Effects of pancreas transplantation on oxidative stress in pulmonary tissue from alloxan-induced diabetic rats

Purpose. There is considerable evidence that cellular oxidative stress caused by hyperglycemia plays an important role in the genesis and evolution of chronic diabetic lesions. In this study, we determined the effectiveness of pancreas transplantation (PT) in preventing the imbalance caused by excessive production of reactive oxygen species over antioxidant defenses in lungs of rats rendered diabetic by alloxan injection.Methods. Sixty inbred male Lewis rats, weighing 250-280 g, were randomly assigned to 3 experimental groups: NC, 20 nondiabetic control rats; DC, 20 untreated diabetic control rats; and PT, 20 diabetic rats that received syngeneic PT from normal donor Lewis rats. Each group was further divided into 2 subgroups of 10 rats each which were killed after 4 and 12 weeks of follow-up. Plasma glucose, glycosylated hemoglobin, and insulin levels were determined in all rats. Lipid hydroperoxide (LPO) concentrations and enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were measured in the pulmonary tissue of all rats.Results. The DC rats showed elevated blood glucose and glycosylated hemoglobin levels, with insulin blood levels significantly lower than the NC rats (P < .001). They also showed significantly increased LPO concentrations in the lungs (P < .01) after 4 and 12 weeks of follow-up. In contrast, SOD, CAT, and GSH-Px antioxidant activities were significantly reduced in these periods (P < .01) 12 weeks after diabetes induction. Successful PT corrected all clinical and metabolic changes in the diabetic rats, with sustained normoglycemia throughout the study. Excessive lung LPO production and low SOD, CAT, and GSH-Px antioxidant activities were already back to normal 4 weeks after PT.Conclusion. PT can control oxidative stress in pulmonary tissue of diabetic rats. It may be the basis for preventing chronic diabetic lesions in lungs.

Evaluation of Hemodynamic, Metabolic, and Electrolytic Changes After Graft Reperfusion in a Porcine Model of Intestinal Transplantation

Background. We sought to establish an anesthetic protocol to evaluate the hemodynamic, metabolic, and electrolytic changes after graft reperfusion in pigs undergoing orthotopic intestinal transplant (ITX).Methods. Fifteen pigs were distributed into two groups: GI (n = 6), without immunosuppression, and GII (n = 9), immunosuppressed before surgery with tacrolimus (0.3 mg/kg). The animals were premedicated at 1 hour before surgery with IM acepromazine (0.1 mg/kg), morphine (0.4 mg/kg), ketamine (10 mg/kg), and atropine (0.044 mg/kg IM). Anesthesia induction used equal proportions of diazepam and ketamine (0.1-0.15 mL/kg/IV) and for maintenance in IV infusion of xylazine (1 mg/mL), ketamine (2 mg/mL), and guaiacol glyceryl ether 5% (50 mg/mL), diluted in 250 mL of 5% glucose solution. In addition, recipient pigs were treated with isofluorane inhalation. Heart rate (HR), systolic (SAP), mean (MAP), and diastolic (DAP) arterial pressure, pulse oximetry, respiratory frequency (f), capnography, body temperature (T), blood gas analysis (pH, PaCO(2), PaO(2), base excess, BE; HCO(3)(-), SatO(2)), serum potassium (K), calcium (Ca), sodium, hematocrit (Hct), and glucose (Glu) were measured at four times; MO: after incision (basal value); M1: 10 minutes before reperfusion; and M2 and M3: 10 and 20 minutes after graft reperfusion.Results. All groups behaved in a similar pattern. There was significant hypotension after graft reperfusion in GI and GII (M2 = 56.2 +/- 6.4 and M3 = 57.2 +/- 8.3 mm Hg and M2 = 65.7 +/- 10.2 and M3 = 67.8 +/- 16.8 mm Hg, respectively), accompanied by elevated HR. The ETCO(2) was elevated at M2 (42 mm Hg) and M3 (40 mm Hg). Metabolic acidosis was observed after reperfusion, with significant increase in K levels.Conclusion. The anesthetic protocol for donors and recipients was safe to perform the procedure, allowing control of hemodynamic and metabolic changes after reperfusion without differences regarding immunosuppression.

