bluuebunny/crossref_metadata_2025 huggingface dataset:
MO985: Physical Function Trajectories Predict Patient Survival in Older Recipients of Deceased Donor Kidneys
Authors: Tsarpali Vasiliki , Midtvedt Karsten , Lønning Kjersti , Bernklev Tomm , Åsberg Anders , Von der Lippe Nanna , Varberg Reisater Anna , Heldal Kristian
Published: May 2022

BACKGROUND AND AIMS

Health-related quality of life (HRQOL) outcomes have been positively associated with patient survival after kidney transplantation (KT). In older recipients, poor HRQOL may indicate risk for clinical deterioration. We aimed to prospectively evaluate if, in older recipients of deceased brain-dead donor (DBD) kidneys, changes in HRQOL during the first year post-transplantation differed between survivor and non-survivors.

METHOD

KT candidates aged ≥65 years who were enlisted between January 2013 and November 2016 at the Norwegian national transplant center and received a deceased brain-dead donor (DBD) kidney were included. HRQOL was assessed using the Kidney Disease Quality of Life Short Form, version 1.3. HRQOL outcomes were collected prior to KT, at 10 weeks, 6 months and 12 months post-KT. A mixed-effect linear regression model was used to examine the development of HRQOL during the first year post-KT in survivors versus non-survivors. Longitudinal HRQOL trajectories were identified using a group-based trajectory modelling. A Cox proportional hazard regression was used to investigate the association of longitudinal HRQOL trajectories for each domain with patient survival.

RESULTS

We included 289 waitlisted candidates, of whom 192 received a DBD kidney. Mean age at KT was 72 (4.1) years, 133 (69%) were males, 47 (24%) were transplanted preemptively and 80% received an expanded criteria donor organ. During a median observation time of 4.6 (3.2, 6.3) years post-KT, 66 recipients died. In survivors, all the generic and kidney-specific HRQOL domains substantially improved during the first year post-KT, whereas HRQOL deteriorated in non-survivors (Figure 1). Three developmental trajectories, describing poor, fair and good outcomes were identified for most of the HRQOL domains. Recipients perceiving poor physical development during the first post-transplant year had a 2.5 higher mortality risk, while recipients with fair physical development had 1.4 increased mortality risk, compared with recipients with good physically development (Figure 2).

CONCLUSION

In elderly kidney transplant recipients, poor post-transplant physical function trajectory may indicate impaired survival. The systematic HRQOL monitoring following KT is warranted to identify high-risk patients and guide therapeutic decisions.
MO996: Immunogenicity Rates After Sars-Cov-2 Vaccination Among Kidney Transplant Recipients: A Meta-Analysis
Authors: Jay Robles Mark , Coronel Marichel
Published: May 2022

BACKGROUND AND AIMS

Various COVID-19 vaccines have been developed across a range of platforms and have been deployed among immunocompetent individuals, but data have been lacking regarding the effects of these vaccines among kidney transplant recipients. While it is true that there is high immunogenicity after COVID vaccination among immunocompetent individuals, disappointing results in the humoral response were seen among kidney transplant recipients. There are studies that undermine the over-all immunogenicity among end-stage renal disease on renal replacement therapy, but little is known regarding data among kidney transplant recipients. Hence, this meta-analysis would like to investigate the over-all immunogenicity rate among kidney transplant recipient after COVID vaccination.

METHOD

A systematic search of relevant articles was performed on two English databases (Pubmed, Cochrane Library) published between January 2020 to November 2021 and we included studies on kidney transplant recipient who reported on antibody response rate after COVID vaccination.

RESULTS

Thirteen studies were included in this meta-analysis with a total of 2231 participants, analyzing immunogenicity rates among kidney transplant recipients towards the following vaccines: [mRNA-1273 SARS-CoV-2 Vaccine (Moderna), Inactivated whole-virus SARS-CoV-2 vaccine, CoronaVac® (Sinovac), mRNA BNT162b2 vaccine (Pfizer-BioNTech), and Oxford–AstraZeneca COVID-19]. The over-all immunogenicity rate among kidney transplant recipient was 43% (95% CI: 36–52%) with I2 = 80%. Compared with controls, kidney transplant recipient had a 53% reduced likelihood of attaining seroconversion after a standard 2 doses of COVID vaccine (RR: 0.47, 95% CI: 0.34–0.65).

