Pretransplant soluble CD30 serum concentration does not affect kidney graft outcomes 3 years after transplantation.

INTRODUCTION: An elevated serum concentration of soluble the form of CD30 (sCD30), an activation marker of mainly T(H)2-type cytokines producing T lymphocytes, has been reported as a predictive factor for acute cellular rejection episodes and poor graft outcomes in kidney transplantation. This historic cohort study investigated the association of a pretransplant sCD30 serum concentrations with kidney graft function and graft survival 3 years posttransplantation in adult recipients of deceased donor kidney grafts, treated with monoclonal anti-CD25 antibodies as an induction treatment combined with a cyclosporine (CsA)-based maintenance triple therapy. MATERIALS AND METHODS: The pretransplant sera of 296 recipients were tested for sCD30 content using a microsphere flow-cytometry assay. The estimated glomerular filtration rate (eGFR) was determined by the 4-variable Modification of Diet in Renal Disease equation. The incidences of graft loss were calculated with the use of Kaplan-Meier survival analysis and compared using the log-rank test. RESULTS: According to the distribution of the pretransplant sCD30 levels concentration ≥2700 pg/mL was defined as high (n = 146) and concentration <2700 pg/mL as low (n = 150). Three years posttransplantation, the eGFR was not significantly different in the recipients in high and low sCD30 groups (65 ± 24 vs 67 ± 21 mL/min/1.73 m(2); P = .43); there was no association between the eGFR 3 years after transplantation and the pretransplant sCD30 levels (r(2) = 0.002; P = .49). Graft survival 3 years after transplantation was also not different in the recipients in high and low sCD30 groups (P = .52). CONCLUSION: In our adult deceased-donor kidney graft recipients, the pretransplant sCD30 serum concentration was not a predictive factor of immunologic risk associated with the kidney graft function 3 years posttransplantation; neither did it affect graft survival 3 years after transplantation. The immunosuppression with anti-CD25 antibodies as an induction treatment combined with the CsA-based maintenance triple therapy could possibly be decisive for our findings.

Subclinical left ventricular echocardiographic abnormalities 1 year after kidney transplantation are associated with graft function and future cardiovascular events.

Cardiovascular events (CVE) are the leading cause of mortality in kidney transplant recipients. Increased left ventricular mass (LVM) is a risk factor for CVE. This study investigated the associations of LVM with impaired kidney graft function expressed as lower glomerular filtration rate (GFR) at 1 year after transplantation and future CVE beyond 1 year. The prospective study cohort included 68 nondiabetic recipients of a kidney transplant between January 2004 and December 2005 who underwent a transthoracic echocardiographic investigation at 1 year after transplantation. LVM and left ventricular hypertrophy (LVH) were assessed using 2-dimensional M-mode echocardiography. GFR was estimated (eGFR) by the 4-variable Modification of Diet in Renal Disease formula. Cox proportional hazards analysis was used to estimate cardiac CVE (angina pectoris, acute myocardial infarct, coronary angioplasty or bypass surgery, or sudden cardiac death) hazard ratios (HRs) for patients with LVH versus control subjects with no LVH at 1 year after transplantation. All patients had normal systolic function (ejection fraction >50%) with no symptoms or signs of heart failure. LVH was present in 44 patients (65%). LVM and incidence of LVH were increased in 28 patients with eGFR <60 mL/min/1.73 m(2) compared with 40 patients with eGFR ≥60 mL/min/1.73 m(2) (248 ± 61 g and 86% vs 210 ± 46 g and 50%, respectively; P < .01). After a median follow-up of 4.5 years, there were 18 (26.5%) cardiac CVE. The incidence of CVE was higher in patients with LVH than in patients with no LVH at 1 year after transplantation (36.4% vs 8.3%; P = .020). In adjusted analyses, LVH was associated with an increased risk for future CVE (HR, 4.69; 95% confidence interval, 1.02-21.5; P = .037). In kidney transplant recipients, a lower eGFR at 1 year after transplantation was associated with greater LVM and higher incidence of LVH. Presence of LVH was associated with an increased risk for future CVE.

Does pretransplant soluble CD30 serum concentration affect deceased-donor kidney graft function 3 years after transplantation?

Elevated serum concentrations of soluble CD30 molecule (sCD30) have been related to acute cellular rejection and poor graft outcomes in kidney transplantation. This historical cohort study investigated the association of pretransplant sCD30 serum concentrations with kidney graft function expressed as estimated glomerular filtration rate (GFR) at 3 years after transplantation. Pretransplant sera from 176 adult deceased-donor kidney graft recipients were tested for sCD30 content using a commercially available automated enzyme-linked immunosorbent assay. The immunosuppression consisted of induction therapy with monoclonal anti-CD25 antibodies and a maintenance regimen of cyclosporine (CsA)-based therapy. GFR was estimated (eGFR) by the four-variable Modification of Diet in Renal Disease (MDRD) Study equation. According to the distribution of pretransplant sCD30 levels (median 66.7 U/mL; interquartile range, 46.6 to 98.6 U/mL), a concentration of 66 U/mL or higher was defined as high (n = 89) and below 66 U/mL as low (n = 87). Three years after transplantation, eGFR was not significantly different among recipients in high versus low sCD30 groups (69 +/- 23 mL/min/1.73m2 vs 66 +/- 21 mL/min/1.73m2; P = .327) and there was no correlation between eGFR and pretransplant sCD30 levels (r2 = 0.001; P = .73). Upon multivariate regression analysis, donor age, recipient body mass index at transplantation, and acute rejection episodes were independent variables affecting eGFR at 3 years after transplantation. This study showed that pretransplant sCD30 serum concentrations were not associated with deceased-donor kidney graft function at 3 years after transplantation. The immunosuppression with anti-CD25 antibodies and a triple CsA-based maintenance regimen could possibly be decisive for our findings.

