Nelson Zocoler Galante

O contexto do transplante renal no Brasil e sua disparidade geográfica

The Brazilian National Transplantation System coordinates and regulates perhaps the largest public transplantation program worldwide. Since its implementation in 1997, the number of kidney transplantations increased from 920 (5.8 pmp) in 1998, to 4,630 (24.1 pmp) in 2010. This growth was primarily due to the increased number of effective donors (from 1.8 pmp in 1998 to 9.3 pmp in 2010), with a corresponding increased number of kidneys transplanted from deceased donors (3.8 pmp in 1999 versus 9.9 pmp in 2010).The number of kidney transplantations from living donors has not increased significantly, from 1,065 (6.7 pmp) in 1998 to 1,641 (8.6 pmp) in 2010, either as a consequence of the observed increase in the deceased donor program or perhaps because of strict government regulations allowing only transplantations from related donors. From 2000 to 2009, the mean age of living donors increased from 40 to 45 years, while it increased from 33 to 41 years for deceased donors, of whom roughly 50% die of stroke. There are clear regional disparities in transplantation performance across the national regions. While the state of Sao Paulo is ranked first in organ donation and recovery (22.5 pmp), some states of the Northern region have much poorer performances. These disparities are directly related to different regional population densities, gross domestic product distribution, and number of trained transplantation physicians. The initial evaluation of the centers with robust outcomes indicates no clear differences in graft survival in comparison with centers in the USA and Europe. Ethnicity and time on dialysis, but not the type of immunosuppressive regimen, decisively influence the measured outcomes. Since the implementation of national clinical research regulations in 1996, Brazilian centers have participated in a number of national and international collaborative trials for the development of immunosuppressive regimens. Besides the challenge of reducing the regional disparities related to access to transplantation, further improvements can be obtained by the creation of a national registry of the outcomes of transplanted patients and living donors, and also by the promotion of clinical and experimental studies to better understand the transplantation-related immune response of the Brazilian population.

Treatment of subcutaneous phaeohyphomycosis and prospective follow-up of 17 kidney transplant recipients

BACKGROUND Subcutaneous phaeohyphomycosis in solid organ recipients may have an adverse outcome. OBJECTIVE We sought to describe the disease course, treatment, and outcome of allograft function in kidney transplant recipients with phaeohyphomycosis. METHODS Seventeen patients were followed for a mean period of 25.4 months to analyze the clinical response to treatment. RESULTS There was no treatment failure or relapsing disease among 12 patients who completed treatment. Two patients were still in treatment with disease remission. One patient discontinued the study during treatment with partial remission, one died after finishing treatment with disease remission, and one was dropped from the study because contact was lost. Immunosuppressive regimens were not changed. Two of 17 patients had a significant reduction in allograft function. LIMITATIONS The follow-up time was short and the number of patients was small. CONCLUSIONS The outcome of phaeohyphomycosis in kidney transplant recipients was favorable with minimal impact on renal allograft function.

Incidência e fatores de risco para complicações infecciosas no primeiro ano após o transplante renal

INTRODUCAO: Complicacoes infecciosas determinam significativas morbidade e mortalidade apos o transplante renal. A imunossupressao utilizada representa o principal fator de risco e apresenta relacao direta com a incidencia e a severidade dos eventos infecciosos. METODOS: Estudo de coorte, retrospectivo, que analisou a incidencia e fatores de risco para ocorrencia de infeccoes em 1.676 receptores de transplante renal durante o primeiro ano de acompanhamento. RESULTADOS: Eventos infecciosos foram observados em 821 (49%) pacientes. O numero medio de episodios infecciosos entre pacientes com pelo menos um episodio foi de 2,3 (1 - 12). As complicacoes infecciosas mais prevalentes foram infeccao do trato urinario (31,3%), infeccoes por citomegalovirus (12%), infeccao da incisao cirurgica (10,3%), infeccao por herpes virus (9,1%), Infeccao pulmonar (5,2%) e infeccao da corrente sanguinea (4,3%). O tempo de isquemia fria e a utilizacao de rins de doadores falecidos foram fatores de risco importantes para a ocorrencia de episodios infecciosos. CONCLUSOES: infeccoes apresentam prevalencia elevada no primeiro ano de acompanhamento apos o transplante. A principal complicacao infecciosa foi a infeccao do trato urinario.

