Factors Influencing Long-Term Survival of Kidney Grafts Transplanted From Deceased Donors-Analysis Based on a Single-Center Experience.

BACKGROUND: Kidney transplantation is a routine procedure in the treatment of patients with kidney failure and requires collaboration of experts from different disciplines. Improvements in the procedure result from numerous factors. METHODS: The analyzed group consisted of 150 patients divided into 2 equal subgroups: long-term (>15 years) and short-term (<6 years) graft survival. The following factors were taken into consideration: graft survival time, HLA mismatches, recipient sex, sex compatibility, panel reactive antibodies (PRA), cold ischemia time (CIT), and cause of kidney insufficiency. Factors were analyzed in groups with the use of Student t and chi-square tests, Kruskal-Wallis analysis of variance (ANOVA), and multifactorial ANOVA. RESULTS: Basic statistical analysis revealed no significance between long-term and short-term survival groups in HLA mismatches, recipient sex, or sex compatibility. There was a very significant difference in CIT. ANOVA revealed no statistical difference between groups in recipient sex, sex compatibility, or recipient disease. There were more patients in the group with long-term survival with lower PRA. There were more women in the group with long-term survival who received kidneys from men. Multifactorial analysis revealed no interactions or independent influence of the selected factors. CONCLUSIONS: CIT was a strong independent factor influencing graft survival. Recipient sex and cause of kidney insufficiency seemed to have no impact. Lower PRA was positively correlated with long-term survival. Women who received kidneys from men lived longer with functioning grafts.

Prostate-Specific Antigen: Nonspecific in Deceased Organ Donors.

Currently, there is no clear position regarding the donation of organs from donors with prostate carcinoma (CaP) in European countries, except Italy. The lengthening of life expectancy increases the probability of prostate cancer among potential organ donors. The concentration of prostate-specific antigen (PSA) >2 ng/mL at 60 years of age is related to the increasing possibility of identifying an advanced form of CaP. In recent years in Poland, the recommendation has been to determine tumor markers in potential donors. In the first year of the recommendation, 10% of potential male cadaveric donors were disqualified in West Pomerania, Poland, on the basis of elevated PSA levels (>10 ng/mL). To avoid reduction of the actual donor pool, each potential male donor reported to the center since January 2010 undergoes a routine histologic evaluation of the whole prostate, regardless of the PSA level, before organ implantation. In the study group (N = 52), histopathologic evaluation revealed 6 cases of CaP (12%). In CaP positive group Gleason score range from 2+2 to 3+4. In CaP donors PSA level have been noticed in range 1.79 ng/mL - 7.66 ng/mL. There was no correlation between histologically confirmed CaP and the PSA level.

Anti-human leukocyte antigen antibodies are present in blood of blood donors: is therapy with blood preparations safe for graft recipients?

BACKGROUND: Blood products infusions are often administrated to graft recipients. Post-transfusion reactions of anti-human leukocyte antigen antibodies (anti-HLA) are responsible for transfusion-related acute lung injury, but cases of graft rejection after blood product infusions were recently also proven. METHODS: The aim of this study was to assess, with the use of the very sensitive Luminex technology and traditional lymphocytotoxic test, the prevalence and cytotoxic activity of anti-HLA in blood donors with different medical histories to evaluate a potential risk of post-transfusion immune complications. Data were analyzed according to different normalized background cutoffs (1.5, 2.2; and the high cutoffs-10.8 for I class and 6.9 for II class anti-HLA). RESULTS: We observed that anti-HLA may be present in 36% of donors, and even in up to 73.6% of risk groups. Significant risk factors included female sex (23.9% to 64.2% for different cutoffs) and pregnancy history (30% to 72.5%), regardless of the cutoff used in analysis, whereas sera from female donors showed lower cytotoxicity (panel reactive antibodies). Anti-HLA were also detected in men (3.7% to 37%), in donors after a transfusion (0% to 62.5%), and even with no known risk factors (3.8% to 26.9%). CONCLUSIONS: Luminex technology is a sensitive tool in anti-HLA detection, but consensus in measurement interpretation for blood donors is needed. Selection of blood products on the basis of medical history can be a useful alternative for routine testing of blood donors. The clinical significance of treatment of graft recipients with blood products requires further study; until then, more attention should be paid to possible complications.

