CXCR3+ Monocytes Increase Significantly in Graft Blood Compared to Peripheral Blood in Patients With Stable Kidney Graft Function.

INTRODUCTION: We have recently reported that some lymphocyte populations do not maintain the same proportion in kidney graft blood as in peripheral blood, despite a stable function of the transplanted kidney. These results suggest that a comparative study between leukocyte cells from graft blood and those obtained from peripheral blood could provide information about the inflammatory state of the transplanted organ. In this work we selected the population of CD4+ lymphocytes and monocytes expressing CXCR3 to test this hypothesis. MATERIAL AND METHODS: The study was performed by flow cytometry during month 3, 6, and 12 after transplantation in 58 patients who received an isolated kidney transplant and the same immunosuppressive regimen. The peripheral blood sample was obtained by venipuncture and the graft blood by fine needle aspiration. RESULTS: We found a significant percentage decrease in CXCR3+ monocytes throughout the first year of transplantation in peripheral blood (15.9 ± 20.7 vs. 12.6 ± 12.4 vs. 6.3 ± 9.0, at 3, 6, and 12 months, respectively; P = .001), whereas the percentage of CXCR3+ monocytes in graft blood did not change over this period. This situation resulted in a significant percentage difference between the CXCR3+ monocytes from the graft blood and those from the peripheral blood at the sixth (15.8 ± 8.1 vs. 12.6 ± 12.4, respectively; P = .008) and 12th months (12.9 ± 8.1 vs. 6.3 ± 9.0, respectively; P < .001). CONCLUSIONS: Therefore, we can conclude that the significant percentage increase of CXCR3+ monocytes in graft blood with respect to peripheral blood suggests the presence of inflammatory activity despite renal function being stable during the second half of the first year post-transplantation.

Glycemic control and maternal and fetal outcomes in pregnant women with type 1 diabetes according to the type of basal insulin.

OBJECTIVE: To examine the potential role of the type of basal insulin on glycemic control and maternal and foetal outcomes in pregnant women with type 1 diabetes (T1DM). STUDY DESIGN: Retrospective cohort study of pregnancies attended at 18 Spanish tertiary hospitals. INCLUSION CRITERIA: T1DM, singleton pregnancies, delivery between 2002-2010, and use of the same basal and prandial insulin from before pregnancy until delivery. RESULTS: A total of 1534 pregnancies were included. The basal insulin most commonly used was Neutral Protamine Hagedorn (NPH) (51.7%), followed by glargine (23.2%) and continuous subcutaneous insulin infusion (CSII) (21.1%). CSII users had longer diabetes duration. Multiple logistic regression analysis showed that CSII was independently associated with lower doses of insulin, higher glycated haemoglobin (HbA1c) in all trimesters, and higher rates of miscarriage, preterm birth and neonatal hypoglycemia. Glargine was related to a higher risk of preterm birth and a small-for-gestational age infant (SGA). The odds ratios (OR) of the associations between insulin type and clinical outcomes (from 0.642 to 4.894) have a relevant magnitude. CONCLUSIONS: In this observational study of pregnant women with T1DM, the type of basal insulin was independently associated with metabolic variables and foetal outcomes.

Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in cirrhosis characterized by organ failure(s) and high mortality rate. There are no biomarkers of ACLF. The LCN2 gene and its product, neutrophil gelatinase-associated lipocalin (NGAL), are upregulated in experimental models of liver injury and cultured hepatocytes as a result of injury by toxins or proinflammatory cytokines, particularly Interleukin-6. The aim of this study was to investigate whether NGAL could be a biomarker of ACLF and whether LCN2 gene may be upregulated in the liver in ACLF. METHODS: We analyzed urine and plasma NGAL levels in 716 patients hospitalized for complications of cirrhosis, 148 with ACLF. LCN2 expression was assessed in liver biopsies from 29 additional patients with decompensated cirrhosis with and without ACLF. RESULTS: Urine NGAL was markedly increased in ACLF vs. no ACLF patients (108(35-400) vs. 29(12-73)µg/g creatinine; p<0.001) and was an independent predictive factor of ACLF; the independent association persisted after adjustment for kidney function or exclusion of variables present in ACLF definition. Urine NGAL was also an independent predictive factor of 28day transplant-free mortality together with MELD score and leukocyte count (AUROC 0.88(0.83-0.92)). Urine NGAL improved significantly the accuracy of MELD in predicting prognosis. The LCN2 gene was markedly upregulated in the liver of patients with ACLF. Gene expression correlated directly with serum bilirubin and INR (r=0.79; p<0.001 and r=0.67; p<0.001), MELD (r=0.68; p<0.001) and Interleukin-6 (r=0.65; p<0.001). CONCLUSIONS: NGAL is a biomarker of ACLF and prognosis and correlates with liver failure and systemic inflammation. There is remarkable overexpression of LCN2 gene in the liver in ACLF syndrome. LAY SUMMARY: Urine NGAL is a biomarker of acute-on-chronic liver failure (ACLF). NGAL is a protein that may be expressed in several tissues in response to injury. The protein is filtered by the kidneys due to its small size and can be measured in the urine. Ariza, Graupera and colleagues found in a series of 716 patients with cirrhosis that urine NGAL was markedly increased in patients with ACLF and correlated with prognosis. Moreover, gene coding NGAL was markedly overexpressed in the liver tissue in ACLF.

Impact of Early Low-Grade Proteinuria and Allograft Dysfunction on Survival in Expanded Criteria Donor Kidney Transplant Recipients.

INTRODUCTION: Recent studies have demonstrated a relationship between low-grade proteinuria and worse graft survival, but this has not been fully studied in expanded criteria donor (ECD) kidney transplant recipients. AIM: The aim of this study was to assess whether the combination of early low-grade proteinuria (<1 g/d) and allograft dysfunction at the third month post-transplantation predicts outcomes in terms of survival in ECD kidney transplant recipients. MATERIAL AND METHODS: We studied a cohort of 269 ECD kidney transplant recipients subdivided into 4 groups according to clinically relevant proteinuria (300 mg/d) and median creatinine (Cr; 1.7 mg/dL; interquartile range, 1.4-2.1 mg/dL) at the third month post-transplantation: Group A (Cr <1.7 mg/dL and proteinuria <300 mg/24 h; n = 97), Group B (Cr <1.7 mg/dL and proteinuria ≥300 mg/24 h; n = 38), Group C (Cr ≥1.7 mg/dL and proteinuria <300 mg/24 h; n = 79), and Group D (Cr ≥1.7 mg/dL and proteinuria ≥300 mg/24 h; n = 55). RESULTS: Death-censored graft survival was significantly lower in Group D compared with the rest (P < .007). Multivariate Cox regression analysis using fixed covariates showed that the combination of low-grade proteinuria and a lower estimated glomerular filtration rate (eGFR) as associated with graft failure (hazard rate [HR] 2.5, 95% confidence interval [CI], 1.09-5.97; P = .03). CONCLUSIONS: The early association of low-grade proteinuria and allograft dysfunction represents an important risk factor for graft loss in ECD kidney transplant recipients. Strategies to optimize renal function could improve the outcome in this specific population.

Relation between lipoprotein subfractions and TSH levels in the cardiovascular risk among women with subclinical hypothyroidism.

OBJECTIVE: Subclinical hypothyroidism (SCH) is a common condition associated with increased cardiovascular risk. A standard treatment is yet to be established, as there is no consensus on the TSH cut-off values which should be used as indicators. Thus, the aim of this study was to assess cardiovascular risk in patients with SCH and to differentiate it according to TSH levels. DESIGN: This was an observational study conducted in an academic medical centre. PATIENTS: The study population consisted of 95 middle-aged women recently diagnosed with SCH and 65 euthyroid controls. MEASUREMENTS: We measured anthropometric parameters, lipid cardiovascular risk markers and lipoprotein subclasses of HDL and LDL. RESULTS: Patients with SCH exhibited a significant increase in triglycerides and atherogenic index of plasma and a significant reduction in HDL-cholesterol with respect to the control group after adjusted by age and BMI. A similar lipid profile was observed in both SCH groups. However, patients with TSH levels higher than 10 mIU/l showed a significant reduction in LDL particle size, which was associated with a higher prevalence of atherogenic pattern B. CONCLUSIONS: Our findings indicate that cardiovascular risk is affected in patients with TSH levels over 10 mIU/l, who have a lipid profile characteristic of atherogenic dyslipidemia.

