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1.
Clin Transplant ; 32(4): e13207, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29345747

RESUMEN

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis; the reported recurrence rate of IgAN after renal transplantation is as high as 13%-50%. The impact of immunosuppressive therapy and steroid withdrawal on the risk of recurrence of IgAN is still under debate. We performed a retrospective single-center study, selecting 123 kidney transplants (rtx) in 120 patients, between January 1995 and December 2012, with IgAN on the native kidney. In 51 of 123 transplants, at least one post-transplantation biopsy for clinical indication was performed; in 28 of 51 transplants, IgAN recurrence (IgANr) was demonstrated. This group (G1; N = 28) was compared with a group without IgANr (G2; N = 23). In our study, clinically evident IgANr rate was 54.9% (28/51) on biopsied patients. At discharge, the use of the immunosuppressant drugs (tacrolimus, cyclosporine A, mycophenolate mofetil, azathioprine, mTor inhibitors) was not associated with an increased risk of IgANr (P = NS). At discharge, all patients were steroid treated. Neither the use of tacrolimus, mycophenolate mofetil, nor mTor inhibitors (mTori) at biopsy time were associated with IgANr. However, IgANr was significantly higher in patients who experienced steroid withdrawal at any post-transplantation time (OR 7.7 P = .03). The median time to recurrence after steroid withdrawal was 59 months (min 4.18, max 113.2).


Asunto(s)
Glomerulonefritis por IGA/etiología , Rechazo de Injerto/etiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias , Esteroides/administración & dosificación , Adulto , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Glomerulonefritis por IGA/patología , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Privación de Tratamiento
2.
Urol Int ; 100(2): 185-192, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29342465

RESUMEN

BACKGROUND AND OBJECTIVES: Renal transplant recipients (RTRs) have a 2- to 7-fold risk of developing a neoplasm compared to general population. Bladder urothelial neoplasms in this cohort has an incidence of 0.4-2%. Many reports describe a more aggressive behavior. The objective of this study is to describe oncologic characteristics of bladder urothelial neoplasms in RTRs and to evaluate its recurrence, progression, and survival rates. METHODS: A retrospective multicentered study was performed evaluating all de novo bladder urothelial neoplasms cases in RTRs from 1988 to 2014. Descriptive statistical analysis and evaluation of recurrence, progression, and survival rates were performed. RESULTS: A total of 28 de novo bladder transitional cell carcinomas (TCCs) were identified (incidence rate 0.64%). Cancer-specific survival rates were 100, 75, and 70% after 1, 5, and 10 years, respectively. Age at diagnosis superior to 60 years was found to be a statistically significant variable for recurrence risk. Progression rate was 14%. Presence of CIS was significantly associated with progression. All cancer-specific deaths were in the high-risk group and all were progressions from non-muscle invasive to muscle invasive bladder cancer. CONCLUSIONS: Bladder urothelial neoplasms following renal transplant is associated with a trend toward worst prognosis. Early aggressive treatments, such as early radical cystectomy, might be advisable to reduce cancer-specific deaths.


Asunto(s)
Carcinoma de Células Transicionales/patología , Trasplante de Riñón/efectos adversos , Receptores de Trasplantes , Neoplasias de la Vejiga Urinaria/patología , Urotelio/patología , Adulto , Anciano , Carcinoma de Células Transicionales/etiología , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/terapia , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Italia , Estimación de Kaplan-Meier , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/etiología , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/terapia , Adulto Joven
3.
Kidney Int ; 86(4): 828-36, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24694989

RESUMEN

The Oxford Classification of IgA Nephropathy (IgAN) identified mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as independent predictors of outcome. Whether it applies to individuals excluded from the original study and how therapy influences the predictive value of pathology remain uncertain. The VALIGA study examined 1147 patients from 13 European countries that encompassed the whole spectrum of IgAN. Over a median follow-up of 4.7 years, 86% received renin-angiotensin system blockade and 42% glucocorticoid/immunosuppressive drugs. M, S, and T lesions independently predicted the loss of estimated glomerular filtration rate (eGFR) and a lower renal survival. Their value was also assessed in patients not represented in the Oxford cohort. In individuals with eGFR less than 30 ml/min per 1.73 m(2), the M and T lesions independently predicted a poor survival. In those with proteinuria under 0.5 g/day, both M and E lesions were associated with a rise in proteinuria to 1 or 2 g/day or more. The addition of M, S, and T lesions to clinical variables significantly enhanced the ability to predict progression only in those who did not receive immunosuppression (net reclassification index 11.5%). The VALIGA study provides a validation of the Oxford classification in a large European cohort of IgAN patients across the whole spectrum of the disease. The independent predictive value of pathology MEST score is reduced by glucocorticoid/immunosuppressive therapy.


