The ratio of plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury in patients undergoing liver transplantation

Background

Postoperative acute kidney injury (AKI) is associated with high morbidity and mortality after liver transplantation (OLT). Previous studies have shown the value of plasma neutrophil gelatinase-associated lipocalin (NGAL) taken 2 hours after reperfusion of the liver graft as an early marker predicting AKI. The study was performed to determine whether plasma NGAL concentrations obtained as early as 1 hour after reperfusion was predictive of AKI and whether the NGAL ratio was an early predictor for AKI in the first 48 hours after OLT.

Methods

Twenty-six liver transplant recipients donated plasma samples for NGAL determinations at induction (T1), at graft reperfusion (T3) as well as after 1 (T4) and hours 2 (T5), and at the end of the surgery (T7). AKI was defined at 48 hours after liver transplantation according to the acute kidney injury network criteria. Predictive ability was assessed using areas under the curve of receiver operator characteristic analyses.

Results

The area under the curve of the receiver operator characteristics curve of (plasma NGAL concentration at T4)/(plasma NGAL concentration at T1) to predict AKI was 0.717 at T5, 0.765 at T7, 0.714 at T8 (24 hours post-OLT), and 0.781 at T9 (48 hours post-OLT).

Conclusion

The plasma NGAL concentrations taken 1 hour after reperfusion of the liver graft seem to be predictive of AKI; the NGAL changing ratio may be an early predictor for AKI in the first 48 hours after OLT.     

The association of promoter gene polymorphisms of the tumor necrosis factor-α and interleukin-10 with severity of lactic acidosis during liver transplantation surgery

Background

Orthotopic liver transplantation (OLT) is a major operation, causing cytokine release and other inflammatory responses that can contribute to postreperfusion syndrome occurrence. During the systemic inflammatory response syndrome, increased lactate levels result from excessive cytokine production despite normal oxygen delivery and carbohydrate metabolism. The goal of the study was to determine the relationship between genetic polymorphisms in interleukin (IL)-10 (−1082G/A) or tumor necrosis factor (TNF)-α (−376 G/A) and lactate levels in patients during OLT surgery.

Patients and Methods

This prospective observational study in 40 consecutive adult patients who underwent OLT documented lactic acid levels at 5 times: Immediately after induction of anesthesia, at the end of the pre-anhepatic phase, at the end of the anhepatic phase, 1 hour after reperfusion, and at the end of surgery. Polymerase chain reaction (PCR; RFLP methodology) was used to examine IL-10 (−1082G/A) and TNF-α (−376 G/A) gene polymorphisms.

Results

Carriers of the IL-10/TNF-α genotype combination GG/GG showed significantly different changes in lactate levels at 1 hour after reperfusion and at the end of surgery. Lactate levels were significantly higher among patients heterozygous for TNF-α (AG genotype) compared with patients homozygous for TNF-α (GG genotype) at same times. In contrast, there was no significant difference among IL-10 polymorphic genotypes (−1082G/A).

Conclusion

Genetic factors play a role in the development of lactic acidosis after OLT. IL-10 (−1082G/A) and TNF-α (−376 G/A) gene polymorphisms could influence the variability of lactate levels after liver transplantation surgery.     

A novel in situ model of liver cold ischemia–reperfusion in rats

Background

Orthotopic liver transplantation (OLT) is being used for studying cold ischemia reperfusion (I/R)-induced injury in experimental animals, but the technique is complicated and it does not accurately reflect the pathophysiology. Here, we report a novel model, termed “in situ liver cold ischemia (ISLCI)”, in Wistar rats.

Methods

ISLCI was achieved in rats by establishing a portal-jugular shunt and a cannula shunt in inferior vena cava, and the liver was continuously perfused with lactate Ringer's solution at a speed of 150 mL/h through the portal vein for 60 min. Portal venous pressure, serum levels of total bilirubin, alkaline phosphatase, alanine aminotransferase and γ-glutamyl transpeptidase (GGT), and hepatic histopathology were examined, and compared with rats undergoing OLT, in which the donor liver was subjected to a 60 min cold ischemia.