Cardiovascular risk in recipients with kidney transplants from expanded criteria donors.

INTRODUCTION: Posttransplant cardiovascular disease (CVD) is the leading cause of death in renal transplant (RT) recipients and is more evident in recipients with transplants from expanded criteria donors (ECD). OBJECTIVES: We analyzed the evolution of cardiovascular risk factors and their association with patient mortality. MATERIALS AND METHODS: We undertook a single-center, prospective study of RT patients (n = 360) between 1999 and 2006. These were 180 recipients with transplants from ECD and 180 controls. We analyzed the baseline characteristics and the cardiovascular risk factors: hypertension, diabetes, dyslipidemia, CVD, and anemia. Posttransplant analyses included the evolution of cardiovascular risk factors and causes of death. RESULTS: The mean age of the ECD was 63.5 ± 5.4 versus 32.0 ± 13.2 years in the non-ECD (P < .001) and the recipient ages were 58.4 ± 8.7 versus 40.8 ± 13.3 years, respectively (P < .001). The median interquartile range [IQR] dialysis time was 25 months (15-39) versus 20 months (12-44; P = .017). The pretransplant body mass index was 26.89 ± 3.91 versus 25.43 ± 4.72 kg/m(2) (P = .002); the median (IQR) number of antihypertensive drugs was two (1-2) versus two (1-2.75; P = .015); dyslipidemia was present in 32.5% versus 21.6% (P = .024), diabetes in 10.6% versus 5.6% (P = .087), and CVD in 13.3% versus 7.8% (P = .086). Treatment with erythropoiesis-stimulating agents (ESA) was received by 84.9% versus 83.9% (P = .857). Concerning transplantation, the mean follow-up was 64.3 ± 33.7 months. Hypertension was present at 3 and 5 years in 85.6% versus 69.5% (P = .001) and 87.9% versus 72.8% (P = .009), respiratory. Treatment with angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers at 3 and 5 years was 79.8% versus 64.5% and 85.6% versus 65%. Dyslipidemia was present at 5 years in 63.1% versus 58.0% (P = .482). De novo diabetes occurred in 16.7% versus 11.1% (P = .128), and CVD in 13.5% versus 4.5% (P = .003). Univariate and multivariate Cox regression proportional hazards models were constructed to analyze the factors associated with patient death. CONCLUSIONS: CVD is the most common cause of death in recipients of ECD, RT, 40% in the ECD group versus 28.6% in the control group. Tight control of cardiovascular risk factors and a good pretransplant patient selection contributed to the good results obtained.

Transplant glomerulopathy: clinical course and factors relating to graft survival.

INTRODUCTION: Transplant glomerulopathy (TG) is usually associated with a poor prognosis for kidney graft survival. AIM AND METHODS: We analyzed 30 cases of TG diagnosed by kidney biopsy among a retrospective review of 579 biopsies performed between January 2006 and October 2011. RESULTS: At the time of biopsy, the mean glomerular filtration rate (GFR), estimated by the abbreviated Modification of Diet in Renal Disease was 31 ± 10 mL/min and the proteinuria, 1.9 ± 2 gr/24 hours. Anti-human leukocyte antigen (HLA) antibodies were present in 40% of patients. The histological findings showed severe duplication of the glomerular basement membrane in 80% of patients; and interstitial fibrosis and tubular atrophy (IFTA) and moderate to severe arteriolar hyalinosis in 53% and 56% respectively. Fourteen patients lost their grafts. Graft survival was significantly associated with IFTA (P = .03) and renal function at the time of diagnosis (P = .03). CONCLUSIONS: TG was associated with a worse prognosis for the graft among kidney transplant patients. It is often associated with the presence of anti-HLA antibodies. Renal function at the time of diagnosis and IFTA were predictive factors for graft survival in these patients.

