[Vascular damage in chronic renal failure. The increase of vascular nitrotyrosine and cytochines accumulation is accompanied by an increase of endothelial nitric oxide synthase (eNOS) expression]. / Daño vascular en la insuficiencia renal crónica. El aumento de depósitos vasculares de nitrotirosina y citocinas se acompaña de una elevación de la expresión vascular de la óxido nítrico sintasa endotelial (eNOS).

Patients with chronic renal failure (CRF) are at a greatly increased risk of cardiovascular mortality. This fact could be due to the presence of conventional risk factor and specific uremic as increase of oxidative stress, hyperhomocystaenemia, deranged calcium-phosphate metabolism and chronic inflammatory state. In order to analyze the vascular effects of CRF, we studied the histomorphometric characteristics (intima-media thickness and monocyte chemoattractant protein (MCP-1) accumulation (inmunohistochemical) on radial artery from 13 patients with CRF. We determined by Western blot analysis, the vascular nitrotyrosin abundance (footprint of nitric oxide (NO) inactivation by reactive oxygen species (ROS), and the endothelial nitric oxide synthase (eNOS) expression. The NOS activity was, also, determined. The results were compared with those obtained in pudenda artery from a healthy control group (n: 16). The CRF group showed a significant increase in intima and media thickness 108 +/- 16 vs 14 +/- 2.5 microm, p < 0.001 and 291 +/- 19 vs 153 +/- 15 microm, p < 0.001, respectively). The CRF group exhibited a marked elevation of MCP-1 vascular expression (2 +/- 0.15 vs 0.6 +/- 0.12 u, p < 0.001). A significant positive correlation was found between MCP-1 vascular expression and its inmunohistochemical deposits (r: 0.98, p < 0.0001). Nitrotyrosin abundance (western blot) was significantly increased in artery of CRF patients (2.1 +/- 0.1 vs 0.42 +/- 0.1 u, p < 0.0001). No significant differences was found in NOS activity between CRF and control groups. However, eNOS expression was greatly increased in the CRF patients (1.73 +/- 0.1 vs 0.67 +/- 0.1 u, p < 0.001). A significant positive correlation was found between nitrotyrosin and eNOS expression and systolic arterial pressure. However, the differences between CRF and control groups persisted after statistically fitting to arterial pressure. The present study demonstrate that in CRF there are arterial preatherosclerotic changes and an increase of vascular nitrotyrosin accumulation, which is the footprint of NO inactivation by ROS. The secondary NO inactivation can, in turn, contribute to eNOS vascular upregulation.

Daño vascular en la insuficiencia renal crónica. El aumento de depósitos vasculares de nitrotirosina y citocinas se acompaña de una elevación de la expresión vascular de la óxido nítrico sintasa endotelial (eNOS) / Vascular damage in chronic renal failure. The increase of vascular nitrotyrosine and cytochines accumulation is accompanied by an increase of endothelial nitric oxide synthase (ENOS) expression

La insuficiencia renal crónica (IRC) se acompaña de un aumento de la morbimortalidadcardiovascular debido a la concurrencia de factores de riesgo cardiovasculartradicionales y otros factores inherentes a la uremia como estrés oxidativo,hiperhomocisteinemia, anomalías del metabolismo fosfocálcico, anemia yfenómenos inflamatorios entre otros.Para analizar la repercusión vascular de la IRC, en este trabajo se hace un estudiohistomorfométrico (grosor íntima-media) y de los depósitos vasculares (inmuno-histoquímica) de la proteína quimiotáctica de monocitos (MPC-1) de la arteriaradial en 13 sujetos con IRC, Se determinan, también, la expresión vascular(western blot) de nitrotirosina (marcador del efecto de especies reactivas de oxígeno(ROS) sobre el óxido nítrico (ON), de la MCP-1 (citocina con efecto aterogénico)y de la óxido nítrico sintasa endotelial (eNOS), y la actividad de la NOS.Los hallazgos se comparan con los observados en la arteria pudenda, arteria muscularde las mismas características que la radial, en un grupo control sano (n: 16),de edad y sexo similares a los enfermos.El grosor de la íntima y de la media fue mayor en los enfermos (íntima 108 ±16 vs 14 ± 2,5 µ, p < 0,001; media: 291 ± 19 vs 153 ± 15 µ, p < 0,001). La expresiónvascular de la MCP-1 en los enfermos fue más elevada que en los controles(2 ± 0,15 vs 0,6 ± 0,12 u, p < 0,001). La expresión de la proteína se correlacionócon los depósitos inmunohistoquímicos de la misma (r: 0,98, p <0,0001). Las arterias de los enfermos con IRC tenían mayor expresión de nitrotirosinaque las de los sujetos sanos (2,1 ± 0,1 vs 0,42 ± 0,1 u, p < 0,0001). Noexistieron diferencias significativas en la actividad de la NOS entre los dos grupos.La expresión de la eNOS, sin embargo, fue significativamente más elevada enlos enfermos con IRC (1,73 ± 0,1 vs 0,67 ± 0,1 u, p < 0,001). La expresión dela nitrotirosina y de la eNOS se correlacionó directamente con la presión arterial sistólica. No obstante, las diferencias entre los grupos persistieron tras los ajustesa los valores de presión arterial.Estos resultados demuestran que en la IRC, a nivel de la arteria radial, existencambios preaterosclerosos, y un aumento de los depósitos de nitrotirosina, marcadordel efecto de ROS sobre el ON. Secundariamente a la disminución de labioactividad del ON, se produce un aumento compensador de la expresión vascularde la eNOS

