Graft Neutrophil Sequestration and Concomitant Tissue Plasminogen Activator Release During Reperfusion in Clinical Kidney Transplantation.

BACKGROUND: Inflammation, coagulation, and fibrinolysis are tightly linked together. Reperfusion after transient ischemia activates both neutrophils, coagulation, and fibrinolysis. Experimental data suggest that tissue plasminogen activator (tPA) regulates renal neutrophil influx in kidney ischemia and reperfusion injury. METHODS: In 30 patients undergoing kidney transplantation, we measured renal neutrophil sequestration and tPA release from blood samples drawn from the supplying artery and renal vein early after reperfusion. tPA antigen levels were measured using a commercial enzyme-linked immunosorbent assay kit. For each parameter, transrenal difference (Δ) was calculated by subtracting the value of the arterial sample (ingoing blood) from the value of the venous sample (outgoing blood). RESULTS: Positive transrenal gradients of tPA antigen occurred at 1 minute [Δ = 14 (3-46) ng/mL, P < .01] and 5 minutes [Δ = 5 (-3 to 27) ng/mL, P < .01] after reperfusion. At 5 minutes after reperfusion, a negative transrenal gradient of neutrophils was observed [Δ = -0.17 (-1.45 to 0.24) x 10E9 cells/L, P < .001]. At 1 minute after reperfusion, neutrophil sequestration into the kidney (ie, negative transrenal neutrophil count) correlated significantly with tPA release from the kidney (ie, positive transrenal tPA concentration), (R = -0.513 and P = .006). CONCLUSIONS: The findings suggest a proinflammatory role for tPA in ischemia and reperfusion injury in human kidney transplantation.

Matrix Metalloproteinase-9 and Graft Preservation Injury in Clinical Renal Transplantation.

BACKGROUND: Deleterious effects of matrix metalloproteinase-9 (MMP-9) have been established in experimental renal ischemia-reperfusion models but not in clinical renal transplantation thus far. METHODS: We studied MMP-9 and its physiological inhibitor tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in 45 consecutive patients of a larger trial in renal transplantation: perioperative anti-thymocyte globulin (group A, n = 15), perioperative basiliximab (group B, n = 16), and conventional triple therapy (group C, n = 14). In addition to systemic blood samples, local blood samples were obtained simultaneously at 1 and 5 minutes after reperfusion from iliac artery and graft vein for calculation of transrenal changes. Because anti-thymocyte globulin activates inflammation, group A was analyzed separately. Groups B and C were pooled (group BC). RESULTS: Anti-thymocyte globulin infusion caused a robust rise of MMP-9 in the systemic circulation in group A. No significant transrenal difference of MMP-9 or TIMP-1 occurred in either group during graft reperfusion. In group BC, strong transrenal release of MMP-9 at 1 minute after reperfusion correlated with cold ischemia time (R = 0.66, P = .0001) and was associated with delayed graft function (P = .052). CONCLUSIONS: Renal production of MMP-9 on graft reperfusion is associated with cold ischemia time and emergence of delayed graft function. MMP inhibition may offer a means to reduce reperfusion injury in renal transplantation.

Impaired renal function after pregnancy in renal transplant recipients.

Twenty-two renal transplant recipients had 29 posttransplant pregnancies and 39 male transplant recipients became fathers to 65 children between 1971 and 1991. Of the deliveries of the female patients, 62% took place between the third and sixth year after transplantation. Seven patients had 2 pregnancies. Mean follow-up time after the first posttransplant pregnancy was 7.5 years. The patients survived the pregnancy well, but the increase in serum creatinine concentration from the prepregnancy level, registered 3 months and 1 year after delivery, was higher than in matched control patients without pregnancy at corresponding times after transplantation (the increase in serum creatinine was 47.7 and 61.2 mumol/L in the pregnant patients versus -2.7 and 5.4 mumol/L in the control patients, P < 0.0001 and P < 0.02, respectively). All pregnant and control patients were alive at the end of follow-up, but the long-term graft survival of those with a pregnancy was significantly (P < 0.005) worse than in the control patients. Ten-year graft survival was 69% in the pregnant versus 100% in the control patients. Although 80% of the neonates born to a mother with a transplanted kidney were below the mean for gestational age, the weight and length at birth were within normal limits and no severe intrauterine growth retardation was documented.

