Cyclosporine A Inhibits the T-bet-Dependent Antitumor Response of CD8(+) T Cells.

Transplant recipients face an increased risk of cancer compared with the healthy population. Although several studies have examined the direct effects of immunosuppressive drugs on cancer cells, little is known about the interactions between pharmacological immunosuppression and cancer immunosurveillance. We investigated the different effects of rapamycin (Rapa) versus cyclosporine A (CsA) on tumor-reactive CD8(+) T cells. After adoptive transfer of CD8(+) T cell receptor-transgenic OTI T cells, recipient mice received either skin grafts expressing ovalbumin (OVA) or OVA-expressing B16F10 melanoma cells. Animals were treated daily with Rapa or CsA. Skin graft rejection and tumor growth as well as molecular and cellular analyses of skin- and tumor-infiltrating lymphocytes were performed. Both Rapa and CsA were equally efficient in prolonging skin graft survival when applied at clinically relevant doses. In contrast to Rapa-treated animals, CsA led to accelerated tumor growth in the presence of adoptively transferred tumor-reactive CD8(+) OTI T cells. Further analyses showed that T-bet was downregulated by CsA (but not Rapa) in CD8(+) T cells and that cancer cytotoxicity was profoundly inhibited in the absence of T-bet. CsA reduces T-bet-dependent cancer immunosurveillance by CD8(+) T cells. This may contribute to the increased cancer risk in transplant recipients receiving calcineurin inhibitors.

Association between individual and combined SNPs in genes related to innate immunity and incidence of CMV infection in seropositive kidney transplant recipients.

In this study, we assessed the association between single-nucleotide polymorphisms (SNPs) in seven candidate genes involved in orchestrating the immune response against cytomegalovirus (CMV) and the 12-month incidence of CMV infection in 315 CMV-seropositive kidney transplant (KT) recipients. Patients were managed either by antiviral prophylaxis or preemptive therapy. CMV infection occurred in 140 patients (44.4%), including 13 episodes of disease. After adjusting for various clinical covariates, patients harboring T-allele genotypes of interleukin-28B (IL28B) (rs12979860) SNP had lower incidence of CMV infection (adjusted hazard ratio [aHR]: 0.66; 95% confidence interval [CI]: 0.46-0.96; p-value = 0.029). In the analysis restricted to patients not receiving prophylaxis, carriers of the TT genotype of toll-like receptor 9 (TLR9) (rs5743836) SNP had lower incidence of infection (aHR: 0.61; 95% CI: 0.38-0.96; p-value = 0.035), whereas the GG genotype of dendritic cell-specific ICAM 3-grabbing nonintegrin (DC-SIGN) (rs735240) SNP exerted the opposite effect (aHR: 1.86; 95% CI: 1.18-2.94; p-value = 0.008). An independent association was found between the number of unfavorable SNP genotypes carried by the patient and the incidence of CMV infection. In conclusion, specific SNPs in IL28B, TLR9 and DC-SIGN genes may play a role in modulating the susceptibility to CMV infection in CMV-seropositive KT recipients.

Elimination of large uremic toxins by a dialyzer specifically designed for high-volume convective therapies.