Asunto(s)
Glomerulonefritis por IGA/clasificación , Glomerulonefritis por IGA/patología , Fallo Renal Crónico/patología , Riñón/patología , Adolescente , Adulto , Atrofia , Niño , Progresión de la Enfermedad , Europa (Continente) , Femenino , Fibrosis , Estudios de Seguimiento , Tasa de Filtración Glomerular , Mesangio Glomerular/patología , Glomerulonefritis por IGA/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Inmunosupresores/uso terapéutico , Riñón/irrigación sanguínea , Fallo Renal Crónico/fisiopatología , Túbulos Renales/patología , Masculino , Persona de Mediana Edad , Neovascularización Patológica/patología , Valor Predictivo de las Pruebas , Proteinuria/patología , Sistema Renina-Angiotensina/efectos de los fármacos , Estudios Retrospectivos , Adulto Joven
4.
Am J Kidney Dis ; 61(2): 300-9, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22938846

RESUMEN

Numerous preclinical and clinical studies suggest that mesenchymal stem cells, also known as multipotent mesenchymal stromal cells (MSCs), may improve pathologic conditions involving different organs. These beneficial effects initially were ascribed to the differentiation of MSCs into organ parenchymal cells. However, at least in the kidney, this is a very rare event and the kidney-protective effects of MSCs have been attributed mainly to paracrine mechanisms. MSCs release a number of trophic, anti-inflammatory, and immune-modulatory factors that may limit kidney injury and favor recovery. In this article, we provide an overview of the biologic activities of MSCs that may be relevant for the treatment of kidney injury in the context of a case vignette concerning a patient at high immunologic risk who underwent a second kidney transplantation followed by the development of ischemia-reperfusion injury and acute allograft rejection. We discuss the possible beneficial effect of MSC treatment in the light of preclinical and clinical data supporting the regenerative and immunomodulatory potential of MSCs.


Asunto(s)
Lesión Renal Aguda/cirugía , Riñón/irrigación sanguínea , Trasplante de Células Madre Mesenquimatosas , Daño por Reperfusión/cirugía , Humanos , Masculino , Persona de Mediana Edad
5.
J Sex Med ; 10(11): 2798-814, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23346948

RESUMEN

INTRODUCTION: The phosphodiesterase type 5 (PDE5) inhibitors are generally well tolerated and effective for treating erectile dysfunction (ED), including in patients with significant comorbidity. Because of this benign safety profile, investigators have used PDE5 inhibitors to treat patients with ED and severe renal disease or those who have received renal transplants. AIM: To assess safety and efficacy of PDE5 inhibitors in patients receiving dialysis or renal transplants. MAIN OUTCOME MEASURES: Erectile function as assessed by the International Index of Erectile Function (IIEF) and Global Assessment Questions; adverse events (AEs). METHODS: We reviewed published studies of PDE5 inhibitors in patients receiving dialysis or renal transplants. RESULTS: In double-blind, placebo-controlled studies in patients receiving dialysis or renal transplants, sildenafil significantly improved erectile function as assessed by the IIEF, and 75-85% of patients reported improved erectile function on Global Assessment Questions; efficacy was more variable in less well-controlled studies. In >260 patients undergoing dialysis who received sildenafil in clinical studies, there were only six reported discontinuations because of AEs (headache [N=3], headache and nausea [N=1], gastrointestinal [N=1], and symptomatic blood pressure decrease [N=1]). In approximately 400 patients with renal transplants who received sildenafil, only three patients discontinued because of AEs. Vardenafil improved IIEF scores of up to 82% of renal transplant recipients in randomized, controlled studies (N=59, total), with no reported discontinuations because of AEs. Limited data also suggest benefit with tadalafil. CONCLUSIONS: ED is common in patients undergoing renal dialysis or postrenal transplant and substantially affects patient quality of life. Sildenafil and vardenafil appear to be efficacious and well tolerated in patients receiving renal dialysis or transplant.


