Fluorescence-based bowel anastomosis perfusion evaluation: results from the IHU-IRCAD-EAES EURO-FIGS registry.

BACKGROUND: Anastomotic leakage (AL) is one of the dreaded complications following surgery in the digestive tract. Near-infrared fluorescence (NIRF) imaging is a means to intraoperatively visualize anastomotic perfusion, facilitating fluorescence image-guided surgery (FIGS) with the purpose to reduce the incidence of AL. The aim of this study was to analyze the current practices and results of NIRF imaging of the anastomosis in digestive tract surgery through the EURO-FIGS registry. METHODS: Analysis of data prospectively collected by the registry members provided patient and procedural data along with the ICG dose, timing, and consequences of NIRF imaging. Among the included upper-GI, colorectal, and bariatric surgeries, subgroup analysis was performed to identify risk factors associated with complications. RESULTS: A total of 1240 patients were included in the study. The included patients, 74.8% of whom were operated on for cancer, originated from 8 European countries and 30 hospitals. A total of 54 surgeons performed the procedures. In 83.8% of cases, a pre-anastomotic ICG dose was administered, and in 60.1% of cases, a post-anastomotic ICG dose was administered. A significant difference (p < 0.001) was found in the ICG dose given in the four pathology groups registered (range: 0.013-0.89 mg/kg) and a significant (p < 0.001) negative correlation was found between the ICG dose and BMI. In 27.3% of the procedures, the choice of the anastomotic level was guided by means of NIRF imaging which means that in these cases NIRF imaging changed the level of anastomosis which was first decided based on visual findings in conventional white light imaging. In 98.7% of the procedures, the use of ICG partly or strongly provided a sense of confidence about the anastomosis. A total of 133 complications occurred, without any statistical significance in the incidence of complications in the anastomoses, whether they were ICG-guided or not. CONCLUSION: The EURO-FIGS registry provides an insight into the current clinical practice across Europe with respect to NIRF imaging of anastomotic perfusion during digestive tract surgery.

Safety and Efficacy of a Novel Double-Stapling Technique for Distal Esophageal Resection and Esophago-Jejunal Anastomosis.

BACKGROUND: The purpose of this study was to evaluate safety and efficacy of a new esophagojejunal anastomosis (EJA) technique allowing the insertion of the anvil of a common circular stapler without hand-sewn securing. METHODS: From August 2014 to May 2015, 20 consecutive patients with esophagogastric junction adenocarcinoma underwent surgery. EJA was performed using a new technique; the free margins of the esophageal stump were suspended and the anvil of a circular stapler on a new dedicated and registered support bar (characterized by a push-rod making possible to hook-unhook the anvil of the circular stapler) was inserted into the lumen. Subsequently, the linear suturing stapler was closed over the bar and fired to suture the distal stump of the esophagus; the bar was retracted and the push-rod of the anvil was pulled out through the linear suture. Finally, the anastomosis was performed using a circular stapler. RESULTS: There were no intraoperative complications, and R0 resection was achieved in all cases. Postoperative course has been uneventful for 18 patients (90%). Only 1 patient (5%) developed fistula, conservatively treated. CONCLUSIONS: Our preliminary clinical experience suggested that this technique was safe and efficient (for all online suppl. material, see www.karger.com/doi/10.1159/000446856).

Safety and efficacy of the percutaneous treatment of bile leaks in hepaticojejunostomy or split-liver transplantation without dilatation of the biliary tree.