Analysis of specificity of anti-human leukocyte antigen antibodies in kidney recipients in reference to clinical outcome.

BACKGROUND: Anti-human leukocyte antigens antibodies (HLA) are not always the main cause of graft injury but can be a marker of immune response to the graft. The aim of this study was to analyze anti-HLA specificities with the use of the most sensitive detection method (Luminex) in reference to clinical condition. METHODS: Sera of 65 kidney recipients (n = 443) were screened with the use of the mixed LABScreen kit, and, for 47 recipients, sera with maximal normalized background ratio (NBG) were subjected to specificity testing. NBG, numbers of specificities, donor-specific antibodies (DSA), and normalized mean fluorescence index (nMFI) of DSA and maximal anti-HLA were analyzed in reference to clinical (acute rejection [AR] diagnosis, immunosuppression), histopathological (C4d staining, chronic allograft nephropathy, AR type), and laboratory parameters (creatinine). RESULTS: We observed 1 to 51 specificities, class I DSA in 26.7%, class II in 10%, and estimated DQ-DSA in 63.3% of tested patients. Patients with AR and humoral AR had significantly higher NBG, number of anti-HLA class I, DQ and DQ-DSA types, and more frequently had anti-HLA and class II DSA-positive sera (P < .052). C4d staining was associated with higher anti-HLA class I (P = .053) and class I DSA (P = .002) type numbers, and maximal anti-HLA nMFI (P = .036) and was more frequent in AR (P = .048) and class II DSA positive patients (P = .046). Patients with chronic allograft nephropathy showed higher DQ-DSA-nMFI (P = .036). DQ-DSA-nMFI and maximal anti-HLA-nMFI correlated with creatinine increase (Spearman range [SR] = 0.64, SR = 0.41). Together with NBG, maximal class I and class II anti-HLA-nMFI correlated with the number of transplantation and maximal panel-reactive antibodies ratio (SR = 0.19-0.40). CONCLUSIONS: Anti-HLA detection allows for humoral AR diagnosis but also for identification of patients with risk of any rejection. However, clear rules of anti-HLA interpretation and studies on their clinical impact are needed.

Proteinuria after kidney transplantation, relationship to allograft histology and survival.

Proteinuria is associated with reduced kidney allograft survival. Herein we assessed the association between proteinuria, graft histology and survival. The cohort included 613 kidney allograft recipients who had proteinuria (measured) and surveillance biopsies at 1-year posttransplant. Proteinuria >150 mg/day was detected in 276 patients (45%) and in 182 of these, proteinuria was below 500. In >84% of patients even low levels of proteinuria were associated with albuminuria. Proteinuria was associated with the presence of graft glomerular pathology and the use of sirolimus. Eighty percent of patients with proteinuria >1500 mg/day had glomerular pathology on biopsy. However, lower levels of proteinuria were not associated with specific pathologies at 1 year. Compared to no sirolimus, sirolimus use was associated with higher prevalence of proteinuria (40% vs. 76%, p < 0.0001) and higher protein excretion (378 + 997 vs. 955 + 1986 mg/day, p < 0.0001). Proteinuria was associated with reduced graft survival (HR = 1.40, p = 0.001) independent of other risk factors including, glomerular pathology, graft function, recipient age and acute rejection. The predominant pathology in lost allografts (n = 57) was glomerular, particularly in patients with 1-year proteinuria >500. Thus, proteinuria, usually at low levels (<500 mg/day), is present in 45% of recipients at 1 year. However, and even low levels of proteinuria relate to poor graft survival. Proteinuria and glomerular pathology relate independently to survival.

Purine and cytokine concentrations in the renal vein of the allograft during reperfusion.