Temporal relationship between successful pancreas transplantation and control of ocular complications in alloxan-induced diabetic rats

Purpose. The impact of pancreas transplantation (PT) on the progression of eye disease is still controversial. This study evaluated the course of retinopathy in transplanted rats in two different diabetic stages.Methods. Sixty inbred male Lewis rats were assigned to four experimental groups: NC-15 nondiabetic control rats; DC-15 untreated diabetic control rats; PT1-15 diabetic rats that received syngeneic pancreas transplants 2 weeks after alloxan diabetes induction; PT2-15 diabetic rats that received pancreas transplants 12 weeks after diabetes onset. Clinical and laboratory parameters and tens opacity were examined in all rats prior to treatment and at 1-, 6-, and 12-months follow-up. Nucleated eyes from five rats in each group processed for ultrastructural study of the retinal at 6 and 12 months after PT or at follow-up.Results. Cataracts were observed in 20%, 60%, and 100% of DC rats at 1-, 6-, and 12-months follow-up, respectively. Early PT (2 weeks) significantly reduced the prevalence of this complication but not late (12 weeks) PT. PT1 rats also showed improved ultrastructure of the superficial and deep capillary plexuses of the retina, and of Muller cells, compared with DC and PT2. In the last group, retinopathy continued to evolve despite successful PT.Conclusion. Our results suggested that prevention of diabetic ocular lesions by PT was closely dependent on earlier performance of the procedure.

Pancreas transplantation prevents cellular oxidative stress in kidneys of alloxan-induced diabetic rats

Purpose. Oxidative stress is one of the most important mechanisms to explain genesis of the complications in the chronic progression of diabetes. In this investigation we studied the effects of pancreas transplantation (PT) on the imbalance caused by excessive production of free oxygen radicals by antioxidant defenses of rats with serious chronic hyperglycemia induced by alloxan.Methods. Ninety inbred male Lewis rats were randomly distributed into three groups: NC-30 nondiabetic controls; DC-30 diabetic controls without any treatment; PT-30 diabetic rats undergoing syngeneic PT from normal donor Lewis rats. Each experimental group was then split into three subgroups of 10 animals for sacrifice after 1, 3, or 6 months. Clinical and laboratory parameters from all rats as well as lipid hydroperoxide (LPO) concentrations and renal tissue enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were recorded for all rats.Results. Successful PT corrected clinical and laboratory alterations in diabetic rats with sustained normoglycemia throughout the study. A significant increase in LPO concentration and a marked reduction in SOD and CAT enzyme activity were observed in DC rats; there was no significant variation in renal tissue GSH-Px in this group. However, alterations in DC rats were completely restored from 1st month after PT; all evaluated enzyme levels did not significantly differ (P < .01) from those in NC controls.Conclusion. Successful PT controlled cellular oxidative stress in diabetic kidneys, which may prevent chronic lesions.

Meningeal tumor: A rare extrahepatic association in patients with polycystic liver disease enrolled for liver transplantation

In the present study, we described a rare association of polycystic liver disease (PCLD) with intracranial meningiomas in patients included on a liver transplant list, focusing on the diagnosis, treatment and possible association with any genetic alterations. Two female patients, aged 39 and 49 years were included on a liver transplant list due to extensive PCLD, with symptoms related to an abdominal compartmental syndrome. Screening for extrahepatic manifestation revealed a right frontal meningioma in the first patient, and a parietal posterior calcified meningioma in the second patient, measuring 1 and 7x3x2 cm in diameter, respectively. Following tumor removal, the histological pattern was compatible with fibrous and transitional meningioma, respectively. Cytogenetic studies conducted following surgery did not reveal any changes in metaphase chromosomes. The postoperative follow-up for the two patients was uneventful, without complications, with the patients remaining on a liver transplant waiting list. We conclude that screening for extrahepatic manifestations of PCLD is mandatory, as certain lesions require treatment prior to liver transplantation. The lack of a genetic or familial association between these two cases show they are likely to have occurred by chance, rather than representing a previously unrecognized association between polycystic liver disease and cranial meningioma.

Pancreas Transplantation Prevents Morphologic and Ultrastructural Changes in Pulmonary Parenchyma of Alloxan-Induced Diabetic Rats

