Efecto regulador de paricalcitol sobre parámetros inflamatorios, fibróticos y anticalcificantes en el paciente con enfermedad renal crónica. Más allá de la regulación de la enfermedad óseo-mineral / Paricalcitol regulatory effect on inflammatory, fibrotic and anticalcificating parameters in renal patiente. Far beyond mineral bone disease regulation

ANTECEDENTES: La principal causa de morbimortalidad en el paciente con enfermedad renal crónica (ERC) es la cardiovascular. La inflamación y las alteraciones en el metabolismo óseo-mineral en estos pacientes conllevan aumento del riesgo cardiovascular. OBJETIVOS: Valorar el papel de paricalcitol sobre distintos parámetros séricos relacionados con inflamación, fibrosis y enfermedad óseo-mineral en la ERC. MATERIAL Y MÉTODOS: Estudio prospectivo, no controlado en 46 pacientes con ERC estadios III-V sin diálisis, con niveles elevados de paratohormona, según su estadio de ERC, por lo que se introdujo tratamiento con el análogo de vitamina D paricalcitol. Durante 4 meses de tratamiento valoramos los parámetros clásicos y novedosos del metabolismo óseo-mineral en suero (calcio, fósforo, paratohormona, factor de crecimiento fibroblástico-23 [FGF-23], Klotho y calcidiol) y parámetros relacionados con el proceso de inflamación-fibrosis y anticalcificantes (interleucina-6 y 10, factor de necrosis tumoral alfa [TNF-a], factor de crecimiento transformante beta [TGF-b], proteína ósea morfogénica-7 [BMP-7], y fetuína-A). RESULTADOS: Tras el uso de paricalcitol los niveles de Klotho aumentaron (p = 0,001) y los de FGF-23 se mantuvieron estables al igual que los de calcio y fósforo; calcidiol aumentó de forma significativa (p = 0,010) y paratohormona descendió (p = 0,002). Los parámetros de inflamación, fibrosis y calcificación mostraron una regulación benigna con descenso significativo de interleucina-6 (p = 0,001), TNF-alfa (p = 0,005) y TGF-β (p = 0,001) y aumento de BMP-7 (p = 0,001), fetuína-A (p = 0,001) e interleucina-10 (p = 0,001). El filtrado glomerular y la proteinuria se mantuvieron estables. CONCLUSIONES: El tratamiento con paricalcitol en el paciente renal sin diálisis parece ser beneficioso en la regulación de los parámetros inflamatorios y anticalcificantes, preservando la función renal y el eje óseo-mineral. Los marcadores elegidos en nuestro estudio podrían indicarnos un efecto positivo de paricalcitol a nivel vascular

BACKWARD: Cardiovascular events are the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Inflammation and mineral-bone disorder are pathological conditions that have been associated with an increased cardiovascular risk. OBJECTIVE: Show paricalcitol regulation overinflammatory, fibrotic and mineral disorder parameters in CKD. MATERIAL AND METHODS: Prospective Study in 46 CKD stages III-V patients without dialysis patients whith elevated parathormone in which we introduced paricalcitol. We evaluated classic and newest mineral and bone metabolism serum parameters (calcium, phosphorus, parathormone, fibroblast growth factor-23 [FGF-23], Klotho, calcidiol), inflammatory-fibrosis and anticalcifying parameters (interleukin-6 and 10, tumor necrosis factor-a [TNF- alfa], transforming growth factor-b [TGF-β],bone morphogenic protein-7 [BMP-7] and fetuin-A) for four months. RESULTS: At the end of study soluble Klotho increased (p = .001), FGF-23 remained stable, calcium and phosphorus levels were not increased, calcidiol increased (p = .010) and PTH decreased (p = .002). Inflammation-fibrosis and calcification parameters showed positive regulation after paricalcitol treatment: interleukin-6 decreased significantly (p = .001) and also TNF-alfa did (p = .005), on the contrary, interleukin-10 and fetuin-A increased (p = .001 for both). Anti-fibrosis marker BMP-7 increased (p = .001) and TGF-b decreased (p = .001). We did not find significant changes in renal function. CONCLUSIONS: Paricalcitol treatment might be profitable in regulating inflammatory and anticalcificant parameters, unmodified calcium or phosphorus seric levels and preserving kidney function in renal patients with no dialysis. Our selected parameters could indicate paricalcitol effects in mineral and endothelial disorder related to renal disease

Paricalcitol regulatory effect on inflammatory, fibrotic and anticalcificating parameters in renal patiente. Far beyond mineral bone disease regulation. / Efecto regulador de paricalcitol sobre parámetros inflamatorios, fibróticos y anticalcificantes en el paciente con enfermedad renal crónica. Más allá de la regulación de la enfermedad óseo-mineral.