Survival of lupus nephritis patients after renal transplantation in Malaga.

BACKGROUND: Studies have shown that the survival of patients with lupus nephritis (LN) who receive a transplant has results similar to those of nondiabetic control subjects. OBJECTIVE: The aim of this study was to evaluate the survival of lupus patients who received a transplant at our center, and to determine risk factors for mortality and graft loss. METHODS: This case-control (1:2) study comprised patients with chronic kidney disease secondary to LN who received a kidney transplant (n = 32) in the Malaga area from 1985 to 2010. The controls subjects (n = 64) were matched by age, sex, and transplant period. We analyzed graft and patient survivals and risk factors compared with long-term transplant patients without LN. RESULTS: No differences were found in the variables analyzed between groups, except for the most frequent cause of donor death, which was almost significant: stroke in LN and traumatic brain injury in control subjects (P = .05). of the whole study sample, 45% lost the graft, primarily owing to chronic kidney disease (53.5%), followed by vascular thrombosis (16.3%); P = .57. Censored graft losses occurred in 63% of the patients transplanted before 2000, whereas it occurred in 20% of those transplanted after 2000 (P < .001). Censored graft survival was similar between the groups throughout the followup, as was patient survival. Cox regression showed that only acute rejection was associated with a 2-fold increased risk of graft loss. CONCLUSIONS: Our lupus transplant population showed no differences in graft or patient survival compared with control subjects. Those patients who received a transplant from 2000 had better results, which may be related to several factors, such as immunosuppression, correction of cardiovascular conditions, or other factors. Risk factors for death and graft loss were similar to the control population.

Pregnancy in kidney transplant recipients: effects on mother and newborn.

INTRODUCTION: Pregnancy is currently considered yet another benefit of kidney transplantation, though doubts still exist concerning the effects of transplantation on the mother and the fetus. MATERIALS AND METHODS: We undertook a retrospective study analyzing 24 pregnancies in 20 kidney transplant recipients between 1986 and 2010. Evaluation was made of different variables related to renal function, both during the pregnancy and afterward, as well as other factors related to the birth and the status of the newborn. RESULTS: The mean age of the kidney transplant recipients was 29 ± 5 years, and the mean time since transplantation was 4.5 years (range = 0.8-12). At the time of pregnancy, the glomerular filtration rate was 59 ± 15 mL/min. Twelve recipients had well-controlled hypertension; none had proteinuria. Renal function and proteinuria remained stable during the pregnancy. There was a significant increase in blood pressure at the end of the pregnancy. It was necessary to raise the dose of calcineurin inhibitor to maintain target levels. No acute rejection episode was observed. One patient had gestational diabetes and two showed preeclampsia. Pregnancy reached term in 20 cases; there were four miscarriages. Delivery was at 36.9 weeks (range = 34-41) and the newborn weight, 2.7 kg (range = 1.5-3.6). One patient had a miscarriage at week 22 and succumbed due to a cardiac arrest during induction of the delivery. Eighteen babies were born healthy; two died. CONCLUSIONS: Pregnancy in kidney transplant recipients is safe if the renal function is adequate before the pregnancy without proteinuria but with a well-controlled blood pressure. In these cases, the maternal complications were similar to those among general population; we detected no increased risk of graft loss.

Biopsies in renal transplant patients with proteinuria: histological findings.