The impairment of organ function derived from ischemia-reperfusion injury is still an important problem in solid organ transplantation. Cell alterations induced by ischemia prime the tissue for subsequent damage during the reperfusion phase. The aim of present study was to examine the association between changes in cytokine and purine metabolite concentrations in graft renal vein during reperfusion. The study included 17 recipients of cadaveric renal grafts: 10 men and seven women of overall mean age of 49 +/- 7 years and cold ischemia time 25 +/- 3 hour. The levels of interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, interferon (INF)-gamma, tumor necrosis factor (TNF)-beta, and TNF-alpha in renal graft vein plasma during 5 first minutes of reperfusion were quantified by flow cytometry. Increased concentrations of IL-6, TNF-alpha, and IL-1beta were observed during reperfusion. The IFN-gamma concentrations correlated negatively with xanthine (Xan) concentrations in renal vein blood during reperfusion, whereas there was a positive correlation between IL-2 and Xan concentrations. Moreover, the concentrations of IL-6 and IL-10 correlated negatively with hypoxanthine concentrations, and the concentrations of IL-4 also correlated negatively with Xan concentrations. The results of this study indicated the enhanced release of some cytokines during kidney graft reperfusion. It occurred in association with release of purine metabolites-the markers of energy status of renal tissue. Therefore, the enhanced cytokine production during reperfusion might influence ischemia-reperfusion injury and the early graft function.

Circulating adhesion molecules during kidney allograft reperfusion.

Adhesion molecule expression is an important event during early transplant failure. The aim of the present study was to examine the release of adhesion molecules during the first minutes of kidney allograft reperfusion in relation to delayed graft function and acute graft rejection. We enrolled 49 renal transplant recipients, including 13 cases of delayed graft function (DGF) and 11 cases of acute graft rejection (AR). Plasma concentrations of E-selectin, VCAM-1 and ICAM-1 after 3 min of reperfusion were significantly higher than in the iliac vein before reperfusion. There was no statistically significant difference between patients with and without DGF as regards E-selectin, VCAM-1 and ICAM-1 concentrations in the iliac vein before and in the renal vein after 3 min of reperfusion. Concentrations of adhesion molecules in the iliac vein before reperfusion and in the renal vein after 3 min of reperfusion did not differ significantly between patients with and without AR except for ICAM-1 iliac vein concentration which was significantly increased in AR patients. Plasma levels of E-selectin, ICAM-1 and VCAM-1 were increased after kidney allograft reperfusion. Moreover, elevated serum levels of ICAM-1 before transplantation correlated with subsequent acute kidney allograft rejection. The results suggest that elevated ICAM-1 levels may be implicated in acute graft rejection.

Interpreting post-transplant proteinuria in patients with proteinuria pre-transplant.

Increasing numbers of patients receive kidney transplants before initiation of dialysis or shortly thereafter. Some of these patients have significant proteinuria pre-transplant making the interpretation of post-transplant proteinuria problematic. In this study, we evaluated post-transplant proteinuria in 115 patients who had urine protein measured within 3 months of transplant and assessed the association of proteinuria with allograft pathology. Proteinuria declined rapidly from 3650 +/- 3702 mg/day pre-transplant to 550 + 918 at 3 weeks (p < 0.0001) and continued to decline until 1 year post-transplant (472 +/- 1116, p < 0.0001 vs. 3 weeks). Proteinuria greater than 3000 mg/day was present in 48 patients (42%) pre-transplant, in 1 patient (1%) at 3 weeks and in 4 patients (4%) at 1 year. Surveillance graft biopsies were done at 1 year in 93% of patients. Proteinuria > or = 1500 mg/day and/or an absolute increase in proteinuria > 500 mg/day after 3 weeks post-transplant was associated with allograft glomerular pathology. In conclusion, pre-transplant proteinuria, even when high grade, declines rapidly after transplantation. Failure to decline or persistence of proteinuria greater than 1500 mg/day is indicative of allograft pathology.

Laparoscopic removal of renal cysts in patients with ADPKD as an alternative method of treatment and patient preparation for kidney transplantation: preliminary results.

