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.

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.

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.

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.

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.

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.

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.

[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.

Trasplante renal: efectos en el perfil cognoscitivo / Impact of kidney transplantation on cognitive profile

Objetivo. Valorar el impacto del Trasplante Renal exitoso sobre el funcionamiento cognoscitivo de los pacientes con Insuficiencia Renal Crónica (IRC). Método. Se aplicó el Neuropsi Atención y Memoria, el Hospital Anxiety and Depression Scale, la Escala de Somnolencia de Epworth y la Escala Isquémica de Hachinski a 42 pacientes con IRC y 41 donadores vivos sanos (grupo control). De los 42 pacientes que fueron sometidos a trasplante renal, se evaluó con los mismos instrumentos a 28 de ellos en un tiempo de 6 meses posterior a su trasplante. Se valoró en los mismos tiempos a sus donadores renales (grupo control). Resultados. El funcionamiento cognoscitivo global del grupo IRC mejoró después del trasplante renal aún controlando los efectos de aprendizaje. Las áreas en las que el grupo postrasplantado mejoraron fueron el Stroop y la evocación verbal a largo plazo haciendo uso de claves. Conclusiones. El trasplante renal se aprecia como una solución ideal que elimina factores (medibles o no medibles) que están impactando en el funcionamiento cognoscitivo.

Aim. To assess the impact of kidney transplantation on neuropsychological functioning of Chronic Kidney Disease(CKD) patients. Methods.: 42 kidney transplant (KT) recipients and 41 healthy living donors –control group- were tested by a comprehensive neuropsychological battery: Neuropsi Attention and Memory, the Hospital Anxiety and Depression Scale, The Epworth Sleepiness Scale and the Hachinski Ischemic Scale. 28 patients were followed up 6 months after KT. Their kidney donors were evaluated pre as well as post donation (at same time of study group) for comparison. Results. An improvement in global cognitive functioning after KT was found (when learning effects were controlled). Patients improved in Stroop test and auditory/verbal delayed recall using cues. Conclusions. Renal transplant is suggested as an ideal solution as it eliminates factors (measurable or not) that have an impact over cognitive functioning.

Mielinólisis pontina despuÚs de un evento de hipoglucemia / Pontine myelinolysis after a hypoglycemic episode

A case of central pontine myelinolysis following hypoglycemia is reported. The case was a 26- year-old female. Diabetes mellitus was found when she was 8 years old and she has hypertension and renal failure. She suffered a severe hypoglycemia at an unknown time. After the episode she developed a vegetative state. A magnetic resonance scan showed features consistent with the presence of central pontine myelinolysis.

Frecuencias y factores de riesgo para depresión en pacientes con diabetes mellitus tipo 2 en un hospital de tercer nivel de atención / Frequency and risk factors of depression in patients with type 2 diabetes mellitus in a third level of attention hospital

Antecedentes: la depresión es un trastorno común en la población general y, en especial, en los pacientes diabéticos. Su identificación es importante, ya que puede tener un profundo impacto en la calidad de vida de las personas con enfermedades crónicas. Objetivo: identificar la frecuencia de depresión en un grupo de pacientes con diabetes mellitus tipo 2 (DM tipo 2) y los factores relacionados. Material y métodos: en una encuesta prolectiva realizada en el Instituto Nacional de la Nutrición y Ciencias Médicas Salvador Zubirán se incluyeron 189 pacientes con DM tipo 2. Para medir la depresión se utilizó la escala de Beck. Se consideraron como variables independientes los aspectos sociodemográficos de los pacientes (sexo, estado civil, religión, escolaridad, ocupación, nivel socioecónomico) y las características de la enfermedad (tiempo de evolución, padecimientos relacionados, cumplimiento con el régimen terapéutico y control glucémico). Resultados: la frecuencia de depresión fue del 39 por ciento (74 pacientes). Entre los factores de riesgo destacaron los siguientes: ser viudo (RM 3.54, IC 1.56 - 8.11, p = 0.0007), perteneciente al sexo femenino (RM 2.95, IC 1.50 - 5.82, p = 0.006), ser ama de casa (RM 2.08, IC 1.10 - 3.94, p = 0.01), incumplimiento terapéutico (RM 2.14, IC 1.12 - 4.10, p = 0.01) y la existencia de enfermedades concomitantes (RM 5.60, IC 1.51 - 24.5, p = 0.002). Los hallazgos más constantes fueron: glucemia en la última consulta ü 200 (RM 3.23, IC 1.59 - 6.60, p = 0.0003), ü 250 (RM 2.15, IC 0.93 - 5.03, p = 0.05), ü 300 (RM 2.67, IC 0.75 - 9.85, p = 0.08) y el promedio de las cinco últimas glucemias fue ü 150 (RM 3.03, IC 1.58 - 5.82, p = 0.002), ü 200 (RM 3.67, IC 1.76 - 7.73, p = 0.0001), ü 250 (RM 4.07, IC 1.61 - 10.49, p = 0.0007), ü 300 (RM 2.12, IC 1.48 - 3.02, p = 0.003), ü 350 (RM 2.65, IC 2.20 - 3.20, p = 0.02). Conclusiones: la frecuencia de depresión en pacientes con DM tipo 2 fue alta (39 por ciento). Destaca como variable relacionada las cifras elevadas de glucemia. Asimismo, se observaron otros factores relacionados, como enfermedades concomitantes, el sexo femenino y ser viudo o divorciado.

Fisiopatología de la nefropatía por medio de contraste / Pathophysiology of contrast media nephropathy

Por el avance tecnológico en los procedimientos diagnósticos y terapéuticos, el uso de medio de contraste intravenoso en el medio hospitalario es cada vez más frecuente y con ello la insuficiencia renal aguda secundaria a su efecto nefrotóxico, lo que se conoce también como nefropatía por medio de contraste. Esta revisión describe los mecanismos fisiopatológicos del daño por medio de contraste, que incluye la citotoxicidad causada por la hiperosmolaridad del medio de contraste, los factores hemodinámicos y el papel que juega el sistema renina-angiotensina, las prostaglandinas, los radicales libres de oxígeno, la endotelina-1, la adenosina, el óxido nítrico entre otros mediadores. El entendimiento de esta información es de vital importancia en el desarrollo de esquemas profilácticos para la nefropatía por medio de contraste.

Patogénesis de la miastenia gravis / Pathogenesis of myasthenia gravis

La miastenia gravis es un trastorno neuromuscular, autoinmune y adquirido, caracterizado por debilidad y fatigabilidad de los músculos esqueléticos. En los últimos 20 años se han generado importantes avances para entender la fisiopatología de la enfermedad y este conocimiento ha sido aplicado en el diagnóstico y el tratamiento de esta enfermedad. La miastenia gravis es una de las enfermedades autoinmunes que ha sido mejor estudiada y sirve como modelo para estudio de otros trastornos autoinmunes. En esta revisión se mencionan los aspectos más relevantes de la fisiopatología de esta enfermedad y su aplicación en la práctica clínica.