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Biomedical subjects

K Salmela

Publications and source records attributed to K Salmela.

At least 37 records · Page 2Linked to original sources

Transplantation of both kidneys from 408 donors; comparison of results.

The outcome of 816 paired kidney transplantations from 408 cadaveric donors was evaluated. The transplantations were divided according to order of transplant surgery into group 1 [mean cold ischemia time (CIT) 22 h] and group 2 (mean CIT 28 h). In group 1 the frequency of delayed onset of graft function (DGF) was 22% versus 35% in group 2 (P < 0.005). The 1-year patient survival and graft survival (GS) in group 1 was 98% and 93% versus 94% (P < 0.005) and 90% in group 2. Hemodialysis patients in group 2 had significantly greater DGF (43%) and poorer GS (88%) than peritoneal dialysis patients and the success of transplantation was particularly poor in recipients over 50 years of age.

Adolescent↗

Cancer incidence in a kidney-transplanted population.

A study on cancer incidence after kidney transplantation was performed using data of national transplant and cancer registries. Since 1964 up to 30 June 1997, 3440 kidney transplantations were performed on 2890 patients. From 1967 to 1997, 230 posttransplantation malignancies were found in 20,817 patient-years of follow up. The standardised incidence ratio (SIR) was 3.33 compared to the general population. The SIR was highest in skin cancer (39.2). The SIRs were high in cancers of the lip (23.0), thyroid (8.08), kidney (8.0), lower urinary tract (3.2), non-Hodgkin lymphoma (4.8), ovary (3.9) and colon (3.9). Skin cancer and lymphomas had much higher SIRs in men than in women whereas lower urinary tract cancer had a higher SIR in women. During the first 10 follow up years, life-table analysis indicates a higher cancer risk in cyclosporine-treated patients, but this may be biased by their shorter follow up as the overall SIR was equal in both groups. This population study shows the increased incidence of cancer in the transplant population and points out the importance of cancer surveillance in the years following kidney transplantation.

Adolescent↗

Bacteremia among kidney transplant recipients: a case-control study of risk factors and short-term outcomes.

Kidney transplant recipients are highly susceptible to life-threatening infections, including bacteremia. To determine the risk factors for bacteremia within the first month after renal transplantation we performed a non-concurrent transplant population-based case-control study involving all 1,000 consecutively operated adult patients at Helsinki University Central Hospital in 1987-93. All patients with at least 1 positive blood culture within 31 d of transplantation were defined as cases. Control patients were drawn systematically from the transplant population with no positive blood cultures within the first 31 d post-transplant. The study included 35 cases and 123 controls. The overall rate of bacteremia in the population was 3.5%. The case patients were more likely to have been on haemodialysis prior to transplantation (71%, vs. 43%, p < 0.05) and to have experienced acute rejection (46% vs. 20%, p < 0.05) than the controls. Local infections (46% vs. 12%, p < 0.05) were also more common among case patients. In the crude analysis an additive interaction of acute rejection and haemodialysis was found, with a 10% rate of bacteremia occurring if both conditions were present. The mortality rate within 2 months of follow-up was higher among case patients than among controls (14%, vs. 1%, p < 0.05) and they also returned more often to dialysis (23% vs. 4%, p < 0.05). Bacteremia during the immediate postoperative period might still have severe outcomes measured as allograft and patient survival at 2 months post-transplant. Further evaluation will confirm whether a lower rate of bacteremia among kidney transplantation patients can be achieved if peritoneal dialysis is preferred to haemodialysis whenever possible.

Adolescent↗

A randomized multicenter trial of the anti-ICAM-1 monoclonal antibody (enlimomab) for the prevention of acute rejection and delayed onset of graft function in cadaveric renal transplantation: a report of the European Anti-ICAM-1 Renal Transplant Study Group.

