Impact of hyperparathyroidism on allograft histology and function after kidney transplantation: Rethinking its causal role in graft dysfunction.

INTRODUCTION: The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford-Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time-zero graft biopsies. METHODS: Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre-transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post-transplant hyperparathyroidism by iPTH >1× and >2× the URL 1 year after transplantation. RESULTS: We included 325 KTRs (56% female, age 38 ± 13 years, follow-up 4.2 years [IQR: 2.7-5.8]). Based on pre-transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of >25% IF/TA between KTRs with pre-transplant iPTH levels above and within target range according to KDIGO (53% vs. 62%, P = .16, HR.94 [95% CI:.67-1.32]) and KDOQI (60% vs. 60%, P = 1.0, HR 1.19 [95% CI:.88-1.60]) criteria. Similarly, there were no differences when using 1 year post-transplant iPTH cut-offs > 88 pg/mL (58% vs. 64%, P = .33) and > 176 pg/mL (55% vs. 62%, P = .19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata. CONCLUSION: In young KTRs who received a healthy graft, no association was found between increased pre- and post-transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation.

Long-term effects of hypercalcemia in kidney transplant recipients with persistent hyperparathyroidism.

BACKGROUND: Hypercalcemia is highly prevalent in kidney transplant recipients with hyperparathyroidism. However, its long-term impact on graft function is uncertain. METHODS: We conducted a prospective cohort study investigating adverse graft outcomes associated with persistent hypercalcemia (free calcium > 5.2 mg/dL in ≥ 80% of measures) and inappropriately elevated intact parathyroid hormone (> 30 pg/mL) in kidney transplant recipients. Asymptomatic mild hypercalcemia was monitored unless complications developed. RESULTS: We included 385 kidney transplant recipients. During a 4-year (range 1-9) median follow-up time, 62% of kidney transplant recipients presented persistent hypercalcemia. Compared to kidney transplant recipients without hypercalcemia, there were no significant differences in graft dysfunction (10% vs. 12%, p = 0.61), symptomatic urolithiasis (5% vs. 3%, p = 0.43), biopsy-proven calcium deposits (6% vs. 5%, p = 1.0), fractures (6% vs. 4%, p = 0.64), and a composite outcome of urolithiasis, calcium deposits, fractures, and parathyroidectomy indication (16% vs. 13%, p = 0.55). In a subset of 76 kidney transplant recipients, subjects with persistent hypercalcemia had higher urinary calcium (median 84 [43-170] vs. 38 [24-64] mg/day, p = 0.03) and intact fibroblast growth factor 23 (median 36 [24-54] vs. 27 [19-40] pg/mL, p = 0.04), and lower 25-hydroxyvitamin D levels (11.3 ± 1.2 vs. 16.3 ± 1.4 ng/mL, p < 0.001). In multivariate analysis, pretransplant intact parathyroid hormone < 300 pg/mL was associated with a reduced risk of post-transplant hypercalcemia (OR 0.51, 95% CI 0.32-0.80). CONCLUSIONS: Long-term persistent mild hypercalcemia (tertiary hyperparathyroidism) was frequent in kidney transplant recipients in our series. This condition presented with lower phosphate and 25-hydroxyvitamin D, and higher urinary calcium and intact fibroblast growth factor 23 levels compared to kidney transplant recipients without hypercalcemia, resembling a mild form of primary hyperparathyroidism. Despite these metabolic derangements, the risk of adverse graft outcomes was low.

Antibodies for ß2-Microglobulin and the Heavy Chains of HLA-E, HLA-F, and HLA-G Reflect the HLA-Variants on Activated Immune Cells and Phases of Disease Progression in Rheumatoid Arthritis Patients under Treatment.