Results

Livers from ISLCI and OLT rats showed histopathologic changes characteristic of I/R-induced injury when examined on days 1 and 7, with complete recovery 14 d after reperfusion. Compared with OLT rats, ISLCI rats had significantly lower levels of portal venous pressure 1 and 10 min after porta hepatis clamping. They suffered a milder degree of I/R-induced hepatic injury, reflected by significantly lower levels of GGT, alanine aminotransferase, and alkaline phosphatase on day 1, and a significant lower level of GGT and a lower histopathologic score on day 7 after reperfusion.

Conclusions

Our preliminary results indicate that the ISLCI model is reliable and technically easier, and is superior to OLT for studying cold I/R injury.     

Ischemic Reperfusion Injury–Induced Oxidative Stress and Pro-inflammatory Mediators in Liver Transplantation Recipients

Objective

Liver ischemic reperfusion injury is harmful to transplant recipients, and is associated with postoperative morbidity and mortality. Our study was designed to investigate the oxidative stress and pro-inflammatory mediators in liver transplant recipients.

Methods

We prospectively analyzed 14 recipients who underwent liver transplantation by measuring their blood levels of malondialdehyde (MDA) and cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, at nine time points perioperatively. We also evaluated the correlations between oxidative stress (MDA levels) and the characteristics of the recipient or the donated graft.

Results

These parameters significantly increased from 1 minute before reperfusion, and the values peaked within 3 to 30 minutes after reperfusion. On the time point at 5 minutes after reperfusion, the MDA levels which were the highest in the recipients correlated with the values of preoperative direct/and total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), model for end-stage liver disease (MELD) score, international normalized ratio (INR), and surgical blood loss.

Conclusion

The levels of MDA, TNF-α, IL-1β, and IL-6 greatly increased with the ischemic reperfusion insult. Recipients with higher values of preoperative direct/and total bilirubin, AST, ALT, MELD score, INR, and surgical blood loss tended to have higher levels of MDA and may suffer more injury from this insult.     

Transplantation Is a Risk Factor for Acute Kidney Injury in Patients Undergoing Total Hip Replacement Arthroplasty for Avascular Necrosis: An Observational Study

Background

The increased number of patients undergoing transplantation has increased the number of transplant recipients undergoing total hip replacement arthroplasty (THRA). We have evaluated the association between transplantation and acute kidney injury (AKI) in patients undergoing THRA.

Methods

Patients who underwent THRA from May 2004 to February 2012 were retrospectively assessed. Their demographic and clinical characteristics, the results of perioperative laboratory tests, the amounts of fluids transfused during surgery, and anesthesia time were evaluated. Patients were divided into 2 groups: transplant (n = 222) and nontransplant (n = 2,044) patients. With use of the maximal Acute Kidney Injury Network criteria, AKI was evaluated by changes in creatinine concentration within 48 hours of THRA. Propensity analyses and logistic regression were performed to evaluate the association between transplantation and postoperative AKI.

Results

Postoperative AKI was significantly associated with transplantation (P < .0001), and transplantation was an independent factor predictive of postoperative AKI (P < .0001).

Conclusions

Transplant recipients are at risk for AKI following THRA. The mechanism by which organ transplantation enhances postoperative AKI warrants further evaluation.     

Association Between Serum C-Reactive Protein and Albumin Levels and Psychiatric Comorbidities in Liver Transplant Recipients

Background

Orthotopic liver transplantation (OLT) is the definitive treatment for patients with end-stage liver disease. Many post-OLT patients have psychiatric comorbidities. The relationship between psychiatric comorbidities and biological factors, such as C-reactive protein (CRP) and albumin levels, in OLT recipients has seldom been investigated.

Methods

We analyzed medical charts of all patients aged over 18 who underwent orthotopic OLT at a tertiary medical center between September 2008 and July 2010 for serum CRP and albumin levels before and 1 month after OLT. Data for baseline characteristics, such as gender, age, and body mass index (BMI), were also collected. Patients who had a psychiatric consultation or took psychotropic medications during the hospitalization were categorized as “with psychiatric comorbidities.”

Results

Psychiatric comorbidities existed in 51 (33.8%) of 151 OLT recipients. By analysis of covariance adjusted for age and BMI, post-OLT CRP levels in patients with psychiatric comorbidities were significantly higher than those without psychiatric comorbidities (P = .015). For patients with psychiatric comorbidities, the paired t test showed significantly increased CRP levels at 1 month after when compared to the pre-OLT baseline levels (P = .044). Patients without psychiatric comorbidities had significantly decreased CRP levels at 1 month after when compared with the pre-OLT baseline levels (P = .009).