BACKGROUND: T-cell activation through T-cell receptor engagement requires co-stimulatory molecules and also adhesion molecules such as ICAM-1. Moreover ICAM-1 mediates leukocyte invasion from the blood into tissue during inflammatory processes. In animal studies using mouse monoclonal antibodies against ICAM-1 (enlimomab), renal allograft survival has been improved and reperfusion damage from ischemia reduced. The European Anti-ICAM-1 Renal Transplant Study (EARTS) was a randomized, double-blind, parallel-group, placebo-controlled study lastingl year and performed in 10 transplant centers in Europe. METHODS: A total of 262 recipients of cadaveric kidneys were given either enlimomab or a placebo for 6 days and were given triple immunosuppressive therapy of cyclosporine, azathioprine, and prednisolone. The primary efficacy endpoint was the incidence of the first acute rejection within 3 months, and each event was assessed by a committee including investigators and independent pathologists. RESULTS: There was no significant difference in the incidences of first acute rejection at 3 months between the placebo and enlimomab groups (39% vs. 45%), and enlimomab did not reduce the risk of delayed onset of graft function (DGF) (26% vs. 31%). Neither was there a difference in patient survival (95% vs. 91%) or graft survival (89% vs. 84%) at 1 year. Fatal events occurred in 19 (7%) patients (7 placebo, 12 enlimomab). Clinically, the most important non-fatal adverse events were infections; however, there was no statistically significant difference between the incidences in the two groups (70% vs. 79%). CONCLUSION: Short term enlimomab induction therapy after renal transplantation did not reduce the rate of acute rejection or DGF.

Acute Disease↗

Renal transplantation in Helsinki: influence on long-term survival of early posttransplant factors.

1. The half-life of kidney grafts performed at Helsinki University Central Hospital has tripled from 6.5 years in 1980-84 to 17.1 years in the 1990's. 2. Delayed graft function constitutes a significant determinant of later kidney graft survival. Five-year graft survival was 81% for patients with early graft function and 71% for those with DGF. 3. High (> 350 mg/L) early (10 +/- 2 days after transplantation) cyclosporine trough levels were associated with inferior long-term graft survival. The 5-year graft survival rate was 74% compared with 86% for patients with trough levels between 250-349 mg/L. 4. Posttransplant conversion of the crossmatch test against the kidney donor, especially in association with DGF, indicates a group with significantly worse prognosis. Among 76 patients who developed antidonor antibody after transplantation, half experienced an acute rejection within 100 days and the 5-year graft survival rate was 68% compared with 83% for non-converters.

Adult↗

Implantation of standardized beta-cell grafts in a liver segment of IDDM patients: graft and recipients characteristics in two cases of insulin-independence under maintenance immunosuppression for prior kidney graft.

Islet allografts in insulin-dependent diabetic (IDDM) patients exhibit variable survival lengths and low rates of insulin-independence despite treatment with anti-T-cell antibodies and maintenance immunosuppression. Use of poorly characterized freshly isolated preparations makes it difficult to determine whether failures are caused by variations in donor tissue. This study assesses survival of standardized beta-cell allografts in C-peptide negative IDDM patients on maintenance immunosuppression following kidney transplantation and without receiving anti-T-cell antibodies or additional immunosuppression. Human islets were isolated from pancreatic segments after maximal 20 h cold-preservation. During culture, preparations were selected according to quality control tests and combined with grafts with standardized cell composition (> or = 50% beta cells), viability (> or = 90%), total beta-cell number (1 to 2 x 10(6)/kg body weight) and insulin-producing capacity (2 to 4 nmol x graft(-1) x h(-1)). Grafts were injected in a liver segment through the repermeabilized umbilical vein. After 2 weeks C-peptide positivity, four out of seven recipients became C-peptide negative; two of them were initially GAD65-antibody positive and exhibited a rise in titre during graft destruction. The other three patients remained C-peptide positive for more than 1 year, two of them becoming insulin-independent with near-normal fasting glycaemia and HbA1c; they remained GAD65- and islet cell antibody negative. The three patients with surviving grafts presented a history of anti-thymocyte globulin therapy at kidney transplantation. Long-term surviving grafts increased C-peptide release following intravenous glucagon or oral glucose but not following intravenous glucose. Thus, cultured human beta-cells can survive for more than 1 year in IDDM patients on maintenance anti-rejection therapy for a prior kidney graft and without the need for an increased immunosuppression at the time of implantation. The use of functionally standardized beta-cell grafts helps to identify recipient and graft factors which influence their survival and metabolic effects. Insulin-independence can be achieved by injection of 1.5 million beta-cells per kg body weight in a liver segment. These beta-cell implants respond well to adenylcyclase activators but poorly to glucose.

Adolescent↗

Long-term follow up of renal function and histology after renal allograft transplantation in early childhood.

