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1.
Transplant Proc ; 54(10): 2652-2657, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35995711

RESUMO

BACKGROUND: There is a dearth of data regarding the consequences of ABO-incompatible kidney transplant (ABOiKTx) among post-COVID-19 candidates. METHODS: The study was designed as a retrospective, multicentric cohort study across 11 sites in India, from August 2020 to December 2021. The data for ABOiKTx conducted for post-COVID-19 candidates were investigated. The primary outcome of biopsy-proven acute rejection was compared with the ABO protocol implemented through Kaplan-Meier analysis. The secondary outcomes were graft loss, patient survival, and infections. RESULTS: A total of 38 ABOiKTx with candidates of median (interquartile range) age of 38.5 (31.25-47.5) years were performed. Nineteen cases had mild COVID-19 severity, while 9 cases (23.6%) had an oxygen requirement. Six (15.7%) donors also were post-COVID-19. The most common ABO incompatibility reported was A to O in 14 (36.8%) pairs followed by B to O in 10 (26.3%) pairs. The maximum isoagglutinin titer cutoff was 1:2048 and 1:64 for baseline and pretransplant levels, respectively. The median time from COVID-19 infection to surgery was 130 (63.2-183) days. Biopsy-proven acute rejection, graft loss, and mortality were 13.1%, 2.6%, and 2.6%, respectively. The Breslow-Wilcoxon's P value in Kaplan-Meier plots were 0.57 and 0.93 for thymoglobulin-based induction and high dose rituximab-based regimen, respectively. The incidence of reinfection was 2.6%. Two (5.2%) urinary tract infections were reported. No cytomegalovirus or BK polyomavirus infection was reported. The median serum creatinine at 1 year of follow-up was 1.1 (0.8-1.3) mg/dL. CONCLUSIONS: Our report implies that ABOiKTx in post-COVID-19 candidates can be successfully performed with no major deviation from standard ABO protocol.


Assuntos
COVID-19 , Transplante de Rim , Humanos , Adulto , Pessoa de Meia-Idade , Transplante de Rim/efeitos adversos , Sistema ABO de Grupos Sanguíneos , Estudos Retrospectivos , Estudos de Coortes , Sobrevivência de Enxerto , Rejeição de Enxerto/epidemiologia , COVID-19/epidemiologia , Incompatibilidade de Grupos Sanguíneos , Rituximab , Resultado do Tratamento , Doadores Vivos
2.
EClinicalMedicine ; 46: 101359, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35350707

RESUMO

Background: There is an enormous knowledge gap on management strategies, clinical outcomes, and follow-up after kidney transplantation (KT) in recipients that have recovered from coronavirus disease (COVID-19). Methods: We conducted a multi-center, retrospective analysis in 23 Indian transplant centres between June 26, 2020 to December 1, 2021 on KT recipients who recovered after COVID-19 infections. We analyzed clinical and biopsy-confirmed acute rejection (AR) incidence and used cox-proportional modeling to estimate multivariate-adjusted hazard ratios (HR) for predictors of AR. We also performed competing risk analysis. Additional outcome measures included graft loss, all-cause mortality, waiting time from a positive real-time polymerase test (RT-PCR) to KT, laboratory parameters, and quality of life in follow-up. Findings: Among 372 KT which included 38(10·21%) ABO-incompatible, 12(3·22%) sensitized, 64(17·20%) coexisting donors with COVID-19 history and 20 (5·37%) recipients with residual radiographic abnormalities, the incidence of AR was 34 (9·1%) with 1(0·26%) death censored graft loss, and 4(1·07%) all-cause mortality over a median (interquartile range) follow-up of 241 (106-350) days. In our cox hazard proportional analysis, absence of oxygen requirement during COVID-19 compared to oxygen need [HR = 0·14(0·03-0·59); p-value = 0·0071], and use of thymoglobulin use compared to other induction strategies [HR = 0·17(0·03-0.95); p-value = 0·044] had a lower risk for AR. Degree of Human leukocyte antigen (HLA) DR mismatch had the highest risk of AR [HR = 10.2(1·74-65·83); p-value = 0·011]. With competing risk analysis, with death as a competing event, HLA DR mismatch, and oxygen requirement continued to be associated with AR. Age, gender, obesity, inflammatory markers, dialysis vintage, steroid use, sensitization and ABO-incompatibility have not been associated with a higher risk of AR. The median duration between COVID-19 real time polymerase test negativity to transplant was 88(40-145) days (overall), and ranged from 88(40-137), 65(42-120), 110(49-190), and 127(64-161) days in World Health Organization ordinal scale ≤ 3, 4, 5, and 6-7, respectively. There was no difference in quality of life, tacrolimus levels, blood counts, and mean serum creatinine assessed in patients with a past COVID-19 infection independent of severity. Interpretation: Our findings support that the outcomes of KT after COVID-19 recovery are excellent with absence of COVID-19 sequelae during follow-up. Additionally, there does not seem to be a need for changes in the induction/immunosuppression regimen based on the severity of COVID-19. Funding: Sanofi.