BACKGROUND: The most frequent genetic disease of the kidneys occurring in 1 of 1000 inhabitants is autosomal-dominant polycystic kidney disease (ADPKD). Growing renal cysts compress the kidney resulting in damage to parenchyma and functional disorders. Around 10% of these patients are dialyzed due to terminal renal insufficiency. With the advent of laparoscopic techniques, the idea of laparoscopic excision of cysts seemed a tempting alternative to nephrectomy. We assessed the preliminary results of laparoscopic treatment of polycystic kidneys compared with open nephrectomy for patients with ADPKD. MATERIALS AND METHODS: Thirty ADPKD patients were treated between 2000 and 2004. Eleven procedures in five men and six women of mean age 51 years included laparoscopic cyst excisions. In the remaining 19 patients (six men and 13 women) of mean age 54 years, nephrectomy was done. Indications for surgery included pain due to compression by large cysts and cyst contamination. Patients after nephrectomy were prepared for renal transplantation when necessary. RESULTS: Laparoscopic polycyst removal produced better effects than nephrectomy. Mean operative time was significantly shorter (86 minutes for cyst removal vs 108 minutes for nephrectomy; P < .05). Postoperative pain measured with the VAS scale was reduced in patients after laparoscopy. Hospital stay was shorter (5 vs 9 days), as well as time to recovery. Other benefits of laparoscopic cyst removal included maintained urination in the patient and no need for erythropoietin substitution, as well as reduced risk of cyst contamination. When eligible for renal transplantation, patients after laparoscopic polycyst removal have smaller kidneys that do not interfere with the graft and the risk of infection during immunosuppression seems lower. CONCLUSION: Although larger series of patients are required in patients with ADPKD, laparoscopic polycyst removal seemed superior to early nephrectomy.

Hypoxanthine as a graft ischemia marker stimulates catalase activity in the renal vein during reperfusion in humans.

BACKGROUND: The impairment of organ function derived from ischemia-reperfusion injury is still an important problem in solid organ transplantation. Cell alterations induced by ischemia prime the tissue for subsequent damage occurring during the reperfusion phase. Purine nucleotides and oxypurines are products of adenine nucleotide degradation. Reperfusion and reoxygenation are characterized by great production of reactive oxygen species and free radicals. On the contrary, superoxide dismutase, catalase, glutathione, and glutathione peroxidase are involved in protecting against free radicals. The aim of the study was to examine the correlation between concentrations of ischemia markers (hypoxanthine or inosine) and the activity of erythrocyte superoxide dismutase, catalase, or glutathione peroxidase. PATIENTS AND METHODS: The study included 40 renal transplant recipients. Before anastomosis of the kidney vessels with the recipient's iliac vessels, a "0" blood sample was taken from the iliac vein. Then, after anastomosis, the renal vein of the graft was cannulated and blood samples I, II, and III were obtained. The reperfusion of the transplanted kidney was measured with a thermovision camera ThermaCAM SC500. RESULTS: The plasma concentrations of hypoxanthine and inosine increased in statistically significant fashion immediately after total tissue reperfusion (P < .0001). Catalase activity at 4 minutes after total tissue reperfusion correlated positively with hypoxanthine concentrations immediately after total tissue reperfusion (Rs = +0.49), 2 minutes after total tissue reperfusion (Rs = +0.47), and 4 minutes after total tissue reperfusion (Rs = +0.46). There were no statistically significant correlations between hypoxanthine or inosine concentrations or superoxide dismutase or glutathione peroxidase activities. CONCLUSIONS: The results of the present study suggest that catalase activity may correlate with the concentration of hypoxanthine in the graft renal vein and other mediators of oxidative stress.

Activity of CuZn-superoxide dismutase, catalase and glutathione peroxidase in erythrocytes in kidney allografts during reperfusion in patients with and without delayed graft function.

