Incidence of cervical intraepithelial lesions and human papilloma virus infection in female renal transplant recipients.

BACKGROUND: Female renal transplant recipients (RTR) are at high risk of human papillomavirus (HPV)-related anogenital premalignancies and cancer. The aim of this study was to estimate the incidence of cervical intraepithelial lesions (IL) and HPV infection, and their associated factors, in Mexican RTR. METHODS: This is a prospective cohort study conducted between January 2011 and December 2017. Demographic, clinical, and gynecological data were collected using a previously designed questionnaire. Gynecological examination, cervical cytology, and detection of high- and low-risk HPV DNA were undertaken prior to and after the renal transplant (RT). Colposcopically guided biopsies were obtained from patients who presented high grade squamous intraepithelial lesions (HSIL) during the follow-up period. Diagnoses were established according to the Bethesda system. RESULTS: Among 130 RTR, 62 were eligible for our study. The overall incidence of IL was 17.7% (95% CI, 8% to 27%), (11/62 patients), at 25.6 ± 10.7 months post-RT. Nine out of the eleven affected patients had low-grade squamous intraepithelial lesions (81.8%) and only two had HSIL (18.2%). The incidence of HPV infection, determined in a subgroup of 30 RTR, was 53.3% (95% CI, 35% to 71%), (16 out of 30 patients), at 18.3 ± 8.9 months post-RT. High-risk HPV genotypes were present in 62.5% of HPV positive cases (10/16). In 11 patients (36.6%), HPV infection was not associated to IL. CONCLUSIONS: HPV infection and cervical IL are common in the early posttransplant period. Our findings support the need of screening for cervical cancer to detect precancerous changes in RTR and the need of strengthening the knowledge of medical personnel on this issue.

Changes in the commercial brand of tacrolimus lead to subtherapeutic trough levels and acute rejection in renal transplant recipients.

BACKGROUND: The vigilance of tacrolimus (TAC) trough levels is an essential part of renal transplant follow up. Reduced TAC trough levels and high variability are related to adverse outcomes. The aim of this study was to evaluate the impact of brand changes on tacrolimus (TAC) subtherapeutic (SubT) trough levels, acute rejection (AR), and kidney function. METHODS: This is a prospective, observational cohort study of renal transplant recipients, between January 2016 and October 2018. Tacrolimus trough levels and brand used by the patient were both registered at every consult. Tacrolimus values ≤3.5 ng/mL were considered SubT. RESULTS: 445 patients were included. The median number of TAC brand changes was 2 (IQR, 1-4). Patients were grouped according to the number of brand changes: Group 1 = 0 (n = 107), Group 2 = 1-4 (n = 236), and Group 3 = ≥5 (n = 102). Patients with the greatest number of brand changes had a greater proportion and number of SubT TAC trough levels (Group 1 = 36.4%, average 0.53; Group 2 = 39.8%, average 0.65, Group 3 = 59.8%, average 1.17, P < .001) and AR (Group 1 = 0.9%, Group 2 = 11%, Group 3 = 14.7%, P < .001). On multivariate analysis, SubT levels and the number of brand changes were related to AR. CONCLUSIONS: In Mexico, changes in TAC brand are associated with an elevated frequency of SubT levels. Brand changes and SubT levels are independently associated with acute rejection. The supply policies on TAC brands in Mexico require revision to avoid changing brands as much as possible.

TREATMENT STRATEGIES AND OUTCOME OF PARVOVIRUS B19 INFECTION IN KIDNEY TRANSPLANT RECIPIENTS: A CASE SERIES AND LITERATURE REVIEW OF 128 PATIENTS.