Survival rates, renal function, and histopathology were evaluated in 49 prospectively followed patients transplanted under 5 years of age at our center. Most patients (84%) suffered from congenital nephrosis of the Finnish type. Triple immunosuppression with cyclosporine administered in three daily doses to pre-school children was used. Patient survival 7 years after transplantation was 98% and graft survival 88%. All graft losses were due to post-transplantation nephrosis. The proportion of pathological findings in the follow-up biopsies did not change substantially with time. Five years after transplantation, 47% showed a normal histology and after 7 years this rose to 67%. Mean glomerular filtration rate (GFR) was 68 and 55 ml min per 1.73 m2 5 years and 7 years, respectively, after transplantation. The decline in GFR with time was significant. We conclude that good long-term results can be achieved with individually tailored triple immunosuppression in the youngest age group, even with cadaveric donors.

Child, Preschool↗

Peripheral arterial disease as a predictor of outcome after renal transplantation.

Our aim was to assess the prevalence of symptomatic and asymptomatic peripheral occlusive arterial disease (POAD) in 129 consecutive diabetic (n = 34) and nondiabetic (n = 95) patients undergoing renal transplantation. The association of pre-existent POAD and complaints of claudication, lower limb amputations, and graft and patient survival were evaluated during a 5-year follow up. A questionnaire on walking capacity, ankle/brachial (ABI) and toe/brachial (TBI) pressure indices as well as the pulse volume recording (PVR) at the ankle were used to assess resting haemodynamics and the presence of POAD 4 days after the transplantation. Unquestionable ischaemia was encountered in 5 (4%) patients all with a history of intermittent claudication and an ABI equal or below 0.77. While using assessment methods not affected by vessel calcification, i.e. toe pressures and PVR damping, a many-fold frequency of arterial disease was observed when compared to previous studies. TBI below 0.65 was found in 11 of diabetic (32%) and in 15 of the others (16%), and a PVR amplitude below 5 min in 28 of diabetics (82%) and in 34 of non-diabetics (36%). During the 5-year follow up, abnormal TBI and PVR values and diabetes at the time of transplantation were the greatest risk factors for proximal foot amputations. The low TBI levels also indicated a shortened patient survival. However, transplant function was not affected by the presence of abnormal haemodynamic indices at the time of transplantation.

Adolescent↗

CMV infection detected in the upper gastrointestinal tract after liver transplantation.

As a pilot series on the frequency of gastroduodenal cytomegalovirus (CMV) involvement after liver transplantation, we examined forceps biopsies of 13 consecutive patients who underwent esophagogastroduodenoscopy during the first 3 months after transplantation. CMV was demonstrated in frozen sections by monoclonal antibody and immunoperoxidase staining. In parallel, peripheral blood was examined for CMV pp65 antigenemia. CMV antigens were detected in biopsies of ten patients, in ten cases in the duodenum and in four in the stomach. At the time of endoscopy, sic patients had CMV antigenemia, five of them had a simultaneous positive finding in the duodenum. Although all ten patients with the positive biopsy finding had some gastrointestinal symptoms, only one had severe enteritis. In liver transplant patients, CMV was commonly detected in leukocytes located in the mucosa of the upper gastrointestinal tract, especially in the duodenum. Further investigation is needed to determine the significance of positive CMV findings in the biopsies and their association with the development of severe gastrointestinal symptoms.

Biopsy↗

Nephrotic syndrome, hyperreninemia and multiple transplant renal arterial stenoses in a patient with diabetes.

Nine months after cadaveric renal transplantation the nephrotic syndrome developed in a patient with insulin-dependent diabetes. Renal biopsy ruled out tissue lesions induced by cyclosporine, chronic rejection, recurrence of diabetic kidney disease and de novo glomerulopathies. Captopril-enhanced nephrography and a high plasma renin response suggested renal artery disease. Angiography revealed five intrarenal arterial stenoses. Four were successfully dilated with a prompt diuretic response and diminished proteinuria. Late angiography showed a moderate restenosis in two of the dilated arteries. Due to persistent proteinuria, elevated blood pressure and higher serum creatinine levels than at nadir after transplantation low-dose ACE inhibitor therapy was started. This normalized proteinuria, blood pressure and serum creatinine levels. This beneficial response to combined renal artery balloon angioplasty and medical treatment has been sustained for 2.5 years.

