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P Fauchald

Publications and source records attributed to P Fauchald.

At least 37 records · Page 2Linked to original sources
PubMed1999

A single dose of dalteparin effectively prevents clotting during haemodialysis.

BACKGROUND: A single bolus dose of LMW heparin at the start of haemodialysis effectively prevents clot formation in the dialyser and bubble trap. However, there are few studies on the appropriate dosage of LMW heparins in haemodialysis. Therefore we examined the relationship between the anticoagulant effect of dalteparin and clinical clotting during haemodialysis. METHODS: We performed an open, prospective study on the effect of decreasing doses of dalteparin in 12 haemodialysis patients during a total of 84 sessions (4-4.5 h). The normally applied dose of dalteparin in each patient was reduced by 25% for each session down to 50% of initial dose if no clotting was observed. Clinical clotting (grade 1-4) was evaluated by visual inspection after blood draining of the air trap every hour and by inspection of the dialyser after each session and compared to corresponding values for anti-FXa activity and dialysis time. Blood flow and ultrafiltration rate were kept within narrow limits throughout the study. RESULTS: No episodes of grade 4 clotting occurred, and no session was interrupted. Eighteen episodes of grade 3 clinical clotting (11%) were observed in patients without warfarin treatment, none with an anti-FXa activity >0.43 IU/ml. Oral warfarin treatment reduced the clinical clotting, and only one grade 3 episode was observed in patients on warfarin therapy. Anti-FXa activity and haemodialysis time were the only factors independently correlated to clotting in a logistic regression model. CONCLUSION: An anti-FXa activity above 0.4 IU/ml after 4 h of dialysis inhibits significant clotting during haemodialysis. A bolus dose of dalteparin of 70 IU/kg usually seems appropriate, but may be reduced in patients on warfarin treatment. Dialysis time is an independent risk factor for clinical clotting.

Adult↗
PubMed1998

A strong impact of matching for a limited number of HLA-DR antigens on graft survival and rejection episodes: a single-center study of first cadaveric kidneys to nonsensitized recipients.

BACKGROUND: A single-center study of 655 nonsensitized recipients of primary cadaveric kidney grafts is presented. RESULTS: Graft survival in serologically HLA-DR 1-10 antigen-matched grafts to nonsensitized recipients at 1 year was 90%, compared with 82% (P=0.004) and 73% (P=0.001) in one and two DR antigen-mismatched grafts. The corresponding figures at 5 years were 76%, 62%, and 56%, respectively. Matching for the DR antigens 11-14, or for some DR alleles only detectable by genomic typing, further improved graft survival, but the differences did not reach statistical significance. Matching also for the serologically defined HLA-A and -B antigens did not significantly further improve overall graft survival, but some effects for grafts surviving at least 1 year were observed. Among recipients of grafts mismatched for zero, one, or two HLA-DR antigens, acute rejection episodes were experienced in 48%, 64% (P<0.001), and 82% (P<0.001), respectively, within the first 3 months. HLA-A and -B mismatches showed no significant correlation to acute rejection episodes. CONCLUSION: Matching for the DR antigens 1-10 significantly secures and prolongs the survival of first cadaveric renal grafts. Our results also show that DR 1-10 antigen-matched combinations can often be obtained even in rather small recipient pools, when actively sought for.

Adolescent↗
PubMed1998

Unrelated living donors in 141 kidney transplantations: a one-center study.

BACKGROUND: Kidney transplantation is the optimal treatment for the majority of patients with end-stage renal disease. However, the shortage of kidneys for transplantation is a global problem, and any attempt to improve the donor situation would be of benefit to the growing number of patients on transplant waiting lists. PATIENTS AND METHODS: Since 1984, we have transplanted 141 kidneys from genetically unrelated living donors. Donors were most often spouses and were accepted regardless of HLA match grade. Preemptive transplantation was performed in 39% of the patients. Standard triple-drug immunosuppression with prednisolone, cyclosporine, and azathioprine was used. The patients were followed from 6 months to 13 years. RESULTS: The incidence of acute rejection during the first 3 months after transplantation was higher in recipients of grafts from unrelated donors than in recipients of grafts from related living donors or cadaveric donors. However, unrelated living donor grafts survived significantly better than did cadaveric grafts (P < 0.02) and had a survival rate similar to that of living-related donor grafts mismatched for one or both HLA haplotypes. The perioperative complication rate for the donor was low. CONCLUSION: We consider unrelated living donors an excellent source for alleviating the shortage of donor kidneys.

Adult↗
PubMed1998

Renal effects of losartan and amlodipine in hypertensive patients with non-diabetic nephropathy.

