Richard V. Perez

Effect of Intravascular Volume Expansion on Renal Function During Prolonged CO2 Pneumoperitoneum

OBJECTIVE To evaluate whether intravascular volume expansion would improve renal blood flow and function during prolonged CO2 pneumoperitoneum. SUMMARY BACKGROUND DATA Although laparoscopic living donor nephrectomies have a considerably reduced risk of complications for the donors, significant concerns exist regarding procurement of a kidney in the altered physiologic environment of CO2 pneumoperitoneum. Recent studies have documented adverse effects of CO2 pneumoperitoneum on renal hemodynamics. METHODS Renal and systemic hemodynamics and renal histology were studied in a porcine CO2 pneumoperitoneum model. After placement of a pulmonary artery catheter, carotid arterial line, Foley catheter, and renal artery ultrasonic flow probe, CO2 pneumoperitoneum (15 mmHg) was maintained for 4 hours. Pigs were randomized into three intravascular fluid protocol groups: euvolemic (3 mLkg/hour isotonic crystalloid), hypervolemic (15 mL/kg/hour isotonic crystalloid), or hypertonic (3 mL/kg/hour isotonic crystalloid plus 1.2 mL/kg/hour 7.5% NaCl). RESULTS In the euvolemic group, prolonged CO2 pneumoperitoneum caused decreased renal blood flow, oliguria, and impaired creatinine clearance. Both isotonic and hypertonic volume expansions reversed the changes in renal blood flow and urine output, but impaired creatinine clearance persisted. CONCLUSIONS Intravascular volume expansion alleviates the effects of CO2 pneumoperitoneum on renal hemodynamics in a porcine model. Hypertonic saline (7.5% NaCl) solution may maximize renal blood flow in prolonged pneumoperitoneum, but it does not completely prevent renal dysfunction in this setting. This study suggests that routine intraoperative volume expansion is important during laparoscopic live donor nephrectomy.

Higher surgical wound complication rates with sirolimus immunosuppression after kidney transplantation: A matched-pair pilot study

Sirolimus, a potent new immunosuppressant, has been anecdotally associated with surgical wound complications. We studied postoperative surgical wound complications in 15 kidney recipients receiving sirolimus, prednisone, and tacrolimus or cyclosporine (study group) compared with 15 recipients receiving tacrolimus, prednisone, and mycophenolate mofetil who were pair-matched for surgical wound complication risk factors. Surgical wound complications were defined as any complication related to the surgical transplant wound requiring reintervention. Fifty-three percent of the study group and 7% of the control group experienced more than one surgical wound complication (P =0.014), and the relaparotomy incidence was 33% and 7%, respectively. Four graft losses have occurred since the beginning of the study: one chronic rejection and two deaths with function in the study group, and one death with function in the control group. At 1 year, graft survival for study recipients compared with control recipients was 87% and 93%, respectively; patient survival was 93% in both groups. Recipients receiving sirolimus demonstrated a significantly higher surgical wound complication rate, but graft and patient survival were not affected. Peritransplant immunosuppression with sirolimus and steroids warrants careful consideration, particularly in recipients with surgical complication risk factors.

Effect of prolonged pneumoperitoneum on intraoperative urine output during laparoscopic gastric bypass.

BACKGROUND Intraoperative oliguria is common during laparoscopic operations. The objective of this study was to evaluate the effects of prolonged pneumoperitoneum during laparoscopic gastric bypass (GBP) on intraoperative urine output and renal function. METHODS 104 patients with a body mass index between 40 and 60 kg/m2 were randomly assigned to laparoscopic (n = 54) or open (n = 50) GBP. Intraoperative urine output was recorded at 30-min intervals. Blood urea nitrogen and creatinine levels were measured at baseline and on postoperative days 1, 2, and 3. Levels of antidiuretic hormone, aldosterone, and plasma renin activity were also measured in a subset of laparoscopic (n = 22) and open (n = 24) GBP patients at baseline, 2 hours after surgical incision, and in the recovery room. RESULTS The laparoscopic and open groups were similar in age, gender, and body mass index. There was no significant difference in amount of intraoperative fluid administered between groups (5.4 +/- 1.6 L, laparoscopic versus 5.8 +/- 1.7 L, open), but operative time was longer in the laparoscopic group (232 min versus 200 min, p < 0.01). Urinary output during laparoscopic GBP was 64% lower than during open GBP at 1 hour after surgical incision (19 mL versus 55 mL, p < 0.01) and continued to remain lower than that of the open group by 31-50% throughout the operation. Postoperative blood urea nitrogen and creatinine levels remained within the normal range in both groups. Serum levels of antidiuretic hormone, aldosterone, and plasma renin activity peaked at 2 hours after surgical incision with no significant difference between the two groups. CONCLUSION Prolonged pneumoperitoneum during laparoscopic gastric bypass significantly reduced intraoperative urine output but did not adversely alter postoperative renal function.

