Andreas Bock

Estimated one-year glomerular filtration rate is the best predictor of long-term graft function following renal transplant

Background. Long-term success of renal transplantation depends upon the quality of the donor organ, avoidance of peritransplant and early posttransplant damage (rejection), and optimal maintenance of graft function after the first 6–12 months. Glomerular filtration rate (GFR) at 1 year is a standard way to evaluate short-term success, whereas calculated GFR at 5 years gives a better appreciation of long-term outcomes. The objective of this study was to assess the effect of various demographic and transplant-related parameters on renal function via GFR at 1 year and 5 years post transplantation, using univariate and multivariate data analysis. Methods. Data on 1-year GFR were available from 10,397 patients, whereas 2,889 patients provided data on both 1-year and 5-year GFR. All patients were enrolled in the Neoral Multinational Observational Study in Transplantation (Neoral-MOST), an ongoing, prospective, observational study of adult renal transplant recipients. Results. One-year GFR was the most relevant predictor for 5-year GFR. In a multifactorial analysis (ANCOVA) using 1-year GFR as a continuous variable, the effects of several highly relevant parameters from univariate analysis (such as acute rejection and delayed graft function) on 5-year GFR appeared to be fully mediated by their influence on 1-year GFR, whereas immunological risk factors like HLA match or previous transplantation had an ongoing effect on graft function beyond year 1. Conclusions. The findings of this study corroborate and augment data from previous registry surveys, and confirm the importance of observational studies in investigating the role of peritransplant parameters on long-term graft outcome.

Use of Neoral C2 monitoring: a European consensus

Large‐scale clinical trials using C2 monitoring of cyclosporine (CsA) microemulsion (Neoral) in renal transplant recipients have demonstrated low acute rejection rates and good tolerability with a low adverse event profile in a variety of settings: with or without routine induction therapy; in combination with mycophenolate mofetil; with standard‐exposure or low‐exposure Neoral; and in patients with immediate or delayed graft function. In liver transplantation, C2 monitoring significantly reduces the severity and incidence of acute rejection compared with C0 monitoring, without adverse consequences in terms of renal function or tolerability. Different C2 targets are appropriate depending on adjunctive immune suppression, level of immunologic risk, CsA tolerability, risk of renal toxicity and time since transplantation. CsA absorption may increase substantially in most patients during the first 1–2u2003weeks post‐transplant, and this should be taken into account to avoid overshooting C2 target range. A patient with a low C2 value may be either a low or a delayed absorber of CsA, or be a normal absorber who is receiving too low a dose of Neoral. C2 monitoring alone is insufficient to differentiate between these types of patients, and measurement of additional timepoints is recommended. Adopting C2 monitoring in maintenance transplant patients identifies those who are overexposed to CsA. In summary, randomized, prospective, multicenter studies and single‐center trials have evaluated Neoral C2 monitoring within a range of regimens in different organ types, providing a robust evidence base for the benefits of this sensitive monitoring technique.

Epidemiological approach to identifying genetic predispositions for atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) is caused by several susceptibility genes. A registry including analyses of susceptibility genes, familial occurrence and genotype‐phenotype correlation should provide classification insights.

Follow-up after renal transplantation with organs from donors after cardiac death

Kidneys obtained from donors after cardiac death (DCD) are known to have higher rates of primary nonfunction and delayed graft function (DGF) than heart beating cadaveric donor (CAD) kidneys, but little is known about long‐term function of DCD grafts that survive to 1u2003year. To investigate the outcomes of renal transplant recipients whose DCD graft functioned for at least 1u2003year, this study analyzed data collected from 326 DCD graft recipients and 340 CAD‐matched controls enrolled in a prospective, multinational, observational study – Neoral®‐MOST (Multinational Observational Study in Transplantation) (Novartis, Basel, Switzerland). No differences were found in the demographics or immunosuppression between the two groups. All patients received a Neoral®‐based immunosuppressive regimen. Donors after cardiac death graft recipients had a higher incidence of DGF (40% vs. 27% CAD; Pu2003<u20030.001). One year glomerular filtration rate (GFR) and GFR‐decline after 1u2003year were similar in DCD and CAD recipients (GFR 56u2003ml/min DCD vs. 59u2003ml/min CAD; GFR‐decline −1.3u2003ml/min DCD vs. −1.4u2003ml/min CAD; Pu2003=u2003not significant). Multifactorial analyses confirmed that GFR at 1u2003year was significantly influenced by donor age and gender, DGF, and acute rejection; however, DCD status was not an independent risk factor in cyclosporine‐treated patients with grafts that had functioned for at least 1u2003year.

