Skeletal Muscle Force and Functional Exercise Tolerance Before and After Lung Transplantation: A Cohort Study

We investigated the impact of lung transplantation and outpatient pulmonary rehabilitation after lung transplantation on skeletal muscle function and exercise tolerance. Skeletal muscle force (Quadriceps force, QF), exercise tolerance (six minute walking distance, 6MWD) and lung function were assessed in 36 patients before and after lung transplantation. Seventeen male and 19 female patients (age 57 ± 4) showed skeletal muscle weakness before the transplantation. A further 32 ± 21% reduction was seen 1.2 (interquartile range 0.9 to 2.0) months after LTX. The number of days on the intensive care unit was significantly related to the observed deterioration in muscle force after LTX. At this time point 6MWD was comparable to pre-LTX.
Rehabilitation started 37 (IQR 29 to 61) days after LTX. 6MWD and QF improved significantly (140 ± 91 m, and 35 ± 48%, respectively; p < 0.05) with rehabilitation. QF remained below pre-LTX values. The evolution of the 6MWD with the transplantation and the subsequent rehabilitation was less in female compared to male subjects.
We conclude that muscle strength deteriorates after lung transplantation, particularly in patients with long ICU stay. Outpatient pulmonary rehabilitation is feasible after lung transplantation and leads to recovery of skeletal muscle function. In female patients this recovery is significantly less compared to male recipients.     

Exercise Training Improves Aerobic Capacity and Skeletal Muscle Function in Heart Transplant Recipients

The aim of this study was to examine the effects of 12 weeks of supervised aerobic and strength training (SET) versus no-training (NT) on peak aerobic power (VO_2peak), submaximal exercise left ventricular (LV) systolic function, peripheral vascular function, lean tissue mass and maximal strength in clinically stable heart transplant recipients (HTR). Forty-three HTR were randomly assigned to 12 weeks of SET (n = 22; age: 57 ± 10 years; time posttransplant: 5.4 ± 4.9 years) or NT (n = 21; age: 59 ± 11 years; time posttransplant: 4.4 ± 3.3 years). The change in VO_2peak (3.11 mL/kg/min, 95% CI: 1.2–5.0 mL/kg/min), leg and total lean tissue mass (0.78 kg, 95% CI: 0.31–1.3 kg and 1.34 kg, 95% CI: 0.34–2.3 kg, respectively), chest-press (10.4 kg, 95% CI: 5.2–15.5 kg) and leg-press strength (34.7 kg, 95% CI: 3.7–65.6 kg) were significantly higher after SET versus NT. No significant change was found for submaximal exercise LV systolic function or brachial artery endothelial-dependent or -independent vasodilation. Supervised exercise training is an effective intervention to improve VO_2peak, lean tissue mass and muscle strength in HTR. This training regimen did not improve exercise LV systolic function or brachial artery endothelial function.     

Predictive Capacity of Pre-Donation GFR and Renal Reserve Capacity for Donor Renal Function After Living Kidney Donation

Kidney transplantation from living donors is important to reduce organ shortage. Reliable pre-operative estimation of post-donation renal function is essential. We evaluated the predictive potential of pre-donation glomerular filtration rate (GFR) (iothalamate) and renal reserve capacity for post-donation GFR in kidney donors. GFR was measured in 125 consecutive donors (age 49 +/- 11 years; 36% male) 119 +/- 99 days before baseline GFR (GFRb) and 57 +/- 16 days after donation (GFRpost). Reserve capacity was assessed as GFR during stimulation by low-dose dopamine (GFRdopa), amino acids (GFRAA) and both (GFRmax). GFRb was 112 +/- 18, GFRdopa 124 +/- 22, GFRAA 127 +/- 19 and GFRmax 138 +/- 22 mL/min. After donation, GFR remained 64 +/- 7%. GFRpost was predicted by GFRb(R2 = 0.54), GFRdopa(R2 = 0.35), GFRAA(R2 = 0.56), GFRmax(R2 = 0.55)and age (R2 = -0.22; p < 0.001 for all). Linear regression provided the equation GFRpost = 20.01 + (0.46*GFRb). Multivariate analysis predicted GFRpost by GFRb, age and GFRmax(R2 = 0.61, p < 0.001). Post-donation renal function impairment (GFR < or = 60 mL/min/1.73 m2) occurred in 31 donors. On logistic regression, GFRb, body mass index (BMI) and age were independent predictors for renal function impairment, without added value of reserve capacity. GFR allows a relatively reliable prediction of post-donation GFR, improving by taking age and stimulated GFR into account. Long-term studies are needed to further assess the prognostic value of pre-donation characteristics and to prospectively identify subjects with higher risk for renal function loss.     