Biliary leaks complicating hepaticojejunostomy (HJA) or fistulas from cut surface are severe complications after liver transplantation (LT) and split-liver transplantation (SLT). The aim of the study was to describe our experience about the safety and efficacy of radiological percutaneous treatment without dilatation of intrahepatic biliary ducts. From 1990 to 2006, 1595 LTs in 1463 patients were performed in our center. In 1199 LTs (75.2%), a duct-to-duct anastomosis was performed, and in 396 (24.8%), an HJA was performed. One hundred twenty-nine anastomotic or cut-surface bile leakages occurred in 115 patients. Sixty-two biliary leaks occurred in 54 patients with HJA; in 48 cases, an anastomotic fistula was found. Cut-surface fistulas occurred in 14 cases: 5 in right SLTs and 5 in left SLTs. Twenty-two patients were treated with 23 percutaneous approaches for 17 HJA fistulas and 6 cut-surface leaks without intrahepatic bile duct dilatation. Two percutaneous therapeutic approaches were used: percutaneous transhepatic biliary drainage (PTBD) for fistula alone and PTBD with percutaneous drainage of biliary collection in patients with both complications. PTBD was successful in 21 cases (91.3%); the median delay from catheter insertion and leak resolution was 10.3 days (range: 7-41). The median maintenance of drainage was 14.8 days. In 1 patient, fistula recurrence after PTBD needed a surgical approach; after that, an anastomotic fistula was still found, and a new PTBD was successfully performed. In another patient, PTBD was immediately followed by retransplantation for portal vein thrombosis. There were no complications related to the interventional procedure. In conclusion, biliary fistulas after HJA in LT or after SLT can be successfully treated by PTBD. The absence of enlarged intrahepatic biliary ducts should not be a contraindication for percutaneous treatment.

Evaluation of a novel real-time PCR system for cytomegalovirus DNA quantitation on whole blood and correlation with pp65-antigen test in guiding pre-emptive antiviral treatment.

Successful pre-emptive anti-cytomegalovirus (CMV) therapy relies on sensitive, specific and reproducible tests for CMV detection. Real-time polymerase chain reaction (PCR) for CMV-DNA provides a superior reproducibility and sensitivity than pp65-antigenemia. Evaluation of a novel commercial real-time PCR for CMV-DNA associated with a fully automated DNA extraction from whole blood (WB) was performed, studying the correlation with pp65-antigenemia in guiding pre-emptive therapy. Analytical evaluation showed that PCR correctly quantitated CMV from 500 to 500,000copies/ml with a close correlation with expected values (r=0.999). Clinical evaluation on 375 consecutive WB samples from 48 infected patients (18 pre-emptively treated for pp65 values >/=50 positive cells) showed that according to pp65-antigenemia of 0, 1-10, 11-49 and >/=50 positive cells, median DNA levels were 3.7, 3.9, 4.6 and 5.6 log(10)copies/ml, respectively. According to existing pre-emptive treatment criteria based on pp65-antigenemia, receiver-operating curve analysis indicated 5.3log/ml (200,000genomes/ml) as the best CMV-DNA level to discriminate between patients requiring pre-emptive therapy and those who did not (positive predictive value: 91%; negative predictive value: 74%; sensitivity and specificity: 68 and 93%). In conclusion, real-time PCR provides reliable results for monitoring the developing of CMV infection, allowing for the definition of CMV-DNA thresholds associated with infection progress.

Comparison of the Cobas Ampliprep/Cobas TaqMan HBV Test versus the Cobas Amplicor HBV monitor for HBV-DNA detection and quantification during antiviral therapy.

Performances of the new automatic system COBAS AmpliPrep/COBAS TaqMan 48 (CAP/CTM) (Roche, Branchburg, NJ) for HBV DNA extraction and real-time PCR quantification were assessed and compared with the endpoint PCR COBAS AMPLICOR HBV Monitor (CAHBM, Roche). Analytical evaluation with proficiency panels from UK National External Quality Assessment Scheme (UK NEQAS) over a 1-year period of distribution showed that CAP/CTM correctly measured HBV DNA levels with a close correlation between expected and observed values (r=0.995). Clinical evaluation as tested with samples from 11 HBsAg-positive patients undergoing antiviral therapy (71 serial specimens of plasma), demonstrated excellent correlation with CAHBM (r=0.958, mean difference in quantitation: 0.14 log, IU/ml), but CAP/CTM detected longer period of residual viremia. HBV DNA reduction was much higher in the combination schedule (Lamivudine+Adefovir), than in Adefovir monotherapy (5.1 vs. 3.5 logs). In conclusion, CAP/CTM allows for an accurate and standardized quantification of HBV DNA in high through-put laboratories. Due to it high sensitivity, it may further improve the detection of emerging drug resistance strains and the assessment of antiviral therapy.

