Karlheinz Tscheliessnigg

Serum osteoprotegerin is a major determinant of bone density development and prevalent vertebral fracture status following cardiac transplantation

Osteoprotegerin (OPG) is an antiresorptive cytokine and a key regulator of osteoclastogenesis and activity. Since OPG is downregulated by glucocorticoids and cyclosporine A in vitro we examined whether immunosuppressive therapy would play a role in the development of transplantation osteoporosis. We enrolled 57 cardiac transplant recipients (median time since transplantation, 3.2 years (1.1-11.5 years)) in this cross-sectional study. Standardized spinal X-rays as well as hip bone density measurements were performed in all patients. Serum OPG was determined using a commercially available ELISA. Vertebral fractures were present in 56% of the patients. Bone densities of all femoral neck subregions were correlated to serum OPG concentrations (r values between 0.40 and 0.48, all P < 0.005). Multiple regression analysis revealed OPG levels to be independently correlated to femoral neck Z scores (r = 0.49, P = 0.002). After adjustment for age, BMI, neck Z score, renal function, and months since transplantation, serum OPG was the only significant predictor of prevalent vertebral fractures (P = 0.001). In a separate 6-month prospective study of 14 heart transplant recipients receiving calcium and vitamin D serum OPG levels fell by 41% (P = 0.0004) after 3 months and 47% (P = 0.0001) after 6 months following cardiac transplantation. Bone loss at the lumbar spine and femoral neck after 6 months was correlated to the decrease in serum OPG at 6 months (r = 0.82, P < 0.0001, and r = 0.60, P = 0.02, respectively) as well as 3 months after cardiac transplantation (r = 0.65, P = 0.01, and r = 0.69, P = 0.006, respectively). Serum OPG alone accounted for 67% of the variance of lumbar spine bone density changes over the first 6 months posttransplantation. We conclude that serum OPG levels decline consistently in all patients following initiation of immunosuppressive therapy and are independently correlated with changes in bone density. We hypothesize that OPG plays a major role in the development of transplantation osteoporosis.

The role of CYP3A5 genotypes in dose requirements of tacrolimus and everolimus after heart transplantation.

Kniepeiss D, Renner W, Trummer O, Wagner D, Wasler A, Khoschsorur GAli, Truschnig‐Wilders M, Tscheliessnigg K‐H. The role of CYP3A5 genotypes in dose requirements of tacrolimus and everolimus after heart transplantation. 
Clin Transplant 2011: 25: 146–150.

Sirolimus has a potential to influent viral recurrence in HCV positive liver transplant candidates.

There is in vitro proof that mTOR proteins play a role in protecting HCV infected cells from apoptosis. The aim of this cohort study was to evaluate the effect of sirolimus as an mTOR inhibitor on hepatitis C recurrence in liver transplant recipients. Hepatitis C virus positive patients were followed prospectively regarding transaminases, immunosuppressive target levels, HCV RNA and influence of donor and recipient factors on viral recurrence and survival. Viral recurrence was defined as elevated liver enzymes combined with active hepatitis diagnosed on the basis of increasing viral load and/or biopsy-proven HCV relapse in the transplanted organ. Sixty-seven HCV positive patients were included: 39 received a regimen including sirolimus; 28 patients received calcineurin inhibitors. Sirolimus patients showed a significant decrease in the HCV PCR levels (p<0.05). Survival of the sirolimus patients was significantly higher (p<0.03) than in the other patient cohort. Sirolimus has been shown to be a potent immunosuppressive agent after liver transplantation, though nothing is known about its effect on HCV. This analysis suggests that sirolimus has potential to suppress viral recurrence in HCV positive liver transplant candidates.

Ibandronate Prevents Bone Loss and Reduces Vertebral Fracture Risk in Male Cardiac Transplant Patients: A Randomized Double-Blind, Placebo-Controlled Trial

Bone loss and fractures are common complications after cardiac transplantation (CTP). The aim of this study was to investigate whether intravenous ibandronate is an effective preventive option. Thirty‐five male cardiac transplant recipients received either ibandronate (IBN) 2 mg intravenously every 3 mo or matching placebo (CTR) in addition to 500 mg calcium carbonate and 400 IE vitamin D3. Sera were collected at CTP and every 3 mo thereafter. At baseline and 6 and 12 mo, standardized spinal X‐rays and BMD measurements were taken. Bone biopsies were taken at CTP and after 6 mo from six patients. In the IBN group, 13% of the patients sustained a new morphometric vertebral fracture compared with 53% in the CTR group (absolute risk reduction [ARR], 40%; relative risk reduction [RRR], 75%; p = 0.04). BMD remained unchanged with IBN treatment but in the CTR group decreased at the lumbar spine by 25% and at the femoral neck by 23% (both p < 0.0001) over the 1‐yr period. Serum bone resorption markers carboxy‐terminal telopeptide region of type I collagen (sCTX) and TRACP 5b were significantly increased in the CTR group and decreased in the IBN group at all time points compared with baseline. In contrast, both osteocalcin and bone‐specific alkaline phosphatase levels showed, after a similar decrease over the first 3 mo in both groups, a marked rise in the CTR subjects and steadily declining levels in the IBN patients throughout the remainder of the study period. Three paired biopsies were available from each group. Despite the small sample size, a difference in the relative change of eroded surface (68% in the CTR versus −23% in the IBN group, p < 0.05) could be shown. Intravenous IBN reduced fractures, preserved bone mass, and prevented uncoupling of bone formation and resorption after CTP. The favorable effects on bone turnover were also supported by histomorphometric findings.