Management of Thrombophilia in Renal Transplant Patients

Renal allograft recipients with thrombophilia (a hypercoagulable state) are at higher risk for early allograft loss. Following an episode of allograft renal vein thrombosis in a patient subsequently diagnosed with protein C deficiency, we adopted universal screening for hypercoagulable risk factors. Patients with a history of a thromboembolic event underwent laboratory screening for thrombophilia. Eight patients with a defined hypercoagulable disorder or a strong clinical history of thrombosis even in the absence of hematologic abnormalities were treated with anticoagulation following renal transplantation. We reviewed the outcomes of these eight patients and all renal transplant recipients at our center who developed thrombotic complications after renal transplantation. Since the introduction of universal screening for hypercoagulable risk factors, 235 consecutive transplants were performed without allograft thrombosis. Eight patients with evidence of thrombophilia, recognized before renal transplantation, received perioperative heparin and postoperative oral anticoagulation. Two of these eight patients developed perinephric hematomas requiring evacuation, blood transfusion, and temporary withholding of anticoagulation. Of interest, two of the remaining 227 patients, not identified with thrombophilia before surgery, developed thrombotic complications after renal transplantation. A hypercoagulable disorder was subsequently documented in each. Identifying patients with thrombophilia before transplantation and defining their management presents many challenges. The risk of allograft thrombosis must be weighed against the risk of perioperative bleeding and the need for long-term anticoagulation. Recommendations for managing thrombophilia in renal transplant recipients are suggested based on our experience and review of the literature.     

Preservation of Residual Renal Function with Limited Water Removal in Hemodialysis Patients

Residual renal function (RRF) is of paramount importance for hemodialysis (HD) adequacy, morbidity, and mortality. Some studies have shown that overhydration is beneficial for preservation of RRF, but it can also increase the probability of adverse events such as hypertension and heart failure in HD patients. To determine the optimal amount of dehydration, we performed HD with limited water removal in HD patients. Eighteen HD patients included in this self-controlled study underwent HD with limited water removal. Water removal volume was determined by a previous volume as follows. Total water removal volume was divided into levels: ≤3.0, 3.0–9.0, and >9.0 L per week. Water removal was performed to obtain dry weight in the last dialysis, and was performed three times with a ratio of 1:1:2 and 2:2:3, respectively. Urine volume, endogenous creatinine clearance rate, Kt/V, hemoglobin, and serum albumin were recorded before and after the study at 3, 6, 9, and 12 months. The follow-up period was 12 months. Ten patients withdrew from the study because of adverse events including hypertension (n = 3), heart failure (n = 3), angina (n = 1), polycystic kidney rupture (n = 1), obvious edema (n = 1), and one patient had too much interdialytic weight gain to continue. As a result, we stopped this study after 1 month. Our data suggest that the preservation of RRF with limited water removal in HD patients must be interpreted with caution.     

Renal Responses to exercise in heart and kidney transplant patients

There is a lack of information about renal responses in heart and kidney transplant patients after intense physical exercise. Eleven heart and ten kidney transplant recipients, as well as two control groups of healthy subjects, were given a maximum exercise test on a bicycle ergometer. One control group was also given a moderate load corresponding to the peak load of the kidney transplant group. Blood and urine samples were collected before and after exercise and assayed for lactate, creatinine, total protein, and albumin. The glomerular filtration rate remained stable at the end of exercise in the transplant patients, while there was a slight (17 %) decrease in the control group. Albumin excretion rates after maximum exercise attained a mean of 237 μg · min^–1in the control group and a mean of 45 and 16 μg · min^–1, respectively, in the heart and kidney groups. Postexercise proteinuria seemed to be related to the absolute intensity of the event, but kidney transplant patients showed a reduced effect as compared to heart transplant patients. We conclude that short-term, maximum exercise in heart and kidney transplant recipients is not detrimental to kidney function. Received: 21 November 1996 Received after revision: 4 March 1997 Accepted: 18 March 1997     