Conclusions

Elevated CRP levels may indicate activation of a systemic inflammatory process caused by psychiatric comorbidities in OLT recipients.     

NKG2D Blockade Significantly Attenuates Ischemia-Reperfusion Injury in a Cardiac Transplantation Model

Background

NKG2D (natural killer group 2 member D), are activating or coactivating receptor on NK cells, γδ T, and CD8⁺ T cells, stimulates cytokine secretion by the former two and plays a costimulatory role for the last CD8⁺ T cells.

Methods

Male Lewis rat hearts were flushed and stored in cold Bretschneider preservation solution for 8 hours. Anti-NKG2D monoclonal antibody (mAb) was administered before transplantation into syngeneic recipients. Expressions of Troponin-T, myeloperoxidase (MPO), tumor necrosis factor (INF), (ICAM) and interleukin (IL)-17 were examined on days 1, 3, and 7 after reperfusion.

Results

We observed that isografts from anti-NKG2D mAb-treated animals showed decreased cardiac troponin-T, low expression of MPO, TNF, and ICAM, and superior cardiac output. Furthermore, blockade of NKG2D significantly reduced the number of γδ T cells, which are the main source of IL-17 production.

Conclusion

Blockade of NKG2D significantly attenuated ischemia-reperfusion injury in a cardiac transplantation model. The effect coincided with a low expression of TNFα, ICAM and a reduced number of infiltrating IL-17–producing γδ T cells.     

Le dosage plasmatique de Neutrophil Gelatinase-Associated Lipocalin (NGAL) prédit la défaillance rénale au cours du choc septique dès l’admission en réanimation

Purpose

To validate plasma Neutrophil Gelatinase-Associated Lipocalin (pNGAL) as an early biomarker in intensive care unit (ICU) for acute kidney injury (AKI) in critically ill adult with septic shock.

Patients and method

Fifty consecutive patients with septic shock were included in this observational cohort study. AKI was defined if patients met any RIFLE or AKIN criteria. The main objective was to evaluate diagnosis value of pNGAL measured with a point-of-care device at admission (D0), at 24 hours (D1) and at 48 hours (D2).

Results

Among the 50 patients enrolled, 86% had AKI, 48% had persistent renal AKI and 30% required renal replacement therapy (RRT) during their ICU stay. At D0, pNGAL concentration was significantly higher in patients with AKI compared to patients without AKI (471 ng/mL versus 134 ng/mL, P < 0.001). This level remained significantly higher in the AKI population at D1 and D2 and pNGAL concentration at D0 among AKI patients increased with kidney failure level. At D1, pNGAL was significantly higher for persistent renal AKI rather than transient prerenal (570 ng/mL versus 337 ng/mL, P = 0.027). pNGAL concentration below 348 ng/mL at D1 was never seen in patients with RRT.

Conclusion

Plasma NGAL is a useful, sensitive and early biomarker to predict persistent AKI in septic shock at ICU admission and help to discuss RRT.     

Role of progesterone in melatonin-mediated protection against acute kidney injury

Background

Melatonin is released by pineal gland and maintains circadian rhythm in the body. It has been reported as renoprotective agent because of its antioxidant property. Recently, a cross talk between progesterone and melatonin has been observed in various preclinical studies. The present study investigated the involvement of progesterone receptors in melatonin-mediated protection against ischemia reperfusion induced acute kidney injury (AKI) in rats.

Materials and methods

The rats were subjected to bilateral renal ischemia for 40 min followed by reperfusion for 24 h to induce AKI. The AKI was assessed by measuring creatinine clearance, serum urea, uric acid level, potassium level, fractional excretion of sodium, lactate dehydrogenase activity, and microproteinuria. The oxidative stress in renal tissues was assessed by quantification of myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, reduced glutathione level, and catalase activity. The hematoxylin–eosin staining was carried out to observe histopathologic changes in renal tissues. The melatonin (4 and 10 mg/kg, intraperitoneally) and progesterone receptor antagonist mifepristone (5 mg/kg, intraperitoneally) were used in the present study.

Results

The renal ischemia reperfusion induced AKI as indicated by significant change in serum, urinary, and tissue parameters that was ameliorated by prior treatment with melatonin. No significant difference in serum progesterone level was observed between various groups used in the present study. The prior administration of mifepristone abolished melatonin-mediated protection against AKI.

