ß,γ-Methylene-ATP and its metabolite medronic acid affect both arterial media calcification and bone mineralization in non-CKD and CKD rats.

Arterial media calcification or pathological deposition of calcium-phosphate crystals in the vessel wall contributes significantly to the high mortality rate observed in patients with CKD. Extracellular nucleotides (ie, ATP or UTP) regulate the arterial calcification process by interacting with (1) purinergic receptors and (2) breakdown via ecto-nucleotidases, such as ectonucleotide pyrophosphatase/phosphodiesterase NPP1 or NPP3, affecting the local levels of calcification inhibitor, pyrophosphate, and stimulator inorganic phosphate (PPi/Pi ratio). Also, it has been shown that ATP analogs (ie, ß,γ-methylene-ATP [ß,γ-meATP]) inhibit vascular smooth muscle cell calcification in vitro. In the first experiment, daily dosing of ß,γ-meATP (2 mg/kg) was investigated in rats fed a warfarin diet to trigger the development of non-CKD-related arterial medial calcifications. This study showed that ß,γ-meATP significantly lowered the calcium scores in the aorta and peripheral vessels in warfarin-exposed rats. In a second experiment, daily dosing of 4 mg/kg ß,γ-meATP and its metabolite medronic acid (MDP) was analyzed in rats fed an adenine diet to promote the development of CKD-related arterial medial calcification. Administration of ß,γ-meATP and MDP did not significantly decrease aortic calcification scores in this model. Moreover, both compounds induced deleterious effects on physiological bone mineralization, causing an imminent risk for worsening the already compromised bone status in CKD. Due to this, it was not possible to raise the dosage of both compounds to tackle CKD-related arterial calcification. Again, this points out the difficult task of targeting solely ectopic calcifications without negatively affecting physiological bone mineralization. On the other hand, aortic mRNA expression of Enpp1 and Enpp3 was significantly and positively associated with aortic calcification scores, suggesting that normalizing the aortic NPP1/3 activity to control values might be a possible target to treat (CKD-induced) arterial media calcifications.

Plomo y nefropatía: biomarcadores urinarios en la detección de daño renal precoz / Blood lead levels and markers of renal dysfunction among mechanical workshop workers

The role of lead (Pb) as an environmental cause of nephropathy is difficult to ascertain due to the difficulty to determine clinically its exposure. Aim: To assess lead levels and renal function in a group of males working in mechanical workshops. Material and Methods: Blood and urine samples were obtained from 100 mechanical workshop workers aged 38 ± 16 years and 95 non-exposed office clerks aged 37 ± 17 years. Blood lead and creatinine levels were determined. In exposed workers, urinary excretion of intestinal alkaline phosphatases (IAP) and N-acetyl-glucosaminidase (NAG) were measured as early markers of renal failure. Results: Blood lead levels were 66.4 ± 43 and 33.6 ± 18 µg/L among mechanical workshop workers and non-exposed controls, respectively, p < 0.01. The figures for serum creatinine were 0.9 ± 0.1 and 0.9 ± 0.1 respectively, p = NS. Among exposed workers urinary excretion of IAP was 0.47 ± 0.6 U/L and of NAG, 0.92 ± 1.1 U/L. There was a positive correlation between blood lead levels and NAG excretion (r = 0.284) and IAP excretion (r = 0.346). Conclusions: Exposed workers had higher blood lead levels and there was a weak positive association between these levels and the urinary excretion of NAG and IAP.

Estroncio y acidosis: efecto combinado sobre los huesos de ratas con falla renal crónica / Strontium anda acidosis: combined effects on bone in rats with chronic renal failure

En once ratas Wistar se realizó nefrectomía 5/6 a fin de conseguir una insuficiencia renal crónica moderada. Tres ratas recibieron cloruro de estroncio (2pto-20.0 g/L) (GS), tres ratas; cloruro de amonio (0.25M) (GAc), tres ratas recibio la conbinación de estroncio y amonio, a la misma concentración que las anteriores (GSAc), y dos ratas fueron el grupo control (GC), las cuáles recibieron agua de canilla. El GS presentó una leve disminución de los niveles de bicarbonato plasmático (de 23,1 a 20,6 mmol/L), sin alcanzar diferencias significativas, por el contrario, lo grupos. GAc y GSAc, presentaron un agran disminución de los niveles de bicarbonato (GA:de 24,7 mmol/L a 13,4 mmol/L). En el GC, no se observaron cambios. Los niveles séricos de estroncio ascendieron significativamente en los grupos GS y GSAc, permaneciendo dentro de valores normales en otros grupos (GAc y GC). En lo que concierne a los huesos, hemos encontrado una gran concentración ósea de estroncio en GS y GSAc, comparados a los otros grupos. En el análisishistológico de los huesos, encontramos en el GS, un gran aumento del tejido osteoide, un bajo ídice de formación ósea, y un prolongado tiempo de mineralización. En el grupo estroncio/ácido, hubo una disminución del tejido osteoide, con una disminución de la formación ósea y una disminución de mineralización. En el GAcy en el GC, no se han encontrado anomalías óseas de valor. Conclusión: En el grupo que recibio solamente estroncio, se ha desarrolado una severa osteomalacia, por el contrario, si esta carga de estroncio ocurre en un ambiente acidótico, el metal conduce a la enfermedad ósea adinámica.