3.
Asian J Transfus Sci ; 15(1): 62-67, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349459

RESUMO

BACKGROUND AND AIM: Renal transplantation (RT) is the most successful and ideal renal replacement therapy for end-stage renal disease patients. Renal allograft rejection has always been one of the major barriers in successful RT. Our aim was to report the role of therapeutic plasma exchange (TPE) in acute humoral rejection (AHR) patients who underwent live-related RT (LRRT) and their renal allograft outcome at our center. MATERIALS AND METHODS: A prospective observational study was conducted from July 1, 2014, to December 31, 2016. Patients with biopsy-proven AHR and treated with TPE along with other lines of treatment after undergoing LRRT were included in the study. ABO-incompatible individuals, pediatric patients, and patients undergoing second transplants were excluded from the study. Clinical history, donor and graft details, management, and patient and graft survival were noted. RESULTS: Of the 1608 patients who underwent LRRT, 49 (37 males, 76%; 12 females, 24%; mean age 39.5 ± 13.3 years) had biopsy-proven AHR (3.04%) and were treated with TPE. A total of 281 TPEs were performed with an average of 5.7 TPE/patient (range 2-12). Of the 49 patients, 38 patients (78%) with favorable response underwent 213 (75.8%) TPEs (average of 5.6 TPE/patient; range: 2-12), whereas 11 patients (22%) with unfavorable response underwent 68 (24.2%) TPEs (average of 6.2 TPE/patient; range: 3-8). Blood urea (P = 0.012) and serum creatinine (P = 0.038) levels at the time of rejection were significant predictors of response to TPE therapy. The average length of stay in our study population was 33 ± 22 days. Six months posttransplant, the patient and graft survival were 93.3% and 89.5%, whereas at 12 months, they were 89.3% and 81.5%, respectively. CONCLUSION: TPE is a safe and effective adjunct therapy for treating AHR patients.

4.
Transplantation ; 105(7): 1423-1432, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33724246

RESUMO

BACKGROUND: There is limited current knowledge on feasibility and safety of kidney transplantation in coronavirus disease-19 (COVID-19) survivors. METHODS: We present a retrospective cohort study of 75 kidney transplants in patients who recovered from polymerase chain reaction (PCR)-confirmed COVID-19 performed across 22 transplant centers in India from July 3, 2020, to January 31, 2021. We detail demographics, clinical manifestations, immunosuppression regimen, laboratory findings, treatment, and outcomes. Patients with a previous diagnosis of COVID-19 were accepted after documenting 2 negative severe acute respiratory syndrome coronavirus 2 PCR tests, normal chest imaging with complete resolution of symptom for at least 28 d and significant social distancing for 14 d before surgery. RESULTS: Clinical severity in patients ranged from asymptomatic (n = 17, 22.7%), mild (n = 36.48%), moderate (n = 15.20%), and severe (n = 7.9.3%) disease. Median duration between PCR positive to transplant was 60 d (overall) and increased significantly from asymptomatic, mild, moderate, and severe disease (49, 57, 83, 94 d, P 0.019), respectively. All recipients and donors were asymptomatic with normal creatinine after surgery at a median (interquartile range) follow-up of 81 (56-117) d without any complications relating to surgery or COVID-19. Patient and graft survival was 100%, and acute rejection was reported in 6.6%. CONCLUSIONS: Prospective kidney transplant recipients post-COVID-19 can be considered for transplantation after comprehensive donor and recipient screening before surgery using a combination of clinical, radiologic, and laboratory criteria, careful pretransplant evaluation, and individualized risk-benefit analysis. Further large-scale prospective studies with longer follow-up will better clarify our initial findings. To date, this remains the first and the largest study of kidney transplantation in COVID-19 survivors.