BACKGROUND: There is no specific antiviral treatment for parvovirus B19 (PVB19) infection. OBJECTIVE: The objective of this study was to study the treatment and outcome of PVB19 infection in kidney transplant recipients (KTR) at our institution, and cases published in the medical literature. METHODS: We conducted a retrospective review of PVB19 infection in KTR at an academic medical center over a 16-year period and summarized the data on its treatment and outcome in 120 KTR in the medical literature. RESULTS: In our cohort of eight patients, the median time to the onset of PVB19 disease was 7.2 weeks after transplantation. All patients had severe aregenerative anemia (mean hemoglobin (Hb) of 6.2 ± 1.0 g/dl); all were treated with a reduction in their immunosuppressive regimen and the administration of single-dose intravenous immunoglobulin (IVIG) (mean total dosage of 0.87 ± 0.38 g/kg). The median time to anemia improvement (Hb >10 g/dl) was 3-week post-treatment. No recurrences were documented during follow-up (median 25 months). Among 128 patients (including our cohort of 8 and 120 reported in literature), therapeutic strategies included: 43% IVIG alone, 39% IVIG and reduced immunosuppression, 9% reduction of immunosuppression, and 9% conservative therapy. Clinical relapses were observed in 35% of 71 reported cases. CONCLUSIONS: In KTR, decreasing immunosuppression and the administration of low-dose immunoglobulin seem to be not worse than the standard dose in PVB19 infection.

Fosfomycin trometamol in the prophylaxis of post-kidney transplant urinary tract infection: A controlled, randomized clinical trial.

BACKGROUND: The aim of this controlled clinical trial was to evaluate the efficacy and safety of fosfomycin trometamol (FOS) in urinary tract infection (UTI) prophylaxis during the first 6 months after renal transplant (RT). METHODS: The intervention group received 3 g of FOS PO every 10 days and trimethoprim-sulfamethoxazole (TMP-SMX, 160/800 mg) three times per week (Group 1), whereas the control group received TMP-SMX (160/800 mg) daily (Group 2). The outcomes were the time until the first UTI (symptomatic infection or asymptomatic bacteriuria (>105  CFU/mL)) and the incidence of UTI during the first 6 months post RT. Intermediate analysis was conducted after one-half of the estimated sample size of patients was enrolled. RESULTS: The recruitment of patients was stopped after the intermediate analysis due showed no emerging trends or reasonable chance of demonstrating benefit. Sixty-seven patients were included (32 in Group 1 and 35 in Group 2). The UTI incidence (40.6% vs 42.8%, P = 0.85) and time until the first episode were similar between the groups (log rank, P = 0.862). UTI due to Klebsiella spp. was observed in both groups at equal rates (25% vs 20%, P = 0.62), episodes due to Escherichia coli were less frequent in Group 1 (12.5% vs 34.2%, P = 0.04), and Enterococcus faecalis infection only occurred in Group 2 (n = 4). Resistance to FOS was observed for Klebsiella spp.; in contrast, E. coli and E. faecalis were susceptible. CONCLUSIONS: The addition of FOS to TMP-SMX was not beneficial for the prevention of UTI after RT in our setting. (ClinicalTrials.gov, NCT01820897).

Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2 Randomized Trial.

BACKGROUND: In a phase 2 study, kidney transplant recipients of low immunologic risk who switched from a calcineurin inhibitor (CNI) to belatacept had improved kidney function at 12 months postconversion versus those continuing CNI therapy, with a low rate of acute rejection and no transplant loss. STUDY DESIGN: 36-month follow-up of the intention-to-treat population. SETTING & PARTICIPANTS: CNI-treated adult kidney transplant recipients with stable transplant function (estimated glomerular filtration rate [eGFR], 35-75mL/min/1.73m2). INTERVENTIONS: At 6 to 36 months posttransplantation, patients were randomly assigned to switch to belatacept-based immunosuppression (n=84) or continue CNI-based therapy (n=89). OUTCOMES: Safety was the primary outcome. eGFR, acute rejection, transplant loss, and death were also assessed. MEASUREMENTS: Treatment exposure-adjusted incidence rates for safety, repeated-measures modeling for eGFR, Kaplan-Meier analyses for efficacy. RESULTS: Serious adverse events occurred in 33 (39%) belatacept-treated patients and 36 (40%) patients in the CNI group. Treatment exposure-adjusted incidence rates for serious infections (belatacept vs CNI, 10.21 vs 9.31 per 100 person-years) and malignancies (3.01 vs 3.41 per 100 person-years) were similar. More patients in the belatacept versus CNI group had any-grade viral infections (14.60 vs 11.00 per 100 person-years). No posttransplantation lymphoproliferative disorder was reported. Belatacept-treated patients had a significantly greater estimated gain in mean eGFR (1.90 vs 0.07mL/min/1.73m2 per year; P for time-by-treatment interaction effect = 0.01). The probability of acute rejection was not significantly different for belatacept (8.38% vs 3.60%; HR, 2.50 [95% CI, 0.65-9.65; P=0.2). HR for the comparison of belatacept to the CNI group for time to death or transplant loss was 1.00 (95% CI, 0.14-7.07; P=0.9). LIMITATIONS: Exploratory post hoc analysis with a small sample size. CONCLUSIONS: Switching patients from a CNI to belatacept may represent a safe approach to immunosuppression and is being further explored in an ongoing phase 3b trial.