Conclusions

It is concluded that melatonin treatment affords protection against ischemia reperfusion induced AKI. Moreover, progesterone receptors are essentially involved in mediating protective role of melatonin against AKI in rats.     

Locally increased concentrations of inflammatory cytokines in an experimental intraabdominal adhesion model

Background

Peritoneal adhesions may cause bowel obstruction, infertility, and pain. This study investigated cytokines, proteins and growth factors thought to promote formation of adhesions in an experimental intraabdominal adhesion model.

Methods

Male Sprague-Dawley rats were subjected to laparotomy, cecal abrasion, and construction of a small bowel anastomosis and examined at various time points after surgery. Concentrations of cytokines and growth factors in plasma and peritoneal fluid were analyzed using electrochemoluminescence and quantitative sandwich enzyme immunoassay technique.

Results

Concentrations of interleukin-6 (IL-6), interleukin-1beta (IL-1β), and tumor necrosis factor alpha (TNF-α) increased in peritoneal fluid from 6 h after incision. Plasma concentrations of IL-6 increased at 6 h, but plasma concentrations of IL-1β and TNF-α remained low. Peritoneal fluid concentrations of platelet-derived growth factor-BB (PDGF-BB), transforming growth factor beta1 (TGF-β1), vascular endothelial growth factor (VEGF), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) were below detection levels at all time points.

Conclusion

Early elevations of IL-6, IL-1β, and TNF-α concentrations in peritoneal fluid correlated to adhesion formation in this rodent model. Our model is relevant and reproducible, suitable for intervention, and indicates that antiadhesion strategies should be early, local and not systemic.     

Preconditioning Donor Livers With Cromolyn or Compound 48/80 Prolongs Recipient Survival in a Rat Orthotopic Liver Transplantation Model

Background

Acute rejection (AR) remains a challenge in organ transplantation. Preconditioning donor organs can reduce AR and prolong survival. Whether preconditioning with cromolyn (CRM), a mast cell (MC) stabilizer, or compound 48/80 (CMP 48/80), a MC degranulator, can alleviate AR and prolong survival has not been studied.

Methods

We used the male-DA-to-female-Lewis-rat orthotopic liver transplantation (OLT) model. Donors were preconditioned with CRM in a MC stabilizing way (CRM group) or CMP 48/80 in a MC depleting way (CMP 48/80 group). Rats preconditioned with phosphate-buffered saline were used as controls (PBS group). After preconditioning, OLT surgeries were carried out. OLT male-Lewis-to-female-Lewis-rats were used as the syngeneic group (syngeneic group).

Results

Rats in the PBS group developed AR rapidly and died at 7.40 ± 1.14 days. Rats in the CRM and CMP 48/80 groups had significantly slower rejections and died at day 17.40 ± 1.67 or 14.20 ± 2.28, respectively (P < .05). Rats in the syngeneic group survived more than 60 days. Rejection activity indexes (RAIs) and liver functions were all alleviated through CRM or CMP 48/80 preconditioning. Interferon-γ messenger RNA (mRNA) expressions were reduced and interleukin-10 mRNA levels were higher in allografts in the CRM and CMP 48/80 groups, compared with the PBS group. These were confirmed by testing serum interferon-γ and interlerkin-10.

Conclusion

Preconditioning donor livers with CRM or CMP 48/80 can reduce AR and prolong survival of recipients after OLT.     

Neutrophil gelatinase associated lipocalin as an indicator of acute kidney injury and inflammation in burned children

Introduction

Neutrophil gelatinase associated lipocalin (NGAL) is a novel predictor of acute kidney injury (AKI), which increases with inflammation. We aimed to assess whether serum NGAL (SNGAL) and urine NGAL (UNGAL) can predict AKI in burned children.

Methods

Patients were referred within the 12 h of burn to our center. Serum samples for SNGAL, C-reactive protein (CRP), procalcitonin (PCT) and urine for UNGAL, microalbumine (Umalb), creatinine (Ucr) were obtained at both admission and the 5th day after burn. Blood urea nitrogen (BUN) and serum creatinine (Scr) were examined daily.

