Local Variation in Inclusion on Kidney Transplant Waiting Lists: Analysis in the Reference Area of a Kidney Transplant Center.

BACKGROUND: Access for end-stage renal disease (ESRD) patients to the renal transplant (RT) waiting list can vary depending on the criteria used and how they are applied in each dialysis unit. METHODS: This study was performed in the reference area (2.5 million inhabitants) of a transplant center. Data were from a regional registry (Information System of the Autonomous Coordination of Transplants in Andalusia) of total dialysis patients. Patients were grouped according to transplant status as: effective waiting list (WL); never recorded or excluded (E); incomplete immunologic study or discharge data (IIS); temporary contraindication (TC); or active (A). RESULTS: There were 1424 dialysis patients. Of these, 58% were E, 18% were IIS, 14% were TC, and 10% were A. Significant differences were detected for proportion of patients listed as active status (A) in 3 hospital dialysis units (2.9%-13.4%) and 12 hemodialysis centers (4.2%-29.2%); proportion of IIS cases in the hospitals (0%-57%) and dialysis centers (0%-58%); and in proportion of TC cases in the hospitals (19%-50%) and dialysis centers (2.5%-19.3%). The mean age of patients varied significantly between IIS, TC, and A groups (60.3, 54.8, and 52.3 years old, respectively, P < .001). Accentuated differences between the 2 provinces included in the sector were verified. There are notable differences in inclusion of pre-dialysis patients between hospital units. CONCLUSION: We detected considerable variability between hospital units and non-hospital dialysis centers in relation to inclusion on the active transplant waiting list and the proportion of patients with IIS or TC status. It is essential to implement a more homogeneous system for case selection through a specific intervention program from the reference center.

Reasons for Noninclusion on the Kidney Transplant Waiting List: Analysis in a Set of Hemodialysis Centers.

INTRODUCTION: End-stage renal disease patients' access to the renal transplant (RT) waiting list (WL) depends on general criteria and their specific application in the different treatment units. METHODS: Study in nonhospital hemodialysis centers (n = 9), dependent on an adult RT center. Cases included 228 patients considered to have nonactive status on the WL due to incomplete immunologic data (no blood group or HLA typing) or temporary contraindication from an incomplete pretransplant study (nonimmunologic) or comorbidity. Each individual situation was studied by reviewing the center's clinical history with the nephrologist in charge. RESULTS: Three situations were classified three groups. (1) Patients in this group had incomplete basic study (65 patients, 28.5%) pending cardiologic evaluation in 34%; urologic evaluation, 26%; both 18%; others, 9%; study not initiated, 12%. (2) Patients in this group had pre-existing or onset comorbidities (117 patients, 51.3%) pending studies or confirmed resolution: obesity, 30%; cancer, 17%; cardiovascular disease, 14%; digestive pathology, 10%; infection, 9%; neuropsychiatric disorders, 7%; multiple, 13%. (3) Patients in this group had other situations contraindicating RT (46 patients, 20.2%): poor therapeutic adherence, 30%; negative will of the patient, 26%; social issues, 9%; excluded by the center (not reported), 35%. CONCLUSIONS: We detected a high incidence of cases pending basic tests for inclusion on the WL. Obesity can be highlighted as the most frequent cause for noninclusion. Further support and coordination is required with referral hospital centers to increase and refine the RT WL.

Survival and Evolution of Renal Function in Kidney Transplant Recipients From Type II Asystolic Donations: A Single-center Experience.

BACKGROUND: In recent years, stagnation in the number of kidneys from after brain-dead donors (DBD) has stimulated the use of non-heart beating donors (NHBDs). Herein we present our 5-year experience with type II Maastricht NHBDs in renal transplantation. METHODS: All patients (n = 50) in this study received type II Maastricht NHBD kidneys (March 2012 to February 2017), with a median follow-up of 33 months. RESULTS: Mean donor age was 39 ± 12 years, mean creatinine 1.24 ± 0.2 mg/dL, and the most frequently observed blood group (donors and recipients) was type A (64%). Recipients were slightly younger (51 ± 11 years old), with mean time on dialysis of 30 ± 24 months. Almost all were primary transplants. Pre-transplant panel-reactive antibodies (PRA) were <25%; initial immunosuppression was thymoglobulin, corticosteroids, mycophenolate mofetil, and delayed introduction of tacrolimus. Six percent were nonfunctioning kidneys; 79.6% presented with delayed renal function (mean duration 14 ± 9 days). Acute rejection was seen in 6% of patients. Mean creatinine at month 3 was 1.7 ± 0.8 mg/dL, and 1.5 ± 0.8 mg/dL in the first year. The last available mean creatinine was 1.54 ± 0.7 mg/dL. Proteinuria in the third month, first year, and third year was 0.70, 0.41, and 0.26 g/d, respectively. Recipient survival at the first, third, and fifth year was 100%, 100%, and 86%, and when graft-censored for death was 94%, 91%, and 91%, respectively. The incidence of acute rejection during first year was 6%, and 2% in the second year. Exitus incidence was 4% and cytomegalovirus infection was 21.3%. BK viremia between 1000 and 10,000 copies/mL was seen in 4.3%, and reached >10,000 copies/mL in 2.1%. CONCLUSIONS: Type II NHBD has shown limited frequency of nonfunctioning kidney and high functional delay. The results in survival and renal function are very acceptable, comparable with levels seen in donation after brain death.