Pretransplant angiotensin II type 1-receptor antibodies are a risk factor for earlier detection of de novo HLA donor-specific antibodies.

BACKGROUND: Angiotensin II type 1 receptor antibodies (AT1Rabs) have been associated with significantly reduced graft survival. Earlier graft loss has been observed in patients who had pretransplant AT1Rabs and posttransplant donor-specific antibodies (DSA). METHODS: The main goal of this retrospective cohort study was to examine the association between AT1Rabs and the time period to detection of de novo human leukocyte antigen (HLA-DSA) posttransplantation in living donor kidney transplant recipients (KTR). The analysis included 141 KTRs. Pretransplant frozen serum samples were tested for AT1Rabs by ELISA and HLA-DSA by SAB (Luminex) at both the pre- and post-KT time points. RESULTS: The median AT1Rab level was 9.13 U (interquartile range 5.22-14.33). After a mean follow-up period of 3.55 years, 48 patients were found to harbour de novo HLA-DSAs. The presence of AT1Rabs [hazard ratio (HR) 1.009, 95% confidence interval (CI) 1.002-1.01, P = 0.010], male-to-male transplantation (HR 2.57, 95% CI 1.42-4.67, P = 0.002) and antecedent borderline changes or acute cellular rejection (ACR) (HR 2.47, 95% CI 1.29-4.75, P = 0.006) were significantly associated with de novo DSA detection. A dose-dependent association between AT1Rab levels (<10 U, 10.1-16.9 U, 17-29.9 U and >30 U) and de novo DSA detection was observed (log-rank P = 0.0031). After multivariate analysis of AT1Rab levels (continuous variable), AT1Rabs >30 U, male-to-male transplantation, donor age, higher class I percentage of Panel Reactive Antibody and antecedent borderline changes or ACR remained as independent significant risk factors for the detection of de novo DSAs. CONCLUSIONS: The findings suggest that higher levels of pretransplant circulating antibodies against AT1R (>30 U) in kidney graft recipients constitute an independent risk factor for earlier de novo HLA-DSA detection during the posttransplant period.

A Three-Gene Assay for Monitoring Immune Quiescence in Kidney Transplantation.

Organ transplant recipients face life-long immunosuppression and consequently are at high risk of comorbidities. Occasionally, kidney transplant recipients develop a state of targeted immune quiescence (operational tolerance) against an HLA-mismatched graft, allowing them to withdraw all immunosuppression and retain stable graft function while resuming immune responses to third-party antigens. Methods to better understand and monitor this state of alloimmune quiescence by transcriptional profiling may reveal a gene signature that identifies patients for whom immunosuppression could be titrated to reduce patient and graft morbidities. Therefore, we investigated 571 unique peripheral blood samples from 348 HLA-mismatched renal transplant recipients and 101 nontransplant controls in a four-stage study including microarray, quantitative PCR, and flow cytometry analyses. We report a refined and highly validated (area under the curve, 0.95; 95% confidence interval, 0.92 to 0.97) peripheral blood three-gene assay (KLF6, BNC2, CYP1B1) to detect the state of operational tolerance by quantitative PCR. The frequency of predicted alloimmune quiescence in stable renal transplant patients receiving long-term immunosuppression (n=150) was 7.3% by the three-gene assay. Targeted cell sorting of peripheral blood from operationally tolerant patients showed a significant shift in the ratio of circulating monocyte-derived dendritic cells with significantly different expression of the genes constituting the three-gene assay. Our results suggest that incorporation of patient screening by specific cellular and gene expression assays may support the safety of drug minimization trials and protocols.