Results

Twenty-two subjects were enrolled and six (27.2%) of them developed AKI within the 48 h of injury. Burn size and abbreviated burn severity index (ABSI) were significantly increased in patients with AKI. CRP, PCT, SNGAL and UNGAL levels at admission and day 5 were significantly higher in patients with AKI than in those without AKI and controls. Scr was not significant between AKI and non-AKI groups at hospital days 1 and 5. A SNGAL level of 315 ng/ml and a UNGAL level of 100 ng/ml were determined as predictive cut-off values of AKI at admission (sensitivity and specificity: 71.4%, 83.3% and 93.3%, 93.7%, respectively). SNGAL and UNGAL were positively correlated with CRP, PCT, ABSI and Umalb/Ucr.

Conclusion

SNGAL and UNGAL are good early predictors of AKI in children with severe burn. NGAL might reflect the severity of burn insult and also could be used as an indicator of inflammation in burn children.     

Clinical Outcomes and Risk Factors of Hepatitis B Virus Recurrence in Patients Who Received Prophylaxis With Entecavir and Hepatitis B Immunoglobulin Following Liver Transplantation

Introduction

Although entecavir (ETV) and hepatitis B immunoglobulin (HBIG) have widely been used for prophylaxis of hepatitis B virus (HBV) recurrence following liver transplantation (OLT), there have been few studies about clinical outcomes and risk factors of HBV recurrence.

Materials and methods

This study retrospectively assessed clinical outcomes and identified risk factors of post-transplant HBV recurrence in 154 patients who received prophylaxis with both ETV and HBIG after OLT.

Results

The median follow-up duration was 28.0 months (range, 1.0–57.8). Post-transplant HBV recurrence occurred in 5 patients (3.2%) without any ETV-resistant mutants. The overall rates of HBV recurrence at 1, 2, and 4 years were 0.6%, 1.6%, and 6.2%, respectively. We found that recurrent hepatocellular carcinoma (HCC) was an independent risk factor of HBV recurrence (hazard ratio = 13.5, 95% confidence interval, 2.4–74.4; P = .006).

Conclusions

Prophylaxis with a combination of ETV and HBIG resulted in a low HBV recurrence rate following OLT without any emergence of ETV-resistant mutants. Recurrent HCC was an independent risk factor of HBV recurrence in patients who received prophylaxis with both ETV and HBIG for prophylaxis following OLT.     

A New Formula as a Predictive Score of Post–Liver Transplantation Outcome: Postoperative MELD-Lactate

Introduction

Liver transplantation (OLT) involves a 5% to 10% 30-day mortality rate. Multiple scores have been used as predictors of early postoperative mortality, such as the original Model for End-stage Liver Disease (MELD) and MELD sodium. Investigations have been conducted over the last 5 years to find new predictors of early post-OLT mortality.

Objective

The aim of this study was to develop a new mathematical model to predict the individual chance of 30-day mortality after OLT.

Methods

The study was conducted on 58 patients submitted to OLT at the University Hospital, between October 2008 and March 2012. The 29 latest survivor and 29 latest nonsurvivor cases were selected. Arterial blood sodium, lactate, international normalized ratio, total bilirubin, and creatinine values were determined 1 hour after the end of surgery. The MELD original equation, MELD sodium, and new MELD lactate were also elaborated. The results were analyzed by the Mann-Whitney and Wilcoxon tests. The level of significance was set at .05.

Results

The new formula elaborated was as follows: MELD lactate = 5.68 × log_e (lactate) + 0.64 × (Original MELD) + 2.68. The MELD lactate values were significantly higher than the MELD sodium and original MELD values (P < .05). The area under the receiver operating characteristic curve of MELD lactate in predicting the outcome of patients submitted to OLT was 0.80, as opposed to 0.71 for the original MELD and 0.72 for MELD sodium (P < .05).

Conclusion

The postoperative MELD lactate score proved to be more specific and sensitive than the original MELD and MELD sodium as a predictive model of the outcome of patients submitted to OLT.     

The 4-week serum creatinine level predicts long-term renal dysfunction after adult living donor liver transplantation

Objectives

Recipients after liver transplantation. (OLT) often experience renal dysfunction. Acute kidney injury (AKI) and chronic kidney disease (CKD) after OLT occur among 20% to 50% and 30% to 90% of recipients, respectively; 2% to 5% of them deteriorate into end-stage renal disease each year. Since the predictable factors for CKD have not been well identified. We sought to investigate the incidence and predictors of CKD at 5 years after OLT.