BACKGROUND: Generation of reactive oxygen species (ROS) is the main mechanism involved in the ischemic/reperfusion damage of the transplanted organ. Oxygen burst is a trigger for complex biochemical events leading to generation of oxygenated lipids and changes in microcirculation. Many markers have been researched to prove the presence of ROS in the transplanted tissue. Some of them, like superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) are considered to play a major role in graft protection against oxygen stress during reperfusion. METHODS: The aim of this study was to examine the changes of SOD1, CAT and GPx activity in erythrocytes during the first minutes after total graft reperfusion. Forty patients undergoing kidney transplantation at our center were assigned to two groups: with or without delayed graft function (DGF). Before anastomosing kidney vessels with recipient's iliac vessels, the '0' blood sample was taken from the iliac vein. Next blood samples I, II and III were taken from the graft's renal vein. The reperfusion of the transplanted kidney was evaluated precisely with the thermovision camera. Erythrocyte SOD1, CAT and GPx activity was measured with a spectrophotometric method. RESULTS: We did not observe statistically significant changes in SOD1, CAT and GPx activity in erythrocytes during the early phase of reperfusion in patients with and without DGF. CONCLUSIONS: Erythrocyte-antioxidative system in graft's vein remain stable during the early phase of reperfusion. The results of the study suggest that further studies on extracellular enzymes are required for the assessment of antioxidant system in the conditions of ischemia/reperfusion.

Soluble HLA class I molecules exert differentiated influence on renal graft condition.

The function of soluble HLA (sHLA) antigens in the process of immunoregulation and especially in graft tolerance versus rejection has not yet been established. It has been suggested that donor-derived sHLA may exert an immunotolerant influence on the graft. We sought to determine the role of sHLA class I in kidney graft survival by evaluating the influence of these molecules on allotypic lymphocytotoxic antibodies and the concentration of gamma interferon (INF-gamma). Analysis of sHLA was performed indirectly utilizing their ability to inhibit lymphocytotoxic reaction dependent on complement activation. To demonstrate the inhibitory properties of sHLA, we modified the NIH microcytotoxic test. Furthermore, we determined the concentration of INF-gamma in all sera samples for comparison with the intensity of the cytotoxic test. The comparison of the intensity of cytotoxic test inhibition with the concentration of INF-gamma revealed that high concentrations of this cytokine were associated with stronger inhibition of the cytotoxic test, thus with higher concentrations of sHLA class I molecules in recipient sera. We observed that high concentrations of sHLA class I molecules in recipient sera significantly inhibited cytotoxic reactions, which could contribute to a protective influence of sHLA on renal grafts. On the other hand, the observed increase of INF-gamma concentration might be caused by sHLA themselves, which would produce a detrimental influence on a transplanted organ. Therefore we concluded that the role of sHLA class I molecules in renal graft condition remains ambiguous.

Impact of presence of HBs antigen and anti-hepatitis C virus and anti-cytomegalovirus antibodies on transplanted kidney survival.

INTRODUCTION: Infections are one of the most common complications after organ transplantation. Viral infections such as hepatitis type B (HBV) and C (HCV) or cytomegalovirus (CMV) infections are among the most serious ones. A high frequency of HBV and HCV infections has been recognized in kidney recipients. Viral infections play a special role in graft recipients because of clinical symptoms influencing graft function and recipient survival. Immunosuppressive treatment to decrease immunological reactions after organ transplantation may increase the risk of viral infections. The aim of this study was to evaluate the impact of the presence of HBs antigen and HCV and CMV antibodies on patient and graft survivals. MATERIAL AND METHODS: Two hundred one enrolled kidney transplantation patients (96 women and 105 men) were treated with the same immunosuppressive regimen. Age, sex, and viral state (HBs antigen, anti-HCV and anti-CMV antibodies) were evaluated in every patient. Statistical analysis was performed with the Gompertz model, Kaplan-Meier curves and Cox proportional hazard tests. RESULTS: The presence of HBs antigen was detected in 161 patients (20.4%), HCV antibodies in 61 recipients (30.3%); and CMV antibodies in 12 patients (5.9%). Eighty-seven recipients (43.4%) were seronegative. Average recipient age was 38.5 years. CONCLUSION: Time of graft function was independent of the presence of HBs antigen or HCV or CMV antibodies.

