Prospective age-matching in elderly kidney transplant recipients--a 5-year analysis of the Eurotransplant Senior Program.

Renal transplantation faces challenges: the organ shortage resulting in extended waiting times and an aging population resulting in death with a functioning graft. The Eurotransplant Senior Program (ESP) allocates kidneys within a narrow geographic area from donors aged >/=65 years to recipients >/=65 years regardless of HLA. This analysis investigates the impact of the ESP on waiting time, graft and patient survival. The ESP group (n = 1406, old to old) was compared to two groups allocated via the Eurotransplant Kidney Allocation System (ETKAS) with either similar donor age (old to any [O/A], donor age >/=65, n = 446) or recipient age (any to old, [A/O], recipient age 60-64, n = 1687). All patients were transplanted between 1999 and 2004. Since initiation of the ESP (1999), availability of elderly donors doubled and waiting time for ESP patients decreased. Local allocation led to shorter cold ischemia time (11.9 vs. >17.0 h, p < 0.001) and less delayed graft function (DGF, ESP 29.7% vs. O/A 36.2%, p = 0.047) but 5-10% higher rejection rates. Graft and patient survival were not negatively affected by the ESP allocation when compared to the standard allocation. The ESP age matching of elderly donors and recipients is an effective allocation system for organs from elderly donors.

Prospective, multicenter, randomized trial to compare incidence of new-onset diabetes mellitus and glucose metabolism in patients receiving cyclosporine microemulsion versus tacrolimus after de novo kidney transplantation.

New-onset diabetes mellitus (NODM) is associated with increased risk of graft failure and death in renal transplant recipients. Some clinical studies have indicated that NODM risk is higher with tacrolimus than cyclosporine, but no comparative trial has used American Diabetic Association (ADA)/World Health Organization (WHO) criteria for diagnosis of diabetes mellitus. The Diabetes Incidence After Renal Transplantation, Neoral C2 Monitoring Versus Tacrolimus (DIRECT) study is a 6-month open-label, multicenter trial comparing the impact of tacrolimus and Neoral (cyclosporine microemulsion) on glucose metabolism in 700 de novo kidney transplant recipients, based on ADA/WHO criteria. Patients are randomized to tacrolimus (C0 monitoring) or Neoral (C2 monitoring), stratified by baseline diabetic status and ethnicity. All patients receive basiliximab, corticosteroids, and mycophenolate mofetil or enteric-coated mycophenolate acid (myfortic). Pooled interim 3-month results from a subset of 115 patients receiving either tacrolimus or Neoral showed that the primary efficacy end-point (biopsy-proven acute rejection [BPAR], graft loss or death) occurred in 11 patients (10%). There were four graft losses and only one death, which occurred after graft loss. Eight patients experienced BPAR (7.3%). Among 99 patients who were nondiabetic at baseline, 14 developed NODM by month 3, 17 developed impaired fasting glucose or impaired glucose tolerance, and another 5 patients received hypoglycemic treatment for at least 14 consecutive days or at the month 3 visit, resulting in a 36% incidence of impaired glucose metabolism. At 3 months, median GFR (Nankivell) was 63.7 mL/min; median serum creatinine was 137 micromol/L. Full complete results are expected in December 2005.

Atherosclerosis and vascular calcification in chronic renal failure.

Cardiovascular complications are a major clinical problem in patients with chronic kidney disease and end-stage renal failure; cardiac death accounts for approximately 40-50% of all deaths in these patients. Death from cardiovascular causes is up to 20 times more common in uremic patients than in the general population with the risk being even higher than in patients with diabetes mellitus. A high rate of myocardial infarction and excessive cardiac mortality have repeatedly been documented in patients with kidney disease and renal failure. Not only is the prevalence of myocardial infarction high, but also the case fatality rate is significantly higher in uremic patients with and without diabetes, respectively, compared to nonuremic patients. This is of particular interest since the prevalence of coronary atheroma in uremic patients was shown to be approximately 30% by autopsy and coronary angiography studies. Thus, coronary factors, i.e. atherosclerosis, and non-coronary factors may play an important role in the genesis of cardiac complications in the renal patient. In addition, renal failure recently has also be identified as a predictor of mortality in different stages of peripheral vascular disease. In particular, marked differences in the pathogenesis, morphology and course of atherosclerosis and arteriosclerosis under the conditions of renal failure have been documented. Among others increased plaque formation and particularly higher proportion and intensity of vascular calcification have been found in clinical and autopsy studies. In addition to the so-called classical or traditional risk factors, an important role for nonclassical risk factors such as microinflammation, hyperphosphatemia and oxidative stress has been documented in patients with renal failure and is discussed in detail.