CONCLUSION

The overall immunogenicity among Kidney Transplant (KT) recipient was 43% and compared with transplant-naïve group, KT recipients have a 53% reduced likelihood of attaining seroconversion. Moreover, KT recipients whom had prior COVID-19 infection, and received mRNA-1273 COVID-19 Vaccine (Moderna) as their COVID vaccine has higher antibody response rate. The addition of booster dose of vaccine showed a slight increase in immunogenicity compared with those whom had two doses only. Lastly, old age and high levels of anti-metabolite might have cause low level of immunogenicity among kidney transplant recipient after COVID vaccination.
MO1004: Non-Antibiotic Prophylaxis with D-MANOSE for Uti in DE-NOVO Kidney Transplant Recipients: The Manotras Study
Authors: Melissa Rau Lertora Ana , Santelli Adrián , Fiol Maria , Riera Luis , Etcheverry Begoña , Ardanuy Tisaire Carmen , Marti Sara , Cruzado Josep , Melilli Edoardo
Published: May 2022

BACKGROUND AND AIMS

Urinary tract infections (UTIs) are one of the most frequent complications in the first 6 months after kidney transplantation. (1) D-Mannose, a simple sugar, could play a very important role in the prevention of urinary infections, inhibiting the attachment of bacterial type one fimbriae to the urothelium, reducing their ability to infect de host. Proanthocyanides (PAC) have also been shown in vitro activity to inhibit the adherence of Escherichia coli by a similar mechanism. Both have shown promising results in reducing the risk of UTI in healthy women, but its efficacy has not been evaluated in kidney transplant population yet. (2) In this single-cantre, double-blind, prospective, randomized clinical trial, we aimed to evaluate the impact and security of a 24-h prolonged release formulation of D-Mannose in de-novo kidney transplantation UTI's.

METHOD

Between April 2019 and September 2020, 60 patients were recruited and randomized in 1:1 ratio according to treatment arm. Control group was treated with PAC, while the study group received PAC plus Mannose. Treatments were given as a prophylaxis strategy immediate after renal transplantation and during the first 3 months. All patients were followed for 6 months.

RESULTS

No statistically differences were observed in the baseline characteristics among study groups (Table 1). During the follow up; 61% of patients had at least one UTI episode (asymptomatic bacteriuria 56%, cystitis 6% and acute graft pyelonephritis 17%). Escherichia coli accounted for 28% of all UTI episodes, followed by Enterococcus faecalis (15%), Enterobacter cloacae (13%) and Klebsiella pneumoniae (13%). The main renal outcomes (eGFR at 6 months, acute rejection and DGF) did not differ among study groups.

We found no statistically differences recording in the incidence of UTI between groups (Fig. 1). At univariate analysis the surgical complications, and female gender were independently associated with UTI. {OR 5.92, [95% confidence interval (95% CI) 1.021–34.36]; P = .041 and OR 3.59 95% CI 1.051–12.27; P = .047} with no effect of treatment with D-mannose.

CONCLUSION

In this study, a prophylaxis strategy based on Mannose + PAC did not show a significant impact compared with PAC alone on UTI in the de-novo kidney transplant population.
MO1009: Early Switch from Fast IR-TAC Metabolizers to LCP-TAC Improves Renal Allograft Function
Authors: Thölking Gerold , Tosun Filiz , Jehn Ulrich , Koch Raphael , Josef Pavenstädt Hermann , Suwelack Barbara , Reuter Stefan
Published: May 2022

BACKGROUND AND AIMS

In contrast to slow tacrolimus (Tac) metabolism, fast metabolism is associated with a more rapid decline in renal function [1–3]. Because the pharmacokinetics of LCP-Tac (LCPT) differ from those of immediate-release Tac (IR-Tac), we hypothesized that the estimated glomerular filtration rate (eGFR) of fast metabolizers, in particular, would be improved by switching from IR-Tac to LCPT.

METHOD

We included renal allograft recipients receiving a de novo immunosuppression with IR-Tac, mycophenolate and prednisolone. A Tac concentration-to-dose ratio (C/D ratio, surrogate for bioavailability) <1.05 ng/mL*1/mg defined fast metabolizers and ≥ 1.05 ng/mL*1/mg slow metabolizers one months after renal transplantation (RTx). All patients were switched to LCPT 1 month after transplantation or later. During a 3-year follow-up, Tac doses, C/D ratios, eGFR, infection and rejection rates were compared between the metabolizer groups.

RESULTS

Fast metabolizers (n = 58) were switched to LCPT earlier than slow metabolizers (n = 22) after RTx (2.0 (1.0–253.1 versus 13.2 (1.2–172.8 months, P = .005). Tac doses were decreased by ∼65% in both groups after 12 months of conversion to LCPT. C/D ratios at 12 months increased from 0.66 (0.24–2.10) to 1.74 (0.42–5.43) (+163%) in fast and from 1.15 (0.32–3.60) to 2.75 (1.08–5.90) (+139%) in slow metabolizers. Fast metabolizers showed significant recovery of mean eGFR as early as one month after conversion (48.5 ± 17.6 versus 41.5 ± 17.0 mL/min/1.73 m²; P = .032) and at all subsequent time points. Conversion to LCPT did not result in relevant eGFR changes in slow metabolizers. Infection and rejection rates were low and did not differ between the groups before and after conversion.

