Gunter Laux

No Improvement of Patient or Graft Survival in Transplant Recipients Treated with Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Type 1 Receptor Blockers: A Collaborative Transplant Study Report

It was reported recently that treatment of kidney transplant recipients with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB) is associated with strikingly improved long-term graft and patient survival. This finding has important implications for future posttransplantation therapy recommendations. In an analysis of 17,209 kidney and 1744 heart transplant recipients, an association of treatment with ACEI/ARB with improved transplant outcome could not be confirmed. It is concluded that recommendations for a widespread use of ACEI/ARB treatment in transplant recipients are unwarranted.

Long‐Term Prospective Study of Steroid Withdrawal in Kidney and Heart Transplant Recipients

A large prospective study of steroid withdrawal was performed within the framework of the Collaborative Transplant Study to analyze long‐term graft and patient outcome in renal and heart transplant recipients. Steroids were withdrawn no earlier than 6 months posttransplantation. A comparison of 7‐year outcomes in renal transplant recipients (94% receiving cyclosporine; 97% Caucasian) showed a benefit of steroid withdrawal versus steroid continuation in retrospectively matched controls, for graft survival (81.9%± 1.8% vs. 75.3%± 1.2%, p = 0.0001), patient survival (88.8%± 1.5% vs. 84.3 ± 1.0%; p = 0.0016) and death‐censored graft survival (91.8%± 1.3% vs. 87.9%± 1.0%: p = 0.0091). Steroid withdrawal was associated with improved graft survival in heart recipients also (76.2%± 2.4% vs. 66.9%± 1.7%, p = 0.0008). A total of 58.6% of renal recipients and 44.3% of heart recipients never required steroids during follow up. Rates of acute rejection and renal dysfunction did not differ between steroid‐free and steroid‐continuation groups. Steroid withdrawal was associated with significantly improved cardiovascular risk factors compared with steroid continuation. Rates of the development of osteoporosis and cataracts did not differ in the entire patient cohort, but were strikingly lower in patients taken off steroids during the first posttransplant year.

Factors associated with physical activity of patients with osteoarthritis of the lower limb

OBJECTIVE In patients with osteoarthritis (OA), moderate physical activity (PA) can reduce the progress of joint damage. PA is therefore an important target of in the non-surgical treatment of OA. To know about factors associated with PA can increase the success of interventions aiming at increasing PA. The aim of the study was to determine predictors of PA in patients suffering from OA to the hip or to the knee. METHODS In total, 1250 outpatients from 75 general practices were consecutively approached, 1021 returned questionnaires containing sociodemographic data, and short forms of the International Physical Activity Questionnaire (IPAQ), the Arthritis Impact Measurement Scale and the Patient Health Questionnaire to assess concomitant depression. A hierarchical stepwise multiple linear regression analysis with the IPAQ continuous score as dependent variable was performed. RESULTS Comparison of our findings with General population suggests that the overall PA of OA patients is decreased. Main predictors of PA were physical limitation to the lower body (beta = -0.179; P = 0.001), social contacts (P = -0.134; P < 0.001), pain (beta =-0.120; P = 0.001), age (beta = -0.110; P = 0.004) and the body mass index (beta =-0.043; P < 0.001). CONCLUSION The findings emphasize the influence of physical as well as psychosocial factors on PA of patients with OA and should help to tailor future interventions more appropriately. Further research is needed to determine if these tailored interventions will result in better compliance and in increased PA.

Diagnosing asthma in general practice with portable exhaled nitric oxide measurement – results of a prospective diagnostic study