Assuntos
COVID-19/complicações , Falência Renal Crônica/cirurgia , Transplante de Rim , Adulto , Idoso , COVID-19/diagnóstico , Seleção do Doador/métodos , Feminino , Seguimentos , Humanos , Índia , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Sobreviventes , Resultado do Tratamento
5.
Transplantation ; 105(4): 842-850, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33394992

RESUMO

BACKGROUND: There is lack of data on feasibility and safety of kidney transplants from living donors who recovered from COVID-19. METHODS: Here, we present a retrospective cohort study of 31 kidney transplant recipients (KTR) from living donors who recovered from polymerase chain reaction confirmed COVID-19 across 19 transplant centers in India from July 3, 2020, to December 5, 2020. We detailed demographics, clinical manifestations, immunosuppression regimen, treatment, and outcomes. Donors with a previous diagnosis of COVID-19 were accepted after documenting 2 negative polymerase chain reaction tests with complete symptom resolution for at least 28 days and significant social distancing for 14 days before surgery. RESULTS: COVID-19 clinical severity in donors ranged from completely asymptomatic (71%, n = 22) to mild infection (29%, n = 9). None progressed to moderate or severe stages of the disease in the entire clinical course of home treatment. Patient and graft survival was 100%, respectively, with acute cellular rejection being reported in 6.4% (n = 2) recipient. All recipients and donors were asymptomatic with normal creatinine at median follow-up of 44 days after surgery without any complications relating to surgery and COVID-19. CONCLUSIONS: Our data support safety of proceeding with living donation for asymptomatic individuals with comprehensive donor, recipients screening before surgery, using a combination of clinical, radiologic, and laboratory criteria. It could provide new insights into the management of KTR from living donors who have recovered from COVID-19 in India. To the best of our knowledge, this remains the largest cohort of KTR from living donors who recovered from COVID-19.


Assuntos
COVID-19/transmissão , Transplante de Rim/efeitos adversos , SARS-CoV-2 , Obtenção de Tecidos e Órgãos , Adolescente , Adulto , Idoso , COVID-19/diagnóstico , COVID-19/epidemiologia , Teste para COVID-19 , Criança , Estudos de Coortes , Transmissão de Doença Infecciosa , Feminino , Humanos , Índia/epidemiologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Fatores de Risco , Segurança , Transplantados , Adulto Jovem
6.
Clin Transplant ; 30(3): 328-34, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26780835

RESUMO

OBJECTIVE: Laparoscopic donor nephrectomy (LDN) is generally considered a better option than open donor nephrectomy (ODN) as it is associated with better cosmesis, less post-operative pain and faster recovery. Mini-incision donor nephrectomy (MDN) has proven to be an effective and less invasive modification of classic ODN. Our aim was to compare the peri-operative outcomes and quality of life of donors following laparoscopic and mini-incision ODN. METHODS: One hundred patients, underwent donor nephrectomy using laparoscopic approach (n = 50) or open mini-incision approach (n = 50) over a period of 18 months. Data were entered into a prospective database and analyzed retrospectively. RESULTS: The mean operative (skin to skin) time for MDN, 53.9 min (range, 40-75 min), was significantly shorter than the 93.7 min (range, 75-140 min) for LDN. The laparoscopic donors had a longer hospital stay, warm ischemia time and higher operative and post-operative cost. There was no significant difference in the pain scores, graft function, or quality of life between the two groups. CONCLUSIONS: MDN compares well with the laparoscopic approach in terms of post-operative pain, graft function and quality of life of donors. Significantly less operative time along with the reduced cost makes it a better option in our predominantly lower BMI patient population.