Transplantation with kidneys retrieved from deceased donors with acute renal failure.

Background The discard rate of kidneys recovered from deceased donors with acute renal failure (ARF) is higher compared with those without ARF mainly due to the uncertainty regarding short-term and long-term outcomes. Methods We retrospectively analyzed 1-year patient, graft, and rejection-free survivals and renal function of transplantations performed with kidneys recovered from deceased donors with or without ARF, defined as serum creatinine level of more than 1.5 mg/dL. We performed multivariable analysis to evaluate whether ARF was an independent risk factor associated with inferior outcomes. Results Of a total of 1518 patients, 253 received kidneys from expanded-criteria donors (ECD; with ARF [n=116] and without ARF [n=137]) and 1265 from standard-criteria donors (SCD; with ARF [n=369] and without ARF [n=896]). The incidence of delayed graft function was higher in ECD (68.1% vs. 58.4%; P=0.072) and SCD (69.9% vs. 50.6%; P<0.001) recipients of kidneys with ARF compared with those without ARF, respectively. At 1 year, patient, graft, and rejection-free survivals were not statistically different in SCD or ECD recipients with or without ARF. Renal function at 1 year was similar in recipients of ECD (41.9±26.3 vs. 40.1±21.7 mL/min; P=0.565) or SCD (50.9±29.9 vs. 53.6±28.5 mL/min; P=0.131) kidneys with and without ARF, respectively. Compared with kidneys without ARF, receiving a kidney allograft with ARF was not associated with increased risk of death, graft lost, or inferior renal function 1 year after transplantation. Conclusion In this cohort of patients, kidneys from deceased donors with ARF provided graft survival and renal function comparable with kidneys from donors without ARF 1 year after transplantation.

Severe intellectual disability does not preclude renal transplantation

BACKGROUND Intellectual disability (ID) in patients with chronic kidney disease is a relative contraindication for kidney transplantation. METHODS We analysed a retrospective cohort of 16 recipients of kidney transplantation with ID and 83 controls. RESULTS Graft survival at 5 years was similar between patients (81.2%) and controls (80.2%), P = 0.9. Patient survival at 5 years was lower among patients (81.2% versus 94.4%, P < 0.05). Patients had more infection episodes, but no risk factors were identified. CONCLUSION Although recipients with ID have lower long-term patient survival, the equivalent graft survival rates support the indication of renal transplantation in such disability.

Longitudinal Pharmacokinetics of Tacrolimus in Elderly Compared With Younger Recipients in the First 6 Months After Renal Transplantation

Background Elderly (Eld) (≥60 years) recipients are receiving renal transplants more frequently. The pharmacokinetics (PK) studies of immunosuppressive drugs in healthy volunteers, rarely, include old patients. Methods We studied 208 12-hour tacrolimus (TAC) PK (0, 20, 40, 60, 90, 120, 180, 240, 360, 480, 600, 720 min) in 44 Eld (65 ± 3 years) and compared the results with 31 younger controls (Ctrl) (35 ± 6 years) recipients, taking oral TAC/mycophenolate sodium (MPS)/prednisone, at 4 different timepoints: PK1 (8 ± 2 days; n = 72), PK2 (31 ± 4 days; n = 61), PK3 (63 ± 6 days; n = 44), and PK4 (185 ± 10 days; n = 31). Tacrolimus PK was measured by ultraperformance liquid chromatography coupled to a mass spectrometer repetition and noncompartmental PKs were analyzed using Phoenix WinNonlin. Results Mean TAC dose was lower in the Eld group than in Ctrl ones throughout timepoints either by total daily dose or adjusted (Adj) per body weight. Mean TAC trough level (Cmin), used to adjust daily dose, was not different between the 2 groups in all timepoints. AdjCmax and AdjTAC-area under the curve at dosing interval were both higher in the Eld compared to the Ctrl group in PKs1, 3, and 4. Estimated total body clearance normalized by dose and weight was lower in the Eld group compared with the Ctrl in all PKs and statistically lower at PKs 1 and 3. Similar to younger recipients TAC trough level has also a high correlation (R2 = 0.76) with area under the curve at dosing interval. Conclusions These data indicate that Eld recipients have a lower TAC clearance and therefore need a lower TAC dose than younger recipients.