INTRODUCTION: Proteinuria is related to a poor prognosis for graft survival. MATERIALS AND METHODS: We undertook a retrospective study of renal transplant biopsies between 2006 and 2009 performed because of proteinuria. Data were collected on demographic, analytical, and histological characteristics. RESULTS: The study included 49 biopsies from 65% men with an overall mean age of 52 ± 13 years. The mean time from transplant to biopsy was 6.5 ± 5.3 years. All cases displayed proteinuria: 2.2 g/24 h (1.2-3.2). In 56% of cases, it was also associated with worsening glomerular filtration rate (GFR) (MDRDa 33 ± 16 mL/min). In 14% of cases, the sample was insufficient to determine glomerular pathology, whereas 51% displayed glomerular disease, among which were transplant glomerulopathy (40%), glomerulonephritis (48%), and diabetes (12%). Interstitial fibrosis and tubular atrophy (IFTA) was present in 85%: 33% mild, 27% moderate, and 25% severe. Arteriolar hyalinosis was present in 60%. Thirty-four percent of subject lost their grafts at a mean of 11 ± 9 months after the biopsy. The GFR at the time of biopsy was worse among those subjects who returned to dialysis than those who retained function (MDRDa 22 ± 7.5 vs 34 ± 15 mL/min; P = .006). Proteinuria was also greater among those who lost their grafts (4.1 ± 3.4 vs 2.1 ± 1.6 g/24 h; P = .007). The absolute increase in the risk of graft loss was 52% among subjects who displayed moderate to severe versus those who had mild IFTA (relative risk [RR] 7; confidence interval [CI] 1.8-28; P < .001). The presence of glomerulosclerosis >50% was also associated with a 48% absolute increased risk of graft loss compared with those patients with no glomerulosclerosis or <50% (RR 3; CI 1.5-12; P = .02). After the biopsy, the dose of angiotensin converting enzyme inhibitors and/or angiotensin receptor antagonist was increased in 90%, with 34% of subjects, experiencing a change in immunosuppression. CONCLUSIONS: Transplant patients undergoing a biopsy due to proteinuria, the occurrence of graft loss was associated with reduced GFR and the amount of proteinuria at the time of the biopsy, as well as with the degree of IFTA and of glomerular involvement.

Solidification of small p-H2 clusters at zero temperature.

We have determined the ground-state energies of para-H(2) clusters at zero temperature using the diffusion Monte Carlo method. The liquid or solid character of each cluster is investigated by restricting the phase through the use of proper importance sampling. Our results show inhomogeneous crystallization of clusters, with alternating behavior between liquid and solid phases up to N = 55. From there on, all clusters are solid. The ground-state energies in the range N = 13-75 are established, and the stable phase of each cluster is determined. In spite of the small differences observed between the energy of liquid and solid clusters, the corresponding density profiles are significantly different, a feature that can help to solve ambiguities in the determination of the specific phase of H(2) clusters.

Evidencias clínicas sobre el uso de los fármacos anti-mTOR en el trasplante renal / Clinical evidence on the use of anti-mTOR drugs in renal transplantation

Los fármacos inhibidores de la calcineurina (ICN) constituyen los pilares de la moderna inmunosupresión en el trasplante renal. Sin embargo, contribuyen significativamente a la pérdida crónica de los injertos renales y a la elevada morbimortalidad en esta población por sus efectos deletéreos sobre el injerto renal, el perfil cardiovascular y la patología tumoral. Los fármacos anti-mTOR, sirolimus (SRL) y everolimus (EVE), son potentes inmunosupresores con capacidad antiproliferativa y antimigratoria, propiedades que les confieren un potencial papel protector en la disfunción del injerto, en la optimización de la función renal y en la aparición de tumores. En efecto, ensayos clínicos controlados y estudios observacionales de conversión han demostrado el efecto beneficioso de estos fármacos en términos de función renal, sin incremento significativo de las tasas de rechazo agudo. En esta revisión se analizan las evidencias del empleo de los fármacos anti-mTOR en los siguientes aspectos clínicos de los pacientes con trasplante renal: 1) prevención de la disfunción inmunológica precoz y preservación de la función renal en el uso de novo y conversión precoz o tardía; 2) disfunción crónica del injerto renal; 3)efectos cardiovasculares; 4) diabetes de novo postrasplante, y5) patología tumoral de novo (AU)

