Hyperlipidemia Is Associated With Accelerated Chronic Kidney Disease Progression After Lung Transplantation

Hyperlipidemia is associated with faster progression of chronic kidney disease (CKD) in the general public. We sought to investigate this association after lung transplantation. Data was retrospectively collected on 230 lung recipients transplanted between January 1997 and December 2003. Estimated glomerular filtration rates (eGFR) and lipid levels were recorded at regular intervals posttransplant. Independent associations between lipid levels early posttransplant and pertinent renal endpoints were investigated. Baseline LDL was 110 ± 35 mg/dL and remained unchanged at 6 months. A faster decline in eGFR was seen in those with 6 month LDLs > versus < the mean level of 110 mg/dL (p = 0.05). By 6 months posttransplant eGFRs were lower in the 6 month LDL > versus < 110 mg/dL group (53 ± 23 vs. 62 ± 29 mL/min/1.73 m², p = 0.01), a difference that persisted at 60 months (39 ± 24 vs. 73 ± 57 mL/min/1.73 m², p = 0.05). On univariate analysis, a 6 month LDL in the highest quartile, i.e. >140 mg/dL, predicted faster progression to CKD, defined as declining to an eGFR < 30 mL/min/1.73 m² (HR 1.5, p = 0.01). This finding persisted in the multivariate Cox-proportional model (HR 1.4, p = 0.02). Hyperlipidemia predicts faster decline in renal function after lung transplant. Prospective trials are needed to confirm this finding.     

Kidney transplantation in patients with Fabry disease

Little is known about the effects of enzyme replacement therapy (ERT) in kidney transplant recipients with Fabry disease. Clinical characteristics of transplant recipients in the Fabry Outcome Survey (FOS) were therefore examined in patients with Fabry disease with or without ERT. Of the 837 European patients in FOS (March 2006), 34 male patients and two female patients had received kidney transplants. Mean age at transplantation was 37.6 ± 10.9 years, mean time since transplantation was 7.7 ± 6.4 years, median estimated glomerular filtration rate (eGFR) was 44.4 ml/min/1.73 m², and median proteinuria was 296 mg/24 h. Of 27 patients with baseline data, 59% had hypertension, 74% had left ventricular hypertrophy, 22% had cardiac valve disease, 30% had arrhythmia, and 22% had transient ischaemic attacks and 15% stroke. Twenty patients (74%; two female patients, 18 male patients) were receiving ERT with agalsidase alfa. At enrolment or at the start of ERT, median eGFRs were 59 and 35 ml/min/1.73 m² ( P  = 0.05) and median proteinuria levels were 240 and 420 mg/24 h (not significant) in treated and untreated patients respectively. Renal function remained stable in patients receiving ERT. In conclusion, agalsidase alfa is well tolerated in patients with Fabry disease who have undergone renal transplantation.     

Estimation of glomerular filtration rate in South Asian healthy adult kidney donors

Aim:   We evaluated the performance of serum creatinine based equations to estimate glomerular filtration rate (GFR) in South Asian healthy renal donors.
Methods:   GFR by 99mTc-diethylenetriamine pentaacetic acid (DTPA) renogram (mGFR) in 599 renal donors was measured. GFR was estimated using a six variable modification of diet in renal disease formula (MDRD1), a four variable MDRD formula (MDRD2), Cockcroft-Gault creatinine clearance (CG CrCl), Cockcroft-Gault glomerular filtration rate (CG GFR) and the Mayo Clinic formula (Mayo GFR). The performance of various prediction equations was compared for global bias, precision (R²) and accuracy (percentage of estimated GFR (eGFR) falling within 15% and 30% of mGFR).
Results:   The mean age was 37.4 ± 11 years and 48.2% were male. The mGFR was 95.5 ± 11.6 mL/min per 1.73 m². The bias (mL/min per 1.73 m²) was 7.5 ± 0.9, −9.0 ± 0.75, 13.1 ± 0.9, 7.5 ± 0.9 and 23.4 ± 0.76 for CG CrCl, CG GFR, MDRD1, MDRD2 and Mayo GFR, respectively. R² was 0.082 for CG CrCl and MDRD1, 0.081 for CG GFR and MDRD2 and 0.045 for Mayo GFR. The percentages of eGFR falling within 15% and 30% of mGFR were 50.5 and 80.1 for CG CrCl, 65.8 and 84 for CG GFR, 50 and 74 for MDRD1, 54.3 and 80.1 for MDRD2 and 32 and 63.4 for Mayo GFR. Overall CG GFR performed better in estimating GFR in all subjects.
Conclusion:   The CG GFR equation was better than other equations to estimate GFR in South Asian healthy renal donors. We propose a new equation derived from the regression model in our study population to estimate GFR in a South Asian healthy adult population.     

