Serum IL-6 predicts risk of kidney transplant failure independently of immunological risk.

Interleukin-6 (IL-6) is an important immune mediator and a target for novel antibody therapies. In this study, we aimed to determine whether serum IL-6 levels are associated with immunological risk, allograft rejection and outcomes in kidney transplant (Ktx) patients. We retrospectively analyzed the data of 104 patients who underwent Ktx at our center between 2011 and 2015. The patients were divided into high- and low-risk groups (n = 52 per group) based on panel reactive antibody (PRA) percentage ≥ 35%, the existence of pre-Ktx donor-specific antibodies (DSA), or a previous transplant. IL-6 concentrations were measured before and at 3 months, 12 months, and 3 years after Ktx. Serum IL-6 levels tended to be higher in high-risk patients than in low-risk patients prior to Ktx and at 12 months after Ktx; however, the difference did not reach statistical significance (pre-Ktx, high-risk: 1.995 ± 2.79 pg/ml vs. low-risk: 1.43 ± 1.76 pg/ml, p = 0.051; 12 mo. high-risk: 1.16 ± 1.87 pg/ml vs. low-risk: 0.78 ± 1.13 pg/ml, p = 0.067). IL-6 levels were correlated with the types (no rejection, T cell mediated rejection (TCMR), antibody-mediated rejection (ABMR), or both) and time (<1 year vs. >1 year after Ktx) of rejection, as well as patient and graft survival. Patients with both TCMR and ABMR had significantly higher IL-6 levels at 3 months (14.1 ± 25.2 pg/ml) than patients with ABMR (3.4 ± 4.8 pg/ml, p = 0.017), with TCMR (1.7 ± 1.3 pg/ml, p < 0.001), and without rejection (1.7 ± 1.4 pg/ml, p < 0.001). Three years after Ktx, patients with AMBR had significantly higher IL-6 levels (5.30 ± 7.66 pg/ml) than patients with TCMR (1.81 ± 1.61 pg/ml, p = 0.009) and patients without rejection (1.19 ± 0.95 pg/ml; p = 0.001). Moreover, three years after Ktx IL-6 levels were significantly higher in patients with late rejections (3.5 ± 5.4 pg/ml) than those without rejections (1.2 ± 1.0 pg/ml) (p = 0.006). The risk of death-censored graft failure was significantly increased in patients with elevated IL-6 levels at 12 months (IL-6 level > 1.396 pg/ml, HR 4.61, p = 0.007) and 3 years (IL-6 level > 1.976 pg/ml, HR 6.75, p = 0.003), but elevated IL-6 levels were not associated with a higher risk of death. Overall, our study highlights IL-6 as a risk factor for allograft failure and confirms that IL-6 levels are higher in patients developing ABMR compared to TCMR alone or no rejection.

Down-regulation of human long non-coding RNA LINC01187 is associated with nephropathies.

Chronic kidney diseases affect a substantial percentage of the adult population worldwide. This observation emphasizes the need for novel insights into the molecular mechanisms that control the onset and progression of renal diseases. Recent advances in genomics have uncovered a previously unanticipated link between the non-coding genome and human kidney diseases. Here we screened and analysed long non-coding RNAs (lncRNAs) previously identified in mouse kidneys by genome-wide transcriptomic analysis, for conservation in humans and differential expression in renal tissue from healthy and diseased individuals. Our data suggest that LINC01187 is strongly down-regulated in human kidney tissues of patients with diabetic nephropathy and rapidly progressive glomerulonephritis, as well as in murine models of kidney diseases, including unilateral ureteral obstruction, nephrotoxic serum-induced glomerulonephritis and ischemia/reperfusion. Interestingly, LINC01187 overexpression in human kidney cells in vitro inhibits cell death indicating an anti-apoptotic function. Collectively, these data suggest a negative association of LINC01187 expression with renal diseases implying a potential protective role.

PLVAP as an Early Marker of Glomerular Endothelial Damage in Mice with Diabetic Kidney Disease.

