RESUMO
Improving long-term renal allograft survival remains an important unmet need. To assess the extent of histologic injury at 10 years after transplantation in functioning grafts, we studied 575 consecutive adult solitary renal transplants performed between 2002 and 2005: 77% from living donors and 81% maintained on tacrolimus-based immunosuppression. Ten-year graft survival was 59% and death-censored graft survival was 74%. Surveillance allograft biopsies were assessed at implantation, 5 years, and 10 years from 145 patients who reached 10 years. At implantation, 5% of biopsies had major histologic abnormalities (chronic transplant glomerulopathy score > 0, other chronic Banff scores ≥ 2, global glomerulosclerosis > 20%, or mesangial sclerosis ≥ 2). This increased to 54% at 5 years and 82% at 10 years. Major lesions at 10 years included the following: arteriolar hyalinosis (66%), mesangial sclerosis (67%), and global glomerulosclerosis > 20% (43%), with 48% of grafts having more than one major lesion. Transplant glomerulopathy and moderate-to-severe interstitial fibrosis were uncommon (12% each). Major lesions were associated with increased proteinuria and decreased graft function. In patients with diabetes at baseline, 52% had diabetic nephropathy/mesangial sclerosis at 10 years. We conclude that almost all renal allografts sustain major histologic injury by 10 years after transplantation. Much damage appears nonimmunologic, suggesting that new approaches are needed to decrease late injury.
Assuntos
Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Nefropatias/patologia , Transplante de Rim/efeitos adversos , Tacrolimo/uso terapêutico , Adulto , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Humanos , Imunossupressores/uso terapêutico , Nefropatias/classificação , Nefropatias/cirurgia , Testes de Função Renal , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Fatores de Risco , Transplante HomólogoRESUMO
Allograft histology 1 year posttransplant is an independent correlate to long-term death-censored graft survival. We assessed prognostic implications of changes in histology first 2 years posttransplant in 938 first kidney recipients, transplanted 1999-2010, followed for 93.4 ± 37.7 months. Compared to implantation biopsies, histology changed posttransplant showing at 1 year that 72.6% of grafts had minor abnormalities (favorable histology), 20.2% unfavorable histology, and 7.2% glomerulonephritis. Compared to favorable, graft survival was reduced in recipients with unfavorable histology (hazards ratio [HR] = 4.79 [3.27-7.00], p < 0.0001) or glomerulonephritis (HR = 5.91 [3.17-11.0], p < 0.0001). Compared to unfavorable, in grafts with favorable histology, failure was most commonly due to death (42% vs. 70%, p < 0.0001) and less commonly due to alloimmune causes (27% vs. 10%, p < 0.0001). In 80% of cases, favorable histology persisted at 2 years. However, de novo 2-year unfavorable histology (15.3%) or glomerulonephritis (4.7%) related to reduced survival. The proportion of favorable grafts increased during this period (odds ratio = 0.920 [0.871-0.972], p = 0.003, per year) related to fewer DGF, rejections, polyoma-associated nephropathy (PVAN), and better function. Graft survival also improved (HR = 0.718 [0.550-0.937], p = 0.015) related to better histology and function. Evolution of graft histologic early posttransplant relate to long-term survival. Avoiding risk factors associated with unfavorable histology relates to improved histology and graft survival.
Assuntos
Aloenxertos/patologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Falência Renal Crônica/fisiopatologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias , Biópsia , Estudos de Coortes , Feminino , Rejeição de Enxerto/etiologia , Humanos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de TempoRESUMO
Determination of the IgG subtypes within the immune deposits in membranous nephropathy (MN) may be helpful in the differential diagnosis. IgG4 is the predominant subtype in idiopathic MN and recurrent MN, while IgG1, IgG2, and IgG3 subtypes are more common in secondary MN and de novo disease in the allograft. The temporal change of IgG subclasses in individual patients and its correlation with clinical variables have not been studied. We reviewed all posttransplantation protocol and indication biopsies (49) in 18 patients with recurrent MN who underwent transplantation at our center between 1998 and 2013 and performed IgG subtyping (IgG1-4). We tested serum for M-type phospholipase A2 receptor (PLA2 R) autoantibodies or performed PLA2 R antigen staining on the kidney biopsy. IgG4 was the (co)dominant IgG subtype in 10 of 14 biopsies at the diagnosis of recurrence regardless of PLA2 R association. In 8 of 12 transplantations with serial biopsies, the (co)dominant subtype did not change over time. There was a trend toward IgG1 and IgG3 (co)dominance in biopsies >1 year from recurrence and more IgG1 (co)dominant subtyping in the setting of more-advanced EM deposits. Treatment with rituximab did not affect the IgG subtype. In conclusion, the dominant IgG subtype did not change over time in recurrent MN.