Increased phosphorylation of the renal Na+-Cl- cotransporter in male kidney transplant recipient patients with hypertension: a prospective cohort.

Evidence in rodents suggests that tacrolimus-induced posttransplant hypertension is due to upregulation of the thiazide-sensitive Na+-Cl- cotransporter NCC. Here, we analyzed whether a similar mechanism is involved in posttransplant hypertension in humans. From January 2013 to June 2014, all adult kidney transplant recipients receiving a kidney allograft were enrolled in a prospective cohort study. All patients received tacrolimus as part of the immunosuppressive therapy. Six months after surgery, we assessed general clinical and laboratory variables, tacrolimus trough blood levels, and ambulatory 24-h blood pressure monitoring. Urinary exosomes were extracted to perform Western blot analysis using total and phospho-NCC antibodies. A total of 52 patients, including 17 women and 35 men, were followed. At 6 mo after transplantation, of the 35 men, 17 developed hypertension and 18 remained normotensive, while high blood pressure was observed in only 3 of 17 women. The hypertensive patients were significantly older than the normotensive group; however, there were no significant differences in body weight, history of acute rejection, renal function, and tacrolimus trough levels. In urinary exosomes, hypertensive patients showed higher NCC expression (1.7±0.19) than normotensive (1±0.13) (P=0.0096). Also, NCC phosphorylation levels were significantly higher in the hypertensive patients (1.57±0.16 vs. 1±0.07; P=0.0049). Our data show that there is a positive correlation between NCC expression/phosphorylation in urinary exosomes and the development of hypertension in posttransplant male patients treated with tacrolimus. Our results are consistent with the hypothesis that NCC activation plays a major role in tacrolimus-induced hypertension.

Changes in frequency of delayed graft function in deceased donor renal transplant recipient in a tertiary care center in Mexico.

BACKGROUND: Delayed graft function (DGF) is defined as the need for dialysis within the first seven days of transplantation. The frequency of DGF has decreased in the last five years compared with the previous 20 years of the kidney transplant program at a Mexican referral hospital. OBJECTIVE: To determine the incidence and risk factors for DGF in the past five years (2009-2013). METHODS: We analyzed a retrospective cohort of renal transplant recipients from deceased donors at our hospital between March 2009 and May 2013 (Period 2), and compared the results with a previously evaluated cohort (Period 1, between January 1990 and February 2009). RESULTS: During the analyzed period, 78 deceased donor transplants were performed. The frequency of DGF was 9%. Multivariate analysis showed that recipient older age (OR: 1.074419; 95% CI: 1.0009-1.155116; p = 0.05), transoperative amines administration (OR: 7.73; 95% CI: 1.037-57.6; p = 0.046), and hypotension during surgery in the recipient (OR: 11.6; 95% CI: 1.33-100.8; p = 0.026) were risk factors for DGF. CONCLUSION: The incidence of DGF has significantly decreased in the past five years when compared to the previous 20 years in our hospital.

A pilot study on dual-energy computed tomography for detection of urate deposits in renal transplant patients with asymptomatic hyperuricemia.

