Pediatric kidney dimensions and risk of persistent albuminuria in Mexican adolescents.

In Mexico, chronic kidney disease of unknown origin is highly prevalent. Screening studies in adolescents have shown persistent microalbuminuria (pACR), adaptive podocytopathy and decreased kidney volume (KV). Here, we sought to develop normality tables of kidney dimensions by ultrasound in the Mexican state of Aguascalientes pediatric population (0 to 18y) and evaluate the relationship between the KV and pACR among the region's adolescents in a cross-sectional study. Kidney length (KL) and KV were determined by ultrasound. Our findings were compared with those in international literature of different populations where tables and graphs of normal kidney dimensions by ultrasound were reported. We compared organ dimensions in individuals above the age of 11 without albuminuria with those in patients with pACR recruited through screening studies in adolescents in Aguascalientes. This included 1068 individuals to construct percentile tables and graphs of the KL. Kidney dimensions were significantly lower when compared with all international comparisons. From a total 14,805 screen individuals, we compared 218 adolescents with pACR and 377 individuals without significant albuminuria. The Total KV adjusted to body surface (TKVBS) was significantly associated with pACR (odds ratio 1.03, 95% confidence interval 1.02-1.03). The upper quartile of TKVBS was highly associated with pACR (7.57, 4.13-13.87), hypertension (2.53, 1.66-3.86), and hyperfiltration (26 vs 11.5%). Thus, TKVBS is directly associated with pACR while greater KV, arterial hypertension, and hyperfiltration in patients with pACR suggest that the increase in volume is secondary to kidney hypertrophy. Additionally, the adaptative podocytopathy with low fibrosis seen on kidney biopsy which was performed in a subset of patients, and the smaller kidney dimensions in our population point to prenatal oligonephronia as the primary cause of the detected kidney disease.

Histologic characterization and risk factors for persistent albuminuria in adolescents in a region of highly prevalent end-stage renal failure of unknown origin.

Background: End-stage renal failure of unknown origin (ESRD-UO) is a public health problem in Mexico and many regions of the world. The prevalence of ESRD-UO in Aguascalientes, Mexico, is one of the highest worldwide, particularly in adults between 20 and 40 years of age. Our aim was to screen adolescents for chronic kidney disease (CKD) to identify risk factors and histologically characterize adolescents with persistent albuminuria. Methods: This was a cross-sectional, observational and comparative study of adolescents in whom serum creatinine and the albumin:creatinine ratio (ACR) were determined when screening for CKD. A clinical evaluation and risk factor survey were conducted. Patients with an abnormal ACR (≥30 mg/g) or a low glomerular filtration rate (GFR) (≤75 mL/min/1.73 m2) were re-evaluated and a renal ultrasound (US) was obtained. A kidney biopsy was performed in patients with persistent albuminuria. Results: A total of 513 students were included; 19 had persistent albuminuria and 494 were controls. The prevalence of persistent albuminuria was 3.7% [95% confidence interval (CI) 2.1-5.3]. Only one patient had a decreased GFR. None of the patients with persistent albuminuria had anatomical abnormalities of the urinary tract by renal US. Patients with persistent albuminuria had a decreased total renal volume compared with the control group (150 versus 195 mL/m2; P < 0.01). Eighteen kidney biopsies were performed; 72% had glomerulomegaly and only one patient had mild fibrosis. Podocyte abnormalities were evident on electron microscopy, including partial fusion (100%), microvillous degeneration (80%) and increased organelles (60%). Risk factors for persistent albuminuria were: homestead proximity to maize crops, the use of pesticides at the father's workplace, a family history of CKD and blood pressure abnormalities. The body mass index and breastfeeding were protective factors. Conclusions: The prevalence of persistent albuminuria in adolescents in Aguascalientes is high and histologic compromise is characterized by podocyte injury in the absence of fibrosis. The renal volume of persistent albuminuria patients was decreased, suggesting oligonephronia. Exposure to environmental toxins such as pesticides, even prenatally, may be responsible for this pathological entity. Screening programs in adolescents by determining ACR are necessary in this setting.

Chronic Kidney Disease Risk Profile in Renal Donors in Aguascalientes, Mexico: A Retrospective Cohort Study.