BackgroundTo evaluate the sensitivity, specificity and predictive values of fractional exhaled nitric oxide (FENO) for the diagnosis of asthma in general practice.MethodsProspective diagnostic study with 160 patients attending 10 general practices for the first time with complaints suspicious of obstructive airway disease (OAD). Patients were referred to a lung function laboratory for diagnostic investigation. The index test was FENO measured with a portable FENO analyser based on electrochemical sensor. The reference standard was the Tiffeneau ratio (FEV1/VC) as received by spirometric manoeuvre and/or results of bronchial provocation. Bronchial provocation with methacholine was performed to determine bronchial hyper-responsiveness (BHR) in the event of inconclusive spirometric results.Results88 (55%) were female; their average age was 43.9 years. 75 (46.9%) patients had asthma, 25 (15.6%) had COPD, 8 (5.0%) had an overlap of COPD and asthma, and 52 (32.5%) had no OAD. At a cut-off level of 46 parts per billion (ppb) (n = 30; 18.8%), sensitivity was 32% (95%CI 23–43%), specificity 93% (95%CI 85–97%), positive predictive value (PPV) 80% (95%CI 63–91%), negative predictive value (NPV) 61% (95%CI 52–69%) when compared with a 20% fall in FEV1 from the baseline value (PC20) after inhaling methacholine concentration ≤ 16 mg/ml. At 76 ppb (n = 11; 6.9%) specificity was 100% (95%CI 96–100%) and PPV was 100% (95%CI 72–100). At a cut-off level of 12 ppb (n = 34; 21.3%), sensitivity was 90% (95%CI 79–95%), specificity 25% (95%CI 17–34%), PPV 40% (95%CI 32–50), NPV 81% (95%CI 64–91%) when compared with a 20% fall of FEV1 after inhaling methacholine concentration ≤ 4 mg/ml. Three patients with unsuspicious spirometric results have to be tested with FENO to save one bronchial provocation test.ConclusionAsthma could be ruled in with FENO > 46 ppb. Mild and moderate to severe asthma could be ruled out with FENO ≤ 12 ppb. FENO measurement with an electrochemical sensor might be reasonable with respect to the time consuming procedure of bronchial provocation, which carries also some risk of severe bronchospasm. Further research is necessary to evaluate the effectiveness of this dual diagnostic strategy. The number needed to diagnose might be improved when the diagnostic precision could be enhanced by future technical developments.

A new epitope-based HLA-DPB matching approach for cadaver kidney retransplants

Background. Several years ago a significant impact of matching for HLA-DPB1 alleles on the survival of cadaver kidney retransplants was shown. Here we report the results of a new approach, based on matching for HLA-DPB1 epitopes. Methods. The analysis is based on 1,478 patients who received a cadaver kidney retransplant between 1988 and 1998. DNA methodology (polymerase chain reaction, sequence-specific oligonucleotides) was used to perform HLA-DPB1 typing. Epitope matching was facilitated with the aid of sequence databases and computer calculations. Results. Matching for the HLA-DP epitopes A, B, E, and F, corresponding to the homonymous hypervariable regions of the second exon of the DPB1 gene, seems to have a greater influence on graft survival than matching for the epitopes C and D. Within a group of 529 retransplants with exactly one allelic HLA-DPB1 mismatch, a significantly better graft outcome was observed when less than two epitope mismatches were found, compared with the group with more than three epitope mismatches (at 2 years: 77.8% vs. 65.8%, P =0.0112). Importantly, patients with two DPB1 allele mismatches who had less than or equal to two epitope mismatches exhibited a significantly better graft outcome than recipients who had one HLA-DPB1 allelic mismatch but more than three epitope mismatches (at 2 years: 77.1% vs. 65.8%, P =0.0488). Conclusions. The findings indicate that the impact of HLA-DPB1 matching on the outcome of kidney retransplants is a result of the predominant immunogenicity of certain epitopes of the HLA-DP molecule. Matching for immunogenic HLA-DPB1 epitopes seems to be functionally more relevant than classical matching at the allelic level.

Effect of donor-specific transfusions on the outcome of renal allografts in the cyclosporine era

Despite the introduction of new immunosuppressive agents, a steady decline of functioning renal allografts after living donation is observed. Thus nonpharmacological strategies to prevent graft loss have to be reconsidered, including donor‐specific transfusions (DST). We introduced a cyclosporine‐based DST protocol for renal allograft recipients from living‐related/unrelated donation. From 1993 to 2003, 200 ml of whole blood, or the respective mononuclear cells from the potential living donor were administered twice to all of our 61 recipient candidates. The transplanted subjects were compared with three groups of patients without DST from the Collaborative Transplant Study (Heidelberg, Germany) during a 6‐year period. Six patients were sensitized without delay for a subsequent cadaveric kidney. DST patients had less often treatment for rejection and graft survival was superior compared with subjects from the other Swiss transplant centers (n = 513) or from Western Europe (n = 7024). To diminish the probability that superior results reflect patient selection rather than effects of DST, a ‘matched‐pair’ analysis controlling for relevant factors of transplant outcome was performed. Again, this analysis indicated that recipients with DST had better outcome. Thus, our observation suggests that DST improve the outcome of living kidney transplants even when modern immunosuppressive drugs are prescribed.