Renal effects of temocapril hydrochloride (CS-622) in patients with benign nephrosclerosis

SUMMARY: The short-term effects of temocapril, a new angiotensin-converting enzyme inhibitor (ACE-I), on renal function were investigated in 10 patients with benign nephrosclerosis (56.2 ± 7.2 years, mean ± SD). Renal plasma flow and glomerular filtration rate (GFR) were examined before and after 12-week administration, using ¹³¹I-hippuran and ^99mTc-DTPA, respectively. Temocapril (mean 4.5 mg/day) decreased systolic and diastolic blood pressure (from 162 ± 6 to 140 ± 12 mmHg, P <0.001, and from 101 ± 5 to 89 ± 8 mmHg, P <0.001, respectively). Temocapril increased both renal plasma flow (from 323 ± 67 to 367 ± 72 mL/min/1.73 m² P <0.05) and GFR (from 74 ± 14 to 81 ± 15 mL/min/1.73 m², P <0.05). These data show that short-term administration of temocapril improves renal function in patients with benign nephrosclerosis.     

Twenty-Year Experience With Heart Transplantation for Infants and Children With Restrictive Cardiomyopathy: 1986–2006

Idiopathic restrictive cardiomyopathy (RCM) is a rare cardiomyopathy in children notable for severe diastolic dysfunction and progressive elevation of pulmonary vascular resistance (PVR). Traditionally, those with pulmonary vascular resistance indices (PVRI) >6 W.U. × m² have been precluded from heart transplantation (HTX). The clinical course of all patients transplanted for RCM between 1986 and 2006 were reviewed. Preoperative, intraoperative and postoperative variables were evaluated. A total of 23 patients underwent HTX for RCM, with a mean age of 8.8 ± 5.6 years and a mean time from listing to HTX of 43 ± 60 days. Preoperative and postoperative (114 ± 40 days) PVRI were 5.9 ± 4.4 and 2.9 ± 1.5 W.U. × m², respectively. At time of most recent follow-up (mean = 5.7 ± 4.6 years), the mean PVRI was 2.0 ± 1.0 W.U. × m². Increasing preoperative mean pulmonary artery pressure (PA) pressure (p = 0.04) and PVRI > 6 W.U. × m² (χ²= 7.4, p < 0.01) were associated with the requirement of ECMO postoperatively. Neither PVRI nor mean PA pressure was associated with posttransplant mortality; 30-day and 1-year actuarial survivals were 96% and 86%, respectively. Five of the seven patients with preoperative PVRI > 6 W.U. × m² survived the first postoperative year. We report excellent survival for patients undergoing HTX for RCM despite the high proportion of high-risk patients.     

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 m² compared with 40 patients with eGFR ≥60 mL/min/1.73 m² (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.     