Platelet-activating factor synthesis and response on pancreatic islet endothelial cells: relevance for islet transplantation.

BACKGROUND: Recent data suggest that donor intraislet endothelial cells may survive islet transplantation and participate to the events that influence islet engraftment. However, the mechanisms that regulate islet endothelial behavior in this setting are poorly known. METHODS: We obtained immortalized human (hIECs) and mouse (mIECs) islet endothelial cells by transfection with SV40-T-large antigen and studied the synthesis and response to Platelet-activating factor (PAF), a multipotent phospholipid that acts as endothelial mediator of both inflammation and angiogenesis. RESULTS: HIECs showed typical endothelial markers such as expression of vWF, CD31, and CD105, uptake of acetylated-LDL and binding to ULE-A lectin. Moreover, they expressed nestin, the PAF-receptor and possess surface fenestrations and in vitro angiogenic ability of forming tubular structures on Matrigel. Likewise, mIECs showed expression of vWF, CD31, nestin, PAF-receptor and CD105, and uptake of acetylated-LDL. HIECs and mIECs rapidly produced PAF under stimulation with thrombin in a dose-dependent way. Exogenous PAF or thrombin-induced PAF synthesis increased leukocyte adhesion to hIECS and mIECs and cell motility of both endothelial cell lines. Moreover, PAF or thrombin-induced PAF synthesis accelerated in vitro formation of vessel-like tubular structures when hIECs are seeded on Matrigel. Notably, gene-microarray analysis detected up-regulation of beta3 integrin gene on hIECs stimulated with PAF, that was confirmed at the protein level. CONCLUSIONS: Based on the novel development of immortalized islet endothelium, these results suggest that PAF may have a dual role that links inflammation to angiogenesis in the early events of islet transplantation.

"Small is beautiful" A series of ileo-anal anastomoses performed with the 25 - mm circular stapler.

AIM: With the idea that a small diameter stapler should cause less sphincter trauma, we began to use the 25mm circular stapler to perform ileo-pouch-anal anastomosis (IPAA) and we report our experience. MATERIAL OF STUDY: A retrospective study using a bowel function questionnaire and a quality of life questionnaire has been conducted on a group of patients who underwent IPAA using a 25mm stapler RESULTS: We performed IPAA using a 25mm circular stapler in 37 patients. Postoperative mortality was nil and morbidity was 27%. One anastomotic stenosis occurred. Long term follow-up information was available on 28 patients. Mean follow-up was 70 months (range 8-177). Mean number of bowel movements was 4.5 (range 2-10, median 4.5) during the day and 0.9 (range 0-10, median 0) at night. Out of 28 patients, 19 (68%) were fully continent and 32% had occasional soiling, no one reported incontinence. All patients except one were able to withold their stool for more than 15 minutes. Daytime pad use was: never 86%, occasionally 3%, frequently 11%; nightime pas use was never 86%, occasionally 7% and frequently 7%. Bowel regulating drugs use was never 82%, occasionally 14%, regularly 4%. Evacuation difficulties were: never 75%, occasionally 21%, frequently 4%. DISCUSSION: Our results compare favourably with the literature, which reports median bowel frequency 6-7.6/24h, 9.4- 33% urgency, 17-44% daytime soiling and 32-61% nighttime soiling. CONCLUSIONS: Our results must be considered preliminary but we found the 25-mm stapler safe and adequate to perform IPAA. KEY WORDS: IPAA, Ulcerative Colitis, Stapler, Function.