BACKGROUND: In the last decade, kidney donation has been recognized as a risk factor for end-stage renal disease (ESRD). ESRD risk calculators have been recently perfected in North American populations. In Mexico, the rates of overweight, obesity, and diabetes mellitus (DM) are among the highest worldwide; nevertheless, most kidney transplants are obtained from living donors. This study aims to describe the risk profile for chronic kidney disease (CKD) development in kidney donors in a highly active transplant center in Central Mexico. METHODS: We conducted a retrospective, observational, descriptive cohort study of kidney donors followed at the Hospital Centenario Miguel Hidalgo (CHMH). We used the pretransplant CKD risk calculator at 15 years and over a lifetime (www.transplantmodels.com/esrdrisk). Aside from the calculator of kidney failure risk, we also used the calculator for postdonation CKD risk (www.transplantmodels.com/donesrd/). Factors associated with a glomerular filtration rate (GFR) <60 mL/min were evaluated by univariate and multivariate analysis. RESULTS: The study included 543 donors. The average follow-up period was 1.7 years (±2.7) with a median of 0.7 years (interquartile range, 0.2-2.1). The average predicted risk for ESRD development at 15 years was 0.08% (±0.1); 25.6% had a risk >0.1%, and only 1 patient had a risk >1%. The lifetime ESRD risk was 0.62% (±0.5); 15% had a risk >1%, and the greatest risk was 3.5%. The median of patients at risk of developing postdonation ESRD was 1 in 10,000 donors (0.6-1.5) at 5 years, 5.7 in 10,000 donors (3.5-8.8) at 10 years, 15 in 10,000 donors (9.1-23.2) at 15 years, and 31 in 10,000 donors (18.9-47.7) at 20 years. During the follow-up period, 52 patients developed a GFR of <60 mL/min. Both risk estimation formulas were significantly associated with a GFR of <60 mL/min. Among the individual factors, the GFR (hazard ratio 0.96, 95% confidence interval 0.94-0.97, P < .001) and the urinary albumin to creatinine ratio (hazard ratio 1.009, 95% confidence interval 1.005-1.01, P < .001) remained statistically significant. CONCLUSION: The risk of ESRD in kidney donors in Aguascalientes, Mexico, is similar to that described in the United States. Risk calculators are an indispensable decision-making tool to better understand kidney donors in our milieu.

Experiencia de trasplante de progenitores hematopoyéticos autólogo en pacientes con esclerodermia sistémica cutánea difusa / Autologous hematopoietic stem cell transplantation experience in patients with diffuse cutaneous systemic scleroderma

Introducción: La progresión y la falta de opciones terapéuticas conlleva a un gran aumento de la morbi-mortalidad en la esclerodermia sistémica cutánea difusa. Caso Clínico: Se presentan tres pacientes con diagnóstico de Esclerodermia sistémica de rápida progresión sin compromiso cardiopulmonar o renal severo con múltiples líneas de tratamiento incluyendo altas dosis de ciclofosfamida, sometidas a trasplante autólogo (2015-2020) con acondicionamiento a base de Ciclofosfamida y Globulina Antitimocitica, como opción terapéutica. Durante el procedimiento no se observaron complicaciones infecciosas severas con un prendimiento medular en el día 10 y una recaída promedio de 9.6 meses. Conclusiones: Ante el buen perfil de toxicidad y la buena tolerancia al procedimiento se debe considerar al Trasplante Autólogo como una opción de tratamiento en pacientes sin altas dosis acumuladas de ciclofosfamida o en estadios precoces de enfermedad.

Introduction: Progression and lack of therapeutic options leads to greatly increased morbi-mortality in diffuse cutaneous systemic scleroderma. Case Report: We present three patients with a diagnosis of rapidly progressive systemic scleroderma without severe cardiopulmonary or renal involvement with multiple lines of treatment including high doses of cyclophosphamide, undergoing autologous transplantation (2015-2020) with Cyclophosphamide and Antithymocyte Globulin based conditioning, as a therapeutic option. No severe infectious complications were observed during the procedure with a medullary attachment on day 10 and a mean relapse of 9.6 months. Conclusions: Given the good toxicity profile and good tolerance to the procedure, Autologous Transplantation should be considered as a treatment option in patients without high accumulated doses of cyclophosphamide or in early stages of disease.

Experiencia de trasplante de progenitores hematopoyéticos autólogo en pacientes con esclerodermia sistémica cutánea difusa / Autologous hematopoietic stem cell transplantation experience in patients with diffuse cutaneous systemic scleroderma

Introducción: La progresión y la falta de opciones terapéuticas conlleva a un gran aumento de la morbi-mortalidad en la esclerodermia sistémica cutánea difusa. Caso Clínico: Se presentan tres pacientes con diagnóstico de Esclerodermia sistémica de rápida progresión sin compromiso cardiopulmonar o renal severo con múltiples líneas de tratamiento incluyendo altas dosis de ciclofosfamida, sometidas a trasplante autólogo(2015-2020) con acondicionamiento a base de Ciclofosfamida y Globulina Antitimocitica, como opción terapéutica. Durante el procedimiento no se observaron complicaciones infecciosas severas con un prendimiento medular en el día 10 y una recaída promedio de 9.6 meses. Conclusiones: Ante el buen perfil de toxicidad y la buena tolerancia al procedimiento se debe considerar al Trasplante Autólogo como una opción de tratamiento en pacientes sin altas dosis acumuladas de ciclofosfamida o en estadios precoces de enfermedad.