Asunto(s)
Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/fisiopatología , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/terapia , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Adulto , Método Doble Ciego , Disfunción Eréctil/metabolismo , Humanos , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Inhibidores de Fosfodiesterasa 5/farmacocinética , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal , Resultado del Tratamiento
6.
G Ital Nefrol ; 40(5)2023 Oct 26.
Artículo en Italiano | MEDLINE | ID: mdl-38010251

RESUMEN

This article, written by several authors, describes the birth and early development of the nephrology at Molinette Hospital in Torino, Italy. In particular, it supplies important information on Antonio Vercellone, very motivated and innovative clinician and one of the fathers of Italian nephrology, and on Giuseppe Piccoli, his right-hand man and then his successor. This article also shows the strong professional and human engagement that was requested to the young doctors who, in the early Sixties and Seventies of the past century, had chosen to devote their professional lives to the patients with kidney diseases: from endless workdays without schedules to the anguish caused by the shortage of artificial kidneys to the cure of very fragile and unfortunate patients, and much more.


Asunto(s)
Enfermedades Renales , Nefrología , Médicos , Humanos , Nefrología/historia , Enfermedades Renales/historia , Hospitales , Italia
7.
J Pathol ; 225(1): 129-41, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21706482

RESUMEN

In autosomal dominant polycystic kidney disease, cysts arise focally and disrupt normal renal tissue leading to renal failure. In the present study, we show that cyst-lining cells express the stem cell marker CD133. CD133+ progenitor cells isolated from polycystic kidney, carrying mutations of PKD genes, showed a dedifferentiated phenotype similar to CD133+ progenitor cells from normal kidney. However, these cells were more proliferative and presented a defective epithelial differentiation phenotype with respect to normal renal CD133+ cells as they were not able to express all tubular epithelial cell markers when cultured in epithelial differentiation medium. Polycystic CD133+ cells, in contrast to normal renal CD133+ cells, formed cysts in vitro in a three-dimensional culture system and in vivo when injected subcutaneously within Matrigel in SCID mice. Rapamycin treatment reduced in vitro proliferation of polycystic CD133+ cells and decreased cystogenesis both in vitro and in vivo. The in vitro epithelial differentiation was only partially improved by rapamycin. These results indicate that polycystic CD133+ cells retain a dedifferentiated phenotype and the ability to generate cysts.


Asunto(s)
Antígenos CD/metabolismo , Glicoproteínas/metabolismo , Péptidos/metabolismo , Riñón Poliquístico Autosómico Dominante/metabolismo , Células Madre/metabolismo , Antígeno AC133 , Animales , Apoptosis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Humanos , Riñón/metabolismo , Ratones , Ratones SCID , Mutación Missense , Riñón Poliquístico Autosómico Dominante/genética , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Canales Catiónicos TRPP/genética , Trasplante Heterólogo
8.
G Ital Nefrol ; 29(5): 579-91, 2012.
Artículo en Italiano | MEDLINE | ID: mdl-23117738

RESUMEN

The recognition of antibody-mediated rejection as an important factor in the reduction of long-term renal graft survival represents a new challenge to the immunosuppressive strategies of recent years, which have been quite successful in reducing the acute rejection rates as well as the side effects of pharmacological immunosuppression. The search for an effective treatment of chronic anti-donor antibody disease has been pursued mostly through limited single-center experiences and therefore in a dispersed fashion, without leading to the definition of a consolidated approach. The most frequently used pharmacological approaches stem from the experience of antibody-mediated acute rejection. In this review we will critically analyze the results reported so far of various intervention strategies and we will discuss future pharmacological novelties targeting the humoral immune response.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Terapia de Inmunosupresión , Trasplante de Riñón , Anticuerpos/inmunología , Predicción , Humanos , Rituximab
9.
G Ital Nefrol ; 29(4): 473-83, 2012.
Artículo en Italiano | MEDLINE | ID: mdl-22843159