BACKGROUND: Unlike conventional hemodialysis treatments, which rely almost solely on diffusion-related mechanisms for solute removal, hemodiafiltration (HDF) allows more efficient removal of higher molecular weight toxins due to convective transport mechanisms. To facilitate the removal of these toxins in HDF treatment modalities, dialyzers with highly efficient high-flux membranes are necessary. This study assessed the large uremic toxin removal ability of a high-flux dialyzer (FX CorDiax 60) specifically designed to facilitate convective therapies compared with a standard high-flux dialyzer (FX 60). METHODS: In an open, randomized, cross-over, single-center, controlled, prospective clinical study, 30 adult chronic hemodialysis patients were treated by post-dilution online HDF with the FX 60 or the FX CorDiax 60 dialyzer. All other dialysis parameters were kept constant in both study arms. The reduction rate (RR) of blood urea nitrogen, phosphate, ß2-microglobulin (ß2-m), myoglobin, prolactin, α1-microglobulin, α1-acid glycoprotein, albumin and total protein as well as the elimination into dialysate was intraindividually compared for the two dialyzer types. RESULTS: For FX CorDiax 60 versus FX 60, the RR was significantly higher for blood urea nitrogen (86.23 ± 4.14 vs. 84.89 ± 4.59%, p = 0.015), ß2-m (84.67 ± 3.79 vs. 81.30 ± 4.82%, p < 0.0001), myoglobin (75.23 ± 10.48 vs. 58.60 ± 12.1%, p < 0.0001), prolactin (72.96 ± 9.68 vs. 56.91 ± 13.01%, p < 0.0001) and α1-microglobulin (20.89 ± 18.27 vs. 13.60 ± 12.50%, p = 0.016). There were no significant differences in the RR for phosphate, α1-acid glycoprotein, albumin and total protein. Mass removal was significantly higher with the FX CorDiax 60 than with the FX 60 for ß2-m (0.26 ± 0.09 vs. 0.24 ± 0.09 g, p = 0.0006), myoglobin (1.83 ± 0.89 vs. 1.51 ± 0.76 mg, p = 0.0017), prolactin (0.17 ± 0.13 vs. 0.14 ± 0.08 mg, p = 0.02) and albumin (4.25 ± 3.49 vs. 3.01 ± 2.37 g, p = 0.03). CONCLUSIONS: This study demonstrates that treating patients with an FX CorDiax 60 instead of an FX 60 dialyzer in post-dilution HDF mode significantly increases the elimination of middle molecules.

Sotrastaurin in calcineurin inhibitor-free regimen using everolimus in de novo kidney transplant recipients.

Sotrastaurin, a novel selective protein-kinase-C inhibitor, inhibits early T cell activation via a calcineurin-independent pathway. Efficacy and safety of sotrastaurin in a calcineurin inhibitor-free regimen were evaluated in this two-stage Phase II study of de novo kidney transplant recipients. Stage 1 randomized 131 patients (2:1) to sotrastaurin 300 mg or cyclosporine A (CsA). Stage 2 randomized 180 patients (1:1:1) to sotrastaurin 300 or 200 mg or CsA. All patients received basiliximab, everolimus (EVR) and prednisone. Primary endpoint was composite efficacy failure rate of treated biopsy-proven acute rejection, graft loss, death or lost to follow-up. Main safety assessment was estimated glomerular filtration rate (eGFR) by MDRD-4 at Month 12. Composite efficacy failure rates at 12 months were higher in sotrastaurin arms (Stage 1: 16.5% and 10.9% for sotrastaurin 300 mg and CsA; Stage 2: 27.2%, 34.5% and 19.4% for sotrastaurin 200 mg, 300 mg and CsA). eGFR was significantly better in sotrastaurin groups versus CsA at most time points, except at 12 months. Gastrointestinal and cardiac adverse events were more frequent with sotrastaurin. Higher treatment discontinuation, deaths and graft losses occurred with sotrastaurin 300 mg. Sotrastaurin combined with EVR showed higher efficacy failure rates and some improvement in renal allograft function compared to a CsA-based therapy.

Three-year outcomes from BENEFIT-EXT: a phase III study of belatacept versus cyclosporine in recipients of extended criteria donor kidneys.

