High RIPK3 expression is associated with a higher risk of early kidney transplant failure.

Renal ischemia-reperfusion injury (IRI) is associated with reduced allograft survival, and each additional hour of cold ischemia time increases the risk of graft failure and mortality following renal transplantation. Receptor-interacting protein kinase 3 (RIPK3) is a key effector of necroptosis, a regulated form of cell death. Here, we evaluate the first-in-human RIPK3 expression dataset following IRI in kidney transplantation. The primary analysis included 374 baseline biopsy samples obtained from renal allografts 10 minutes after onset of reperfusion. RIPK3 was primarily detected in proximal tubular cells and distal tubular cells, both of which are affected by IRI. Time-to-event analysis revealed that high RIPK3 expression is associated with a significantly higher risk of one-year transplant failure and prognostic for one-year (death-censored) transplant failure independent of donor and recipient associated risk factors in multivariable analyses. The RIPK3 score also correlated with deceased donation, cold ischemia time and the extent of tubular injury.

Increased femoral curvature and trochlea flexion in high-grade patellofemoral dysplastic knees.

PURPOSE: High-grade patellofemoral dysplasia is often associated with concomitant axial and frontal leg malalignment. However, curvature of the femur and sagittal flexion of the trochlea has not yet been studied in patellofemoral dysplastic knees. The aim of the study was to quantify the femoral curvature and sagittal flexion of the trochlea in both high-grade patellofemoral dysplastic and healthy knees. METHODS: A retrospective case-control study matched 19 high-grade patellofemoral dysplastic knees (Dejour types C and D) with 19 healthy knees according to sex and body mass index. Three-dimensional (3D) femoral curvature and sagittal trochlea flexion were analysed. To analyse femoral curvature, the specific 3D radius of curvature (ROC) was calculated. Trochlear flexion was quantified through the development of the trochlea flexion angle (TFA), which is a novel 3D measurement in relation to the anatomical and mechanical femur axis and is referred to as 3D TFAanatomic and 3D TFAmech. The influence of age, gender, height, weight and frontal and axial alignment on ROC and TFA was analysed in a multiple regression model. RESULTS: Overall ROC was significantly smaller in dysplastic knees, compared with the control group [898.4 ± 210.8 mm (range 452.9-1275.1 mm) vs 1308.4 ± 380.5 mm (range 878.3-2315.8 mm), p < 0.001]. TFA was significantly higher in dysplastic knees, compared with the control group, for 3D TFAmech [13.8 ± 7.2° (range 4.4-33.4°) vs 6.5 ± 2.3° (range 0.8-10.2°), p < 0.001] and 3D TFAanatomic [12.5 ± 7.2° (range 3.1-32.2°) vs 6.4 ± 1.9° (range 2.1-9.1°), p = 0.001]. A smaller ROC was associated with smaller height, female gender and higher femoral ante torsion. An increased TFA was associated with valgus malalignment. CONCLUSION: High-grade patellofemoral dysplastic knees demonstrated increased femoral curvature and sagittal flexion of the trochlea, compared with healthy knees. The ROC and newly described TFA allowed the quantification of the sagittal femoral deformity. TFA and ROC should be incorporated in future deformity analysis to investigate their potential as a target for surgical correction. LEVEL OF EVIDENCE: Level III.

Effect of the Reversed L-Shaped Osteotomy on the Round Sign: Not All Hallux Valgus Deformities May Need Proximal Derotation to Correct the Radiographic Appearance of Metatarsal Pronation.