Patients and methods

Between August 2002 and December 2005, we enrolled 77 patients who underwent adult living donor OLT with over 2 years of follow-up. The strategies to prevent renal dysfunction included induction with basiliximab to delay the use of tacrolimus: addition of mycophenolate mofetil to reduce the tacrolimus dosage; avoidance of the calcineurin inhibitor using sirolimus or administration of an angiotensin II receptor antagonist. The clinical variables were reviewed for analysis.

Results

The mean follow-up was 76 ± 14 months. The incidence of AKI (over 50% increase level of creatinine) was 29%. Ten (13.0%) patients developed CKD (creatinine > 2 mg/dL). One (1.3%) subject developed end-stage renal disease requiring hemodialysis. Upon multivariate analysis the development of CKD was significantly associated with the posttransplant 4-week creatinine level: 0.92 ± 0.23 versus 1.37 ± 0.93 mg/dL (P = .008).

Conclusion

The 4-week creatinine value was predictive of the occurence of CKD over 5 years after OLT.     

Experience of Combined Liver-Kidney Transplantation for Acute-on-Chronic Liver Failure Patients With Renal Dysfunction

Background

The aim of this study was to evaluate the outcomes of orthotopic liver transplantation (OLT) or combined liver-kidney transplantation (CLKT) for acute-on-chronic liver failure (ACLF) patients with renal dysfunction.

Methods

From January 2001 to December 2009, 133 patients underwent OLT for ACLF at our center. Among them, 30 had both ACLF and renal dysfunction. Of the 30 patients, 12 underwent CLKT for end-stage renal disease (ESRD), and the other 18 with hepatorenal syndrome type 1 (HRS1) underwent OLT alone. ACLF was defined according to the Asian Pacific Association for the Study of Liver Consensus Meeting. Clinical data were reviewed for survival outcomes.

Results

The median model for end-stage liver disease score (MELD) of patients with ACLF was 28. Among the 133 patients, all of whom received deceased donor liver grafts, 12 also got the kidney grafts from the same deceased donor. The hospital mortality rate was 21.8% for all patients with ACLF. The 5-year survival rates were 72.8% for patients without renal dysfunction and 70% for patients with renal dysfunction. The results of patients with ESRD who underwent CLKT were better than those of subjects without renal dysfunction or patients with HRS1 who underwent OLT alone.

Conclusions

OLT alone improved renal function in most patients with HRS1, including those requiring short-term hemodialysis. Simultaneous liver-kidney transplantation was an excellent strategy for patients with both ACLF and ESRD. It provided protection to the kidney allograft for liver-based metabolic diseases affecting the kidney. The rate of acute rejection episodes in kidneys was low.     

De Novo Malignancies Following Liver Transplantation: Results From a Multicentric Study in Central and Southern Italy, 1990–2008

Objective

The objective of this study was to quantify incidence rates (IR) and risks of de novo tumors (except nonmelanoma skin cancers) in patients who underwent orthotopic liver transplantation (OLT) in central and southern Italy.

Methods

Data were collected on 1675 patients (75.5% males) who underwent OLT in six Italian transplantation centers in central and southern Italy (1990–2008). The time at risk of cancer (person years [PY]) was computed from OLT to the date of cancer diagnosis, death, or last follow-up, whichever occurred first. The number of observed cancer cases were compared with the expected one using data from population-based cancer registries. We computed gender- and age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs).

Results

During 10,104.3 PYs (median follow-up, 5.2 years), 98 patients (5.9% of the total) were diagnosed with a de novo malignancy (for a total of 100 diagnoses). Twenty-two of these cancers were post-transplantation lymphoproliferative disorders (PTLD; 18 non-Hodgkin lymphoma [NHL] and 2 Hodgkin's lymphoma [HL]), 6 were Kaposi's sarcoma (KS), and 72 were solid tumors (19 head and neck [H&N], 13 lung, 11 colon-rectum, 6 bladder, and 4 melanoma). The overall incidence was 9.9 cases/10³ PYs, with a 1.4-fold significantly increased SIR (95% CI, l.2–1.7). Significantly increased SIRs were observed for KS (37.3), PTLD (3.9), larynx (5.7), melanoma (3.1), tongue (7.1), and H&N (4.5) cancers.

