Cláudio S. Melaragno

Multivariate Analysis of Risk Factors for Early Loss of Pancreas Grafts Among Simultaneous Pancreas–Kidney Transplants

UNLABELLED To evaluate the risk factors for pancreas graft loss within 3 months postoperatively among 170 simultaneous pancreas-kidney transplantation (SPKT) we examined 38 variables. METHODS Twenty-two variables were related to recipients; 12 to donors and 4 to the surgical procedure. In addition the latest follow-up dates as well as the transplant and/or death dates. Independent variables were examined with reference to the dependent pancreatic loss variable, excluding losses owing to deaths. Variables with statistical significance were analyzed to predict early graft loss. RESULTS Univariate analyses determined the following significant variables: kidney cold ischemia time, older donors, non-white donors, death cause related to vascular disease, wound infection, and length of extended hospitalization. However, multivariate analysis showed that only donor age and kidney cold ischemia time were significant predictors for early pancreatic graft loss. CONCLUSION Donor age and kidney cold ischemia time were independently related to pancreatic loss after SPKT within 3 months posttransplantation.

Transplante de pâncreas e ilhotas em portadores de diabetes melito

Pancreas and kidney transplants have specific indications, benefits and risks. The procedure has become more common and more often as long-term success has improved and risks have decreased. Compared with a patient being on dialysis, simultaneous pancreas-kidney transplant offers a distinct advantage when it comes to mortality, quality of life and diabetic complications. Since there can be a living-donor kidney transplant,, a possibly similar patient and graft survival by 10 years follow-up, this procedure should be considered. Pancreas after kidney transplants, when successful, can improve microvascular complications compared with kidney transplant alone, but immediate mortality may be higher. Solitary pancreas transplantation can improve the quality of life in selected patients, but it may also increase the immediate risk of mortality due to the complexity of the surgery and the risks of immunosupression. The results of Islet transplantation differ from the higher metabolic performance achieved by whole pancreas allotransplantation and its applicability is limited to selected adult diabetic patients.

Charcot neuroarthropathy after simultaneous pancreas-kidney transplant.

Background Immunosuppressive regimen is associated with several metabolic adverse effects. Bone loss and fractures are frequent after transplantation and involve multifactorial mechanisms. Methods A retrospective analysis of 130 patients submitted to simultaneous pancreas-kidney transplantation (SPKT) and an identification of risk factors involved in de novo Charcot neuroarthropathy by multivariate analysis were used; P<0.05 was considered significant. Results Charcot neuroarthropathy was diagnosed in 4.6% of SPKT recipients during the first year. Cumulative glucocorticoid doses (daily dose plus methylprednisolone pulse) during the first 6 months both adjusted to body weight (>78 mg/kg) and not adjusted to body weight were associated with Charcot neuroarthropathy (P=0.001 and P<0.0001, respectively). Age, gender, race, time on dialysis, time of diabetes history, and posttransplantation hyperparathyroidism were not related to Charcot neuroarthropathy after SPKT. Conclusions Glucocorticoids are the main risk factors for de novo Charcot neuroarthropathy after SPKT. Protocols including glucocorticoid avoidance or minimization should be considered.

Estudo prospectivo de 2151 pacientes com doença renal crônica em tratamento conservador com abordagem multidisciplinar no Vale do Paraíba, SP

INTRODUCTION Chronic Kidney Disease (CKD) is common, severe and treatable. Its detection involves low cost tests. AIM To evaluate the effect of a multidisciplinary (nephrologist, social worker, nurse, nutritionist, and psychologist) intervention comparing clinical and laboratory parameters in patients with CKD. METHODS A prospective study with 2,151 patients attended at the State Center for Kidney Diseases of the Vale do Paraiba, São Paulo, from February 2008 to March 2011. The kidney function was measured using albuminuria and estimated glomerular filtration rate (eGRF) using the MDRD formula The clinical outcomes were the occurrence of cardiovascular disease (CAD), hospitalization episodes, need of renal replacement therapy (RRT) and death. RESULTS Participants had a mean (range) age of 62 years (14-101), a mean follow-up of 546 days (90-1540) and the majority was in the stage 3 of CKD (59%). The most common primary diagnoses were hypertension (41.2%) and diabetes (32.4%). Mean blood pressure values at the beginning and at the end of treatment were 143 ± 26 mmHg x 87 ± 14 mmHg and 123 ± 16 mmHg x 79 ± 9 mmHg, respectively (p < 0.001); the eGRF decreased from 58.5 ± 31 ml/min. to 56.3 ± 23 ml/min (p < 0.01). Mean value of proteinuria decreased from 1.04 ± 1.44 g/day to 0.61 ± 1.12 g/day, p < 0.001, and the fasting glicemia decreased from 137 ± 73 mg/dl to 116 ± 42 mg/dl. One hundred and twenty-two patients (5.7%) had a CAD episode, the hospitalization rate was 6.6% (n = 143 patients), 7.3% patients died (n = 156), and 1.1% (n = 23) patients needed to start RRT. The risk of cardiovascular events, hospitalization, or death was inversely related to eGRF, and the rates of these events were low compared with the international literature. CONCLUSION The multidisciplinary care with well defined targets is effective for the preservation of renal function and reduction in morbidity and mortality of CKD patients.