Transradial approach for renal artery stenting.

Percutaneous interventional procedures in the renal arteries are usually performed using a femoral or brachial vascular access. The transradial approach, which has been extensively investigated for coronary angiography and intervention, could be an attractive new technique for renal artery angioplasty and stenting. In 18 patients with hemodynamically relevant unilateral renal artery stenosis (mean diameter stenosis, 83% +/- 18%; right, n = 7; left, n = 11), interventional treatment with PTA and stenting was performed using a left (n = 16) or right (n = 2) radial artery access. Indications for the transradial approach were acute aorto-renal angles or severe peripheral arterial obstructions. After engagement of the renal artery ostium with a 6 Fr Multipurpose guiding catheter (length, 125 cm; Cordis) the stenosis was passed with a 0.014" guidewire followed by stent implantation (ACS Multi-Link RX Ultra, Guidant; length, 18 mm; diameter, 5 mm). Direct stenting was successfully performed in 16 cases. Predilatations were required in two cases. In five patients, optimal stent expansion was achieved by additional postdilatations. A primary technical success (residual stenosis < 30%) could be achieved in all cases. There were no periprocedural complications. According to color-coded doppler ultrasound, all access site arteries showed a normal perfusion. Clinically blood pressure control was improved in 11 patients with a significant reduction in systolic and diastolic blood pressure values. Serum creatinine values dropped from 1.81 +/- 0.3 mg/dl to 1.49 +/- 0.3 mg/dl (P < 0.001). Transradial renal artery angioplasty and stenting is technically feasible and safe. Particularly in patients with unfavorable vessel anatomy, this new cranio-caudal approach is an attractive alternative technique.

Pneumatic external counterpulsation: a new noninvasive method to improve organ perfusion.

Pneumatic external counterpulsation, which is operated by applying electrocardiographic-triggered diastolic pressure via air-filled cuffs to the vascular limbs of lower limbs, is a relatively new therapeutic option for patients with angina pectoris and cerebrovascular diseases like transient ischemic attacks or sudden deafness. In this study, an augmentation in flow volume in the carotid, renal, and hepatic arteries from 20% to 25% and in the coronary arteries from 20% to 40%, as well as an increase in stroke volume by 12% was demonstrated; this shows the therapeutic results in patients with diseases caused by disturbed organ perfusion.

Evaluation of endocarditis and its complications by biplane and multiplane transesophageal echocardiography.

Echocardiography is currently the method of choice for the diagnosis of endocarditis-associated vegetations or complications such as abscess formation. Thereby, the transesophageal approach (TEE) is clearly superior to precardial echocardiography and, at present, biplane TEE can be considered as the standard TEE technique. Compared with the monoplane technique, biplane TEE provides additional qualitative and quantitative information concerning the presence and amount of valvular destruction. Multiplane TEE facilitates (and abbreviates) the examination procedure, and may be helpful for easier detection of small initial abnormalities, those developing on native valves with preexisting lesions, or on prosthetic valves. It allows more accurate measurements and three-dimensional reconstruction of vegetations and abscess areas and provides more anatomical details of the disease. However, it remains to be shown by future studies if multiplane TEE will identify endocarditis-associated lesions more frequently than the biplane technique doses.

Comparison of intermittent and continuous oral administration of calcitriol in dialysis patients: a randomized prospective trial.