Assuntos
Transplante de Rim , Laparoscopia/métodos , Doadores Vivos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Nefrectomia/métodos , Qualidade de Vida , Adulto , Idoso , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Adulto Jovem
7.
Int Urol Nephrol ; 47(7): 1123-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25987343

RESUMO

PURPOSE: Live related renal donors with urolithiasis are made suitable for renal transplantation in two-stage procedure in most of the centers: first making the donor kidney stone free surgically or by ESWL and then proceeding to renal transplantation. To reduce the cost and morbidity of two surgical procedures in donors, we did a pilot study of removing subcentimeter renal calculi in live donors, after explanting the kidney, during bench surgery. MATERIALS AND METHODS: We included all prospective renal donors with subcentimeter (4-10 mm) calculi in one kidney in our study (n = 14). All these patients underwent standard donor evaluation and metabolic work up. After the donor nephrectomy, bench retrograde intra-renal surgery (RIRS) with or without pyelotomy was done for stone clearance followed by renal transplantation. RESULTS: Stone clearance was achieved in 13 out of 14 donors. Donors and recipients were followed for 6-24 months. No stone recurrence or graft dysfunction was seen in the follow-up period. CONCLUSION: We concluded that bench RIRS is an excellent modality in the management of small renal calculi in prospective renal donors who are not having metabolically active disease. This reduced the cost and morbidity to the donor and minimized waiting time for transplant.


Assuntos
Cálculos Renais , Transplante de Rim , Nefrectomia , Coleta de Tecidos e Órgãos/métodos , Transplantes/cirurgia , Ureteroscopia/métodos , Adulto , Feminino , Humanos , Rim/patologia , Rim/fisiopatologia , Cálculos Renais/diagnóstico , Cálculos Renais/cirurgia , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto , Estudos Prospectivos , Fatores de Tempo
8.
Saudi J Kidney Dis Transpl ; 25(2): 367-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24626005

RESUMO

The external iliac vein is commonly used in renal transplantation for vascular anastomosis of the allograft renal vein. However, there are rare instances when the transplant surgeon may encounter thrombosis of the ilio-caval vein during surgery, making renal transplantation a challenge. Often, these patients are considered unsuitable for renal transplantation. We report a case of thrombosis of the inferior vena cava in an asymptomatic pediatric patient in whom the splenic vein was used, at transplantation, for venous drainage. This case highlights that pre-operative Doppler screening should be performed in all potential renal transplant recipients.


Assuntos
Transplante de Rim/métodos , Síndrome Nefrótica/complicações , Veia Cava Inferior , Trombose Venosa/etiologia , Anastomose Cirúrgica , Doenças Assintomáticas , Criança , Humanos , Veia Ilíaca , Achados Incidentais , Falência Renal Crônica/etiologia , Falência Renal Crônica/cirurgia , Masculino , Veia Esplênica/cirurgia , Trombose Venosa/diagnóstico
9.
Indian J Surg ; 75(Suppl 1): 313-5, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24426602

RESUMO

Primary juxtrarenal leiomyosarcoma of the inferior vena cava (IVC) is a rare disease and is invariably malignant. Prognosis depends on early patient diagnosis and management. We report a case of a primary IVC tumor in a 66-year-old woman which was managed successfully by surgical resection of involved IVC along with right nephrectomy. IVC reconstruction was done using a Dacron interposition graft, and the left renal vein was anastomosed end to side to the Dacron graft.

10.
Indian J Tuberc ; 59(1): 32-5, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22670509

RESUMO

A rare case of port site tubercular infection is reported. A young male patient presented, one month after laparoscopic inguinal hernia repair with discharging sinuses at the port sites. Biopsy of the sinus tract showed features of tuberculosis. Excision of sinus tract was done and the patient was started on anti-tubercular therapy, sinuses healed. Probably, the source of tubercular infection was laparoscopic instruments. Proper sterilization of laparoscopic instruments is necessary.