CONCLUSION

Switching to LCPT increases the Tac bioavailability. This was associated with a significant recovery of renal function in fast metabolizers. Conversion to LCPT is safe and beneficial early after RTx.
MO1048: The Influence of Online Kidney School on Dialysis Choice
Authors: Ørsted Schultz Anders , Hayes Bauer Eithne , Kampmann Jan
Published: May 2022

BACKGROUND AND AIMS

Factors influencing dialysis choice are multifaceted. Detailed and unbiased information is pivotal in order to assist patients in making decisions. Hence, patient education is a cornerstone in the treatment of advanced chronic kidney disease. At the hospital of Southern Jutland, a kidney school has existed for more than 15 years teaching patients about their illness and treatment options at end-stage renal disease (ESRD). Due to the coronavirus disease (COVID-19) pandemic, an online kidney school (OKS) was established. We present the latest results of this ongoing study regarding the change of preferences of ESRD treatment options among patients after participation in online renal education.

METHOD

The OKS consists of a 3-h synchronous class taught by a nephrologist and a dialysis nurse combined with asynchronous short films on treatment options and advice from a dietitian. The OKS has been held six times with 45 patients in total. A questionnaire was distributed to participants before and after the OKS. Patients were asked to choose between center haemodialysis, home haemodialysis, peritoneal dialysis, transplantation, maximal conservative medical treatment and ‘not enough information to make the decision’.

RESULTS

Out of the 45 patients, 36 patients answered the questionnaire before OKS and of those, 19 also answered the questionnaire after OKS. A total of 76% % of the participants were male, 52% answered the questionnaire on their own and 48% answered the questions together with a relative. The percentage of patients not feeling informed enough to make the decision decreased from 56% prior to participation in OKS in comparison to 32% following participation in OKS. The percentage of patients who prefer peritoneal dialysis as their ESRD treatment of choice increased from 6% to 32%.

CONCLUSION

Online education on treatment choices for end-stage renal patients leads to change of treatment preferences. This is especially true for peritoneal dialysis. The OKS is designed to help patients make an informed decision on treatment options in ESRD. Although the number of patients feeling unsure about what kind of treatment to choose is decreased, the number of patients unsure about the best treatment option for them remains high. These patients require a follow-up consultation in order for them to make the final decision for ESRD treatment. The number of patients who answered the questionnaire prior to OKS is higher in comparison to after OKS. However, this is an ongoing study and we will be able to confirm or dismiss these preliminary findings at a later stage.
MO1056: Music Therapy Reduces Anxiety and Pain and Improves Satisfaction in Patients Undergoing Percutaneous Renal Biopsy
Authors: Giordano Filippo , Pesino Alessandra , Cortese Cosma , Esposito Flavia , Campobasso Nicla , Grandolfo Nicola , Rossini Michele , Mitrotti Adele , Gesualdo Loreto
Published: May 2022

BACKGROUND AND AIMS

Percutaneous kidney biopsy (PRB) is an invasive procedure performed under local anaesthesia that often creates anxiety, stress and pain in the patient before, during and after the procedure. Music therapy (MT), defined as the clinical- and evidence-based use of music, is administered by a trained professional to achieve individualized goals within a therapeutic relationship between patient, music and music therapist. MT can be used as a complementary non-drug intervention to prevent and treat emotional distress and pain. The main objectives of the study were

1. evaluate the effectiveness of MT in managing anxiety, pain and satisfaction in patients undergoing PRB.

2. investigate the effect of MTI on heart rate variability (HRV).

METHOD

This study was a two-arm, single-centre, parallel-group and pre–post PRB randomized controlled trial. Patients programmed for PRB were enrolled (n = 80) and assigned to the MT intervention group (MG, n = 40) or standard treatment [control group (CG), n = 40]. MG received, from a FAMI-certified music therapist, a personalized playlist administered during the PRB, adapted to the individual patient. Patient anxiety was assessed before and after PRB using the State Y-1 Trait Anxiety Inventory (STAI-Y1). A visual analog scale (VAS) was used for self-assessment of pain (VAS-P) and satisfaction (VAS-S). Physiological stress parameters (PRE–POST) were assessed using HRV (SDNN, RMSSD, LH/HF, SD1, SD2) from E4 wristbands—Empatica Inc.1. The bracelet was placed 5 min before the patient entered the operating room for the procedure and removed after the completion of the PRB. The data of each session were divided into two segments: (1) pre, before the administration of the local anesthetic and (2) post, after the conclusion of the biopsy.

RESULTS

A statistically significant difference in anxiety levels was observed between the MG and CG groups (35.35 ± 6.208 versus 42.83 ± 9.027; P < 0.001, Fig. 1). The MG group showed significantly lower VAS-P values ​​(4.95 ± 1.377 versus 6.28 ± 1.281; P < 0.001, Fig. 2) and higher VAS-S values ​​(7.75 ± 0.981 versus 6.03 ± 0.800; P < 0.001) after PRB compared with the CG group (Fig. 3). The SDNN (P < 0.034), RMSDD (P < 0.04) and SD2 (P < 0.027) measurements of HRV were significantly higher in MG than in CG, while LF/HF decreased (P < 0.033).