Conclusions

These results confirmed that OLT patients are at greater risk for cancer, mainly malignancies either virus-associated or related to pre-existent factors (eg, alcohols). These observations point to the need to improve cancer surveillance after OLT. The on-going enrollment of patients in the present cohort study will help to elucidate the burden of cancer after OLT and better identify risk factors associated with its development.     

Involvement of peroxisome proliferator–activated receptor gamma in vitamin D–mediated protection against acute kidney injury in rats

Background

Vitamin D has been reported as renoprotective agents in various studies. Recently, a few in vitro studies highlighted cross talk between vitamin D and peroxisome proliferator–activated receptor gamma (PPAR-γ). The present study investigated the activation of PPAR-γ as novel mechanism in vitamin D–mediated protection against ischemia reperfusion–induced acute kidney injury (AKI) in rats.

Materials and methods

The AKI was induced by clamping renal pedicles for 40 min followed by reperfusion for 24 h. The AKI was assessed by measuring creatinine clearance, serum urea, uric acid level, and lactate dehydrogenase activity. Moreover, serum potassium, calcium level, fractional excretion of sodium, and microproteinuria were measured in rats. The oxidative stress in renal tissues was assessed by quantification of thiobarbituric acid–reactive substances, superoxide anion generation, reduced glutathione level, and catalase and myeloperoxidase activities. The hematoxylin-eosin staining was carried out to observe histopathologic changes in renal tissues. Vitamin D (0.25, 0.5, and 1 μg/kg) was administered for 7 d before subjecting rats to renal ischemia reperfusion injury (IRI).

Results

The renal IRI in rats induced significant changes in serum, urinary, and oxidative stress parameters in renal tissues. Moreover, hematoxylin-eosin staining revealed marked damage produced by IRI in renal tissues. The administration of vitamin D at 0.5 μg/kg dose afforded maximum protection against renal IRI. The prior treatment with PPAR-γ antagonist bisphenol A diglycidyl ether significantly attenuated protective effect of vitamin D, thus confirming involvement of PPAR-γ in vitamin D–mediated renoprotection.

Conclusions

It is concluded that activation of PPAR-γ significantly contributes toward vitamin D–mediated protection against ischemia reperfusion–induced AKI.     

Gonadotropin-releasing Hormone Agonists and Acute Kidney Injury in Patients with Prostate Cancer

Background

Androgen deprivation therapy (ADT) might increase the risk of acute kidney injury (AKI) in patients with prostate cancer (PCa).

Objective

To examine the impact of ADT on AKI in a large contemporary cohort of patients with nonmetastatic PCa representing the US population.

Design, setting, and participants

Overall, 69 292 patients diagnosed with nonmetastatic PCa between 1995 and 2009 were abstracted from the Surveillance Epidemiology and End Results–Medicare database.

Outcomes measurements and statistical analyses

Patient in both treatment arms (ADT vs no ADT) were matched using propensity-score methodology. Ten-year AKI rates were estimated. Competing-risks regression analyses tested the association between ADT and AKI, after adjusting for the risk of death during follow-up.

Results and limitations

Overall, the 10-yr AKI rates were 24.9% versus 30.7% for ADT-naive patients versus those treated with ADT, respectively (p < 0.001). When patients were stratified according to the type of ADT, the 10-yr AKI rates were 31.1% versus 26.0% for men treated with gonadotropin-releasing hormone (GnRH) agonists and bilateral orchiectomy, respectively (p < 0.001). In multivariable analyses, the administration of GnRH agonists (hazard ratio [HR]: 1.24; 95% confidence interval [CI], 1.18–1.31; p < 0.001), but not bilateral orchiectomy (HR: 1.11; 95% CI, 0.96–1.29; p = 0.1), was associated with the risk of experiencing AKI. Our study is limited by its retrospective design.

Conclusions

ADT is associated with an increased risk of AKI in patients with nonmetastatic PCa. In particular, the administration of GnRH agonists, but not surgical castration, may substantially increase the risk of experiencing AKI. These observations should help provide physicians with better patient selection to reduce the risk of AKI.

Patient summary

The administration of gonadotropin-releasing hormone agonists, but not bilateral orchiectomy, increases the risk of acute kidney injury (AKI) in patients with prostate cancer (PCa). These observations should help provide physicians with better patient selection to reduce the risk of AKI in PCa patients.