Transpondo limites com doadores falecidos: transplantes bem-sucedidos com rins de doador com creatinina sérica igual a 13,1 mg/dL

Non-expanded deceased donors with acute kidney failure can be a safe option to increase the number of kidneys for transplantation. Histological evaluation is fundamental to establish the functional prognosis of those grafts. Two kidney transplantations were performed from a young deceased donor with severe acute kidney failure and no structural change in the renal parenchyma. Both patients had postoperative delayed graft function, but one of them, who had good initial urinary volume, required no dialysis. Adequate renal function was present at day 30 after transplantation. Severe acute kidney failure in deceased donors is not an independent risk factor for short-term outcome of renal graft and should not be considered an absolute contraindication for transplantation.

Longitudinal Pharmacokinetics of Everolimus when Combined with Low-level of Tacrolimus in Elderly Renal Transplant Recipients.

Background Although the proportion of elderly patients among renal transplant recipients has increased, pharmacokinetic (PK) studies of immunosuppressants rarely include older patients. Methods We studied 12-hour everolimus (EVL) PK in 16 elderly renal transplant recipients (all whites; 10 men; mean age, 64 ± 2 years (61-71 years), in 4 separate timepoints (at 7, 30, 60, and 150 days) after EVL introduction, corresponding to a mean postrenal transplantation day: PK1 (43 ± 4 days), PK2 (65 ± 7 days), PK3 (106 ± 17 days), and PK4 (206 ± 40 days). Patients received EVL (target trough level (Ctrough, 3-8 ng/mL), prednisone, and tacrolimus (TCL) (target Ctrough, 2-5 ng/mL). Results Mean TCL-Ctrough was 7.2 ± 3.8, 4.9 ± 2.2, 4.9 ± 2.2, and 4.5 ± 1.2 ng/mL at PK1, PK2, PK3, and PK4, respectively. There were no differences among timepoints for mean EVL daily dose (data shown as PK3) (3.5 ± 1.3 mg/d), Ctrough (4.7 ± 2.5 ng/mL), AUC0-12h (106 ± 51 ng/h per mL), Caverage (8.8 ± 4.2 ng/mL), Cmax (19.2 ± 9.7 ng/mL), apparent Half-life (11.7 ± 4.2 hours), estimated total body clearance (0.39 ± 0.27 L/h), or fluctuation (166 ± 65%). Also, none of those PK parameters differed statistically when adjusted for body weight. EVL-Ctrough showed a very high correlation (r2 = 0.849) with AUC0-12h. Conclusions Our data indicate that elderly renal transplant recipients starting EVL 1 month after transplantation along with a steady-state TCL level, present stable EVL-PK parameters without significant changes in dose or exposure during the first 6 months after renal transplantation.

Impacto da função retardada do enxerto pancreático no transplante simultâneo pâncreas-rim

: A incidencia de funcao retardada do enxerto pancreatico foi 11%. A idade do receptor superior a 45 anos apresentou associacao com o risco de desenvolvimento de funcao retardada do enxerto pancreatico (Razao de chances 2,26; p < 0,05). Os pacientes com funcao retardada do enxerto pancreatico apresentaram maior incidencia de rejeicao aguda renal (47

Buttonhole: an old technique rediscovered

, portanto perfeitamen-te adequado. Esse termo tambem ja foi empregado pela comunidade medica por -tuguesa. Sugerimos ao JBN, e a comuni-dade nefrologica brasileira em geral, a normatizacao deste termo em trabalhos futuros.O segundo comentario refere-se aos aspectos medicos. Em nossa experien-cia, recentemente publicada (Galante