CONCLUSION

This study supports the efficacy of MT in reducing anxiety and pain and improving satisfaction in patients undergoing PRB. MT modulates the autonomic nervous system, reducing sympathetic activity, increasing parasympathetic activity and inducing physiological relaxation.
FC013: Shear Wave Elastography Effective in Ultrasound Diagnosis of Chronic Kidney Disease in Patients With hyperuricaemia And Gout
Authors: Rostyslav Rbubnov
Published: May 2022

BACKGROUND AND AIMS

Shear wave elastography (SWE) is a well-known ultrasound method for assessing liver, yet has a limited use in nephrology. Gout is associated with risk of chronic kidney disease (CKD, nephropathy) progression. Ultrasonography (US) can provide accurate information for detecting kidney disease in gout (Bubnov and Melnyk. Evaluation of biomarkers for diagnostic decision making in patients with gout using novel mathematical model. Complex PPPM approach. EPMA J. 2014;5(Suppl 1): A58. doi:10.1186/1878-5085-5-S1-A58) and can help monitoring treatment effect (Short-term probiotics regimen may help treat gout, kidney disease. Personalized medicine approach may improve signs of metabolic syndrome. American Physiological Society (APS) News Room, 03.10.2019 https://www.the-aps.org/detail/news/2019/10/04/short-term-probiotics-regimen-may-help-treat-gout-kidney-disease?SSO=Y).

 The aim was to study the added diagnostic value of SWE effective in ultrasound diagnosis of CKD in patients with hyperuricaemia and gout.

 The aim was also to study the relevance of US markers of kidney including SWE and B-flow to provide advantages to grey scale and Doppler in assessing kidney disease in gout.

METHOD

We included 43 patients (38–75 years; 15 women) with gout/increased levels of uric acid in blood, gout attacks according to disease history. The control group included 38 healthy individuals (20 women), mean age 44 ± 8 years without clinical, laboratory signs of nephropathy and liver pathology. All patients underwent general clinical, lab tests; abdominal US including precise multiparameter US of kidneys measuring SWE, and B-flow in parenchyma and vessels were conducted using curved abdominal transducer of LOGIQ 9 systems (GE Healthcare).

RESULTS

CKD signs included thinning, increasing echogenicity of kidney parenchyma (P < 0.05), detection of fibrotic changes and small hyperechoic inclusions, hilly margins, anechoic strips under the capsule, RI increasing in segmental arteries over 0.7. The SWE change was 8.7 ± 1.5 (6–13 kPa) versus 4.5 ± 1.2 kPa (P < 0.05). High spatial resolution of B-flow imaging helped to display complex perfusion, pyramids structure, detect vascular flow in areas of heterogeneity on grey scale and evaluate arcuate arteries. We detected signs of fatty liver in all patients (LF2–4); liver size in the right lobe was 170 ± 7 versus 142 ± 8 mm in controls; liver size and SWE data demonstrated positive correlation with kidney SWE.

CONCLUSION

SWE is and effective and accessible complementary technique capable of providing added diagnostic value to assess the kidney parenchyma. Multiparameter ultrasound is an effective method for early detection of CKD in patients with hyperuricaemia and gout. Petrifications, deformations parenchyna, blood flow abnormalities and SWE markers are the most reliable ultrasound signs, specific for kidney disease in gout.
FC025: Physiological Role of KV Channel in Ureter Smooth Muscle Cell Investigated Quantitatively by Electrophysiological Modeling
Authors: Mahapatra Chitaranjan , Pradhan Ashish
Published: May 2022

BACKGROUND AND AIMS

Spontaneous peristaltic contraction disorder of the ureter smooth muscle (USM) is an important etiology of congenital giant ureter, congenital ureteropelvic junction deformity and non-obstructive hydronephrosis [1]. The USM cell action potential (AP) plays a key role in commencing USM contraction by allowing influx of Ca2+ from the extra cellular space [2]. Therefore, an in-depth quantitative investigation of the USM cell AP generation will assist in developing better pharmacological therapies for the USM abnormal contraction. The purpose of this in-silico study is to unfold the physiological role of Kv channel in modulating the USM AP generation.

METHOD

The model consists voltage- dependent Na+ currents (INa), hyperpolarization-activated cyclic nucleotide- gated current (Ih), voltage- dependent Ca2+ currents (ICa), Ca2+ dependent potassium channel (IBKCa) and voltage-dependent potassium channels (IKv) as the components of active electrophysiological characteristics [3]. All ion channels are represented by the Hodgkin–Huxley formalism. The maximum conductance of the is varied to investigate the physiological role of the Kv channel in modulating the USM AP generation.

RESULTS

The whole cell IKv current is generated by applying the voltage clamp protocol, where the membrane potential is stepped from a holding potential of –80 mV–60 mV for a duration of 500 ms. The half activation potential, half inactivation potential, activation slope factor and inactivation slope factors are: 43 mV, –76.1 mV, 15.4 mV and 6.5 mV, respectively, to fit the Boltzmann function equation. The model reveals that fast activation and inactivation properties are the essential feature of IKv for the USM cell. The resting membrane potential (RMP) is set at –50 mV. The AP was induced in the whole cell model by applying an external stimulus current (10–30 pA), as a brief square pulse of 500 ms duration. It is demonstrated that IKv opposes the Ca2+ current during the first 50 ms of the AP duration and then inactivated. It doesn't contribute to the repolarizing phase of the AP.