RESUMEN

The Piedmont Group of Clinical Nephrology has compared the activity of 18 nephrology centers in the region Piedmont/Valle d'Aosta with regard to renal biopsy (RB). Data on the RBs performed in every nephrology unit, taking into account their entire experience (in some cases spanning more than 30 years), were analyzed. 3396 RBs were performed between 1996 and 2011. Thirty to forty percent were done in patients aged >-65 years (1568 in patients >-65 years, 29 in patients >-85 years). 598 BRs were performed in children over the last 20 years. The following contraindications to RB were considered: chronic renal failure by 8 centers (44.4%), serum creatinine (SCr >3 mg/dL) by 3 centers, longitudinal renal size <8 cm by 3 centers, and renal cortex thickness <1 cm by 2 centers. 1798 RBs were performed in patients with SCr >2 mg/dL and 275 in patients on dialysis. The percentage of RBs performed in patients with SCr >2 mg/dL ranged from 27% to 55% between centers. As regards RB in the course of acute renal failure in an ANCA-positive context, 4 centers allowed administration of corticosteroids and 8 centers administration of immunosuppressive treatment as well, even in the absence of histological data. In drug-related nephropathies, RB was considered indicated to confirm the farhypothesis of immunoallergic interstitial nephropathy either if the responsible drug was not among the traditional ones known to induce tubulo-interstitial renal disease or if the pharmacological hypothesis seemed no longer sufficient to justify the renal presentation. All centers but one were against performing RB in case of atheroembolic disease. Three centers performed RB in the intensive care unit. As regards RB in patients undergoing treatment with anticoagulants, aspirin was discontinued 5-14 days before the procedure (mean 8 days) and given again 7-15 days afterwards (mean 11.4 days). Ten centers replaced the anticoagulants with low-dose heparin, which was discontinued the day before the procedure; 11 centers asked advice from cardiologists. RB was repeated in 113 cases after a delay of 1 month to 8 years from the first RB. Our analysis shows uniformity in the approach to RB in this Italian region, with some differences compared with the literature: particular attention was paid to severely critical patients, elderly patients, and patients treated with anticoagulant drugs.


Asunto(s)
Riñón/patología , Insuficiencia Renal/patología , Anciano , Anciano de 80 o más Años , Biopsia , Humanos , Italia , Estudios Retrospectivos , Encuestas y Cuestionarios
10.
G Ital Nefrol ; 29(5): 621-7, 2012.
Artículo en Italiano | MEDLINE | ID: mdl-23117742

RESUMEN

In 2010 a questionnaire was administered to the renal units of Piedmont and Valle d'Aosta to analyze their procedures for renal biopsy (RB). Seventy-eight percent of units performed RBs, 57% for more than 20 years, but only 43% performed at least 20 BRs per year. 20/21 units performed RB in an inpatient setting and 1/21 in day hospital with the patient remaining under observation the night after. Thirty-two percent did not consider a single kidney as a contraindication to RB, 59% considered it a relative contraindication and 9% considered it an absolute contraindication. In 90.5% of units there was a specific protocol for patient preparation for RB and 86% used a specific informed consent form. Ninety-five percent of units performed ultrasound-guided RB, 60% of them using needle guides attached to the probe. In 81% of units the left side was preferred; 71% put a pillow under the patient's abdomen. All units used disposable, automated or semi-automated needles. Needle size was 16G in 29%, 18G in 58%, and both 16G and 18G in 14% of units; 1 to 3 samples were drawn. One third of units had a microscope available for immediate evaluation of specimen adequacy. After RB, 86% of units kept patients in the prone position for 2-6 hours and all prescribed a period of bed rest (at least 24 hours in 90.5%). 90.5% of units followed a specific postbiopsy observation protocol consisting of blood pressure, heart rate and red blood cell measurements at different times, and urine monitoring and ultrasound control within 12-24 hours (only half of them also employing color Doppler). One third of all units discharged patients after 1 day and two thirds after 2-3 days; all prescribed abstention from effort and from antiplatelet drugs for 7-15 days. In 9 units both RB and tissue processing and examination were done in the same hospital, while 12 units sent the samples elsewhere. 76% obtained results in 2-4 days, 19% in 6-7 days, and 5% in 10-15 days. Less than 20% of the interviewed operators were fully familiar with the clauses of hospital insurance securing their activity. Use of RB is widespread in Piedmont and Valle d'Aosta but its practice shows variation between centers.


