Search PubMed⌕ Search

Biomedical subjects

Anders Hartmann

Publications and source records attributed to Anders Hartmann.

At least 37 records · Page 2Linked to original sources
PubMed2004

Impact of early cytomegalovirus infection and disease on long-term recipient and kidney graft survival.

BACKGROUND: The impact of cytomegalovirus (CMV) infection and disease on long-term outcome after kidney transplantation is still unsettled. METHODS: Between 1994 and 1997, 397 consecutive first kidney graft recipients and 74 retransplants were included in the study and followed prospectively until December 31, 2001. CMV infection (CMV pp65 antigenemia) and CMV disease were recorded once weekly during the first 100 days after transplantation. No CMV prophylaxis or preemptive therapy was given. In a multiple Cox proportional hazard model allowing time-dependent covariates, the effects of asymptomatic CMV infection and CMV disease, recipient age and gender, retransplantation, living donor, panel-reactive cytotoxid antibodies, acute rejection, and graft loss were tested on overall mortality beyond 100 days post-transplantation. In a similar analysis, the effect of asymptomatic CMV infection and CMV disease plus other factors were tested on death censored graft loss beyond 100 days. RESULTS: Median (range) follow up time was 66.6 (<1-86.9) months. The incidence of CMV infection and disease during the first 100 days was 62.8% and 23.4%, respectively. The number of total deaths was 96 (20%), 82 occurred after the first 100 days. Independent risk factors for overall mortality beyond 100 days were asymptomatic CMV infection, RR = 2.90 (95% CI 1.61-5.22) (P= 0.001), CMV disease, RR = 2.50 (95% CI 1.31-4.79) (P= 0.006), both compared to no infection or disease, recipient age, RR = 1.066 per year (95% CI 1.048-1.084) (P < 0.001), and graft loss in the whole study period RR = 7.88 (95% CI 4.75-13.08) (P < 0.001). Asymptomatic CMV infection and CMV disease were not independent risk factors for death censored graft loss, but they significantly reduced graft survival uncensored for death, (log rank P= 0.001, respectively). CONCLUSION: Asymptomatic CMV infection and overt CMV disease during the first 100 days increase the risk of recipient mortality beyond 100 days. This raises the question whether CMV prophylaxis should be given routinely after kidney transplantation.

Adolescent↗
PubMed2004

Effect of fluvastatin on renal end points in the Assessment of Lescol in Renal Transplant (ALERT) trial.

BACKGROUND: Hyperlipidemia is a risk factor for long-term renal transplant dysfunction, but no prospective clinical trials have investigated the effects of statin treatment on graft function in renal transplant recipients. The aim of the present study was to evaluate the effect of fluvastatin on long-term renal transplant function and development of chronic allograft nephropathy in the ALERT (Assessment of Lescol in Renal Transplantation) study. METHODS: ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin, 40 mg and 80 mg daily, in renal transplant recipients. Patients were randomized to receive either fluvastatin (N= 1050) or placebo (N= 1052) and followed for five to six years. Renal end points included graft loss or doubling of serum creatinine or death; glomerular filtration rate (GFR) was also measured during follow-up in a subset of patients (N= 439). RESULTS: There were 283 patients (13.5%) with graft loss, mainly due to chronic rejection (82%), yielding an annual rate of 2.4%. Fluvastatin treatment significantly lowered mean low-density lipoprotein (LDL)-cholesterol levels by 32% (95% CI -33 to -30) compared with placebo, but had no significant effect on the incidence of renal graft loss or doubling of serum creatinine, or decline in GFR throughout follow-up in the whole study population. Neither was any treatment effect by fluvastatin found in any of the subgroups analyzed. CONCLUSION: Fluvastatin treatment significantly improves lipid values in renal transplant recipients but has no effect on graft loss or doubling of serum creatinine.

Adult↗
PubMed2003

Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial.