CONCLUSION

The plateau phase of the USM AP shows that the total AP duration much longer than that in other smooth muscle cells. It strongly supports the phenomenon is due to the activation of Ca2+-dependent K+ channel and inactivation of L-type Ca2+ channel. In ureter cells, the IKv does not contribute significantly to the repolarization of the AP, but it may regulate membrane excitability by opposing Ca2+ current activated around the threshold of the AP. Therefore, the agonist and antagonist of the IKv might be useful partially as new pharmacological targets for the USM abnormal contraction.
FC053: Weaning of Maintenance Immunosuppressive Therapy in Lupus Nephritis (Win-Lupus): A multicenter randomized controlled trial
Authors: Jourde-Chiche Noemie , Costedoat-Chalumeau Nathalie , Baumstarck Karine , Bouillet Laurence , Burtey Stephane , Caudwell Valerie , Chiche Laurent , Couzi Lionel , Daniel Laurent , Deligny Christophe , Dussol Bertrand , Faguer Stanislas , Gobert Pierre , Gondran Guillaume , Huart Antoine , Hummel Aurélie , Kalbacher Emilie , Alexandre Karras , Lambert Marc , Le Guern Veronique , Loubiere Sandrine , Maillard Helene , Maurier Francois , Pha Micheline , Queyrel-Moranne Viviane , Sarrot Francoise , Verhelst David , Hachulla Eric , Amoura Zahir , Daugas Eric
Published: May 2022

BACKGROUND AND AIMS

Lupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with an induction immunosuppressive therapy (IST), followed by a maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance IST for proliferative LN is unknown. The WIN-Lupus trial tested whether IST discontinuation after 2–3 years in proliferative LN was non-inferior to IST continuation for 2 more years.

METHOD

WIN-Lupus is an investigator-initiated academic randomized controlled trial, conducted in 28 French centres. Patients on maintenance IST with azathioprine

or mycophenolate mofetil for a minimum of 2 years and a maximum of 3 years, and those who were taking hydroxychloroquine were randomized (1:1) between two groups: IST continuation and IST discontinuation. The primary endpoint was the relapse rate of proliferative LN at 24 months. Secondary endpoints were the rate of severe SLE flares, survival without renal relapse or severe flare, adverse events, kidney function, disease activity, corticosteroid exposure, patient-reported outcome and medico-economic impact.

RESULTS

Between 2011 and 2016, 125 patients were screened and 96 were randomized in the trial: 48 in the IST continuation group and 48 in the IST discontinuation group. In the per-protocol population, a relapse of proliferative LN occurred in 5/40 (10.4%) patients with IST continuation, and in 12/44 (25%) patients with IST discontinuation (difference 14.8%, 95% CI [−1.9; 31.5]). Noninferiority was not demonstrated for relapse rate. Time to renal relapse did not differ between groups (P = 0.092). Severe SLE flares (renal or extrarenal) were less frequent in patients with IST continuation compared to IST discontinuation (5/40 versus 14/44 patients; P = 0.035). IST discontinuation was associated with lower health-related costs. Adverse events did not differ between groups.

CONCLUSION

Noninferiority of maintenance IST discontinuation after 2 to 3 years was not demonstrated for renal relapse. IST discontinuation was associated with a higher risk of severe SLE flare.
FC075: Role of Factor H and its Related Proteins (FHR-1, FHR-2 FHR-5) in ANCA-Associated Vasculitis: A Genetic and Longitudinal Serological Study
Authors: Maria Fernandez Juarez Gema , Villacorta Javier , Lucientes Laura , Goicoechea De Jorge Elena
Published: May 2022

BACKGROUND AND AIMS

The complement system was not initially thought to be associated with the development of ANCA-associated vasculitis (AAV). Convincing evidence from animal models and clinical observations indicates, however, that activation of the complement system, the alternative pathway (ACP) in particular, is pivotal for the development of AAV. Recently, a phase 3 clinical trial has shown that C5a receptor inhibition with avacopan was effective in replacing high dose glucocorticoids in AAV patients treated with rituximab or cyclophosphamide during induction treatment. We hypothesized that in AAV, a disorder in regulatory factors of ACP or in its related proteins (FHR-1, FHR-2, FHR-5) could be present, similar to other diseases in which its dysregulation have been shown.

Method

We measured longitudinal levels of alternative complements factors (FH, FB, properdin, FHR-1, FHR-2, FHR-5) and performed a genetic study for these factors in three cohorts: active renal ANCA vasculitis (active AAV, n = 54), inactive ANCA vasculitis (remission, n = 48) and in a control cohort of healthy individuals (n = 99).