Plasmalemma vesicle-associated protein (PLVAP) is the main component of endothelial diaphragms in fenestrae, caveolae, and transendothelial channels. PLVAP is expressed in the adult kidney glomerulus upon injury. Glomerular endothelial injury is associated with progressive loss of kidney function in diabetic kidney disease (DKD). This study aimed to investigate whether PLVAP could serve as a marker for glomerular endothelial damage in DKD. Glomerular PLVAP expression was analyzed in different mouse models of DKD and their respective healthy control animals using automatic digital quantification of histological whole kidney sections. Transgenic mice expressing a dominant-negative GIP receptor (GIPRdn) in pancreatic beta-cells as a model for diabetes mellitus (DM) type 1 and black and tan brachyuric (BTBR) ob/ob mice, as a model for DM type 2, were used. Distinct PLVAP induction was observed in all diabetic models studied. Traces of glomerular PLVAP expression could be identified in the healthy control kidneys using automated quantification. Stainings for other endothelial injury markers such as CD31 or the erythroblast transformation-specific related gene (ERG) displayed no differences between diabetic and healthy groups at the time points when PLVAP was induced. The same was also true for the mesangial cells marker α8Integrin, while the podocyte marker nephrin appeared to be diminished only in BTBR ob/ob mice. Glomerular hypertrophy, which is one of the initial morphological signs of diabetic kidney damage, was observed in both diabetic models. These findings suggest that PLVAP is an early marker of glomerular endothelial injury in diabetes-induced kidney damage in mice.

The Interplay of NEAT1 and miR-339-5p Influences on Mesangial Gene Expression and Function in Various Diabetic-Associated Injury Models.

Mesangial cells (MCs), substantial cells for architecture and function of the glomerular tuft, take a key role in progression of diabetic kidney disease (DKD). Despite long standing researches and the need for novel therapies, the underlying regulatory mechanisms in MCs are elusive. This applies in particular to long non-coding RNAs (lncRNA) but also microRNAs (miRNAs). In this study, we investigated the expression of nuclear paraspeckle assembly transcript 1 (NEAT1), a highly conserved lncRNA, in several diabetes in-vitro models using human MCs. These cells were treated with high glucose, TGFß, TNAα, thapsigargin, or tunicamycin. We analyzed the implication of NEAT1 silencing on mesangial cell migration, proliferation, and cell size as well as on mRNA and miRNA expression. Here, the miRNA hsa-miR-339-5p was not only identified as a potential interaction partner for NEAT1 but also for several coding genes. Furthermore, overexpression of hsa-miR-339-5p leads to a MC phenotype comparable to a NEAT1 knockdown. In-silico analyses also underline a relevant role of NEAT1 and hsa-miR-339-5p in mesangial physiology, especially in the context of DKD.

Role of Periostin and Nuclear Factor-κB Interplay in the Development of Diabetic Nephropathy.

Diabetic nephropathy (DN) remains the most common reason for end-stage renal disease and a leading cause of kidney replacement therapy. Multifactorial pathophysiological mechanisms underlie the development of DN. Among the signalling pathways involved, nuclear factor-κB (NF-κB) plays a key role in pathogenesis triggering inflammation, oxidative stress and fibrosis. Recent evidence shows that periostin, a matricellular protein, is involved in the development of renal glomerular diseases through interaction with NF-κB signalling. The aim of the present study is to investigate the contribution of periostin and its interaction with NF-κB in DN development. To this end, we used the BTBR ob/ob mice model of diabetes type 2, and we applied transcriptomic analysis, immunostaining and methods quantifying protein and mRNA expressions. We found that increased periostin expression was correlated with decreased renal function, advanced stage renal damage and fibrosis, and NF-κB activation. Subsequently, we identified novel pathways and genes regulated by the NF-κB-periostin interaction which are involved in the mechanisms of progression of DN. Some of these genes, such as FGF1 and GDF15, have the potential to be new biomarkers and/or targets for the therapy of DN.

Assessment of Physiological Rat Kidney Ageing-Implications for the Evaluation of Allograft Quality Prior to Renal Transplantation.

Due to organ shortage and rising life expectancy the age of organ donors and recipients is increasing. Reliable biomarkers of organ quality that predict successful long-term transplantation outcomes are poorly defined. The aim of this study was the identification of age-related markers of kidney function that might accurately reflect donor organ quality. Histomorphometric, biochemical and molecular parameters were measured in young (3-month-old) and old (24-month-old) male Sprague Dawley rats. In addition to conventional methods, we used urine metabolomics by NMR spectroscopy and gene expression analysis by quantitative RT-PCR to identify markers of ageing relevant to allograft survival. Beside known markers of kidney ageing like albuminuria, changes in the concentration of urine metabolites such as trimethylamine-N-oxide, trigonelline, 2-oxoglutarate, citrate, hippurate, glutamine, acetoacetate, valine and 1-methyl-histidine were identified in association with ageing. In addition, expression of several genes of the toll-like receptor (TLR) pathway, known for their implication in inflammaging, were upregulated in the kidneys of old rats. This study led to the identification of age-related markers of biological allograft age potentially relevant for allograft survival in the future. Among those, urine metabolites and markers of immunity and inflammation, which are highly relevant to immunosuppression in transplant recipients, are promising and deserve further investigation in humans.