Left ventricular mass is associated with ventricular repolarization heterogeneity one year after renal transplantation.

Ventricular repolarization heterogeneity (VRH) is associated with the risk of arrhythmia and cardiac death. This study investigated the association between VRH and left ventricular mass (LVM) in renal transplant recipients 1 year after transplantation. Echocardiography and 5-min 12-lead electrocardiogram were recorded and GFR was estimated (eGFR) in 68 nondiabetic patients. Beat-to-beat QT interval variability algorithm was used to calculate SDNN-QT and rMSSD-QT indices of VRH. To quantify QT interval variability relative to heart rate fluctuations, QTRR index was calculated. Left ventricular hypertrophy (LVH) was present in 44 patients (65%). LVM and incidence of LVH were increased in 28 patients with eGFR <60 mL/min/1.73 m(2) compared with 40 patients with eGFR > or =60 mL/min/1.73 m(2) (248 +/- 61 g and 86% vs. 210 +/- 46 g and 50%, respectively; p < 0.01). A direct correlation was found between LVM and SDNN-QT (R = 0.47, R(2)= 0.23; p < 0.001), rMSSD-QT (R = 0.27; R(2)= 0.10; p = 0.034), and QTRR (R = 0.55; R(2)= 0.31; p < 0.001) indices. In conclusion, greater LVM is associated with increased VRH in renal transplant recipients, providing a link with the high risk of arrhythmia and cardiac death, specifically in patients with decreased graft function.

Basiliximab versus daclizumab combined with triple immunosuppression in deceased donor renal graft recipients.

In this prospective, randomized, open-label, single-center study, we compared the efficacy and safety of two anti-interleukin-2 receptor monoclonal antibodies among adult recipients of at least 1 HLA-mismatched deceased donor renal grafts. Eligible patients were randomized to induction with either basiliximab or daclizumab. Both groups received cyclosporine microemulsion (CsA Neoral), mycophenolate mofetil, and methylprednisolone. An intent-to-treat analysis of 1-year data assessed the incidence of acute rejection episodes, the renal graft function, the safety, and the patient and graft survivals. Among 127 patients, six (10.0%) and seven (11.5%) patients experienced biopsy-confirmed acute rejection at 12 months, in the basiliximab and the daclizumab groups, respectively. Two renal grafts were lost in the basiliximab and six in the daclizumab cohort, one of them due to rejection. One basiliximab and two daclizumab patients died. Hospital treatment was required for 25 and 33 infections in basiliximab and daclizumab groups, respectively. One basal cell carcinoma of skin was detected. One hypersensitivity reaction was observed with daclizumab. At 12 months, serum creatinine was 101+/-28 micromol/L with basiliximab and 109+/-41 micromol/L with daclizumab. Patient survival was 98.4% with basiliximab and 96.7% with daclizumab, and graft survival was 96.8% versus 90.8%, respectively. No significant differences were observed between the groups. Basiliximab or daclizumab combined with triple therapy was an efficient and safe immunosuppression strategy, demonstrated with low incidence of acute rejection episodes, an acceptable adverse event profile, excellent graft function, and high survival rates in adult recipients within the first year after deceased donor renal transplantation.

Effective immunoprophylaxis with basiliximab plus triple therapy in renal transplantation: five-year single-center experience.

We studied prospectively the efficacy and safety of basiliximab combined with triple immunosuppression in adult recipients of > or = 1 HLA-mismatched deceased donor renal grafts. All studied patients received equal immunosuppressive drugs: 20 mg infusion of basiliximab on day 0 and on day 4, cyclosporine microemulsion (Neoral), mycophenolate mofetil, and methylprednisolone. An analysis of 1-year data assessed the incidence of acute rejection episodes, safety of this therapy, renal graft function, and patient and graft survivals. One hundred seventy-two patients were studied. The HLA-antigen mismatches were 2.9 +/- 0.9 (mean +/- SD), and the cold ischemia time was 22.0 +/- 7.5 hours. Fifty-three (31.5%) patients experienced delayed graft function. At 12 months, 5 (3.0%) patients experienced acute rejection. Six renal grafts were lost, but not from rejection. Two patients died. Sixty-six infections required treatment in the hospital. One carcinoma of cervix (in situ) and two basal cell carcinomas of skin were detected. Hypersensitivity reactions and cytokine-release syndrome were not observed. At 12 months, serum creatinine was significantly higher (119 +/- 46 micromol/L; P < .001) in patients with delayed graft function than in patients with immediate graft function (99 +/- 26 micromol/L). Patient and graft survivals were 98.8% and 97.1%, respectively. Basiliximab combined with this triple therapy was an efficient and safe immunosuppression strategy, demonstrated with very low incidence of acute rejections, an acceptable adverse event profile, excellent graft function, and high short-term survival rates in adult recipients of deceased donor renal transplant.