Intermittent bolus administration of calcitriol--i.e., 1,25-dihydroxycholecalciferol or 1,25-(OH)2D3--is highly efficacious in dialysis patients. In experimental studies, intermittent administration of calcitriol is superior to continuous administration in suppressing preproparathyroid hormone (PTH) mRNA and circulating PTH concentrations. In a randomized, prospective, open multicenter trial 45 dialysis patients with elevated 1,84-iPTH (> or = 20 pmol/l, normal 1-6 pmol/l) levels were randomly allocated to daily administration of 0.75 microgram calcitriol (continuous) or twice weekly administration (intermittent); the two protocols provided an identical total weekly doses of 5.25 micrograms calcitriol. Patients were dialyzed with a dialysate Ca concentration of 1.75 mmol/l and had oral CaCO3 or Ca acetate. 1,84-iPTH (immunoradiometric assay) and serum Ca and Pi levels were measured weekly. At the beginning of the study, the median 1,84-iPTH value was 37 pmol/l (range 20-115) in the intermittent versus 36 pmol/l (range 21-72) in the continuous calcitriol group. After 2 weeks, the median 1,84-iPTH level was 18.5 pmol/l (range 1.4-106) versus 18 pmol/l (range 1.2-48). After 12 weeks, 11 of 21 of the patients in the intermittent and 18 of 24 patients in the continuous group had reached the treatment goal, i.e., 1,84-iPTH < or = 10 pmol/l without hypercalcemia or hyperphosphatemia. There were seven episodes of hypercalcemia (> 2.7 mmol/l) in the intermittent versus two in the continuous group; the mean peak Ca level was 2.8 mmol/l (range 2.76-3.0) versus 2.9 mmol/l (range 2.74-3.06). There were 21 versus 17 episodes, respectively, of hyperphosphatemia (> 2.2 mmol/l).

In vitro production of interleukin-1 from blood mononuclear cells of patients on chronic hemodialysis therapy.

A monocyte defect is thought to be involved in the impaired immune response in patients on regular hemodialysis therapy. As an indicator of cell function, we studied in vitro IL-1 beta production of mononuclear cells from hemodialysis patients in comparison to normal controls. Mononuclear cells were stimulated with endotoxin or Staphylococcus epidermidis in parallel with control incubations in tissue culture medium alone. Spontaneous as well as stimulated total IL-1 beta production (cell-associated plus extracellular) did not differ significantly in cells obtained from patients compared to those from normal controls. However, the relative amounts of IL-1 beta released into the cell supernatants were significantly reduced in mononuclear cells from hemodialysis patients when stimulated with endotoxin but not with Staphylococcus epidermidis. These data indicate a stimulus-dependent defect in the mechanism of IL-1 beta release. As IL-1 is necessary for T-cell activation this alteration in mononuclear cell function may play a role in the impaired cellular immunity observed in patients on chronic hemodialysis therapy.

Colour Doppler ultrasound assessment of arteriovenous haemodialysis fistulas.

Satisfactory function of the arteriovenous fistula (AVF) is essential for adequate haemodialysis in patients with chronic renal failure. Existing methods to assess AVF function are imprecise (eg, clinical examination) or invasive (eg, angiography). We assessed the value of colour flow-doppler ultrasound (CFDU) in the investigation of clinically suspected AVF dysfunction. 51 patients with suspected impairment of AVF function were studied by CFDU, and 28 also underwent angiography. The findings were compared with the reference standard of the findings at reoperation. CFDU showed AVF stenoses in 18 patients, which were all confirmed at reoperation; the results of angiography in 13 of these 18 patients showed complete agreement with the findings of CFDU and surgery. CFDU showed partial or complete AVF thrombosis in 33 patients, confirmed in all patients at reoperation; 15 patients also underwent angiography, and thrombi were not found in 6 (in 4 because of technical failure). 7 patients had aneurysms on CFDU that were confirmed by surgery in all patients and by angiography in 2 of the 3 patients studied. CFDU enables reliable non-invasive assessment of AVF morphology and function and may become the procedure of choice for AVF assessment in patients with suspected AVF abnormalities.

[Destructive non-infectious spondylopathy during hemodialysis]. / Destruierende nicht-infektiöse Spondylopathie bei Hämodialyse.