Correlation of Nuclear Morphometry and Immunostaining for p53 and Proliferating Cell Nuclear Antigen in Transitional Cell Carcinoma of the Bladder

Background :
In an attempt to determine the biological significance of nuclear morphometric findings, measurements of mean nuclear volume (MNV) and nuclear roundness factor (NRF) were compared to the immunoreactivityof p53 expression and proliferating cell nuclear antigen (PCNA) in human bladder cancer.
Methods :
MNV and NRF were measured using stereological methods. Expression of p53 and PCNA were determined by immunohistochemical staining. Specimens from 111 patients with previously untreated bladder cancer were analyzed.
Results :
The mean MNV was 235.8 ± 1 33.6 μm³ for the 81 patients with p53-labeling index (LI) less than 10% and 337.2 ± 141.0 μn³ for the 30 patients with p53 LI greater than 10% (P = 0.008). There was Resign if icant correlation between NRF and expression of p53. The mean MNV was 220.1 ± 1 20.5 μm³ for the 67 patients with PCNA LI less than 28% (the mean value of PCNA LI) and 328.9 ± 149.2 μm³ in 44 patients with PCNA LI greater than 28% (P= 0.0001). The mean NRF was 80.7 ± 4.2 for the 67 patients with PCNA LI less than 28%, and 82.3 ± 3.4 for the 44 patients with PCNA LI more than 28% (P= 0.04). Conclusion: Nuclear morphometric findings may reflect the proliferative potential of cancer eel Is of the bladder, as indicated by findings of immunostaining for p53 and PCNA.     

Results of Positive Cross-Match Transplantation in African American Renal Transplant Recipients

Positive cross-match (PXM) renal transplantation has been utilized to address the issue of the increasing demand for transplantation with the shortage of suitable organs. Our primary objective was to analyze the outcomes of African American (AA) PXM renal transplant recipients utilizing AA negative cross-match (NXM) renal transplant recipients as a comparator group. This was a retrospective study consisting of all PXM patients who underwent a desensitization protocol and all AA NXM transplant recipients at the University of Illinois at Chicago from July 2001 to March 2007. We found that AA PXM recipients had significantly lower estimated glomerular filtration rate (eGFR) at 1 year than AA NXM (46.2 vs. 60.6, p = 0.007). AA PXM who experienced acute rejection within the first year were more likely to have an eGFR less than 30 mL/min/1.73 m² at 1 year compared to their NXM counterparts (45.5% vs. 12.5%, p = 0.034). Positive cross-match renal transplantation in AA seems to be associated with a high degree of AR and severe renal compromise at 1 year. Larger studies are needed to determine if protocols that are associated with good short-term outcomes in non-AA need to be modified for the AA population.     

The Effect of Rosuvastatin on Insulin Sensitivity and Pancreatic Beta-Cell Function in Nondiabetic Renal Transplant Recipients

Interventions to attenuate abnormal glycemia posttransplantation are required. In addition, surrogate markers of declining glycemic control are valuable. Statins may have pleiotropic properties that attenuate abnormal glucose metabolism. We hypothesized statins would improve glucose metabolism and HbA1c would be advantageous as a surrogate for worsening glycemia. We conducted a prospective, randomized, placebo controlled, crossover study in 20 nondiabetic renal transplant recipients at low risk for NODAT and compared effects of rosuvastatin on insulin secretion/sensitivity. Mathematical model analysis of an intravenous glucose tolerance test determined first-phase insulin secretion, insulin sensitivity and disposition index. Second-phase insulin secretion was determined with a meal tolerance test. Biochemical/clinical parameters were also assessed. Rosuvastatin significantly improved total cholesterol (−30%, p < 0.001), LDL cholesterol (−44%, p < 0.001) and triglycerides (−19%, p = 0.013). C-reactive protein decreased but failed to achieve statistical significance (−31%, p = 0.097). Rosuvastatin failed to influence any glycemic physiological parameter, although an inadequate timeframe to allow pleiotropic mechanisms to clinically manifest raises the possibility of a type II statistical error. On multivariate analysis, glycated hemoglobin (HbA1c) correlated with disposition index (R²= 0.201, p = 0.006), first-phase insulin secretion (R²= 0.106, p = 0.049) and insulin sensitivity (R²= 0.136, p = 0.029). Rosuvastatin fails to modify glucose metabolism in low-risk patients posttransplantation but HbA1c is a useful surrogate for declining glycemic control.     

