Impact of Difelikefalin on the Health-Related Quality of Life of Haemodialysis Patients with Moderate-To-Severe Chronic Kidney Disease-Associated Pruritus: A Single-Arm Intervention Trial.

OBJECTIVE: Chronic kidney disease-associated pruritus (CKD-aP) can have a substantial negative impact on health-related quality of life (HRQoL), including an increased risk of depression, anxiety and sleep disturbance. This trial aimed to assess the impact of intravenous difelikefalin on HRQoL in haemodialysis patients with moderate-to-severe CKD-aP. METHODS: Post hoc analysis of an open-label, multicentre, single-arm intervention trial assessed pruritus severity and HRQoL at baseline and at 12 weeks of difelikefalin treatment using Worst Itching Intensity Numerical Rating Scale (WI-NRS), Sleep Quality Numeric Rating Scale (SQ-NRS), 5-D itch scale, Skindex-10 scale, EQ-5D-5L with Pruritus Bolt-On (EQ-PSO). RESULTS: A total of 222 patients received ≥ 1 dose of difelikefalin, and 197 patients completed 12 weeks of difelikefalin treatment. Clinically meaningful changes from baseline to 12 weeks were observed in all disease-specific measures: 73.7% of patients achieved a ≥ 3-point reduction in the weekly mean of 24 h WI-NRS scores and 66% of patients experienced ≥ 3-point improvements in SQ-NRS scores. Improvements were also observed in all Skindex-10 scale and 5-D itch scale domain scores. The percentage of patients reporting no problems in all EQ-PSO domains increased from 1.4 to 24.7% (p < 0.001), respectively. Patients' generic HRQoL EQ-5D-5L mean utility and EQ-5D visual analogue scale scores increased from baseline to 12 weeks: mean changes 0.04 (p = 0.001) and 2.8 (p = 0.046), respectively. CONCLUSIONS: Patients undergoing haemodialysis with moderate-to-severe CKD-aP receiving difelikefalin reported experiencing clinically meaningful improvements in both their pruritus symptoms and itch-related QoL. CLINICALTRIALS: gov registration number, NCT03998163; first submitted, 7 May 2019.

Kidney disease and thyroid dysfunction: the chicken or egg problem.

Patients with non-dialysis-dependant chronic kidney disease (NDD-CKD) and dialysis-dependant chronic kidney disease (DD-CKD) frequently also suffer from thyroid disorders, especially hypothyroidism which is found two to five times more often among them compared to the general population. Emerging research has illustrated the potential prognostic implications of this association as NDD-CKD and DD-CKD patients with hypothyroidism have been shown to have higher mortality rates, and treatment of subclinical hypothyroidism in NDD-CKD patients has been reported to attenuate the decline of glomerular filtration rate over time. This review illustrates the bidirectional, multi-layered interplay between the kidneys and the thyroid gland explaining how pathologies in one organ will affect the other and vice versa. Additionally, it outlines the impact of thyroid disorders on routine parameters of kidney function (especially serum creatinine and serum cystatin C) that nephrologists should be aware of in their clinical practice. Lastly, it summarizes the emerging evidence from clinical studies on how treatment of subclinical hypothyroidism in NDD-CKD and DD-CKD patients may potentially have beneficial effects on kidney function as well as mortality. While most of the research in this area has been performed on adult patients, we specifically discuss what is currently known about thyroid dysfunctions in paediatric CKD patients as well and provide management suggestions. The evidence accumulated so far clearly indicates that further, prospective studies with meticulous methodology are warranted to refine our understanding of thyroid disorders in paediatric and adult CKD patients and establish optimal treatment pathways.

Outcome of kidney transplantations from ≥65-year-old deceased donors with acute kidney injury.