Assuntos
Hérnia Inguinal/cirurgia , Laparoscopia , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/terapia , Tuberculose/diagnóstico , Tuberculose/terapia , Adulto , Antituberculosos/uso terapêutico , Biópsia , Terapia Combinada , Quimioterapia Combinada , Contaminação de Equipamentos , Humanos , Masculino
11.
Saudi J Kidney Dis Transpl ; 23(3): 577-80, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22569449

RESUMO

Kidney donation from hypertensive donors is now an accepted norm in live related kidney transplantation. The use of hypertensive donors with renal artery stenosis due to atherosclerosis and fibromuscular dysplasia is still debated. The prime concern is about the deleterious effect of hypertension on the donor and the risk of recurrence of such lesions in the solitary kidney. Even as the response of atherosclerotic renal artery stenosis to revascularisation is unpredictable, there is an improvement in blood pressure following revascularisation of kidneys with fibro-muscular dysplasia. The first use of such kidney donors was reported in 1984 and, since then, there have been a few reports of successful use of kidneys from donors with renal artery stenosis. We report here two interesting cases of successful transplantation of kidneys from live related kidney donors with hypertension due to renal artery stenosis who became normotensive with good graft function in the recipient. We conclude that moderately hypertensive donors with renal artery stenosis are fit to donate.


Assuntos
Seleção do Doador , Hipertensão Renovascular/diagnóstico , Transplante de Rim , Doadores Vivos , Nefrectomia , Obstrução da Artéria Renal/diagnóstico , Idoso , Angiografia Digital , Anti-Hipertensivos/uso terapêutico , Feminino , Humanos , Hipertensão Renovascular/diagnóstico por imagem , Hipertensão Renovascular/tratamento farmacológico , Hipertensão Renovascular/etiologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Obstrução da Artéria Renal/complicações , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/tratamento farmacológico , Resultado do Tratamento
12.
Am J Clin Pathol ; 137(5): 816-24, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22523222

RESUMO

Acute rejection in renal transplant recipients is diagnosed by renal biopsy at an advanced disease stage. There is no modality for sequential monitoring of graft status. We studied the role of urine cytology in predicting acute cellular rejection (ACR) and its ability to correctly diagnose ACR and differentiate it from drug toxicity (DT). Urine samples from 203 renal transplant recipients were studied to determine the cellular composition using cytology and immunocytochemistry for HLA-DR, intercellular adhesion molecule (ICAM)-1, and interleukin (IL)-2R. In a 3-month follow-up period, there were 36 episodes of graft dysfunction, of which 28 occurred due to ACR and 8 due to DT. The cytology results showed a significantly increased percentage of lymphocytes and polymorphonuclear cells in samples obtained before and during the clinical manifestations of ACR. A greater level of expression of antigens was observed before and during ACR. The use of IL2-R-, ICAM-1-, and HLA class II-specific monoclonal antibodies gave very high specificity, sensitivity, and positive predictive values in diagnosing rejection through urine cytology, suggesting that routine cytology along with immunocytochemistry of urine sediment has clinical potential for early diagnosis and management of ACR and DT.


Assuntos
Rejeição de Enxerto/diagnóstico , Transplante de Rim/patologia , Rim/patologia , Urinálise/métodos , Adolescente , Adulto , Idoso , Criança , Diagnóstico Precoce , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/urina , Humanos , Rim/imunologia , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
13.
Indian J Tuberc ; 58(3): 120-4, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21941951

RESUMO

A 24-year-old male patient presented with abdominal pain, obstructive jaundice, anorexia and weight loss. Ultrasound abdomen revealed pancreatic head mass with dilated common hepatic duct and intrahepatic bliliary radicles. CECT abdomen was suggestive of pancreatic head mass invading portal vein, splenic artery and hepatic artery. Provisional diagnosis of unresectable carcinoma head of pancreas was established. Endoscopic ultrasound (EUS) was done, which was also suggestive of pancreatic head mass infiltrating portal vein. EUS guided Fine Needle Aspiration Cytology (FNAC) was taken with an intent to obtain tissue diagnosis and to start palliative chemotherapy. EUS guided FNAC features were suggestive of tuberculosis (TB). Patient was started on anti-tubercular therapy, to which he responded and was cured. Pancreatic tuberculosis should be considered as a possibility, in pancreatic mass, especially in countries where TB is endemic and establishing its diagnosis with the aid of FNAC can save trauma of major surgery to the patient, which prompted us to report this case.