RESULTS

ANCA serology was positive in all patients; 83.3% showed activity against MPO, whereas activity against PR3 was identified in 16.7% of patients. Median BVAS at the onset was 15 (IQR 14–19). Extrarenal involvement was present in 46.3% of participants. Haplotype CFH-H6 and the allele CFB32R are significantly associated with increased risk to develop AAV [OR 3.32; 95% confidence interval (95% CI) 1.39–7.89; P = 0.008 and OR 1.71, 95% CI 1.11–2.54; P = 0.008, respectively]. The allele frequency of ΔCFHR3/1 was significantly decreased in patients with severe AAV (T3, BVAS > 16) compared with patients with a lower BVAS score (T1-T2 ≤ 15). Circulating levels of regulatory factors (FH, FB, properdin) were significantly lower in patients with active disease compared to samples in remission, and FHR1 (FH competitor) levels were higher. C3 levels increased over time, while sC5b-9 decreased after initiating the immunosuppressive treatment, with the biggest change observed after the first month of treatment. After 12 months of follow-up, FHR-1 levels decreased in responder patients and did not decrease in nonresponders.

CONCLUSION

This is the first study to associate the presence of certain alleles of regulatory factors of the alternative complement pathway (Factor H and Factor B) with an increased risk of developing ANCA-associated vasculitis. Likewise, the absence of the ΔCHR3-CFHR1 deletion was associated with more severe forms of the disease. We could conclude that ACP is not a simple additional factor in the inflammatory loop in AAV and, like in other glomerular diseases related to ACP, dysregulation of FH and its regulatory proteins play an essential role in its development.
FC 111: A Comorbidity Index and Pretransplant Physical Status Predict Survival in Older Kidney Transplant Recipients
Authors: Tsarpali Vasiliki , Midtvedt Karsten , Lønning Kjersti , Bernklev Tomm , Åsberg Anders , Von der Lippe Nanna , Varberg Reisater Anna , Heldal Kristian
Published: May 2022

BACKGROUND AND AIMS

Regardless of age, kidney transplantation (KT) is considered the optimal treatment for patients with end-stage kidney disease (ESKD). In the increasing elderly ESKD population, KT should be reserved for carefully selected candidates who are expected to experience favorable outcomes. We aimed to prospectively evaluate pre-transplant recipient factors that may predict post-transplant patient survival and can eventually guide therapeutic decisions in elderly with ESKD.

METHOD

Recipient factors were evaluated in KT candidates aged ≥65 years, who were enlisted for KT between January 2013 and November 2016 at the Norwegian national transplant centre. Pretransplant comorbidity was assessed at waitlisting, according to the Liu Comorbidity Index (LCI). Self-reported health-related quality of life was assessed using the Kidney Disease Quality of Life Short Form version 1.3 (KDQOL-SF). The Cox proportional hazard regression was used to evaluate predictors of patient survival.

RESULTS

We included 289 waitlisted candidates, of whom 192 received a deceased brain-dead donor kidney. Mean age at KT was 72 (4.1) years, 133 (69%) were male, 47 (24%) were transplanted preemptively and 80% received an expanded criteria donor organ. During a median observation time of 4.6 (3.2–6.3) years post-KT, 66 recipients died. LCI ≤ 3 was observed in 136 recipients (71%), between 4–6 in 39 recipients (20%) and 17 recipients (9%) had LCI ≥ 7. Elevated LCI ≥ 4 predicted poor patient survival, and was associated with a 2.2-times increase in mortality risk (Figure 1). In recipients with LCI ≥ 4, dialysis ≥2 years comprised a 2.5-fold higher mortality risk, compared with recipients on dialysis ≤2 years (Figure 2). Self-reported pretransplant physical function was also proven to be a significant positive predictor of survival, with scores ≤60 being associated with a 2-fold increase in mortality risk.

CONCLUSION

The implementation of LCI and a physical function score during the evaluation of older kidney transplant candidates may improve the selection and thereby optimize post-transplant outcomes.
MO092: Prevalence and Renal Prognosis of Left Ventricular Diastolic Dysfunction in Nondialysis Chronic Kidney Disease Patients With Preserved Systolic Function
Authors: Borrelli Silvio , De Nicola Luca , Garofalo Carlo , Lembo Eugenio , Netti Antonella , Lucà Sergio , Lucà Stefano , Chiodini Paolo , Paoletti Ernesto , Stanzione Giovanna , Conte Giuseppe , Minutolo Roberto
Published: May 2022

BACKGROUND AND AIMS

Left ventricular (LV) diastolic dysfunction is common in nondialysis chronic kidney disease (ND-CKD) patients; however, the prevalence estimated according to the new diagnostic criteria as well as the prognostic role of diastolic dysfunction on CKD progression remain unknown.

METHOD

We longitudinally evaluated consecutive ND-CKD patients and preserved systolic function (LV ejection fraction > 50%). According to the recently updated guidelines, LV diastolic dysfunction was assessed by four echocardiographic variables (annular e’ velocity, average mitral valve E-wave/e’ ratio, left atrial volume index and tricuspid regurgitation). Patients were classified as diastolic dysfunction, indeterminate and normal. Time-dependent eGFR change was assessed by mixed-effects regression model. Cumulative incidence of composite renal outcome (eGFR decline > 50% or chronic dialysis) was also estimated.