Kidney transplantation (KT) from donors with acute kidney injury (AKI) has been associated with delayed graft function (DGF) but similar graft survival compared with KT from donors without AKI. Kidneys from ≥65-year-old donors with comorbidities are more susceptible to cold ischemia time (CIT) and DGF and it is unknown whether such elderly kidneys with AKI can also be transplanted with satisfactory outcomes. All KTs from ≥65-year-old donors performed at our center from 1999 to 2019 (n = 233) were retrospectively analyzed and short- as well as long-term outcomes were compared for KTs from donors with (n = 64) and without AKI (n = 169). There were no significant differences regarding the frequency of DGF as well as the estimated glomerular filtration rate (eGFR) 1 and 3 years post-transplant between the no-AKI and the AKI group (DGF: no-AKI 30.2% vs. AKI 40.6%, P = .17; eGFR at 1-year: 31.9 ml/min/1.73 m2 vs. 35.5 ml/min/1.73 m2 , P = .32; at 3-years: 33.8 ml/min/1.73 m2 vs. 40.9 ml/min/1.73 m2 , P = .18; respectively). Death-censored graft survival and patient survival were also not significantly different. Multivariable Cox regression analysis did not identify AKI as a significant risk factor for graft loss or death. Following careful donor and recipient selection, kidneys from ≥65-year-old AKI donors may potentially be transplanted with satisfactory outcomes.

Influence of Calcineurin Inhibitor Choice on Outcomes in Kidney Transplant Recipients Aged ≥60 Y: A Collaborative Transplant Study Report.

BACKGROUND: Patients aged ≥60 y represent the fastest growing population among kidney transplant recipients and waitlist patients. They show an elevated infection risk and are frequently transplanted with multiple human leukocyte antigen mismatches. Whether the choice of calcineurin inhibitor influences graft survival, mortality, or key secondary outcomes such as infections in this vulnerable recipient population is unknown. METHODS: A total of 31 177 kidney transplants from deceased donors performed between 2000 and 2019 at European centers and reported to the Collaborative Transplant Study were analyzed using multivariable Cox and logistic regression analyses. All recipients were ≥60 y old and received tacrolimus (Tac) or cyclosporine A on an intention-to-treat basis, combined with mycophenolic acid or azathioprine plus/minus steroids. RESULTS: The risk of 3-y death-censored graft loss and patient mortality did not differ significantly between Tac- and cyclosporine A-treated patients (hazard ratio 0.98 and 0.95, P = 0.74 and 0.20, respectively). No difference was found in the overall risk of hospitalization for infection (hazard ratio = 0.95, P = 0.19); however, a lower incidence of rejection treatment (hazard ratio = 0.81, P < 0.001) was observed in Tac-treated patients. Assessment of pathogen-specific hospitalizations revealed no difference in the risk of hospitalization due to bacterial infection (odds ratio = 1.00, P = 0.96), but a significantly higher risk of hospitalization due to human polyomavirus infection was found among Tac-treated patients (odds ratio = 2.45, P = 0.002). The incidence of de novo diabetes was higher for Tac-based immunosuppression (odds ratio = 1.79, P < 0.001). CONCLUSIONS: Calcineurin inhibitor selection has no significant influence on death-censored graft survival, mortality, and overall infection risk in ≥60-y-old kidney transplant recipients.

Impact of the explanting surgeon's impression of donor arteriosclerosis on outcome of kidney transplantations from donors aged ≥65 years.

PURPOSE: Careful donor selection is important for kidney transplantations (KT) from suboptimal donors aged ≥65 years. Several tools such as histopathological assessment of preimplant biopsies have been shown to predict allograft survival and can be applied for selection. Whether the explanting surgeon's appraisal is associated with outcomes of KTs from suboptimal donors is unknown. METHODS: We compared outcomes of KTs from ≥65-year-old deceased donors performed at our centre between 1999 and 2018 for which grading of macroscopic 'donor arteriosclerosis' (n=104) and 'organ quality' (n=208) as judged by the explanting surgeon and documented on the Eurotransplant kidney organ report was available. RESULTS: No association was observed between degree of macroscopic donor arteriosclerosis and death-censored graft survival in univariable or multivariable regression analyses. Compared to KTs from donors with no/mild arteriosclerosis, KTs from donors with moderate/severe arteriosclerosis were associated with a significantly impaired allograft function 3 months, 1 year and 3 years after transplantation (e.g. at 3 years: 176.8 µmol/l vs 137.0 µmol/l, P=0.003). Following multivariable regression analysis, these differences remained significant at 3 months and 3 years after KT. No association was observed between degree of macroscopic arteriosclerosis and mortality or primary non-function as well as no consistent association with delayed graft function and histological arteriosclerosis. Assessment of 'organ quality' was not associated with outcomes. CONCLUSION: Our data suggest that the explanting surgeon's assessment of donor arteriosclerosis is associated with allograft function. Larger studies and better standardization of kidney inspection after explantation are required to further explore the impact of surgeon's appraisal in KT.