Recipients of extended-criteria donor (ECD) kidneys have poorer long-term outcomes compared to standard-criteria donor kidney recipients. We report 3-year outcomes from a randomized, phase III study in recipients of de novo ECD kidneys (n = 543) assigned (1:1:1) to either a more intensive (MI) or less intensive (LI) belatacept regimen, or cyclosporine. Three hundred twenty-three patients completed treatment by year 3. Patient survival with a functioning graft was comparable between groups (80% in MI, 82% in LI, 80% in cyclosporine). Mean calculated GFR (cGFR) was 11 mL/min higher in belatacept-treated versus cyclosporine-treated patients (42.7 in MI, 42.2 in LI, 31.5 mL/min in cyclosporine). More cyclosporine-treated patients (44%) progressed to GFR <30 mL/min (chronic kidney disease [CKD] stage 4/5) than belatacept-treated patients (27-30%). Acute rejection rates were similar between groups. Posttransplant lymphoproliferative disorder (PTLD) occurrence was higher in belatacept-treated patients (two in MI, three in LI), most of which occurred during the first 18 months; four additional cases (3 in LI, 1 in cyclosporine) occurred after 3 years. Tuberculosis was reported in two MI, four LI and no cyclosporine patients. In conclusion, at 3 years after transplantation, immunosuppression with belatacept resulted in similar patient survival, graft survival and acute rejection, with better renal function compared with cyclosporine. As previously reported, PTLD and tuberculosis were the principal safety findings associated with belatacept in this study population.

Proliferation signal inhibitors and post-transplant malignancies in heart transplantation: practical clinical management questions.

Although malignancy is a major threat to long-term survival of heart transplant (HT) recipients, clear strategies to manage immunosuppression in these patients are lacking. Several lines of evidences support the hypothesis of an anticancer effect of proliferation signal inhibitors (PSIs: mammalian target of rapamycin [mTOR] inhibitors) in HT recipients. This property may arise from PSI's ability to replace immunosuppressive therapies that promote cancer progression, such as calcineurin inhibitors or azathioprine, and/or through their direct biological actions in preventing tumor development and progression. Given the lack of randomized studies specifically exploring these issues in the transplant setting, a collaborative group reviewed current literature and personal clinical experience to reach a consensus aimed to provide practical guidance for the clinical conduct in HT recipients with malignancy, or at high risk of malignancy, with a special focus on advice relevant to potential role of PSIs.

Long-term experience with kidney transplantation from hepatitis C-positive donors into hepatitis C-positive recipients.

Kidney transplantation from hepatitis C virus (HCV) antibody positive donors (HCVD+) into HCV antibody positive recipients (HCVR+) is controversial. We implemented this policy in our units in 1990. Herein, we report the long-term safety of this strategy. From March 1990 to March 2007, 162 HCVR+ received a kidney from HCVD+ (group 1) and 306 from HCVD- (group 2) in our units. Mean follow-up was 74.5 months. Five-and 10-year patient survival was 84.8% and 72.7% in group 1 vs. 86.6% and 76.5% in group 2 (p = 0.250). Three deaths in group 1 and two in group 2 were liver-disease related. Five- and 10-year graft survival was 58.9% and 34.4% versus 65.5% and 47.6% respectively (p = 0.006) while death-censored graft survival was 69% and 47% versus 72.7% and 58.5% (p = 0.055). Decompensated chronic liver disease was similar: 10.3% versus 6.2%. Cox-regression analysis could not identify the donor's HCV serology as a significant risk factor for death, graft failure and severe liver disease in HCVR+. In conclusion, long-term outcome of HCVR+ transplanted with kidneys from HCVD+ seems good in terms of patient survival, graft survival and liver disease. HCVD+ was not a significant risk factor for mortality, graft failure and liver disease among HCVR+. These data strongly suggest that the use of kidneys from HCVD+ in HCVR+ is a safe long-term strategy that helps to prevent kidney loss.

Comparative transcriptional and phenotypic peripheral blood analysis of kidney recipients under cyclosporin A or sirolimus monotherapy.