The calcineurin inhibitor drugs (CNI) are the mainstays of modern immunosuppression in renal transplantation, but they contribute significantly to the chronic graft loss and the high morbidity and mortality in this population for their deleterious effects on renal graft, cardiovascular profile and malignancies. The anti-mTOR drugs, sirolimus (SRL) and everolimus (EVE), are potent immunosuppressants with antiproliferative and anti-migration properties. This confers them a potential protective role in graft dysfunction, the optimization of renal function and the appearance of malignancies. Indeed, clinical trials and observational studies have demonstrated that conversion from CNI to anti-mTOR-based maintanace therapy has beneficial effects on transplant outcomes in terms of renal function, without significant increase in acute rejection rates. In this review, we analyze the evidence of the use of anti-mTOR in the following clinical situations following renal transplantation: 1) Prevention of immune dysfunction and renal function preservation in de novo kidney transplantation and after early or late CNI withdrawal; 2) Chronic, 3) Cardiovascular complications, 4) Diabetes de novo posttransplantation; and 5) De novo malignancies (AU)

Clinical evidence on the use of anti-mTOR drugs in renal transplantation.

Calcineurin inhibitor drugs (CNI) are the mainstay of modern immunosuppression in renal transplantation. However, they contribute significantly to the chronic loss of renal grafts and the high morbidity and mortality in this population due to their deleterious effects on the renal graft, cardiovascular profile and tumour pathology. Anti-mTOR drugs, sirolimus (SRL) and everolimus (EVE) are potent immunosuppressants with antiproliferative and anti-migratory capacities. These properties mean that they have a potential protective role in graft dysfunction, in renal function optimisation and the appearance of malignant tumours. Indeed, clinical trials and observational studies have demonstrated that conversion from CNI to anti-mTOR-based maintenance therapy has beneficial effects on transplant outcomes in terms of renal function, without significant increase in acute rejection rates. This review article examines the evidence of the use of anti-mTOR in the following clinical situations following renal transplantation: 1) prevention of immune dysfunction and renal function preservation in de novo renal transplantation and after early or late CNI withdrawal; 2) chronic dysfunction of the renal graft; 3) cardiovascular effects; 4) de novo post-transplant diabetes, and 5) de novo tumour pathology.

Renal transplantation in old recipients from expanded criteria donors selected by kidney biopsy.

BACKGROUND: In Spain, the number of ideal kidney transplant donors has fallen, with at the same time an increase in the number of older recipients on the waiting list. AIM: To analyze the results of expanded criteria cadaveric donor kidney transplants into older recipients using grafts selected by kidney biopsy. PATIENTS AND METHODS: We studied 360 kidney transplant recipients who had been followed to December 2009: 180 in the study group and 180 in a control group composed of younger patients who received grafts from non-expanded criteria donors between 1999 and 2006. A paraffin-embedded kidney biopsy was evaluated by the percentages of sclerosed glomeruli, arteriolar hyalinosis, intimal wall thickening, interstitial fibrosis, and tubular atrophy. RESULTS: Significant differences were observed in donor age (63.50±5.46 vs 31.90±13.29 years; P<.001) and recipient age (58.40±8.80 vs 40.71±13.23 years; P<.001). Donor renal function was significantly worse among the expanded criteria group (90.80 vs 108.11 mL/min/1.73 m2; P=.006), remaining so over time in the recipient (at 1 year: 42.08 vs 63.71 [P<.001]; at 3 years: 41.25 vs 62.31 [P<.001], and at 7 years: 38.17 vs 64.18 [P<.001]). Censored 7-year graft survivals were 73% versus 87% (P<.001) with similar patient survivals (90.5% vs 95%; P=.39). CONCLUSIONS: Selection of expanded criteria donors by kidney biopsy resulted in good renal function as well as graft and patient survivals at 7 years in older recipients.

Late conversion to mammalian target of rapamycin inhibitor/proliferation signal inhibitors in kidney transplant patients: clinical experience in the last 5 years.