Rheumatoid arthritis (RA) is a progressive, inflammatory, autoimmune, symmetrical polyarticular arthritis. It is characterized by synovial infiltration and activation of several types of immune cells, culminating in their apoptosis and antibody generation against "altered" autoantigens. ß2-microglobulin (ß2m)-associated heavy chains (HCs) of HLA antigens, also known as closed conformers (Face-1), undergo "alteration" during activation of immune cells, resulting in ß2m-free structural variants, including monomeric open conformers (Face-2) that are capable of dimerizing as either homodimers (Face-3) or as heterodimers (Face-4). ß2m-free HCs uncover the cryptic epitopes that can elicit antibodies (Abs). We report here the levels of IgM and IgG Abs against both ß2m and HCs of HLA-E, HLA-F, and HLA-G in 74 RA patients receiving immunosuppressive drugs. Anti-ß2m IgM was present in 20 of 74 patients, whereas anti-ß2m IgG was found in only 8 patients. Abs against ß2m would be expected if Abs were generated against ß2m-associated HLA HCs. The majority of patients were devoid of either anti-ß2m IgM or IgG but had Abs against HCs of different HLA-Ib molecules. The paucity of anti-ß2m Abs in this cohort of patients suggests that Abs were developed against ß2m-free HLA HCs, such as Face-2, Face-3, and Face-4. While 63 of 68 patients had IgG Abs against anti-HLA-F HCs, 36 and 50 patients showed IgG Ab reactivity against HLA-E and anti-HLA-G HCs, respectively. Evidently, anti-HLA-F HC Abs are the most predominant anti-HLA-Ib HC IgG Abs in RA patients. The incidence and intensity of Abs against HLA-E, HLA-F, and HLA-G in the normal control group were much higher than those observed in RA patients. Evidently, the lower level of Abs in RA patients points to the impact of the immunosuppressive drugs on these patients. These results underscore the need for further studies to unravel the nature of HLA-F variants on activated immune cells and synoviocytes of RA patients.

Renal arterial resistive index, monocyte chemotactic protein 1 and neutrophil gelatinase-associated lipocalin, for predicting acute kidney injury in critically ill cancer patients.

PURPOSE: We evaluated the renal arterial resistive index (RRI), urine monocyte chemotactic protein 1 (uMCP-1), and urine neutrophil gelatinase-associated lipocalin (uNGAL) to predict acute kidney injury (AKI) in critically ill cancer patients. METHODS: In this prospective study, we included patients without AKI. We compared the area under the curve (AUC) of RRI, uMCP-1, and uNGAL to predict any stage of AKI and stage-3 AKI with the DeLong method, and we established cutoff points with the Youden index. RESULTS: We included 64 patients, and 43 (67.2%) developed AKI. The AUC to predict AKI were: 0.714 (95% CI 0.587-0.820) for the RRI, 0.656 (95% CI 0.526-0.770) for uMCP-1, and 0.677 (95% CI 0.549-0.789) for uNGAL. The AUC to predict stage-3 AKI were: 0.740 (95% CI 0.615-0.842) for the RRI, 0.757 (95% CI 0.633-0.855) for uMCP-1, and 0.817 (95% CI 0.701-0.903) for uNGAL, without statistical differences among them. For stage 3 AKI prediction, the sensitivity and specificity were: 56.3% and 87.5% for a RRI > 0.705; 70% and 79.2% for an uMCP-1 > 2169 ng/mL; and 87.5% and 70.8% for a uNGAL > 200 ng/mL. The RRI was significantly correlated to age (r = 0.280), estimated glomerular filtration rate (r = - 0.259), mean arterial pressure (r = - 0.357), and serum lactate (r = 0.276). CONCLUSION: The RRI, uMCP-1, and uNGAL have a similar ability to predict AKI. The RRI is more specific, while urine biomarkers are more sensitive to predict stage 3 AKI. The RRI correlates with hemodynamic variables. The novel uMCP-1 could be a useful biomarker that needs to be extensively studied.

A.L.L. Y.O.U. N.E.E.D. I.S. L.O.V.E. Manual on health self-management and patient-reported outcomes among low-income young adult Mexicans on chronic dialysis: Feasibility study.