Assuntos
Glomerulonefrite Membranosa/imunologia , Imunoglobulina G/imunologia , Adulto , Idoso , Autoanticorpos/imunologia , Feminino , Humanos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Recidiva , Transplante HomólogoRESUMO
About 70% of patients with primary membranous nephropathy (MN) have circulating anti-phospholipase A2 receptor (PLA2R) antibodies that correlate with disease activity, but their predictive value in post-transplant (Tx) recurrent MN is uncertain. We evaluated 26 patients, 18 with recurrent MN and 8 without recurrence, with serial post-Tx serum samples and renal biopsies to determine if patients with pre-Tx anti-PLA2R are at increased risk of recurrence as compared to seronegative patients and to determine if post-Tx changes in anti-PLA2R correspond to the clinical course. In the recurrent group, 10/17 patients had anti-PLA2R at the time of Tx versus 2/7 patients in the nonrecurrent group. The positive predictive value of pre-Tx anti-PLA2R for recurrence was 83%, while the negative predictive value was 42%. Persistence or reappearance of post-Tx anti-PLA2R was associated with increasing proteinuria and resistant disease in 6/18 cases; little or no proteinuria occurred in cases with pre-Tx anti-PLA2R and biopsy evidence of recurrence in which the antibodies resolved with standard immunosuppression. Some cases with positive pre-Tx anti-PLA2R were seronegative at the time of recurrence. In conclusion, patients with positive pre-Tx anti-PLA2R should be monitored closely for recurrent MN. Persistence or reappearance of antibody post-Tx may indicate a more resistant disease.
Assuntos
Glomerulonefrite Membranosa/imunologia , Falência Renal Crônica/cirurgia , Receptores da Fosfolipase A2/química , Receptores da Fosfolipase A2/imunologia , Adulto , Idoso , Biópsia , Feminino , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteinúria/imunologia , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Death with function (DWF) is a major cause of kidney allograft failure. Allograft dysfunction may contribute to DWF. The aim of this study was to examine the relationship between DWF and allograft function using estimated GFR (eGFR) and histology. We retrospectively analyzed 1842 kidney allografts transplanted at our center from 1996 to 2010. eGFR was estimated using the MDRD equation. Biopsies obtained 12 months posttransplant and within 1 year of DWF were analyzed. Proportional hazards models were used to examine the relationship between eGFR and DWF. During 68 ± 43 months of follow-up, 14% (n = 256) of recipients experienced DWF. Risk factors of DWF included increasing recipient age (hazard ratio [HR] = 2.07, confidence interval [CI] 1.77-2.43, p < 0.0001), diabetes (HR = 2.58, CI 1.81-3.69, p < 0.0001), prior dialysis (HR = 1.47, CI 1.05-2.06, p = 0.03) and eGFR <40 mL/min/1.73 m(2) (HR 2.26 per 10 mL/min/1.73 m(2) decrease in eGFR, CI 1.82-2.81, p < 0.0001). Prior to death, only 15.9% (n = 39) of DWF recipients had stage 4 chronic kidney disease (CKD) and only 4.9% (n = 12) had stage 5 CKD. Most biopsies performed within 1 year of DWF (68%) demonstrated benign histology and were comparable to biopsies from matched controls. In conclusion, allograft dysfunction is independently associated with DWF. However, the majority of DWF recipients have well-preserved allograft function and histology prior to death.