Background:The progression and lack of therapeutic options leads to a large increase in morbidity and mortality in diffuse cutaneous systemic scleroderma. Clinical Case: Three patients with a diagnosis of rapidly progressing systemic scleroderma without severe cardiopulmonary or renal involvement with multiple lines of treatment including high doses of cyclophosphamide, submitted to autologous transplant (2015-2020) with conditioning based on Cyclophosphamide and Antithymocyte Globulin are presented as a therapeutic option. During the procedure, no various infectious infections were observed with a medullary seizure on day 10 and an average relapse of 9.6 months. Conclusions: Due to the good toxicity profile and good tolerance to the procedure, Autologous Transplantation should be considered as a treatment option in patients without high accumulated doses of cyclophosphamide or in early stages of disease.

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.

Extended focused assessment with sonography for trauma (EFAST) in the diagnosis of pneumothorax: experience at a community based level I trauma center.

INTRODUCTION: Early identification of pneumothorax is crucial to reduce the mortality in critically injured patients. The objective of our study is to investigate the utility of surgeon performed extended focused assessment with sonography for trauma (EFAST) in the diagnosis of pneumothorax. METHODS: We prospectively analysed 204 trauma patients in our level I trauma center over a period of 12 (06/2007-05/2008) months in whom EFAST was performed. The patients' demographics, type of injury, clinical examination findings (decreased air entry), CXR, EFAST and CT scan findings were entered into the data base. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated. RESULTS: Of 204 patients (mean age--43.01+/-19.5 years, sex--male 152, female 52) 21 (10.3%) patients had pneumothorax. Of 21 patients who had pneumothorax 12 were due to blunt trauma and 9 were due to penetrating trauma. The diagnosis of pneumothorax in 204 patients demonstrated the following: clinical examination was positive in 17 patients (true positive in 13/21, 62%; 4 were false positive and 8 were false negative), CXR was positive in 16 (true positive in 15/19, 79%; 1 false positive, 4 missed and 2 CXR not performed before chest tube) patients and EFAST was positive in 21 patients (20 were true positive [95.2%], 1 false positive and 1 false negative). In diagnosing pneumothorax EFAST has significantly higher sensitivity compared to the CXR (P=0.02). CONCLUSIONS: Surgeon performed trauma room extended FAST is simple and has higher sensitivity compared to the chest X-ray and clinical examination in detecting pneumothorax.

[Renal transplantation program at the Centenario Hospital Miguel Hidalgo in Aguascalientes, Mexico]. / Programa de trasplante renal del centenario Hospital Miguel Hidalgo en Aguascalientes, México.

INTRODUCTION: Miguel Hidalgo Hospital in Aguascalientes is dependent from the Federal Secretary of Health and operates in integrity with State health system in Aguascalientes. It capacity is based on 132 censored beds and 71 no censored beds. Is considered a specialty hospital in the region of Bajío. Renal transplant program activity was initiated in 1990 and gives care for adult and pediatric population. MATERIAL AND METHODS: Retrospective, comparative and longitudinal study to describe and analyze our experience. Data base and clinical charts of renal transplant recipients were reviewed. Age, gender, date of transplant, etiology of renal disease, type of donor, HLA compatibility and PRA, immunosuppressive therapy, acute rejection, serum creatinina, graft loss and mortality were registered. Statistical analysis included 2, unpaired Student T test and Kaplan-Meier survival analysis with Log Rank test. Cox Analysis was also done. RESULTS: 1050 renal transplants were done from November 1990 to June 2011. 50 were excluded because follow-up was not longer than 3 months. 1000 consecutive renal transplant patients from January 1995 to June 2011 were included for analysis. Patients were divided in 2 groups: group A transplanted January 1995 to December 2004; group B transplanted January 2005 to June 2011. Etiology for end stage renal disease is unknown in 61% of cases, 11% developed renal disease to diabetes mellitus. 93% patient survival was observed at median follow-up and 84.9% graft survival at median follow-up (6 years). Biopsy proven acute rejection in group A 19.9 vs. 10% in group B. Two haplotype matching shows 92% graft survival. Diabetic patients exhibit 73% graft survival vs. other as hypertension (87%). PRA >0 and serum creatinine > 2.0 mg/dL increase risk for graft loss according to Cox analysis. CONCLUSION. Results are comparable to international data. Importance of developing regional transplant centers is emphasized.

[Prevalence of posttransplant hypertension in pediatric kidney transplant recipients: effect on long term allograft survival]. / Prevalencia de la hipertensión arterial postrasplante renal en receptores pediátricos: Efecto en la supervivencia del injerto a largo plazo.