PURPOSE: We evaluated disease knowledge/self-management skills among low-income Mexican young adults maintained on dialysis and to test the effectiveness of the A.L.L. Y.O.U. N.E.E.D. I.S. L.O.V.E (AYNIL) Manual - Spanish Version on patient-reported outcomes. This is a low literacy teaching tool designed with patients and educators' input. DESIGN AND METHODS: A quasi-experimental study was conducted in 17 chronic dialysis patients at Mexico City's Hospital General de México, Dr. Eduardo Liceaga. Ages 18-30-year-old completed disease knowledge/self-management and quality of life measures before the intervention and 6 weeks later. RESULTS: Significant increases were observed on disease knowledge/self-management scores in the STARx questionnaire from 47 (IQ: 40,51) to 50 (IQ: 48,54) p = 0.04. The UNC-TRxANSITION Index increased significantly from 4.8 (IQ: 3.9,5.7) to 7.7 (IQ: 7.5,8.2) p ≤0.001. Significant increases in scores were detected in the "Burden of kidney disease" (p = 0.008), "Effects of kidney disease" " (p = 0.03) and " Dialysis staff encouragement" (p = 0.027) based on the KDQoL survey. CONCLUSIONS: In this vulnerable population, the Spanish version of the A.L.L. Y.O.U. N.E.E.D. I.S. L.O.V.E. - AYNIL Manual improved CKD/ESRD disease knowledge/self-management skills and HRQoL. This study highlighted the need for low-literacy educational tools to improve patient-reported outcomes. PRACTICE IMPLICATIONS: Young adults with CKD/ESRD can benefit from patient-centered educational interventions to enhance their autonomy and the development of self-management behaviors that improve patient-reported outcomes and potential complications of the disease. Special attention is needed in low-income patients with low rates of adherence to treatments and poor self-management skills.

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.

Evaluation of cerebral dysfunction in patients with chronic kidney disease using neuropsychometric and neurophysiological tests.

BACKGROUND: Uremic encephalopathy is defined as cerebral dysfunction due to toxin accumulation in patients with chronic kidney disease (CKD). This condition is characterized by subtle to florid symptoms, and its clinical course is always progressive when untreated but partially reversible with renal replacement therapy. While no test exists to measure subclinical uremic encephalopathy, two tests have been validated to measure minimal hepatic encephalopathy: the critical flicker frequency (CFF) test and the psychometric hepatic encephalopathy score (PHES). OBJECTIVE: To use CFF and PHES to measure the prevalence of cerebral dysfunction in individuals with CKD. METHODS: This cross-sectional study included a total of 69 patients with stage-5 CKD. Cutoff points for minimal encephalopathy were established using existing clinical guidelines: ≤39 Hz for CFF and < -4 for PHES. All participants were also screened for cognitive function and depression. RESULTS: Eighteen cases (26.1%) of cerebral dysfunction linked to uremic encephalopathy were detected with CFF, while twelve (17.4%) were detected by PHES; only six cases (8.7%) were diagnosed by both methods. Half of the cases (50%) had diabetes, and 61% were on hemodialysis. Cognitive function scores did not differ significantly between those receiving dialysis, hemodialysis, or no renal replacement therapy. CONCLUSIONS: It is essential to identify cerebral dysfunction when uremic encephalopathy is in early subclinical stages to reduce preventable events as traffic and work accidents.

TRPV4: A Physio and Pathophysiologically Significant Ion Channel.

Transient Receptor Potential (TRP) channels are a family of ion channels whose members are distributed among all kinds of animals, from invertebrates to vertebrates. The importance of these molecules is exemplified by the variety of physiological roles they play. Perhaps, the most extensively studied member of this family is the TRPV1 ion channel; nonetheless, the activity of TRPV4 has been associated to several physio and pathophysiological processes, and its dysfunction can lead to severe consequences. Several lines of evidence derived from animal models and even clinical trials in humans highlight TRPV4 as a therapeutic target and as a protein that will receive even more attention in the near future, as will be reviewed here.