RESULTS

Among 140 patients (age 66.2 ± 14.5 years; 61% males; eGFR 39.8 ± 21.8 mL/min/1.73 m2; 43.6% diabetics), diastolic dysfunction occurred in 22.9%, indeterminate in 45.7% and normal in 31.4%. Prevalence of diastolic dysfunction was much lower than that estimated with older criteria (62.1%). Logistic regression (OR, 95%CI) showed that diastolic dysfunction was associated with lower eGFR (0.97, 0.94–0.99), older age (1.08, 1.01–1.06) and nighttime systolic blood pressure (1.04, 1.00–1.07). Across 1702 eGFR measurements collected during a median follow-up of 4.6 years, eGFR decline (mL/min/1.73 m2/year) was faster in patients with diastolic dysfunction (−2.12, 95%CI from −2.68 to −1.56) and in the indeterminate (11.2/100 pts/year) as compared with normal (−1.14, 95%CI from −1.64 to −0.63) (Figur 2). Incidence of composite renal outcome was significantly higher in diastolic dysfunction (13.8/100 pts/year) than in normal group (3.5/100 pts/year).

CONCLUSION

In ND-CKD population, LV diastolic dysfunction is less frequent than previously described and acts as independent predictor of CKD progression.

Mixed-effect regression was adjusted for age, gender, diabetes, prior cardiovascular disease, log(proteinuria), systolic office blood pressure (BP), diurnal and nocturnal systolic ambulatory BP and left ventricular hypertrophy.
MO352: The Effect and Mechanism of Renal Targeted Delivery of MSC Exosomes in the Treatment of AKI
Authors: Jiang Wei , Wang Bin , Liu Bicheng
Published: May 2022

BACKGROUND AND AIMS

AKI occurs in ∼15% hospitalized patients and over 50% intensive care unit patients. However, effective therapeutic strategies for AKI are urgently needed. The exosomes derived from mesenchymal stem cells (MSC-exos) have achieved great focus as a cell-free therapy. As foremost metabolic organs, MSC-exos mainly collect in the liver and spleen. More attention should be considered how to induce more exosomes targeted to the injured kidney. In addition, the potential role of MSC-exos in injured kidney and the underlying mechanisms still need further research.

METHOD

Transmission electron microscopy, western blotting and nanoparticle tracking analysis were used to identify the properties of human umbilical cord mesenchymal stem cells (hucMSCs) derived exosomes. Kidney targeting peptide was chosen by the IVIS spectrum imaging system. Moreover, kidney targeting peptide (peptide-CGA) and CD63 targeting peptide were loaded to the MSC-exos by co-incubated (CGA-exos). Flow cytometry and immunofluorescence staining were utilized to confirm this. IVIS spectrum imaging system was used to assess MSC-exos distribution in vivo.

RESULTS

In vivo imaging showed that Peptide-CGA was efficiently homing to the ischemic kidney and predominantly accumulated in proximal tubules. Further Immunoprecipitation study showed that Peptide- CGA treatment group produced a specific stripe in silver staining compared with other groups. CGA-exos was successfully constructed. MSC-exos could alleviate murine ischemic kidney injury and reduced the renal tubules injury. Furthermore, in vivo imaging showed CGA-exos treatment group could attract more MSC-exos into the injured kidney, and its therapeutic effect was significantly better than that of the MSC-exos treatment group. without causing significant organ side effects.

CONCLUSION

Novel kidney targeting MSC-exos was constructed. It exhibited a preferential tendency to injured kidney and was localized to proximal tubules in AKI. We demonstrate that MSC-exos ameliorate ischemic AKI. But its further mechanisms need more insight. All in all, this highlights the potential of MSC-exos as a promising therapeutic strategy for AKI.
MO356: Protective Effects of Remote Ischemic Per-Conditioning Against Heart Injury Induced by Renal Ischemic/Reperfusion: The Role of Apelin
Authors: Karimi Zeinab , Masjedi Fatemeh , Janfeshan Sahar , Roozbeh Jamshid
Published: May 2022

BACKGROUND AND AIMS

Apelin is an endogenous hormone defined as a ligand for G-protein-coupled (APJ) receptor. Apelin and APJ are produced in the peripheral tissues, including the heart and renal tissues. Renal ischemia outcomes in distant effects and the alterations observed in the heart may be important in the morbidity and mortality observed clinically. This study is designed to investigate the possible protective effect of remote ischemic per-conditioning on heart injury induced by renal ischemia-reperfusion (I/R) through the apelin-RAS axis.

METHOD

Male Sprague-Dawley rats were randomly allocated into three (n = 10) groups. (1) Sham group; (2) BIR (bilateral ischemic-reperfusion) group, renal ischemia was applied for 60 min by followed with reperfusion for 24 h; and (3) BIR+RIPerC (remote ischemic per-conditioning) group, four cycles of 5-min ischemia of the left femoral artery followed by 5-min reperfusion were applied at the starting of renal ischemia. The concentrations of BUN, Cr, Troponin-I, nitrite, nitrate and the angiotensin-converting enzyme (ACE) activity from plasma samples were measured. Gene expression of iNOS and ACE2 was determined in the renal and heart tissue samples. Renal and heart pathological studies were done by H&E staining.