BACKGROUND: Arterial hypertension after renal transplantation has been identified as an adverse factor over the long term allograft function, thus identification and treatment of this entity has an impact on graft survival, as in patient survival. Studies about pediatric receptor populations have reported a prevalence of hypertension after renal transplantation ranging from 58 to 90%. In Mexico, the pre-valence of arterial hypertension after renal transplantation has been reported as 71% for an adult population attending a main hospital center in Mexico. No pediatric receptor studies in Mexico have reported the prevalence of hypertension after renal transplantation so far. The purpose of our study was to document the prevalence of arterial hypertension after renal transplantation in pediatric receptors, as well as its impact on allograft survival on a long term basis. MATERIAL AND METHODS: We performed a retrospective analysis among pediatric patients who underwent renal transplantation at our center, Centenario Hospital Miguel Hidalgo, between years 2000 to 2006. RESULTS: A total of 111 pediatric renal transplantation receptors were included, among whom 56 patients were classified as hypertensive (HT) and 54 patients were classified as nomotensive (NT) (one patient had to be excluded due to early allograft dysfunction). The mean age at the time of transplantation for the population under study was 14 +/- 3 years, with a predominance of male gender over females (1.5:1). In 89% of the transplantations, the source of the allograft was a living donor. The prevalence of arterial hypertension after renal transplantation in our population was 50.5%. Among patients in the HT group at least an episode of acute rejection presented in 8.9% (n=5) of the cases, compared to only 3.7% (n=2) of patients in the NT group with an episode of acute rejection. Likewise, the prevalence of chronic allograft nephropathy detected in the HT group was 11% (n=6) vs. 7% (n=4) in the NT group. The mean serum creatinine levels were 1.0 +/- 0.4 mg/dL for the HT group and 0.9 +/- 0.3 mg/dL for the NT group at the first month followup, however mean serum creatinine levels addressed at the last consult were different among groups: 1.7 +/- 1.8 mg/dL for the HT group versus 1.1 +/- 0.5 mg/dL for the NT group. Patient survival was similar for both groups (98%) and the follow-up period was also similar, being 39 +/- 12 months for the HT group and 39 +/- 17 months for the NT group. The multivariate Cox proportional hazard analysis demonstrated that the number of antihypertensive drugs needed to achieve the control of blood pressure, and the presence of chronic allograft nephropathy, were the independent risk factors associated to a graft loss at long term. CONCLUSION: The prevalence of hypertension after renal transplantation in our pediatric population was 50.5%, which is clearly towards the inferior limit of the reported prevalence in other studies (50-90%). The tight control of blood pressure is an intervention that may have a significant impact on graft survival at long term. In our study, the severity of arterial hypertension after renal transplantation represented as the number of antihypertensive drugs needed to achieve control of blood pressure, as well as the presence of chronic allograft nephropathy, were the factors associated to long term graft loss.

[Systemic hypertension after kidney transplantation: associated risk factors and influence on graft survival]. / Hipertensión arterial postrasplante renal: factores de riesgo asociados e influencia en la supervivencia del injerto renal.

Systemic hypertension after kidney transplant (HAPT) has been associated with a reduction in graft survival and increased morbidity and mortality of kidney transplant recipients. With the use of calcinuerin inhibitors, prevalence of HAPT has increased to 60-80%. The purpose of this study was to document the prevalence of HAPT in kidney transplant recipients attending the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" associated risk factors and the effect of hypertension in long term graft survival. We retrospectively reviewed the clinical charts of all the patients that underwent kidney transplant from 1984 to 1994. The following risk factors were studied: age, gender, cause of renal failure, presence of hypertension before kidney transplant, histocompatibility, acute rejection episodes, chronic rejection, serum creatinine values and use of cyclosporine. We divided subjects in two groups: normotensive (NT) and hypertensive (HT). HAPT included 3140/90 mmHg blood pressure level observed at least during two consecutive evaluations or the use of antihypertensive medication. We analyzed 215 grafts from 205 patients (10 patients had two kidney transplants); mean age at transplant of 30 +/- 9 years, 131 subjects were female and 84 male. One hundred and eighty eight patients (88%) displayed pretransplant hypertension. The mean follow up was 56+/-32 months. In the postransplant period 152 (71%) were HT and 63 (29%) NT. The HT group had significantly higher blood pressure and serum creatinine values than the NT group (P < 0.001), in spite of an adequate blood pressure control in 65% of the patients from the HT group. The NT group displayed a higher graft survival than the HT group; 60 +/- 30 months vs. 51 +/- 32 months respectively (p<0.01). Multivariate analysis did not show any risk factors independently associated with the development of HAPT. The prevalence of HAPT in our series is similar to the one reported in the literature. During the postransplant period there was a reduction of hypertensive patients (88% pretransplant vs. 71% postransplant). HAPT is a significant risk factor associated with long term survival of the graft.

Hipertensión arterial postrasplante renal: factores de riesgo asociados e influencia en la supervivencia del injerto renal / Systemic hypertension after kidney transplantation: Associated risk factors and influence on graft survival