Tres desafortunados enemigos de la salud de la población / Three unfortunate enemies of the health of the population

Resumen Tres enfermedades con alta prevalencia en la población adulta, especialmente en México, son la diabetes mellitus tipo 2, la hipertensión arterial y la hiperuricemia-gota; entre ellas comparten características fisiopatológicas que favorecen su aparición como Aceptado: 11 de junio 2019 un conjunto en los pacientes y cuyos tratamientos van frecuentemente de la mano, lo que ha permitido que en las siguientes líneas puedan describirse tales enfermedades Correspondencia como los tres desafortunados enemigos de la salud de la población. Manuel González Ortiz.

Abstract Three diseases with a high prevalence in the adult population, especially in Mexico, are type 2 diabetes mellitus, arterial hypertension and hyperuricemia-gout; they share among them pathophysiological characteristics that favor their appearance as a group in the patients and whose treatments are frequently in the same way, the above-mentioned has allowed that in the following lines can be described such diseases as the three to;35(4):596-608. unfortunate enemies of the health of the population.

Spironolactone reduces oxidative stress in living donor kidney transplantation: a randomized controlled trial.

Mineralocorticoid receptor antagonism prevents acute kidney injury induced by ischemia-reperfusion in rodent and pig preclinical models. In a pilot study, we showed that spironolactone (25 mg) reduced oxidative stress after 5 days of kidney transplant (KT). In the present study, we investigated the effects of higher doses (50 and 100 mg) of spironolactone on kidney function, tubular injury markers, and oxidative stress in living donor KT recipients. We included KT recipients aged 18 yr or older who received immunosuppression therapy with IL-2 receptor antagonist, mycophenolate mofetil, corticosteroids, and tacrolimus with negative cross-match, and compatible blood group. Patients were randomized to receive placebo (n = 27), spironolactone (50 mg, n = 25), or spironolactone (100 mg, n = 25). Treatment was given from 3 days before and up to 5 days after KT. Serum creatinine, K+, urine neutrophil gelatinase-associated lipocalin-2, heat shock protein 72, and 8-hydroxy-2-deoxyguanosine levels were assessed. As expected, kidney function was improved after KT. Serum K+ remained in the normal range along the study. There was no significant effect of spironolactone on urinary neutrophil gelatinase-associated lipocalin-2 levels, whereas the increase in urinary heat shock protein 72 levels tended to be less intense in the 100 mg spironolactone-treated group (P = 0.054). In the placebo-treated group, urinary 8-hydroxylated-guanosine levels increased on days 3 and 5 after transplantation. This effect was prevented in patients that received spironolactone. In conclusion, spironolactone reduces the acute increase in urinary oxidative stress in living donor KT recipients.

Is delayed graft function associated with ureteral stenosis in the kidney transplant recipient? A case-control study.

INTRODUCTION: Ureteral stricture (US) in the kidney transplant recipient is a rare complication that can lead to morbidity and graft loss. Risk factor recognition is crucial in the prevention and management of this entity. Delayed graft function (DGF), as defined by the need for dialysis in the first week after transplantation, has been proposed as a risk factor in previous studies. Our objective is to determine the impact of DGF in US development in kidney transplant patients. METHODS: We designed a matched case-control study. US cases in kidney transplant recipients were identified in the 2008-2017 period. We defined US as the rise in serum creatinine associated with findings suggesting obstruction in ultrasound, scintigraphy, or retrograde pyelogram; any other cause of graft dysfunction was excluded. Controls were defined as kidney transplant recipients from the same population and period without US, matched in a 1:2 fashion by age, sex, and donor type. RESULTS: From 532 kidney transplant patients, 31 cases and 62 controls were included. Cumulative US incidence was 58 per 1000 cases. When calculating for odds ratio (OR), post-operative urinoma (OR 3.2; 95% confidence interval [CI] 2.36-4.37) and ureteral duplication (OR 3.29; 95% CI 2.40-4.51) were associated with an increased risk for US, while DGF was not found to be statistically significant as a risk factor (OR 3.3; 95% CI 0.96-11.52). No statistically significant differences were found between groups in other pre- and post-transplant-related factors CONCLUSIONS:: DGF was not associated with US in our cohort; however, ureteral duplication and postoperative urinoma were associated with an increased risk of graft ureteral stenosis development.