Mycophenolate Mofetil Versus Enteric-Coated Mycophenolate Sodium After Simultaneous Pancreas-Kidney Transplantation

INTRODUCTION Adverse gastrointestinal events are frequent after mycophenolate use. The objectives of the present study were to report the incidence of acute noninfectious diarrhea, to determine the risk factors, and to compare the severity of reactions between mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) after simultaneous pancreas kidney transplantation (SPKT). METHODS We included 165 SPKT patients from December 2000 to May 2007. Uni- and multivariate analyses were performed, using acute noninfectious diarrhea as the dependent variable. P < .05 was considered significant. RESULTS Mean age and duration of dialysis and of diabetes were 34.9 +/- 8.2 years, 27.3 +/- 18.3 months, and 21.9 +/- 16.2 years, respectively. Sixty-three percent used MMF, 36.4% used EC-MPS, and 0.6% used azathioprine. Multivariate analysis showed that the duration of diabetes (P = .049, confidence interval [CI] 1.0- 1.13) and MMF use (P = .013, 95% CI 0.2-0.82) were the main determinants of acute diarrhea after SPKT. MMF dose reduction (79.2% vs 62.3%, P = .024) and severity of diarrhea associated with orthostatic hypotension were more pronounced among MMF than EC-MPS patients (42.4% vs 15.1%, P = .001). There was no difference between MMF and EC-MPS after dose reduction in relation to the occurrence of acute kidney rejection (30.8% vs 26.7%, P = .53). CONCLUSIONS Acute noninfectious diarrhea after SPKT was related to the duration of diabetes and to prescription of MMF. Preferential use of EC-MPS was associated with a lower necessity of dose reduction and less severe episodes of acute diarrhea compared with MMF, although dose reduction was equally associated with acute episodes of kidney rejection.

Extreme Subcutaneous, Intramuscular and Inhaled Insulin Resistance Treated by Pancreas Transplantation Alone

Diabetes mellitus with resistance to insulin administered subcutaneously or intramuscularly (DRIASM) is a rare syndrome and is usually treated with continuous intravenous insulin infusion. We present here two cases of DRIASM in 16 and 18 years female patients that were submitted to pancreas transplantation alone (PTA). Both were diagnosed with type 1 diabetes as young children and had labile glycemic control with recurrent episodes of diabetic ketoacidosis. They had prolonged periods of hospitalization and complications related to their central venous access. Exocrine and endocrine drainages were in the bladder and systemic, respectively. Both presented immediate graft function. In patient 1, enteric conversion was necessary due to reflux pancreatitis. Patient 2 developed mild postoperative hyperglycemia in spite of having normal pancreas allograft biopsy and that was attributed to her immunosuppressive regimen. Patient 1 died 9 months after PTA from septic shock related to pneumonia. In 8 months of follow‐up, Patient 2 presented optimal glycemic control without the use of antidiabetic agents. In conclusion, PTA may be an alternative treatment for DRIASM patients.

Simultaneous Pancreas-Kidney Transplantation: Which Organ Should Be Transplanted First?

Simultaneous pancreas-kidney transplantation (SPKT) has been accepted as treatment for type I diabetic patients with end-stage renal disease. Its success depends largely on the surgical technique. This study sought to compare groups of SPKT with initial pancreas implantation versus initial kidney implantation. From December 2000 to September 2006, 151 SPKT were performed by a single center. In 85 cases, the pancreas was implanted first (group 1), and in 66 cases the order was inverted (group 2). Variables were implantation sequence, pancreas and kidney ischemia time, donor age, venous drainage, previous donor peritoneal dialysis, and recipient age and gender. Outcome variables included pancreas vascular thrombosis, 3-month graft survival, 3-month patient survival, pancreas rejection episodes, intra-abdominal infection, diabetes control and reoperations. We observed a 10.6% incidence of vascular thrombosis in group 1 but none in group 2 (P = .005). In groups 1 and 2, the 3-month pancreas survivals were 74.1% and 89.4% (P = .022), and the mean hospital stays were 24.3 and 15.8 days, respectively (P = .002). Our results suggested that, when 2 different teams are involved in SPKT, with >1 exposure and the need for retractor replacement, the kidney should be transplanted first, because the pancreas may be damaged during the surgical procedure.