Delivery of antioxidative enzyme genes protects against ischemia/reperfusion–induced liver injury in mice

Hepatic ischemia/reperfusion (I/R) injury is characterized by the generation of reactive oxygen species (ROS), such as superoxide anions and hydrogen peroxide. The aim of this study is to investigate whether antioxidative gene delivery by our polylipid nanoparticles (PLNP) is an effective approach for prevention of the injury. Polyplexes of extracellular superoxide dismutase (EC‐SOD) and/or catalase genes were injected via the portal vein 1 day prior to a warm I/R procedure in mice. The effects of the gene delivery were determined 6 hours after starting reperfusion. PLNP‐mediated antioxidative gene delivery led to a marked increase in human EC‐SOD and catalase gene expression in the liver. Liver superoxide dismutase (SOD) and catalase activity both increased approximately 10‐fold. Increased liver superoxide anion levels caused by the I/R procedure were reduced to normal levels by EC‐SOD gene delivery. The overexpression of these 2 antioxidative genes significantly suppressed the I/R‐induced elevation of serum alanine aminotransferase (ALT) levels, decreased liver malondialdehyde content, restored glutathione reserve, and improved liver histology. In conclusion, EC‐SOD or catalase gene delivery by PLNP resulted in high levels of the transgene activity in the liver, and markedly attenuated hepatic I/R injury. The protection is directly associated with elevated antioxidative enzyme activity as the result of the gene delivery. This novel approach may become a potential therapy to improve graft function and survival after liver transplantation. Liver Transpl 12:1869–1879, 2006.

Laparoscopic (vs open) live donor nephrectomy: a UNOS database analysis of early graft function and survival.

The impact of laparoscopic (lap) live donor nephrectomy on early graft function and survival remains controversial.

Improvements in diabetic microangiopathy after successful simultaneous pancreas-kidney transplantation: a computer-assisted intravital microscopy study on the conjunctival microcirculation.

A computer-assisted intravital microscopy technology has been developed to noninvasively and objectively study diabetic microangiopathy in the conjunctival microcirculation of type-1 diabetics. Quantitative characterization of the conjunctival microcirculation was performed on 12 patients pre- and 18 months postsimultaneous pancreas-kidney transplantation (SPK). Healthy nondiabetic volunteers (n=12), solitary kidney (K) transplanted type-1 diabetics (n=5), and nontransplanted type-1 diabetics (n=12) served as controls. Pre-SPK diabetics showed abnormal-sized venules (diameter=66+/-7 microm) and reduced presence of arterioles (arteriole length/area=18+/-6 microm(-1)) compared with nondiabetic controls (53+/-4 microm; 31+/-8 microm(-1); P<0.05). The computed vascular perfusion capacity of the conjunctival microvasculature was diminished in the same patients (pre-SPK diabetics=49+/-9%; nondiabetic healthy controls=71+/-6%; P<0.05). Significant improvement in microangiopathy was observed in all post-SPK diabetics (diameter=58+/-6 microm; arteriole length/area=26+/-9 microm(-1); vascular perfusion=63+/-8%; P<0.05) 18 months post-SPK. Blood flow velocities in the conjunctival microcirculation in the same post-SPK patients showed noticeable but not significant improvements (nondiabetic controls=2.94+/-0.57 mm/sec; pre-SPK=1.23+/-0.49 mm/sec; post-SPK=1.65+/-0.42 mm/sec). The solitary kidney transplant controls (post-K) showed no significant improvements in diabetic microangiopathy, confirming the unique role of the pancreas in SPK. In general, significant improvements (P<0.05) in diabetic microangiopathy were observed in all 12 diabetics 18 months post-SPK but not in the controls.

Role of cytomegalovirus infection in allograft rejection: a review of possible mechanisms.