Diabetes Mellitus, Type 1↗

Paediatric kidney transplantation.

Renal transplantation is the optimal form of renal replacement therapy leading to substantial improvement in the quality of life. It has rapidly become the standard treatment for end-stage renal disease in children. However, despite impressive short-term results significant long-term problems remain unsolved. Because of the lack of effective treatment for chronic rejection and common recipient noncompliance, allograft half-life has not improved significantly during the last decade. A paediatric recipient is likely to need several retransplantations in adulthood. Moreover, the immunosuppressive drugs used today have potentially serious side-effects including nephrotoxicity and de novo malignancy. These are especially relevant for paediatric recipients who will continue to receive therapy for several decades. Most therapeutic protocols used for children are derived from those used for adults. However, the metabolic differences between an adult and a growing and developing paediatric transplant recipient are not always adequately appreciated before these new therapies are initiated. In the near future, we are likely to see new and more efficient drugs become available. It is important that we try to understand their properties in children and use them and our current arsenal on an individual basis aiming at optimal graft survival but also at avoiding unnecessary adverse effects.

Adolescent↗

Scandiatransplant: thirty years of cooperation in organ transplantation in the Nordic countries.

The Nordic organ exchange organization, Scandiatransplant was established in 1969. The organization, which covers a population of 23.9 million inhabitants, includes all 11 organ transplant centers in the 5 Nordic countries Denmark, Finland, Iceland, Norway and Sweden. The economy is solely based on transplant center fees. All Nordic patients waiting for an organ transplant are registered on one common waiting list. Rules for the exchange of organs are settled by unanimous decision, and the compliance to the rules is excellent. Kidney exchange is based on HLA matching, whereas the exchange of livers and hearts is based on clinical urgency. In 1997, 43% of the liver transplantations in Scandiatransplant were performed with an exchanged organ and the exchange rate for kidneys was 20%. Currently, the Scandiatransplant waiting list includes 1,538 patients waiting for a kidney transplant, 20 patients are waiting for a liver, 37 for a heart, and 156 patients are waiting for a lung transplant. The organ donation rate in Scandiatransplant has declined in recent years, from 16.0 per million population (PMP) in 1993 to a level of 13.5 PMP in 1997. The number of kidney transplants has varied between 800-900 per year during the past 10 years, corresponding to 33-38 transplants PMP. Approximately 30% of the renal transplants were performed with kidneys from living donors. The liver transplantation activity was approximately 7 PMP per year. Heart transplantation was performed at a rate of 4-5 PMP per year, and lung transplants at 4 PMP per year.

Cadaver↗

Is obesity still a risk factor in renal transplantation?

At our center, since 1982, a body mass index (BMI) of less than 30 has been a prerequisite for placing a patient on the waiting list for renal transplantation. This decision was made because obese transplant recipients seemed to have a less than favorable post-transplant outcome. The aim of this study was to evaluate whether this requirement is still justified. Forty-six patients with a BMI above 30 underwent primary cadaveric renal transplantation between 1972 and 1993. For each of these obese patients, five consecutive non-obese (BMI 20-25) control patients were selected. Patient and graft survival, causes of graft loss, and acute rejection rate were evaluated for the two patient groups before and after the year 1982. Within the first 30 post-transplant days, one patient (2%) and 11 grafts (24%) were lost in the group of obese patients whereas seven patients (3%) and 36 grafts (16%) were lost in the control group. Among the obese patients, renal circulatory complications were a major cause of graft loss. In the period 1973-1981, the 1-year patient survival rate was 65% among obese patients versus 75% among controls from 1982 to 1993, this was 90% versus 93%. From 1973 to 1981, the 1-year graft survival rate was 25% among obese patients versus 53% among controls (P < 0.05); from 1982 to 1993, it was 68% versus 84% (P = NS). Multivariate analysis showed that the immunosuppressive regimen, age of the patient, BMI, and cold ischemia time of the graft had a significant influence on graft survival. The acute rejection rate within the first 30 days was 28% among obese patients and 35% among controls (P = NS). We conclude that a BMI below or equal to 30 is still justified as a prerequisite for placement on the waiting list for renal transplantation, for despite an overall improvement, the outcome of renal transplantation in obese patients remains worse than that in non-obese patients.