Impact of cardiopulmonary resuscitation on outcome of kidney transplantations from braindead donors aged ≥65 years.

INTRODUCTION: Patients with a history of cardiopulmonary resuscitation (CPR) and subsequent brain death are frequently evaluated for organ donation. Whether kidneys from ≥65-year-old braindead donors with a history of CPR can be transplanted with satisfactory outcomes is unknown. MATERIAL & METHODS: All kidney transplants (KTs) from ≥65-year-old donors performed at our center from 1999 to 2018 (n = 185) were retrospectively analyzed and outcome was compared for KTs from donors with and without a history of CPR (n = 27 and n = 158, respectively). RESULTS: No significant differences in the incidence of delayed graft function (DGF) as well as 1- and 3-year graft function were observed between the CPR and the no-CPR group (DGF: 26.0% vs. 31.0%, p = .76; 1-year serum creatinine: 150.4 µmol/L vs. 177.0 µmol/L, p = .11; 3-year serum creatinine: 150.4 µmol/L vs. 168.2 µmol/L, p = .52, respectively). Death-censored graft survival was comparable after 1 and 5 years (CPR group: 81.5% and 76.7% vs. no-CPR group: 86.6% and 75.7%, p = .70). Likewise, patient survival was not significantly different. Multivariable Cox regression analysis also did not identify CPR as a significant risk factor for graft loss or death. CONCLUSION: Our study suggests that, following stringent donor selection, the outcome of KTs from ≥65-year-old braindead donors with and without a history of CPR is comparable.

Influence of Cold Ischemia Time on the Outcome of Kidney Transplants from Donors Aged 70 Years and Above-A Collaborative Transplant Study Report.

BACKGROUND: The use of kidney allografts from ≥70-y-old donors has increased persistently over the last 20 y. Prolonged cold ischemia time (CIT) is well known to increase graft failure risk. However, despite their growing importance, no data are available on the impact of CIT, specifically on survival of allografts from ≥70-y-old donors. METHODS: In total, 47 585 kidney transplantations from expanded criteria donors (ECDs) performed during 2000-2017 and reported to the Collaborative Transplant Study were analyzed. The impact of CIT on 5-y death-censored graft and patient survival was studied for transplantations from <70-y (n = 33 305) and ≥70-y-old ECDs (n = 14 280). RESULTS: Compared with the reference of ≤12 h CIT, a CIT of 13-18 h did not increase the risk of graft failure significantly, either for recipients of kidneys from <70-y or from ≥70-y-old ECDs. In contrast, graft failure risk increased significantly when CIT exceeded 18 h, both in recipients of kidneys from <70-y and, more pronounced, from ≥70-y-old ECDs (CIT 19-24 h: hazard ratio [HR] = 1.19 and 1.24; P < 0.001; CIT ≥24 h: HR = 1.28 and 1.32, P < 0.001 and P =0.003, respectively). Within the 18-h CIT interval, additional HLA matching further improved survival of ECD transplants significantly, whereas the negative impact of a prolonged CIT >18 h was stronger in ≥65-y-old recipients and for transplants with multiple HLA mismatches. The influence of CIT on patient survival was less pronounced. CONCLUSIONS: CIT, as long it is kept ≤18 h, has no significant impact on survival of kidney transplants, even from ≥70-y-old ECDs.

Impact of HLA compatibility in recipients of kidneys from expanded criteria donors: A Collaborative Transplant Study Report.