BACKGROUND: An increasing role of dual-energy computed tomography (DECT) scan in tophaceous gout assessment is recognized, whereas its role in asymptomatic hyperuricemia is unknown. OBJECTIVE: The objective of this study was to assess the prevalence of joint and renal monosodium urate deposits by DECT in asymptomatic hyperuricemia. METHODS: Among a renal transplant population with at least 1 year of follow-up, we included 27 patients with sustained hyperuricemia and 11 with normal serum uric acid (SUA) levels. We excluded patients with gout or history of monoarthritis or oligoarthritis. We registered demographic data, drugs, hyperuricemia onset, comorbidities, renal function, and SUA. We used a 128-slice dual-source CT system, and the acquisition protocol included the pelvis and imaging of elbows, wrists, hands, knees, ankles, and feet. The reading process was performed by 2 radiologists. RESULTS: The mean age was 43.7 ± 12 years, 57.8% were males, and median follow-up was 7 years. Hyperuricemia presented after a median time of 0.61 years after transplantation and had persisted for a median of 3.2 years (0.5-16.8 years). For the hyperuricemic group, the median SUA at the DECT scan and the maximum SUA levels were 7.9 and 8.9 mg/dL, respectively. Groups were similar in most of the clinical variables. We did not find any articular or renal deposit; conversely, we demonstrated a quadriceps tendon deposition in 1 patient with hyperuricemia (prevalence of 0.03%; 95% confidence interval, 0.006%-0.17%). CONCLUSIONS: In these patients with asymptomatic hyperuricemia, the prevalence of monosodium urate deposition assessed by DECT was low; however, larger studies need to be performed for further validation.

Pre-transplant angiotensin II type 1receptor antibodies: a risk factor for decreased kidney graft function in the early post-transplant period?

Angiotensin II type 1 receptor antibodies (AT1Rab) are associated to a significantly lower graft survival and a higher risk of acute rejection after kidney transplantation. This study aimed to evaluate graft function and BPAR during the 1st year post-transplant (PT) in adult kidney transplant recipients (KTR), between 03/2009 and 08/2012. Pre-KT sera were screened for AT1Rab (ELISA) and HLA-DSA (Luminex). Three groups were analyzed: AT1Rab only (n = 13); HLA-DSA only (n = 8); and no AT1Rab or HLA-DSA (n = 90). No differences were observed in clinical characteristics across groups. A higher percentage of BPAR was observed in the AT1Rab positive group, but this difference was not significant. KTR with AT1Rab had a lower mean eGFR (20 mL/min/1.73m2) when compared to KTR with no Abs at 12 months. The significant difference in eGFR was observed since the 1st month PT. Multivariate analysis showed 4 factors independently and significantly associated with eGFR at 12mos PT: BPAR (-18.7 95%, CI -28.2 to -9.26, p<0.001), AT1Rab (-10.51, CI -20.9 to -0.095, p = 0.048), donor age (-0.42, CI -0.75 to -0.103 p = 0.010), and recipient age (-0.36, CI -0.67 to -0.048, p = 0.024). In this study AT1Rab in pre-transplant sera from KTR, was an independent and significant risk factor contributing to a lower eGFR 12 months. PT. This finding deserves to be confirmed in a larger KTR population.

Mineralocorticoid receptor blockade reduced oxidative stress in renal transplant recipients: a double-blind, randomized pilot study.

BACKGROUND: Previous experimental studies from our laboratory have demonstrated that aldosterone plays a central role in renal ischemic processes. This study was designed to evaluate the effect of mineralocorticoid receptor blockade in renal transplant recipients from living donors. METHODS: 20 adult kidney transplant recipients from living donors were included in a double-blind, randomized, placebo-controlled clinical pilot study that compared spironolactone and placebo. Placebo or spironolactone (25 mg) was administered 1 day before and 3 days posttransplantation. Renal function and urinary kidney injury molecule-1, interleukin-18, and heat shock protein 72 as well as urinary hydrogen peroxide (H2O2) levels were quantified. RESULTS: No significant differences were seen between the groups studied regarding age, gender, indication for kidney transplantation, residual renal function, renal replacement therapy, or warm and cold ischemia periods. In contrast, spironolactone administration significantly reduced the oxidative stress assessed by the urinary H2O2 excretion, in spite of no differences in renal function or reduction in tubular injury biomarkers. CONCLUSIONS: The findings of this exploratory study strongly suggest that aldosterone promotes oxidative stress and that the administration of spironolactone reduces the production of urinary H2O2 as a result of lesser formation of surrogate reactive oxygen species secondary to the ischemia-reperfusion phenomenon.