Unusual Presentation of Recurrent Early Stage Endometrial Carcinoma 28 Years after Primary Surgery.

Endometrial carcinoma is the most common neoplasia of female genital tract. The prognosis of early stage disease (FIGO I and FIGO II) is excellent: recurrence after surgery is less than 15%, most of which are reported within 3 years after primary treatment. Herein we report a case of late rectal recurrence from FIGO Ib endometrial adenocarcinoma. Patient had also familiar and personal history of colonic adenocarcinoma and previous findings of microsatellite instability (MSI); molecular analysis evidenced heterozygotic somatic mutation in MLH1 gene. Twenty-eight years after hysterectomy and bilateral salpingoovariectomy, a rectal wall mass was detected during routine colonoscopy. Patients underwent CT scan, pelvic MRI, and rectal EUS with FNA: histopathological and immunohistochemical analysis revealed differentiated carcinoma cells of endometrial origin. No neoadjuvant treatment was planned and low rectal anterior resection with protective colostomy was performed; histology confirmed rectal lesion as metastasis from endometrial carcinoma. Recurrence of early stage endometrial carcinoma after a long period from primary surgery is possible. It is important to keep in mind this possibility in order to set a correct diagnostic and therapeutic algorithm, including preoperative immunohistochemical staining, and to plan a prolonged follow-up program.

A rare case of IgG4-related systemic disease manifesting with pancreatic head mass mimicking borderline resectable cancer.

INTRODUCTION: Autoimmune pancreatitis (AIP) is a rare pancreatic disorder among chronic pancreatitis that can mimick pancreatic cancer (PC). Patients with type 1 AIP usually present obstructive jaundice associated with high level of IgG4 in serum and a pancreatic mass at radiological imaging; these disorders may be associated with other organs lesions presenting the same histopathological features, and in these cases AIP should be considered a pancreatic localization of an IgG4-related systemic disease. PRESENTATION OF CASE: We report the case of a young man with initial suspect of PC to be treated with surgery, and final diagnosis of AIP in the context of an IgG4-related systemic disease. DISCUSSION: Because of its similar features, several algorithms have been proposed for AIP diagnosis, based on combination of clinical/serological and radiological criteria. However, histology represents the only way to obtain definitive diagnosis, even if sometimes it is difficult to obtain biological samples. CONCLUSION: IgG4-related systemic disease must be taken into account among differential diagnosis during the workup for PC, in order to avoid unnecessary surgery.

Efficacy, safety, and pharmacokinetics of intramuscular hepatitis B immune globulin, Igantibe, for the prophylaxis of viral B hepatitis after liver transplantation.

BACKGROUND: Long-term prophylaxis of hepatitis B virus (HBV) positive liver transplanted subjects with intravenous hepatitis B immunoglobulin (HBIG) is effective, however use of intramuscular HBIG could be as effective with fewer adverse events and lower cost. AIM: We conducted a prospective, non-randomized, clinical study to assess the efficacy and safety of HBIG from Grifols, Igantibe, for the prophylaxis of HBV reactivation. METHODS: Eighteen adult patients submitted to liver transplantation for HBV-related disease more than 18 months earlier were treated with doses of 2000 I.U. intramuscular Igantibe every 14 days for 6 months. RESULTS: Mean trough serum HBsAb IgG titers from months 4 to 6 (primary efficacy variable) were protective (>or=150 I.U./L) at each time point. Individual measurements were also protective throughout the study. HBV replication remained negative for all available subjects until study completion. Pharmacokinetic analysis showed a half-life of 27 days and extensive exposure to the study drug. Safety and tolerability of intramuscular Igantibe were good, with only one adverse event. CONCLUSION: Standard-dose intramuscular Igantibe administration proved efficacious in post-liver transplantation prophylaxis by attaining protective levels for up to 6 months, was safe and well tolerated. Pharmacokinetic analysis revealed a long half-life and extensive exposure.