[Prediction of Return to Work following Multiple Trauma in Patients with ISS of at least 25]. / Prädiktion des Return to Work nach Polytrauma bei Patienten mit einem ISS von 25 und höher.

PURPOSE: Survival rates after severe multiple trauma have continually increased in the last decades. Return to work (RTW) of persons affected by severe multiple trauma is important to assure their quality of life and social participation. Therefore, knowledge about aspects associated with RTW is essential for acute and rehabilitative care and treatment. Aim of the study is to analyze RTW in patients with multiple trauma and to identify predictors for RTW. METHODS: To identify aspects that predict RTW, 84 patients in working age and with ISS ≥ 25 were included in a mono-center study. Data were collected by using routine data of the German TraumaRegister DGU® and POLO chart, a standardized patient-reported outcome assessed during follow-up. Bivariate analyses (Chi-Quadrat-test, Wilcoxon Mann-Whitney-test, t-test) were used to test for associations with RTW. Selected variables were included in a logistic regression model to predict RTW. RESULTS: In total, 58% of patients returned to work during follow-up. Age, duration of treatment in ICU and time between admission and follow-up were selected as predictors for RTW. Self-reported general health was also crucial for RTW in patients, whereas pre-existing comorbidities or other stressful events do not contribute to the prediction of RTW. CONCLUSION: RTW of patients with severe multiple trauma is determined by several factors. Older patients with low general health have problems to return to previous work.

Glomerular expression pattern of long non-coding RNAs in the type 2 diabetes mellitus BTBR mouse model.

The prevalence of type 2 diabetes mellitus (T2DM) and by association diabetic nephropathy (DN) will continuously increase in the next decades. Nevertheless, the underlying molecular mechanisms are largely unknown and studies on the role of new actors like long non-coding RNAs (lncRNAs) barely exist. In the present study, the inherently insulin-resistant mouse strain "black and tan, brachyuric" (BTBR) served as T2DM model. While wild-type mice do not exhibit pathological changes, leptin-deficient diabetic animals develop a severe T2DM accompanied by a DN, which closely resembles the human phenotype. We analyzed the glomerular expression of lncRNAs from wild-type and diabetic BTBR mice (four, eight, 16, and 24 weeks) applying the "GeneChip Mouse Whole Transcriptome 1.0 ST" array. This microarray covered more lncRNA gene loci than any other array before. Over the observed time, our data revealed differential expression patterns of 1746 lncRNAs, which markedly differed from mRNAs. We identified protein-coding and non-coding genes, that were not only co-located but also co-expressed, indicating a potentially cis-acting function of these lncRNAs. In vitro-experiments strongly suggested a cell-specific expression of these lncRNA-mRNA-pairs. Additionally, protein-coding genes, being associated with significantly regulated lncRNAs, were enriched in various biological processes and pathways, that were strongly linked to diabetes.

Treating patella fractures with a locking patella plate - first clinical results.

The standard treatment for patella fractures is tension band wiring. However, with tension band wiring anatomical reduction and rigid fixation can be challenging and the clinical outcome after patella fracture is often not satisfying. The purpose of this prospective clinical observation was to evaluate the clinical outcome in patients with patella fractures treated with an angular stable patella plate. Between 2011 and 2015 a total of 67 patients were treated with an angular stable patella plate. Outcome in these patients was evaluated by the Knee Outcome Survey Activities of Daily Living Scale (KOS-ADL) and range of motion of the knee joint was assessed. Complete follow up was obtained for 35 patients. In these patients, we found one implant-related complication. None of the patients reported any deficits in extension capabilities. The flexion was on average 127° (SD 21°). The patients classified the function of their knee in daily life on average with 77% (SD 24%) in comparison to their function before the trauma. Only kneeling or squatting was a problem in some patients. In conclusion, angular stable patella plating appears to be a promising alternative treatment for patella fractures. The patella plate provides increased mechanical stability for fracture fixation which appeared to result in a reduction of complications and improvement of functional outcome compared to tension band wiring. Especially patients with a multi-part or comminuted fracture or with osteoporotic bone are likely to benefit from the stability provided by the plate and the locking screws.