BACKGROUND: The objective of this study was to examine the effects of angiotensin II receptor blocker losartan versus the calcium channel blocker amlodipine on proteinuria, renal haemodynamics, glomerular sieving and tubular function in hypertensive patients with non-diabetic nephropathy. METHODS: The study design was a prospective, double blind, placebo controlled, randomized crossover trial with amlodipine and losartan. Renal parameters were measured at baseline and at the end of each 4-week active treatment period. Fifteen patients with a diagnosis of non-diabetic renal disease and hypertension were included. RESULTS: Mean arterial blood pressure decreased from 123+/-13 mmHg at baseline to 113+/-10 mmHg (P<0.01) on losartan and to 114+/-10 mmHg on amlodipine (P<0.01). Urinary albumin excretion significantly decreased from 3510+/-2586 mg/24 h at baseline to 2684+/-2051 mg/24 h (P<0.01) on losartan and increased non-significantly to 3748+/-3355 mg/24 h on amlodipine. Filtration fraction significantly decreased from a baseline value of 22.8+/-9.3% to 21.2+/-10.2% (P<0.05) on losartan and increased to 23.6+/-8.9% (ns) on amlodipine. Either drug did not significantly alter glomerular sieving of neutral dextrans. CONCLUSION: Our results demonstrate that losartan, but not amlodipine, decreased albumin excretion in hypertensive patients with non-diabetic nephropathy.

Adult↗
PubMed1998

Morphological studies of baseline needle biopsies from living donor kidneys: light microscopic, immunohistochemical and ultrastructural findings.

Fifty-seven consecutive living donors (31 women and 26 men aged 20.7-72.3 years, mean 50.6 years) were subjected to needle biopsy during nephrectomy, immediately before removal of the kidney. By light microscopy, semiquantitative scoring (0-3) was performed for arteriosclerosis, arteriolar hyalinosis (hyalin arteriolosclerosis), glomerulosclerosis, interstitial mononuclear cell infiltration, and interstitial fibrosis/tubular atrophy. Whereas vascular changes were striking in many biopsies (arteriosclerosis grades 2-3: 28/54 cases, arteriolar hyalinosis grades 2-3: 15/55 cases), glomerular and tubulointerstitial changes were mostly low grade. The morphological changes tended to be more pronounced in middle-aged and older individuals, but, in particular, vascular changes were seen also in the younger age group. Immunofluorescence microscopy revealed glomerular granular staining for IgM in 52.7% of the cases, IgA in 9.1%), IgG in 1.8%, and C3 in 12.7%. The main ultrastructural finding was glomerulosclerosis; one case with diffuse glomerular IgA showed distinct dense deposits, and one case showed similar dense deposits without IgA deposition. Arteriolar wall deposition of C3 was found in 58.2% of the cases, and IgM in 10.9%. Especially C3 occurred both with arteriolar hyalinosis and in arterioles without light microscopic alterations. The observation of significant vascular changes in baseline biopsies is relevant especially in the differential diagnosis of chronic rejection and cyclosporine nephropathy. The immunohistochemical findings strongly indicate the occurrence of immunoglobulins and complement factor C3 in both glomeruli and arterioles without clinical or morphological signs of renal disease. The possible pathophysiological significance of such deposits remains, however, uncertain.

Adult↗
PubMed1998

Percutaneous transluminal renal artery angioplasty using the coaxial technique. Ten years of experience from 591 procedures in 419 patients.

PURPOSE: To evaluate the angiographic and clinical results of all percutaneous transluminal renal angioplasties (PTRAs) performed at one centre in Norway since the introduction of the method. Most of the PTRAs were performed with the coaxial technique (guiding-catheter-assisted angioplasty). MATERIAL AND METHODS: In 419 patients, 595 PTRAs of 552 stenoses were performed from 1982 to 1993. The cases included 295 patients with arteriosclerotic vascular disease (AVD), 49 with fibromuscular dysplasia (FMD), and 74 transplantation patients (TX). Angiographic and clinical follow-up were undertaken. RESULTS: Initial angiographic success was obtained in 92% of the patients and another 3% improved. The rates of immediate success were 92%, 98% and 84% for AVD, FMD and TX respectively. The corresponding rates for primary patency were 57%, 67% and 54%, and for secondary patency (after 1 to 6 angioplasties) 77%, 93% and 64%. Lower long-term results were obtained for: recanalized vessels; long lesions; bifurcation stenoses; stenoses in patients with abdominal aortic aneurysm; smaller vessels; and segmental branches in native and TX kidneys. Of 252 patients with hypertension, 8% were cured and another 58% improved. Of 215 patients with reduced renal function, 38% were normalized or improved and 42% unchanged. Major complications including 2 deaths were seen in 2.9% of the procedures and other complications in 4.7%. CONCLUSION: PTRA with a guiding catheter can be performed in most patients with a high success rate and a low complication rate. This study points to two major problems with PTRA: the high restenosis rate and the low response to treatment of hypertension. The careful selection of patients for PTRA is important for increasing the success rate, and follow-up to detect restenosis is mandatory.