Assuntos
Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/fisiopatologia , Sobrevivência de Enxerto , Falência Renal Crônica/cirurgia , Transplante de Rim , Complicações Pós-Operatórias/mortalidade , Adulto , Aloenxertos , Feminino , Seguimentos , Taxa de Filtração Glomerular , Sobrevivência de Enxerto/fisiologia , Humanos , Falência Renal Crônica/fisiopatologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
Kidney allografts are frequently lost due to alloimmunity. Still, the impact of early acute rejection (AR) on long-term graft survival is debated. We examined this relationship focusing on graft histology post-AR and assessing specific causes of graft loss. Included are 797 recipients without anti-donor antibodies (DSA) at transplant who had 1 year protocol biopsies. 15.2% of recipients had AR diagnosed by protocol or clinical biopsies. Compared to no-AR, all histologic types of AR led to abnormal histology in 1 and 2 years protocol biopsies, including more fibrosis + inflammation (6.3% vs. 21.9%), moderate/severe fibrosis (7.7% vs. 13.5%) and transplant glomerulopathy (1.4% vs. 8.3%, all p < 0.0001). AR were associated with reduced graft survival (HR = 3.07 (1.92-4.94), p < 0.0001). However, only those AR episodes followed by abnormal histology led to reduced graft survival. Early AR related to more late alloimmune-mediated graft losses, particularly transplant glomerulopathy (31% of losses). Related to this outcome, recipients with AR were more likely to have new DSA class II 1 year posttransplant (no-AR, 11.1%; AR, 21.2%, p = 0.039). In DSA negative recipients, early AR often leads to persistent graft inflammation and increases the risk of new DSA II production. Both of these post-AR events are associated with increased risk of graft loss.
Assuntos
Aloenxertos , Biópsia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Transplante de Rim/efeitos adversos , Adulto , Idoso , Aloenxertos/patologia , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Humanos , Rim/imunologia , Rim/patologia , Rim/fisiologia , Nefropatias , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Doadores de TecidosRESUMO
Increased urinary protein excretion is common after renal transplantation and portends worse outcome. In this study we assessed the prognostic contribution of several urinary proteins. Urinary total protein, albumin, retinol binding protein (RBP), α-1-microglobulin, IgG and IgM were measured in banked urine samples from 221 individuals 1 year after renal transplantation (age 52 ± 13 years, 55% male, 93% Caucasian and 82% living donor). Levels of all proteins measured were higher than in normal nontransplant populations. Patients with glomerular lesions had higher urinary albumin than those with normal histology, while those with interstitial fibrosis and tubular atrophy plus inflammation (ci>0, cg = 0, i>0) had higher levels of IgG, IgM, α-1-microglobulin and RBP. Concomitant normal levels of urinary albumin, IgM and RBP identified normal histology (specificity 91%, sensitivity 15%,). Urinary levels of the specific proteins were highly correlated, could not differentiate among the histologic groups, and appeared to result from tubulointerstitial damage. Increased urinary excretion of the low molecular weight protein RBP was a sensitive marker of allografts at risk, predicting long-term graft loss independent of histology and urinary albumin. This study highlights the prognostic importance of tubulointerstitial disease for long-term graft loss.
Assuntos
Biomarcadores/urina , Rejeição de Enxerto/diagnóstico , Sobrevivência de Enxerto/fisiologia , Nefropatias/urina , Transplante de Rim , Adulto , Albuminúria , alfa-Globulinas/urina , Creatinina/urina , Feminino , Rejeição de Enxerto/urina , Humanos , Imunoglobulina G/urina , Imunoglobulina M/urina , Nefropatias/patologia , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Peso Molecular , Prognóstico , Proteinúria , Proteínas Celulares de Ligação ao Retinol/urina , Microglobulina beta-2/urinaRESUMO
Pretransplant cardiac troponin T(cTnT(pre) ) is a significant predictor of survival postkidney transplantation. We assessed correlates of cTnT levels pre- and posttransplantation and their relationship with recipient survival. A total of 1206 adult recipients of kidney grafts between 2000 and 2010 were included. Pretransplant cTnT was elevated (≥0.01 ng/mL) in 56.4%. Higher cTnT(pre) was associated with increased risk of posttransplant death/cardiac events independent of cardiovascular risk factors. Elevated cTnT(pre) declined rapidly posttransplant and was normal in 75% of recipients at 3 weeks and 88.6% at 1 year. Elevated posttransplant cTnT was associated with reduced patient survival (cTnT(3wks) : HR = 5.575, CI 3.207-9.692, p < 0.0001; cTnT(1year) : 3.664, 2.129-6.305, p < 0.0001) independent of age, diabetes, pretransplant dialysis, heart disease and allograft function. Negative/positive predictive values for high cTnT(3wks) were 91.4%/50% respectively. Normalization of cTnT posttransplant was associated with reduced risk. Variables related to elevated cTnT posttransplant included pretransplant diabetes, older age, time on dialysis, high cTnT(pre) and lower graft function. Patients with delayed graft function and those with GFR < 30 mL/min at 3 weeks were more likely to have an elevated cTnT(3wks) and remained at high risk. When allografts restore sufficient kidney function cTnT normalizes and patient survival improves. Lack of normalization of cTnT posttransplant identifies a group of individuals with high risk of death/cardiac events.