Shape of the left ventricle and its computer modelling.

A simple computer program was made to draw different left ventricle shapes in order to support the theory of elongation and to get a visual presentation of the shape of the left ventricle. Experimental data, obtained from echocardiography and Simpson's rule, were used for this program. The results yielded different shapes under different physiological circumstances, indicating the sensitivity of the method. It was concluded that these figures (shapes) support the use of elongation as a shape index.

Elongation as a new shape index for the left ventricle.

OBJECTIVES: This study was done to quantify the shape of the left ventricle (LV). It was proposed that the shape of the LV is intimately related to its performance and that its elongation (ELO) is a sensitive measure of this performance. The performance was tested against classical cardiovascular parameters. METHODS: Using echocardiography and Simpson's rule, the endocardial surface area of the LV was calculated noninvasively with a simple experimental-mathematical model at enddiastole and endsystole. ELO as shape index was derived from the endocardial surface area of the LV with a simple formula. The endocardial surface area of the LV and ELO were determined in volunteers, in patients with mild heart failure and in patients with severe heart failure. RESULTS: The normal value of endocardial surface area of LV at enddiastole is 138.3 cm2 while the normal value at endsystole is 99 cm2. The endocardial surface area of the LV is significantly bigger in patients with mild heart failure than in volunteers (p < 0.01) while the parameters ELO, ejection fraction and Doppler measurements are similar. The normal values of ELO at diastole and systole are 12 and 25 respectively. The value of ELO at endsystole is lower only in patients with severe heart failure. This means a more spherical shape and poor systolic function of the LV. CONCLUSION: ELO is usefull as quantitative and qualitative index of left ventricular shape. ELO could be integrated and applied with new diagnostic tools such three-dimensional and contrast echocardiography.

Interstitial capillary in normal and in transplanted kidneys: an ultrastructural study.

Knowledge about the normal structure and pathology of interstitial capillary is limited. Splitting and multilayering of the basal membrane (BM), as a marker of chronic rejection, has been published in association with transplant glomerulopathy. The authors investigated the ultrastructural features of the interstitial capillary basal membrane in normal (15 biopsies) and in transplanted kidneys (27 biopsies from 21 patients), expressing transplant glomerulopathy (8 biopsies from 6 patients), acute tubulo-interstitial rejection (9 biopsies from 6 patients), and recurrent or de novo glomerulonephritis (10 biopsies from 8 patients). All biopsies were fixed in 1% OsO4, embedded in Epon, and examined by electron microscope. Measurements of the interstitial capillary BM were made. The BM of interstitial capillary of intact kidney was a homogenous continuous structure, 88 nm in width on average. Thickening with diffuse multilayering of BM was most intensive in patients with transplant glomerulopathy, and much less intensive in patients with acute tubulointerstitial rejection and in patients with recurrent or de novo glomerulonephritis. These findings may provide the first information about the morphology of the normal basal lamina of interstitial capillary and support the diagnostic value of interstitial capillary changes in chronic rejection.

Contrast-enhanced ultrasound voiding cystography as a screening examination for vesicoureteral reflux in the follow-up of renal transplant recipients: a new approach.

BACKGROUND: The aim of the study was to evaluate a new diagnostic procedure, ultrasound contrast-enhanced voiding cystography (USVC), for vesicoureteral reflux (VUR) in renal transplant recipients and to compare it with radionuclide voiding cystography (RVC). METHODS: Twenty-three renal transplant recipients with recurrent urinary tract infection were investigated simultaneously by RVC and USVC. After catheterization, the empty bladder was filled with normal saline (mean 250+/-30 ml) and 30-45 mBq of (99m)Tc-labelled colloid. At the end of filling the bladder, 19.5 ml of galactose-based, microbubble-containing echo-enhancing agent, at a concentration of 200 mg/ml, was instilled. During the filling and voiding phases the movement of the radiotracer was recorded by a gamma camera and the presence of microbubbles in the urinary tract by ultrasound. RVC was used to detect and grade the degree of VUR. RESULTS: Nuclear studies identified VUR in 16 (69.6%) of 23 recipients with recurrent urinary tract infection: VUR grade I in three (13%) recipients, grade II in eight (34.8%) and grade III in five (21.7%) using a simplified grading system. USVC with contrast-enhancement detected VUR in 14 (60.9%) recipients. Overall sensitivity and specificity of contrast-enhanced USVC was 75 and 71%, respectively. Statistical analysis showed that the accuracy of this procedure increased with higher grades of VUR and its sensitivity reached 100% for detection of VUR grade III. CONCLUSION: In our preliminary study, contrast-enhanced USVC has proved to be an effective examination, with the same accuracy rate as RVC in detecting grade III VUR episodes with low diagnostic accuracy for low reflux grades.