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.

Evaluation of the Spanish Urological Association quality care indicators in a kidney transplantation programme. / Evaluación de los indicadores de calidad asistencial de la Asociación Española de Urología en un programa de trasplante renal.

INTRODUCTION: Indicators show the presence of a phenomenon and its intensity. They assess the level of quality care and identify potential situations for improvement. Our objective is to assess the 2013 and 2014 quality care indicators of our department's kidney transplantation area. MATERIAL AND METHOD: For 2013 and 2014, we reviewed 88 and 106 kidney transplants and 47 and 66 extractions. We evaluated the quality care indicators developed by the Spanish Urological Association, analysing the results with the SPSS v 21.0 programme. RESULTS: The mean cold ischaemia time (CIT) was 14.96hours in 2013 and 18.07hours in 2014. The CIT was ≤18h in 53% and 56% of cadaveric donor kidneys in 2013 and 2014, respectively. The rate of relevant early onset urinary fistulae was 1.14% and 2.83% for each year. The rate of early transplantectomy due to a vascular complication was 3.41% and 2.83% for 2013 and 2014, respectively. Overall patient survival at 1 year was 100% for both periods, and graft survival at 1 year was 95% and 94.34% for 2013 and 2014, respectively. The rate of living-donor transplantation was 14.77% and 17.92%, and 92.31% and 68.42% of the living-donor extractions were laparoscopic for 2013 and 2014, respectively. Resident medical interns were the first surgeon in 6.67% and 12.64% of the transplantations and in 55.88% and 19.14% of the cadaveric extractions during 2013 and 2014, respectively. CONCLUSIONS: During the evaluated period, all quality care standards in kidney transplantation were met, except for CIT in both years and resident medical intern participation in kidney implantation in 2013. This analysis promotes improvements in quality care, highlighting weak spots that need work.

Assessment of the Renal Function in Potential Donors of Living Kidney Transplants: Expanded Study.

INTRODUCTION: It is very important to determine as accurately as possible the renal function in potential living renal transplant donors, especially those with limited renal function (CrCl <90 mL/m/1.73 m(2)), age older than 50 years, and cardiovascular risk factors that might favor the development of long-term kidney diseases. OBJECTIVE: The objective of this study was to compare the direct measurement of glomerular filtration rate (GFR) using EDTA-Cr51 and the estimations based on creatinine (eGFR): Cr clearance (CCr) with 24-hour urine and estimated using Cockroft-Gault (adjusted by using body surface area-Mosteller formula-SC), MDRD-4, MDRD-6, and CKD-EPI to determine the usefulness of different methods from EDTA-Cr51to evaluate the kidney function. PATIENTS AND METHODS: The kidney function evaluation has been made to 105 potential kidney donors using the EDTA-Cr51 method. The GFR obtained through the EDTA-Cr51 is compared with the CCr values in 24-hour urine and eGFR based on creatinine (Cockcroft-Gault, MDRD4, MDRD6, and CKD-EPI). RESULTS: Using the Bland Altman graphic we have observed that the most dispersed results are obtained with the eGFR using CCr in 24-hour urine and CKD-EPI. By means of Pasing & Bablock, we realized that MDRD-4 and MDRD-6 show the highest approximation to the reference method proposed to be substituted, whereas CCr shows a high dispersion. CONCLUSIONS: eGFR using MDRD-4 and MDRD-6 formulas reveal the best adjustment to the measure by EDTA-Cr51. This might represent the best option if a direct eGFR measure is not available.

Influence of donor specific HLA antibodies detected by Luminex in kidney graft survival: a multivariate analysis.

Some studies have demonstrated the clinical relevance of a positive virtual crossmatch in graft survival; nevertheless, other donor and recipient variables influence the outcome of the transplant. The aim of this study was to investigate the relevance of a positive virtual crossmatch in the graft survival performing a multivariate analysis including other pretransplant variables. A total of 879 deceased kidney transplantations were included. Univariate and multivariate analyses were performed using Cox regression model. After performing the multivariate analysis, a positive virtual crossmatch against class I (adjusted HR 6.613; 95% CI 3.222-13.573), class II (adjusted HR 2.419; 95% CI 1.170-5.002) and class I+II (adjusted HR 5.717; 95% CI 1.925-16.975) detected by single antigen Luminex was the variable conferring the greatest relative risk of graft loss. A positive virtual crossmatch predicts a worse kidney graft survival even after correction by other variables and therefore, transplantation of patients with positive virtual crossmatches should be avoided.

A form of apolipoprotein a-I is found specifically in relapses of focal segmental glomerulosclerosis following transplantation.

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) following kidney transplantation occurs in a large percentage of patients. Accurate prediction of recurrence and elucidation of its pathogenesis are major therapeutic goals. To detect differential proteins related to FSGS recurrence, proteomic analysis was performed on plasma and urine samples from 35 transplanted idiopathic FSGS patients, divided into relapsing and nonrelapsing. Several proteins were detected increased in urine of relapsing FSGS patients, including a high molecular weight form of apolipoprotein A-I, named ApoA-Ib, found exclusively in relapsing patients. This finding was verified by Western blot individually in the 35 patients and validated in an independent group of 40 patients with relapsing or nonrelapsing FSGS, plus two additional groups: FSGS-unrelated patients showing different proteinuria levels (n = 30), and familial FSGS transplanted patients (n = 14). In the total of 119 patients studied, the ApoA-Ib form was detected in 13 of the 14 relapsing FSGS patients, and in one of the 61 nonrelapsing patients. Only one of the 30 patients with FSGS-unrelated proteinuria tested positive for ApoA-Ib, and was not detected in familial patients. Urinary ApoA-Ib is associated with relapses in idiopathic FSGS and warrants additional investigation to determine its usefulness as biomarker of relapse following transplantation.