Assuntos
Doenças Cardiovasculares/diagnóstico , Transplante de Rim/métodos , Miocárdio/metabolismo , Troponina T/metabolismo , Adulto , Doenças Cardiovasculares/metabolismo , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
The effect of acute allograft rejection (AR) on long-term pancreas allograft function is unclear. We retrospectively studied 227 consecutive pancreas transplants performed at our institution between January 1, 998 and December 31, 2009 including: 56 simultaneous pancreas and kidney (SPK), 69 pancreas transplantation alone (PTA); and 102 pancreas after kidney (PAK) transplants. With a median follow-up of 6.1 (IQR 3-9) years, 57 patients developed 79 episodes of AR, and 19 experienced more than one episode. The cumulative incidence for AR was 14.7%, 19.7%, 26.6% and 29.1% at 1, 2, 5 and 10 years. PTA transplant (hazards ratio [HR]=2.28, p=0.001) and donor age (per 10 years) (HR=1.34, p=0.006) were associated with higher risk for AR. The first AR episode after 3 months post PT was associated with increased risk for complete loss (CL) (HR 3.79, p<0.001), and the first AR episode occurring during 3- to 12-month and 12- to 24-month periods after PT were associated with significantly increased risk for at least partial loss (PL) (HR 2.84, p=0.014; and HR 6.25, p<0.001, respectively). We conclude that AR is associated with increased risk for CL and at least PL. The time that the first AR is observed may influence subsequent graft failure.
Assuntos
Rejeição de Enxerto , Transplante de Pâncreas/métodos , Doença Aguda , Adolescente , Adulto , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Nefropatias/mortalidade , Nefropatias/terapia , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Pancreatopatias/mortalidade , Pancreatopatias/terapia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Transplante Homólogo , Adulto JovemRESUMO
Postkidney transplant hyperparathyroidism is a significant problem. Vitamin D receptor agonists are known to suppress parathyroid hormone (PTH) secretion. We examined the effect of oral paricalcitol on posttransplant secondary hyperparathyroidism by conducting an open label randomized trial in which 100 incident kidney transplant recipients were randomized 1:1 to receive oral paricalcitol, 2 µg per day, for the first year posttransplant or no additional therapy. Serial measurements of serum PTH, calcium and bone alkaline phosphatase, 24-h urine calcium and bone density were performed. The primary endpoint was the frequency of hyperparathyroidism 1-year posttransplant. Eighty-seven patients completed the trial. One-year posttransplant, 29% of paricalcitol-treated subjects had hyperparathyroidism compared with 63% of untreated patients (p = 0.0005). Calcium supplementation was discontinued in two control and 15 treatment patients due to mild hypercalcemia or hypercalcuria. Paricalcitol was discontinued in four patients due to hypercalcuria/hypercalcemia and in one for preference. Two subjects required decreasing the dose of paricalcitol to 1 µg daily. Hypercalcemia was asymptomatic and reversible. Incidence of acute rejection, BK nephropathy and renal function at 1 year were similar between groups. Moderate renal allograft fibrosis was reduced in treated patients. Oral paricalcitol is effective in decreasing posttransplant hyperparathyroidism and may have beneficial effects on renal allograft histology.