[Risk factors in the development of delayed graft function in deceased donor kidney transplant recipients and their impact on patient and graft survival]. / Factores de riesgo para el desarrollo de función retardada del injerto en receptores de trasplante renal de donante fallecido y su impacto en la supervivencia de paciente e injerto.

BACKGROUND: Delayed graft function (DGF) is an early complication of kidney transplant (KT) and it is related to a higher incidence of acute rejection (AR) and lower graft survival. The incidence of DGF ranges from 2 to 29% in different series. Several risk factors for DGF have been described, including inotropic use in the deceased donor, long cold ischemia time, cardiovascular brain death, age > 55 years, hypovolemia, previous transplant, preformed antibodies and OKT3 use. MATERIAL AND METHODS: This study is a retrospective cohort of the kidney transplant recipients (KTR) of deceased donors from 1990 to 2009, at the INCMNSZ. We analyzed the incidence of DGF, risk factors associated to its development, and patient and graft outcome. To compare the groups, we used chi2 test or Student's t test for categorical and numeric variables, respectively. Patient and graft survival were calculated using Kaplan-Meier method; a p value < 0.05 was considered statistically significant. RESULTS: Data from 105 KTR were analyzed. DGF occurred in 21%, AR in 27%, graft loss in 15.2%. The only risk factor associated to DGF was brain death due to vascular disease (p = 0.028). CONCLUSIONS: Brain death due to vascular disease was the only risk factor associated to DGF. A non-significant higher incidence of AR was observed in patients with DGF. Survival was significantly lower in patients who developed DGF compared to those without DGF, and it was not related to renal function.

Improvement in renal function in kidney transplant recipients switched from cyclosporine or tacrolimus to belatacept: 2-year results from the long-term extension of a phase II study.

Kidney transplant recipients who switched from a calcineurin inhibitor (CNI) to belatacept demonstrated higher calculated glomerular filtration rates (cGFRs) at 1 year in a Phase II study. This report addresses whether improvement was sustained at 2 years in the long-term extension (LTE). Patients receiving cyclosporine or tacrolimus were randomized to switch to belatacept or continue CNI. Of 173 randomized patients, 162 completed the 12-month main study and entered the LTE. Two patients (n = 1 each group) had graft loss between Years 1-2. At Year 2, mean cGFR was 62.0 ml/min (belatacept) vs. 55.4 ml/min (CNI). The mean change in cGFR from baseline was +8.8 ml/min (belatacept) and +0.3 ml/min (CNI). Higher cGFR was observed in patients switched from either cyclosporine (+7.8 ml/min) or tacrolimus (+8.9 ml/min). The frequency of acute rejection in the LTE cohort was comparable between the belatacept and CNI groups by Year 2. All acute rejection episodes occurred during Year 1 in the belatacept patients and during Year 2 in the CNI group. There were more non-serious mucocutaneous fungal infections in the belatacept group. Switching to a belatacept-based regimen from a CNI-based regimen resulted in a continued trend toward improved renal function at 2 years after switching.

Sub-classification of borderline changes into diffuse or focal and its impact on long-term renal transplant outcomes.