La hipertensión arterial postrasplante renal (HAPT) se ha asociado con una disminución de la supervivencia del injerto renal y aumento de la morbilidad y mortalidad de los receptores de trasplante. La prevalencia de la HAPT es de 50% y con el uso de inhibidores de calcineurina se ha incrementado a 60-80%. Con el objeto de conocer la frecuencia de la HAPT en la población de pacientes del Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán ", los factores de riesgo asociados a su desarrollo y el efecto de ésta en la supervivencia del injerto renal a largo plazo, se analizaron retrospec tivamente los expedientes de los pacientes sometidos a trasplante renal de 1984 a 1994. Los factores de riesgo analizados fueron: edad, género, causa de insuficiencia renal, hipertensión arterial pretrasplante, histocompatibilidad, presencia de episodios de rechazo agudo, presencia de rechazo crónico, creatinina sérica (CrS) y uso de Ciclosporina A. Se dividió a la población en dos grupos: normotensos (NT) e hipertensos (HT). Se definió HAPT como presión arterial (PA) > 140/90 mmHg por lo menos en dos visitas consecutivas o la utilización de tratamiento antihipertensivo. Se analizaron 215 seguimientos en 205 pacientes (10 pacientes con dos trasplantes), con edad al momento del trasplante de 30 ± 9 años y género masculino/femenino 131/84. Cursaron con hipertensión arterial pretrasplante 188 (88%). El seguimiento postrasplante promedio fue de 56 ± 32 meses. En el período postrasplante se encontraron 152 HT (71 %) y 63 (29%) NT. El grupo HT mostró una PA y CrS mayores que el grupo de NT (P <0.001) a pesar de contarse con un control antihipertensivo adecuado en 65% de los casos de HT. El grupo de NT tuvo mayor supervivencia del injerto que el grupo de HT, 60 ± 30 meses vs 51 ± 32 meses (p <0.01). El análisis multivariado de los diversos factores de riesgo estudiados no mostró alguna asociación independiente con el desarrollo de HAPT. La prevalencia de la HAPT en nuestro estudio es similar a lo informado en la literatura. En la etapa postrasplante disminuyó el porcentaje de pacientes hipertensos (88% pre vs 71% postrasplante). La presencia de HAPT constituye un factor de mal pronóstico para la supervivencia del injerto a largo plazo.

Systemic hypertension after kidney transplant (HAPT) has been associated with a reduction in graft survival and increased morbidity and mortalityof kidney transplant recipients. With the use of calcineurin inhibitors, prevalence of HAPT has increased to 60-80%. The purpose of this study was to document the prevalence of HAPT in kidney transplant recipients attending the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" associated risk factors and the effect of hypertension in long term graft survival. We retrospectively reviewed the clinical charts of all the patients that underwent kidney transplant from 1984 to 1994. The following risk factors were studied: age, gender, cause of renal failure, presence of hypertension before kidney transplant, histocompatibility, acute rejection episodes, chronic rejection, serum creatinine values and use of cyclosporine. We divided subjects in two groups: normotensive (NT) and hypertensive (HT). HAPT included >140/90 mmHg blood pressure level observed at least during two consecutive evaluations or the use of antihypertensive medication. We analyzed 215 grafts from 205 patients (10 patients had two kidney transplants); mean age at transplant of 30 ± 9 years, 131 subjects were female and 84 male. One hundred and eighty eight patients (88%) displayed pretransplant hypertension. The mean follow up was 56± 32 months. In the postransplant period 152 (71 %) were HT and 63 (29%) NT. The HT group had significantly higher blood pressure and serum creatinine values than the NT group (P <0.001), in spite of an adequate blood pressure control in 65% of the patients from the HT group. The NT group displayed a higher graft survival than the HT group; 60 ± 30 months vs. 51 ± 32 months respectively (p<0.01). Multivariate analysis did not show any risk factors independently associated with the development of HAPT. The prevalence of HAPT in our series is similar to the one reported in the literature. During the postransplant period there was a reduction of hypertensive patients (88% pretransplant vs. 71% postransplant). HAPT is a significant risk factor associated with long term survival of the graft.

In vivo IL-10 and TGF-beta production by PBMC from long-term kidney transplant recipients with excellent graft function: a possible feedback mechanism participating in immunological stability.

BACKGROUND: Interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) are Th2-derived multifunctional cytokines that exhibit potent immunoregulatory and anti-inflammatory properties which might prolong graft survival. The aim of this study was to explore whether spontaneous production of IL-10 and TGF-beta by blood mononuclear cells correlates with excellent long-term graft function. METHODS: A cross-sectional study was carried out in 32 kidney transplant recipients, without albuminuria, treated with azathioprine and prednisone. Spontaneous IL-10 and TGF-beta were measured by enzyme-linked immunosorbent assay in supernatants from 24 h cultured unstimulated peripheral blood mononuclear cells. Both cytokines were also determined in 10 healthy kidney donors. RESULTS: There was no correlation between IL-10 or TGF-beta with any variable tested, namely age, SCr, histocompatibility, and post-transplant follow-up. In vivo IL-10 production displayed a statistical trend to be higher in transplant recipients than in controls (362.3 +/- 465, range 12.5-1929.3 pg/ml, and 189 +/- 170, range 4.17-485.7 pg/ml, respectively; p = 0.08), whereas no difference was observed in TGF-beta among the same groups (134.7 +/- 79.2, range 68-421 pg/ml, and 121.4 +/- 25.8, range 75-151 pg/ml, respectively). Interestingly, a statistically significant inverse correlation was observed between IL-10 and TGF-beta in kidney transplant recipients (p = 0.03). CONCLUSIONS: The higher IL-10 production observed in long-term kidney transplant recipients supports the notion that this cytokine contributes in decreasing allogenic immune responses and allows prolongation of allograft survival. The balance between TGF-beta and IL-10 may be of paramount importance in graft acceptance.