Asunto(s)
Riñón/patología , Biopsia con Aguja , Humanos , Italia , Pautas de la Práctica en Medicina
11.
Eur J Dermatol ; 21(2): 242-7, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21382788

RESUMEN

Kidney transplant recipients frequently suffer from skin infections and malignancies, due to the effects of long-term immunosuppressive therapy. Herein, a dermatological screening was performed to evaluate the relationship between risk factors, cutaneous tumours and other skin diseases in a group of 282 kidney transplant patients. Infectious diseases (16.7%) were the most frequent dermatological disorders, whereas cutaneous inflammatory and autoimmune diseases were relatively rare, probably due to an indirect therapeutic role of immunosuppressive regimens. Thirty patients experienced cutaneous side effects from immunosuppressants, mainly when receiving corticosteroids (p = 0.0372). We identified 99 patients (35.1%) who developed cutaneous tumours after transplantation. Cumulative tumour incidence was observed during long-term immunosuppressive therapy; no relationships were identified between skin cancer risk and single class of drug or combination regimens. When we evaluated the eventual relevance of other risk factors for skin cancers, we demonstrated a statistical significance in univariate analysis for male gender, more advanced age at transplantation, long duration of immunosuppressive regimens, no sunscreen usage, outdoor job, absence of cherry angiomas and presence of actinic keratoses (AKs). Age at transplantation (p = 0.0174), presence of AKs (p = 0.0005) and duration of immunosuppression (p = 0.0011) also confirmed their significance in multivariate analysis.


Asunto(s)
Huésped Inmunocomprometido , Trasplante de Riñón/inmunología , Enfermedades de la Piel/epidemiología , Neoplasias Cutáneas/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Basocelular/epidemiología , Carcinoma Basocelular/inmunología , Femenino , Humanos , Inmunosupresores/administración & dosificación , Italia/epidemiología , Queratosis Actínica/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo , Enfermedades de la Piel/inmunología , Neoplasias Cutáneas/inmunología , Adulto Joven
13.
Clin Transplant ; 24(4): 488-92, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-19758268

RESUMEN

The presence of non-organ-specific (NOSA) and anti-endothelial antibodies (AECAs) and the onset of rejection in relation to cytomegalovirus (CMV) infection was investigated in 96 renal transplant recipients: 48 CMV pp65-antigenemia-negative (group 1) and 48 positive (group 2). The presence of autoantibodies (autoAbs) was evaluated before and following renal transplantation (first three months) by indirect immunofluorescence. Before transplantation, none of the patients was positive to AECAs, while eight (8.3%) were positive to NOSAs. Post-transplantation, AECA were found in none of patients from group 1 vs. 15/48 (31.2%) from group 2 (p<0.05); NOSAs were detected in 9/48 (18.8%) and 9/48 patients from group 1 and 2, respectively. An acute rejection was diagnosed in ten cases: six of interstitial type (antigenemia-, and AECA-negative; two NOSA-positive); four of vascular type (all of them NOSA-negative, 3/4 antigenemia-, and AECA-positive). CMV infection did not seem to be significantly associated with the appearance of NOSAs, while there was a significant correlation with the occurrence of AECAs. No significant correlation was found between acute rejection and the occurrence of NOSAs, while 75% of the cases of vascular rejection was associated to CMV infection and AECA-positivity, suggesting the pathogenic role of CMV-mediated endothelial damage.


Asunto(s)
Autoanticuerpos/sangre , Infecciones por Citomegalovirus/inmunología , Rechazo de Injerto/inmunología , Rechazo de Injerto/virología , Trasplante de Riñón , Enfermedad Aguda , Adulto , Anciano , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/patología , Infecciones por Citomegalovirus/virología , Femenino , Estudios de Seguimiento , Rechazo de Injerto/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Adulto Joven
14.
Clin Transplant ; 24(1): E1-9, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-19925464