BACKGROUND: Borderline changes (BL) with stable renal function is a controversial category in renal transplantation, given its contradictory outcomes. The aim of this study was to compare the clinical outcomes of BL in patients with stable renal function classified as focal and diffuse according to the extent of tubulitis. METHODS: Patients with no history of rejection with a surveillance graft biopsy at 3 or 12 months showing BL (n = 40), acute cellular rejection (n = 20) or normal biopsies (n = 20), were included in this study. Biopsies with BL were divided into diffuse BL (BLD) and focal BL (BLF) according to the extent of tubulitis. Because of the low frequency of subclinical ACR (ACRND) (n = 12), biopsies with ACR and graft dysfunction (ACRD) (n = 8) were also included. A composite outcome that included the presence of rejection in subsequent biopsies, graft loss, patient death, decrease in GFR ≥30% or presence of de novo DSA (dnDSA) during the first year of follow-up was evaluated. RESULTS: The primary composite outcome occurred in five patients of each of the Normal, BLF and ACRND, eight patients with BLD and six patients with ACRD (p = 0.105). A trend towards more rejection episodes was observed in the ACRND and ACRD. Also, a shorter time to rejection in the BLD, ACRND and ACRD groups compared to BLF and Normal groups (p = 0.039) was observed. During the first year of follow-up, no patient in the ACRND group developed dnDSA, compared to 15-25% in the other groups. The median time of dnDSA development in the BLF group was 45 months, and in the BLD group was 10 months (p = 0.020). CONCLUSION: Classifying BL biopsies with stable renal function into focal and diffuse categories, is a simple and feasible strategy that helps to differentiate between BLD with a phenotype that shows a trend towards worse outcomes, and BLF that behaves more similar to normal biopsies.

Neurocognitive profile of an adult sample with chronic kidney disease.

Chronic kidney disease (CKD) is a common and debilitating illness that impacts neurocognitive function. However, the majority of previous studies varied in methodologic design and rigor, thus minimizing definitive conclusions. The present study was designed to determine the impact of CKD on neurocognitive function through specific examination of CKD factors and therapeutic interventions. We evaluated 120 CKD outpatients and 41 healthy donors (controls) in terms of neurocognitive function, anxiety, and depressive symptomatology, and somnolence. Information regarding medical and treatment history was recorded. Twenty-three percent of CKD patients presented with cognitive impairment. Stage 5 patients had lower scores (p < .05) compared with controls and patients in stage 3 and 4 on measures of global cognitive function. No differences in global cognitive function were found between stage 3 and 4 patients and controls. A greater proportion of patients undergoing hemodialysis relative to those treated with peritoneal dialysis showed impairment on measures of memory functions. Results suggest that stage 5 CKD patients may present with impaired cognitive functions. Anemia appeared to be a key variable that may explain the memory impairment in this sample. Future longitudinal investigations of CKD are warranted to determine the trajectory of cognitive impairment.

Assessment of emotional distress in chronic kidney disease patients and kidney transplant recipients.

OBJECTIVE: To assess the presence of emotional distress in patients with chronic kidney disease (CKD), and the effect of kidney transplant on these symptoms. MATERIAL AND METHODS: This was a two-part study. Part one was cross-sectional, observational, and descriptive, where 75 patients with CKD were evaluated for emotional distress with the Hospital Anxiety and Depression Scale (HAD) and the Symptom Checklist 90 (SCL-90). In part two, we longitudinally followed 19% of the study cohort to examine symptomatological changes after their kidney transplantation. RESULTS: The results of the HAD indicated that 30.7% of the study cohort with End-Stage Renal Disease (ESRD) showed anxious symptoms, and 25.3% showed depressive symptoms. The change in the HAD total score before and after kidney transplant was not significant. However, a significant decrease in total score on the SCL-90 was observed before and after transplantation. CONCLUSION: Improvement on emotional distress was found after kidney transplantation.

Extended major histocompatibility complex haplotypes, ancestry and acute kidney transplant rejection in Mexicans.