Acute vascular rejection in renal transplantation--diagnosis and outcome.

Thirty episodes of histologically verified acute vascular rejection in kidney transplant recipients were studied. In 11 grafts the rejection was mainly vascular, whereas in 19 grafts a concomitant cellular rejection was seen. Histological features prognostic for bad outcome were glomerular necrosis and thrombi in the arteries and arterioles. Characteristic findings in transplant cytology, i.e., high number of monocytes and low number of lymphocytes and blast cells were noted prior to the onset of clinical signs of rejection, and this finding was also persisting throughout the rejection episode. The numbers of lymphocytes and blast cells were significantly lower in grafts with a pure vascular rejection than in grafts with a concomitant cellular rejection. Vascular rejection was reversible in 15 cases. As rescue therapy plasmapheresis and added immunosuppression were often successful.

Peritoneal dialysis access: prospective randomized comparison of the Swan neck and Tenckhoff catheters.

OBJECTIVE: To examine the impact of peritoneal catheter configuration on mechanical complications, catheter survival, probability of episodes of peritonitis, and probability of exit-site infections associated with the use of catheters for continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Prospective randomized trial. SETTING: CAPD unit in one university hospital, serving a population of 1.2 million. PATIENTS: Forty consecutive patients requiring their first dialysis catheter for future CAPD were randomized to receive either a two-cuff permanently bent Swan neck catheter or a two-cuff straight Tenckhoff catheter. The skin exit was downward-directed in the Swan neck group and upward-directed in the Tenckhoff group. RESULTS: Dialysate leak, catheter migration, or tunnel infection did not occur in any of the patients. Three outer cuff extrusions needing cuff shaving occurred, all in the Tenckhoff group (p = 0.1). No significant differences could be demonstrated in catheter survival at 2 years, probability of episodes of peritonitis, or probability of exit-site infections. CONCLUSION: Catheter configuration did not influence the catheter-related mechanical or infectious complications, and equally good results were obtained with both catheter types studied.

Catheter configuration and outcome in patients on continuous ambulatory peritoneal dialysis: a prospective comparison of two catheters.

OBJECTIVE: To examine the impact of peritoneal catheter configuration on mechanical complications, catheter survival, probability of episodes of peritonitis, and probability of exit-site infections associated with the use of catheters for continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Prospective randomized trial. SETTING: CAPD unit in one university hospital. PATIENTS: Forty consecutive patients requiring a dialysis catheter for future CAPD were randomized to receive either a single-cuff straight Tenckhoff catheter or a permanently bent single-cuff Swan neck catheter. The skin exit was upward-directed in the Tenckhoff group and downward-directed in the Swan neck group. RESULTS: Dialysate leak occurred in one patient and symptomatic catheter tip migration in 3 patients with the Tenckhoff catheter but in none with the single-cuff Swan neck catheter (p = 0.5, p = 0.12). No significant differences in catheter survival at 2 years, probability of episodes of peritonitis, or probability of exit-site infections could be demonstrated. CONCLUSION: Catheter configuration did not influence the catheter-related mechanical or infectious complications. We were unable to demonstrate any advantage of the newer, permanently bent single-cuff Swan neck catheter over the conventional straight type.

Two decades of experience with cyclosporine in renal transplantation in Helsinki.