Increased early morbidity and mortality with acceptable long-term function in severely obese patients undergoing liver transplantation

The effect of obesity on outcomes following liver transplantation remains unclear. We reviewed our experience with 302 liver transplants in 277 patients from September 1989 to September 1996 to determine the effect of body mass on outcome. Two hundred and seventeen transplants were performed in patients with a body mass index (BMI)<30 kg/m², 55 in patients with a BMI of 30–34 kg/m² (obese), and 30 in patients with a BMI>35 kg/m² (severely obese). Non-weight related pre-operative demographics were similar between groups with the exception of an increased frequency of cryptogenic cirrhosis among the obese and severely obese patients. Intra-operative transfusion requirements were greater for the severely obese group (16.2±3.5 units versus 9.1±0.8 units for the non-obese, p=0.0004), though not when normalized to body weight (0.14±0.03 units/kg versus 0.13±0.01 units/kg, p>0.05). Post-operatively, severely obese patients had a higher rate of wound infection (20 versus 4%, p=0.0001) and death attributed to multisystem organ failure (15 versus 2%, p=0.0001), although overall mortality prior to discharge and total complications were not different between groups. Actual 1-yr graft survival showed a negative trend in the severely obese group (67 versus 81% for non-obese, p=0.07), but both 3-yr graft survival and patient survival were similar to non-obese patients (p=0.12 and 0.17, respectively by the Cox–Mantel test). Liver transplantation in severely obese patients is associated with wound infection and early death from multisystem organ failure, but has similar long-term outcomes when compared to non-obese controls.     

Mycophenolate Mofetil Monotherapy for Severe Side Effects of Calcineurin Inhibitors Following Liver Transplantation

Withdrawal of calcineurin inhibitors (CNI) followed by mycophenolate mofetil (MMF) monotherapy after liver transplantation (LT) remains controversial due to the increased risk of acute rejection and graft loss. The aim of the present study, performed in a large cohort of liver-transplanted patients with severe CNI-induced side effects, was to assess renal function recovery, and safety in terms of liver function, of complete CNI withdrawal and replacement by MMF monotherapy. Fifty-two patients treated with MMF monotherapy for CNI-induced toxicity were analyzed. Mean estimated glomerular filtration rate (eGFR) increased significantly during the period of MMF monotherapy, from 37 ± 10 to 44.7 ± 15 mL/min/1.73 m² at 6 months (p = 0.001) corresponding to a benefit of +17.4% in renal function. eGFR stabilized or improved in 86.5%, 81% and 79% of cases, and chronic renal dysfunction worsened in 13.5%, 19% and 21% of cases, at 6, 12 and 24 months after CNI withdrawal, respectively. Only two patients experienced acute rejection. MMF monotherapy may be efficient at reversing/stabilizing CRD, and appears relatively safe in terms of liver graft function in long-term liver-transplanted patients. However, clinicians must bear in mind the potential risk of rejection and graft loss, and should be very cautious in the management of such 'difficult-to-treat patients'.     

Assessing Glomerular Filtration Rate by Estimation Equations in Kidney Transplant Recipients