Due to a widespread organ shortage, the use of expanded criteria donors (ECDs) in kidney transplantation has increased persistently, reaching approximately 40% in recent years. Whether human leucocyte antigen (HLA) matching between donor and recipient should be part of allocation algorithms in transplantation of ECD kidneys, and especially of ECD kidneys from ≥70-year-old donors, is still in question. To this end, 135,529 kidney transplantations performed between 2000 and 2017 and reported to the Collaborative Transplant Study were analysed and the impact of HLA-A+B+DR mismatches on death-censored graft and patient survival as well as on rejection episodes was investigated. Results were stratified according to donor status (standard criteria donor (SCD) versus ECD) and age of ECD. HLA incompatibility increased the five-year death-censored graft failure risk similarly strong in recipients of ECD and SCD transplants (hazard ratio (HR) per HLA mismatch 1.078 and 1.075, respectively; p < .001 for both). Its impact on rejection treatments during the first post-transplant year was also significant but slightly weaker for recipients of ECD transplants (risk ratio (RR) per HLA mismatch 1.10 for ECD transplants and 1.13 for SCD transplants; p < .001 for both). Mortality increased gradually from zero to six HLA mismatches in recipients of SCD transplants, whereas for ECD transplants a significant increase was notable only from zero to more than zero mismatches. A significant but slightly less pronounced impact of HLA incompatibility on graft failure was observed in transplants from ≥70- compared with <70-year-old ECDs (HR per mismatch 1.047 and 1.093; p = .009 and < 0.001, respectively). The influence of HLA mismatches on rejection treatments was the same for both ECD age groups (RR = 1.10, p < .001 and p = .004, respectively). Our data indicate that HLA matching should be part of allocation algorithms not only in transplantation of kidneys from SCDs but also from ECDs.

Kidney injury as post-interventional complication of TAVI.

Transcatheter aortic valve implantation (TAVI) is an accepted treatment approach of aortic stenosis. In the beginning, this technique was executed in high-risk patients only. Today, intermediate-risk patients are also amenable for TAVI, as long as the transfemoral approach is chosen. Numerous predictors have been identified that could lead to periprocedural complications and are defined by patient co-morbidities as well as being inherent to the technical approach. Although vascular complications and postinterventional paravalvular regurgitation have been minimized over the past years by revised technologies and techniques, there is a prevailing individual risk brought about by the specific pathophysiology of the cardiorenal syndrome.

Immunosuppression in sensitized recipients.

PURPOSE OF REVIEW: Due to a substantial lack of kidney donor organs and an increasing number of sensitized recipients, a growing number of kidney transplantations has to be performed across human leukocyte antigen (HLA) and ABO barriers. These transplantations carry an inherent risk of antibody-mediated rejection (AMR) with subsequently impaired graft and patient survival. This review focuses on new developments in desensitization strategies and dedicated programs for sensitized allograft recipients. RECENT FINDINGS: Whereas ABO-incompatible kidney transplantation using rituximab-based desensitization achieves long-term survival rates comparable with ABO-compatible kidney transplantation, HLA-incompatible living kidney transplantation shows no definite survival advantage as compared with staying on the waiting list for an HLA-compatible organ. To overcome HLA-incompatibilities dedicated programs for highly sensitized recipients (such as the Eurotransplant Acceptable Mismatch program) have been established. For optimal graft outcome, these programs should be based on proven acceptable mismatches and not just on avoiding unacceptable antigens. Novel desensitizing agents (e.g. complement inhibitors) that specifically inhibit the molecular pathways of AMR have shown promising results in HLA-incompatible kidney transplantation in smaller studies. SUMMARY: Despite ever more challenging conditions, kidney transplantation in highly sensitized patients can be achieved with the use of dedicated programs, well established desensitizing agents and new drugs that specifically inhibit the molecular processes of AMR.

Kidneys From Elderly Deceased Donors-Is 70 the New 60?