Adolescent↗
PubMed1998

The national kidney transplant program in Norway still results in unchanged waiting lists.

1. Of 2,670 patients starting renal replacement therapy for end-stage renal disease in Norway from 1989-1997, 76% were candidates for transplantation. The annual need for transplantations increased from 47 to 64 grafts PMP as the number of elderly patients increased. The national waiting list has remained almost stable during the period from 1989-1997 at levels of 25-30 PMP, but the dialysis population has increased from 57-105 PMP. 2. A total of 1,681 transplants was performed at an annual rate varying between 38 and 46 grafts PMP. The grafts were procured from LDs in 41% and CDs in 59% of cases. Totally 69% of all patients in need were transplanted and 54% of all patients requiring replacement therapy for end-stage renal disease received a transplant. 3. Graft survival rates in recipients of first LD grafts (n = 641) were 91% and 77% at one and 5 years, respectively. One-year graft survival was 97% in HLA-identical grafts (n = 71), 92% in haploidentical grafts (n = 419), 88% in 2 haplotype-mismatched related grafts (n = 43), and 87% in spousal donor grafts (n = 108). 4. Graft survival rates in recipients of first CD grafts (n = 801) were 84% and 65% at one and 5 years, respectively. The rates were 86% and 74% in younger (n = 557) versus 78% and 46% in older (> 65 years) (n = 244) patients. Death with a functioning graft caused approximately 45% and 75% of all graft losses in younger and older patients, respectively. Cardiovascular disease was the major cause of death. 5. A significant beneficial effect of HLA-DR matching was observed in CD grafts performed after 1989, in particular in patients older than age 65.

Adolescent↗
PubMed1997

Glucose intolerance after renal transplantation depends upon prednisolone dose and recipient age.

BACKGROUND: Retrospective studies on the prevalence of posttransplant diabetes mellitus (PTDM) in patients on triple-drug immunosuppressive therapy have shown great dispersity, while the incidence of posttransplant impaired glucose tolerance (IGT) is unknown. The aim of our study was to prospectively examine the incidence of posttransplant glucose intolerance and to assess potential risk factors. METHODS: Glucose intolerance was prospectively examined in 173 consecutive kidney transplant recipients by oral glucose tolerance tests (n=167) or the diagnosis of manifest diabetes mellitus (n=6) at 10 weeks after transplant. RESULTS: We found a high incidence of PTDM (18%) and IGT (31%). Univariate analysis revealed that age, family history of diabetes, HLA-B27 phenotype, DR mismatch, rejection, actual prednisolone dose, total methylprednisolone dose, total steroid dose, cytomegalovirus (CMV) infection, and the use of furosemide were associated with PTDM. Age, prednisolone dose, CMV infection, and the use of beta-blockers were associated with IGT. Gender, body mass index, donor source, and cyclosporine level did not influence glucose tolerance. Prednisolone dose, age, family history of diabetes, CMV infection, and HLA-B27 phenotype were independent predictors of PTDM with the use of multiple stepwise logistic regression analysis. Age, prednisolone dose, and the use of a beta-blocker were associated with IGT in the multivariate model. Both univariate and multivariate linear regression analysis revealed a significant relationship between the 2-hr serum glucose and prednisolone dose. The risk of developing PTDM was 5% per 0.01 mg/kg/day of increase in prednisolone dose. CONCLUSIONS: Increased prednisolone dose and older age are strongly associated with the development of posttransplant glucose intolerance.

Adult↗
PubMed1997

Serum amyloid A protein is a clinically useful indicator of acute renal allograft rejection.