Assuntos
Ergocalciferóis/administração & dosagem , Hiperparatireoidismo Secundário/prevenção & controle , Transplante de Rim/efeitos adversos , Administração Oral , Conservadores da Densidade Óssea , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Hiperparatireoidismo Secundário/epidemiologia , Hiperparatireoidismo Secundário/etiologia , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Prevalência , Estudos Prospectivos , Resultado do TratamentoRESUMO
This study assessed the development of allograft interstitial fibrosis and inflammation (GIF+"i"), a histologic pattern associated with reduced graft survival. Included are 795 adults, recipients of kidney allografts from 2000 to 2006. GIF+"i" was diagnosed in surveillance and clinical biopsies that had no transplant glomerulopathy. With time, posttransplant increasing number of grafts showed GIF+"i" and these patients had reduced death-censored graft survival (HR = 4.33 (2.49-7.53), p < 0.0001). Development of GIF+"i" was related to prior acute cellular rejection (ACR), BK nephropathy (PVAN), increasing number of HLA mismatches, retransplantation and DGF. However, 46.4% of GIF+"i" cases had no history of ACR or PVAN. Anti-HLA antibodies at transplant did not relate to GIF+"i" and these patients had no increased frequency of new antibody formation posttransplant. Post-ACR biopsies showed that GIF+"i" developed more commonly after clinically and/or histologically more severe ACR. Graft inflammation persisted in 38.7 and 29.6% of grafts 2 and 12 months post-ACR. Twelve months post-ACR, 27.1% of biopsies developed moderate-severe GIF and 51.8% showed GIF and inflammation. Persistent inflammation and progressive GIF is often subclinical but may lead to graft failure. GIF+"i" can be initiated by multiple etiologies but it is often postinfectious or due to persistent cellular immune-mediated injury.
Assuntos
Fibrose/etiologia , Rejeição de Enxerto/etiologia , Inflamação/etiologia , Transplante de Rim/efeitos adversos , Nefrite/etiologia , Adulto , Feminino , Fibrose/mortalidade , Fibrose/patologia , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Inflamação/mortalidade , Inflamação/patologia , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Nefrite/mortalidade , Nefrite/patologia , Prognóstico , Taxa de Sobrevida , Transplante HomólogoRESUMO
We assessed the earliest manifestations of recurrent membranous glomerulonephritis (MGN) in renal allografts. Clinical, laboratory and pathologic data were reviewed in 21 patients at the initial biopsy within 4 months post-transplant with evidence of MGN and on follow-up biopsies, compared to a biopsy control group of eight transplants without recurrent MGN. The mean time of first biopsy with pathologic changes was 2.7 months. In each earliest biopsy, immunofluorescence (IF) showed granular glomerular basement membrane (GBM) staining for C4d, IgG, kappa and lambda. IF for C3 was negative or showed trace staining in 16/21. On each MGN biopsy positive by IF, 14/19 showed absence of deposits or rare tiny subepithelial deposits by electron microscopy (EM). At the earliest biopsy, the mean proteinuria was 1.1 g/day; 16 patients had <1 g/day proteinuria. Follow-up was available in all patients (mean 35 months posttransplant). A total of 13 patients developed >1 g/day proteinuria; 12 were treated with: rituximab (n = 8), ACEI and increased prednisone dose (n = 2), ACEI or ARB only (n = 2). All patients showed reduction in proteinuria after treatment. A total of 11/16 patients showed progression of disease by EM on follow-up biopsy. Recognition of early allograft biopsy features aids in diagnosis of recurrent MGN before patients develop significant proteinuria.
Assuntos
Glomerulonefrite Membranosa/etiologia , Glomerulonefrite Membranosa/patologia , Nefropatias/cirurgia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias , Adulto , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Feminino , Imunofluorescência , Seguimentos , Glomerulonefrite Membranosa/tratamento farmacológico , Humanos , Fatores Imunológicos/uso terapêutico , Nefropatias/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Proteinúria/patologia , Recidiva , Estudos Retrospectivos , Rituximab , Transplante HomólogoRESUMO
New-onset diabetes after transplantation is recognized as one of the metabolic consequences which may increase the risk of morbidity and mortality after solid organ transplantation. The pathophysiology of new-onset diabetes after transplantation has not been clearly defined and may resemble that of Type 2 diabetes, characterized by predominantly insulin resistance or defective insulin secretion, or both. This review aims to summarize the current state of knowledge regarding the prevalence, consequences, pathogenesis, and management of new-onset diabetes after transplantation, with a major focus on the possible mechanisms involved in the pathogenesis of the disorder. The aetiology of new-onset diabetes after transplantation is multifactorial, with diabetogenic immunosuppressive drugs playing a major role. Multiple cellular and physiologic mechanisms are involved in the process. Selection of an appropriate maintenance immunosuppressive regimen should involve balancing the risk of patient and graft survival vs. the potential for new-onset diabetes after transplantation.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Hipoglicemiantes/uso terapêutico , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/efeitos adversos , Insulina/uso terapêutico , Transplante de Órgãos/efeitos adversos , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/mortalidade , Transplante de Coração/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Resistência à Insulina , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Transplante de Órgãos/mortalidade , Fatores de RiscoRESUMO
It has become cliché to state that improvements in early renal allograft survival over the past two decades have not led to increased long-term renal allograft survival. However, it is not clear how long-term graft survival can be improved. Here, we present the viewpoint that the road forward does not involve searching for new and more ideal immunosuppressive regimens, but rather detailed patient follow-up to identify specific causes of late renal allograft loss and the development of new therapy designed to address these problems before allograft damage becomes irreversible.