Intellectual performance of kidney transplant recipients' offspring: a cross-sectional, multicenter study.

OBJECTIVE: The number of successful pregnancies in kidney transplant (KT) recipients has increased in recent years. Little evidence is available about the risk of in utero immunosuppressive exposure for long-term cognitive consequences. The aim of this study was to evaluate the impact of immunosuppression during pregnancy on intellectual performance of children born to KT recipients. METHODS: Using a cross-sectional design, women who had undergone KT and their children (aged 4+ years) were recruited at the outpatient follow-up in five transplant centers. Women who did not receive immunosuppression during pregnancy with similar distributions of socioeconomic status and length of gestation and their children were also recruited. Children were assessed with Wechsler Intelligence Scales. RESULTS: The study sample included 50 exposed and 50 unexposed children. No differences between groups in all the proposed confounding factors were found. Full-scale IQ did not differ significantly between both groups. Also, significant differences in any index or subscale score were not observed, with the exception of time required to complete the Wechsler preschool and primary scale of intelligence (WPPSI) Zoo locations subtest, which was done quicker in the unexposed group (p = .007). Exposure to immunosuppression during pregnancy was not a significant predictor of low IQ in logistic regression after adjustment for other factors. CONCLUSIONS: Immunosuppression therapy during pregnancy of KT women did not affect global intellectual performance of their offspring, except maybe for visuospatial working memory in preschool children.

Antibody-mediated rejection in the Banff classifications of 2007 and 2017: A comparison of renal graft loss prediction capability.

BACKGROUND: Antibody-mediated rejection (ABMR) is the leading cause of kidney graft loss worldwide. Criteria for acute humoral rejection (currently labeled active humoral rejection) established by the 2007 Banff classification are highly specific but lack sensitivity. Modifications to the Banff classification were introduced for its 2013 and 2017 versions in order to identify more cases of this entity. PURPOSE: We intend to demonstrate that, compared to its 2007 version, the 2017 Banff classification bears an improved capacity for graft loss prediction when histologic criteria for active ABMR are met. PATIENTS AND METHODS: Single-center retrospective cohort study. A random sample of 201 kidney recipients who underwent a graft biopsy since January 2004 was analyzed. Patients were classified as ever developing histologic characteristics of acute ABMR (2007 Banff) or not and renal survival between groups was compared. The same patients were then classified as ever developing histologic characteristics of active ABMR (2017 Banff) or not and renal survival was again compared. Presence of circulating donor-specific antibodies (DSA) was not taken into consideration. RESULTS: Patients were followed for a median 13.9 ±â€¯7.9 years, during which grafts were biopsied on 537 occasions (2.7 ±â€¯1.6 biopsies per graft). Baseline eGFR was 73.26 ±â€¯17.6 ml/min and baseline creatinine 1.14 ±â€¯0.25 mg/dl. Graft loss occurred in 38 recipients (18.9%) mainly due to ABMR (60.5%). Acute ABMR (2007 Banff) was identified in 11 recipients (5.5%) and graft survival did not differ between groups with and without active ABMR occurrence (log-rank p = 0.939). Active ABMR (2017 Banff) was found in 59 recipients (29%) and graft survival was better from the second post-transplant year onward in the group of patients without active ABMR occurrence (log-rank p = 0.001). Moderate microvascular inflammation was present in 89.6% of the 48 additional patients with active ABMR. CONCLUSION: The 2017 Banff classification identifies more patients who develop active ABMR and stratifies graft loss risk better than the 2007 version.

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).