There is a growing shortage of kidney donors leading to extended transplant waiting times associated with increased mortality. To expand the donor pool, clinicians nowadays regularly accept organs from elderly donors, including those aged ≥70 years. There is only limited and conflicting data whether kidneys from these elderly donors allow for satisfactory allograft outcome rates. To asses this question, the 5-year death censored graft survival of 116,870 adult first deceased donor kidney allograft recipients that were transplanted at European centers between 1997 and 2016 and reported to the "Collaborative Transplant Study" were analyzed using Kaplan-Meier analysis and country stratified Cox regression. The combinations of the two transplant periods 1997-2006 and 2007-2016 with the donor age categories 18-49, 50-59, 60-69, and ≥70 years were considered. From 1997-2006 to 2007-2016, the median donor age increased from 50 to 55 years and the proportion of kidneys from ≥60-year-old donors rose from 24.1 to 38.8%. At the same time, the proportion of kidneys from ≥70-year-old donors more than doubled (6.7 vs. 15.4%). Between 1997-2006 and 2007-2016, the 5-year graft survival improved in all donor age categories. During 2007-2016, the 5-year death censored graft survival of kidneys from ≥70-year-old donors was comparable to that of kidneys from 60 to 69-year-old donors during 1997-2006. This was true both for younger recipients (18-64 years) and older recipients (≥65 years). Among the younger recipients, 45-64-year-old recipients showed the best death censored graft survival rates for kidneys from old donors. In the country-stratified Cox regression analysis, compared to the reference of grafts from 18 to 49-year-old donors, the hazard ratio for grafts from ≥70-year-old donors during 2007-2016 was 1.92, exactly the same as the hazard ratio for grafts from 60 to 69-year-old donors during 1997-2006. Our analysis indicates that within only one further decade (1997-2006 vs. 2007-2016) the 5-year death censored graft survival of kidneys from ≥70-year old donors improved to the level of kidneys from 60 to 69-year-old donors in the previous decade.

Clinical course of hantavirus-induced nephropathia epidemica in children compared to adults in Germany-analysis of 317 patients.

BACKGROUND: Hantavirus infections are endemic worldwide, and its incidence in Europe has been steadily increasing. In Western Europe, hantavirus infections are typically caused by Puumala hantavirus and cause nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome. Up to now, there is only little data about the course of acute NE in children, but it has been suggested that hantavirus infections take a lighter course in children when compared to adults. We performed a retrospective analysis of adults and children diagnosed with acute NE in two counties in South-Western Germany to investigate if there are differences in the course of the disease. METHODS: We reviewed the medical records of 295 adults and 22 children with acute NE regarding clinical presentation, laboratory findings, complications and outcome. RESULTS: Acute kidney injury (AKI) and thrombocytopenia occurred at similar frequencies and severity in both groups. Sudden onset of fever and back/loin pain were two of the three most common symptoms in both adults and children. However, adults presented more frequently with arthralgia and visual disturbances, whereas abdominal pain and nausea/vomiting could be detected more often in children. No significant differences were found in the incidence of complications (haemodialysis, long-term outcome of kidney function, length of hospital stay). CONCLUSIONS: The clinical course of acute NE was similar in adults and children with high frequency of AKI as well as thrombocytopenia, but with full recovery of all patients.

Advanced myocardial tissue characterisation by a multi-component CMR protocol in patients with rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) patients are at increased risk of suffering from adverse cardiovascular events. Cardiovascular magnetic resonance (CMR) mapping techniques might be appropriate tools to complement late gadolinium enhancement (LGE) for the assessment of myocardial involvement. This study aimed to perform advanced myocardial tissue characterisation in RA patients by a multicomponent CMR protocol. METHODS: 22 RA patients were prospectively enrolled and underwent CMR, including LGE and T1/T2 mapping sequences; 20 volunteers served as controls. RESULTS: Mean LV-EF was 66%; prevalence of LGE was 18%. RA patients had increased native T1 (985 vs. 959 ms, p = 0.03), expanded extracellular volume (ECV) (27 vs. 25%, p = 0.02) and higher T2 values (52 vs. 49 ms, p < 0.001) compared to controls irrespective of the presence of LGE. T2 mapping showed the highest prevalence of values beyond the 95% percentile of controls. CONCLUSION: RA patients demonstrated higher T1, ECV and T2 values compared to controls, with most significant differences for T2. Since these results seem to be independent of the presence of LGE, advanced myocardial tissue characterisation including CMR mapping techniques in addition to LGE-CMR might be useful in the evaluation of myocardial involvement in RA patients. KEY POINTS: • RA patients had higher T1, ECV and T2 values compared to controls. • Most significant differences were observed for T2. • Our results seem to be independent of the presence of LGE. • Mapping might be useful in the evaluation of myocardial involvement in RA.

Alteration of membrane complement regulators is associated with transporter status in patients on peritoneal dialysis.