Purpose. The aim of this study was to evaluate whether pancreas transplantation (PT) is a suitable method for controlling histopathologic changes in lungs of alloxan-induced diabetic rats.Methods. Sixty inbred male Lewis rats were randomly assigned to 3 experimental groups: NC, 20 nondiabetic control rats; DC, 20 untreated diabetic control rats; and PT, 20 diabetic rats that received syngeneic PT from normal donor Lewis rats. Each group was further divided into 2 subgroups of 10 rats each, which were killed after 4 and 12 weeks of follow-up. Clinical and laboratory parameters, fresh and fixed lung weights, and fixed lung volumes were recorded for all rats. Total number of alveoli, alveolar perimeter, alveolar surface area, and alveolar epithelial (AE) and endothelial capillary (EC) basal laminae thickening were randomly measured in 5 rats from each subgroup by using an image analyzer. For light microscopy, 250 alveoli were analyzed in each subgroup. For electron microscopy, 50 electron micrographs were examined for each subgroup.Results. The DC rats showed elevated blood glucose and glycosylated hemoglobin levels, with insulin blood levels significantly lower than the NC rats (P < .001). Fresh and fixed lung weights and fixed volumes were significantly reduced in these rats, although their proportions to body weight were increased at 12 weeks (P < .01). The total number of alveoli in diabetic rats was higher than in control rats, whereas alveolar perimeter and surface area were significantly diminished (P < .01). AE and EC basal laminae were significantly thicker in DC than in NC (P < .01). Successful PT corrected all clinical and metabolic changes in diabetic rats, with sustained normoglycemia throughout the study. Morphologic and morphometric changes observed in diabetic lungs were completely prevented in PT rats from 4 weeks after transplant.Conclusion. We conclude that PT can control morphologic and ultrastructural changes in pulmonary parenchyma, suggesting a promising perspective for preventing other chronic diabetic lesions.

Opinion of hepatic transplant waiting list patients regarding split liver transplantation

Background. Split liver transplantation (SLT) increases organ supply for hepatic transplantation. Long-term patient survival and complication rates seem to be equivalent between orthotopic liver transplantation (OLT) and SLT. There are controversies among transplant physicians due to an ethical dilemma between benefiting individual needs or those of society. Barshes and Goss (Am J Transplant 5:2047, 2005) demonstrated that the majority of adult liver transplant candidates are favorable to SLT. The aim of our study was to evaluate the opinions of patients at a Brazilian university hospital regarding SLT.Materials and Methods. A questionnaire with 14 questions was applied to 50 patients included in a hepatic transplant waiting list regarding SLT.Results. The overall attitudes of 66% of the participants were classified as utilitarian, 31% were classified as self-preserving, and 3% were undecided. Ninety-one percent of patients would be willing to share even if their expected survival after SLT was shorter than that with OLT. For 77% of patients, children must have priority over adults. However, 83% were unaware of the donors for pediatric transplantations.Conclusions. SLT is a consistent solution for organ demand despite controversies among transplant physicians. The present study demonstrated that most patients were favorable to SLT. In conclusion, attitudes toward graft sharing are not barriers to SLT.

Effect of haematocrit on pump and kidney dysfunction after myocardial revascularization

Objective - Kidney dysfunction is a common complication after cardiac surgery. It occurs in 7 to 31% of the patients. The lowest haematocrit after cardiopulmonary bypass surgery (LHCT) has been identified as a risk factor for kidney dysfunction after cardiac surgery. The aim of this study is to determine whether different levels of haematocrit during cardiopulmonary bypass surgery are related to kidney dysfunction.Methods and results-A prospective study was conducted on consecutive adult patients undergoing myocardial revascularization. Preoperative renal function was assessed by baseline serum creatinine level (CrPre). Peak postoperative creatinine (CrPost) was defined as the highest daily in-hospital postoperative value. Peak fractional change in creatinine (% Delta Cr) was defined as the difference between the CrPre and CrePost represented as a percentage of the preoperative value. The LHTC was defined as the lowest recorded haematocrit prior to weaning from the initial pump run. A category variable was created for haematocrit based on the distribution of values. The category variable had the following cut-off points: less than 23%, 23.1 to 28% and greater than 28.1 %. Lowest haematocrit (26.62 +/- 4.15%), CPB (74.71 +/- 24.90 min), CrPre (1.23 +/- 0.37 mg/dl) and highest CrPost (1.52 +/- 0.47 mg/dl) data varied in near-normal fashion. Statistical significance has been observed in the < 23% lowest haematocrit group (CrIPOD and Cr5POD; P = 0.006) and the 23.1 28% lowest haematocrit level group (CrPre and Cr2POD; P = 0.047). CrPre and Cr5POD did not differ between groups (P > 0.05). The multiple linear regression model confirmed that the determinants for higher %Delta Cr were age, body surface area and preoperative serum creatinine level.Conclusion - The LHTC was not identified as a risk factor for kidney dysfunction after myocardial revascularization.