Improvement of long-term treatment with hemodialysis requires an optimized radiological differential diagnosis of bone changes associated with long-term hemodialysis. 85 patients with chronic renal failure on maintenance hemodialysis were examined. In a conventional radiographic skeletal survey of the whole spine, 22 patients (26%) had involved intervertebral discs. The site of predilection was the cervical spine followed by the lumbar spine; oligosegmental involvement was seen in nine patients. Eighteen patients with destructive non-infectious spondyloarthropahy had juxtaarticular cystic bony changes associated with the hip, shoulder and wrist. Bone biopsy in eight patients revealed amyloid as content of these cysts. The interrelation between the duration of preterminal and terminal renal failure on one hand and destructive bone changes in the spine and cysts on the other hand seems to point to destructive spondyloarthropathy as an important complication of renal insufficiency and dialysis.

Improvement in the diagnosis of abscesses associated with endocarditis by transesophageal echocardiography.

BACKGROUND: Echocardiography is recognized as the method of choice for the noninvasive detection of valvular vegetations in patients with infective endocarditis, with transesophageal echocardiography being more accurate than transthoracic echocardiography. The diagnosis of associated abscesses by transthoracic echocardiography is difficult or even impossible in many cases, however, and it is not known whether transesophageal echocardiography is any better. METHODS: To determine the value of transesophageal echocardiography in the detection of abscesses associated with endocarditis, we studied prospectively by two-dimensional transthoracic and transesophageal echocardiography 118 consecutive patients with infective endocarditis of 137 native or prosthetic valves that was documented during surgery or at autopsy. RESULTS: During surgery or at autopsy, 44 patients (37.3 percent) had a total of 46 definite regions of abscess. Abscesses were more frequent in aortic-valve endocarditis than in infections of other valves, and the infecting organism was more often staphylococcus (52.3 percent of cases) in patients with abscesses than in those without abscesses (16.2 percent). The hospital mortality rate was 22.7 percent in patients with abscesses, as compared with 13.5 percent in patients without abscesses. Whereas transthoracic echocardiography identified only 13 of the 46 areas of abscess, the transesophageal approach allowed the detection of 40 regions (P less than 0.001). Sensitivity and specificity for the detection of abscesses associated with endocarditis were 28.3 and 98.6 percent, respectively, for transthoracic echocardiography and 87.0 and 94.6 percent for transesophageal echocardiography; positive and negative predictive values were 92.9 and 68.9 percent, respectively, for the transthoracic approach and 90.9 and 92.1 percent for the transesophageal approach. Variation between observers was 3.4 percent for transthoracic and 4.2 percent for transesophageal echocardiography. CONCLUSIONS: The data indicate that transesophageal echocardiography leads to a significant improvement in the diagnosis of abscesses associated with endocarditis. The technique facilitates the identification of patients with endocarditis who have an increased risk of death and permits earlier treatment.

Improved physical performance after treatment of renal anemia with recombinant human erythropoietin.

The physical performance of 12 anemic patients on renal dialysis was investigated following treatment of renal anemia with recombinant human erythropoietin (rhEPO; 40-120 U/kg, 3 times a week). Exercise intensity at a heart rate of 130 beats/min (PWC130) on a bicycle ergometer was assessed before rhEPO treatment, after reaching the target hematocrit (73 +/- 18 days), and in the maintenance phase (211 +/- 53 days). Hemoglobin concentrations measured at these time points were 7.3 +/- 1.2, 11.9 +/- 1.5, and 12.1 +/- 1.4 g/dl, respectively. PWC130 rose from 77 +/- 27 to 104 +/- 37 and 104 +/- 51 W, respectively. Aerobic threshold (i.e. blood lactic acid concentration of 2 mmol/l) shifted to higher workloads indicating improved muscle oxygen supply.

Hypertension as a possible complication of recombinant human erythropoietin therapy.