Intraoperative placement of transparietohepatic biliary drainage in remedial hepaticojejunostomy: technique and clinical experience.

Remedial biliary surgery most often entails a Roux-en-Y hepaticojejunostomy. Sometimes the duct wall at the porta hepatis has been so damaged by inflammatory changes that the postoperative external drainage of bile away from a biliodigestive suture at risk of dehiscence is advisable. A technique of intraoperative placement of transparietohepatic biliary drainage was devised. The maneuver implies retrograde cannulation of a major intrahepatic duct with a vascular irrigation needle that is pushed to create the transhepatic path. Of 220 remedial hepaticojejunostomies performed in 211 patients (including 151 liver transplant recipients), the technique was applied in 49 (22%) of the most difficult cases in which the preoperative radiologic approach to the biliary tree had failed, was unsafe, or was unfeasible. The only major complication was a parenchymal tear needing perihepatic packing when the maneuver was performed too early after liver transplantation. Postoperative biliary fistula occurred in 2 patients (4%) and access to the biliary tract for percutaneous bilioplasty was provided in the short-term follow-up evaluation of 14 patients (29%).

COBAS AmpliPrep-COBAS TaqMan hepatitis B virus (HBV) test: a novel automated real-time PCR assay for quantification of HBV DNA in plasma.

Success in antiviral therapy for chronic hepatitis B is supported by highly sensitive PCR-based assays for hepatitis B virus (HBV) DNA. Nucleic acid extraction from biologic specimens is technically demanding, and reliable PCR results depend on it. The performances of the fully automatic system COBAS AmpliPrep-COBAS TaqMan 48 (CAP-CTM; Roche, Branchburg, NJ) for HBV DNA extraction and real-time PCR quantification were assessed and compared to the endpoint PCR COBAS AMPLICOR HBV monitor (CAHBM; Roche). Analytical evaluation with a proficiency panel showed that CAP-CTM quantitated HBV DNA levels in one single run over a wide dynamic range (7 logs) with a close correlation between expected and observed values (r = 0.976, interassay variability below 5%). Clinical evaluation, as tested with samples from 92 HBsAg-positive patients, demonstrated excellent correlation with CAHBM (r = 0.966, mean difference in quantitation = 0.36 log(10) IU/ml). CAP-CTM detected 10% more viremic patients and longer periods of residual viremia in those on therapy. In lamivudine (LAM)-resistant patients, the reduction of HBV DNA after 12 months of Adefovir (ADF) was higher in the combination (LAM+ADF) schedule than in ADF monotherapy (5.1 logs versus 3.5 logs), suggesting a benefit in continuing LAM. CAP-CTM detected HBV DNA in liver biopsy samples from 15% of HBsAg-negative, anti-HBcAg-positive graft donors with no HBV DNA in plasma. The amount of intrahepatic HBV DNA was significantly lower in occult HBV infection than in overt disease. CAP-CTM can improve the management of HBV infection and the assessment of antiviral therapy and drug resistance, supporting further insights in the emerging area of occult HBV infection.

Quantitation of cytomegalovirus DNA by real-time polymerase chain reaction in peripheral blood specimens of patients with solid organ transplants: comparison with end-point PCR and pp65 antigen test.