RESUMEN

Side effects of steroid use have led to efforts to minimize their use in transplantation. Two corticosteroid-free regimens were compared with a triple immunosuppressive therapy. Data from the original intent-to-treat (ITT) population (153 tacrolimus/basiliximab [Tac/Bas], 151 tacrolimus/MMF [Tac/MMF], and 147 tacrolimus/MMF/steroids [control]) were analyzed in a 12-month follow-up. Percentage of graft survival were 92.8%, 95.4%, and 95.9% (KM estimates 89.9%, 95.3%, 95.9%), percentage of surviving patients were 98.7%, 98.0%, and 100% (KM estimates 95.9%, 92.8%, and 100%). During months 7-12, graft loss occurred in 3 Tac/Bas, 2 Tac/MMF, and zero control patients, patient deaths in 1 Tac/Bas, 2 Tac/MMF, and zero control, and biopsy-proven acute rejection episodes in 4 Tac/Bas, 3 Tac/MMF, and zero control. Mean serum creatinine at month 12 was 141.9 +/- 69.6 microM, 144.0 +/- 82.1 microM, and 134.5 +/- 71.2 microM (ns). New-onset insulin use in previously non-diabetic patients at month 12 was 1/138, 6/127, and 4/126. Patient and graft survival as well as renal function at 12 months were not different between patient groups, despite considerably higher rates of acute rejection occurring within the first six months after transplantation in both steroid-free patient groups. Tac/Bas therapy might offer benefits in terms of a trend for a more favorable cardiovascular risk profile.


Asunto(s)
Glucocorticoides/administración & dosificación , Inmunosupresores/administración & dosificación , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Tacrolimus/administración & dosificación , Adulto , Anticuerpos Monoclonales/administración & dosificación , Basiliximab , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/patología , Masculino , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/análogos & derivados , Proteínas Recombinantes de Fusión/administración & dosificación , Tasa de Supervivencia , Resultado del Tratamiento
15.
Crit Care ; 14(1): R4, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20064258

RESUMEN

INTRODUCTION: A pro-apoptotic effect of circulating mediators on renal tubular epithelial cells has been involved in the pathogenesis of sepsis-associated acute kidney injury (AKI). Adsorption techniques have been showed to efficiently remove inflammatory cytokines from plasma. The aim of this study was to evaluate the efficiency of the hydrophobic resin Amberchrom CG161 M to adsorb from septic plasma soluble mediators involved in tubular injury. METHODS: We enrolled in the study 10 critically ill patients with sepsis-associated AKI and we evaluated the effects of their plasma on granulocyte adhesion, apoptosis and functional alterations of cultured human kidney tubular epithelial cells. We established an in vitro model of plasma adsorption and we studied the protective effect of unselective removal of soluble mediators by the Amberchrom CG161 M resin on septic plasma-induced tubular cell injury. RESULTS: Plasma from septic patients induced granulocyte adhesion, apoptosis and altered polarity in tubular cells. Plasma adsorption significantly decreased these effects and abated the concentrations of several soluble mediators. The inhibition of granulocyte adhesion to tubular cells was associated with the down-regulation of ICAM-1 and CD40. Resin adsorption inhibited tubular cell apoptosis induced by septic plasma by down-regulating the activation of caspase-3, 8, 9 and of Fas/death receptor-mediated signalling pathways. The alteration of cell polarity, morphogenesis, protein reabsorption and the down-regulation of the tight junction molecule ZO-1, of the sodium transporter NHE3, of the glucose transporter GLUT-2 and of the endocytic receptor megalin all induced by septic plasma were significantly reduced by resin adsorption. CONCLUSIONS: Septic plasma induced a direct injury of tubular cells by favouring granulocyte adhesion, by inducing cell apoptosis and by altering cell polarity and function. All these biological effects are related to the presence of circulating inflammatory mediators that can be efficiently removed by resin adsorption with a consequent limitation of tubular cell injury.