The analysis of the hemodynamics accompanying correction of renal anemia by rhEPO shows that--although they behave qualitatively as in nonuremic anemic patients--cardiac output and peripheral resistance may change inadequately and thereby cause a rise of blood pressure. The underlying mechanisms are not yet fully understood but to a great part may be related to preexisting pathology due to a history of longlasting hypertension. In some patients the development of hypertension may only represent a temporary phenomenon of hemodynamic dysregulation. To avoid cardiovascular complications the following should be considered: Patients with a history of hypertension, even if they are normotensive in the anemic state, are at a higher risk of developing hypertension during therapy with rhEPO. Hypertensive complications may be rare events when anemia is corrected slowly. In case of the development or aggravation of hypertension a reduction of the target hematocrit is indicated.

Imaging of dialysis-related amyloid (AB-amyloid) deposits with 131I-beta 2-microglobulin.

The diagnosis of dialysis-related amyloid (AB-amyloid) has been based usually on clinical and radiological criteria. Following the discovery that beta 2-microglobulin was the major protein of this amyloid, we isolated and radiolabelled uremic plasma beta 2-microglobulin. After intravenous injection, gamma-camera images of selected joint areas were obtained from 42 patients who were on regular hemodialysis therapy. Positive scans involving the shoulder, hip, knee and carpal regions were found in 13 of 14 patients treated for more than 10 years and 10 of 16 patients treated for 5 to 10 years. Patients treated for less time had negative scans. Specificity was indicated by negative scans in non-amyloid inflammatory lesions in control hemodialysis patients. Up to 48-fold tracer enrichment was detected in excised AB-amyloid containing tissue as compared to amyloid-free tissue. These findings suggest that circulating radiolabelled beta 2-microglobulin is taken up by the amyloid deposits. This method may non-invasively detect tissue infiltrates of amyloid. It may also permit prospective evaluation of the efficacy of prophylactic dialysis strategies which are designed to prevent or delay the onset of this complication of long-term dialysis.

Skin microcirculation and regional peripheral resistance in patients with chronic renal anaemia treated with recombinant human erythropoietin.

Skin microcirculation and regional peripheral resistance were studied in 14 patients with renal anaemia during therapy with recombinant human erythropoietin. Haematocrit was raised from 20.0 to 31.3% after 10-12 weeks of treatment and remained stable over another period of 12 weeks. Antihypertensive treatment had to be intensified in five patients. Regional calf blood flow decreased significantly; accordingly, calculated peripheral vascular resistance was increased by more than 100%. However, transcutaneous oxygen pressure (37 degrees C and 44 degrees C) increased significantly. The pathological vasoconstrictor response of skin capillaries was not influenced. There were no significant differences of any parameter between the patients requiring reinforced antihypertensive therapy and those with stable blood pressure. In conclusion skin oxygenation may be improved by erythropoietin treatment to a large extent despite an increase in calculated total limb vascular resistance.

Long-term effects of treatment with recombinant human erythropoietin on haemodynamics and tissue oxygenation in patients with renal anaemia.

Regional peripheral vascular resistance, transcutaneous oxygen pressure and blood pressure were studied in seven normotensive, chronically haemodialysed patients with renal anaemia before and after 3 and 12 months of rHuEpo therapy. Haematocrit increased from 21% to 33% within 3 months of commencing therapy, and remained stable throughout the following observation time. Though regional blood flow of the calf was markedly reduced after 3 and 12 months of rHuEpo compared to pretreatment values, transcutaneous oxygen pressure was significantly increased after 3 months and remained constantly elevated after 12 months. Mean arterial blood pressure increased significantly by 7.3 mmHg after 3 months of rHuEpo treatment but did not reach hypertensive values and was no longer different from pretreatment values 12 months after the start of rHuEpo. Results of peripheral haemodynamic studies were compared to those obtained by measurement of central haemodynamics in four further normotensive anaemic patients. In these patients cardiac output decreased, total peripheral vascular resistance increased and blood pressure increased slightly (by 5.5 mmHg) when a haematocrit of 37% was reached after 8 weeks of rHuEpo therapy. These effects were partly reversed when the maintenance haematocrit decreased to 32% (after 16 weeks of rHuEpo). In summary rHuEpo treatment induced a long-term increase of the total and regional peripheral resistance, an increase of blood pressure within the normal range, and a decrease in cardiac output. Despite these changes tissue oxygenation improved.