The polymerase chain reaction (PCR) for cytomegalovirus (CMV) DNA quantitation provides sensitive and specific data for detecting CMV as well as monitoring the infection and determining the appropriate antiviral strategy. A recently introduced real-time PCR assay for CMV DNA quantitation was applied on 158 peripheral blood leukocytes (PBLs) from 32 liver-transplanted patients with CMV asymptomatic infection and correlated with a commercial quantitative end-point PCR (COBAS AMPLICOR CMV Monitor) and CMV pp65 antigenemia. A good correlation was found between real-time PCR and pp65 antigen test (r2 = 0.691) and the two PCR assays (r2 = 0.761). Real-time PCR data were higher in pre-emptive treated patients (>20 pp65 + positive cells, median CMV DNA value: 3.8 log(10) copies/500,000 PBLs) than in not-treated ones (2.9 logs). According to pp65 levels of 0, 1-10, 11-20, 21-50, 51-100, and >100 positive cells/200,000 PBLs, median CMV DNA by real-time PCR was 2.6, 3.0, 3.6, 4.0, 4.2, and 4.8 logs, respectively, (CMV DNA levels by COBAS AMPLICOR: 2.8, 2.9, 3.8, 3.7, 3.9, and 4.0 logs). For samples with >20 pp65 + cells, real-time PCR gave significantly higher values than in groups with <20 pp65 + cells, whereas the COBAS AMPLICOR results showed a slower progression rate. Dilutions of CMV AD169 strain were used to probe real-time PCR reproducibility (between and intra-assay variability <2%) and sensitivity (100% detection rate at 10 copies/reaction, 28.5% with end-point PCR). In conclusion, real-time PCR significantly improves the study of CMV DNA dynamics due to a more reliable quantitation of CMV DNA for moderate and high DNA level compared to end-point PCR with better sensitivity and specificity. Real-time PCR provides more precise information for evaluating infection progress and assessing antiviral response, simplifying and accelerating the process of producing a reliable quantitation of CMV DNA for clinical purposes.

Bacterial- and fungal-positive cultures in organ donors: clinical impact in liver transplantation.

Infection transmission from donor to recipient is a dreadful complication in transplantation. Although bacteremia was previously detected in 5% of donors without negative impact on recipient outcome, the current expansion of graft pool requires consideration of the infectious risk associated with suboptimal donors. This study aims to evaluate the incidence and risk factors of infection in unselected cadaveric liver donors, the occurrence of microorganism transmission to recipient and its influence on patient survival. Results of microbiologic cultures obtained before harvesting in intensive care unit (ICU) and routinely at harvesting from 610 consecutive liver donors were retrospectively analyzed. Evidence for bacterial and fungal transmission to the recipient was searched for in each culture-positive donor. One or more cultures were positive in 293 donors (48%), while bacteremia was present in 128 (21%). Culture-positive and bacteremic donors were of significantly older age and had longer ICU stays. At multivariate analysis, an ICU stay of 3 or more days was the only significant predictor of donor infection. Although 1-year patient/graft survival rates were not influenced by donor culture positivity, pathogen transmission occurred in 11 cases with high recipient 1-year mortality (45%). In those 11 cases, median donor age was 74 years, significantly much older than that of the other culture-positive donors. In conclusion, donors with a prolonged ICU stay are at increased risk of infection, while older donor age is associated with pathogen transmission to the recipient. Adequate donor maintenance and careful microbiologic surveillance and treatment, especially of elderly donors, may limit transmission of donor infection.

Transplantation of hepatitis B surface antigen-positive livers into hepatitis B virus-positive recipients and the role of hepatitis delta coinfection.