[Renal graft survival in patients with systemic lupus erythematosus]. / Sobrevida del injerto renal en pacientes con lupus eritematoso generalizado.

BACKGROUND: End-stage renal disease is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). In 1975, the US Renal Transplant Registry reported the first lupus patients, who received a renal transplant. This study reported 60% and 55% patient/graft survival respectively at a mean time of two years; these results were similar to those of non-lupus transplanted patients in this same post-transplant lapse time. Renal transplantation is a world wide accepted therapeutic option in the treatment of SLE patients. PATIENTS AND METHODS: In order to identify the risk factors associated to renal graft loss in SLE patients and to compare graft survival between these patients and control transplant patients, matched by age, gender, haplotype match, and transplant date (+/- three years), we performed a retrospective analysis of all SLE patients that received a renal transplant in our Institute. RESULTS: From 1967 to March 1997, 25 (5.5%) out of 452 renal transplants were performed in 22 SLE patients, mean age 29 +/- 10 years, 20 were female (90%). In 18 patients (85.7%) we obtained pre-transplant histological diagnosis: 13 (72%) type IV glomerulonephritis according to the OMS classification, three (17%) type VI, and two (11%) type III. Twelve patients (57%) were subjected to hemodialysis in the pre-transplant period and none (43%) to peritoneal dialysis. The time elapsed between the diagnosis of SLE and the start of dialysis was 50 +/- 70 months, the time on dialysis was 18 +/- 17 months, the post-transplant renal follow-up 46.9 +/- 41.5 months, and the graft source: 18 (78%) from living related (three sharing 0 haplotypes, 12 sharing 1 haplotype, and three sharing 2 haplotypes), and five (22%) from cadaver donors. Triple drug immunosuppresive therapy (cyclosporine, azathioprine, and prednisone) was employed in 17 patients and double drug therapy (azathioprine and prednisone) in the remaining six cases. We registered seven acute rejection episodes in five patients (30%), one of them lost the graft. Five patients presented a post-transplant thrombotic event, two of these were in the graft's artery. In two patients post-transplant SLE activity was documented, one case in with renal activity in the graft and the other with extrarenal activity. Risk factors analyzed for graft loss: number of pre-transplant thrombosis events, time elapsed between diagnosis of SLE at start of dialysis (< or = 6 months), time on dialysis (< or = 12 months), graft source, chronic rejection, and follow-up were not significant; in contrast, post-transplant thrombosis was the only identified risk factor for graft loss. Graft survival analysis at 50 months in SLE transplanted patients versus control non-SLE transplanted patients did not show significant differences (74% vs. 83%, log rank 0.11). CONCLUSIONS: Post-transplant thrombosis was identified as a risk factor for graft loss. In concordance with recent studies, pre-transplant thrombosis, time elapsed between diagnosis of SLE at start of dialysis and time on dialysis were not risk factors for graft loss in this study. Graft survival in renal transplants recipients with SLE was not different from that of the general renal transplant population.

Sobrevida del injerto renal en pacientes con lupus eritematoso generalizado / Renal graft survival in patients with systemic lupus erythematosus

BACKGROUND: End-stage renal disease is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). In 1975, the US Renal Transplant Registry reported the first lupus patients, who received a renal transplant. This study reported 60 and 55 patient/graft survival respectively at a mean time of two years; these results were similar to those of non-lupus transplanted patients in this same post-transplant lapse time. Renal transplantation is a world wide accepted therapeutic option in the treatment of SLE patients. PATIENTS AND METHODS: In order to identify the risk factors associated to renal graft loss in SLE patients and to compare graft survival between these patients and control transplant patients, matched by age, gender, haplotype match, and transplant date (+/- three years), we performed a retrospective analysis of all SLE patients that received a renal transplant in our Institute. RESULTS: From 1967 to March 1997, 25 (5.5) out of 452 renal transplants were performed in 22 SLE patients, mean age 29 +/- 10 years, 20 were female (90). In 18 patients (85.7) we obtained pre-transplant histological diagnosis: 13 (72) type IV glomerulonephritis according to the OMS classification, three (17) type VI, and two (11) type III. Twelve patients (57) were subjected to hemodialysis in the pre-transplant period and none (43) to peritoneal dialysis. The time elapsed between the diagnosis of SLE and the start of dialysis was 50 +/- 70 months, the time on dialysis was 18 +/- 17 months, the post-transplant renal follow-up 46.9 +/- 41.5 months, and the graft source: 18 (78) from living related (three sharing 0 haplotypes, 12 sharing 1 haplotype, and three sharing 2 haplotypes), and five (22) from cadaver donors. Triple drug immunosuppresive therapy (cyclosporine, azathioprine, and prednisone) was employed in 17 patients and double drug therapy (azathioprine and prednisone) in the remaining six cases. We registered seven acute rejection episodes in five patients (30), one of them lost the graft. Five patients presented a post-transplant thrombotic event, two of these were in the graft's artery. In two patients post-transplant SLE activity was documented, one case in with renal activity in the graft and the other with extrarenal activity. Risk factors analyzed for graft loss: number of pre-transplant thrombosis events, time elapsed between diagnosis of SLE at start of dialysis (< or = 6 months), time on dialysis (< or