Resistant Cytomegalovirus Infection After Renal Transplantation: Literature Review.

BACKGROUND: Resistant cytomegalovirus (R-CMV) is an emerging problem in the renal transplantation population. The most frequent CMVs are high-resistance mutations (UL97 gene). METHODS: We describe our experience in management of R-CMV after renal transplant at our center (2012-2016). RESULTS: We encountered 3 cases of R-CMV infection after renal transplant (all primary infections). All 3 patients received induction therapy with corticosteroids, tacrolimus, and mycophenolate mofetil. The first patient (basiliximab induction, preemptive CMV) developed CMV replication on day +53, which responded poorly both to standard-dose valganciclovir (vGCV) and high-dose ganciclovir (GCV) (creatinine clearance [CrCl] >70 mL/min; vGCV 900 mg twice daily for 50 days and GCV 7.5 mg/kg twice daily for 8 days). Hematologic toxicity occurred. The R-CMV test was positive and foscarnet (FOS) was initiated (90 mg/kg twice daily for 21 days). The second patient presented CMV infection (day +30, thymoglobulin induction, CMV prophylaxis), which was not controlled with the high dose (CrCl 23 mL/min; GCV 3.5 mg/kg twice daily and vGCV 900 mg twice daily), resulting in severe neutropenia. R-CMV was detected and FOS initiated (FOS 50 mg/kg twice daily for 7 days and 50 mg/kg every 2 days for 13 days). The third patient's infection occurred on day +22 (basiliximab induction, preemptive CMV). Standard-dose vGCV was uneffective (CrCl >70 mL/min, vGCV 900 mg twice daily) and it did not respond to the high dose (GCV 7.5 mg/kg twice daily and vGCV 2700 mg/d). Moderate hematologic toxicity occurred. R-CMV was diagnosed and FOS treatment begun (FOS 70 mg/kg per day for 2 weeks). CONCLUSIONS: Resistant CMV infection may be severe due to viral infection and side effects of high-dose antiviral treatment. We presented 3 cases requiring the use of FOS in the absence of response or toxic effects from the usual treatment, with an optimal sustained response (temporary in case 2) and without serious side effects.

Hepatitis C Virus in Kidney Transplant Recipients: A Problem on the Path to Eradication.

BACKGROUND: Hepatitis C virus (HCV) still has significant prevalence in kidney transplant (KT) recipients and is related to poor recipient and graft survival. New direct-acting antivirals (DAA) are leading to a radical change in the problem. METHODS: We studied HCV prevalence at the time of transplantation and in follow-up patients, the way cases are handled, and the results of DAA. RESULTS: A total of 2,001 KT had been performed in our center since 1978. Pre- or post-transplantation HCV serology was present in 1,880 cases and was positive in 13.4%. A total of 1,195 transplant recipients were still being monitored by us, with only 60 (5%) HCV+ and 45 (3.6%) RNA+ cases. Of these 45 HCV+/RNA+, 25 had been or were being treated, 7 were about to begin treatment, 1 was awaiting new DAA treatment owing to low glomerular filtration rate (GFR), 3 were being evaluated, 2 had been excluded owing to high comorbidity, 2 refused to be treated, 2 needed to return to hemodialysis, and 1 was lost to follow-up. Except 1 case where Viekira Pak was used because of low GFR, all cases included sofosbuvir as the main drug associated with either ledipasvir (70%) or daclatasvir (25%). Ribavirin was added as coadjuvant in 35% of cases. Twenty-one patients had completed treatment (84%). Two patients had to interrupt DAA therapy (8%), one because of hepatotoxicity and the other as a result of a liver transplantation. In every case, the graft maintained function and negativization of viral replication occurred. CONCLUSIONS: Side effects have been low, anemia related to ribavirin being the main one. Just one case needed to be interrupted at the 7th week of DAA therapy due to hepatotoxicity. It has frequently been necessary to adjust immunosuppression treatment with the use of higher doses of tacrolimus.