Assuntos
Transplante de Rim/mortalidade , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Humanos , Transplante Homólogo/mortalidadeRESUMO
We assessed the relationship between living donor (LD) age and kidney survival in 1063 adults transplanted between 1980 and 2007. Increasing LD age was associated with lower kidney function (GFR) before and after transplantation and loss of GFR beyond 1 year. Increasing LD age was also associated with low-moderate proteinuria posttransplant (151-1500 mg/day, p < 0.0001). By univariate analysis, reduced graft survival related to lower GFR at 1 year [HR = 0.925 (0.906-0.944), p < 0.0001], proteinuria [HR = 1.481 (1.333-1.646), p < 0.0001] and increasing LD age [HR = 1.271 (1.219-1.326), p = 0.001]. The impact of LD age on graft survival was noted particularly >4 years posttransplant and was modified by recipient age. Thus, compared to a kidney graft that was within 5 years of the recipient age, younger kidneys had a survival advantage [HR = 0.600 (0.380-0.949), p = 0.029] while older kidneys had a survival disadvantage [HR = 2.217 (1.507-3.261), p < 0.0001]. However, this effect was seen only in recipients <50 years old. By multivariate analysis, the relationship between LD age and graft survival was independent of GFR but related to proteinuria. In conclusion, LD age is an important determinant of long-term graft survival, particularly in younger recipients. Older kidneys with reduced survival are identifiable by the development of proteinuria posttransplant.
Assuntos
Fatores Etários , Transplante de Rim , Doadores Vivos , Resultado do Tratamento , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The aim of this study was to assess the safety of bilateral native ureteral ligation (BNUL) without nephrectomy in the management of native proteinuria in kidney transplant (KTx) recipients. We retrospectively studied 17 patients who underwent BNUL between 2002 and 2010 with a median preoperative 24 h protein concentration of 2140 (range 1020-25 000) mg/L. Fifteen of the 17 patients had focal segmental glomerulosclerosis as their primary renal disease and ligation was employed to facilitate the diagnosis of early recurrence. The BNUL was performed simultaneously with KTx in 14 patients. Surgical techniques were: open (n = 5), pure laparoscopic (n = 1) and a hybrid of hand-assisted laparoscopic surgical/open approach (n = 12) used at the time of transplantation via the transplant incision. At a median follow-up of 46 months (range 1-59), no patient had a complication related to BNUL and none required interventions associated with their native kidneys. BNUL without nephrectomy seems to be a safe technique to manage native proteinuria in renal transplant candidates.
Assuntos
Transplante de Rim/efeitos adversos , Nefrectomia , Complicações Pós-Operatórias , Proteinúria/prevenção & controle , Ureter/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Ligadura , Masculino , Pessoa de Meia-Idade , Proteinúria/etiologia , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Previous studies suggest that the majority of renal allografts are affected by progressive, severe chronic histologic injury, yet studies using current protocols are lacking. The goal of this study was to examine the prevalence and progression of histologic changes using protocol allograft biopsies at 1 and 5 years after solitary kidney transplantation in patients transplanted between 1998 and 2004. Chronic histologic changes generally were mild at both 1 and 5 years and were similar in deceased and living donor kidneys. The overall prevalence of moderate or severe fibrosis was 13% (60/447) at 1 year and 17% (60/343) at 5 years. In a subgroup of 296 patients who underwent both 1- and 5-year biopsies, mild fibrosis present at 1 year progressed to more severe forms at 5 years in 23% of allografts. The prevalence of moderate or severe arteriolar hyalinosis was similar in tacrolimus and calcineurin inhibitor-free immunosuppression. These results in the recent era of transplantation demonstrate fewer, less severe and less progressive chronic histologic changes in the first 5 years after transplantation than previously reported.