Surveillance of glomerular filtration rate (GFR) is crucial in the management of kidney transplant recipients. With especial emphasis on serum creatinine (SCr) calibration assay, we assessed the performance of estimation equations as compared to iothalamate GFR (iGFR) in 209 patients using the modification of diet in renal disease (MDRD), Nankivell and Cockcroft-Gault methods. Fifty-five percent of patients were treated with a calcineurin inhibitor (CNI) and all were taken trimethroprim-sulfametoxazole at the time of SCr measurement. The mean iGFR was 44 ± 26 mL/min/1.73 m². The MDRD equation showed a median difference of 0.9 mL/min/1.73 m² with 53% of estimated GFR within 20% of iGFR. Median differences were 7.5 and 7.0 mL/min/1.73 m² for Nankivell and Cockcroft-Gault formulas, respectively. The accuracy of the Nankivell and Cockcroft-Gault formulas was such that only 38% and 37% of estimations, respectively, fell within 20% of iGFR. The performance of all equations was not uniform throughout the whole range of GFR, with some deterioration at the extremes of GFR levels. In addition, good performance of the MDRD equation was seen in subjects taking CNI. In conclusion, the overall performance of the MDRD equation was superior to the Nankivell and Cockcroft-Gault formulas in renal transplant recipients including subjects treated with CNI.     

Pharmacokinetics and Placental Transmission of Fazadinium in Elective Caesarean Sections

The pharmacokinetics and placental transmission of fazadinium (0.75-0.80 mg kg^-1) were studied in seven pregnant women undergoing elective caesarean section. Plasma levels of the drug were determined by a spectrofluorimetric method and pharmacokinetics were derived according to a 2-compartment open model. Distribution and elimination half-lives averaged 0.07 ±0.03 (t½alpha) and 1.24 ± 0.34 (t½ beta) h; the volume of distribution was 20.75± 5.81 1, and the plasma clearance was 202.33 ± 39.2 ml min^-1 1.73 m². The ratio between umbilical venous blood and maternal blood at delivery ranged from 2.57 to 17.5%. Urinary elimination accounted for 37% of the injected dose within 24 h. It is concluded that because of early good intubating conditions and favourable pharmacokinetics with a modest placental passage, fazadinium might be particularly useful in obstetrics.     

The Effect of Surgical Stress on Haemodynamics During Neurolept Anaesthesia

The influence of surgical stress on haemodynamics during neurolept anaesthesia (NLA) was studied in ten patients, while they were awake, under anaesthesia prior to surgery and peroperatively. Systemic arterial, pulmonary arterial, right atrial and pulmonary capillary wedge pressures, as well as cardiac output (Q_t), arterial oxygen content and mixed venous oxygen content, were measured. Systemic and pulmonary vascular resistances, arterial-venous oxygen content difference (AVD), oxygen consumption (v_o2 and cardiac index (CI) were calculated.
On institution of anaesthesia, CI fell from 2.8 ±.11 /min. m² to 2.5±0.2 l /min.m² and systolic arterial pressure (SBP) fell from 13.4±0.5 kPa to 10.2±0.3 kPa. During surgery CI rose to 3.3±0.1 1/min.m² and SBP rose to 15.7±0.6 kPa. Prior to anaesthesia, AVD was 40.2±0.2 ml/l Under anaesthesia prior to surgery, AVD did not change, but v_O2 declined from 207±13 ml/min to 171±10 ml/min. During surgery, AVD fell to 30.5±0.3 ml/l, while V_o2 remained unchanged.
It is concluded that NLA has a direct metabolic depressant effect and, in association with surgery, is accompanied by hyperkinetic circulation.     

Dosing of MMF in combination with tacrolimus for steroiD-resistant vascular rejection in pediatric renal allografts

Abstract SteroiD-resistant vascular rejection was treated in seven adolescent renal allograft recipients using the combination of mycopheno-late mofetil (MMF) and tacrolimus (FK506). Since there are no published pediatric dose recommendations for MMF using this combination, trough concentrations and pharmacokinetic profiles were used for therapeutic drug monitoring. In order to keep the mycophenolic acid (MPA) concentrations between 2–5 μg/ml, mean MMF doses were reduced from 600 to 250 mg/m² b. i. d. Apparent clearance of MPA decreased from 5 to 1 ml/min per kg within 2 weeks. Pharmacokinetic monitoring revealed substantial variability among patients of both MMF and FK506. The MPA dose ranged from 178 to 1008 mg/m² per day to achieve an area under the curve (AUC) of 59.9 μg × h/ml ± 10.5 SD (range 49–65 μg). FK506 dose ranged from 1.3 to 8.8 mg/m² per day to achieve an AUC of 116 ng × h/ml ± 27 SD (range 83–145). We recommend adjusting MMF doses using therapeutic drug monitoring.     