New Antivirals for Hepatitis C Infection Among Infected Kidney Transplant Recipients: A Case Report.

The most common hepatopathy in end-stage renal disease is chronic hepatitis C virus (HCV) infection, which decreases allograft and patient survival in kidney transplants. Until last year we did not have treatments free of interferon, which was contraindicated after renal transplantation owing to the risk of allograft rejection. Recently, new drugs have been discovered for interferon-free regimens. These drugs present a cure rate of up to 90% and can be used in transplant recipients. Here we present our 1st 3 cases. In our experience, new antivirals have proven to be effective and safe for the treatment of HCV hepatopathy in kidney transplant recipients and liver-kidney transplantation, thus helping us to prevent complications related to HCV infection in transplant recipients.

Conservative treatment of de novo renal carcinoma on kidney graft.

BACKGROUND: De novo renal carcinoma in kidney transplants is an uncommon but not exceptional condition and is of significant importance due to the potential for recipient mortality and graft loss. The aim of our study was to determine the management and outcome of these tumors in our Kidney Transplantation Unit. MATERIAL AND METHODS: We analyzed cases of de novo kidney tumors among patients who underwent transplantation in the last 17 years in our Kidney Transplantation Unit. We detected 3 cases of clear cell carcinoma and 1 case of papillary carcinoma on the graft. We conducted follow-up on the tumor and renal function and analyzed patient responses to changes in immunosuppression. RESULTS: Tumorectomy was performed in all cases, and subsequent transplantectomy was required for patients with papillary carcinoma. None of the patients had relevant surgical complications. We also changed the patients' regimen to a proliferation signal inhibitor or mTOR inhibitor and completely withdrew all anticalcineurin agents. With a mean follow-up of 43.5 months (15-61), the 3 patients with clear cell carcinoma survived with good graft function and with no evidence of tumor recurrence. The patient with papillary carcinoma underwent follow-up at another hospital center. CONCLUSIONS: Conservative surgery along with conversion to a proliferation signal inhibitor appears to be a safe option for treating primary tumors in kidney grafts and offers good oncological and renal function results in the short and medium term.

Impact of cold ischemia time on initial graft function and survival rates in renal transplants from deceased donors performed in Andalusia.

INTRODUCTION: Prolonged cold ischemic time (CIT) in cadaveric renal transplants has been associated with a high rate of delayed graft function, acute rejection, and even reduced graft survival. We analyzed the influence of CIT on both initial graft function (IGF) and survival rate. METHODS: We studied 2525 noncombined cadaveric cases in recipients over 17 years of age between 2000 and 2008, using data from the renal transplant records of Andalusia. We defined IGF as the need to resume dialysis within the first week or a nonfunctional kidney. The multivariate analyses were corrected by center and year of transplantation. RESULTS: The mean and median cold ischemic time was 17 hours. The duration of CIT was significantly associated (P < .001) with older donor and recipient age. The frequency of IGF increased progressively with longer CIT and older donors. However, the influence of CIT persisted among all donor age strata. Logistic regression analysis using both donor and recipient age as covariables showed a relative risk per hour of 1.05 (95% confidence interval = 1.04-1.07; P < .0001). In a univariable study, longer CIT led to a significant reduction in both recipient and graft survival rates. The multivariate study (Cox) using preprocedure covariables, showed CIT to produce significantly worse survival rates for both recipients (relative risk: 1.03, 1.005-1.05, P = .02) and for grafts (relative risk: 1.03, 1.01-1.04, P = .002). However, the survival rates showed no clear progression in terms of CIT within each individual donor age stratum. CONCLUSIONS: A longer CIT was associated with an increase in IGF independent of the age of both the donor and the recipient. Our data also suggested that CIT influenced patient and graft survival rates.

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.

Results of living kidney donation in Andalusia: 2006-2009.

Renal transplantation is the best therapeutic choice in patients with end-stage renal disease (ESRD), with donation from living donors the alternative that offers the best medium- and long-term results. Because of the limited number of cadaver donors and the progressive increase in donor age, transplantation from living donors has become the renal replacement treatment of choice. Several studies have demonstrated that donation does not increase the donor's risk of developing ESRD in the long term. Some studies have asserted that a donor's life expectancy increases as a result of the comprehensive study and screening process they must undergo. The objective of the present study was to evaluate the vital status and onset of chronic renal disease in 101 living kidney donors in Andalusia, Spain, during 2006-2009, based on data obtained from the Sistema de Información de la Coordinación Autonómica de Trasplantes de Andalucía (Regional Transplants Coordination of Andalusia). Donor survival was 99%, and the only death, from lung cancer, was not associated with the surgical procedure. Only 5 transplants failed during this period, and no donors developed ESRD. Neither the probability of survival nor the risk of developing ESRD in donors was influenced by kidney donation.