Assuntos
Fibrose/patologia , Rejeição de Enxerto/patologia , Nefropatias/patologia , Transplante de Rim , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Doadores de Tecidos , Transplante Homólogo , Adulto JovemRESUMO
Sensitized renal transplant recipients with high levels of donor-specific alloantibody (DSA) commonly develop antibody-mediated rejection (AMR), which may cause acute graft loss or shorten allograft survival. We examined the efficacy of terminal complement inhibition with the humanized anti-C5 antibody, eculizumab, in the prevention AMR in renal transplant recipients with a positive crossmatch against their living donor. The incidence of biopsy-proven AMR in the first 3 months posttransplant in 26 highly sensitized recipients of living donor renal transplants who received eculizumab posttransplant was compared to a historical control group of 51 sensitized patients treated with a similar plasma exchange (PE)-based protocol without eculizumab. The incidence of AMR was 7.7% (2/26) in the eculizumab group compared to 41.2% (21/51) in the control group (p = 0.0031). Eculizumab also decreased AMR in patients who developed high levels of DSA early after transplantation that caused proximal complement activation. With eculizumab, AMR episodes were easily treated with PE reducing the need for splenectomy. On 1-year protocol biopsy, transplant glomerulopathy was found to be present in 6.7% (1/15) eculizumab-treated recipients and in 35.7% (15/42) of control patients (p = 0.044). Inhibition of terminal complement activation with eculizumab decreases the incidence of early AMR in sensitized renal transplant recipients (ClincalTrials.gov number NCT006707).
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Inativadores do Complemento/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Isoanticorpos/sangue , Transplante de Rim , Adulto , Complemento C5/antagonistas & inibidores , Feminino , Rejeição de Enxerto/imunologia , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Troca PlasmáticaRESUMO
Renal transplant candidates with donor-specific alloantibody (DSA) have increased risk of antibody-mediated allograft injury. The goal of this study was to correlate the risk of antibody-mediated rejection (AMR), transplant glomerulopathy (TG) and graft survival with the baseline DSA level (prior to initiation of pretransplant conditioning). These analyses include 119 positive crossmatch (+XM) compared to 70 negative crossmatch (-XM) transplants performed between April 2000 and July 2007. Using a combination of cell-based crossmatch tests, DSA level was stratified into very high +XM, high +XM, low +XM and -XM groups. In +XM transplants, increasing DSA level was associated with increased risk for AMR (HR = 1.76 [1.51, 2.07], p = 0.0001) but not TG (p = 0.18). We found an increased risk for both early and late allograft loss associated with very high DSA (HR = 7.71 [2.95, 20.1], p = 0.0001). Although lower DSA recipients commonly developed AMR and TG, allograft survival was similar to that of -XM patients (p = 0.31). We conclude that the baseline DSA level correlates with risk of early and late alloantibody-mediated allograft injury. With current protocols, very high baseline DSA patients have high rates of AMR and poor long-term allograft survival highlighting the need for improved therapy for these candidates.
Assuntos
Nefropatias/diagnóstico , Transplante de Rim/métodos , Doadores de Tecidos , Adulto , Anticorpos/imunologia , Biópsia , Estudos de Coortes , Feminino , Rejeição de Enxerto , Teste de Histocompatibilidade/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Resultado do TratamentoRESUMO
Nephrogenic systemic fibrosis (NSF) is a debilitating disease in patients with severely diminished kidney function. Currently, no standard treatment exists but improvement has been reported after restoration of kidney function. We retrospectively studied 17 NSF patients with and without successful kidney transplantation (KTx) to evaluate the effects of KTx on NSF. Nine of the 11 KTx developed NSF pretransplant whereas two developed NSF immediately after KTx with delayed graft function. Two of the six dialysis patients had previous failed kidney transplants. Age and sex were well matched. All but one patient was dialysis dependent at the time of NSF. Median follow-up was 35 months for KTx patients and 9 months for dialysis patients. Kidney transplants achieved adequate renal function with median serum creatinine of 1.4 (0.9-2.8) mg/dL and a glomerular filtration rate of 42 (19-60) mL/min/1.73 m(2). NSF improved in 54.6% of the transplanted patients and 50% of the nontransplanted patients (p = 0.86). Two KTx patients had complete resolution of their symptoms whereas four had partial improvement. Improvement in the dialysis patients was all partial. Successful KTx did not insure improvement in NSF and in fact appeared to have no significant benefit over dialysis.