Due to its low level of nephrotoxicity and capacity to harness tolerogenic pathways, sirolimus (SRL) has been proposed as an alternative to calcineurin inhibitors in transplantation. The exact mechanisms underlying its unique immunosuppressive profile in humans, however, are still not well understood. In the current study, we aimed to depict the in vivo effects of SRL in comparison with cyclosporin A (CSA) by employing gene expression profiling and multiparameter flow cytometry on blood cells collected from stable kidney recipients under immunosuppressant monotherapy. SRL recipients displayed an increased frequency of CD4 + CD25highFoxp3 + T cells. However, this was accompanied by an increased number of effector memory T cells and by enrichment in NFkB-related pro-inflammatory expression pathways and monocyte and NK cell lineage-specific transcripts. Furthermore, measurement of a transcriptional signature characteristic of operationally tolerant kidney recipients failed to detect differences between SRL and CSA-treated recipients. In conclusion, we show here that the blood transcriptional profile induced by SRL monotherapy in vivo does not resemble that of operationally tolerant recipients and is dominated by innate immune cells and NFkB-related pro-inflammatory events. These data provide novel insights on the complex effects of SLR on the immune system in clinical transplantation.

Combined liver-kidney transplantation in patients with cirrhosis and chronic kidney disease.

The outcome of patients with cirrhosis and chronic kidney disease treated with combined liver-kidney transplantation (CLKT) is not well known because most series of patients treated with CLKT include not only patients with cirrhosis but also patients with inherited diseases without cirrhosis. To evaluate to what extent the combined kidney transplantation impairs posttransplantation outcome compared to liver transplantation (LT) alone, the outcome of patients with cirrhosis and chronic kidney disease treated with CLKT (n = 20) was compared to that of a group of patients with cirrhosis without chronic kidney disease treated with LT alone matched by age, sex, year of transplantation and severity of cirrhosis (n = 60). The primary end point of the study was survival, and secondary end points were outcome of renal function and complications within 6 months of transplantation. Patients with CLKT had a higher incidence of bacterial infections and transfusion requirements compared to LT patients. The incidence of acute renal failure during the first 6 months was similar, yet the severity of renal failure was greater in patients with CLKT. Hospital and intensive care unit (ICU) stays were longer in the CLKT group. One- and three-year survival probabilities in patients treated with CLKT were 80 and 75% compared to 97 and 88%, respectively, in patients treated with LT. In conclusion, CLKT for patients with cirrhosis and chronic kidney disease is associated with a relatively high frequency of postoperative complications that moderately impairs short-term survival. However, 3-year survival of patients with cirrhosis treated with CLKT is excellent.

[In vitro dynamics of parathyroid hormone secretion regulated by calcium and effects on the cell cycle: parathyroid hyperplasia versus adenoma]. / Dinámica in vitro de la secreción de hormona paratiroidea regulada por calcio y efecto sobre el ciclo celular: adenoma frente a hiperplasia paratiroidea.

AIM: To compare the dynamics of calcium-regulated PTH secretion in vitro from adenomatous versus hyperplastic glands and to investigate the relationship between the parathyroid cell cycle and the calcium-regulated PTH secretion in these glands. MATERIALS AND METHODS: A total of 31 parathyroid glands (8 adenomatous and 23 hyperplastic) from 8 patients with primary hyperparathyroidism and 7 with secondary hyperparathyroidism respectively were studied. For the evaluation of calcium-regulated PTH secretion, small parathyroid pieces of 1 mm were sequentially transferred to wells with varying Ca concentrations: 0.4, 0.6, 0.8, 1, 1.25 and 1.35 or 1.5 mM. PTH concentrations were determined in the medium. For the parathyroid cell cycle studies, parathyroid cells were isolated without the use of enzymes and cell cycle was analyzed using the method described by Vindelov. The nuclei were acquired by flow cytometer and analyzed using the CELLFIT software. RESULTS: In parathyroid tissues from hyperplastic glands, the increase in extracellular calcium produced a decrease in PTH secretion which was apparent with a calcium level as low as 0.8 mM and the maximal inhibition of PTH secretion was obtained with a calcium of 1.25 mM, by the contrary, adenomatous glands required a calcium of 1.2 mM to produce a minimal decrease in PTH secretion. In hyperplastic parathyroid glands but not in parathyroid adenomas there was a significant correlation between the percentage of cells in G0/G1 phase with the set point (r = 0.914; P < 0.005) and the basal serum Ca (r = 0.862; P < 0.02). CONCLUSIONS: The control of the extracellular calcium-PTH release in vitro is less sensitive in parathyroid adenomas than hyperplasic parathyroid glands. In parathyroid hyperplasia the cell proliferation may be regulated by the extracellular calcium concentration (higher calcemia less proliferation).