Paracrine regulation of Leydig cells by the seminiferous tubules

Testes of adult control and unilateral cryptorchid rats were fixed by vascular perfusion. The cell profile area of peritubular Leydig cells surrounding tubules in different stages of spermatogenesis, and the cell profile area of perivascular Leydig cells were determined. The size of peritubular Leydig cells was dependent on which type of tubulus the cells were surrounding. Some peritubular Leydig cells, especially those surrounding stages VII–VIII (88.1 ± 7.1 μm², mean ± SD, n = 6 rats), were larger than perivascular Leydig cells (69.3 ± 5.9 μm²). The size of Leydig cells surrounding stages IX–XIV was similar to that of perivascular cells. In the abdominal testes no spermatogenic cycle was present and the sizes of peritubular and perivascular Leydig cells were equal (63.0 ± 5.1, vs 66.7 ± 7.3 μm², mean ± SD, n = 5 rats). It is suggested that the tubules and the spermatogenic cycle locally modulate Leydig cell activity and that Leydig cell malfunction in abdominal testes may be due to a decreased stimulatory influence from the damaged tubules.     

Rapid Decline in 51Cr-EDTA Measured Renal Function During the First Weeks Following Lung Transplantation

We previously described a 54% decline in renal function at 6 months after lung transplantation (LTx). We hypothesized that this decline is a very early event following LTx.
Thirty-one consecutive patients (16 females/15 males), mean age 49 (±13) years, with emphysema, cystic fibrosis/bronchiectasis or idiopathic pulmonary fibrosis were included in an analysis of renal function before and after LTx. The glomerular filtration rate (GFR) was measured using the ⁵¹Cr-ethylenediaminetetra acetic acid plasma clearance single injection technique (mGFR) at baseline before transplantation and at 1, 2, 3 and 12 weeks postoperatively.
Mean mGFR declined from 103 ± 18 to 65 ± 22, 53 ± 16 and 57 ± 18 mL/min/1.73m² at 1-, 3- and 12-weeks post-LTx (p < 0.0001), respectively. In a time-dependent repeated measures ANOVA, risk factors for a decline in mGFR posttransplant included: time (p < 0.0001), acute renal failure within 2 weeks post-LTx (p = 0.0003), use of heart and lung machine (p = 0.04), and the use of ephedrine (p = 0.048), as well as increasing age, older than 18 years at LTx (p = 0.006). These data demonstrate that renal function, measured with an isotope method, decreases dramatically during the first week after LTx.     

Ascites in Hepatitis C Liver Transplant Recipients Frequently Occurs in the Absence of Advanced Fibrosis

Ascites after liver transplantation is uncommon (3–7%) but causes morbidity and mortality. Although hepatitis C (HCV), pretransplant ascites, encephalopathy and cold ischemia time have been identified as predictors, neither posttransplant renal function nor the severity of recurrent HCV (inflammatory grade; fibrosis stage) has been systematically assessed. Among 173 HCV transplants (1 January 1998 to 31 December 2002), 18 patients (10%) developed posttransplant ascites. Cox proportional hazards models identified recipient female gender (hazard ratio [HR]= 12.18; p = 0.0001), cold ischemia time (HR = 1.17 per incremental hour; p = 0.021) and posttransplant creatinine (Cr) (HR = 1.56 per incremental 1.0 mg/dL; p = 0.0052) as independent predictors. Ludwig–Batts inflammation grade (HR = 1.32; p = 0.36) and fibrosis stage (HR = 1.63; p = 0.12) were not significant predictors. The 18 recipients had 19 ascites episodes; 12/19 had fibrosis stage 0, 1 or 2 (10/12 with stage 0 or 1). All 12 lacked diagnostic parenchymal or vascular histopathology. Renal function at ascites diagnosis were similar for transplants with fibrosis stage 0, 1 or 2 versus 3 or 4 (1.8 ± 1.6 vs. 1.6 ± 0.6 mg/dL; Cr clearance 39.6 ± 15.6 vs. 39.3 ± 13.4 mL/min/1.73 m²). In conclusion, recipient female gender, cold ischemia time and poor posttransplant renal function were independent predictors of ascites after HCV liver transplantation. Two thirds of ascites episodes, however, occurred without significant fibrosis or histopathology.     