INTRODUCTION: A growing body of evidence from animal models and cell culture studies indicate an important role of a local regulatory complement system (CS) in peritoneal injury during peritoneal dialysis (PD). We investigated the expression of the local regulatory CS (reflected by CD46,CD55,CD59) in the peritoneal tissue of patients with different membrane function characteristics. PATIENTS AND METHODS: Biopsies from the parietal peritoneum were taken from 24 patients on PD, 22 uremic patients prior to PD. PD patients were grouped according to the dialysate-to-plasma ratio of creatinine (D/P Cre) and ratio of dialysate glucose at 4 hours versus dialysate glucose at time zero (D/D0 glucose) into low or low-average peritoneal transport status (L/LA) and high-average or high-transport status (HA/H) groups. CD46, CD55, and CD59 RNA expression were analyzed by real-time polymerase chain reaction (RT-PCR). Further localization of membrane complement regulators (CRegs) and semiquantitatively analysis was done by immunohistochemistry (IHC). RESULTS: CD46 and CD59 expression were similar in all groups. CD55 expression was significantly decreased in the HA/H group compared to the L/LA group and to uremic controls (p < 0.05 and p = 0.05, respectively). No statistically significant differences in CD46, CD55, and CD55 expression were detected when considering the history of peritonitis. There was no statistically significant correlation between PD duration and the expressions of CD46, CD55, and CD59. IHC revealed strong CD46, CD55, and CD59 expression in mesothelial cells. CD55 and CD59 were additionally detected in the vasculature. Using IHC, CD46 was lower in PD patients compared to uremic controls (p>0.05), but there was no difference between the L/LA compared to the H/HA group. Moreover IHC confirmed decreased expression of CD55 in the HA/H group compared to the L/LA group and uremic controls (p<0.0001 and p = 0.0001, respectively). CONCLUSION: CD55 expression is decreased in patients with fast transporter membrane function, whereas peritonitis and PD duration do not appear to alter CReg expression.

Gender-Specific Differences in Peritoneal Dialysis.

BACKGROUND/AIMS: Gender-specific differences between patients on renal replacement therapy have so far rarely been investigated. In the present study we aimed to describe gender-specific differences in a large cohort of peritoneal dialysis (PD) patients. METHODS: Clinical information for all patients who started PD at our center has been collected since the start of the PD-program in 1979. We used Cox regression to examine associations between technique failure and gender. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 745 patients (315 women and 430 men with a median age of 57 years; IQR 43-67) started PD between 1979 and 2015 in our center. Women were significantly younger at PD start 54 (40-65) years vs. 58 (47-68) years, p<0.001. Within the last almost 15 years, more man than women started PD, but technical survival rates were significantly better in female compared to men (HR=0.662, CI 95% (0.496-0.885) P=0.005). Cardiovascular events were the main cause of death over the study period in both sexes, but decreased over time. Additionally, death due to PD-associated peritonitis decreased significantly over the three decades in both sexes. CONCLUSIONS: Our data suggest that technical survival rates were significantly better in female compared to men over three decades and death due to cardiovascular events and PD-associated peritonitis decreased significantly over the three decades in both sexes.

CD147 expression in peritoneal injury.

BACKGROUND: Peritoneal injury is an important cause of technical failure of long-term peritoneal dialysis (PD). Encapsulating peritoneal sclerosis (EPS) is a severe complication of long-term PD with potentially life threatening consequences. CD147 is a glycoprotein with diverse functions including modulation of extracellular matrix via induction of matrix metalloproteinases, cell adhesion, and regulation of immune reactions. We hypothesized that CD 147 plays a role in the peritoneal cavity. METHODS: In this retrospective study, we localized CD147 by immunohistochemistry in peritoneal biopsies from uremic patients not on PD (n = 8), on PD without signs of EPS (n = 7), and in biopsies in patients with the diagnosis of EPS (n = 7). Double immunofluorescence was used to co-localize α-smooth-muscle actin (α-SMA) and CD147 in selected biopsies from each group. Expression was scored semi-quantitatively. RESULTS: In biopsies from uremic controls, CD147 was prominently expressed in mesothelial cells, focally between fat cells and by some perivascular cells. In patients on PD, a similar distribution was present (although mesothelium was rarely conserved), with some focal accentuation. In EPS, layers of fibroblastic cells were positive for CD147. EPS biopsies demonstrated a significantly higher score in a blinded evaluation, compared to uremic patients. Cells expressing CD147 were α-SMA positive myofibroblasts as demonstrated by double immunofluorescence. Mean CD147 scores did not differ between patients with different transporter status. CONCLUSIONS: This is the first study demonstrating CD147 on a major part of fibroblastic cells in EPS. Future studies need to address the role of these cells in this severe complication of long-term PD.