Lesión renal rápidamente progresiva como presentación de necrosis tubular aguda de origen incierto en un maratonista. Diagnóstico diferencial nо siempre sencillo / Rapidly progressive renal injury as a manifestation of acute tubular necrosis with an uncertain origin in a marathonist: A differential diagnosis is not always simple

Resumen El síndrome de deterioro rápidamente progresivo de la función renal, corresponde a una forma de lesión renal aguda que cursa con un decremento acelerado y progresivo de la tasa de filtrado glomerular en horas a días o semanas. Una vez descartadas las causas prerrenales, es necesario establecer el diagnóstico diferencial con causas glomerulares, vasculares renales (trombosis), obstructivas, nefritis intersticial y necrosis tubular aguda. Se presenta un caso de deterioro rápidamente progresivo de la función renal, que fue manejado con esteroide intravenoso y plasma fresco congelado, por la probabilidad diagnóstica de microangiopatía trombótica, nefritis intersticial y glomerulonefritis rápidamente progresiva (GNRP). Posteriormente, se confirmó el diagnóstico de necrosis tubularaguda mediante biopsia renal, sin habertenidoalgún antecedente evidente que sugiriera la presencia y etiología de dicha entidad.

Abstract The rapidly progressive renal failure syndrome corresponds to an acute kidney injury that causes an accelerated decrease of the glomerular filtration rate in hours to days or weeks. After pre-renal causes were dismissed, a differential diagnosis with glomerularcauses, vascularcauses (thrombosis), obstructive causes, interstitial nephritis and acute tubular necrosis must be established. We describe the case of a rapidly progressive decline of the renal function that was managed with intravenous steroids and freshly frozen plasma due to the diagnostic probability of thrombotic microangiopathy, interstitial nephritis and rapidly progressive glomerulonephritis. Subseguently, an acute tubular necrosis was confirmed by a renal biopsy without any previous clinical evidence suggesting a clear presence or etiology of this entity.

Impact of pretransplant exposure to allosensitization factors generating HLA antibodies in the Luminex era.

AIM: To identify the frequency of exposure to sensitizing factors and evaluate the risk ascribable to each sensitizing factor generating HLAabs measured by Luminex. METHODS: This is a retrospective cohort study that included 502 transplanted patients and 51 patients on the waiting list for a deceased donor graft. Patients were divided into 4 groups according to the %PRA: 0%, 1 to 19%, 20 to 49% and ≥50%. The OR attributable to each sensitizing factor or combination were calculated. RESULTS: Of the total 553 subjects, 53.5% were male, with an average age 35.42±12.96years. 69.1% were exposed to one or more sensitizing factors; 44.8% had %PRA class I≥1 and 38.9% had %PRA class II≥1. Independently or combined, sensitizing factors persist as a risk factor for the development of a %PRA >1%, >20% or >50%. After multivariate analysis, the three sensitizing factors remained significantly associated to HLAab development. CONCLUSIONS: In spite of using a most sensitive technique such as Luminex to measure the %PRA, a clear association persists between exposure to sensitizing factors and a high %PRA. The risk increases after exposure to more than one sensitizing factor.

Comparison of Lupus Nephritis Induction Treatments in a Hispanic Population: A Single-center Cohort Analysis.

OBJECTIVE: To evaluate response rates in an adult lupus nephritis (LN) cohort in Mexico City, Mexico. METHODS: We analyzed 165 patients with biopsy-proven LN histological International Society of Nephrology/Renal Pathology Society classes III, IV, or V, distributed by treatment drug in 3 groups: mycophenolate mofetil (MMF; dosage > 2 g/day per 6 mos, n = 63), intravenous cyclophosphamide (IVC; 0.7 g/m(2) body surface area monthly per 6 pulses, n = 66), or azathioprine (AZA; dosage > 1.5 mg/kg/day per 6 mos, n = 36). Median followup was 31 ± 18 months. The primary endpoint was the proportion of patients achieving complete renal response (CR). Secondary endpoints included the proportion of patients achieving renal response (complete or partial), renal flare-free survival, doubling of serum creatinine, and progression to endstage renal disease (ESRD). RESULTS: MMF induction was superior to IVC (HR 2.00, 95% CI 1.23-3.25, p = 0.005) and AZA (HR 2.12, 95% CI 1.23-3.66, p = 0.007) in the primary endpoint. Censored CR rates at 6, 12, 24, and 36 months were 32.6%, 56.1%, 76.6%, and 94.1% for MMF; 24.2%, 34.4%, 57.9%, and 62.1% for IVC; and 8.4%, 39.8%, 49.7%, and 49.7% for AZA. MMF was also superior in renal response to treatment and renal flare-free survival outcomes. There were no differences between groups in doubling of serum creatinine or progression to ESRD. The induction treatment with MMF (HR 2.04, 95% CI 1.25-3.33, p = 0.005) and absence of vascular lesions on renal biopsy (HR 2.05, 95% CI 1.25-3.37, p = 0.004) were associated with CR, whereas proteinuria at the time of presentation was negatively associated with CR (HR 0.91, 95% CI 0.84-0.98, p = 0.013). CONCLUSION: MMF induction therapy is superior to IVC and AZA in patients with LN of Mexican-mestizo race.