INTRODUCTION: Treatment with proliferation signal inhibitors (PSIs; sirolimus/everolimus) is a therapeutic option for renal transplant recipients, especially those who develop chronic graft nephropathy (CGN) or a neoplasm. We sought to analyze the efficacy and safety of conversion to PSIs. MATERIAL AND METHODS: We undertook a retrospective study of 77 patients converted between January 2005 and October 2009 to PSIs: 53 sirolimus and 24 everolimus. The causes for conversion were 63% tumors, 30% for chronic graft nephropathy (CGN), and 7% for other reasons. Mean time from transplant to conversion was 8 years. Patients were followed for a mean of 18 months (range, 1-61). RESULTS: A significant 14% improvement in renal function was observed at 1 year after conversion: baseline Modification of Diet in Renal Disease (MDRD) 45±20 versus 51±20.1 mL/min/1.73 m2 (P=.03). The benefit was greater among patients converted for CGN: baseline MDRD 31.5±8.8 versus 40.9±13.1 mL/min/1.73 m2 (P=.02), a 30% increase. The side effects experienced by 40% of patients included: 12% diarrhea, 15% edema, 20% buccal aphthae, 10% pneumonitis, and 20% skin alterations. PSIs were withdrawn in 25% of patients: 13% for side effects, 2.5% for patient death, and 3.8% for graft loss. We observed increases in serum lipids and proteinuria with a mild decrease in hemoglobin. CONCLUSION: Conversion to PSIs is a safe, useful therapeutic option for carefully selected patients, when renal function has not undergone marked deterioration and there is no proteinuria. Although side effects are common, most are mild; withdrawal of PSIs was necessary in a relatively low percentage of cases.

Renin-angiotensin system dual blockade using angiotensin receptor plus aliskiren decreases severe proteinuria in kidney transplant recipients.

BACKGROUND: Renin-angiotensin system (RAS) blockade has cardioprotective and renoprotective effects in the general population; however, whether dual blockade using angiotensin-receptor blockade (ARB) plus a renin inhibitor, aliskiren, can minimize severe proteinuria in kidney transplant recipients remains undetermined. OBJECTIVE: To analyze the efficacy and safety of dual blockade of the RAS with an ARB and aliskiren in kidney transplant recipients with severe proteinuria and creatinine concentration 2.5 mg/dL or less. PATIENTS AND METHODS: This prospective study included 16 patients (mean age 56 years; 10 men [62%] who had undergone cadaveric renal transplantation between 1992 and 2004. Immunosuppression therapy included a calcineurin inhibitor in 9 patients (56%) or mammalian target of rapamycin inhibitor in 7 (44%), and mycophenolate mofetil in 15 (94%). All received high-dose ARB II (1.0-3.5 g/24 h) because of marked proteinuria, with poor response. Accordingly, 11 patients also received aliskiren, and in 5 who were receiving an angiotensin-converting enzyme inhibitor, therapy was changed to aliskiren. Mean (range) follow-up was 11 (3-18) months. RESULTS: At 3 months, proteinuria decreased by 40%, and at 6 months by 60%. In addition, mean blood pressure was decreased significantly. Renal function remained stable, as did the serum potassium concentration. A slight but significant decrease in hemoglobin concentration was observed, with no clinical repercussions. CONCLUSIONS: Dual blockade of the RAS with ARB II plus aliskiren therapy demonstrated an additive effect to decrease severe proteinuria and blood pressure in kidney transplant recipients. Neither relevant adverse effects in renal function nor anemia or hyperkalemia were observed. These findings might contribute to prolonging long-term kidney graft survival.

Does JC polyomavirus cause nephropathy in renal transplant patients?