Long-term expression of glomerular genes in diabetic nephropathy.

Background: Although diabetic nephropathy (DN) is the most common cause for end-stage renal disease in western societies, its pathogenesis still remains largely unclear. A different gene pattern of diabetic and healthy kidney cells is one of the probable explanations. Numerous signalling pathways have emerged as important pathophysiological mechanisms for diabetes-induced renal injury. Methods: Glomerular cells, as podocytes or mesangial cells, are predominantly involved in the development of diabetic renal lesions. While many gene assays concerning DN are performed with whole kidney or renal cortex tissue, we isolated glomeruli from black and tan, brachyuric (BTBR) obese/obese (ob/ob) and wildtype mice at four different timepoints (4, 8, 16 and 24 weeks) and performed an mRNA microarray to identify differentially expressed genes (DEGs). In contrast to many other diabetic mouse models, these homozygous ob/ob leptin-deficient mice develop not only a severe type 2 diabetes, but also diabetic kidney injury with all the clinical and especially histologic features defining human DN. By functional enrichment analysis we were able to investigate biological processes and pathways enriched by the DEGs at different disease stages. Altered expression of nine randomly selected genes was confirmed by quantitative polymerase chain reaction from glomerular RNA. Results: Ob/ob type 2 diabetic mice showed up- and downregulation of genes primarily involved in metabolic processes and pathways, including glucose, lipid, fatty acid, retinol and amino acid metabolism. Members of the CYP4A and ApoB family were found among the top abundant genes. But more interestingly, altered gene loci showed enrichment for processes and pathways linked to angioneogenesis, complement cascades, semaphorin pathways, oxidation and reduction processes and renin secretion. Conclusion: The gene profile of BTBR ob/ob type 2 diabetic mice we conducted in this study can help to identify new key players in molecular pathogenesis of diabetic kidney injury.

CCR7 Is Important for Mesangial Cell Physiology and Repair.

The homeostatic chemokine receptor CCR7 serves as key molecule in lymphocyte homing into secondary lymphoid tissues. Previous experiments from our group identified CCR7 also to be expressed by human mesangial cells. Exposing cultured human mesangial cells to the receptor ligand CCL21 revealed a positive effect on these cells regarding proliferation, migration, and survival. In the present study, we localized CCR7 and CCL21 during murine nephrogenesis. Analyzing wild-type and CCR7 deficient (CCR7-/-) mice, we observed a retarded glomerulogenesis during renal development and a significantly decreased mesangial cellularity in adult CCR7-/- mice, as a consequence of less mesangial cell proliferation between embryonic day E17.5 and week 5 postpartum. Cell proliferation assays and cell-wounding experiments confirmed reduced proliferative and migratory properties of mesangial cells cultured from CCR7-/- kidneys. To further emphasize the role of CCR7 as important factor for mesangial biology, we examined the chemokine receptor expression in rats after induction of a mesangioproliferative glomerulonephritis. Here, we demonstrated for the first time that extra- and intraglomerular mesangial cells that were CCR7-negative in control rats exhibited a strong CCR7 expression during the phase of mesangial repopulation and proliferation.

Identification of a urine metabolite constellation characteristic for kidney allograft rejection.

INTRODUCTION: Allograft rejection is still an important complication after kidney transplantation. Currently, monitoring of these patients mostly relies on the measurement of serum creatinine and clinical evaluation. The gold standard for diagnosing allograft rejection, i.e. performing a renal biopsy is invasive and expensive. So far no adequate biomarkers are available for routine use. OBJECTIVES: We aimed to develop a urine metabolite constellation that is characteristic for acute renal allograft rejection. METHODS: NMR-Spectroscopy was applied to a training cohort of transplant recipients with and without acute rejection. RESULTS: We obtained a metabolite constellation of four metabolites that shows promising performance to detect renal allograft rejection in the cohorts used (AUC of 0.72 and 0.74, respectively). CONCLUSION: A metabolite constellation was defined with the potential for further development of an in-vitro diagnostic test that can support physicians in their clinical assessment of a kidney transplant patient.