Assuntos
Biópsia por Agulha Fina/métodos , Endossonografia , Pancreatopatias/diagnóstico , Tuberculose/diagnóstico , Dilatação Patológica , Veias Hepáticas/patologia , Humanos , Masculino , Pancreatopatias/microbiologia , Veia Porta/patologia , Tuberculose/tratamento farmacológico , Tuberculose/patologia , Adulto Jovem
15.
Surg Endosc ; 25(5): 1431-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20976495

RESUMO

INTRODUCTION: After the first report of laparoscopic incisional and ventral hernia repair (LIVHR) in 1993, several studies have proven its efficacy over open method. Among the technical issues, the technique of mesh fixation to the abdominal wall is still an area of debate. This prospective randomized study was done to compare two techniques of mesh fixation, i.e., tacker with four corner transfascial sutures versus transfascial sutures alone. MATERIALS AND METHODS: 68 patients admitted for LIVHR repair (defect size less than 25 cm2) were randomized in two groups: group I, tacker fixation (36 patients) and group II, suture fixation (32 patients). Various intraoperative variables and postoperative outcomes were recorded and analyzed. RESULTS: The patients in the two groups were well matched in terms of age, sex, body mass index (BMI), and hernia characteristics. Mean BMI was 29.0 kg/m2. Operative time was found to be significantly higher in group II (77.5 versus 52.6 min, p=0.000). Patients in group I were found to have significantly higher pain scores at 1 h, 6 h, 24 h, 1 week, 1 month, and 3 months postoperatively. At follow-up, incidence of seromas was higher in group II but the difference was not significant (7 versus 4, p=0.219). During long-term follow-up, patients in group II were satisfied cosmetically. CONCLUSION: Suture fixation is a cost-effective alternative to tacker fixation, for small and medium-sized defects in anatomically accessible areas. However, suture fixation requires significantly longer operation time, but patients have statistically significantly less postoperative pain.


Assuntos
Hérnia Ventral/cirurgia , Laparoscopia , Telas Cirúrgicas , Técnicas de Sutura , Adulto , Idoso , Feminino , Hérnia Ventral/economia , Hérnia Ventral/patologia , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Medição da Dor , Polipropilenos , Politetrafluoretileno , Recidiva , Seroma/etiologia , Telas Cirúrgicas/economia , Infecção da Ferida Cirúrgica , Adulto Jovem
16.
Indian J Pathol Microbiol ; 53(4): 651-7, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21045386

RESUMO

BACKGROUND: Calcineurin inhibitors (cyclosporine and tacrolimus) are important constituents of post renal transplant immunosuppression. However, renal toxicity limits their utility. Histological features of calcineurin inhibitor toxicity (CNIT) have been the subject of few studies using protocol biopsy samples, and consensus on diagnostic criteria is still evolving. AIMS: To analyze the spectrum of histological changes in protocol renal allograft biopsies with evidence of CNIT and identify additional features that are likely to help the pathologist in arriving at a diagnosis. MATERIALS AND METHODS: One hundred and forty protocol allograft biopsies performed at 1, 6 and 12 months post renal transplant were studied. The defining features of CNIT included: isometric vacuolization of proximal tubular cells, arteriolar hyalinosis with medial/peripheral nodules and striped pattern of tubular atrophy/interstitial fibrosis. Other features such as global glomerulosclerosis, vacuolization of smooth muscle cells of arterioles, tubular microcalcinosis, ischemic shrinkage of glomeruli and hyperplasia of juxtaglomerular apparatus (JGA) were also analyzed and graded semiquantitatively. RESULTS: CNIT was seen in 17/140 protocol biopsies (12.1%). In addition to the diagnostic criteria, arteriolar hyalinosis, smooth muscle cell vacuolization of arterioles and hyperplasia of JGA were found to be useful indicators of CNIT. CONCLUSIONS: There is a relatively high incidence of CNIT in protocol allograft biopsies. A critical analysis of renal biopsy in adequate number of serial step sections to identify these features is mandatory, as many of these features are subtle and are likely to be missed if not specifically sought.