Early initiation of dialysis: mortality and renal function recovery in acute kidney injury patients

INTRODUÇÃO: A decisão de quando iniciar a diálise em pacientes com lesão renal aguda (LRA) que apresentam síndrome urêmica está bem estabelecida, entretanto, com ureia < 200 mg/dl o melhor momento para iniciar a diálise torna-se incerto. OBJETIVO: Este estudo teve como objetivo avaliar a mortalidade e a recuperação da função renal em pacientes com LRA, cujo início da diálise ocorreu em diferentes níveis de ureia. MÉTODOS: Estudo retrospectivo desenvolvido em hospital escola, no estado de São Paulo, Brasil, envolvendo 86 pacientes submetidos à diálise. RESULTADOS: A diálise foi iniciada com uréia > 150 mg/dl em 23 pacientes (grupo I) e uréia > 150 mg/dl em 63 pacientes (grupo II). Hipervolemia e mortalidade foram mais frequentes no grupo I que no grupo II (65,2 x 14,2% - p < 0,05; 39,1 x 68,9% - p < 0,05, respectivamente). Entre os sobreviventes, a recuperação renal foi maior no grupo I (71,4 e 36,8%, respectivamente, p < 0,05). A análise multivariada mostrou risco independente de mortalidade relacionado à sepse, idade > 60 anos, diálise peritoneal e uréia > 150 mg/dl no início da diálise. CONCLUSÃO: Menor mortalidade e maior recuperação renal estão associadas com o diálise iniciada precocemente, conforme baixos níveis de ureia, em pacientes com LRA.

Can Delivery Dialysis Dose Affect Survival of Acute Kidney Injury Patients?

Intensity of dialysis dose in acute kidney injury (AKI) might benefit critically ill patients. The aim of this study was to evaluate the effect of intermittent hemodialysis (IHD) dose on mortality in patients with AKI. Methods: Prospective observational study was performed on AKI patients treated with IHD. The delivered dialysis dose per session was calculated based on single-pool Kt/V urea. Patients were allocated in two groups according to the weekly delivered median Kt/V: higher intensity dialysis dose (HID: Kt/V higher than median) and lower intensity dialysis dose (LID: Kt/V lower than median). Thereafter, AKI patients were divided according to the presence or absence of sepsis and urine output. Clinical and lab characteristics and survival of AKI patients were compared. Results: A total of 121 AKI patients were evaluated. Forty-two patients did not present with sepsis and 45 did not present with oliguria. Mortality rate after 30 days was lower in the HID group without sepsis (14.3% x 47.6%; p = 0.045) and without oliguria (31.8% x 69.5%; p = 0.025). Survival curves also showed that the HID group had higher survival rate when compared with the LID group in non-septic and non-oliguric patients (p = 0.007 and p = 0.003, respectively). Conclusion: Higher dialysis doses can be associated with better survival of less seriously ill AKI patients.

High volume peritoneal dialysis vs daily hemodialysis: A randomized, controlled trial in patients with acute kidney injury

There is no consensus in the literature on the best renal replacement therapy (RRT) in acute kidney injury (AKI), with both hemodialysis (HD) and peritoneal dialysis (PD) being used as AKI therapy. However, there are concerns about the inadequacy of PD as well as about the intermittency of HD complicated by hemodynamic instability. Recently, continuous replacement renal therapy (CRRT) have become the most commonly used dialysis method for AKI around the world. A prospective randomized controlled trial was performed to compare the effect of high volume peritoneal dialysis (HVPD) with daily hemodialysis (DHD) on AKI patient survival. A total of 120 patients with acute tubular necrosis (ATN) were assigned to HVPD or DHD in a tertiary-care university hospital. The primary end points were hospital survival rate and renal function recovery, with metabolic control as the secondary end point. Sixty patients were treated with HVPD and 60 with DHD. The HVPD and DHD groups were similar for age ( 64.2 +/- 19.8 and 62.5 +/- 21.2 years), gender ( male: 72 and 66%), sepsis ( 42 and 47%), hemodynamic instability ( 61 and 63%), severity of AKI ( Acute Tubular Necrosis-Index Specific Score (ATN-ISS): 0.68 +/- 0.2 and 0.66 +/- 0.2), Acute Physiology, Age, and Chronic Health Evaluation Score (APACHE II) (26.9 +/- 8.9 and 24.1 +/- 8.2), pre-dialysis BUN (116.4 +/- 33.6 and 112.6 +/- 36.8mg per 100 ml), and creatinine ( 5.8 +/- 1.9 and 5.9 +/- 1.4 mg per 100 ml). Weekly delivered Kt/V was 3.6 +/- 0.6 in HVPD and 4.7 +/- 0.6 in DHD ( P<0.01). Metabolic control, mortality rate ( 58 and 53%), and renal function recovery ( 28 and 26%) were similar in both groups, whereas HVPD was associated with a significantly shorter time to the recovery of renal function. In conclusion, HVPD and DHD can be considered as alternative forms of RRT in AKI.