Potential role of NKG2D and its ligands in organ transplantation: new target for immunointervention.

NKG2D is one of the best characterized activating receptors on Natural Killer (NK) and CD8+ T cells. This receptor recognizes several different ligands (MICA/MICB and ULBPs) induced by cellular stress and infection. In addition to the role described in cancer surveillance, recent data highlight the importance of NKG2D and its ligands in organ transplantation. Allografts show evidence of MICA and MICB expression in both acute and chronic rejection. The presence of anti-MICA antibodies has been correlated with incidence of graft rejection. Furthermore, NKG2D-ligand engagement activates NK cells, which provides T-cell costimulation, and enhances antigen specific CTL-mediated cytotoxicity. Activated NK cells may function as a bridge between innate and adaptive immunity associated with transplantation. Activated NK cells in response to IL-15 can also trigger organ rejection through NKG2D and affect the maturation of both donor and recipient antigen presenting cells (APCs) and ultimately the T-cell allogeneic response. Regulatory T cells, which modulate T-cell responses in organ transplantation and infections, were reduced in numbers by NK cells exposed to intracellular pathogens, possibly via interaction with one NK2GD receptor. Blockage of NKG2D-NKG2D-L interactions provides a novel pathway for development of inhibitors. These studies have important clinical and therapeutic implications in solid organ transplantation.

Single dose of Rituximab plus plasmapheresis in an HIV patient with acute humoral kidney transplant rejection: a case report.

Before the highly active antiretroviral therapy (HAART) era, kidney transplantation was not considered an option for patients infected with human immunodeficiency virus (HIV) because of its poor outcome. However, recent studies have demonstrated results comparable to those of recipients without HIV infections. They have shown that HIV-positive patients maintained on HAART mount an immune response. Immunosuppressive agents are chosen to minimize aggravation of HIV infection, bearing in mind the potential side effects of the combination of HAART and immunosuppressive drugs. Herein we have reported the case of a 43-year-old HIV- and hepatitis C virus-infected woman with preserved immune function who received a cadaveric kidney transplant and developed an acute humoral rejection, which was successfully treated with Rituximab.

[Renal transplantation in HIV-infected patients in Spain]. / Trasplante renal en pacientes con infección VIH en España.

HIV infection has experienced dramatic improvement in morbidity and mortality with the highly active antiretroviral therapy (HAART). This prompted a reevaluation of organ-solid transplantation as a treatment option for HIV-infected patients. Some trials in the United States have shown that one- and 2-year graft and patient survival is comparable to HIV-negative transplant population. In Europe the experience is still scarce. The aim of this study is to analyse the outcome and the clinical characteristics of HIV-infected patients who received kidney transplantation in Spain in the HAART era. Ten patients were transplanted in our country since 2001. Only one patient was black. The main cause of end-stage renal disease reported was glomerulonephritis. Six of the recipients were coinfected by hepatitis C virus. Inclusion criteria included undetectable HIV viral load and CD4 counts greater than 200/pL. Immunosuppression consisted of steroids, tacrolimus and mycophenolate mofetil, with antibody induction in 4 cases. The median and mean follow-up was 11 and 16.3+/-15.6 (3-46) months, respectively. One recipient lost his graft because of early renal venous thrombosis. The remaining patients are functioning graft with mean serum creatinina level of 1.5 +/- 0.5 mg/dl. Biopsy-proven acute rejection was diagnosed in 4 recipients and was reversed in all cases with antirejection treatment. The plasma HIV RNA levels have remained controlled and CD4 counts have been stable in excess of 200 cell/microL. None of patients have developed AIDS complications. Recipients receiving protease inhibitor-based HAART regimens required significant dosing modification to maintain appropriate tacrolimus levels. Our results show that renal transplantation can be a safe and effective treatment in select HIV-infected patients. Like other series, the acute rejection rate was higher than in non-HIV recipients. The reasons of this rejection incidence remain unknown.

Cytomegalovirus replication and "herpesvirus burden" as risk factor of cardiovascular events in the first year after renal transplantation.

Cytomegalovirus (CMV) infection alone or in combination with other pathogens ("pathogen burden") has been postulated as a factor producing arteriosclerosis in some solid organ transplant recipients. The aim of this study was to assess whether the patients with CMV replication and/or "herpesvirus burden" experienced a greater incidence of cardiovascular events during the first year after kidney transplantation. One hundred twenty-one consecutive transplant recipients were prospectively studied for CMV replication using antigenemia and polymerase chain reaction (PCR) weekly during the 4 first months, and monthly thereafter for 1 year. Simultaneously, nested-PCR for human herpes virus (HHV)-6 and HHV-7 were performed to yield a herpesvirus burden (as determined by seropositivity), including CMV, herpes simplex virus (HSV), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV). The following additional parameters were analyzed: gender, age, smoking, duration of dialysis, preexistent diabetes, and preexistent cardiovascular events. After 1 year posttransplantation cardiovascular events, body mass index, arterial hypertension, number of antihypertensive drugs, use of ACE and/or ARBs inhibitors, diabetes, anemia, homocysteine, creatinine, cholesterol, HDLc, LDLc, PTH-i, proteinuria, and immunosuppression with cyclosporine or tacrolimus. CMV replication was present in 79 (65.3%) patients. Among 121 renal transplant recipients, 13 presented cardiovascular events, all associated with CMV replication (P = .004). Neither HHV-6 or HHV-7 replication influenced this complication. All patients with these events were seropositive for CMV, HSV, VZV, and EBV, as opposed to 64.8% without them (P = .009). Other factors that showed differences between patients with versus without events were as follows: preexistent events (76.9% vs 14.8%; P = .000), age (60 +/- 10 vs 49 +/- 14; P = .002), serum triglyceride value (191 +/- 82 vs 135 +/- 72; P = .02), and anemia (23.1% vs 5.6%; P = .05). Multiple logistic regression analysis for statistically significant variables only showed that preexistent events influenced the development of posttransplantation events (odds ratio, 27; 95% confidence interval, 4.7-154; P = .0005). In conclusion, cardiovascular events within 1 year after transplantation were more frequent among patients with CMV replication and seropositivity for other herpesviruses. An important risk factor was the presence of preexistent events.