[Dynamics of calcium-regulated PTH secretion in secondary hyperparathyroidism: comparison between "in vivo" vs. "in vitro" responses]. / Dinámica de la secreción de PTH regulada por calcio en el hiperparatiroidismo secundario: comparación de la respuesta in vivo frente a in vitro.

AIM: To compare the dynamics in vivo and in vitro calcium-PTH release of uremic patients with secondary hyperparathyroidism and their hyperplasic parathyroid glands after parathyroidectomy. MATERIALS AND METHODS: Seven patients with secondary HPT and their 23 hyperplasic glands obtained after surgical parathyroidectomy were evaluated. In vivo studies of the PTH secretion curve were obtained by induction of hypocalcemia and hypercalcemia with a continuous endovenous infusion of sodium EDTA and Ca gluconate, respectively. For the in vitro studies, small parathyroid pieces of 1 mm were sequentially transferred to wells with varying Ca concentrations: 0.4, 0.6, 0.8, 1, 1.25 and 1.5 mM. iPTH concentrations were determined in the medium. RESULTS: The in vivo set point did not correlate with the basal, maximal or minimal PTH concentrations, although it correlated significantly with the basal serum Ca concentration (r = 0.62, p < 0.02). Both in vivo and in vitro PTH secretion curves were sigmoidal, although the in vivo set point was higher than the in vitro (1.57 +/- 0.05 vs. 1.27 +/- 0.07 mM, p < 0.001). The degree of maximal PTH inhibition were similar in both circumstances (30.5 +/- 8.1 vs. 33.6 +/- 5.4 %; p = NS) with a significant direct correlation (r = 0.901; p < 0.01). CONCLUSIONS: The in vivo set point of calcium is more closely related to serum calcium concentration than to basal iPTH concentration. Although there are differences between the in vivo and in vitro calcium set point the maximal degree of PTH inhibition was similar in both circumstances.

[Guidelines for automated manual infusion: a practical way of prescribing postdilution on-line hemodiafiltration]. / Pauta de infusión manual automatizada: una forma práctica de prescribir la hemodiafiltración on-line posdilucional.

Post-dilution on-line hemodiafiltration (OL-HDF) is the most efficient infusion mode to obtain maximum clearances of uremic toxins, with a recommended manual infusion flow (Qi) of 25% of the blood flow with the main limitation that causes alarms by hemoconcentration throughout the session. Recent technical advances allow automatic prescription of Qi if hematocrit and total protein (TP) values are specified. As these analytical results are not possible to obtain in each dialysis session, a practical way to prescribe Qi is to make an automatic prescription adjusting the hematocrit and total protein values at the beginning of the session to obtain the manual prescription required and we will call it automatic-manual prescription. The aim of this study was to compare manual Qi with automatic-manual Qi in postdilution OL-HDF. 30 patients (16 men and 14 women), 59.9 +/- 15 years old, in hemodialysis program for 50.1 +/- 67 months were included. Every patient underwent four OL-HDF sessions, two with manual Qi (4008-S and 5008 monitors) and two with automatic-manual Qi (A-M), one with the same Qi and one with manual Qi +20 (A-M+20). The same usual dialysis parameters were maintained: helixone dialyzer, dialysis time of 266 +/- 39 minutes, blood flow of 420 +/- 36. Recirculation, Kt and intradialysis alarms were measured at each session. No significant differences in the fistula recirculation or dialysis dose measured using Kt. Total infusion volume was 24.9 +/- 4 (4008 S), 23.4 +/- 4 L (5008) with manual Qi, 23.6 +/- 4 L (A-M) Qi (NS) and 25.8 +/- 5 L (A-M+20). Only 14% of patients had no incidents. The number of alarms was significantly higher with manual prescription 55 alarms with 4008 and 40 with 5008 vs. AM (11) p < 0.01) and A-M+20 (16 alarms) We concluded that automatic-manual Qi is a practical way for post-dilutional OL-HDF prescription where the same efficiency and total reinfusion volume with an important reduction of intradialysis alarms are obtained, allowing to rise Qi by 20% without increasing intradialysis alarms.