T1 and T2 mapping for evaluation of myocardial involvement in patients with ANCA-associated vasculitides.

BACKGROUND: Myocardial involvement in AAV patients might be silent, presenting with no or nonspecific symptoms, normal ECG, and preserved left-ventricular ejection fraction (LV-EF). Since up to 50% of deaths in these patients may be due to myocardial involvement, a reliable diagnostic tool is warranted. In contrast to LGE-CMR, which has its strengths in detecting focal inflammatory or fibrotic processes, recent mapping techniques are able to detect even subtle, diffuse inflammatory or fibrotic processes. Our study sought to investigate ANCA (antineutrophil cytoplasmic antibody) associated vasculitides (AAV) patients for myocardial involvement by a cardiovascular magnetic resonance (CMR) protocol, including late gadolinium enhancement (LGE) and mapping sequences. METHODS: Thirty seven AAV patients were prospectively enrolled and underwent CMR imaging. Twenty healthy volunteers served as controls. RESULTS: Mean LV-EF was 64%; LGE prevalence of the AAV patients was 43%. AAV patients had higher median native T1 (988 vs. 952 ms, p < 0.001), lower post-contrast T1 (488 vs. 524 ms, p = 0.03), expanded extracellular volume (ECV) (27.5 vs. 24.5%, p < 0.001), and higher T2 (53 vs. 49 ms, p < 0.001) compared to controls, with most parameters independent of the LGE status. Native T1 and T2 in AAV patients showed the highest prevalence of abnormally increased values beyond the 95% percentile of controls. CONCLUSION: AAV patients demonstrated increased T1, ECV, and T2 values, with native T1 and T2 showing the highest prevalence of values beyond the 95% percentile of normal. Since these findings seem to be independent of LGE, mapping techniques may provide complementary information to LGE-CMR in the assessment of myocardial involvement in patients with AAV.

Comprehensive Cardiovascular Magnetic Resonance Assessment in Patients With Sarcoidosis and Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Cardiac sarcoidosis (CS) may manifest as arrhythmia or even sudden cardiac death. Because patients with CS often present with nonspecific symptoms, normal electrocardiography, and preserved left ventricular ejection fraction, a reliable diagnostic tool for the work-up of CS is needed. Late gadolinium enhancement-cardiovascular magnetic resonance has proven diagnostic value in CS but has some limitations that may be overcome by adding newer cardiovascular magnetic resonance mapping techniques. The aim of our study was to evaluate a comprehensive cardiovascular magnetic resonance protocol, including late gadolinium enhancement and mapping sequences in sarcoid patients with no symptoms or unspecific symptoms and preserved left ventricular ejection fraction. METHODS AND RESULTS: Sixty-one sarcoid patients were prospectively enrolled and underwent comprehensive cardiovascular magnetic resonance imaging. Twenty-six healthy volunteers served as control group. Mean left ventricular ejection fraction was 65%; late gadolinium enhancement was only present in sarcoid patients (n=15). Sarcoid patients had a higher median native T1 (994 versus 960 ms; P<0.001), lower post contrast T1 (491 versus 526 ms; P=0.001), expanded extracellular volume (28 versus 25%; P=0.001), and higher T2 values (52 versus 49 ms; P<0.001) compared with controls. Among patients with values higher than the 95% percentile of healthy controls, most significant differences were observed for native T1 and T2 values. Most of these patients were late gadolinium enhancement negative. CONCLUSIONS: Patients with sarcoidosis demonstrate higher T1, extracellular volume, and T2 values compared with healthy controls, with most significant differences for native T1 and T2. While promising, the clinical significance of the newer mapping techniques with respect to early diagnosis and therapy of CS will have to be determined in future studies.