Patients with chronic renal failure (CRF) are at a greatly increased risk of cardiovascularmortality. This fact could be due to the presence of conventional riskfactor and specific uremic as increase of oxidative stress, hyperhomocystaenemia,deranged calcium-phosphate metabolism and chronic inflammatory state.In order to analyce the vascular effects of CRF, we studied the histomorphometriccharacteristics (intima-media tickness and monocyte chemoattractant protein(MCP-1) accumulation (inmunohistochemical) on radial artery from 13 patientswith CRF. We determined by Western blot analysis, the vascular nitrotyrosinabundance (footprint of nitric oxide (NO) inactivation by reactive oxygen species(ROS), and the endothelial nitric oxide synthase (eNOS) expression. The NOS activitywas, also, determined. The results were compared with those obtained inpudenda artery from a healthy control group (n: 16).The CRF group showed a significant increase in intima and media tickness 108± 16 vs 14 ± 2,5 µ, p < 0,001 and 291 ± 19 vs 153 ± 15 µ, p < 0,001, respectively).The CRF group exhibited a marked elevation of MCP-1 vascular expression(2 ± 0,15 vs 0,6 ± 0,12 u, p < 0,001). A significant positive correlationwas found between MCP-1 vascular expression and its inmunohistochemical deposits(r: 0,98, p < 0,0001). Nitrotyrosin abundance (western blot) was significantlyincreased in artery of CRF patients (2,1 ± 0,1 vs 0,42 ± 0,1 u, p < 0,0001).No significant differences was found in NOS activity between CRF and controlgroups. However, eNOS expression was greatly increased in the CRF patients(1,73 ± 0,1 vs 0,67 ± 0,1 u, p < 0,001). A significant positive correlation wasfound between nitrotyrosin and eNOS expression and systolic arterial pressure.However, the differences between CRF and control groups persisted after statisticallyfitting to arterial pressure.The present study demonstrate that in CRF there are arterial preatheroscleroticchanges and an increase of vascular nitrotyrosin accumulation, wich is the footprintof NO inactivation by ROS. The secondary NO inactivation can, in turn, contributeto eNOS vascular upregulation

Free protein S deficiency in hemodialysis patients due to vascular calcifications?

Vascular calcifications are frequent in hemodialysis patients. Its incidence ranges from 25 to 67% depending of different series. Thirty hemodialysis patients were selected from a dialysis population of 150 patients. These 30 patients were divided into two groups: group I included 15 hemodialysis patients with severe secondary hyperparathyroidism and severe, roentgenographically visible diffuse vascular calcifications, and group II included 15 other hemodialysis patients with moderate hyperparathyroidism without radiographic evidence of arterial calcifications. The control group comprised 20 normal volunteers. In all patients, measurements of protein C activity, free protein S and intact parathyroid hormone (PTH) were performed. Statistical analysis showed that free protein S in the patients of group I had a tendency to be lower than in the patients of group II (p < 0.01) and the control group (p < 0.001). We did not find significant differences in free protein S between group II and control group patients nor a significant correlation between intact PTH and free protein S in groups I and II. Protein C activity was found to be in the normal range in both groups. Free protein S deficiency in patients of group I would suggest a synthesis defect by impaired endothelial cells-due to vascular calcifications (?). Free protein S deficiency could increase the risk of thrombotic complications in these patients.

Treatment of severe secondary hyperparathyroidism with administration of calcium carbonate, intermittent high oral doses of 1,25-dihydroxyvitamin D3 and dialysate with 3 mEq/1 calcium concentration.

In this study, we evaluated the effect of long-term administration of daily calcium carbonate (2-4 g/day) and intermittent high oral doses of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3, 3-4 micrograms, given twice a week] in conjunction with a 3-mEq/1 calcium concentration in the dialysate for the treatment of severe secondary hyperparathyroidism in 6 hemodialysis patients. All patients had reduced serum levels of 1,25-(OH)2D3, which increased significantly (p < 0.005) reaching the maximum level in the 4th month. Serum total and ionized calcium levels significantly increased also, in relation to those before treatment. No patients developed hypercalcemia. Serum phosphorus did not significantly change during the study. Initial serum intact parathyroid hormone (PTH) (1,241 +/- 233 pg/ml, mean +/- SEM) markedly decreased after starting treatment with 1,25-(OH)2D3, being 542 +/- 174 pg/ml in the 5th month and 477 +/- 174 pg/ml in the 8th month. These changes are statistically significant (p < 0.05 and < 0.007, respectively). Alkaline phosphatase behavior was similar to that of intact PTH. A constant direct correlation between intact PTH and alkaline phosphatase and an inverse significant correlation between intact PTH and 1,25-(OH)2D3 was evidenced by us. We conclude that oral 1,25-(OH)2D3 pulse therapy is very effective in suppressing PTH secretion. The administration of calcium carbonate and the use of dialysate with a reduced calcium concentration would allow to prevent hyperphosphatemia and the administration of high oral doses of 1,25-(OH)2D3 without concomitant hypercalcemia.

Renal artery thrombosis occurring in an adult with the idiopathic nephrotic syndrome: results of local treatment with streptokinase.

A 55 year old male with the idiopathic nephrotic syndrome (minimal glomerular lesions by light microscopy and negative immunofluorescent stainings) presented righ renal artery thrombosis as evidenced by clinical and arteriographic findings. Local Streptokinase infusion by means of a renal artery catheter resulted in revascularization of the arterial tree, although recovery of renal function was only partial.