Evolución y factores pronósticos de la nefropatía lúpica / Evolution and prognostic factors of lupus nephritis

El presente estudio un análisis retrospectivo de una cohorte de 154 pacientes con diagnóstico de nefropatía lúpica, que fueron biopsiados entre enero de 1984 y diciembre de 1990. El objetivo fue conocer evolución de la función renal y los factores asociados al desarrollo de insuficiencia renal crónica terminal (IRCT). Métodos. Se revisaron expedientes en busca de siguientes variables al momento de la biopsia: edad, sexo, criterios de lupus de acuerdo al Colegio Americano de Reumatología, tensión arterial, creatinina sérica, BUN, albúmina sérica, anticuerpos antinucleares, captación de DNA y proteinuria. Se registró el tiempo de seguimiento en meses. Todas las biopsias fueron analizadas con microscopia de luz. Los puntos finales fueron IRCT, muerte o fin del estudio. Se construyeron tablas de Kaplan-Meier para análisis de supervivencia. La asociación entre las variables y evolución a IRCT se llevó a cabo en forma univariada con análisis de logrank y multivariada mediante el análisis de riesgos proporcionales de Cox. Resultados. El seguimiento fue completo en 144 enfermos (68 ñ 38 meses), de los cuales el 93 por ciento eran mujeres. La edad media fue 28 ñ 9 años, el tiempo de evolución de LEG al momento de la biopsia renal de 44.8 ñ 42 meses y tiempo de evolución la nefropatía al momento de la biopsia renal de 35 ñ 38 meses. El número promedio de criterios para diagnóstico de lupus fue de 4 ñ 1. Desde el punto de vista renal, 60 por ciento de los pacientes se presentaron con síndrome nefrótico, 40 por ciento con proteinuria no nefrótica, 2 por ciento con síndrome nefrítico y 61 por ciento con hipertensión arterial. El diagnóstico histológico mostró nefropatía tipo I en 2 por ciento, tipo II en 8 por ciento, tipo III en 6 por ciento, tipo IV en 71 por ciento y tipo V en 11 por ciento. Al final del estudio, 28 pacientes habían desarrollado insuficiencia renal crónica terminal y otros 15 tenían el doble o más de la creatinina sérica inicial. En el grupo total la posibilidad de mantenerse fuera de diálisis fue de 85 por ciento a 70 meses y 70 por ciento a 140 meses. El análisis de Cox mostró que las variables con asociación independiente para el desarrollo de insuficiencia renal crónica terminal fueron edad y creatinina sérica inicial. A mayor creatinina sérica y menor edad, mayor es la posibilidad de desarrollar IRCT

Biopsia renal percutánea, análisis de 26 años: tasa de complicaciones y factores e riesgo / Percutaneous renal biopsy, a 26 years analysis: complications rate and risk factors

La biopsia renal percutánea es un procedimiento invasivo que puede producir complicaciones mayores y menores. El presente estudio se realizó con el objetivo de conocer el número y tipo de complicaciones relacionadas con el procedimiento, así como la efectividad del mismo para obtener material adecuado para el diagnóstico. Pacientes y métodos. Estudio retrospectivo con revisión de expedientes clínicos de los pacientes a quienes se les realizó una biopsia renal percutánea de riñones nativos entre enero de 1970 y marzo de 1996. Los datos recabados fueron: edad, sexo, diagnóstico clínico e histopatológico, así como las siguientes complicaciones asociadas a la biopsia: menores (hematuria, infecciones limitadas, hematoma) y mayores (transfusiones, infecciones graves, requerimiento de cirugía, nefrectomía, arteriografía, embolización y muerte). Resultados. En total se analizaron 1,005 biopsias renales percutáneas efectuadas en 840 pacientes, en los que la edad fue de 31.7 ñ 13.1 años y el 67 por ciento eran del sexo femenino. En 88.8 por ciento de los casos (893 procedimientos) no se presentaron complicaciones. En el 8.65 por ciento hubo complicaciones menores (87 procedimientos) y solo en el 2.4 por ciento se registraron complicaciones mayores (25 biopsias). Se dividieron los pacientes en dos grupos: biopsias renales percutáneas sin complicaciones (n = 893, 89 por ciento) y biopsias renales percutáneas con complicaciones (n = 112, 11 por ciento). La hematuria fue la complicación más frecuente (91 casos, 9.1 por ciento), seguida de la formación de hematoma perirrenal en 29 (2.7 por ciento). Estas dos complicaciones sólo requirieron transfusión en 26 casos (2.4 por ciento). Las complicaciones infecciosas fueron urosepsis en siete (0.7 por ciento), bacteremia, sepsis y absceso perirrenal (un caso cada uno, 0.1 por ciento respectivamente). Un paciente murió por complicaciones múltiples (0.1 por ciento). Se observó un mayor riesgo de presentar complicaciones graves en quienes la biopsia fue realizada por insuficiencia renal aguda (RM 4.03, P < 0.003). Discusión. En nuestra experiencia, la biopsia renal percutánea es un procedimiento con bajo riesgo. La mayoría de las complicaciones son menores y no tienen repercusiones clínicas. Sin embargo, la presencia de complicaciones graves, aun en bajo porcentaje, obliga a tener una estricta selección del paciente al que se le pretende practicar una biopsia renal percutánea.