The scarcity of liver donors requires consideration of grafts from sources not previously used. Allografts from hepatitis B surface antigen (HBsAg)-carriers without a significant liver disease have been proposed for liver transplant recipients with hepatitis B virus (HBV)-related cirrhosis and hepatocellular carcinoma (HCC). Combination prophylaxis schemes against HBV post-liver transplantation (LT) recurrence are currently available; the efficacy of those schemes in HBV-related cirrhosis and HCC must be assessed. This report describes the allocation of HBsAg-positive grafts in three HBsAg-positive recipients, with HBV-related cirrhosis and evolving HCC lesions, two of them with hepatitis Delta virus (HDV) coinfection. Patients were administered anti-hepatitis B immunoglobulins (HBIGs) and lamivudine in order to prevent HBV recurrence. In spite of anti-HBV prophylaxis, HBV infection did persist after LT in all patients (no serum clearance of HBsAg). HBV replication assessed by serum HBV deoxyribonucleic acid (DNA) presence was detected in the first month after LT in the 3 recipients. A prompt HDV reinfection with a clinical and histological pattern of hepatitis was observed in the 2 HBV / HDV coinfected recipients. In 1 of them, an evolving chronic hepatitis required a second LT. The non-HDV-infected patient showed an uneventful follow-up, but the lack of the neutralizing effect of HBIGs and the high risk of escape mutants forced the addition of adefovir-dipivoxil to lamivudine, in order to prevent viral variants and hepatitis recurrence. In conclusion, allografts from HBsAg-positive donors in HBsAg-positive recipients are associated with the persistence of the HBsAg after LT due to the failure of HBIG prophylaxis, even if lamivudine does inhibit virion production. This condition favors HDV replication and HDV hepatitis recurrence in coinfected patients. The allocation of HBsAg-positive grafts in HBsAg-positive recipients could be justified only in recipients without HDV coinfection and a combined prophylaxis with lamivudine and adefovir-dipivoxil is currently the best way to manage escape mutants in these recipients.

Severe course of primary hyperoxaluria and renal failure after domino hepatic transplantation.

We report herein a domino orthotopic liver transplantation (LT), from a 38-year-old woman undergoing liver-kidney transplantation (LKT) for primary hyperoxaluria type I (PH1) to a recipient with cirrhosis and hepatocellular carcinoma. Delayed onset of PH1 and renal failure and 10% residual alanine-glyoxylate aminotransferase (AGT) activity in domino liver justified its use for domino procedure. The clinical course after LKT was similar to that described in other series, including ours. Renal function started promptly and maintained despite sustained hyperoxaluria from dissolution of oxalotic deposits. Conversely, the domino recipient manifested severe hyperoxaluria and developed nephrolithiasis and renal insufficiency with rapid progression over 2 months. A new LT resulted in slow decrease of oxaluria and improvement of renal function. Therefore, PH1 behaved quite differently in these two patients, leading us to conclude that domino LT using livers from PH1 patients should be considered very carefully, only as a bridge to definitive LT in recipients with critical clinical conditions.

Posttransplantation chronic renal damage in nonrenal transplant recipients.

BACKGROUND: The growing problem of relentless deterioration of renal function in patients who undergo transplantation of nonrenal solid organs is bound to have an increasingly important impact as it may not only worsen patient morbidity and mortality but also increase transplantation costs. METHODS: We reviewed the literature in order to provide a sum of the most important data on the incidence, clinical picture, renal pathology pattern, damage mechanisms, and risk factors, along with strategies for prevention and treatment of chronic renal damage following nonrenal solid organ transplantation. RESULTS: Literature data report that 10% to 80% of transplanted patients have some degree of renal dysfunction and that they share a common clinical picture characterized by relentless asymptomatic progression, frequent hypertension, mild urinary abnormalities, and pathology features of vascular, glomerular, tubular, and interstitial involvement. These changes are very similar to those reported for chronic nephrotoxicity from calcineurin inhibitors. The occurrence of end-stage renal disease (ESRD) requiring chronic dialysis has been reported in up to 20% of nonrenal transplant recipients. Although there are some organ-specific differences, a group of common risk factors has been recognized, including the use of calcineurin inhibitors as immunosuppressive agents, age, pretransplantation renal function, intraoperative/perioperative factors, concomitant use of other nephrotoxic drugs, infections, and posttransplantation acute renal failure. CONCLUSION: Calcineurin inhibitor-induced nephrotoxicity is a growing problem and, as the age of recipients of nonrenal organs is increasing, this problem is destined to increase. It would therefore be advisable for nephrologists to share their experiences in immunomodulation with other specialties, so as to favor the cautious extension of calcineurin inhibitor-sparing protocols to the area of life-saving transplants.