Are we still making progress in patient survival after kidney transplantation? Results of a regional registry.

Many studies have shown a trend to improved long-term survival of renal transplant recipients. We analyzed the survival of recipients in Andalusia, Spain, from 1984-2007. The study included all the deceased donor, non-multiorgan grafts (n = 5599), grouped over successive 6-year periods, compared for corrected recipient survival. Changes were noted in the recipient characteristics: increased age, diabetes, vascular nephropathy, retransplantation, duration of prior replacement therapy, and reduction in positive hepatitis C virus (HCV+) serology. The univariate analysis showed a significantly worse survival associated with increased age (P < .001), diabetes (P < .001), HCV+ serology (P < .01; 1996-2007), and longer times on replacement therapy, but not with sex or retransplantation. The respective survivals at 1, 5, and 10 years in 1984-1989 were 93%, 86%, and 75%; in 1990-1995, 97%, 92%, and 84%; in 1996-2001, 96%, 91%, and 84%; and in 2002-2007, 96% and 92%, respectively. There was a significant improvement between the first and second periods (P < .001), but no change thereafter. The multivariate analysis (Cox) showed, a significant influence of age >40 years, female gender (relative risk [RR] 0.8; 95% confidence interval [CI] 0.7-0.9), diabetes (RR 2.5; 95% CI 1.8-3.4), and duration of prior replacement therapy (RR 1.08; 95% CI 1.05-1.1). The risk varied significantly depending on the period: using 2002-2007 as the reference period, the RR in 1984-1989 was 3.4 (95% CI 2.6-4.5); in 1990-1995, 1.8 (95% CI 1.3-2.3); and in 1996-2001, 1.4 (95% CI 1.1-1.8; all P < .02). The model remained for 1996-2007, though HCV+ serology was not significant. In conclusion, we showed a significant improvement in recipient survival in Andalusia over time. Correction for worse recipient characteristics suggests continued advances.

Regional survey of patient survival after cadaver renal transplant failure.

Graft failure with return to dialysis is associated with higher mortality, but the determining factors have not been completely studied. We determined predictive factors for survival after renal transplant failure by analyzing demographic and clinical data on kidney recipients in a Spanish regional registry (Andalusia). Among 5547 single-organ cadaveric grafts in Andalusia between 1984 and 2007, 1534 patients returned to dialysis and were followed to death (n = 450), retransplantation (n = 574), or the end of the study period. The most frequent cause of death was cardiovascular disease (36.9%). Actuarial survival rates were 89%, 72%, and 51% at 1, 5, and 10 years, respectively. Upon univariate (Kaplan-Meier) analysis, survival was significantly related only to age at return to dialysis and diabetes. Cox forward step wise multivariate regression analysis showed that predictive factors for lower survival (relative risk -95% confidence interval) were: age (per year), 1.05 (1.05-1.06); male sex, 1.33 (1.1-1.6); and duration of pre-graft renal replacement therapy (per year), 1.02 (1.00-1.05). According to Cox backward stepwise regression analysis, a more saturated model, the predictive factors were: age; male sex; duration of pre-graft renal replacement therapy (per year), 1.03 (1.01-1.06); later study period (1996-2007), 0.81 (0.6-1.0); and primary etiology of chronic kidney disease (CKD). Survival after renal transplant failure was lower among male recipients of advanced age or with a long period of prior renal replacement therapy. Time of transplantation and primary etiology of CKD may also play roles.

Treatment of anemia in renal transplantation: impact of a stricter application of hemoglobin targets.

OBJECTIVE: The CREATE and CHOIR studies showed a higher risk for cardiovascular events associated with hemoglobin (Hb) values >13 g/dL in patients with stage 3-4 chronic kidney disease. In 2007, a stricter policy on the use of erythropoietin (EPO) was adopted at our center, with an Hb target of 11 to 12 g/dL and withdrawal or reduction of EPO when Hb was >12.5 to 13 g/dL. This study was designed to evaluate this new approach. MATERIALS AND METHODS: The study included patients under follow-up at the transplant outpatient clinic on December 31, 2006 (n = 725), and December 31, 2007 (n = 768). Data were compared between the study populations concerning renal function, Hb, use of EPO, and associated costs. RESULTS: No significant differences in creatinine or Hb values were observed between the 2 groups (1.47 +/- 0.6 vs 1.42 +/- 0.9 mg/dL and 13.7 +/- 1.5 vs 13.7 +/- 1.6 g/dL, respectively). After implementation of the new protocol, the frequency of severe anemia (Hb <11 g/dL) increased (2% vs 4%; P = .10), the use of EPO decreased (22.1% vs 17.2%; P = .017), and the mean Hb of EPO-treated patients decreased (12.5 +/- 1.4 vs 11.9 +/- 1.0; P < .001). The Hb target (11-12 g/dL) was met in fewer than one third of patients, with no significant differences between the 2 study times. CONCLUSIONS: A strict policy on EPO application reduces its use and the rate of patients with "excessive" Hb values (which are associated with increased cardiovascular risks), with an acceptable slight increase in severe anemia cases.