Delayed Kidney Allograft Function after Simultaneous Pancreas-Kidney Transplantation

BACKGROUND Simultaneous pancreas-kidney transplantation (SPKT) is one of the treatments for insulin-dependent chronic renal failure patients. METHODS One-year patient and kidney allograft survival rates of 150 patients undergoing SPKT were subjected to Cox regression and Kaplan-Meier analyses. Uni- and multivariate methods identified risk factors involved in allograft and patient survival. RESULTS One-year patient and kidney allograft survival rates were 82% and 80%, respectively. Delayed graft function (DGF) (P = .001; hazard ratio [HR]5.41) and acute kidney rejection episodes (P = .016; HR 3.36) were related to 1 year patient survival as well as intra-abdominal infection (IAI) rates. (IAI). One-year kidney allograft survival was related to DGF (P = .013; odds ratio [OR] 3.39), acute rejection (P = .001; OR 4.74), and IAI (P = .003, OR 6.29). DGF was related to a time on dialysis >27 months (P = .046; OR 2.59), cold kidney ischemia time >14 hours (P = .027; OR 2.94), donor age >25 years (P = .03; OR 2.82), and donor serum sodium concentration >155 mEq/L (P < .0001; OR 1.09). Female kidney to male recipient in 17% of the cases did not increase the risk of DGF. We observed an important correlation between donor serum sodium and creatinine (P < .0001), which suggested undertreatment of diabetes insipidus secondary to brain death. CONCLUSIONS DGF, acute rejection, and IAI were the main determinants of survival after SPKT. Improving the care of deceased donors may reduce DGF occurrence.

Asynchronous Kidney Allograft Loss After Simultaneous Pancreas-Kidney Transplantation: Impact on Pancreas Allograft Outcome at a Single Center

OBJECTIVE We analyzed the clinical evolution of pancreas allografts in simultaneous pancreas-kidney transplantation (SPKT) cases after asynchronous kidney allograft loss and kidney retransplantation at a single non-United States center. PATIENTS AND METHODS We performed a retrospective analysis of 168 SPKT from December 2000 to June 2007. RESULTS The 5-year kidney allograft survival rate was 71%. Excluding cases of death with a functioning graft after SPKT (n = 35; 74.4%), 12 kidney allografts were lost due to acute rejection (n = 7; 15%) or chronic allograft nephropathy (n = 5; 10.6%). Delayed graft function contributed to kidney allograft loss. Five of 12 patients underwent kidney retransplantation. Sixty percent of pancreas allografts were lost after this procedure, which was attributed to either the diabetogenic effects of the immunosuppressive regimen or to the perioperative stress. Oral glucose tolerance tests performed before kidney retransplantation identified patients with good pancreas allograft function versus those with intolerance on glucose tests who received reduced glucocorticoid doses. CONCLUSIONS In SPKT, pancreas allograft function was seriously affected by kidney retransplantation. Oral glucose tolerance tests performed before kidney retransplantation were helpful to assess beta-cell function and suggest prescription of lower steroid doses to decrease the pancreas allograft dysfunction.

Opções técnicas utilizadas no transplante pancreático em centros brasileiros

OBJETIVO: Analisar o perfil dos principais centros de transplantes do Brasil, quanto as opcoes tecnicas no transplante de pâncreas. METODO: Foi encaminhado um questionario por correio eletronico (email) para um membro de cada equipe de 12 centros de transplante do Brasil, com casuistica minima de um transplante de pâncreas. O questionario continha 10 perguntas, abordando aspectos controversos e nao padronizados. RESULTADOS: A maioria dos centros (90,9%) utiliza incisao mediana. O orgao de escolha a ser implantado primeiro foi principalmente o rim, em 63% dos centros. Em relacao a drenagem venosa, 90,9% utilizam a drenagem sistemica. A ligadura da veia iliaca interna e realizada em 54,5% dos centros. A maioria dos centros (90,9%) utiliza a drenagem enterica para transplante combinado pâncreas-rim. Para o transplante de pâncreas isolado, apenas cinco centros responderam, sendo que dois utilizam a drenagem enterica e tres a vesical. A utilizacao de dreno na cavidade abdominal ocorre em 63% dos centros. Em 72,7% dos centros e realizada algum tipo de inducao na imunossupressao para o transplante combinado pâncreas-rim, sendo a imunossupressao basica a associacao de tacrolimus (FK506), micofenolato mofetil (MMF) e corticoide. A antibioticoprofilaxia e realizada por todos os centros e profilaxia para fungos e realizada por seis centros (54,5%). Oito centros (72,7%) utilizam algum tipo de profilaxia para trombose vascular, em esquemas diversos. CONCLUSAO: Existem diversos caminhos tecnicos na conducao do transplante pancreatico. A falta de padronizacao dificulta a analise e a comparacao dos resultados. Apesar dessa heterogeneidade das equipes, observamos uma tendencia para a realizacao de incisao mediana, drenagem venosa sistemica e exocrina enterica, com a utilizacao de algum tipo de profilaxia para trombose vascular nos transplantes combinados pâncreas-rim.