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1.
Clin Transplant ; 32(4): e13207, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29345747

RESUMO

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).


Assuntos
Glomerulonefrite por IGA/etiologia , Rejeição de Enxerto/etiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias , Esteroides/administração & dosagem , Adulto , Feminino , Seguimentos , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/patologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Suspensão de Tratamento
2.
Urol Int ; 100(2): 185-192, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29342465

RESUMO

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.


Assuntos
Carcinoma de Células de Transição/patologia , Transplante de Rim/efeitos adversos , Transplantados , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia , Adulto , Idoso , Carcinoma de Células de Transição/etiologia , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/terapia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Itália , Estimativa de Kaplan-Meier , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Neoplasias da Bexiga Urinária/etiologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/terapia , Adulto Jovem
3.
Kidney Int ; 86(4): 828-36, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24694989

RESUMO

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.


Assuntos
Glomerulonefrite por IGA/classificação , Glomerulonefrite por IGA/patologia , Falência Renal Crônica/patologia , Rim/patologia , Adolescente , Adulto , Atrofia , Criança , Progressão da Doença , Europa (Continente) , Feminino , Fibrose , Seguimentos , Taxa de Filtração Glomerular , Mesângio Glomerular/patologia , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Imunossupressores/uso terapêutico , Rim/irrigação sanguínea , Falência Renal Crônica/fisiopatologia , Túbulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Valor Preditivo dos Testes , Proteinúria/patologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Estudos Retrospectivos , Adulto Jovem
4.
Am J Kidney Dis ; 61(2): 300-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22938846

RESUMO

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.


Assuntos
Injúria Renal Aguda/cirurgia , Rim/irrigação sanguínea , Transplante de Células-Tronco Mesenquimais , Traumatismo por Reperfusão/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade
5.
J Sex Med ; 10(11): 2798-814, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23346948

RESUMO

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.


Assuntos
Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/fisiopatologia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Inibidores da Fosfodiesterase 5/uso terapêutico , Adulto , Método Duplo-Cego , Disfunção Erétil/metabolismo , Humanos , Falência Renal Crônica/metabolismo , Falência Renal Crônica/cirurgia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Inibidores da Fosfodiesterase 5/farmacocinética , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal , Resultado do Tratamento
6.
G Ital Nefrol ; 40(5)2023 Oct 26.
Artigo em Italiano | MEDLINE | ID: mdl-38010251

RESUMO

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.


Assuntos
Nefropatias , Nefrologia , Médicos , Humanos , Nefrologia/história , Nefropatias/história , Hospitais , Itália
7.
J Pathol ; 225(1): 129-41, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21706482

RESUMO

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.


Assuntos
Antígenos CD/metabolismo , Glicoproteínas/metabolismo , Peptídeos/metabolismo , Rim Policístico Autossômico Dominante/metabolismo , Células-Tronco/metabolismo , Antígeno AC133 , Animais , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Rim/metabolismo , Camundongos , Camundongos SCID , Mutação de Sentido Incorreto , Rim Policístico Autossômico Dominante/genética , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Canais de Cátion TRPP/genética , Transplante Heterólogo
8.
G Ital Nefrol ; 29(5): 579-91, 2012.
Artigo em Italiano | MEDLINE | ID: mdl-23117738

RESUMO

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.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Terapia de Imunossupressão , Transplante de Rim , Anticorpos/imunologia , Previsões , Humanos , Rituximab
9.
G Ital Nefrol ; 29(4): 473-83, 2012.
Artigo em Italiano | MEDLINE | ID: mdl-22843159

RESUMO

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.


Assuntos
Rim/patologia , Insuficiência Renal/patologia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Humanos , Itália , Estudos Retrospectivos , Inquéritos e Questionários
10.
G Ital Nefrol ; 29(5): 621-7, 2012.
Artigo em Italiano | MEDLINE | ID: mdl-23117742

RESUMO

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.


Assuntos
Rim/patologia , Biópsia por Agulha , Humanos , Itália , Padrões de Prática Médica
11.
Eur J Dermatol ; 21(2): 242-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21382788

RESUMO

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.