BACKGROUND: Renal transplant recipients are at increased risk of premature cardiovascular disease. Although statins reduce cardiovascular risk in the general population, their efficacy and safety in renal transplant recipients have not been established. We investigated the effects of fluvastatin on cardiac and renal endpoints in this population. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled trial in 2102 renal transplant recipients with total cholesterol 4.0-9.0 mmol/L. We randomly assigned patients fluvastatin (n=1050) or placebo (n=1052) and follow up was for 5-6 years. The primary endpoint was the occurrence of a major adverse cardiac event, defined as cardiac death, non-fatal myocardial infarction (MI), or coronary intervention procedure. Secondary endpoints were individual cardiac events, combined cardiac death or non-fatal MI, cerebrovascular events, non-cardiovascular death, all-cause mortality, and graft loss or doubling of serum creatinine. Analysis was by intention to treat. FINDINGS: After a mean follow-up of 5.1 years, fluvastatin lowered LDL cholesterol concentrations by 32%. Risk reduction with fluvastatin for the primary endpoint (risk ratio 0.83 [95% CI 0.64-1.06], p=0.139) was not significant, although there were fewer cardiac deaths or non-fatal MI (70 vs 104, 0.65 [0.48-0.88] p=0.005) in the fluvastatin group than in the placebo group. Coronary intervention procedures and other secondary endpoints did not differ significantly between groups. INTERPRETATION: Although cardiac deaths and non-fatal MI seemed to be reduced, fluvastatin did not generally reduce rates of coronary intervention procedures or mortality. Overall effects of fluvastatin were similar to those of statins in other populations.

Adult↗
PubMed2003

Diagnosing PTDM.

Explore the source record for details and available documents.

Diabetes Mellitus↗
PubMed2003

Fluvastatin reduces atherogenic lipids without any effect on native endothelial function early after kidney transplantation.

BACKGROUND: Cardiovascular risk is greatly increased in renal transplant recipients. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) therapy may reduce cardiovascular risk by improving both dyslipidemia and endothelial function. We therefore performed this study to assess the effect of fluvastatin on endothelial function in renal transplant recipients. METHODS: This randomized, placebo-controlled, double-blind designed study investigated the effect of fluvastatin on endothelial function. Thirty-seven recipients received fluvastatin 40 mg/d and 35 received placebo during the first 12 wk following transplantation. All patients initially received cyclosporin A, prednisolone and azathioprine. At the end of treatment, endothelial function was assessed in the forearm skin microvasculature by laser Doppler flowmetry following acetylcholine stimulation. Samples were taken for measurements of serum lipids and vasoactive markers. RESULTS: There were no differences in endothelial function between fluvastatin recipients and controls, AUCACh was 656 +/- 479 and 627 +/- 518 AU min, respectively (fluv vs. control, p > 0.65). In the placebo limb, total cholesterol and LDL cholesterol increased 22 +/- 12% and 22 +/- 18%, respectively in the first 12 wk following transplantation. The respective values were 18 +/- 13% (p = 0.010) and 34 +/- 19% (p = 0.0013) lower at 12 wk in the fluvastatin treated patients. Plasma ET-1, BigET-1 and urinary excretion of cGMP were not significantly different between treatment groups (p > 0.55). CONCLUSION: Although fluvastatin 40 mg/d significantly lowers cholesterol it does not affect endothelial function the first 3 months after renal transplantation. The lack of effect on endothelial function is consistent with a lack of effect on vasoactive substances.

Cholesterol↗
PubMed2003

Individualized T cell monitored administration of ATG versus OKT3 in steroid-resistant kidney graft rejection.

