemia and CMS score, while NAC improved CMS score without significantly lowering hematocrit. Only a small proportion of subjects had cobalt toxicity, which may relate to the closing of contaminated water sources and several other environmental protection measures.

Vitamin D receptor gene, biochemical bone markers and bone mineral density in Mexican women on dialysis.

BACKGROUND: The influence of the Bsm1 polymorphism of the vitamin D receptor (VDR) gene on mineral and bone disorders in chronic kidney disease (CKD) is still under discussion. The aim of this study was to analyse the relationship between VDR polymorphism, bone mineral density (BMD), biochemical bone markers and clinical factors in women on peritoneal dialysis (PD) and haemodialysis (HD). METHODS: In a cross-sectional study, 197 women (42 +/- 10 years; 25% with diabetes mellitus (DM); body mass index (BMI) 25.26 +/- 4.77 kg/m(2)) treated by PD (72%) or HD (28%) underwent measurements of BMD (measured at the calcaneus by quantitative ultrasound; expressed as T- and Z-scores) and plasma total calcium (tCa), intact parathyroid hormone 1-84 (iPTH), phosphorus, albumin, glucose, osteoprotegerin (OPG), fetuin-A, intact osteocalcin-49 and N-MID fragment 1-43 aa (N-MID osteocalcin) N-terminal propeptide of type 1 procollagen (PINP) and C-terminal telopeptide-beta aspartic acid (BCL). DNA was extracted from peripheral blood. PCR products were digested with Bsm1 to analyse VDR polymorphism. RESULTS: The Z-score of BMD was -1.1 +/- 1.03. According to the values of osteopenia (T-score = -1.0), patients with higher BMD were younger, had lower frequency of amenorrhoea and diabetes and had higher serum creatinine and fetuin levels as well as lower levels of PINP. In a stepwise multivariate logistics analysis, osteopenia was associated with presence of genotype BB+Bb (OR = 3.26, P < or = 0.003) and age (OR = 0.95, P = 0.050). According to the B allele, bb: n = 126 (64%) and BB+Bb: n = 71(36%), group bb had significantly higher mean Z-scores (-0.97 +/- 1.0 vs -1.3+/-0.92; P < or = 0.021). CONCLUSIONS: The high frequency of osteopenia observed in female CKD patients on dialysis is associated with age and genetic predisposition as revealed by its association to the Bsm1 VDR polymorphism.

Impact of fill volume on peritoneal clearances and cytokine appearance in peritoneal dialysis.

BACKGROUND: Current adequacy guidelines for peritoneal dialysis encourage the use of large fill volumes for the attainment of small solute clearance targets. These guidelines have influenced clinical practice in a significant way, and adoption of higher fill volumes has become common in North America. Several studies, however, have challenged the relevance of increasing small solute clearance; this practice may result in untoward consequences in patients. OBJECTIVE: The present study was designed to explore the relationship between dialysate volume and the clearance of different sized molecules, fluid dynamics, and appearance of peritoneal cytokines. METHODS: Thirteen adult prevalent patients on continuous ambulatory peritoneal dialysis were studied. Three different dialysate volumes (2.0, 2.5, and 3.0 L) were infused on consecutive days in a random order. Several measurements of peritoneal fluid dynamics (intraperitoneal pressure, net ultrafiltration, fluid absorption), solute clearances (urea, creatinine, beta2-microglobulin, albumin, IgG, and transferrin), and appearance of interleukin-6 and tumor necrosis factor alpha (TNFalpha) were assessed. RESULTS: Increase in dialysate fill volume (from 2 to 2.5 to 3 L) was examined in relationship to body surface area (BSA). The dialysate volume/BSA (DV/BSA) ratio increased from 1262 to 1566 to 1871 mL/m2 on 2.0, 2.5, and 3.0 L dialysate volumes, respectively. In parallel, diastolic blood pressure increased from 82.7 +/- 8.8 to 87.0 +/- 9.5 to 92 +/- 8.3 mmHg (p < 0.05). Net ultrafiltration rate also increased, from 0.46 +/- 0.48 to 0.72 +/- 0.42 to 0.97 +/- 0.49 mL/minute (p < 0.01), despite a concomitant increase in fluid absorption, from 1.05 +/- 0.34 to 1.21 +/- 0.40 to 1.56 +/- 0.22 mL/min (p < 0.01). Urea peritoneal clearance increased from 8.27 +/- 0.68 to 9.92 +/- 1.6 to 12.98 +/- 4.03 mL/min (p < 0.01); creatinine peritoneal clearance increased from 6.69 +/- 1.01 to 7.64 +/- 1.12 to 8.69 +/- 1.76 mL/min (p < 0.01). Clearance of the other measured molecules did not change. Appearance of interleukin-6 increased 17% and 43% (p < 0.01), and TNFalpha appearance increased 14% and 50% (p < 0.01) when dialysate volumes of 2.5 and 3.0 L were used, compared with 2.0 L. CONCLUSIONS: These results show that, with higher values of DV/BSA ratio, small solute peritoneal clearance is increased, but clearances of large molecules remain unchanged. With the use of higher volumes, fluid absorption rate and the appearance of proinflammatory cytokines in the dialysate are increased.