INTRODUCTION: Extended major histocompatibility complex (MHC) haplotypes are associated with several autoimmune diseases, and these appear to depend on ancestry. OBJECTIVE: To evaluate the association of extended MHC gene frequencies, ancestry, and acute rejection. MATERIAL AND METHODS: 127 living kidney transplant recipients who underwent kidney transplantation in Mexico City between January 2004 and October 2007 with follow up until October 2008. The primary outcome was biopsy proven acute rejection. Ancestry was considered as either Amerindian or admixtures with Caucasian, African or Oriental genes. Allele and haplotype frequencies were estimated for HLA A, B and DR loci. Hardy Weinberg (HW) and delta values were analyzed to test for linkage disequilibrium (LD). RESULTS: There were no significant differences in the baseline characteristics between groups. 50% were men, and 28, 61 and 10% of the patients shared zero, one or two haplotypes, respectively. The whole population was Hispanic and born in Mexico. Median PRA was 0%. Allelic variance in all MCH loci was in HW equilibrium, 14% developed acute rejection. There was a high frequency of Amerindian haplotypes; admixture genes and LD were higher in the group with acute rejection. When compared to the group without acute rejection, the haplotype A1*B8*DR3 was more frequent in donors in whom their recipients had acute rejection (p = 0.008), while A28*B39*DR4 was more common in the recipients with acute rejection (p = 0.003). Multivariate Cox regression models did not attenuate these associations. CONCLUSIONS: Ancestry and LD may be associated with risk of acute rejection and may therefore be useful in directing immunosuppression.

[Is a calcineurin inhibitor required as part of the immunosuppression scheme in kidney transplant recipients that share 2-haplotypes with their donors?]. / Es necesario un inhibidor de calcineurina como parte del esquema de inmunosupresión en receptores de trasplante renal que comparten dos haplotipos con su donador?

INTRODUCTION: The recipients of HLA-identical live-donors grafts (RKT 2HP) have a low immunologic risk, and it is common to use immunosuppressive regimen with two medicaments excluding the calcineurin inhibitor. This study compares the long term outcomes of the double immunosuppressive therapy versus the triple therapy in RKT 2HP. MATERIALS AND METHODS: This study is a retrolective cohort. The patients were divided in two groups: (1) RKT 2HP who receive double immunosupresive therapy and (2) RKT 2HP with triple immunosupresive therapy. The outcomes evaluated were: renal function, acute rejection rate, lost of renal allograft, death rate, infections and hospitalization, change in the immunosupresive therapy and its causes. RESULTS: We analyzed 85 kidney transplant recipients who share two haplotypes, 60 in the group 1 and 25 in the group 2. The median of time of follow-up in the group 1 was 138 months (min 23 and max 302) and 55 months (min 12 and max 106) in the group 2. There were four cellular acute rejection and nine allograft lost in patients of the group 1. There wasn't any significant difference between the allograft outcome and the renal function at 60 months of follow out between the groups. 23 patients had change in the immunosuppressive therapy, 12 (53%) in the group 1 and 11 (47%) in the group 2. The major cause of change of therapy in the group 1 was leucopenia by azatioprin (five patients); and in the group 2 was nephrotoxicity for calcineurin inhibitor (six patients). DISCUSSION: Despite the evident nephrotoxicity, the use of calcineurin inhibitor is useful even in patients with low immunologic risk. According to the time of follow-up between the groups, even when the allograft survival was superior in group 2, the difference wasn't significative, it might be because the lower number of patients in group 1.

A urine score for noninvasive accurate diagnosis and prediction of kidney transplant rejection.

Accurate and noninvasive monitoring of renal allograft posttransplant is essential for early detection of acute rejection (AR) and to affect the long-term survival of the transplant. We present the development and validation of a noninvasive, spot urine-based diagnostic assay based on measurements of six urinary DNA, protein, and metabolic biomarkers. The performance of this assay for detecting kidney injury in both native kidneys and renal allografts is presented on a cohort of 601 distinct urine samples. The urinary composite score enables diagnosis of AR, with a receiver-operator characteristic curve area under the curve of 0.99 and an accuracy of 96%. In addition, we demonstrate the clinical utility of this assay for predicting AR before a rise in the serum creatinine, enabling earlier detection of rejection than currently possible by standard of care tests. This noninvasive, sensitive, and quantitative approach is a robust and informative method for the rapid and routine monitoring of renal allografts.