INTRODUCTION: BK polyomavirus (BKV) reactivation characterized by active viruria occurs in 23%-57% of renal allograft recipients and BKV-associated nephropathy in as many as 8% of renal allograft recipients. Only a few cases of nephritis have been attributed to JC polyomavirus (JCV) with limited information about JCV replication and its impact on graft function and survival of kidney transplant patients. We sought to determine the prevalence of BKV and JCV replication, the risk factors associated with viral reactivation, and their implications for the development of polyomavirus nephropathy (PVN) among renal transplant patients. MATERIALS AND METHODS: The study included 186 kidney transplant recipients who were transplanted between 2005 and 2009 with a 1-year follow-up. If the urine polymerase chain reaction (PCR) was positive, we performed a PCR on blood. If this was positive or renal dysfunction was present, we performed a renal biopsy. RESULTS: Viruria was positive in 72 cases (39%) and viremia in 12 (6.5%); including, 3 patients (1.6%) who developed PVN. In the patients with viruria, BKV was detected in 47% and JCV in 46%; both were detected in 7%, although the combination of viremia and nephropathy were caused by BKV in all cases. CONCLUSION: In renal transplant patients, the incidence of BKV and JCV viruria was similar, although in our series the JCV serotype did not cause viremia or PVN. Our experience suggested that JCV did not have the ability to cause PVN.

Pharmacokinetics of once- versus twice-daily tacrolimus formulations in kidney transplant patients receiving expanded criteria deceased donor organs: a single-center, randomized study.

BACKGROUND: Noncompliance to immunosuppressive treatment is 1 of the risk factors for kidney graft loss. The once-daily, prolonged-release tacrolimus formulation may improve treatment adherence. We sought to compare the pharmacokinetics of both tacrolimus formulations in older de novo recipients of a cadaveric renal transplant from an expanded-criteria donor. PATIENTS AND METHODS: This randomized study included 27 patients (14 on once daily prolonged-release formulation [QD] and 13, on the twice-daily formulation [BID]), who were treated with 0.1 mg/kg per day of tacrolimus (target blood level, 5-8 ng/mL) mycophenolate mofetil prednisone and basiliximab induction. RESULTS: At 24 hours, in combination with the blood levels were 4.70±2.50 versus 4.70±3.04 ng/mL (P=NS). There were no significant differences in the AUC0-24 of tacrolimus (QD/BID) at 3 days (300.8±60.15 vs 287.7±125.78 ng.h/mL) or 21 days (303.05±99.79 vs 275.26±75.37 ng.h/mL), nor in blood levels (ng/mL) at 1 month (8.76±2.46 vs 8.8±1.89), 3 months (7.30±1.72 vs 8.80±1.89) and 6 months (7.19±1.89 vs 6.60±1.71). At 3 days, there was a strong correlation between AUC0-24 and Cmin both for tacrolimus QD (r=.872) and BID (r = 1.0). The incidences of acute rejection episodes were: 0% versus 16.6%; graft survivals, 100% versus 92.3% (P=NS); and patient survivals, both 100%. CONCLUSION: For older de novo recipients of kidneys from expanded criteria donors tacrolimus QD is comparable to the same dose in the BID formulation with similar at least short-term transplant outcomes.

Renal Transplant Register of Andalusia, 2010 Report: survival in relation to the factors used in recipient selection.

Kidney transplantation is the best therapeutic alternative for patients suffering from end-stage renal disease (ESRD). In recent years a significant advance has been made in Andalusia in graft and recipient survival as seen in our 2009 publication. In the current work we analyzed 2989 kidney transplantations performed between January 1, 2000 and December 31, 2009 based on data obtained from the Renal Transplant Registry of Andalusia. We studied the influence on graft and patient survival of factors, such as donor and recipient age, HLA matching, HLA immunization, and duration of previous renal replacement therapy. Patient survival was influenced by age at the time of transplantation and by donor age; the younger the donor, the more it was improved. Graft survival was determined by the donor age group, with no differences at each level according to the recipient age group. No significant differences were observed in patient survival or graft or death-censored graft survival according to HLA matching. Patient and graft survivals were significantly affected by the duration of the previous renal replacement therapy. Despite this being a preliminary study, we have shown the importance of nonmodifiable factors in transplant survival, such as donor and recipient age, with HLA matching having a limited effect. These latter findings should be confirmed in the future by multivariate analyses.