Increased oxidative stress following acute and chronic high altitude exposure.

The generation of reactive oxygen species is typically associated with hyperoxia and ischemia reperfusion. Recent evidence has suggested that increased oxidative stress may occur with hypoxia. We hypothesized that oxidative stress would be increased in subjects exposed to high altitude hypoxia. We studied 28 control subjects living in Lima, Peru (sea level), at baseline and following 48 h exposure to high altitude (4300 m). To assess the effects of chronic altitude exposure, we studied 25 adult males resident in Cerro de Pasco, Peru (altitude 4300 m). We also studied 27 subjects living in Cerro de Pasco who develop excessive erythrocytosis (hematocrit > 65%) and chronic mountain sickness. Acute high altitude exposure led to increased urinary F(2)-isoprostane, 8-iso PGF(2 alpha) (1.31 +/- 0.8 microg/g creatinine versus 2.15 +/- 1.1, p = 0.001) and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.37 +/- 0.09, p = 0.002), with a trend to increased plasma thiobarbituric acid reactive substance (TBARS) (59.7 +/- 36 pmol/mg protein versus 63.8 +/- 27, p = NS). High altitude residents had significantly elevated levels of urinary 8-iso PGF(2 alpha) (1.3 +/- 0.8 microg/g creatinine versus 4.1 +/- 3.4, p = 0.007), plasma TBARS (59.7 +/- 36 pmol/mg protein versus 85 +/- 28, p = 0.008), and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.55 +/- 0.19, p < 0.0001) compared to sea level. High altitude residents with excessive erythrocytosis had higher levels of oxidative stress compared to high altitude residents with normal hematological adaptation. In conclusion, oxidative stress is increased following both acute exposure to high altitude without exercise and with chronic residence at high altitude.

C-reactive protein and anti-Chlamydia pneumoniae antibodies as risk factors of cardiovascular death in incident patients on peritoneal dialysis.

