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.

Rate of long-term graft loss has fallen among kidney transplants from cadaveric donors.

First-year renal allograft survival has increased, but whether this is associated with improvement in the long term is controversial. We analyzed 1045 consecutive adult deceased donor kidney transplant recipients from 1986 to 2001, with a follow-up to 2011. The aim of this study was to compare the graft half-life and attrition rates stratified by year of transplant in patients who received the graft in the periods 1986 to 1995 versus 1996 to 2001. The graft half-life increased significantly in the second period (P = .000) and the rate of graft loss stratified per year of evolution fell in all the study periods (P = .0000). In addition, the study period 1996 to 2001 was significantly associated with a reduction in graft failure risk compared with 1986 to 1995 in the multivariate analysis (P = .005). In conclusion, both short- and long-term graft survival increased significantly at our center.

Concordance of estimated glomerular filtration rates using Cockcroft-Gault modification of diet in renal disease, and chronic kidney disease epidemiology in renal transplant recipients.

INTRODUCTION: Various equations have been used to estimate the glomerular filtration rate (GFR) in renal patients, including kidney transplant recipients. Controversy exists concerning which equation is more precise to determine kidney failure. AIM: The aim of this study was to analyze the concordance (bias, variability, and exactness) of GFR estimated by the Modification of Diet in Renal Disease (MDRD4) and the Chronic Kidney Disease Epidemiology (CKD-EPI) equations using the Cockcroft-Gault (CG) method as the reference. MATERIAL AND METHODS: This observational, cross-sectional study included 153 clinically stable patients who underwent kidney transplantation between 2007 and 2009. The GFR was estimated at 12 months after the transplantation using the MDRD and CKP-EPI formula, using CG as the reference. RESULTS: The mean GFR for the various methods was as follows: CG = 65.6 ± 23.3 mL/min/1.73 m(2), MDRD4 = 54.9 ± 19.3 mL/min/1.73 m(2), and CKD-EPI = 55.8 ± 19.6 mL/min/1.73 m(2). Good correlations were found between CG-MDRD4 (r = 0.84; P < .001), CG-CKD-EPI (r = 0.87; P < .001), and MDRD4-CKD-EPI (r = 0.98; P < .001). The analysis of concordance detected a bias (normal difference) of -10.6 ± 12.7 versus -9.8 ± 11.3 mL/min/1.73 m(2) (P = .006), a variability (percent difference) of 14.5 ± 15.4% versus 13.6 ± 14.5% (P = .031), and an exactness (P30) of 81.7% versus 86.9% (P < .001) of CG-MDRD4 versus CG-CKD-EPI, respectively. For a GFR >60 mL/min/1.73 m(2) the exactness was 75.3% versus 83.5% (P < .001) for CG-MDRD4 versus CG-CKD-EPI, and for a GFR ≤ 60 mL/min/1.73 m(2) it was 89.7% versus 91.2% (P < .001). CONCLUSIONS: In our population the CKD-EPI method most approached the CG values, particularly when the GFR was >60 mL/min/1.73 m(2).

Mycophenolate mofetil and tacrolimus reduce mortality after deceased donor kidney transplantation.

A study of mortality in renal transplantation recipients showed that the combination of mycophenolate mofetil (MMF) and tacrolimus (TaC) reduced the mortality rate. We studied 1045 consecutive adult deceased donor kidney transplant recipients from 1986-2001, where follow-up to 2011 was a minimum of 10 years, to analyze the impact of these immunosuppressive drugs on patient survival. Cox multivariate analysis showed that treatment with MMF and the use of TaC instead of cyclosporine reduced the risk of death by 43%. In conclusion, both immunosuppressive drugs reduced the risk of death of patients receiving from renal transplants deceased donors.

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.

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.

Nefropatía asociada a infección por poliomavirus BK / BK virus-associated nephropathy

La infección por el poliomavirus BK (PBK) es un problema emergente en el trasplante renal que contribuye a la pérdida crónica de los injertos renales, y en el que la inmunosupresión desempeña un papel decisivo en su aparición. El conocimiento de los factores de riesgo y la monitorización estrecha de marcadores urinarios y serológicos de la infección pueden mitigar los efectos indeseables de esta infección. En esta revisión se profundiza en los aspectos clínicos y epidemiológicos de la infección por PBK, así como en las medias profilácticas y terapéuticas disponibles para su control en pacientes con trasplante renal que reciben moderna inmunosupresión (AU)

BK polyomavirus (BKV) infection is a problem which is becoming more prominent during kidney transplantation and contributes to chronic rejection of kidney grafts. This means that immune suppression plays a crucial role when the virus appears in kidney transplant patients. Knowing and understanding the risk factors and closely monitoring the urine and blood serum markers can alleviate undesired effects that are associated with this infection. This review details the clinical and epidemiological aspects of BKV, and the prophylactic and therapeutic methods available to control this virus in kidney transplant patients receiving modern immunosuppression (AU)

[BK-virus-associated Nephropathy]. / Nefropatía asociada a infección por poliomavirus BK.