Relevance of IL10, TGFbeta1, TNFalpha, and IL4Ralpha gene polymorphisms in kidney transplantation: a collaborative transplant study report.

Single nucleotide polymorphisms (SNPs) of cytokine genes have been shown to influence cytokine plasma levels. Cytokines are important mediators during organ graft rejection. It was reported that certain cytokine genotypes are associated with improved kidney graft survival.

Osteoarthritis of the knee and hip: a comparison of factors associated with physical activity

To assess factors associated with physical activity (PA) in a large sample of primary care patients, 1,250 outpatients from 75 general practices were approached consecutively. Of these, 1,021 (81.7%) returned short forms of the international physical activity questionnaire (IPAQ) and the arthritis impact measurement scale (AIMS2-SF). In addition, the patient health questionnaire (PHQ-9) was used to assess concomitant depression. A stepwise multiple linear regression analysis with the IPAQ score as dependent variable was performed separately for knee and hip patients. The impact of osteoarthritis (OA) on patients with an affected knee (594/58.2%) was more severe, as reflected in higher scores in the “symptom”, “lower body”, and “affect” scales of the AIMS2-SF (p < 0.01 for all). These patients were also less active than patients with OA to the hip (p = 0.02 for IPAQ score). Main predictors of PA [change in p(F) for all factors ≤0.001] in knee OA patients were physical limitation to the lower limb (R2 = 0.180), social network (R2 = 0.121), pain (R2 = 0.111), body mass index (R2 = 0.041), and age (R2 = 0.032). Predictors for OA at the hip (427/41.8%) differed slightly [change in p(F) for all factors ≤0.003): physical limitation to the lower limb (R2 = 0.162), pain (R2 = 0.131), PHQ-9 score (R2 = 0.092), social network (R2 = 0.078), and disease duration (R2 = 0.043). Our findings suggest that factors associated with PA differ depending on the localization of the OA. Our results may help to tailor future interventions more appropriately. Further research is needed to determine whether these tailored interventions will result in increased PA.

Analysis of KIR ligand incompatibility in human renal transplantation

Natural killer cells express killer immunoglobulin-like receptors (KIR) that bind to MHC class I antigens. Lack of self-MHC on the target cell can cause NK-cell mediated killing. Here, we analyzed the effect of KIR ligand incompatiblity on renal allograft survival in humans. Kidney recipient/donor pairs were separated according to their HLA-Cw alleles and HLA-Bw4 specificity which are considered epitopes for KIR. A total of 2,757 renal transplants were examined. Graft survival rates were computed according to the Kaplan-Meier method. No effect of KIR ligand matching on graft survival was observed in cadaver kidney transplants. Our results indicate that KIR ligand matching cannot be recommended as a strategy for improving renal allograft survival.

Recording of risk-factors and lifestyle counselling in patients at high risk for cardiovascular diseases in European primary care.

Background: Detection and registration of high risk for cardiovascular diseases (CVD) by assessing individual’s absolute cardiovascular risk is recommended in clinical guidelines. Effective interventions to reduce cardiovascular risk are available, but not optimally implemented. The aim of this study was to assess the quality of cardiovascular risk-factor recording and lifestyle counselling in high-risk patients in European primary care and to identify factors related to these clinical processes. Methods: An international cross-sectional observational study was conducted in stratified samples of primary care practices in nine European countries. Patient records were audited, using a structured data-abstraction tool based on internationally developed quality indicators. To identify factors associated with the recording, additional data were collected in a patient survey. Descriptive and multilevel data analyses were conducted. Results: In 268 general practices across Europe, 3723 records of individuals at high risk for cardiovascular diseases were audited. We found important variations in the quality of documentation of risk factors and lifestyle interventions. Recording of risk factors was best for blood pressure (92.5% of audited records, 95% CI 0.89–0.96). Lifestyle advice was recorded best for smoking cessation (65.6%, 95% CI 0.58–0.73) and worst for physical activity (38.8%, 95% CI 0.31–0.47). Of the study population, 50.6% (0.42–0.59) had elevated blood pressure levels, 59.8% (0.51–0.69) had total cholesterol >5 mmol/l, and 30.5% (0.22–0.39) were smokers. Multivariate analyses showed that recording of risk factors and counselling were related to specific patient characteristics more than to country effects. Conclusions: Analysis of different country results can be helpful for developing quality-improvement strategies.