OBJECTIVE: Recently it has been pointed out that inflammation and infections caused by germs such as Chlamydia pneumoniae are independent cardiovascular risk factors for the general population, but information about these relationships in dialysis patients is scarce. This work was done to analyze the association of C-reactive protein (CRP) and IgG anti-Chlamydia pneumoniae antibodies (anti-Chlp-IgG) as independent cardiovascular risk factors in incident patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Single-cohort, prospective observational study. SETTING: Three CAPD centers from the Instituto Mexicano del Seguro Social, and one from the Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Mexico. PATIENTS: A cohort of 75 adult incident patients on CAPD, without clinical signs of congestive heart failure, coronary heart disease, or peripheral arterial insufficiency. No restrictions for age, gender, or cause of renal failure were applied. PRIMARY OUTCOME: Mortality. METHODS: Demographic variables, body composition by electrical bioimpedance, serum glucose, urea, creatinine, lipids, homocysteine, nutritional markers (albumin, prealbumin, and transferrin), CRP, and anti-Chlp-IgG were measured and registered at the time of the first admission. When a patient died, the cause of death was determined by review of the clinical chart. RESULTS: Mean follow-up time was 10.25 patient-months. There were 14 cardiovascular deaths. CRP was positive (> 10 mg/L) in 64% of the patients, and anti-Chlp-IgG in 64%; 29% of the patients were positive for both markers. The relative risk for cardiovascular mortality was 6.23 for patients positive for either CRP or anti-Chlp-IgG, and increased to 9.52 when both markers were positive. Multivariate analysis revealed that CRP and anti-Chlp-IgG were stronger cardiovascular death predictors than age, diabetes, and nutritional status. CONCLUSION: These data suggest that inflammation and the presence of Chlamydia pneumoniae infections are important predictors of cardiovascular death in patients on CAPD.

Glomerunefritis membranosa secundaria a tuberculosis / Membranous secondary Glumeronefritis to tuberculosis

La tuberculosis (TBC) es una enfermedad multisistémica causada por Mycobacterium tuberculosis, el riñón puede ser afectado en diversas formas, la glomerulonefritis ha sido descrita en forma ocasional, en estos casos el daño es producido por mecanismo inmunológico. Los linfocitos Thelper (Th) se diferencian funcionalmente en dos subtipos Th1 y Th2, que producen dos grupos distintos de citoquinas, las que determinan respuesta inmune diferente. La respuesta inmune en TBC es mediada por inmunidad celular a predominio del tipo Th1. Sin embargo los pacientes que desarrollan TBC extrapulmonar o TBC miliar, presentan una respuesta a predominio del tipo Th2. Presentamos dos pacientes con diagnóstico de TBC extrapulmonar (ganglionar, pleural), glomérulonefritis membranosa (sugerente de activación tipo Th2). Los pacientes con TBC con comprmiso renal en particular en presencia de proteinuria, deben ser mas ampliamente estudiados desde el punto de vista renal e inmunológico.

Hyperuricemia, hypertension, and proteinuria associated with high-altitude polycythemia.

Chronic exposure to high altitude is associated with the development of erythrocytosis, proteinuria, and, in some cases, hyperuricemia. We examined the relationship between high-altitude polycythemia and proteinuria and hyperuricemia in Cerro de Pasco, Peru (altitude, 4,300 m). We studied 25 adult men with hematocrits less than 65% and 27 subjects with excessive erythrocytosis (EE; hematocrit > 65%) living in Cerro de Pasco, Peru and compared them with 28 control subjects living in Lima, Peru (at sea level) and after 48 hours of exposure to high altitude. Serum urate levels were significantly elevated in patients with EE at altitude, and gout occurred in 4 of 27 of these subjects. Urate level strongly correlated with hematocrit (r = 0.71; P < 0.0001). Urate production (24-hour urine urate excretion and urine urate-creatinine ratio) was increased in this group compared with those at sea level. Fractional urate excretion was not increased, and fractional lithium excretion was reduced, in keeping with increased proximal reabsorption of filtrate. Significantly higher blood pressures and decreased renin levels in the EE group were in keeping with increased proximal sodium reabsorption. Serum urate levels correlated with mean blood pressure (r = 0.50; P < 0.0001). Significant proteinuria was more prevalent in the EE group despite normal renal function. Hyperuricemia is common in subjects living at high altitude and associated with EE, hypertension, and proteinuria. The increase in uric acid levels appears to be caused by increased urate generation secondary to systemic hypoxia, although a relative impairment in renal excretion also may contribute.

Excessive erythrocytosis, chronic mountain sickness, and serum cobalt levels.