Acute steroid-resistant rejection episodes are recommended to be treated with set doses of anti-thymocyte globulin (ATG) or anti-CD3 monoclonal antibody (OKT3). Individualized T cell monitoring has been proposed as a tool for dose finding. A randomized study comparing the efficacy and safety of ATG (n = 27) with OKT3 (n = 28) in the treatment of biopsy verified acute steroid-resistant rejection (ASRR) when both drugs were administered on the basis of daily individualized T cell measurements. A drop to below 50 cells/mm3 CD2+ T cells was considered adequate and used to guide the dose of ATG/OKT3. Demographic, clinical and histopathological severities of rejections were equal in the two groups. During the 10 days of T cell monitoring and antibody treatment, 13 patients were in need of dialysis (ATG = 7/OKT3 = 6). Two grafts did not respond to antibody treatment and were lost due to rejection (ATG = 1/OKT3 = 1). There were 26 biopsy verified re-rejections (ATG = 12/OKT3 = 14) within the first 3 months following antibody treatment. Mean serum creatinine (micromol/L) was similar in the two groups (ATG/OKT3: before rejection 157 +/- 72/151 +/- 88, at start of antibody treatment 308 +/- 125/330 +/- 94, end of antibody treatment 254 +/- 122/246 +/- 144 and at follow-up after a mean of 32 months 166 +/- 55 (n = 24)/164 +/- 57(n = 23)). To keep the T cell count below 50 cells/mm3, average dose ATG given was 354 +/- 151 mg (2.3 administrations, range 1-4) and average OKT3 was 32.5 +/- 6.8 mg in 10 doses. In conclusion, individualized T cell monitored administration of ATG and OKT3 is safe and seems as effective as a standard set dose in treatment of ASRR. Tailoring the dose for each individual patient lowers the cost.

Antilymphocyte Serum↗
PubMed2003

Determinants of insulin secretion after renal transplantation.

The high prevalence of post-transplant glucose intolerance and insulin resistance (IR) is associated with older age, family history of diabetes, immunosuppressive drugs, and antihypertensive therapy. However, the potential determinants of post-transplant beta-cell dysfunction are largely unknown. The objective of the present study was to address this issue in detail. A total of 167 previously nondiabetic renal transplant recipients underwent a 75-g oral glucose tolerance test (OGTT)10 weeks after transplantation. Serum glucose and insulin were measured at 0, 1, and 2 hours. Three insulin release indices (Secr(AUC), Secr(1.phase), and Secr(2.phase)) were calculated to assess the insulin secretory response as the dependent variable. To account for variations in insulin sensitivity (IS), beta-cell function was also estimated as the disposition index (DI); the product of the IS index (ISI(TX)) and Secr(1.phase). Increasing age was strongly and independently associated with a blunted insulin secretory response even after adjustment for IS (P =.001). An 80-year-old recipient had an approximately 50% lower insulin release than a 20-year-old individual, based on the linear regression model. Cytomegalovirus (CMV) disease and treatment with furosemide were both independently associated with beta-cell dysfunction (DI; P <.001 and P =.008). Patients treated with angiotensin-converting enzyme (ACE)-inhibitors had an enhanced absolute insulin release, but the DI was similar in both treated and untreated recipients. We conclude that older age is an important determinant of beta-cell dysfunction after renal transplantation. CMV disease and treatment with furosemide may also negatively influence pancreatic insulin release in renal transplant recipients.

Adolescent↗
PubMed2003

Pre-emptive therapy of CMVpp65 antigen positive renal transplant recipients with oral ganciclovir: a randomized, comparative study.

BACKGROUND: About one-quarter of renal transplant patients will suffer from symptomatic cytomegalovirus (CMV) disease if no preventive therapeutic measures are taken. In this prospective, randomized single-centre study pre-emptive therapy with oral ganciclovir is compared with conventional deferred treatment. METHODS: Renal transplant recipients (n= 455) over 18 years of age were screened weekly for CMV pp65 antigenaemia during the first 12 weeks post-transplantation. If CMV pp65 antigen in leukocytes appeared within 8 weeks post-transplantation patients were randomized and included in the study. Five patients developed CMV disease before positive CMV pp65, and 14 patients with a positive antigen test developed CMV disease before randomization could take place, all these representing a limitation of the applicability of the results in the overall renal transplant population. Altogether 179 patients were not randomized for various reasons. Eighty patients completed the study, 42 were randomized to receive pre-emptive oral ganciclovir therapy and 38 to conventional deferred treatment (control group). RESULTS: Time from transplantation to start of ganciclovir capsules was 36 (12-60) days and duration of oral ganciclovir therapy was 49 (27-70) days, median (range). No patient in the pre-emptive treatment group, but nine of 38 patients (23.7%) in the control group, developed CMV disease during the first 12 weeks post-transplantation (P= 0.0009). In the period from 3 months to 1 year post-transplantation, two patients in each group developed CMV disease. There were no significant differences in acute rejection or renal function between treatment groups during the first post-transplant year. CONCLUSIONS: Pre-emptive oral ganciclovir therapy in renal transplant recipients during the first 12 weeks post-transplantation effectively prevents CMV disease during this time period. The incidence of late CMV disease (3 months to 1 year after transplantation) was similar in the two groups, indicating that pre-emptive therapy does not result in late onset of CMV disease.