Background: Metatarsal pronation has been claimed to be a risk factor for hallux valgus recurrence. A rounded shape of the lateral aspect of the first metatarsal head has been identified as a sign of persistent metatarsal pronation after hallux valgus correction. This study investigated the derotational effect of a reversed L-shaped (ReveL) osteotomy combined with a lateral release to correct metatarsal pronation. The primary hypothesis was that most cases showing a positive round sign are corrected by rebalancing the metatarsal-sesamoid complex. We further assumed that the inability to correct the round sign might be a risk factor for hallux valgus recurrence. Methods: We retrospectively evaluated 266 cases treated with a ReveL osteotomy for hallux valgus deformity. The radiologic measurements were performed on weightbearing foot radiographs preoperatively, at an early follow-up (median, 6.2 weeks), and the most recent follow-up (median, 13 months). Univariate and multivariate logistic regression analyses identified risk factors for hallux valgus recurrence (hallux valgus angle [HVA] ≥ 20 degrees). Results: A preoperative positive radiographic round sign was present in 40.2% of the cases, of which 58.9% turned negative after the ReveL osteotomy (P < .001). Hallux valgus recurred in 8.6%. Risk factors for recurrence were a preoperative HVA >30 degrees (odds ratio [OR] = 5.3, P < .001), metatarsus adductus (OR = 4.0, P = .004), preoperative positive round sign (OR = 3.3, P = .02), postoperative HVA >15 degrees (OR = 74.9; P < .001), and postoperative positive round sign (OR = 5.3, P = .008). Cases with a positive round sign at the most recent follow-up had a significantly higher recurrence rate than those with a negative round sign (22.7% vs 5.9%, P < .001). Conclusion: The ReveL osteotomy corrected a positive round sign in 58.9%, suggesting that not all hallux valgus deformities may need proximal derotation to negate the radiographic appearance of the round sign. A positive round sign was found to be an independent risk factor for hallux valgus recurrence. Further 3-dimensional analyses are necessary to better understand the effects and limitations of distal translational osteotomies to correct metatarsal pronation. Level of Evidence: Level IV, case series.

The Kidney Donor Profile Index (KDPI) Correlates With Histopathologic Findings in Post-reperfusion Baseline Biopsies and Predicts Kidney Transplant Outcome.

Background: The increasing organ shortage in kidney transplantation leads to the necessity to use kidneys previously considered unsuitable for transplantation. Numerous studies illustrate the need for a better decision guidance rather than only the classification into kidneys from standard or expanded criteria donors referred to as SCD/ECD-classification. The kidney donor profile index (KDPI) exhibits a score utilizing a much higher number of donor characteristics. Moreover, graft biopsies provide an opportunity to assess organ quality. Methods: In a single center analysis 383 kidney transplantations (277 after deceased and 106 after living donation) performed between January 1st, 2006, and December 31st, 2016, retrospectively underwent SCD/ECD and KDPI scoring. Thereby, the quality of deceased donor kidneys was assessed by using the KDPI and the living donor kidneys by using the living KDPI, in the further analysis merged as (L)KDPI. Baseline biopsies taken 10 min after the onset of reperfusion were reviewed for chronic and acute lesions. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards analysis within a 5-year follow-up. Results: The (L)KDPI correlated with glomerulosclerosis (r = 0.30, p < 0.001), arteriosclerosis (r = 0.33, p < 0.001), interstitial fibrosis, and tubular atrophy (r = 0.28, p < 0.001) as well as the extent of acute tubular injury (r = 0.20, p < 0.001). The C-statistic of the (L)KDPI concerning 5-year death censored graft survival was 0.692. Around 48% of ECD-kidneys were classified as (L)KDPI<85%. In a multivariate Cox proportional hazard analysis including (preformed) panel reactive antibodies, cold ischemia time, (L)KDPI, and SCD/ECD-classification, the (L)KDPI was significantly associated with risk of graft loss (hazard ratio per 10% increase in (L)KDPI: 1.185, 95% confidence interval: 1.033-1.360, p = 0.025). Survival analysis revealed decreased death censored (p < 0.001) and non-death censored (p < 0.001) graft survival in kidneys with an increasing (L)KDPI divided into groups of <35, 35-85, and >85%, respectively. Conclusion: With a higher granularity compared to the SCD/ECD-classification the (L)KDPI is a promising tool to judge graft quality. The correlation with chronic and acute histological lesions in post-reperfusion kidney biopsies underlines the descriptive value of the (L)KDPI. However, its prognostic value is limited and underlines the urgent need for a more precise prognostic tool adopted to European kidney transplant conditions.

Tibial internal rotation in combined anterior cruciate ligament and high-grade anterolateral ligament injury and its influence on ACL length.