[ABO incompatible living donor kidney transplantation: a dream come true. Experience of Hospital Clínic of Barcelona]. / Trasplante renal ABO incompatible: de un sueño a una realidad. Experiencia del Hospital Clínic de Barcelona.

INTRODUCTION: During the last years the number of patients on waiting list for kidney transplantation has been stable. Living donor kidney transplantation is nowadays a chance to increase the pool of donors. However, there are a group of patients with ABO incompatibility, making impossible the transplant until now. The aim of the present study is to describe the experience of Hospital Clinic Barcelona on ABO incompatible living transplantation. METHODS: A retrospective- descriptive study was made based on 11 living donor kidney recipients with ABO incompatibility in Hospital Clinic of Barcelona from October'06 to January'09. Selective blood group, antibody removal with specific immunoadsortion, immunoglobulin and anti- CD 20 antibody were made until the immunoglobulin (IgG) and isoaglutinine (IgM) antibody titters were 1/8 or lower. Immunosuppressive protocol was adjusted to particular recipient characteristics. Isoaglutinine titters were set before, during and post desensitization treatment and two weeks after transplant. Immunological, medical and surgical evaluation was the standard in living donor kidney transplant program. RESULTS: Medium age of donors and recipients were 47.8 +/- 12.4 and 44.4 +/- 14.1 years, respectively. 90% of donors were females and 73% of recipients males. Follow-up time was 10.2 +/- 10.2 months. Siblings and spouses were the most frequent relation (n=4, 36.4%, respectively). Chronic glomerulonephritis, adult polycystic kidney disease and Alport syndrome, the most frequent cause of end-stage renal disease. All the patients acquire appropriate isoaglutinine titters pre transplant (< 1/8), requiring 5.54 +/- 2.6 immunoadsorption sessions pretransplant and 2.82 posttransplant. One patient didn t need any immunoadsorption session (incompatibility blood group B) and another patient plasma exchange instead of immunoadsorption for being hypersensitized with positive flow cytometry crossmatch. Posttransplant isoaglutinine titters remained low. Two patients had cellular acute rejection episode (type IA and IB of Banff classification) with good response to corticosteroid treatment. Patient and graft survival were 91% at first year and remain stable during the follow-up. A graft lost by death of patient in relation to haemorrhagic shock developed within the first 72 hours after transplantation. Renal graft function at first year was excellent with serum creatinine of 1.3 +/- 0.8 mg/dl, creatinine clearance of 62.6 ml/min/1.73 m2 and proteinuria of 244.9 mg/U-24h. CONCLUSION: ABO incompatible living donor kidney transplantation represent an effective and safe alternative in certain patients on waiting list for renal transplant, obtaining excellent results in patient and graft survival, with good renal graft function.

[Institute for clinical management of nephro-urological diseases: the benefits of a quality care programme]. / Instituto de gestión clínica para las enfermedades nefrourológicas: utilidad de un programa de calidad asistencial.