Administration, Oral↗
PubMed2003

A 6-year prospective study on new onset diabetes mellitus, insulin release and insulin sensitivity in renal transplant recipients.

BACKGROUND: It is well known that both insulin resistance and insulin deficiency are involved in the pathogenesis of post-transplant diabetes mellitus (PTDM), but the relative importance of the two different mechanisms is still under debate. The present prospective longitudinal study was performed over 6 years to investigate the impact of impaired insulin secretion (ISec) and insulin sensitivity (IS) in the development of PTDM in renal transplant recipients. METHODS: A total of 95 non-diabetic patients underwent a 75 g oral glucose tolerance test (OGTT) 10 weeks post-transplant. Six years later, 63 of these recipients were re-examined, the majority (n = 58) with an OGTT. Fasting, 1- and 2-h insulin and glucose levels were measured and used to estimate the insulin secretory response and IS both at baseline and at follow-up. RESULTS: The proportion of recipients with normal glucose tolerance (NGT) rose from 46% (baseline) to 65% (follow-up) (P = 0.008), and median fasting and 2-h serum glucose were reduced by 0.7 mmol/l (P < 0.001) and 1.3 mmol/l (P = 0.039), respectively. The recipients with PTDM at follow-up had a significant decline in the estimated median first and second phase ISec (-58 and -47%, respectively, P = 0.005 for both). The patients who normalized their glucose tolerance from PTDM or IGT at baseline to NGT at follow-up increased their IS significantly (68%, P = 0.002) without significant alterations in ISec. CONCLUSIONS: Impaired ISec seems to be the dominant mechanism in the development of PTDM after renal transplantation. In contrast, normalization of glucose intolerance is associated with improved IS.

Adult↗
PubMed2002

[Protein-creatinine ratio--a simple method for proteinuria assessment in clinical practice].

BACKGROUND: Proteinuria is an indicator of renal disease. Measurement of protein excretion is important for diagnosis and follow-up of renal disease, but measuring 24-hour protein excretion is a cumbersome procedure. MATERIAL AND METHODS: A simplified validated method for measuring excretion is obtained by measuring urine protein/creatinine concentration in a spot urine sample. RESULTS: We have implemented such ratios for clinical routine measurements of proteinuria at Rikshospitalet University Hospital in Oslo. Whenever protein or albumin in urine is requested, the laboratory also measures urine creatinine and reports the ratio in mg protein/mmol creatinine. 24-hour excretion is approximately 10 times the ratio. The rationale for using the ratio is given and proteinuria pathophysiology and potential risks and treatment options are discussed. INTERPRETATION: Our experience is that use of the urine protein/creatinine ratio is a significant improvement. Measurements are now routinely made whereas quantification was rarely performed when 24-hour urine samples were used. We recommend that physicians and laboratories implement the use of this ratio in their daily routines.

Albuminuria↗
PubMed2002

Diagnosing PTDM.

Explore the source record for details and available documents.

Blood Glucose↗
PubMed2002

Development of renal structural lesions in type-1 diabetic patients with microalbuminuria. Observations by light microscopy in 8-year follow-up biopsies.