COPD患者肌肉衰减综合征发病现状及风险评估模型构建

目的 探讨慢性阻塞性肺疾病（COPD）患者肌肉衰减综合征的发病现状及影响因素,并建立风险诊断模型。方法 对225例COPD患者进行问卷调查及骨骼肌含量、力量及运动功能的体格测量。描述及对比分析不同特征患者肌肉衰减综合征分布情况,风险模型构建采用多因素Logistic回归分析并绘制列线图,计算各诊断模型的受试者工作特征曲线下面积进行验证。结果 225例COPD患者肌肉衰减综合征前期、衰减期及严重衰减期的比例分别为44.00%,13.78%,5.33%。肌肉衰减综合征中肌肉含量降低的比例最高（占63.11%）。多因素风险诊断模型构建结果显示骨骼肌含量、力量、运动功能共同的危险因素为：每日更少的膳食蛋白量,轻、中度体力活动水平及COPD分级的C级与D级。每日膳食蛋白量、体力活动水平及COPD分级对肌肉衰减综合征的诊断价值分别为0.954、0.917、0.860。结论 COPD患者的蛋白摄入、疾病分级及体力活动水平与肌肉衰减综合征密切相关,应采取精准评估及综合干预,有效预防及延缓肌肉衰减综合征的发生发展,提高患者健康水平。     

Sleep Disordered Breathing in Renal Transplant Patients

Sleep disordered breathing (SDB) is a prevalent, important nontraditional cardiovascular (CV) risk factor in end-stage renal disease patients. The prevalence of SDB in renal transplant patients is unknown. We compared polysomnographic studies in 163 transplant patients with matched samples in the general population and explored longitudinally the effect of return to dialysis after graft failure on SDB in three consecutive cases. Episodes of nocturnal hypoxemia, average and minimal O₂ saturation overnight in transplant patients did not differ from those in individuals in the general population matched for age, gender and body mass index (BMI). The prevalence of moderate-to-severe SBD in these patients did not exceed the estimated prevalence of the same disturbance in the general population. The respiratory disturbance index in transplant patients was directly associated with BMI (p < 0.001). In the longitudinal study all indicators of SDB coherently increased after transplant failure. The prevalence of SDB in transplant patients does not differ from that in well-matched individuals in the general population. The favorable effect of renal transplantation on CV risk may be at least partially explained by the lack of risk excess for SDB in this population. Longitudinal observations after transplant failure are compatible with the hypothesis that renal transplantation reverses SDB.     

Laparoscopy-Assisted Radical Nephrectomy for Renal Cell Carcinoma in Patients on Long-term Hemodialysis: Report of 2 Patients

We successfully performed a laparoscopy-assisted radical nephrectomy for renal cell carcinoma in 2 patients on long-term hemodialysis. Both tumors were incidentally discovered on screening by abdominal CT scanning. There were no complications during the operation or in the postoperative period, and both patients resumed normal activities by the fifth postoperative day. A laparoscopic-assisted radical nephrectomy may be useful for the treatment of renal cell carcinoma in hemodialysis patients.     

Association Between Pulse Pressure and Cardiovascular Disease in Renal Transplant Patients

Elevated pulse pressure in general population has been shown to be associated with cardiovascular disease, which is the main cause of death in renal transplant patients. We investigated the effect that a wider pulse pressure range may have on cardiovascular disease after renal transplantation in 532 transplant patients with functioning graft for more than 1 year. Patients were classified into two groups depending on 1-year pulse pressure (< or >/=65 mmHg) and we analyzed patient and graft survival, post-transplant cardiovascular disease and main causes of death. Higher pulse pressure was associated with older recipient age (40.8 +/- 10.8 vs. 50 +/- 11.3), higher systolic blood pressure (132.7 +/- 16.1 vs. 164.5 +/- 16), lower blood diastolic pressure (84.5 +/- 11.6 vs. 84.4 +/- 11.2), higher prevalence of diabetes (12% vs. 23%) and total cardiovascular disease (20.9% vs. 33.6%). Five- and 10-year patient survivals were lower in the group with higher pulse pressure, being vascular disease the main cause of death in both groups. In a Cox regression model increased pulse pressure was associated with higher cardiovascular disease (RR = 1.73, 95% CI: 1.13-2.32 p < 0.01). In conclusion, pulse pressure was an independent risk factor for increased cardiovascular morbidity and mortality in renal transplant patients.     

