Kidney Transplant Research Today is a free monthly online journal that collates and summarizes the latest research about Kidney Transplant, including details on risks, prognosis, procedure, surgery, organ donation.

Chemokine receptor Ccr5 deficiency induces alternative macrophage activation and improves long-term renal allograft outcome.

Dehmel S, Wang S, Schmidt C, Kiss E, Loewe RP, Chilla S, Schlöndorff D, Gröne HJ, Luckow B

Klinikum der Universität München, Medizinische Poliklinik-Innenstadt, München, Germany.

The chemokine (C-C motif) receptor 5 (CCR5) has been implicated in experimental and clinical allograft rejection. To dissect the function of CCR5 in acute and chronic renal allograft rejection, bilaterally nephrectomized WT and Ccr5-/- C57BL/6 mice were used as recipients of WT BALB/c renal allografts and analyzed 7 and 42 days after transplantation. Lesion scores (glomerular damage, vascular rejection, tubulointerstitial inflammation) and numbers of CD4+, CD8+, CD11c+ and alpha smooth muscle actin (alphaSMA)+ cells were reduced in allografts from Ccr5-/- recipients during the chronic phase. Increasing creatinine levels indicated deterioration of allograft function over time. While mRNA expression of Th1-associated markers decreased between 7 and 42 days, Th2-associated markers increased. Markers for alternatively activated macrophages (arginase 1, chitinase 3-like 3, resistin-like alpha, mannose receptor, C type 1), were strongly upregulated (mRNA and/or protein level) only in allografts from Ccr5-/- recipients at 42 days. Ccr5 deficiency shifted intragraft immune responses during the chronic phase towards the Th2 type and led to accumulation of alternatively activated macrophages. Additionally, splenocytes from unchallenged Ccr5-/- mice showed significantly increased arginase 1 and mannose receptor 1 mRNA levels, suggesting constitutive alternative activation of splenic macrophages. We conclude that Ccr5 deficiency favors alternative macrophage activation. This finding may be relevant for other inflammatory diseases that involve macrophage activation and may also influence future therapeutic strategies targeting CCR5.

Published 4 January 2010 in Eur J Immunol, 40(1): 267-78.
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Articles on Kidney Transplant published 23 December 2009:

HLA class I (ABC) upregulation on peripheral blood CD3+/CD8+ T lymphocyte surface is a potential predictor of acute rejection in renal transplantation.   Transplantation, 88(12): 1393-7.

BACKGROUND: Renal transplantation is currently the prevalent therapy for most patients with end-stage renal disease. No clinical markers for such rejection have been universally accepted. We aimed to investigate the possibility of use of human leukocyte antigen (HLA) class I (ABC) on peripheral blood CD3+/CD8+ T lymphocytes as a marker of acute rejection. METHODS: For recipients undergoing renal transplantation from September 2007 to November 2008, peripheral blood samples were obtained ... [Abstract] [Full-text]

Donor and recipient contribution to transplant vasculopathy in chronic renal transplant dysfunction.   Transplantation, 88(12): 1386-92.

BACKGROUND: Chronic transplant dysfunction is the leading cause of long-term renal allograft loss. One of the histologic hallmarks of chronic transplant dysfunction is transplant vasculopathy characterized by accumulation of smooth muscle cells (SMCs) in the arterial subendothelial space, leading to ischemic graft failure. Currently, no therapy is available for transplant vasculopathy, and knowledge of the origin (donor vs. recipient) of neointimal cells may contribute to develop adequate ... [Abstract] [Full-text]

Effect of hemodialysis before transplant surgery on renal allograft function--a pair of randomized controlled trials.   Transplantation, 88(12): 1377-85.

BACKGROUND: Hemodialysis immediately before kidney transplant surgery has been suggested to adversely affect early graft function. On the other hand, considering its profound antiinflammatory effects, a beneficial impact of regional citrate anticoagulation on the evolution of graft function can be speculated. We sought to assess the clinical impact of preoperative hemodialysis and dialysis anticoagulation in two related randomized trials. METHODS: Eligible kidney transplant candidates with a ... [Abstract] [Full-text]

A study of renal outcomes in African American living kidney donors.   Transplantation, 88(12): 1371-6.

BACKGROUND: Little is known about the long-term outcomes of African American living kidney donors (AALKDs). We undertook this study to describe renal outcomes of AALKDs several years after donation. METHODS: We invited 107 AALKDs to come for follow-up health evaluation. RESULTS: Thirty-nine subjects (36.4%) completed evaluation at a mean of 7.1+/-1.6 (range, 3.9-10.2) years postdonation. The mean estimated glomerular filtration rate using the abbreviated Modification of Diet in Renal Disease ... [Abstract] [Full-text]

Maximizing growth in children after renal transplantation.   Transplantation, 88(12): 1321-2.

Achieving normal height in children after renal transplantation is a crucial issue for both quality of life and self-esteem. The management of growth retardation in renal transplant recipients includes adequate nutritional intake, correction of acidosis, optimal drug compliance, limited calcineurin inhibitor nephrotoxicity, steroid-sparing strategies, and sometimes recombinant human growth hormone. [Abstract] [Full-text]

Articles on Kidney Transplant published 22 December 2009:

Kidney donation from children after cardiac death.   Crit Care Med, 38(1): 249-53.

OBJECTIVE: Pediatric kidney donation after cardiac death is an underutilized donor source because of ethical concerns and limited knowledge of the outcome after transplantation. The purpose of this study was to report the Dutch experience of kidney transplantation using pediatric donation after cardiac death. DESIGN: Observational cohort study of a series of consecutive kidney transplantations from pediatric donation after cardiac death from January 1995 to July 2006. SETTING: Kidneys were ... [Abstract] [Full-text]

Articles on Kidney Transplant published 17 December 2009:

Randomized clinical trial of laparoscopic versus open donor nephrectomy.   Br J Surg, 97(1): 21-8.

BACKGROUND: This randomized controlled trial was designed to determine the safety and efficacy of laparoscopic donor nephrectomy (LDN) in comparison with short-incision open donor nephrectomy (ODN). METHODS: Eighty-four live kidney donors were randomized in a 2 : 1 ratio to LDN (56 patients) or short-incision ODN without rib resection (28). Primary endpoints were pain relief and duration of inpatient stay. RESULTS: There was no donor death or allograft thrombosis in either group. The first warm ... [Abstract] [Full-text]

Articles on Kidney Transplant published 16 December 2009:

Cadmium, mercury, and lead in kidney cortex of living kidney donors: Impact of different exposure sources.   Environ Res, 110(1): 47-54.

BACKGROUND: Most current knowledge on kidney concentrations of nephrotoxic metals like cadmium (Cd), mercury (Hg), or lead (Pb) comes from autopsy studies. Assessment of metal concentrations in kidney biopsies from living subjects can be combined with information about exposure sources like smoking, diet, and occupation supplied by the biopsied subjects themselves. OBJECTIVES: To determine kidney concentrations of Cd, Hg, and Pb in living kidney donors, and assess associations with common ... [Abstract] [Full-text]

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