Asunto(s)
Citocinas/aislamiento & purificación , Mediadores de Inflamación/aislamiento & purificación , Enfermedades Renales/prevención & control , Túbulos Renales Proximales/patología , Polímeros/farmacología , Sepsis/sangre , Adsorción , Anciano , Células Cultivadas , Citocinas/sangre , Femenino , Humanos , Técnicas In Vitro , Mediadores de Inflamación/sangre , Enfermedades Renales/etiología , Enfermedades Renales/patología , Masculino , Persona de Mediana Edad , Sepsis/complicaciones
16.
J Am Soc Nephrol ; 20(6): 1404-15, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19470683

RESUMEN

Cyclosporine A (CsA) is a substrate of P-glycoprotein, an efflux transporter encoded by the ABCB1 gene. Compared with carriers of the wild-type gene, carriers of T allelic variants in exons 21 or 26 have reduced P-glycoprotein activity and, secondarily, increased intracellular concentration of CsA; therefore, carriers of T variants might be at increased risk for CsA-related adverse events. We evaluated the associations between ABCB1 genotypes (in exons 12, 21, and 26) and CsA-related outcomes in 147 renal transplant recipients who were receiving CsA-based immunosuppression and were included in the Mycophenolate Steroids Sparing study. During a median of 65.5 mo follow-up, carriers of T allelic variants in exons 21 or 26 had a three-fold risk for delayed graft function (DGF), a trend to slower recovery of renal function and lower GFR at study end, and significantly higher incidences of new-onset diabetes and cytomegalovirus reactivation compared with carriers of the wild-type genotype. T variants in both exons 21 and 26 were independently associated with 3.8- and 3.5-fold higher risk for DGF, respectively (P = 0.022 and P = 0.034). The incidence of acute rejection and the mean CsA dose and blood levels were comparable in genotype groups. In conclusion, renal transplant recipients with T allelic variants in ABCB1 exons 21 or 26 are at increased risk for CsA-related adverse events. Genetic evaluation may help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Ciclosporina/efectos adversos , Funcionamiento Retardado del Injerto/etiología , Inmunosupresores/efectos adversos , Trasplante de Riñón , Subfamilia B de Transportador de Casetes de Unión a ATP , Adulto , Femenino , Genotipo , Tasa de Filtración Glomerular , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
17.
G Ital Nefrol ; 27 Suppl 50: S34-9, 2010.
Artículo en Italiano | MEDLINE | ID: mdl-20922693

RESUMEN

The incidence of lymphomas, especially non-Hodgkin's lymphoma (NHL), has shown a steady increase over the last decades. At the same time, the prognosis has improved. Given the longer survival of lymphoma patients, pathological manifestations related to malignancy might become more frequent. In this setting, the kidney is one of the most important solid organs affected by direct or indirect lymphomatous involvement. Kidney involvement can be related to obstruction or treatment-induced toxicity, but more intriguing are 1) direct infiltration (NHL); 2) renal malignancies in patients affected by Hodgkin's disease or NHL; 3) associated glomerular diseases. Primary infiltration is rarely seen, while secondary infiltration is described most frequently in autopsy series, even in the absence of renal failure. These alterations may mimic glomerular and/or interstitial disease. The association with kidney malignancies, mostly renal cell carcinoma but also urothelial tumors in Hodgkin''s disease, is higher in lymphoma patients than in the general population: the relative risk at 10 years is about 1.5. Glomerulonephritis is described in patients with Hodgkin's disease or NHL; in the former minimal change disease is most frequent, in the latter the glomerular pattern varies widely. Glomerulonephritis can precede, be concurrent with, or follow lymphoma manifestations. Renal biopsy is often needed in this setting.


Asunto(s)
Enfermedades Renales/etiología , Linfoma/complicaciones , Glomerulonefritis/etiología , Humanos
18.
G Ital Nefrol ; 27(6): 639-48, 2010.
Artículo en Italiano | MEDLINE | ID: mdl-21132646