BACKGROUND: Early diagnosis of acute rejection after renal transplantation is important. There is evidence that measurement of the acute phase proteins, C-reactive protein (CRP) and serum amyloid A protein (SAA) is helpful. METHODS: In 64 consecutive patients, CRP was measured in a routine clinical system (Technicon RA1000, Bayer) and SAA in a new sensitive automated immunoassay on the Abbott IMx instrument, daily or on alternate days for 30 days after renal transplantation. RESULTS: Patients all received triple immunosuppression with cyclosporin, azathioprine, and prednisolone and all mounted a post-surgical acute phase response of SAA, but the CRP response was reduced or absent. Serum creatinine rose significantly in 36 patients, leading to treatment for first rejection. Thirty of these episodes were confirmed rejection, three were definitely not and three were uncertain. SAA. normally < 10 mg/l, rose to more than 100 mg/l in all episodes except when rejection was definitely absent. In six cases SAA rose above 100 mg/l 1-3 days before the rise in creatinine leading to antirejection therapy, and only twice did creatinine rise 1 day before SAA. In contrast, CRP responses to rejection were modest or absent. In four patients there were SAA and CRP responses unrelated to rejection, three associated with intercurrent infection and one with administration of antilymphocyte globulin. There were also two unexplained isolated spikes of SAA. CONCLUSIONS: SAA is a sensitive marker of acute renal allograft rejection. It is not specific, but the differential behaviour of CRP in patients receiving cyclosporin helps to distinguish infection from rejection. Availability of rapid assays for these analytes should facilitate management of renal allograft recipients.

Acute Disease↗
PubMed1996

[Mycophenolate mofetil--a new immunosuppressive agent].

Mycophenolate mofetil is a prodrug that is rapidly converted to the active immunosuppressant mycophenolic acid. This substance inhibits the enzyme inosine monophosphate dehydrogenase, leading to a depletion of (deoxy-)guanosine nucleotides and thereby a reduction of de novo purine synthesis. Lymphocytes are relatively dependent on this pathway, particularly for RNA and DNA synthesis, and are thereby more susceptible to the antiproliferative effects of mycophenolate. In three randomised, double-blind, multicentre trials, lower rejection rates have been demonstrated in renal allograft recipients during the first months after transplantation. Side effects were more frequent in the mycophenolate mofetil groups. The most important adverse reactions to mycophenolate mofetil are leucopenia, gastrointestinal effects and the increased risk of infections and malignancies associated with immunosuppression in general. At 12 months, graft survival was similar in all groups. The future role of mycophenolate mofetil in immunosuppressive therapy during transplantation has not yet been established. As a start it may be found to have specific use in subgroups of allograft recipients at high risk of rejection.

Clinical Trials as Topic↗
PubMed1996

Half dose of OKT3 is efficient in treatment of steroid-resistant renal allograft rejection.

Rejection episodes in renal allograft recipients are usually efficiently treated with high doses of intravenous methylprednisolone. Rejection therapy with OKT3 is often reserved for steroid-resistant episodes. However, the optimal dose of OKT3 in the treatment of steroid-resistant rejection is not known. Therefore, we randomized renal transplant recipients with steroid-resistant rejection to treatment with a standard daily intravenous dose of either 5 mg of OKT3 (n=15) or 2.5 mg of OKT3 (n=15) for 10 days. Circulating T cells (measured as CD2+ cells) were adequately and equally depleted in the two groups. Three grafts were lost due to rejection within the first 3 months following OKT3 administration, one in the 2.5 mg OKT3 group and two in the 5 mg OKT3 group. Two nonimmunologic graft losses occurred in the 2.5 mg OKT3 group. Median serum creatinine values were not different between the two groups, neither at the start (median values: 200 micormol/L in the 5 mg OKT3 group vs. 188 micromol/L in the 2.5 mg group) nor immediately after OKT3 rescue therapy (202 micromol/L vs. 185 micromol/L, respectively). Eight cytomegalovirus infections occurred in each group. Two re-rejection episodes occurred in the 5 mg OKT3 group and one occurred in the 2.5 mg OKT3 group. All responded to treatment. Function of the remaining grafts estimated by serum creatinine after a mean long-term follow-up of 18 months (range, 6-36 months) revealed no differences (185 micromol/L in the 5 mg OKT3 group vs. 170 micromol/L in the 2.5 mg OKT3 group). We conclude that OKT3 treatment of steroid-resistant rejections in renal transplant recipients is equally effective in daily doses of 2.5 mg and 5 mg with respect to reversal rate and long-term outcome.

Adult↗
PubMed1996

Pharmacokinetics and immunodynamics of chimeric IL-2 receptor monoclonal antibody SDZ CHI 621 in renal allograft recipients.