The Clinic Institute of Nefro and Urology (ICNU) was formed in Clinic Hospital of Barcelona in 1999. It grouped together services of Nephrology, Urology and Renal Transplant. At the same time, in order to ensure Quality in this process of change, we designed a specific quality program. In this program, we defined objectives to improve the quality of these services in one year and we defined different quality indicators in order to maintain and monitor health quality. The indicators referred to technical quality and perceived quality and we periodically evaluated their evolution. The results of the last five years indicate that the majority of the indicators have improved, except those concerning infections surgery and the response to complaints. This has helped the consolidation and recognition of the work of this innovatory project in the health management of the nephrologic and urinary systems that locate the patient in the center of the organization and recognize the health professionals as the true managers of this model.

Risk factors for infection with extended-spectrum and AmpC beta-lactamase-producing gram-negative rods in renal transplantation.

Increasing prevalence of infections caused by multiresistant gram-negative enteric bacilli due to synthesis of extended-spectrum beta-lactamase (ESBL) or to desrepressed chromosomic AmpC beta-lactamase (AmpC) is a major concern in the hospitalized patient population. Renal transplant recipients are especially susceptible to these infections. A cohort observational study in a 3-year period was performed. ESBL-production was determined by phenotypic analysis based on the CLSI recommendations. A multi-variate logistic regression analysis was performed to identify independent variables associated with multi-resistant gram-negative bacilli infection. The study included 417 patients (61 double kidney-pancreas recipients). The incidence of ESBL-producing and desrepressed chromosomic AmpC beta-lactamase resistance was 11.8% (49 patients). The most frequent bacteria isolated was E. coli (35/60 isolations), followed by Klebsiella spp(12/60 isolations). Double kidney-pancreas transplantation(OR 3.5, CI95% 1.6-7.8), previous use of antibiotics(OR 2.1,CI95% 1.1-4.1), posttransplant dialysis requirement (OR 3.1, CI95% 1.5-6.4) and posttransplant urinary obstruction (OR 5.8, CI95% 2.2-14.9) were independent variables associated with these multiresistant gram-negative enteric bacilli infections. The incidence of ESBL-producing and desrepressed AmpC beta-lactamase gram-negative enteric bacilli infection in our population was high. These infections are associated with significant morbidity after renal transplantation.

Localising imaging in secondary hyperparathyroidism.

Preoperative imaging has proved its use successful in the localization of solitary parathyroid adenomas in patients with suspected primary hyperparathyroidism. However, due to multiglandular disease at presentation patients with renal hyperparathyroidism need to be analyzed separately, making the usefulness of imaging techniques controversial. Recently, improved methods of functional imaging like parathyroid scan with 99mTc-sestamibi or positron emission tomography, especially when combined with computed tomography, can provide additional quantitative and qualitative information that has yet to be assessed. Nuclear medicine procedures could prove useful not only in preoperative diagnosis, but also in the selection of medical or surgical therapeutic alternatives in secondary hyperparathyroidism patients. There is evidence that 99mTc-sestamibi uptake in parathyroid hyperplasia or adenoma is related to biochemical markers of parathyroid function. We are only beginning to identify the factors involved in radiotracer uptake by parathyroid cells and how it can be modulated to obtain more accurate results. This review analyzes the current use of non-invasive imaging modalities in patients with secondary hyperparathyroidism, taking into account the latest trends in the field combining anatomic and functional modalities and the relevant factors linked to radiotracer uptake in abnormal hyperfunctioning parathyroid glands.

Minimizing the risk of posttransplant malignancy.