Assuntos
Hospedeiro Imunocomprometido , Transplante de Rim/imunologia , Dermatopatias/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/imunologia , Feminino , Humanos , Imunossupressores/administração & dosagem , Itália/epidemiologia , Ceratose Actínica/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Dermatopatias/imunologia , Neoplasias Cutâneas/imunologia , Adulto Jovem
13.
Clin Transplant ; 24(4): 488-92, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19758268

RESUMO

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.


Assuntos
Autoanticorpos/sangue , Infecções por Citomegalovirus/imunologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/virologia , Transplante de Rim , Doença Aguda , Adulto , Idoso , Citomegalovirus/imunologia , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/virologia , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
14.
Clin Transplant ; 24(1): E1-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19925464

RESUMO

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.


Assuntos
Glucocorticoides/administração & dosagem , Imunossupressores/administração & dosagem , Falência Renal Crônica/cirurgia , Transplante de Rim , Tacrolimo/administração & dosagem , Adulto , Anticorpos Monoclonais/administração & dosagem , Basiliximab , Quimioterapia Combinada , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/mortalidade , Falência Renal Crônica/patologia , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/análogos & derivados , Proteínas Recombinantes de Fusão/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento
15.
Crit Care ; 14(1): R4, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20064258

RESUMO

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.


Assuntos
Citocinas/isolamento & purificação , Mediadores da Inflamação/isolamento & purificação , Nefropatias/prevenção & controle , Túbulos Renais Proximais/patologia , Polímeros/farmacologia , Sepse/sangue , Adsorção , Idoso , Células Cultivadas , Citocinas/sangue , Feminino , Humanos , Técnicas In Vitro , Mediadores da Inflamação/sangue , Nefropatias/etiologia , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Sepse/complicações
16.
J Am Soc Nephrol ; 20(6): 1404-15, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19470683

RESUMO

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.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Ciclosporina/efeitos adversos , Função Retardada do Enxerto/etiologia , Imunossupressores/efeitos adversos , Transplante de Rim , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adulto , Feminino , Genótipo , Taxa de Filtração Glomerular , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
G Ital Nefrol ; 27 Suppl 50: S34-9, 2010.
Artigo em Italiano | MEDLINE | ID: mdl-20922693

RESUMO

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.


Assuntos
Nefropatias/etiologia , Linfoma/complicações , Glomerulonefrite/etiologia , Humanos
18.
G Ital Nefrol ; 27(6): 639-48, 2010.
Artigo em Italiano | MEDLINE | ID: mdl-21132646

RESUMO

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.


Assuntos
Corticosteroides/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Fidelidade a Diretrizes/estatística & dados numéricos , Imunossupressores/uso terapêutico , Hormônio Adrenocorticotrópico/uso terapêutico , Anticorpos Monoclonais Murinos/administração & dosagem , Clorambucila/administração & dosagem , Ciclofosfamida/administração & dosagem , Ciclosporina/administração & dosagem , Progressão da Doença , Quimioterapia Combinada , Glomerulonefrite Membranosa/diagnóstico , Hormônios/uso terapêutico , Humanos , Itália , Guias de Prática Clínica como Assunto , Rituximab , Resultado do Tratamento
19.
J Clin Virol ; 44(1): 20-3, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18819837

RESUMO

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.


Assuntos
Vírus BK/isolamento & purificação , DNA Viral/isolamento & purificação , Vírus JC/isolamento & purificação , Transplante de Rim/efeitos adversos , Rim/virologia , Infecções por Polyomavirus/diagnóstico , Adulto , Idoso , Vírus BK/genética , Biópsia , DNA Viral/genética , Feminino , Humanos , Vírus JC/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Transplante Homólogo , Adulto Jovem
20.
Nephrol Dial Transplant ; 24(2): 670-2, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19001562

RESUMO

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.


Assuntos
Transplante de Rim , Rim/patologia , Imageamento por Ressonância Magnética/métodos , Pielonefrite/diagnóstico , Doadores de Tecidos , Adulto , Cadáver , Feminino , Humanos , Transplante de Rim/patologia , Coleta de Tecidos e Órgãos
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