We present our experience on cyclosporine (CsA) triple immunosuppression in 2445 cadaveric kidney transplantations performed from 1984 to 2002 in Helsinki. Overall, delayed onset of graft function occurred in 30.2% and acute rejection in 25.6% of the transplantations. The 1-, 5-, and 10-year patient survival was 95.1%, 84.5%, and 69.1%; the graft survival rates were 90.0%, 74.9%, and 56.7%; and the death-censored graft survival, 93.3%, 83.5%, and 72.4%. During the study period, the 5-year patient survival improved from 70.8% to 90.6% and the graft survival from 58.2% to 88.0% with the graft half-life estimate of 1-year survivors improving from 7.6 to 21.8 years. Acute rejection episodes decreased from 33.0% to 19.9% and the calculated creatinine clearance at 1 year improved from 50.3 mL/min to 74.3 mL/min. Mean CsA dose diminished significantly, both at 3 weeks (from 8.2 mg/kg to 4.9 mg/kg) and at 1 year posttransplant (from 3.7 mg/kg to 2.8 mg/kg). In 16.7% of transplantations where azathioprine had to be discontinued early, significantly more rejections occurred (38.0% vs 23.2%) with inferior 1-year graft survival (80.2% vs 94.8%) compared to the transplantations continuing on triple therapy. Among 1-year survivors, the 6-month serum creatinine level was strongly associated with death-censored long-term graft survival. In this material, the CsA dosage at 1 year did not predict long-term graft survival.

Heme oxygenase 1 gene polymorphisms and outcome of renal transplantation.

Heme oxygenase isoenzyme HO-1 has been linked to several cytoprotective functions with a potentially beneficial role in transplantation. In the present study, the effect of genetic variation in HO-1 on renal allograft outcome was investigated. Six hundred and eighty patients subject to renal transplantation in a single transplant unit and their cadaveric kidney donors were included in this study. Four single-nucleotide polymorphisms and one microsatellite marker in the HO-1 gene region were analysed. Some statistically nominally significant associations were observed in preliminary analyses between polymorphisms studied and clinical outcomes, but after correction for multiple comparisons none remained significant. Our data suggest that the HO-1 gene polymorphisms studied have no significant role on outcome of kidney transplantation in the Finnish population.

Carcinoma of the colon in Finland. A nation-wide clinical study of cases from 1975.

All 455 colon carcinomas diagnosed in Finland in 1975 (19 at autopsy) were reviewed. The age-adjusted incidence was 8.0/100,000 population, equal in both sexes. Histologic verification was obtained in 88.4% of the cases. The stages at diagnosis were A 11%, B 44%, C 17% and D 28%. Of the tumours diagnosed during life, 8% were not operated on. Resectability was 75% in the cases with surgery and resectability for cure 59%. Operative mortality was 10.7% overall and 6.3% in elective surgery. Emergency surgery was performed on 27% of the total series and carried 22% mortality rate. The crude 5-year survival rate was 31% in the total series. The relative rate was 41% overall and 75% after resection for cure. All survival rates were significantly higher in women than in men. Following resection with curative intent, relative 5-year survival was 91% in stage A and 68% in stage B and C tumours. Survival was level with rates in population studies elsewhere, and greatly improved as compared with earlier Finnish Cancer Registry studies.

Obstruction and perforation complicating colorectal carcinoma. An epidemiologic and clinical study with special reference to incidence and survival.

Comparisons were made between all patients who underwent emergency surgery for complicated colorectal carcinoma in Finland in 1975 and all who were electively operated on for the disease in the same period. The overall incidence of tumour complications was 18% (29% in colon and 7% in rectum). Obstruction alone was present in 15% and perforation with or without obstruction in 4%. The mean age in the "emergency group", 69.5 years, was 4 years higher than in the "elective group". Resectability for cure was 47% and 66% in the respective groups. The 21% mortality associated with emergency surgery was four times the rate after elective surgery. The observed 5-year survival rates were 18% and 35%. Relative 5-year survival, excluding surgical mortality, was 31% vs. 48%, overall and 54% vs. 68% after resection for cure. The excess mortality in the emergency compared with the elective group accrued only in the first 6 postoperative months. In complicated colorectal cancer, intensive treatment is necessary even after the immediate postoperative period. Early diagnosis should be sought even in elderly patients, as the prospects are better after elective than after emergency surgery.

Carcinoma of the rectum in Finland--changes in two decades. An epidemiologic and clinical study.