Recent improvements in immunosuppressive therapies have reduced the incidence of acute rejection and increased patient survival. These agents may however contribute to higher rates of mortality due to an increased risk of cardiovascular disease or malignancy. Transplant patients are immunocompromised with a reduced ability to combat the development of malignancy. The higher risk for the activity of oncoviruses may also contribute to the higher incidence and determine specific tumor types. Some immunosuppressants seem to have direct oncogenic effects. In vitro data have demonstrated that calcineurin inhibitors (CNIs) may show direct effects on tumor growth and the development of metastases. In contrast, mTOR inhibitors have demonstrated anti-tumoral properties in vitro and perhaps potent anti-angiogenic effects thereby. Recent studies and registry analyses have confirmed that mTOR inhibitors are associated with a reduced incidence of malignancies. UNOS data demonstrated that an mTOR inhibitor, with or without a CNI, is associated with a reduced incidence of tumors compared to regimens without mTOR inhibitors. The Rapamune Maintenance Regimen study demonstrated that patients receiving sirolimus-based, CNI-free therapy after CsA withdrawal at 3 months showed a reduced incidence of malignancy at 5 years posttransplant, compared with those who continued on a regimen that included CsA. In the CONVERT study, patients converted to sirolimus revealed a significantly lower malignancy rate at 24 months (3.1%) compared with those who continued CNI-based therapy (9.8%, P < .001). The elimination of CNIs and the introduction of sirolimus may, therefore, have a role to reduce the risk of cancer among posttransplant patients.

Factor deficiency in the anemia of renal transplant patients with grade III-IV chronic kidney disease: baseline results of the ARES Study.

ARES is a multicenter, prospective study of the prevalence, management, and repercussions on the quality of life of anemia in renal transplant patients with a reduced renal function (creatinine clearance according to Cockcroft-Gault: 15 mL/min). The frequency of factor deficiency and its relationship with anemia were analyzed at the baseline time of the study. Of the 500 patients included in the main study, valid data were available for iron metabolism in n = 419 microg/dL; folic acid, n = 205 ng/mL; and vitamin B12, n = 210 pg/mL. Anemia was defined as hemoglobin

[How much should dialysis time be increased when catheters are used?]. / ¿Cuánto tiempo es necesario aumentar la prescripción de hemodiálisis con la utilización de catéteres?

SUMMARY: The use of central catheters in hemodialysis patients as a permanent vascular access has increased during the last years, reaching numbers of around 7% of prevalent patients and between 25% of incident patients. Although the current catheters allow higher sanguineous flows with smaller incidence of infectious complications and dysfunction, the dose of dialysis that is reached is still inferior to that obtained with native arterio-venous fistula (AVF) and grafts. The aim of the present study was to evaluate the possible additional time supposed by dialysis using central venous catheters with respect to habitual vascular access as a consequence of the lesser blood flow (Qb) and the irregularity of its function (frequent lowering of the Qb and necessity of inverting the lines on many occasions). A total of 48 patients (31 men/17 women) with an average age of 61,6 +/- 14 years old (rank: 28-83), 20 with tunnelled catheter and the remaining with AVF, were included in the study. All the patients were dialyzed in the modality of high flux hemodialysis with a polisulphone of 1,9 m2 dialyzer, dialysis time of 240 minutes, dialysate flow 500 ml/min and monitors equipped with ionic dialysance (ID) with the objective of obtaining a Kt of 45 litres with each one of the different vascular accesses. The patients with AVF received 3 sessions, with variations of Qb to 300, 350 and 400 ml/min. The patients with tunnelled catheter received two sessions, to the maximum Qb, one with normal connection and other with inverted one. In the results obtained it is possible to emphasize that only the patients with AVF and 400 ml/min reached the objective of 45 L of Kt. The patients with AVF needed to increase 12 minutes of hemodialysis with a Qb of 350 ml/min and 28 minutes with a Qb of 300 ml/min; the catheters on normal position needed to increase 24 minutes and finally in the inverted catheters an increase of 59 minutes was necessary to reach the same Kt objective. We concluded that the patients dialyzed with central catheters on average needed to increase by 30 minutes the time of dialysis if the catheter worked in a normal position but 60 minutes if the arterio-venous lines were inverted so as to reach the minimum dose of dialysis.