Kidney biopsies were obtained in 18 type-1 diabetic patients with microalbuminuria and again 8 years later. Over the first 30 months, a treatment protocol (conventional versus intensified treatment) was followed. The biopsies were embedded into plastic and sectioned serially. The volume of individual glomeruli and the vascular pole area was determined. The number of glomeruli showing capsular drops, fibrinoid lesions, adhesions, extra efferent arterioles and corpuscles totally occluded were counted and expressed as a percentage of the total number of corpuscles. Cortical interstitium and degenerated tubules were estimated by point counting. From baseline to the 8-year biopsy, the group of patients showed significant increase in interstitial volume fraction, mean glomerular volume and vascular pole area. The frequency of glomerular occlusion, fibrinoid lesions, adherences and extra efferent arterioles increased, whereas the frequency of capsular drops did not change, and degenerated tubular profiles showed a non-significant increase. No correlation was seen between these light microscopic observations and the concomitant development of diabetic glomerulopathy. Increase in albumin excretion rate was associated with increase in glomerular volume and vascular pole area. No correlation was seen with the glomerular filtration rate, blood pressure or metabolic control. The increase in structural parameters illustrates the slowly ongoing alteration of renal structures in type-1 diabetic patients with microalbuminuria.

Adult↗
PubMed2002

The impact of impaired insulin release and insulin resistance on glucose intolerance after renal transplantation.

The current knowledge of the pathogenesis of post-transplant glucose intolerance is sparse. This study was undertaken to assess the relative importance of insulin secretion (ISec) and insulin sensitivity (IS) in the pathogenesis of post-transplant diabetes mellitus (PTDM), impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) after renal transplantation. An oral glucose tolerance test (OGTT) was performed in 167 non-diabetic recipients 10 wk after renal transplantation. Fasting, 1-h and 2-h insulin and glucose levels were used to estimate the insulin secretory response and IS. One year after transplantation 89 patients were re-examined with an OGTT including measurements of fasting and 2 h glucose. Ten weeks after transplantation the PTDM-patients had significantly lower ISec and IS than patients with IGT/IFG, who again had lower ISec and IS than those with normal glucose tolerance (NGT). One year later, a similar difference in baseline ISec was observed between the three groups, whereas baseline IS did not differ significantly. Patients who improved their glucose tolerance during the first year, were mainly characterized by a significantly greater baseline ISec, and they received a significantly higher median prednisolone dose at baseline with a subsequent larger dose reduction during the first year, than the patients who had their glucose tolerance unchanged or worsened. In conclusion, both impaired ISec and IS characterize patients with PTDM and IGT/IFG in the early course after renal transplantation. The presence of defects in insulin release, rather than insulin action, indicates a poor prognosis regarding later normalization of glucose tolerance.

Adolescent↗
PubMed2002

The impact of cytomegalovirus infection and disease on rejection episodes in renal allograft recipients.

Cytomegalovirus (CMV) infection and disease are potential risk factors for acute allograft rejection in renal transplant recipients. The present study specifically addresses this issue. From October 1994 to July 1997, 477 consecutive renal allograft recipients (397 first transplants and 80 retransplants) were included in the study. CMV infection (cytomegalovirus pp65 antigen in leukocytes) and disease (infection and clinical symptoms or signs of disease) were examined prospectively for 3 months. No CMV prophylaxis was given, and CMV disease was treated with intravenous (i.v.) ganciclovir. The retransplantation of four patients transplanted twice during the study and 22 patients receiving kidneys from human leucocyte antigen (HLA)-identical siblings were excluded from statistical analysis. Rejections were evaluated clinically [277(61%)] and 173 (38%) also had a biopsy verified rejection. CMV infection occurred in 64% of the patients and 24% experienced CMV disease. In a multiple time-dependent Cox analysis, CMV infection and CMV disease were independent significant predictors for clinical acute rejections, RR = 1.6 (1.1-2.5, p = 0.02) and RR = 2.5 (1.2-5.1, p = 0.01), respectively. Among 173 patients with biopsy verified rejection, 72% of the patients had tubulointerstitial rejection whereas 28% had a vascular rejection. CMV disease, but not CMV infection was a predictor of tubulointerstitial rejection, RR = 3.1 (1.1-9.3, p = 0.04). CMV infection and disease are independent risk factors for clinical acute rejection in kidney allograft recipients. CMV disease is an independent risk factor for biopsy verified acute tubulointerstitial rejection in kidney allograft recipients.

Cytomegalovirus↗