Data from all new cases of rectal carcinoma diagnosed in Finland in 1975 were compared with corresponding data from 1953-1956. Operability increased from 67 to 90% and, among surgically treated cases, resectability for cure from 60 to 66%. In major resection for cure, restorative surgery increased from 10.2 to 21.8%. The surgical mortality diminished (16-5%). Of the 1975 series, 25% were classified as tumour stage A, and 43, 11 and 22% as B, C and D, respectively. Relative 5-year survival rose overall from 20% in the 1953-1956 cases to 38% in those from 1975, and following resection with curative intent from 52 to 59%. Crude survival rates among the patients with tumour resected for cure rose from 54 to 61% in stage A and from 15 to 43% in stage B, but were unchanged in stage C, 22 v. 21%. Our figures were comparable with available reports on rectal carcinoma in defined populations. The reasons for longer survival were increased operability and resectability and reduced surgical mortality. Improved quality of tumour staging in national statistics is mandatory for valid comparisons of treatment results.

Completeness and accuracy of registration of colorectal cancer in Finland.

The Finnish Cancer Registry notifications of colorectal cancer diagnosed in Finland in 1975 were compared against original patient records, and hospital archives were searched for unregistered cases. 1027 cases had been registered. 4.7% of them were erroneous: 1.6% had been diagnosed before or after 1975, 1.5% had no verifiable malignancy, and in 1.7% the correct primary site was other than the colorectum. Unregistered cases amounting to 1.2% of the total were found. Only one case was unknown to the Cancer Registry, the others had been inaccurately registered as to the site of tumour or date of diagnosis. The corrected age-adjusted incidence rate (males/females) of colon cancer was 8.2/8.6 and that of rectal cancer 9.1/6.1 per 100,000. In the light of the present study, cancer registry data in Finland offer a reliable basis for timetrends and international comparisons of incidence rates of colorectal cancer.

The clinical significance of conversion of complement-dependent cytotoxic T cell crossmatch test after renal transplantation.

The purpose of this study was to investigate the clinical relevance of conversion of post-transplant T cell crossmatch between kidney donor and recipient. This study comprises 892 cadaveric renal transplantations performed on 874 adult patients between August 1991 and December 1997. Recipient selection was based on a negative complement-dependent cytotoxic T cell crossmatch test with current (< or = 2 months old) serum. For this study, on day 0 and day 14 after transplantation, serum samples were collected for later crossmatching. On day 14 after transplantation, the crossmatch had converted to positive in 76 transplantations (8.5%). Acute rejection occurred in 50% of the converters and 22% of the non-converters (P < 0.005), and graft survival was significantly poorer (P < 0.025), being 85 vs 94% at 1 and 68 vs 83% at 5 years, respectively. In patients with delayed graft function, 1-year graft survival was 77% in the converters and 91% in the non-converters (P < 0.05). Conversion of T cell crossmatch, especially in connection with delayed graft function, identifies a subgroup of patients at high risk of severe rejection and poor graft survival.

Long-term results of 1047 cadaveric kidney transplantations with special emphasis on initial graft function and rejection.

We studied the effect of initial graft function and acute rejection on graft survival in 1047 cadaveric renal transplantations during 1991-1997 with a constant policy of donor selection, graft allocation, and immunosuppression. The overall 1- and 5-year patient survival rates were 96 % and 88 %, and the 1- and 5-year graft survival (GS) rates were 92 % and 78 %. Delayed graft function (DGF) occurred in 31 % and there were 1.2 % never-functioning grafts. One-year GS in transplantations with early graft function (EGF) was 95 % compared to 87 % in DGF (P < 0.001). Donor age and cause of death, type of graft perfusion and cold ischemia time, and type and length of dialysis treatment were significant factors in determining the onset of graft function. These factors did not have a significant direct effect on GS. Early ( < 100 days) acute rejection occurred in 25 %. In transplantations without rejection, the 1 and 5-year GS was 93.3 % and 80.8 %. In acute rejection responding to steroids, the GS was equal to that up to 3 years, but after that a significantly worse survival rate was observed (1- and 5-year GS: 93.6 % and 73.4 %). DGF was detrimental to GS both in transplantations without rejection and in all rejection types.