SDZ CHI 621 is a murine-human chimeric monoclonal antibody (mAb) to the interleukin-2 (IL-2) receptor (CD25) intended for prophylactic immunosuppression against acute rejection in the first several weeks following kidney transplantation. A multicentre, prospective, dose-finding study was conducted in 37 primary, mismatched cadaver kidney transplant patients to assess its tolerability, pharmacokinetics and immunodynamics. Successive cohorts of patients were stratified to receive total doses of 20, 30, 40 or 60 mg (n = 4, 4, 14, 15, respectively) administered as 15- or 20-mg intravenous infusions with the first dose given preoperatively and subsequent doses within the first 10 days posttransplant. Daily mAb serum concentrations were analysed by a radioimmunoassay method and the percentage of peripheral T-lymphocytes expressing CD25 from serial blood samples was determined by FACScan. Intravenous administrations were well tolerated. mAb concentration profiles exhibited a biphasic decline with an initial t1/2 of 14.4 +/- 14.2 h, terminal t1/2 of 13.4 +/- 6.0 days, distribution volume (Vss) of 6.9 +/- 3.31 and clearance of 17.4 +/- 7.8 ml/h. The concentration-effect (mAb-CD25) relationship indicated that mAb concentrations exceeding a threshold of about 0.7 microgram/ml corresponded to complete suppression of CD25 (< or = 3% CD25+ T-cells). The threshold mAb concentration was exceeded at all dose levels, whereas the duration above the threshold (and thus of CD25 suppression) rose with increasing dose: 20 mg, 20 +/- 7 days; 30 mg, 32 +/- 6 days; 40 mg, 37 +/- 10 days; and 60 mg, 53 +/- 17 days. As mAb concentrations declined below the threshold following the last dose, CD25 expression returned to baseline (18-44% CD25+ T-cells) within a few days.

Adolescent↗
PubMed1996

Bilateral nephrectomy simultaneously with renal allografting does not alleviate hypertension 3 months following living-donor transplantation.

Severe hypertension prior to renal transplantation has traditionally been an indication for bilateral nephrectomy. The reasons for hypertension after successful renal transplantation are however many, and the impact of simultaneous bilateral nephrectomy (BN) in this setting has not been well documented. We retrospectively evaluated 158 living-donor renal graft recipients. BN had been performed in 76 patients at the time of the transplantation and 82 were not nephrectomized (controls). All received a triple immunosuppressive drug regimen. Before transplantation, patients in the BN group used 1.8 +/- 0.9 (mean +/- SD) antihypertensive drugs/day, significantly more than in the control group (1.3 +/- 0.8; P < 0.05). Three months after renal transplantation no difference was found (0.9 +/- 1.0 drugs/day in the BN group vs 1.0 +/- 0.8 drugs/day in the control group). No difference was found with respect to serum creatinine, whole blood cyclosporin A (CsA) concentration or blood pressure between the groups. The number of blood transfusions during the first week after transplantation was significantly increased in the BN group (66 SAG units vs 4 SAG units). The median hospitalization length was also longer in the BN group (21 days vs 16 days). In order to circumscribe the pre-transplant difference in use of antihypertensive medication we studied a subgroup of 62 hypertensive recipients (BN/control = 31/31) matched for number of antihypertensive drugs at the time of transplantation (2.3 +/- 0.5 drugs/day in the BN group, 2.1 +/- 0.3 drugs/day in the control group). Three months after transplantation the use of antihypertensive drugs remained the same in the two groups (1.3 +/- 1.0 drugs/day in the BN group vs 1.3 +/- 0.9 drugs/day in the control group). At 3 months no difference was found between the two hypertensive subgroups regarding serum creatinine, whole blood CsA and haemoglobin concentration or systolic blood pressure. However, the BN patients were younger than the control group (38 +/- 10 years vs 49 +/- 11 years, P < 0.05) and this may explain the marginally lower diastolic blood pressure observed in the BN group (82 +/- 10 mmHg vs 87 +/- 7 mmHg, P < 0.05). It is concluded that, in recipients of living-donor grafts, bilateral nephrectomy performed at the time of transplantation did not influence the number of antihypertensive drugs used 3 months after a successful transplantation. Bilateral nephrectomy did however increase the need of blood transfusions during the first week after transplantation and also the hospitalization length.

Adult↗
PubMed1996

Effect of oral terbinafine treatment on cyclosporin pharmacokinetics in organ transplant recipients with dermatophyte nail infection.

Eleven patients with either kidney, heart or lung transplants, immunosuppressed with cyclosporin A, and with culture-proven dermatophyte toe nail infection, were given 250 mg terbinafine orally daily for 12 weeks. No changes in cyclosporin A dosage were made. A statistically significant decrease in mean specific cyclosporin A blood trough levels was found at 4, 8 and 12 weeks. No other statistically significant changes in the pharmacokinetic profile of cyclosporin A were seen. Terbinafine possibly induces a cyclosporin A metabolic degradation, which, however, is of little clinical significance. Terbinafine treatment is a safe therapeutical option in cyclosporin A-treated patients with dermatophyte nail infection. Cyclosporin A levels should be controlled during treatment.

Administration, Oral↗