Renal allograft rejection, lymphocyte infiltration, and de novo donor-specific antibodies in a novel model of non-adherence to immunosuppressive therapy.

BACKGROUND: Non-adherence has been associated with reduced graft survival. The aim of this study was to investigate the immunological mechanisms underlying chronic renal allograft rejection using a model of non-adherence to immunosuppressive therapy. We used a MHC (major histocompatibility complex) -mismatched rat model of renal transplantation (Brown Norway to Lewis), in which rats received daily oral cyclosporine A. In analogy to non-adherence to therapy, one group received cyclosporine A on alternating days only. Rejection was histologically graded according to the Banff classification. We quantified fibrosis by trichrome staining and intra-graft infiltration of T cells, B cells, and monocytes/macrophages by immunohistochemistry. The distribution of B lymphocytes was assessed using immunofluorescence microscopy. Intra-graft chemokine, chemokine receptor, BAFF (B cell activating factor belonging to the TNF family), and immunoglobulin G transcription levels were analysed by RT-PCR. Finally, we evaluated donor-specific antibodies (DSA) and complement-dependent cytotoxicity using flow cytometry. RESULTS: After 28 days, cellular rejection occurred during non-adherence in 5/6 animals, mixed with humoral rejection in 3/6 animals. After non-adherence, the number of T lymphocytes were elevated compared to daily immunosuppression. Monocyte numbers declined over time. Accordingly, lymphocyte chemokine transcription was significantly increased in the graft, as was the transcription of BAFF, BAFF receptor, and Immunoglobulin G. Donor specific antibodies were elevated in non-adherence, but did not induce complement-dependent cytotoxicity. CONCLUSION: Cellular and humoral rejection, lymphocyte infiltration, and de novo DSA are induced in this model of non-adherence.

Infiltration of Macrophages Correlates with Severity of Allograft Rejection and Outcome in Human Kidney Transplantation.

OBJECTIVE: Despite substantial progress in recent years, graft survival beyond the first year still requires improvement. Since modern immunosuppression addresses mainly T-cell activation and proliferation, we studied macrophage infiltration into the allografts of 103 kidney transplant recipients during acute antibody and T-cell mediated rejection. Macrophage infiltration was correlated with both graft function and graft survival until month 36 after transplantation. RESULTS: Macrophage infiltration was significantly elevated in antibody-mediated and T-cell mediated rejection, but not in kidneys with established IFTA. Treatment of rejection with steroids was less successful in patients with more prominent macrophage infiltration into the allografts. Macrophage infiltration was accompanied by increased cell proliferation as well as antigen presentation. With regard to the compartmental distribution severity of T-cell-mediated rejection was correlated to the amount of CD68+ cells especially in the peritubular and perivascular compartment, whereas biopsies with ABMR showed mainly peritubular CD68 infiltration. Furthermore, severity of macrophage infiltration was a valid predictor of resulting creatinine values two weeks as well as two and three years after renal transplantation as illustrated by multivariate analysis. Additionally performed ROC curve analysis showed that magnitude of macrophage infiltration (below vs. above the median) was a valid predictor for the necessity to restart dialysis. Having additionally stratified biopsies in accordance to the magnitude of macrophage infiltration, differential CD68+ cell infiltration was reflected by striking differences in overall graft survival. CONCLUSION: The differences in acute allograft rejection have not only been reflected by different magnitudes of macrophage infiltration, but also by compartment-specific infiltration pattern and subsequent impact on resulting allograft function as well as need for dialysis initiation. There is a robust relationship between macrophage infiltration, accompanying antigen-presentation and resulting allograft function.

Biomechanical Assessment of Locked Plating for the Fixation of Patella Fractures.

OBJECTIVE: To analyze the mechanical stability of locked plating in comparison with tension-band wiring for the fixation of fractures of the patella. METHODS: Biomechanical tests were performed on artificial foam patella specimens comparing an angular stable plate and monocortical screws with tension-band wiring. Tests were performed under combined tension and bending until failure simulating physiological loading of the tibia during walking. RESULTS: Tension-band wiring failed at 66% of the failure load of plating (1052 N, P = 0.002) and had 5 times larger fracture gap displacements (P = 0.002). CONCLUSIONS: Based on the biomechanical advantages, locked plating of the patella may constitute a reasonable alternative in the treatment of patella fractures.