Several lines of evidence indicate that viral infections, particularly with cytomegalovirus (CMV), play a role in the pathogenesis of solid organ allograft rejection. A diagnostic feature of acute rejection is infiltration of allograft parenchyma by lymphocytes, a process regulated by induction of adhesion molecules on vascular endothelial cells and their ligand on leucocytes. Data derived from biopsies of CMV-infected transplant recipients, as well as from experimental models of transplantation, indicate that CMV infection can result in an upregulation of such adhesion molecules, thereby facilitating the inflammatory process. Infection with CMV is also associated with an increased expression of MHC class II on multiple cell types. Since recognition of nonself MHC antigens is the major determinant of allograft rejection, an upregulation of these molecules could contribute to graft failure. Infection with CMV has also been implicated in the induction of smooth muscle proliferation and intimal thickening, both hallmarks of transplant atherosclerosis, which constitutes the most common cause of heart allograft failure. CMV can be classified into four, possibly five, different genotypes based on restriction length polymorphism of the envelope glycoprotein B gene; these genotypes may exhibit varied geographic and demographic frequency distributions and also differ in their pathogenicity and cell tropism. Further studies are needed to evaluate these issues and in particular the genetic contribution of the recipient to CMV modulation of rejection.

Laparoscopic Live Donor Nephrectomy: A Risk Factor for Delayed Function and Rejection in Pediatric Kidney Recipients? A UNOS Analysis

The impact of laparoscopic (vs. open) donor nephrectomy on early graft function and survival in pediatric kidney recipients (≤18 years) is unknown.

Pretransplant systemic inflammation and acute rejection after renal transplantation.

BACKGROUND There are presently no established pre-transplant tests that consistently identify patients who may be at increased risk for acute rejection episodes after renal transplantation. We studied whether pretransplant serum levels of C-reactive protein (CRP), a marker for the presence of systemic inflammation, would predict the occurrence of acute rejection episodes after renal transplantation. METHODS Pretransplant serum was tested for CRP level in 97 consecutive renal transplant recipients. Time to acute rejection after transplantation was stratified by CRP level and compared using the Kaplan-Meier method. In addition, Cox regression multivariate analysis was performed to assess whether any pretransplant covariates could independently predict the subsequent occurrence of acute rejection episodes. RESULTS Pretransplant mean CRP levels were higher in patients who subsequently had a rejection episode versus those who had no rejection (22.2+/-2.9 vs. 11.7+/-1.8 microg/ml, respectively, P=0.003). Patients less than the median CRP value had a significantly longer time to rejection compared to those with higher CRP levels (P=0.002). Similarly, patients within the lowest CRP quartile had longer times to rejection when compared with the highest quartile (P=0.006). Cox proportional hazards regression multivariate analysis identified CRP level as the only independent pretransplant risk factor for rejection identified (P=0.044). CONCLUSIONS Pretransplant systemic inflammation as manifested by elevated serum CRP level independently predicts the risk of acute rejection after renal transplantation and may be useful in stratifying patients at the time of transplantation according to immunological risk. Thus, assessment of pretransplant systemic inflammatory status may be helpful in prospective individualization of immunosuppression therapy after renal transplantation.

Similar Long-Term Outcomes for Laparoscopic Versus Open Live-Donor Nephrectomy Kidney Grafts : An OPTN Database Analysis of 5532 Adult Recipients

Prior studies that included both adult and pediatric recipients suggested slower early graft function for laparoscopically (vs. openly) procured live donor kidney grafts (LD-Ktxs). Any potential long-term impact, however, remains unknown. We compared long-term outcomes of 2685 (49%) laparoscopic vs. 2847 (51%) open LD-Ktxs reported to the Organ Procurement and Transplantation Network performed in adult (≥18 yrs) recipients between November 1999 and December 2000, with follow-up to February 2006. Acute and chronic rejection accounted for 152 laparoscopic (51%) vs. 148 (46%) open graft losses (P=NS). At discharge and at 5 years, graft function was similar for both groups; graft survival at 5 years was 79% (laparoscopic) vs. 80% (open) (P=NS). We conclude that despite prior reports of slower early laparoscopic LD-Ktx function, both laparoscopic and open nephrectomy are equally effective for procurement of kidneys for adult recipients with regard to short- and long-term (>5 years) function and survival. Future studies must investigate whether these findings apply also to pediatric LD-Ktx recipients.