Assuntos
Inibidores de Calcineurina , Ciclosporina/efeitos adversos , Imunossupressores/efeitos adversos , Nefropatias/induzido quimicamente , Transplante de Rim , Tacrolimo/efeitos adversos , Transplante Homólogo , Adulto , Biópsia , Ciclosporina/uso terapêutico , Feminino , Seguimentos , Histocitoquímica , Humanos , Imunossupressores/uso terapêutico , Incidência , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Tacrolimo/uso terapêutico
17.
Pediatr Transplant ; 14(7): 836-43, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20946517

RESUMO

We report our experience and long-term outcome of pediatric renal transplantation at a referral center in New Delhi. During 1995-2008, 45 transplants were performed in 43 patients at a mean age of 13.3 ± 4.0 (range 3.8-18) yr. The chief causes for ESRD were reflux nephropathy, obstructive uropathy, vasculitis, renal dysplasia, and focal segmental glomerulosclerosis. Most (91.1%) donors were living related. Post-transplant immunosuppression comprised prednisolone, a calcineurin inhibitor and azathioprine or MMF. AR and CR were seen in 14 (31.1%) and 12 (26.7%) allografts, respectively. Predictors of CR were unsatisfactory compliance and multiple episodes of AR (p = 0.002 each). Urinary infections (n = 13), septicemia (4), tuberculosis (4), CMV disease (7), viral hepatitis (7), and pneumonia (3) were important causes of morbidity. Two patients each had lymphoproliferative disease and new-onset diabetes. There were eight (17.8%) graft losses and six (14%) deaths. The one-, five- and 10-yr graft survivals were 91.1%, 80.4% and 75.1%, respectively; the mean graft survival was 119.4 ± 8.38 months. The respective patient survivals were 95.3%, 87.9%, and 76.9% at one-, five- and 10 yr. Our results affirm that despite scarcity of resources and frequent infections, long-term outcomes of pediatric renal transplantation are highly satisfactory.


Assuntos
Transplante de Rim/métodos , Pediatria/métodos , Insuficiência Renal/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Índia , Doadores Vivos , Masculino , Resultado do Tratamento
18.
Exp Clin Transplant ; 8(2): 161-71, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20565374

RESUMO

OBJECTIVES: In this study, we assessed the immunosuppressive potential of curcumin, a pharmacologically safe and cost-effective naturally occurring polyphenolic phytochemical, on the induction of Th1 cytokines that are frequently overexpressed in patients experiencing rejection after renal transplant. MATERIALS AND METHODS: Peripheral blood lymphocytes obtained from 68 renal transplant recipients and 17 healthy controls were treated with curcumin before stimulation with phorbol myristate acetate and were analyzed with flow cytometry for interferon-alpha and interleukin 4 positive cells. RESULTS: Patients experiencing acute rejection exhibited a high level of interferon-alpha (38.3% +/- 11.2%) and a low level of interleukin 4 (4.2% +/- 2.0%) in their activated peripheral blood lymphocytes. The use of curcumin dose-dependently decreased interferon-alpha induction in cultures from healthy controls (28.1% +/- 4.8%-10.7% +/- 5.3%, P < .001), patients experiencing acute rejection (38.3%-18.3%, P < .001), and those experiencing chronic rejection (40.6%-12.9%, P = .01) when compared with corresponding untreated cultures. In contrast, curcumin exerted only a marginal effect on interleukin 4 expression. Interestingly, curcumin was found to inhibit nuclear factor kappa beta activation by blocking the degradation of the inhibitory unit I kappa B alpha. We also noted the synergistic inhibitory effect of in vitro treatment with curcumin in combination with cyclosporine on the peripheral blood lymphocytes of patients experiencing acute rejection. CONCLUSIONS: These data provide a rationale for the use of curcumin as an affordable, pharmacologically safe, adjuvant immunosuppressant when used with cyclosporine and suggest that curcumin can effectively suppress Th1 cytokine induction after renal transplant.