BACKWARD: Cardiovascular events are the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Inflammation and mineral-bone disorder are pathological conditions that have been associated with an increased cardiovascular risk. OBJECTIVE: Show paricalcitol regulation overinflammatory, fibrotic and mineral disorder parameters in CKD. MATERIAL AND METHODS: Prospective Study in 46 CKD stages III-V patients without dialysis patients whith elevated parathormone in which we introduced paricalcitol. We evaluated classic and newest mineral and bone metabolism serum parameters (calcium, phosphorus, parathormone, fibroblast growth factor-23 [FGF-23], Klotho, calcidiol), inflammatory-fibrosis and anticalcifying parameters (interleukin-6 and 10, tumor necrosis factor-a [TNF- α], transforming growth factor-b [TGF-ß],bone morphogenic protein-7 [BMP-7] and fetuin-A) for four months. RESULTS: At the end of study soluble Klotho increased (p=.001), FGF-23 remained stable, calcium and phosphorus levels were not increased, calcidiol increased (p=.010) and PTH decreased (p=.002). Inflammation-fibrosis and calcification parameters showed positive regulation after paricalcitol treatment: interleukin-6 decreased significantly (p=.001) and also TNF-α did (p=.005), on the contrary, interleukin-10 and fetuin-A increased (p=.001 for both). Anti-fibrosis marker BMP-7 increased (p=.001) and TGF-b decreased (p=.001). We did not find significant changes in renal function. CONCLUSIONS: Paricalcitol treatment might be profitable in regulating inflammatory and anticalcificant parameters, unmodified calcium or phosphorus seric levels and preserving kidney function in renal patients with no dialysis. Our selected parameters could indicate paricalcitol effects in mineral and endothelial disorder related to renal disease.

Surgical Techniques for Catheter Placement and 5/6 Nephrectomy in Murine Models of Peritoneal Dialysis.

Peritoneal dialysis (PD) is a renal replacement therapy consistent on the administration and posterior recovery of a hyperosmotic fluid in the peritoneal cavity to drain water and toxic metabolites that functionally-insufficient kidneys are not able to eliminate. Unfortunately, this procedure deteriorates the peritoneum. Tissue damage triggers the onset of inflammation to heal the injury. If the injury persists and inflammation becomes chronic, it may lead to fibrosis, which is a common occurrence in many diseases. In PD, chronic inflammation and fibrosis, along with other specific processes related to these ones, lead to ultrafiltration capacity deterioration, which means the failure and subsequent cessation of the technique. Working with human samples provides information about this deterioration but presents technical and ethical limitations to obtain biopsies. Animal models are essential to study this deterioration since they overcome these shortcomings. A chronic mouse infusion model was developed in 2008, which benefits from the wide range of genetically modified mice, opening up the possibility of studying the mechanisms involved. This model employs a customized device designed for mice, consisting of a catheter attached to an access port that is placed subcutaneously at the back of the animal. This procedure avoids continuous puncture of the peritoneum during long-term experiments, reducing infections and inflammation due to injections. Thanks to this model, peritoneal damage induced by chronic PD fluid exposure has been characterized and modulated. This technique allows the infusion of large volumes of fluids and could be used for the study of other diseases in which inoculation of drugs or other substances over extended periods of time is necessary. This article shows the method for the surgical placement of the catheter in mice. Moreover, it explains the procedure for a 5/6 nephrectomy to mimic the state of renal insufficiency present in PD patients.

Corrigendum to "T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage".

[This corrects the article DOI: 10.1155/2015/416480.].

T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage.

Fibrosis is a general complication in many diseases. It is the main complication during peritoneal dialysis (PD) treatment, a therapy for renal failure disease. Local inflammation and mesothelial to mesenchymal transition (MMT) are well known key phenomena in peritoneal damage during PD. New data suggest that, in the peritoneal cavity, inflammatory changes may be regulated at least in part by a delicate balance between T helper 17 and regulatory T cells. This paper briefly reviews the implication of the Th17/Treg-axis in fibrotic diseases. Moreover, it compares current evidences described in PD animal experimental models, indicating a loss of Th17/Treg balance (Th17 predominance) leading to peritoneal damage during PD. In addition, considering the new clinical and animal experimental data, new therapeutic strategies to reduce the Th17 response and increase the regulatory T response are proposed. Thus, future goals should be to develop new clinical biomarkers to reverse this immune misbalance and reduce peritoneal fibrosis in PD.

Are the Mesothelial-to-Mesenchymal Transition, Sclerotic Peritonitis Syndromes, and Encapsulating Peritoneal Sclerosis Part of the Same Process?

Mesothelial-to-mesenchymal transition (MMT) is an autoregulated physiological process of tissue repair that in uncontrolled conditions, such as peritoneal dialysis (PD), can lead to peritoneal fibrosis. The maximum expression of sclerotic peritoneal syndromes (SPS) is the encapsulating peritoneal sclerosis (EPS) for which no specific treatment exists. The SPS includes a wide range of peritoneal fibrosis that appears progressively and is considered as a reversible process, while EPS does not. EPS is a serious complication of PD characterized by a progressive intra-abdominal inflammatory process that results in bridles and severe fibrous tissue formation which cover and constrict the viscera. Recent studies show that transdifferentiated mesothelial cells isolated from the PD effluent correlate very well with the clinical events such as the number of hemoperitoneum and peritonitis, as well as with PD function (lower ultrafiltration and high Cr-MTC). In addition, in peritoneal biopsies from PD patients, the MMT correlates very well with anatomical changes (fibrosis and angiogenesis). However, the pathway to reach EPS from SPS has not been fully and completely established. Herein, we present important evidence pointing to the MMT that is present in the initial peritoneal fibrosis stages and it is perpetual over time, with at least theoretical possibility that MMT initiated the fibrosing process to reach EPS.