Medication Adherence Assessment: High Accuracy of the New Ingestible Sensor System in Kidney Transplants

Background This open-label single-arm exploratory study evaluated the accuracy of the Ingestible Sensor System (ISS), a novel technology for directly assessing the ingestion of oral medications and treatment adherence. Methods ISS consists of an ingestible event marker (IEM), a microsensor that becomes activated in gastric fluid, and an adhesive personal monitor (APM) that detects IEM activation. In this study, the IEM was combined to enteric-coated mycophenolate sodium (ECMPS). Twenty stable adult kidney transplants received IEM-ECMPS for a mean of 9.2 weeks totaling 1227 cumulative days. Results Eight patients prematurely discontinued treatment due to ECMPS gastrointestinal symptoms (n=2), skin intolerance to APM (n=2), and insufficient system usability (n=4). Rash or erythema due to APM was reported in 7 (37%) patients, all during the first month of use. No serious or severe adverse events and no rejection episode were reported. IEM detection accuracy was 100% over 34 directly observed ingestions; Taking Adherence was 99.4% over a total of 2824 prescribed IEM-ECMPS ingestions. ISS could detect accurately the ingestion of two IEM-ECMPS capsules taken at the same time (detection rate of 99.3%, n=2376). Conclusions ISS is a promising new technology that provides highly reliable measurements of intake and timing of intake of drugs that are combined with the IEM.

Geographical prevalence, risk factors and impact of hepatitis B and C after renal transplantation

BACKGROUNDnHepatitis B (HBV) and hepatitis C (HCV) virus infections are major risk factors affecting long-term morbidity and mortality after renal transplantation. Hepatitis prevalence is subject to geographical variations.nnnOBJECTIVEnTo compare and analyze the geographical prevalence, risk factors and impact of HBV and HCV infection in multinational cohorts of renal transplant recipients.nnnMETHODSnFrom 1989 - 2002, data on 12,856 kidney transplant recipients in 37 countries were collected within the prospective MOST (Multinational Observational Study in Transplantation). Subgroup analyses of hepatitis-related prevalence, risk factors and impact were conducted on patients whose HBV and HCV status was available at time of transplantation. Countries were substratified according to population prevalence of > or = 5% HBV or > or = 10% HCV.nnnRESULTSnThe prevalence of HBV was 2.9%, of HCV 8.7% and of HBV together with HCV 0.4%. Risk factors for hepatitis infection in renal transplant recipients were long dialysis time, retransplantation and blood transfusions. At each study endpoint up to 5 years after transplantation, no significant differences in graft function were observed, although the 1-year acute rejection rate tended to be lower in HCV+ patients. At 5 years post-transplant, there were no differences between the subgroups and regions regarding infections, post-transplant diabetes mellitus or malignancies including PTLD.nnnCONCLUSIONSnOverall, HCV infections are more prevalent than HBV. Despite large geographical differences in prevalence, HBV and HCV status did not appear to have a significant impact on renal graft function, infections, malignancies and post-transplant diabetes mellitus up to 5 years after renal transplantation throughout the MOST countries.

Malignant hemangiosarcoma in a renal allograft: diagnostic difficulties and clinical course after nephrectomy and immunostimulation

Hemangiosarcomas are rare tumors of endothelial cell origin. To date, only 20 cases of hemangiosarcoma have been described after renal transplantation, occurring mostly in the skin or in a dialysis fistula. We report a primary metastasizing hemangiosarcoma arising from a renal allograft. The patient was treated with transplant nephrectomy, discontinuation of immunosuppression, and immunostimulation with pegylated interferon‐α‐2a and has now been in complete remission for 3 years.

Management of secondary hyperparathyroidism: practice patterns and outcomes of cinacalcet treatment with or without active vitamin D in Austria and Switzerland - the observational TRANSIT Study.