The infection by the BK Polyomavirus (BKV) is an emerging problem in kidney transplants that contributes to a chronic loss of kidney grafts, and in which immunosuppression plays a decisive role. Understanding its risk factors and strictly monitoring urine and serological markers of the infection could mitigate the undesirable effects of this disease. In this review, we investigate the clinical and epidemiological aspects of the BKV infection, as well as go over the available prophylactic and treatment methods currently available for controlling the infection in kidney transplant patients that receive modern immunosuppression.

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.

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.

Evaluation of the efficacy and safety of conversion to sirolimus in 85 renal transplant recipients.

OBJECTIVE: Treatment with sirolimus (SRL) is a potential therapeutic option for renal transplant recipients, especially those who have developed chronic graft nephropathy (CGN) or a neoplasm. Our aim was to analyze the efficacy and safety of conversion to SRL in renal transplant recipients. MATERIALS AND METHODS: We undertook a retrospective study of 85 patients converted to SRL, 47% for tumors, 39% for CGN, and 14% for other causes. The follow-up period was 34 months (range, 1-93 months). RESULTS: Baseline creatinine was 1.8 +/- 0.69 mg/dL (1.6 +/- 0.59 for tumors and 2.3 +/- 0.6 for CGN). At 1 year, the creatinine was the same in both groups: 1.8 mg/dL (P = NS). Graft survival at 12 months was 89% (81% for tumors, 81% for CGN, and 100% for other causes). SRL was withdrawn in 34% of patients: 18% for severe side effects, 7% for patient death, and 9% for graft loss. The serum creatinine and proteinuria were significantly increased among those subjects who returned to dialysis because of CGN compared with those with conserved renal function. Patients who developed pneumonitis showed a lower baseline aMDRD, but no difference in SRL levels. Side effects occurred in 40% of patients, with no difference in renal function, proteinuria, or SRL levels. Renal function showed a significant improvement in the patients who continued SRL (aMDRD 45.7 vs 50.7 mL/min/1.73 m(2) at 12 months; P = .08), more marked among those who converted due to CGN. Increases were seen in levels of serum lipids, as well as in the percentage of patients treated with statins. Proteinuria increased significantly, as did the percentage of patients treated with ACE inhibitors/ARA2. CONCLUSIONS: Conversion to SRL in patients with CGN was safe when renal function had not undergone marked worsening and there was no proteinuria. Patients who were converted experienced an improvement in renal function.

Treatment with cinacalcet in 29 kidney transplant patients with persistent hyperparathyroidism.

OBJECTIVE: Persistent hyperparathyroidism (HPT) with hypercalcemia and hypophosphatemia is common after renal transplantation, resulting in the need for parathyroidectomy. Cinacalcet may be a therapeutic option for these patients. We sought to analyze the efficacy of treatment with cinacalcet for patients with hypercalcemia (Ca > 10.5 mg/dL) secondary to HPT. PATIENTS AND METHODS: We undertook a prospective study of 29 kidney transplant recipients with HPT who started treatment with 30 mg of cinacalcet. The mean follow-up was 13 months (range, 3-29 months). RESULTS: Treatment with cinacalcet effectively reduced levels of calcium (baseline, 11.1 +/- 0.8 vs 9.7 +/- 0.6 mg/dL at 12 months; P < .05) and intact parathyroid hormone (iPTH; baseline, 288 +/- 155 vs 236 +/- 118 pg/mL at 12 months; P = NS). Phosphorus levels increased from 2.5 +/- 0.6 to 3.2 +/- 0.8 mg/dL (P < .05). The mean dose of cinacalcet was 60 mg (range, 30-120 mg). Two patients required parathyroidectomy. Cinacalcet was well tolerated, except in 2 patients who had nausea and epigastralgia. CONCLUSIONS: Cinacalcet was safe and effective in kidney transplant patients with hypercalcemia secondary to HPT. Of note was the low incidence of adverse side effects despite the high doses prescribed for these patients.

Treatment with thymoglobulin as the cause of acuted emyelinating polyneuropathy in arenal transplant patient

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Enfermedad por CMV resistente a ganciclovir. ¿Está indicado monitorizar niveles plasmáticos de valganciclovir en pacientes de alto riesgo? / No disponible

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Treatment with ezetimibe in kidney transplant recipients with uncontrolled dyslipidemia.

INTRODUCTION: Cardiovascular disease is the leading cause of death in kidney transplant recipients. Hyperlipidemia is a cardiovascular risk factor present in over 70% of recipients. Ezetimibe has proved effective for the treatment of dyslipidemia in these patients. AIM: To evaluate the efficacy and safety of treatment with ezetimibe in kidney transplant recipients with uncontrolled hyperlipidemia. MATERIALS AND METHODS: We undertook a prospective study of 25 kidney transplant recipients with dyslipidemia who started treatment with 10 mg of ezetimibe. Statins were being taken by 96% of these patients. Monotherapy was used in one case. Measurements were made at baseline and after 3, 6, and 12 months of the lipid and hepatic profiles, CPK, lactose dehydrogenase, renal function and levels of immunosuppressive agents. RESULTS: A significant reduction was noted in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. No patient had changes in the hepatic profile, increased CPK and lactose dehydrogenase levels, or important adverse effects. Renal function remained stable, with no significant variations in plasma levels of the different immunosuppressive agents. CONCLUSIONS: The use of ezetimibe associated with statins is an efficient and safe therapeutic alternative for the treatment of poorly controlled dyslipidemia in recipients of a kidney graft.