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

Alendronate in kidney transplant patients: a single-center experience.

INTRODUCTION: Osteoporosis following a renal transplant is an important cause of morbidity. Several studies have demonstrated the efficiency of diphosphonates for the prevention and treatment of osteoporosis. METHODS: We evaluated the effect of alendronate treatment on bone mineral density (BMD) in patients with osteoporosis (lumbar spine and/or hip t-scores < or = -2.5). Two study groups were established: group A (n = 13), patients treated orally with vitamin D, calcium, and alendronate (70 mg/week) and group B (n = 12) patients receiving only vitamin D and calcium. The immunosuppression regimen mostly used was steroids and cyclosporine. BMD was determined at the lumbar spine and hip using a Hologic 4500 QDR densitometer at the start of treatment and after 1 year. RESULTS: The study groups showed no significant differences in age, sex, menopause, or transplant time. Group A received a mean of 1.80 +/- 1.3 microg vitamin D/week and 1.3 +/- 2.1 g calcium/d, compared to 1.1 +/- 1 microg and 1.25 +/- 2.3 g, respectively for group B (NS). After a mean of 411.15 +/- 107.75 days of treatment, a significant increase in BMD at the femoral neck was recorded in group A, but not at the level of the spine (+5.57% +/- 3.5%, P < .05 and -0.42% +/- 12%, NS, respectively). No significant changes were observed in group B (-1.45% +/- 8% femoral neck and +1.69% +/- 3.5% hip, NS). Dyspepsia was reported by 7% of patients. CONCLUSIONS: In this preliminary analysis, alendronate produced, improvements are so far limited to an increased BMD in the hip.

[Treatment of hyperphosphatemia with sevelamer in patients with chronic renal failure]. / Tratamiento de la hiperfosfatemia con sevelamer en pacientes con insuficiencia renal crónica avanzada.

UNLABELLED: Sevelamer is a recent phosphate binder that is mineral-free, and represents a great advance in the treatment of hyperphosphatemia in patients with hypercalcemia and/or gastric intolerance to calcium-based phosphate binders. The communications about the experience with the use of sevelamer in patients non-yet in dialysis is scanty. The aim of our study is to investigate retrospectively the gastrointestinal tolerance of sevelamer, their efficacy as phosphate binder and other parameters in a group of 89 patients with chronic renal failure in predialysis. We have analysed the effects of sevelamer at baseline and after 1, 3 and 6 months on the following data and parameters: calcium, phosphate, intact PTH, venous bicarbonate, urea, creatinine, creatinine clearance, side-effects, number of patients that were discontinued, and co-treatment during the study period with phosphate-based binders, calcitriol, lipid-lowering drugs and sodium bicarbonate. RESULTS: 19 patients (21.3%) refused to continue with sevelamer at the first month (16 patients had digestive intolerance and 3 several symptoms). Serum phosphate fell at 3 months (5 +/- 0.8 mg/dl basal vs 4.8 +/- 0.7 mg/dl, p = 0.02) and 6 months (5 +/- 0.8 mg/dl basal vs 4.7 +/- 0.9 mg/dl, p = 0.07). Serum calcium fell at 6 months (9.8 +/- 0.7 mg/dl basal vs 9.4 +/- 0.6 mg/dl, p = 0.03). Venous bicarbonate and iPTH were unchanged, but the quantity of sodium bicarbonate administered increased significantly. Blood cholesterol fell at 1 months (193 +/- 49 mg/dl basal vs 173 +/- 52 mg/dl, p = 0.001) and 3 months (205 +/- 49 mg/dl basal vs 170 +/- 49 mg/dl, p = 0.004), in spite of a significant reduction of the dose of statins. CONCLUSIONS: Sevelamer is an effective phosphate binder in predialysis patients and also reduces significantly the serum cholesterol, improving the blood lipid profile. The levels of venous bicarbonate remained unchanged, at expenses of an increment in the dose of sodium bicarbonate supplementation.