Pretransplant nephrectomy in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and a frequent cause of end-stage renal failure. Transplantation in patients with ADPKD is associated with specific cyst-related problems, especially urinary tract infections (UTI). Although pretransplant nephrectomy has been applied in this group of patients, evidence of the benefits of this strategy is lacking. Therefore, we compared the outcomes and posttransplant complications among patients with or without pretransplant nephrectomy. PATIENTS AND METHODS: ADPKD patients (73) transplanted from cadaveric donors were reviewed retrospectively with regard to posttransplant complications and outcomes. The groups either underwent pretransplant unilateral nephrectomy (n = 30) or were transplanted with native kidneys intact (n = 43). RESULTS: Two patients underwent simultaneous bilateral nephrectomy due to a large size of the polycystic kidneys interfering with the transplant operation. Overall postransplant complications were more frequent in the group without nephrectomy (34% vs 20%); however, the difference was not statistically significant. Most complications were related to cyst infections with 3 deaths (12%) due to lethal septicemia in the group without nephrectomy. No infection-related deaths were noted in the group with pretransplant nephrectomy. CONCLUSIONS: Graft and patient outcomes as well postransplant complications were similar in both groups, independent of previous nephrectomy. It seems that pretransplant unilateral nephrectomy should not be routine and has no advantage over transplantation with both native kidneys intact, although this conclusion is limited by the small number of patients. An Individualized approach should be applied especially when there has been a history of cyst-related infection.

Variations in temperature of the donor kidney during cold ischemia time and subsequent assessment of reperfusion using the application of thermovision camera.

Cold ischemia time (CIT) and graft reperfusion events are important nonimmunological factors that influence kidney graft function. The optimal temperature for the organs during CIT ranges from 4 degrees C to 8 degrees C. However, preservation of the designated temperature is usually not controlled during standard storage procedures. Aspects of initial graft reperfusion are usually assessed indirectly. Better evaluation of the effectiveness of the early blood supply may improve the surgical outcome. The aim of the study was to monitor the temperature during CIT in the kidney and surrounding area and subsequently to assess graft reperfusion using thermography. Temperature values of the area surrounding the kidney were registered during 8 organ procurements. We observed that the area surrounding the kidney displayed the optimal temperature range only during the first 5 minutes of CIT; later the temperature oscillated between 1 degrees C and 3.5 degrees C. The study proved that the temperature of the preservation fluid is frequently below prescribed. Analysis of the thermograms of 40 transplanted kidneys with the use of a thermovision camera ThermaCAM SC500 showed usefulness of this method to assess reperfusion and blood distribution in the transplanted kidney.

Organ procurements in West Pomerania in years 2000-2001.

Year by year the actual number of transplanted organs has been growing in Poland. In the event of the Województwo Zachodniopomorskie (Western Pomeranian Province) the primary activities were focused on informing medical personnel at hospital departments about approaching donors through trainings for such medical personnel. Such activities resulted in both acceptance and support, especially by medical personnel of medium as well as lower ranks. Since 1983 two transplant units have been functioning in the Province: SPSK-2 and S. P. W. S. Z. in Szczecin, and since 2000 two co-ordination offices, too. Main result of our activities can be seen in the number of organs procured for transplantation. In 2000 we had 27.7 procurements per million (ppm), in 2001 there were 39.9 ppm.

[ANalysis of upper extremity injuries in the Szczecin shipyard S.A. in the years 1989-1993]. / Analiza urazów konczyn górnych w Stoczni Szczecinskiej S.A. w latach 1989-1993.

The study covered 534 cases of work-related injuries of upper extremities among workers of the Szczecin Shipyard, registered during the years 1989-93. Some factors influencing the rate and structure of accidents (age, kind of work, section of the plant, occupational exposure and work experience) were analysed. The study showed that hand injuries were the most common effect of work-related accidents involving upper extremities among males employed in the shipyard.