Outcome after severe multiple trauma: a retrospective analysis.

BACKGROUND: Aim of this study was to evaluate prognosis of severely injured patients. METHODS: All severely injured patients with an Injury Severity Score (ISS) ≥ 50 were identified in a 6-year-period between 2000 and 2005 in German Level 1 Trauma Center Murnau. Data was evaluated from German Trauma Registry and Polytrauma Outcome Chart of the German Society for Trauma Surgery and a personal interview to assess working ability and disability and are presented as average. RESULTS: 88 out of 1435 evaluated patients after severe polytrauma demonstrated an ISS ≥ 50 (6.5%), among them 23% women and 77% men. 66 patients (75%) had an ISS of 50-60, 14 (16%) 61-70, and 8 (9%) ≥ 70. In 27% of patients trauma was caused by motor bike accidents. 3.6 body regions were involved. Patients had to be operated 5.3 times and were treated 23 days in the ICU and stayed 73 days in hospital. Mortality rate was 36% and rate of multi-organ failure 28%. 15% of patients demonstrated severe senso-motoric dysfunction as well as residues of severe head injury. 25% recovered well or at least moderately. 29 out of 56 survivors answered the POLO-chart. A personal interview was performed with 13 patients. The state of health was at least moderate in 72% of patients. In 48% interpersonal problems and in 41% severe pain was observed. In 57% of patients problems with working ability regarding duration, as well as quantitative and qualitative performance were observed. Symptoms of post-traumatic stress disorder were found in 41%. The more distal the lesions were located (foot/ankle) the more functional disability affected daily life. In only 15%, working ability was not impaired. 8 out of 13 interviewed patients demonstrated complete work disability. CONCLUSIONS: Even severely injured patients after multiple trauma have a good prognosis. The ISS is an established tool to assess severity and prognosis of trauma, whereas prediction of clinical outcome cannot be deducted from this score.

The influence of patellar resurfacing on patellar kinetics and retropatellar contact characteristics.

BACKGROUND: Femoropatellar complications are one of the most common problems after total knee arthroplasty (TKA). However, the question of whether to resurface the patella remains controversial. Therefore, we evaluated the kinetics and the retropatellar contact characteristics of patella resurfacing with fixed and gliding surfaces. METHODS: Eight Thiel-embalmed cadaver knees were tested--first intact, then after TKA without patellar resurfacing, and finally with additional patellar resurfacing--while flexing the knee from 0° to 100°. We tested a fixed as well as a gliding patella surface. During the examination, quadriceps and hamstring forces were applied. The retropatellar pressure was determined with a special patella sensor, and the patellar kinetics were measured using an optical three-dimensional motion analysis system. RESULTS: Resurfacing the patella caused a significant increase in retropatellar pressure and a significant decrease in retropatellar contact area. Using a fixed patella, the retropatellar pressure nearly quadrupled in higher flexion compared to the native patella. Furthermore, the lateral movement of the patella increased after TKA, especially after additional patellar resurfacing. CONCLUSIONS: Resurfacing the patella routinely is not advised. When osteoarthritis of the patella is found, the gliding patella should be preferred.

Influence of total knee arthroplasty on patellar kinematics and contact characteristics.

PURPOSE: Femoro-patellar complications are one of the most common problems after total knee arthroplasty (TKA). TKA components that reduce patellar loads and preserve physiological patellar kinematics should reduce these problems. Therefore, we evaluated the patellar kinematics and the retro-patellar contact characteristics in both the intact knee and in the TKA-knee. METHODS: Eight Thiel-embalmed cadaver knees were tested first intact and then after TKA using rotating as well as gliding inlay and with additional patellar resurfacing while flexing the knee from 0° to 100°. During the examination quadriceps and hamstring forces were applied. RESULTS: TKA with additional patellar resurfacing led to an increased retro-patellar pressure, a decreased contact area and an increased lateral movement. Although patellar kinematics could not be changed by using a gliding inlay compared to a rotating inlay, the gliding inlay improved retro-patellar contact characteristics by reducing the pressure and increasing the contact area, especially in higher flexion. CONCLUSIONS: The increased retro-patellar pressure together with the increased lateral movement of the patella after TKA may be one important cause for anterior knee pain appearing after TKA. In view of the improved retro-patellar contact characteristics using a gliding inlay this inlay should be preferred, providing that the posterior cruciate ligament is intact.