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Injury of the renal tubulointerstitial compartment is recognized to play an important role in hypertension. Its damage may in turn, impair the activity of vasodepressor systems, like the kallikrein–kinin, in blood pressure regulation. The overload proteinuria model induces tubulointerstitial injury with activation of the renin–angiotensin system, but renal kallikrein and the development of hypertension have not received special attention. Sprague–Dawley rats received seven intraperitoneal doses of bovine serum albumin (BSA) 2 g/day under normosodic diet and were hydrated ad libitum. A second group received a high potassium diet to stimulate kallikrein production during the previous four weeks and while under BSA administration. A third one received potassium and BSA in the same schedule, but with the kinin B2 receptor antagonist, HOE140, added during the protein load phase. A control group received seven saline injections. Kallikrein protein was detected by immune labeling on renal sections and enzymatic activity in the urine. The BSA group showed massive proteinuria followed by intense tubulointerstitial damage. Blood pressure increased after the third dose in BSA animals, remaining elevated throughout the experiment, associated with significant reductions in renal expression and urinary activity of kallikrein, compared with controls. An inverse correlation was found between blood pressure and immunohistochemistry and urinary activity of kallikrein. Potassium induced a significant increase in both urinary activity and renal kallikrein expression, associated with significant reduction in blood pressure. The HOE140 antagonist blunted the antihypertensive effect of kallikrein stimulation in proteinuric rats. Loss of renal kallikrein, produced by tubulointerstitial injury, may participate in the pathogenesis of the hypertension observed in this model.Kidney International (2006) 69, 53–59 doi:10.1038/sj.ki.5000005 [ABSTRACT FROM AUTHOR]

Abstract: To describe HLA antigen distribution, looking for possible markers of renal disease in Mapuche and non-Mapuche people in the renal transplantation program, we reviewed data from 1297 histocompatibility studies of the Chilean national renal transplantation program (421 donors and 876 recipients), performed between 2000 and 2005. Mapuche people were classified according to their family surnames. The most frequent antigens found among the total Chilean population were A2 (48%), A19 (33%), B16 (33%), B35 (26%), DR4 (38%), and DR6 (28%), without significant differences between donors and recipients. Among the 114 individuals (9%) classified as Mapuche, the most frequent antigens were A28 (49%), A2 (44%), B16 (63%), B35 (24%), DR4 (48%), and DR8 (30%), with A28/B16/DR4 as the most common haplotype. In contrast, A28, B16, DR4, and DR8 were significantly more frequent in Mapuche compared with non-Mapuche people. B8 was significantly more frequent in Mapuche recipients than in non-Mapuche recipients and Mapuche donors. The higher frequency of some HLA antigens in Mapuche people was confirmed, possibly corresponding to ethnic markers. The special concentration of B8 among Mapuche recipients might represent a genetic factor predisposing to chronic renal disease in this human group. [Copyright &y& Elsevier]

Abstract: Background: Chronic allograft nephropathy (CAN) is the most frequent cause of chronic dysfunction and late loss of renal allografts. Epithelial mesenchymal transition (EMT) has been identified as responsible for the presence of activated interstitial fibroblasts (myofibroblasts) and transforming growth factor beta (TGF-β)/Smad is the key signaling mediator. It has been proposed that the bone morphogenetic protein 7 (BMP-7) antagonist, Gremlin, could participate in EMT, as a downstream mediator of TGF-β. Methods: We evaluated 33 renal allograft biopsies, 16 of which showed CAN, versus 17 controls. By in situ hybridization we studied the expression of TGF-β and Gremlin mRNA. Gremlin, BMP-7, E-cadherin, and α-smooth muscle actin (α-SMA) proteins were evaluated by immunohistochemistry and Smad3 activation by Southwestern. In cultured human tubuloepithelial cells (HK2 cell line), Gremlin induction by TGF-β was studied by confocal microscopy. Results: Among renal biopsies of transplanted patients with CAN, we detected up-regulation of TGF-β in colocalization with Gremlin (RNA and protein), mainly in areas of tubulointerstitial fibrosis. In the same tubules, we observed decreased expression of E-cadherin and induction of vimentin and α-SMA. BMP-7 was significantly decreased in the CAN biopsies. In addition, HK2 stimulated with TGF-β (1 ng/mL) induced Gremlin production at 72 hours. Conclusion: We postulated that Gremlin is a downstream mediator of TGF-β, suggesting a role for Gremlin in EMT observed in CAN. [Copyright &y& Elsevier]

Abstract: An active regional transplantation program established in the southern region of Chile has allowed the incorporation of ethnic minorities particularly Mapuche living in this geographic area in the development of a histocompatibility database. To identify possible differences in the human leukocyte (HLA) antigen distribution in Chilean Mapuche compared with non-Mapuche, we reviewed 442 HLA tissue-typing studies. Seventy-eight of 309 recipients (25%) and 18 of 133 donors (13%) were Mapuche. Among recipients, Mapuche people showed a significantly higher frequency of the HLA antigens, A28, B16, DR4, and DR8, and a lower one for A19, B15, and DR1 (P < .05) compared with non-Mapuche individuals. A particularly higher frequency of the haplotype A28, -B16, -DR4 was also evidenced in Mapuche. Besides, these recipients showed a higher frequency of the allele -DR4 when compared with Mapuche donors. A greater frequency of some histocompatibility antigens in patients with chronic renal disease might be attributed to allelic concentration due to a high index of endogamy, but a possible association with the development of progressive renal disease cannot be ignored, especially when a higher prevalence of DR4 was observed among Mapuche recipients. [Copyright &y& Elsevier]

Abstract: Previous studies have demonstrated higher concentrations of some histocompatibility antigens in Mapuche people compared with non-Mapuche Chileans in the renal transplantation program. With the aim of evaluating whether those antigenic differences might induce differences in the outcomes of renal transplantation among patients belonging to that ethnic group, we reviewed HLA studies and at least 6 months follow-up of all patients with a first kidney transplant between 1980 and 2006. The 248 patients had a mean age of 37.6 years, 40% were females, and 48% had living related donors. The mean kidney follow-up was 90 months and patient follow-up was 106 months. Thirty-nine patients (16%) were classified as Mapuche, according to their surnames, including 16 women with overall mean age of 34.5 years, and 14 had been transplanted from a living related donor. Mapuche patients received organs with better HLA matching expressed as number of identities (3.4 ± 0.1 versus 2.8 ± 0.1 among non-Mapuche; P < .05), and the proportion receiving organs with ≥3 compatibilities was significantly higher (Mapuche 38% versus non-Mapuche 22%; P < .05). Kaplan-Meier survival curves showed nonsignificant differences in kidney survival: 86% at 5 years and 68% at 10 years in Mapuche; and 83% and 65%, respectively, for non-Mapuche. Patient survival rates were 97% at 5 years and 86% at 10 years in the Mapuche group versus 91% and 79%, respectively, in the non-Mapuche group; both results were not significantly different. Our results showed similar outcomes of kidney and patient survivals among Mapuche people even when they received organs with better HLA matches. [Copyright &y& Elsevier]