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.

[Incidence of acute rejection in patients with renal graft dysfunction]. / [Incidencia de rechazo agudo en pacientes con disfunción del injerto renal].

INTRODUCTION: Acute rejection has been identified as the main cause of renal graft dysfunction during the first year after transplantation; it is associated with chronic structural and functional damage, which causes loss of graft and decrease in patient survival. MATERIAL AND METHODS: We performed a retrospective and descriptive research consisting in a review of the final reports of biopsies performed due to renal graft dysfunction during the postransplant period. Patients included were transplanted at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ) from January 2007 to December 2011. RESULTS: A total number of 223 patients underwent renal transplantation during the period considered for this study purpose, 222 biopsies were performed due to renal graft dysfunction in 118 patients (52.9%). 74.5% of patients developed graft dysfunction in the first year after transplantation. The main histopathological findings reported were immunologic events in both living donor (LDRTR) and deceased donor renal transplant recipients (DDRTR), borderline changes were the most common diagnosis. The median time to detect immune events as cause of dysfunction was shorter for DDRTR and they tend to occur in the first 4 months after transplantation. CONCLUSION: We observed an incidence of 11.8% for acute rejection in the first year after transplantation for LDRTR and 17.4% for DDRTR. Further studies are needed to determine the causes of immunological events and their implications in the evolution of renal graft and patient's survival.

CYP3A5 polymorphism in Mexican renal transplant recipients and its association with tacrolimus dosing.

BACKGROUND AND AIMS: Variability in CYP3A5 expression associated with differences in tacrolimus bioavailability has been documented. The wild-type allele CYP3A5*1 expresses the functional protein, whereas the CYP3A5*3 allele is a splice variant with a premature stop codon and encodes a truncated nonfunctional protein. The aim of the study was to determine the frequency of CYP3A5*1 and CYP3A5*3 in 291 (124 adults, 167 pediatric) Mexican renal transplant recipients, evaluate the tacrolimus dose requirements by genotype and compare genotype frequency data with that of other populations. METHODS: We carried out a multicenter study. Patients were recruited from three institutions located in Mexico City. Genotyping of the CYP3A5*1 and CYP3A5*3 alleles was performed by direct DNA sequencing. RESULTS: Eighteen patients (6.2%) were CYP3A5*1*1 homozygous carriers or functional protein expresser homozygous, 121 patients (41.6 %) were CYP3A5*1*3 were heterozygous carriers or heterozygous expressers, and 152 patients (52.2%) were CYP3A5*3*3 homozygous carriers or homozygous nonexpressers. There was a statistically significant difference in frequency of the functional and nonfunctional expresser phenotypes from those reported for Black and Caucasian, but not for South Asian populations. The CYP3A5 phenotype had a significant impact in tacrolimus bioavailability, as wild-type carriers required higher dosing compared to mutated carriers to achieve similar drug trough levels. Patients with CYP3A5*1*1 genotype had a median dose requirement of 0.16 mg/kg/day, CYP3A5*1*3 patients had a median tacrolimus dose of 0.13 mg/kg/day and CYP3A5*3*3 had a median dose of 0.07 mg/kg/day (Kruskal-Wallis, p <0.0001). CONCLUSIONS: Of the Mexican transplant recipients, 52.2% were CYP3A5*3*3 and required significantly lower tacrolimus dose than those with CYP3A5*1 allele.