Assuntos
Curcumina/farmacologia , Rejeição de Enxerto/prevenção & controle , Imunossupressores/farmacologia , Transplante de Rim , Doadores Vivos , Linfócitos/efeitos dos fármacos , Doença Aguda , Adulto , Estudos de Casos e Controles , Células Cultivadas , Doença Crônica , Curcumina/uso terapêutico , Ciclosporina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Citometria de Fluxo , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/uso terapêutico , Índia , Interferon gama/metabolismo , Interleucina-4/metabolismo , Transplante de Rim/efeitos adversos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Mitógenos/farmacologia , NF-kappa B/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Fatores de Tempo , Adulto Jovem
19.
Transpl Int ; 23(4): 407-16, 2010 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-19912591

RESUMO

Calcineurin inhibitors (cyclosporine and tacrolimus; CNIs) continue to be used as constituents of post-transplant immunosuppression in most centers. However, renal toxicity associated with the use of these drugs remains a problem adversely affecting the long-term graft survival. Fifteen adequate protocol renal allograft biopsies, with histological features of CNI toxicity among 140 protocol biopsies performed at 1-, 6-, and 12-month post-transplant, were included. Mitochondrial alterations in the tubular epithelial cells and endothelia of glomerular, peritubular capillaries and arterioles were graded semiquantitatively and further ultrastructural morphometric evaluation of numerical density and area of the mitochondria was performed. Immunohistochemical staining for nitrotyrosine (marker of peroxynitrite formation) and vascular endothelial growth factor (VEGF) was performed and expression graded semiquantitatively. Higher grades of alterations were seen in endothelial mitochondria as compared with tubular mitochondria in biopsies with calcineurin inhibitor toxicity (CNIT). Endothelial mitochondrial numerical density showed progressive decline over 1-, 6- and 12-month biopsies while area showed progressive increase in biopsies with CNIT as compared with controls. Upregulation of nitrotyrosine was seen even at 1-month post-transplant, persisted at 6 and 12 months, and was significantly greater than that in control biopsies. Intense VEGF expression was noted in early CNIT while progressive reduction was seen in 6- and 12-month protocol biopsies. This study shows a relatively high incidence of CNIT in protocol renal allograft biopsies, indicating that this might be an important mechanism of background damage to the allograft. Structural alterations in endothelial mitochondria are consistent findings in protocol biopsies with CNIT and this relatively specific mitochondrial damage may stem from the peroxynitrite-mediated damage associated with progressive loss of protective function of VEGF.


Assuntos
Inibidores de Calcineurina , Ciclosporina/antagonistas & inibidores , Endotélio Vascular/metabolismo , Transplante de Rim/métodos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Tacrolimo/antagonistas & inibidores , Tirosina/análogos & derivados , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Biópsia , Ciclosporina/toxicidade , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Tacrolimo/toxicidade , Transplante Homólogo , Tirosina/química , Fator A de Crescimento do Endotélio Vascular/biossíntese
20.
JSLS ; 12(3): 252-5, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18765047

RESUMO

BACKGROUND: Newer, energy-based devices like the ultrasonic coagulator (Harmonic Scalpel, Ethicon Endo-Surgery, Inc., Cincinnati, OH) and the LigaSure vessel-sealing system (Valleylab, Boulder, CO) are increasingly being used in advanced laparoscopic procedures. Use of these devices has resulted in shorter operative time, less blood loss, and lower conversion rates. We present our experience with these devices for laparoscopic removal of adrenal and extra-adrenal tumors. METHODS: Ten patients with adrenal tumors and 4 with extra-adrenal tumors were operated on laparoscopically with the ultrasonic shears and LigaSure vessel-sealing system. The entire surgery was carried out using these energy-based devices without using any clips or sutures. RESULTS: No conversions were necessary. None of the patients experienced any major intraoperative or postoperative bleeding. The mean size of the tumor was 6.2 cm (range, 3 to 8). The mean operative time was 123 minutes (range, 80 to 210), and the mean blood loss was 70 mL (range, 10 to 150). Histopathology revealed pheochromocytomas in 7 patients. CONCLUSIONS: Use of the LigaSure vessel-sealing device along with ultrasonic shears for laparoscopic removal of adrenal and extra-adrenal tumors is safe and effective.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Laparoscopia/métodos , Feocromocitoma/cirurgia , Adolescente , Adrenalectomia/métodos , Adulto , Criança , Feminino , Humanos , Ligadura/instrumentação , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Terapia por Ultrassom/instrumentação
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