Is the loss of health-related quality of life during renal replacement therapy lower in elderly patients than in younger patients?

BACKGROUND: Previous studies have reported that elderly (aged 65 years or over) end-stage renal disease (ESRD) patients have poorer health-related quality of life (HRQOL) than both younger patients and healthy subjects of the same age. The aim of present study was to evaluate the effect of ESRD and its treatment on the HRQOL, and to determine the effects of age and gender. METHODS: A cross-sectional multicentric study was carried out with 485 haemodialysis and renal-transplant patients, using the SF-36 Health Survey to evaluate their HRQOL. SF-36 scores were standardized by age and gender using Spanish normative data. Karnofsky scale score (KS), socio-demographic, and clinical data were also collected. RESULTS: In renal-replacement therapy (RRT), chronic haemodialysis, and renal-transplant patients, SF-36 standardized scores of elderly patients were higher than in younger patients. Therefore the reduction in HRQOL of elderly patients, in relationship with that of the general population of the same age and gender, was lower than in younger patients. In the case of renal-transplant patients, standardized scores in elderly patients were higher than in the general population for all parameters. CONCLUSIONS: Using standardized scores, elderly patients on renal replacement therapy (haemodialysis and kidney transplant) had relatively better HRQOL than younger patients, and in the case of transplant patients, they had even better HRQOL than in the general population of the same age and gender.

Health related quality of life (HRQOL) of kidney transplanted patients: variables that influence it.

UNLABELLED: The incidence and prevalence of patients on renal replacement therapy (RRT) who receive a renal transplant are continuously increasing in Spain. At the moment, they are the main group of end-stage renal disease (ESRD) patients in our region (60% of total RRT patients). The aim of the present study was to assess the health related quality of life (HRQOL) of kidney transplanted patients of our region, and to identify socio-demographic and clinical variables that influence it. The intention was also to compare the HRQOL of these patients with that of chronic haemodialysis (HD) patients and of the general population. METHODS: Two hundred and ten kidney transplanted patients and 170 HD patients were evaluated using the Karnofsky performance scale (KPS), sickness impact profile (SIP), and SF-36 Health Survey (SF-36). Socio-demographic and clinical data, including a comorbidity index (CI), were also collected. To compare our patients with the general population we used SF-36 mean scores from an aleatory sample taken from our region. RESULTS: Transplant patients had lower mean scores on SIP dimensions and higher scores on SF-36 dimensions than chronic HD patients. In transplant patients, we found significant differences on SIP and SF-36 scores in gender, educational level, haematocrite and haemoglobin, CI, time since transplantation, and KPS. CONCLUSIONS: The HRQOL of transplant patients is clearly better than that of chronic HD patients and similar to that of the general population. Differences in the HRQOL within transplant patients did not appear to be as a result of patient's age, but rather it would appear to be a consequence of gender, analytic figures, CI, KPS score, time with transplant, and educational level.

Health-related quality of life (HRQOL) in end stage renal disease (ESRD) patients over 65 years.

OBJECTIVES: The aim of the study was to assess Health Related Quality of Life (HRQOL) of elderly patients on renal replacement therapy (RRT) of our region, and to identify socio-demographic and clinical variables which influence it. We also attempted to compare HRQOL of transplant patients, with that of chronic hemodialysis patients. DESIGN: Cross-sectional study. SETTING: Institutional Hospital Nephrology Unit. PATIENTS: All patients from 9 of the 10 hemodialysis centres in our region, aged 65 years or more, who had been on RRT (chronic hemodialysis and kidney transplantation) for at least three months, showing no cognitive problems, were included. The sample included 124 patients. INTERVENTIONS: These patients participated in a structured interview using two generic HRQOL questionnaires: Sickness Impact Profile and SF-36 Health Survey. Karnofsky Scale, Comorbidity Index, socio-demographic and clinical data, were also collected. RESULTS: The median age was 71 years (range 65-75); 55.6% of the patients were male; 19.8% of the sample were transplant patients and 80.2%, hemodialysis patients (only 2% on renal transplant waiting list); 69.2% had a low-intermediate socio-economic level, 52.9% had elementary studies, and 10.6% lived alone. Transplant patients had higher HRQOL than hemodialysis patients. Women had lower HRQOL than men. A higher economic level, higher educational level, higher Karnofsky Performance Scale, and lower Comorbidity Index score, were associated with higher HRQOL. CONCLUSIONS: The good HRQOL of elderly transplant patients, in comparison with hemodialysis patients, is an important reason for advising kidney transplants in elderly patients. Economic and educational levels, functional status and comorbidity are variables which influence the HRQOL of these patients.