The Relationship Between Activity Pattern and Muscle Adaptation in Skeletal Muscle

Muscle is highly plastic in terms of size (maximum force), speed, maximum power, and endurance. Well‐controlled studies in animals have shown that the adult skeletal muscle fiber has a remarkable ability to modify its gene expression so that with long‐term substantial changes in the daily activity pattern the contractile phenotype can be modified across the whole spectrum of fiber type found in control muscle. The contractile phenotype in this context includes the isoform content of myosin and therefore the maximum velocity of shortening, the mitochondrial content and therefore the specific force and aerobic capacity (endurance), and the calcium handling proteins and therefore the speed of activation and relaxation. With voluntary exercise in human subjects, similar responses are observed, although the degree of transformation is restricted by the practical limitations of exercise dosing to changes in mitochondrial activity and muscle size rather than the more profound changes in contractile protein isoform that can be induced with artificial activation over a substantial proportion of the day.     

Sirolimus Does Not Exhibit Nephrotoxicity Compared to Cyclosporine in Renal Transplant Recipients

Sirolimus and cyclosporine (CsA) prevent acute rejection in man when used as primary therapies in triple drug regimens. Sirolimus does not act via the calcineurin pathway and therefore is not expected to produce the same renal side-effects. This paper presents the pooled 2-year data analysis of renal function parameters from two open-label, randomized, multicenter studies. Patients (18-68 years) receiving a primary renal allograft were randomized to receive concentration-controlled sirolimus (n = 81) or CsA (n = 80), in combination with azathioprine and steroids (n = 83), or mycophenolate mofetil (MMF) and steroids (n = 78). From week 10 through year 2, calculated glomerular filtration rate (GFR) was significantly higher in sirolimus--than in CsA-treated patients (69.3 vs. 56.8 mL/min, at 2 years, p = 0.004). Serum uric acid was significantly higher in the CsA-treated patients and magnesium was significantly lower; these parameters were more likely to be within normal limits in the sirolimus group. Mean serum potassium and phosphorus were lower in sirolimus-treated patients. In conclusion, sirolimus, when administered as primary therapy in combination with azathioprine or MMF, has a favorable safety profile compared to CsA with regards to renal function.     

Therapy Modalities for Antibody Mediated Rejection in Renal Transplant Patients

Introduction: The aim of our study was to determine the effectiveness of immunoglobulin, rituximab and plasmapheresis in renal transplant patients with antibody mediated rejection (AMR). Patients and Methods: Fourteen renal transplant patients with AMR were included in this study. The mean age of the patients was 33.9 ± 10.3 years and 10 (71.4%) of them were male. Lymphocyte cross match was negative for all patients and 10 (71.4%) of them were living donor transplants. Six patients were administered tacrolimus, three patients cyclosporine, two patients everolimus, and three patients sirolimus for immunosuppression. The patients with AMR were administered IVIG, rituximab and plasmapheresis. Results: Patient survival rate was 100%, graft survival rate after AMR was 50% in the first year and 33% in the 2nd and third years. AMR developed 31.9 ± 25.9 months after transplantation. Seven (50%) patients lost their grafts. Delayed graft function was observed in 28.6%, chronic allograft dysfunction in 78.5%, diabetes after transplantation in 14.3%, and cytomegalovirus infection in 7.1% of the patients. At the last follow-up, the mean blood creatinine was 3.1 ± 1.4, the mean proteinuria was 2300 (1300–3300) mg/day and the mean GFR was 34.5 ± 17.6 ml/min. C4d was positive in peritubullar capillaries in all patients, while neutrophil accumulation in peritubular and glomerular capillaries was observed in 8 patients. Chronic allograft vasculopathy was observed in 12 patients. Conclusion: AMR leads to progressive loss of renal function and has low graft survival. More effective treatment alternatives are needed for this clinical issue.     

Bilateral Pharmacokinetic Interaction Between Cyclosporine A and Atorvastatin in Renal Transplant Recipients

Atorvastatin is increasingly used as a cholesterol-lowering agent in solid organ transplant recipients receiving cyclosporine A (CsA). However, the potential bilateral pharmacokinetic interaction between atorvastatin and CsA in renal transplant recipients has not previously been examined. Baseline 12-h CsA pharmacokinetic investigation was performed in 21 renal transplant recipients and repeated after 4 weeks of atorvastatin treatment (10 mg/ d). At week 4, 24-h pharmacokinetics of atorvastatin was also performed. All patients received basiliximab induction followed by CsA and prednisolone immunosuppression. Compared with historic controls, CsA-treated patients showed, on average, sixfold higher plasma HMG-CoA reductase inhibitory activity after 4 weeks of atorvastatin treatment (p < 0.05). Atorvastatin had a moderate effect on the pharmacokinetics of CsA and reduced the AUC0-12 (area under curve, 0-12h) by 9.5 +/- 18% (p = 0.013) and Cmax (maximal concentration) by 13.5 +/- 24% (p =0.009), while C12 (trough level) was unchanged (p =0.42). Total and LDL cholesterol decreased by 26.8 +/- 8.4% (p < 0.0001) and 41.5 +/- 11.0% (p < 0.0001), respectively. Bilateral pharmacokinetic interaction between atorvastatin and CsA resulted in sixfold higher plasma HMG-CoA reductase inhibitory activity, but only a moderate decrease in systemic exposure of CsA.     