Adolescent↗

Persistent cytomegalovirus in liver allografts with chronic rejection.

Cytomegalovirus (CMV) infection is one of the suggested risk factors for chronic allograft rejection. Clinical and experimental studies have shown that CMV is somehow implicated in rejection mechanisms and in the generation of graft arteriosclerosis, characteristic of chronic rejection. In liver transplantation, there is also evidence of an association between CMV and vanishing bile duct-syndrome (VBDS), which is characteristic of chronic liver allograft rejection. In this study, the role of posttransplant CMV infection and of acute rejection in the patients with irreversible, histologically confirmed chronic liver rejection with VBDS and vasculopathy was analyzed. Ten of 200 (5%) consecutive liver transplants were lost due to chronic rejection, from between 5 and 28 months from transplantation. In these 10 patients, acute rejections were frequent, and nine of ten patients had at least one episode of rejection early after transplantation. All patients (10 of 10) had a history of CMV infection usually following acute rejection. To investigate the role of CMV in chronic rejection, nine available removed grafts were examined for the presence of the CMV genome by DNA-hybridization in situ using a biotinylated CMV-DNA probe. Persistent CMV-DNA was found in all of those available grafts with chronic rejection. CMV-DNA was strongly expressed in the remaining bile ducts and moderately expressed in the endothelial cells of the vascular structures, the CMV positivity of hepatocytes varied from graft to graft. Thus, persistent CMV genome was found in those structures that are the major targets of the chronic rejection process in the liver. These findings support the previous suggestion of an association between CMV and chronic allograft rejection.

Bile Ducts↗

Peritoneal dialysis access: prospective randomized comparison of single-cuff and double-cuff straight Tenckhoff catheters.

BACKGROUND: A prerequisite to the technical success of chronic peritoneal dialysis is a functioning peritoneal catheter. The option of using Tenckhoff catheters with single or double Dacron cuffs has been available for almost 3 decades, but still there is no consensus as to which is the preferable type. METHOD: Sixty consecutive patients requiring a catheter for CAPD were randomized to receive either a straight deep single-cuff Tenckhoff catheter or a double-cuff Tenckhoff catheter. The catheters were surgically inserted. RESULTS: There were no early failures. Two subcutaneous cuff extrusions were treated with shaving of the cuff. In the long term, eight patients in both groups required transfer to haemodialysis (5 and 3 prolonged peritonitis, 1 and 0 exit-site infection, 2 and 5 unable to cope or inadequacy of dialysis). There was no significant difference in the probability of developing first episode of peritonitis or exit site infection between the groups. Overall probability of catheter survival was 95.5 and 96.7% at 1 year, 82.7 and 79.9% at 2 in the two groups respectively. CONCLUSIONS: There was no significant difference between catheters with single or double cuffs with respect to catheter survival, episodes of peritonitis and exit-site infections.

Adult↗

Alloimmunization against platelet antigens in renal transplant patients with acute vascular rejection.

Acute vascular rejection (AVR) of a kidney graft, in which the graft vascular endothelium is main target for the injury, is considered antibody-mediated. Integrins of vascular endothelium and platelets have several alloantigenic epitopes in common, e.g. human platelet alloantigen (HPA) 1 on beta(3) integrin of glycoprotein (GP) IIbIIIa and HPA-5 on alpha(2) of GP IaIIa. The clinical significance of HPA expression by vascular endothelial cells is unknown. Platelet antibodies in serum samples from 26 renal allograft recipients with AVR and 30 patients without AVR were studied. Also the HPA-types of the patients and their respective graft donors were determined. Strong platelet alloantibodies were observed in seven of the 26 AVR patients (27%). In five of these cases the antibodies had HPA-specificity. No reference patient without AVR had strong platelet antibodies. In two AVR patients strong HPA-5b antibodies coexisted with an HPA-5b-positive graft. Despite acute rejection episodes, neither of the grafts was lost. It seems likely that, with current immunosuppressive treatment, anti-HPA-5b does not necessarily cause permanent dysfunction of a graft originating from HPA-5b-positive donor.

Acute Disease↗

Kidney transplantation.

The authors present a short overview on the history of clinical renal transplantation and an update of the results of renal transplantation today. Factors contributing to chronic renal allograft failure and immunotherapy-related exposure to malignant diseases complicating life after transplantation are discussed.

Graft Rejection↗