Information channels and the dynamics of uptake of living kidney donors: a retrospective study in a reference area.

INTRODUCTION: Activity in renal transplantation at our center continues to grow due to the gradual increase in living donor kidney transplantations (LDKT). Our objective was to describe the generation process of living donation in our area of influence including two provinces and 18 chronic kidney disease (CKD) treatment units in particular the origin of paired donor/recipients and information channels. METHODS: We included all actual and discarded potential donors from 2005 to 2009. History and telephone interviews provided a description of the cases, sources and process information. RESULTS: Among 95 potential pairs we performed 44 LDKT during this period. The recipients were predialysis (38%), on dialysis (54%), or after prior transplantation (8%). Among the 10 dialysis centers, the referral rate ranged between 0 and 8.6 pairs per 100 patients. We contacted 78 (83%) donors for an interview, among whom 53% first learned of LDKT when the recipient already had advanced CKD at predialysis or dialysis stages. Television was the main means of this first knowledge (38%), followed by the health care staff. LDKT was not primarily a treatment option offered by the nephrologist for 65% of subjects; however, the nephrologists were the major reference sources followed by the Internet and transplant coordinators. CONCLUSIONS: The majority of donations are initiated before the recipient is on dialysis, but eventuates predialysis in only 38% of cases. The possibility of being referred seems to be influenced by the recipient's treatment center. We need a more proactive role of nephrologists to offer this therapeutic option. This study identified the importance of public information to identify targets and design strategies to disseminate quality information on LDKT.

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.

Influence of renal insufficiency on pharmacokinetics of ACYL-glucuronide metabolite of mycophenolic acid in renal transplant patients.

The acyl glucuronide of mycophenolic acid (AcMPAG) is a metabolite with in vitro immunosuppressive activity. The chemical properties of acyl glucuronides have been associated with the toxicity of some drugs. The aim of our study was to analyze the influence of renal insufficiency on the pharmacokinetics of AcMPAG. Areas under the 12-hour curve (AUC(0-12h)) of MPA, glucuronide of MPA (MPAG), and AcMPAG were determined by high performance liquid chromatography performed in 20 renal transplantation patients under treatment with mycophenolate mofetil (MMF), cyclosporine, and steroids. They were divided between a group with preserved renal function (group I, mean creatinine clearance [Clcr] of 105 +/- 7 mL/min) and one with advanced renal insufficiency (group II, mean Clcr of 27 +/- 5 mL/min). There was no difference in MMF dose or MPA-AUC(0-12h) values between groups. Mean predose levels of AcMPAG-C0 and AcMPAG-AUC(0-12h) were much higher in group II than in group I (0.5 +/- 2 vs 1.6 +/- 1 microg/mL and 12 +/- 2 vs. 32 +/- 19 microg*h/mL respectively, P < .005). The present data suggested that AcMPAG, a metabolite with immunosuppressive activity that may be related to toxic effects of MPA, is renally eliminated. Its levels can significantly rise in patients with renal insufficiency. Although further studies with more patients are required to determine the role of AcMPAG in MPA toxicity, we believe that this accumulation may be of clinical relevance.

Pharmacokinetics of mycophenolate mofetil in kidney transplant patients with renal insufficiency.

Mycophenolate mofetil (MMF) is an immunosuppressant that is widely used for prophylaxis of rejection in solid organ transplantation. In this study, we examined the effect of renal insufficiency on the pharmacokinetics of MMF, particularly on the free fraction of drug in renal transplant patients. Our study was performed on 10 patients with severe renal insufficiency (creatinine clearance [CrCl] <30 mL/min), and 10 control patients with preserved renal function (CrCl >90 mL/min). All the patients had received a cadaveric donor graft at least 1 year prior and were clinically stable under treatment with MMF and cyclosporine. For each patient, we determined 12-hour areas under the curve (AUC(0-12 h)) for the metabolites: mycophenolic acid (MPA), 7-O-mycophenolic acid glucuronide (MPAG), and the free non-protein-bound fraction of MPA (f-MPA). The two groups were matched for age, sex, and MMF dose. Mean AUC(0-12 h) values for MPA were similar in both groups. The renal insufficiency group showed a significantly increased AUC(0-12 h) for MPAG (1550 +/- 392 vs 3527 +/- 1130 microg.h/mL, P < .001) and increased trough and AUC(0-12 h) values for f-MPA (0.023 +/- 0.02 vs 0.094 +/- 0.07 microg/mL, P = .003, and 0.87 +/- 0.3 vs 1.52 +/- 0.8 microg . h/mL, P = .016, respectively). We proposed that these differences should be taken into account when deciding upon the dose of this drug for the subset of patients with impaired transplant function.

[Interstitial pneumonitis associated with sirolimus administration in a renal transplantation patient: a clinical case]. / Neumonitis intersticial asociada al uso de sirolimus en un trasplantado renal: un caso clínico.

Sirolimus is an immunosuppressive drug which has proved its effectivity to reduce the incidence of acute rejection in renal transplantation receptors. As this drug lacks nephrotoxic effects, its simultaneous use with other anticalcineurinic drugs allows the use of reduced doses. Thrombocytopenia and hyperlipidemia are the best known side-effects of sirolimus administration. Alterations in hepatic biochemistry results are also common. Some instances of interstitial pneumonitis associated to its use have been recently reported. In this paper we present a clinical case related to this rare but already confirmed adverse side-effect, which apart from the other more common nosologies occurring in immunosuppressed patients, should be taken into account in the differential diagnosis of interstitial pneumonitis in patients who are being administered this drug.