Improved Results after Repair of Complete Atrioventricular Septal Defect

Abstract  Background: This study evaluates the historical impact on the outcomes of early primary repair of complete atrioventricular septal defect (AVSD) at our institute. Methods: Since 1976, a total of 185 children with complete AVSD have been referred to our unit. Prior to 1990, 78 children received conservative therapy, and selected 51 patients underwent surgical repair (group 1). After 1990, all referred children underwent surgical repair (n = 56; group 2). Pre- and postoperative parameters were analyzed and compared among the groups. Results: Age at operation was 15.4 ± 20.4 versus 9.9 ± 18.0 months in group 1 and group 2, respectively. Association with Down syndrome (53% vs. 82%; p < 0.01) and with patent ductus arteriosus (16 vs. 34%; p < 0.05) was less frequent in group 1. No difference was seen regarding preoperative pulmonary vascular resistance index (RPI). Actuarial survival at 15 years has improved in group 2 (69.3 ± 6.7 vs. 90.8 ± 3.9%; p < 0.05). Freedom from reoperation of the left atrioventricular valve at 15 years was not significantly different (78.8 ± 6.8 vs. 90.6 ± 4.7%; p = 0.23). Risk factor analysis identified an RPI >6.0 WU/m² as a risk for early death. Conclusion: By operating on the patients with complete AVSD earlier and not excluding patients with Down syndrome, recent results had definitely improved over the last decades. Despite this positive result, a high RPI exceeding 6 WU/m² still remains a risk factor for early mortality independent of early primary repair.     

A Randomized, Multicenter Study of Steroid Avoidance, Early Steroid Withdrawal or Standard Steroid Therapy in Kidney Transplant Recipients

In a randomized, open-label, multicenter study, de novo renal transplant patients received no steroids (n = 112), steroids to day 7 (n = 115), or standard steroids (n = 109) with cyclosporine microemulsion (CsA-ME), enteric-coated mycophenolate sodium (EC-MPS) and basiliximab. The primary objective, to demonstrate noninferiority of 12-month GFR in the steroid-free or steroid-withdrawal groups versus standard steroids, was not met in the intent-to-treat population. However, investigational groups were not inferior to standard steroids in the observed-case analysis. Median 12-month GFR was not significantly different in the steroid-free or steroid-withdrawal groups (58.6 mL/min/1.73 m² and 59.1 mL/min/1.73 m²) versus standard steroids (60.8 mL/min/1.73 m²). The 12-month incidence of biopsy-proven acute rejection (BPAR), graft loss or death was 36.0% in the steroid-free group (p = 0.007 vs. standard steroids), 29.6% with steroid withdrawal (N.S.) and 19.3% with standard steroids. BPAR was significantly less frequent with standard steroids than either of the other two regimens. Reduced de novo use of antidiabetic and lipid-lowering medication, triglycerides and weight gain were observed in one or both steroid-minimization group versus standard steroids. For standard-risk renal transplant patients receiving CsA-ME, EC-MPS and basiliximab, steroid withdrawal by the end of week 1 achieves similar 1-year renal function to a standard-steroids regimen, and may be more desirable than complete steroid avoidance.