RESUMEN

The treatment of membranous glomerulonephritis (MGN) is controversial, especially in cases of no response to first-line treatment or multiple relapses. The Clinical Nephrology Group of Piedmont carried out a multicenter analysis of the treatment of patients affected by MGN in 15 nephrology units in Piedmont. The first treatment is usually started after a waiting period of 3-6 months in case of proteinuria in the nephrotic range but normal or slightly impaired renal function. A history of cancer, the presence of infectious disease, and secondary forms of MGN are criteria for exclusion from treatment. As first-line treatment, Piedmont nephrologists prescribe corticosteroids alternated with immunosuppressive drugs, generally preferring cyclophosphamide to chlorambucil. Only one nephrology unit uses cyclosporin A (CyA) as the first choice. In case of no response to treatment, a second therapeutic approach is undertaken after 2-12 months. Second-line treatment consists of CyA if immunosuppressive drugs were given before, and corticosteroids/ immunosuppressive drugs if CyA was the first treatment. A further choice may be ACTH or rituximab. In case of multiple relapses the treatment options are the same but previous immunosuppressive treatment, patient age, and the duration of kidney disease with a greater probability of renal failure and progression towards sclerosis require careful attention. Concern has been expressed regarding the potentially severe side effects of ACTH including myopathy, cataract and diabetes. In conclusion, the applied therapeutic approaches in Piedmont reflect the difficulty reported in the literature in identifying simple recommendations. ACTH and rituximab are increasingly preferred for the treatment of MGN and there is a need for prospective studies to determine the best protocol for rituximab and the safety profile of ACTH.


Asunto(s)
Corticoesteroides/uso terapéutico , Glomerulonefritis Membranosa/tratamiento farmacológico , Adhesión a Directriz/estadística & datos numéricos , Inmunosupresores/uso terapéutico , Hormona Adrenocorticotrópica/uso terapéutico , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Clorambucilo/administración & dosificación , Ciclofosfamida/administración & dosificación , Ciclosporina/administración & dosificación , Progresión de la Enfermedad , Quimioterapia Combinada , Glomerulonefritis Membranosa/diagnóstico , Hormonas/uso terapéutico , Humanos , Italia , Guías de Práctica Clínica como Asunto , Rituximab , Resultado del Tratamiento
19.
J Clin Virol ; 44(1): 20-3, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18819837

RESUMEN

BACKGROUND: Polyomavirus-associated nephropathy (PVAN) is one of the most common viral disease affecting renal allograft, with BK being the most frequent causal agent and JCV being considered responsible in <3% of the cases. OBJECTIVES: To quantify polyomaviruses BK and JC load by real-time TaqMan PCR in tissue specimens (renal and ureteral) from kidney transplant recipients. STUDY DESIGN AND METHODS: One-hundred-thirty-eight specimens (125 kidneys, 13 ureters) obtained from 109 patients were evaluated by quantitative real-time PCR for the detection of BKV- and JCV-DNA. Demographic, virological, and histopathological data were collected. RESULTS: BKV-DNA was positive in 32 of 109 patients (29.6%) and JCV-DNA in 20 of 109 patients (18.3%). The highest BK viral loads (>10(4) genome equivalents/cell) were found in two renal samples with histopathologically confirmed PVAN; while JC viral load was >10(4) genome equivalents/cell in one ureteral sample. CONCLUSIONS: Although quantitation of viral DNA on renal allograft biopsies could be complementary to histopathological evaluation and the highest viral load are detectable in renal specimens with PVAN, the identification of a diagnostic cut-off should require further studies.


Asunto(s)
Virus BK/aislamiento & purificación , ADN Viral/aislamiento & purificación , Virus JC/aislamiento & purificación , Trasplante de Riñón/efectos adversos , Riñón/virología , Infecciones por Polyomavirus/diagnóstico , Adulto , Anciano , Virus BK/genética , Biopsia , ADN Viral/genética , Femenino , Humanos , Virus JC/genética , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Trasplante Homólogo , Adulto Joven
20.
Nephrol Dial Transplant ; 24(2): 670-2, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19001562

RESUMEN

We present the first case in which magnetic resonance imaging (MRI) has been utilized to rule out lesions compatible with acute pyelonephritis in kidneys from a cadaveric organ donor before transplanting them. A 40-year-old female underwent diagnosis of brain death following a septic shock. The ecotomography of the kidneys showed areas compatible with micro-abscesses raising the hypothesis of acute pyelonephritis. Our radiologist proposed to perform a bench-MRI (maintaining kidneys within the sterile preservation bags constantly on ice); this did not show lesions except little cysts not relevant by the clinical point of view. We transplanted kidneys without infective complications and results were very good.


Asunto(s)
Trasplante de Riñón , Riñón/patología , Imagen por Resonancia Magnética/métodos , Pielonefritis/diagnóstico , Donantes de Tejidos , Adulto , Cadáver , Femenino , Humanos , Trasplante de Riñón/patología , Recolección de Tejidos y Órganos
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