Incisional hernia following liver transplantation: incidence and predisposing factors

Abstract:  Background:  Patients after orthotopic liver transplantation (OLT) have a high risk of developing incisional hernia (IH). In the literature incidences between 5% and 17% are reported.

Dyslipidemia during sirolimus therapy in patients after liver transplantation

Abstract:  Introduction:  Sirolimus (SRL) is an immunosuppressive agent of potential benefit in clinical liver transplantation (LTX). One of the major side effects of SRL is hyperlipidemia, which is reported in up to 44% of patients. In this report, we describe the lipid profiles of 20 stable liver transplant recipients who received SRL for immunosuppression.

Serum albumin, subjective global assessment, body mass index and the bioimpedance analysis in the assessment of malnutrition in patients up to 15 years after liver transplantation.

Wagner D, Adunka C, Kniepeiss D, Jakoby E, Schaffellner S, Kandlbauer M, Fahrleitner‐Pammer A, Roller RE, Kornprat P, Müller H, Iberer F, Tscheliessnigg KH. Serum albumin, subjective global assessment, body mass index and the bioimpedance analysis in the assessment of malnutrition in patients up to 15 years after liver transplantation.
Clin Transplant 2011: 25: E396–E3400.

Morphological and functional characterization of a pancreatic beta-cell line microencapsulated in sodium cellulose sulfate/poly(diallyldimethylammonium chloride).

Abstract:  Background:  Late diabetic complications cannot be prevented totally by current antidiabetic strategies. Therefore, new therapeutic concepts of insulin replacement such as pancreas transplantation are evolving. Due to the shortage of human donor organs, transplantation of microencapsulated xenogeneic pancreatic islet cells has attracted considerable attention. Sodium cellulose sulfate/poly(diallyldimethylammonium chloride) (NaCS/PDADMAC) is a material with favorable biogenic properties that has been used for microencapsulation of various cell types. However, there are no data on the suitability of NaCS/PDADMAC for microencapsulation of pancreatic β‐cells.

Noninvasive measurement of pulmonary vascular resistances by assessment of cardiac output and pulmonary transit time.

Müller HM, Tripolt MB, Rehak PH, et al. Noninvasive measurement of pulmonary vascular resistances by assessment of cardiac output and pulmonary transit time. Invest Radiol 2000;35:727–731. RATIONALE AND OBJECTIVES.Pulmonary vascular resistance is of special interest in many diseases. Usually it is determined invasively by catheterization, but cardiac output and pulmonary transit time can be ascertained by several noninvasive methods. METHODS.Fourteen heart recipients (age 34–71 years) were examined by electron-beam CT of the heart. Cine and flow studies were performed using a total of 60 mL of contrast and a breath-hold of 20 seconds. RESULTS.A mathematical model for calculating pulmonary vascular resistances from noninvasively measured cardiac outputs and pulmonary transit times was developed. Right-sided heart catheterization served as the reference method. CONCLUSIONS.The formula created seems to allow a clinically valid estimate of pulmonary vascular resistance from noninvasively acquired data.

The assessment of GFR after orthotopic liver transplantation using cystatin C and creatinine‐based equations

The measurement of kidney function after orthotopic liver transplantation (OLT) is still a clinical challenge. Cystatin C (CysC) has been proposed as a more accurate marker of renal function than serum creatinine (sCr). The aim of this study was to evaluate sCr‐ and CysC‐based equations including the Chronic kidney disease (CKD)‐EPI to determine renal function in liver transplant recipients. CysC and sCr were measured in 49 patients 24 months after OLT. The glomerular filtration rate (GFR) was calculated using the MDRD 4, the Cockroft‐Gault, Hoek, Larsson, and the CKD‐EPI equations based on sCr and/or CysC. As reference method, inulin clearance (IC) was estimated. Bias, precision, and accuracy of each equation were assessed and compared with respect to IC. Forty‐five percent had a GFR < 60 ml/min/1.73 m2 according to the IC. The Larsson, the Hoek and the CKD‐EPI‐CysC formula identified the highest percentage of patients with CKD correctly (88%, 88%, and 84%, respectively). The sCr‐based equations showed less bias than CysC‐based formulas with a similar precision. All CysC‐based equations were superior as compared with sCr‐based equations in the assessment of renal function in patients with an IC < 60 ml/min/1.73 m2.