BACKGROUND: Assessment of combined anterolateral ligament (ALL) and anterior cruciate ligament (ACL) injury remains challenging but of high importance as the ALL is a contributing stabilizer of tibial internal rotation. The effect of preoperative static tibial internal rotation on ACL -length remains unknown. The aim of the study was analyze the effect of tibial internal rotation on ACL length in single-bundle ACL reconstructions and to quantify tibial internal rotation in combined ACL and ALL injuries. METHODS: The effect of tibial internal rotation on ACL length was computed in a three-dimensional (3D) model of 10 healthy knees with 5° increments of tibial internal rotation from 0 to 30° resulting in 70 simulations. For each step ACL length was measured. ALL injury severity was graded by a blinded musculoskeletal radiologist in a retrospective analysis of 61 patients who underwent single-bundle ACL reconstruction. Preoperative tibial internal rotation was measured in magnetic resonance imaging (MRI) and its diagnostic performance was analyzed. RESULTS: ACL length linearly increased 0.7 ± 0.1 mm (2.1 ± 0.5% of initial length) per 5° of tibial internal rotation from 0 to 30° in each patient. Seventeen patients (27.9%) had an intact ALL (grade 0), 10 (16.4%) a grade 1, 21 (34.4%) a grade 2 and 13 (21.3%) a grade 3 injury of the ALL. Patients with a combined ACL and ALL injury grade 3 had a median static tibial internal rotation of 8.8° (interquartile range (IQR): 8.3) compared to 5.6° (IQR: 6.6) in patients with an ALL injury (grade 0-2) (p = 0.03). A cut-off > 13.3° of tibial internal rotation predicted a high-grade ALL injury with a specificity of 92%, a sensitivity of 30%; area under the curve (AUC) 0.70 (95% CI: 0.54-0.85) (p = 0.03) and an accuracy of 79%. CONCLUSION: ACL length linearly increases with tibial internal rotation from 0 to 30°. A combined ACL and high-grade ALL injury was associated with greater preoperative tibial internal rotation. This potentially contributes to unintentional graft laxity in ACL reconstructed patients, in particular with concomitant high-grade ALL tears. STUDY DESIGN: Cohort study; Level of evidence, 3.

Pretransplant Serum Uromodulin and Its Association with Delayed Graft Function Following Kidney Transplantation-A Prospective Cohort Study.

Delayed graft function (DGF) following kidney transplantation is associated with increased risk of graft failure, but biomarkers to predict DGF are scarce. We evaluated serum uromodulin (sUMOD), a potential marker for tubular integrity with immunomodulatory capacities, in kidney transplant recipients and its association with DGF. We included 239 kidney transplant recipients and measured sUMOD pretransplant and on postoperative Day 1 (POD1) as independent variables. The primary outcome was DGF, defined as need for dialysis within one week after transplantation. In total, 64 patients (27%) experienced DGF. In multivariable logistic regression analysis adjusting for recipient, donor and transplant associated risk factors each 10 ng/mL higher pretransplant sUMOD was associated with 47% lower odds for DGF (odds ratio (OR) 0.53, 95% confidence interval (95%-CI) 0.30-0.82). When categorizing pretransplant sUMOD into quartiles, the quartile with the lowest values had 4.4-fold higher odds for DGF compared to the highest quartile (OR 4.41, 95%-CI 1.54-13.93). Adding pretransplant sUMOD to a model containing established risk factors for DGF in multivariable receiver-operating-characteristics (ROC) curve analysis, the area-under-the-curve improved from 0.786 [95%-CI 0.723-0.848] to 0.813 [95%-CI 0.755-0.871, p = 0.05]. SUMOD on POD1 was not associated with DGF. In conclusion, higher pretransplant sUMOD was independently associated with lower odds for DGF, potentially serving as a non-invasive marker to stratify patients according to their risk for developing DGF early in the setting of kidney transplantation.

Kidney transplantation after rescue allocation-meticulous selection yields the chance for excellent outcome.

BACKGROUND: The small number of organ donors forces transplant centres to consider potentially suboptimal kidneys for transplantation. Eurotransplant established an algorithm for rescue allocation (RA) of kidneys repeatedly declined or not allocated within 5 h after procurement. Data on the outcomes and benefits of RA are scarce to date. METHODS: We conducted a retrospective 8-year analysis of transplant outcomes of RA offers based on our in-house criteria catalogue for acceptance and decline of organs and potential recipients. RESULTS: RA donors and recipients were both older compared with standard allocation (SA). RA donors more frequently had a history of hypertension, diabetes or fulfilled expanded criteria donor key parameters. RA recipients had poorer human leucocyte antigen (HLA) matches and longer cold ischaemia times (CITs). However, waiting time was shorter and delayed graft function, primary non-function and biopsy-proven rejections were comparable to SA. Five-year graft and patient survival after RA were similar to SA. In multivariate models accounting for confounding factors, graft survival and mortality after RA and SA were comparable as well. CONCLUSIONS: Facing relevant comorbidities and rapid deterioration with the risk of being removed from the waiting list, kidney transplantation after RA was identified to allow for earlier transplantation with excellent outcome. Data from this survey propose not to reject categorically organs from multimorbid donors with older age and a history of hypertension or diabetes to aim for the best possible HLA matching and to carefully calculate overall expected CIT.