SummarySecondary hyperparathyroidism is axa0complex disorder requiring an individualized multicomponent treatment approach. This study was conducted to identify treatment combinations used in clinical practice in Austria and Switzerland and the potential to control this disorder. Axa0total of 333 adult hemodialysis and peritoneal dialysis patients were analyzed. All patients received conventional care prior to initiation of axa0cinacalcet-based regimen. During the study, treatment components, e.g. cinacalcet, active vitaminxa0D analogues and phosphate binders, were adapted to individual patient requirements and treatment dynamics were documented. Overall, the mean intact parathyroid hormone (iPTH) increased from 64.2u2009pmol/l to 79.6u2009pmol/l under conventional therapy and decreased after cinacalcet initiation to 44.0u2009pmol/l after 12 months (mean decrease between baseline and 12 months −45%). Calcium remained within the normal range throughout the study and phosphorus ranged around the upper limit of normal. The Kidney Disease: Improving Global Outcomes (KDIGO) target achievement for iPTH increased from 44.5% of patients at baseline to 65.7% at 12 months, corrected calcium from 58.9% to 51.9% and phosphorus from 18.4% to 24.4%. On average, approximately 30% of patients adapted their regimen from one observation period to the next. The reasons for changing axa0given regimen were to attain or maintain any of the bone mineral markers within recommended targets and to avoid developments to extreme values. Some regional differences in practice patterns were identified. No new safety signals emerged. In conclusion, cinacalcet appears to be axa0necessary treatment component to achieve recommended targets. The detailed composition of the treatment mix should be adapted to patient requirements and reassessed on axa0regular basis.

Delayed Graft Function: Risk Factors, Consequences And Parameters Affecting Outcome. Results From Most, A Multinational Observational Study.

BACKGROUNDnDelayed graft function (DGF) is a common complication after renal transplantation, and may affect graft function. The aim of this analysis was to evaluate risk factors for DGF, as well as parameters and events influencing graft function after DGF. We analyzed data collected in an ongoing international, prospective; observational study, the Neoral-MOST (Multinational Observational Study in renal Transplantation), and included in the analysis all patients with cadaveric kidney transplants for whom renal function at 1 year posttransplantation was documented (N = 8950). Logistic regression was used to evaluate the risk factors for DGF occurrence, and multifactorial analysis of variance (ANCOVA) to assess the relevance of different factors for GFR at 1 year.nnnRESULTSnHigher donor age, longer CIT, male recipients, Caucasian recipients, high recipients body mass index, and PRA were all associated with a higher risk for DGF. Renal function of former DGF kidneys at 1 year was lower in kidneys of elder donors, or which had experienced rejection or CMV infection. Variations of the maintenance regimen at 1 year posttransplantation were not associated with better graft function. Multifactorial analysis showed donor age and acute rejection as significant independent factors.nnnCONCLUSIONSnMost factors increasing the risk for DGF or having a negative impact on renal function at 1 year in grafts with DGF are predetermined. Additional posttransplant damage by acute rejection was associated with further reductions in GFR. Preventing acute rejection is an important step in achieving optimal function of DGF grafts.

2222 kidney transplantations at the University Hospital Basel: a story of success and new challenges.

QUESTIONS UNDER STUDYnThe aim was to investigate changes in kidney allograft donor/recipient characteristics and outcomes at our centre.nnnMETHODSnWe retrospectively reviewed all 2222 kidney transplantations performed between 1967 and 2015. The population was divided into four eras on the basis of time intervals corresponding to major changes in immunosuppression and pretransplant risk stratification: (i.) 1967-1980 (n = 231), (ii.) 1981-1997 (n = 883), (iii.) 1998-2004 (n = 437), (iv.) 2005-2015 (n = 671).nnnRESULTSnIn deceased donor transplants, we observed a continuous increase of the median recipient (45, 51, 56 and 58 years; p <0.0001) and donor (26, 36, 49 and 54 years; p <0.0001) age. Notably, the frequency of expanded criteria donors increased dramatically (1%, 10%, 28%, 40%, p <0.0001). Graft survival at 1 year (63%, 82%, 89%, 95%), 5 years (46%, 66%, 72%, 78%) and 10 years (27%, 46%, 48%, 61%) significantly improved (p <0.0001). Patient survival also significantly improved and remained stable at a high level within the last three eras (1 year: 97%; 5 years: 87%; 10 years: 71%). Similar trends along with slightly better outcomes were noticed in living donor transplantations. In the most recent era, graft losses in elderly patients were in 81% of cases related to the patients death, whereas in young patients 83% of graft losses were caused by transplant failure (mainly rejection). Allograft function at the time of patients deaths would have allowed for calculated 10 additional years with an estimated glomerular filtration rate >15 ml/min.nnnCONCLUSIONnDespite increasing donor and recipient age, outcomes improved, illustrating ongoing progress in kidney transplantation. A major new challenge is to match the functional capacity of the donor organ with the anticipated lifespan of the recipient.