In a subset of high-altitude dwellers, the appropriate erythrocytotic response becomes excessive and can result in chronic mountain sickness. We studied men with (study group) and without excessive erythrocytosis (packed-cell volume >65%) living in Cerro de Pasco, Peru (altitude 4300 m), and compared them with controls living in Lima, Peru (at sea-level). Toxic serum cobalt concentrations were detected in 11 of 21 (52%) study participants with excessive erythrocytosis, but were undetectable in high altitude or sea-level controls. In the mining community of Cerro de Pasco, cobalt toxicity might be an important contributor to excessive erythrocytosis.

Cistitis aguda: tratamiento por tres días norfloxacino vs. cotrimoxazol / Acute cystitis: treatment for three days norfloxacino vs. cotrimoxazole

Se realizó un estudio prospectivo, doble ciego, randomizado, en el Servicio de Nefrología del Hospital Nacional Arzobispo Loayza, entre los meses de enero a diciembre de 1995, para evaluar un esquema de tratamiento corto, eficaz y económico para pacientes con cistitis aguda en Perú. Se incluyeron 46 pacientes que acudieron al Servicio de Emergencia del hospital con síntomas de cistitis aguda y que cumplían los siguientes criterios: tiempo de enfermedad menor de cinco días, sexo femenino, edad comprendida entre 18 y 50 años, y sedimento de orina patológico. las pacientes se dividieron en dos grupos al azar: las que recibieron tratamiento con Cotrimoxazol-CTM (n igual 22) y con Norfloxacino-NFX (n igual 24). La edad promedio fue 32.02 mas menos 11.7 años. El 80 por ciento de los pacientes fueron menores de 40 años. El tiempo de enfermedad promedio fue de 2.9 mas menos 1.5 días. El 30 por ciento presentaron historia de un episodio previo de cistitis. Los gérmenes aislados fueron E. coli 93.48 por ciento, Proteus sp. 4.35 por ciento y Klebsiella sp. 1.7 por ciento. La sensibilidad antibiótica para CTM fue del 73 por ciento con una curación del 95.45 por ciento. La sensibilidad para NFX fue del 100 por ciento y curación del 87.5 por ciento. El porcentaje de curación fue similar para CTM y NFX (95 vs. 87 por ciento). El costo de tratamiento con CTM fue menor comparado con el tratamiento con NFX. Se concluye que el CTM tiene una buena respuesta clínica a pesar de una menor sensibilidad in vitro y que tanto el CTM como el NFX son antibióticos adecuados para el tratamiento de cistitis aguda, en un esquema acortado de tres días.

Uso de furosemida en insuficiencia renal aguda oligúrica secundaira a cólera / Use of furosemida in renal insuficiency acute secondary oligúrica to rage

Se revisó en forma retrospectiva el comportamiento de 50 pacientes con insuficiencia renal aguda (IRA) oligúrica secundaria a cólera, que recibieron furosemida vía endovenosa. Cuarentiún pacientes (82 por ciento) revirtieron la IRA oligúrica. Veintiseis pacientes que no fueron hemodializados (No HD) tuvieron edad (54. 1ñ 12 vs 50.8 ñ13 años) y tiempo de enfermedad (4.35ñ4.35 vs 5ñ2.6 días) similar a los pacientes hemodializados (HD). La creatinina sérica máxima fue menor en los HD (7.3ñ 2.5 vs 9.8ñ2.0,p <0.01)., fallecieron 6 pacientes HD (p<0.05), la dosis promedio de furosemida fue menos en los No HD (204ñ188 vs 420 ñ233 mg/día, p <0.001). Se concluye que la furosemida logró revertir la IRA oligúrica en el 82 por ciento de pacientes, aquellos que no requirieron HD recibieron dosis menores de furosemida, se plantea que este medicamento a dosis promedio de 200 mg/día selecciona a un grupo de pacientes con menor grado de compromiso renal.