High‐Intensity Interval Training Improves Peak Oxygen Uptake and Muscular Exercise Capacity in Heart Transplant Recipients

Heart transplant (HTx) recipients usually have reduced exercise capacity with reported VO_2peak levels of 50–70% predicted value. Our hypothesis was that high‐intensity interval training (HIIT) is an applicable and safe form of exercise in HTx recipients and that it would markedly improve VO_2peak. Secondarily, we wanted to evaluate central and peripheral mechanisms behind a potential VO_2peak increase. Forty‐eight clinically stable HTx recipients >18 years old and 1–8 years after HTx underwent maximal exercise testing on a treadmill and were randomized to either exercise group (a 1‐year HIIT‐program) or control group (usual care). The mean ± SD age was 51 ± 16 years, 71% were male and time from HTx was 4.1 ± 2.2 years. The mean VO_2peak difference between groups at follow‐up was 3.6 [2.0, 5.2] mL/kg/min (p < 0.001). The exercise group had 89.0 ± 17.5% of predicted VO_2peak versus 82.5 ± 20.0 in the control group (p < 0.001). There were no changes in cardiac function measured by echocardiography. We have demonstrated that a long‐term, partly supervised and community‐based HIIT‐program is an applicable, effective and safe way to improve VO_2peak, muscular exercise capacity and general health in HTx recipients. The results indicate that HIIT should be more frequently used among stable HTx recipients in the future.     

Acute Post-Bacterial Glomerulonephritis in Renal Transplant Patients: Description of Three Cases and Review of the Literature

Only a few cases of acute post-infectious glomerulonephritis have been described in renal transplant patients. We report here three cases of acute post-bacterial glomerulonephritis in renal transplants. In contrast to the classic cases of post-streptococcal glomerulonephritis the type of infection was heterogeneous: respectively, Escherichia coli bacteremia, a skin abscess, and cholangitis. The clinical presentation was characterized by a deterioration of graft function in two of our three patients. Acute renal dysfunction recovered in both patients, but in the long term the outcome was severe; two of the three patients lost their graft function. It is difficult to ascertain whether progression was due to chronic allograft nephropathy, to glomerulonephritis, or both. It may be concluded that acute post-infectious glomerulonephritis is a possible, although rare, complication in renal transplant recipients. It has an unusual presentation and may have a poor outcome in the long term. The role of therapy, if any, is still undefined.     

危重症患者肾功能与凝血功能变化的关系

目的:探讨危重症患者肾功能与凝血功能变化关系.方法:通过检测危重症患者肾功能(Scr和BUN)和凝血功能指标(TT、PT、APTT、PLG、FIB、Ⅷ:C、ATⅢ、VWF、D-D和3P试验),根据血肌酐值分为正常组(N组,Scr＜130 μmol/L)和血肌酐异常组(A组,Scr≥130 μmol/L),采用t检验分析两组凝血功能各项指标差异.结果:在全部63例入选病例中,有27例发生急性肾衰竭(acute renal failure,ARF),确诊弥散性血管内凝血(disseminated intravascular coagulation,DIC)有10例.3P试验阳性率N组为1.7%,A组为12.7%,A组显著高于N组.A组PT明显延长,与N组比较有统计学差异(P＜0.01).FIB、PLG和ATⅢ明显下降,D-D升高,与N组比较有统计学差异(P＜0.01).Ⅷ:C和VWF均较正常高值显著升高.与N组比较,A组Ⅷ:C轻度降低,VWF轻度升高,但均无统计学差异(P＞0.05),而A组Ⅷ:C/VWF比值明显降低,有统计学差异(P＜0.01).结论:危重症患者发生ARF时,常合并凝血功能的异常,凝血功能异常可能参与了ARF的进展.