Cuatro casos de cáncer de paratiroides / Four cases of parathyroid carcinoma

El carcinoma de paratiroides es una causa poco frecuente de hiperparatiroidismo primario, con una prevalancia que oscila entre 0.5 y 4 por ciento. Estas neoplasias tienen un curso agresivo por lo que es importante establecer un diagnóstico oportuno y realizar tratamiento quirúrgico precoz. En el Instituto Nacional de la Nutrición en un periodo de siete años, se realizaron 88 cirugías por hiperparatiroidismo primario, encontrándose en cuatro casos un carcinoma de paratiroides (prevalencia del 4.5 por ciento). Presentamos aquí las características clínicas, diagnóstico, tratamiento y evolución de estos pacientes

Carcinoma ecrino de células claras en región plantar. Seguimiento de un caso por histoquímica, inmunohistoquímica y citometría de flujo / Clear cell ecrine carcinoma of the sole. Case report with histochemical, immunohistochemical, and flow cytometry studies

Se han informado 47 casos de carcinomas ecrinos de células claras, y solamente uno en la región plantar. El presente caso corresponde a una mujer de 38 años de edad, con una lesión de 3.2 cm de diámetro en la región lateral de la planta del pie derecho, de 18 años de evolución, con metástasis inguinales cuatro y cinco meses después de la resección del tumor plantar y recidivas locales en dos ocaciones. El estudio histológico del tumor evidenció una lesión constituida en más del 80 por ciento por células claras. En las metástasis y en las zonas de recidiva la lesión presentaba menor porcentaje de células claras y, se agregaron otros patrones histológicos. Se identificó positividad para la tinción de PAS, con labilidad para la diastasa en las células claras. La reactividad de la tinción de PAS mostró una relación inversa con el número de células claras en los tumores resecados. En las células sebáceas y estructuras tubulares se observó reactividad focal para hierro coloidal y mucina. Las tinciones de inmunohistoquímica resultaron positivas para el antígeno epitelial de membrana en las células claras y focal en las células poroides, sebáceas y estructuras tubulares y, focalmente, la proteína S-100 marcó a las células de aspecto sebáceo. Las células neoplásicas de la lesión plantar y de las metástasis mostraron contenido nuclear euploide. Los carcinomas ecrinos de células claras son un grupo de lesiones de comportamiento biológico y heterogéneo, con características morfológicas, histoquímicas e inmunohistoquímicas variables en el tumor primario y en las metástasis, pero que permiten su identificación

Carcinoma ecrino de células claras de región plantar. Estudio histoquímico e inmunohistoquímico de un caso / Cutaneous clear cell eccrine carcinoma of the foot sole. histochemistry and immunohistochemistry study of one case

Los carcinomas ecrinos de células claras son neoplasias infrecuentes descritas en la literatura bajo diversos términos. Han sido consignados 47 casos con esta lesión y sólo en 30 se describe el sitio anatómico del tumor primario; de éstos, sólo uno estuvo localizado en la región plantar. El presente caso correspondió a una mujer de 38 años de edad; la lesión medía 3.2 cm, estaba ubicada en la porción lateral de la planta del pie derecho y tenía 18 años de evolución. El estudio histopatológico del espécime quirúrgico inclyó marcadores histoquímicos e inmunohistoquímicos para neoplasias de glándulas ecrinas. Las neoplasia estaba compuesta principalmente por células claras positivas para la tinción de PAS y lábiles a la distasa. En menor proporción, también se identificaron células con diferenciación sebácea, así estructuras tubulares, que mostraron reactividad focal para la tinción de hierro coloidal y mucicarmín. La tinción de inmunoperoxidasa contra el antígeno epitelial de membrana resultó positiva en forma difusa en la superficie y el citoplasma de las células claras; mientras que, en las células basaloides, sebáceas y estructuras tubulares, fue focal. Estas células además fueron positivas para el antígeno carcinoembrionario. La proteína S-100 de manera focal marcó a las células con diferenciación sebácea. Se concluye que los carcinomas ecrinos de células claras corresponden a un grupo de tumores primarios cutáneos que poseen marcadores morfológicos, histoquímicos e inmunohistoquímicos útiles para establecer su diagnóstico