RESULTS

Renal ischemia-reperfusion induced significant renal and cardiac structural disturbance. The plasma levels of BUN, Cr, Troponin-I, nitritem nitrate and ACE activity increased in the BIR group. Here, we have shown that ACE2 and apelin were downregulated, and iNOS was upregulated in the renal and heart tissue of the BIR group. Renal ischemia along with ischemic per-conditioning of the left femoral artery upregulated gene expression of apelin and ACE2, but not iNOS. Functional and structural biomarkers of kidney and heart, plasma content of nitrite and nitrate, and ACE activity decreased in the BIR+RIPeRC group.

CONCLUSION

Remote ischemic per-conditioning had a protective effect on kidney and heart lesions through apelin. These data confirm that the apelin-ACE2 (a negative regulator of the renin–angiotensin system) axis is a therapeutic target for cardiovascular diseases.
FC 133: Knockout Of ZEB2 Ameliorates Progression of Renal Tubulointerstitial Fibrosis in a Mouse Model of Renal Ischemia-Reperfusion Injury
Authors: Terada Yohsio , Inotani Satoxhi , Horino Taro , Taginiguchi Yoshinori , Sano Shigetoshi , Yanagita Motoko , Fujimoto Shimpei
Published: May 2022

BACKGROUND AND AIMS

Zeb2, a zinc finger E-box-binding homeobox transcription factor, reportedly regulates transforming growth factor (TGF)-β signaling pathway. However, its role in the pathogenesis of acute kidney injury (AKI) and AKI to chronic kidney disease (CKD) transition is unclear.

METHOD

We evaluated Zeb2 function in a bilateral renal ischemia-reperfusion injury (IRI)-induced AKI model using proximal tubule-specific Zeb2 conditional knockout (Zeb2-cKO) and wild-type (WT) mice. In Zeb2-cKO mice, plasma creatinine and blood urea nitrogen levels post-IRI were significantly lower than those in WT mice. Immunohistological analysis revealed mild tubular injury, less fibrotic changes, and reduced expression of fibrotic proteins, such as collagen type IV, α-smooth muscle actin (α-SMA), fibronectin and connective tissue growth factor (CTGF), at 3–14 days post-IRI in Zeb2-cKO mice. We also evaluated Zeb2 expression in human renal biopsy samples, including AKI to CKD patients, by immunohistological methods.

RESULTS

Zeb2 expression was mainly upregulated in proximal tubular cells post-IRI in WT mice. Zeb2 siRNA transfection reduced TGF-β-stimulated mRNA and protein expression of collagen type IV, α-SMA, fibronectin and CTGF in cultured renal tubular cells. Notably, patients with AKI to CKD transition showed high Zeb2 expression in renal tubules, as determined by evaluation of their renal biopsy samples. Furthermore, hypoxia and CoCl2-treatment upregulated Zeb2 promoter activity and mRNA and protein expression in cultured renal tubular epithelial cells, suggesting regulatory role of hypoxia.

CONCLUSION

Thus, we demonstrated Zeb2 upregulation in renal tissues in both mice and humans with AKI and showed that Zeb2 regulates fibrotic pathways in pathogenesis of AKI and AKI to CKD transition. Our findings suggest that Zeb2 blockage could serve as a potential therapeutic strategy in AKI.
Going, but Where? The Resettlement of Japanese Americans from the Heart Mountain Relocation Center
Authors: Kekki Saara
Published: May 2022

After the Japanese attack on Pearl Harbor in December 1942, the United States incarcerated (interned) 120,000 people of Japanese descent, two thirds of whom were U.S. citizens. Half of the incarcerated people returned to the West Coast, while the rest were dispersed across the country through the government's resettlement program. In this article, I study the resettlement of Japanese Americans away from the Heart Mountain, Wyoming, incarceration camp through historical big data and network analysis. The overarching goal of this article is to understand post-camp resettlement and its driving forces—or its obstacles—in light of the networks the inmates created at Heart Mountain. In particular, I draw attention to the ways in which resettlement choices could be seen to reflect individual agency: how resettlement decisions and actions mirror a person’s position in the incarceration community. I will uncover a variety and depth of networks that at times are indicative of compliance with authorities, while at times they may enforce separation from the dominant, i.e. White, society. This separation should not automatically be seen as negative or alienating, but rather as resistance to White expectations. Overall, these strategies highlight individual choice and agency.
SNPs in a Large Genomic Scaffold Are Strongly Associated withCr1R, Major Gene for Resistance to White Pine Blister Rust in Range-Wide Samples of Sugar Pine (Pinus lambertiana)
Authors: Wright Jessica W. , Stevens Kristian A. , Hodgskiss Paul , Langley Charles H.
Published: May 2022

Sugar pine, Pinus lambertiana Douglas, is a keystone species of montane forests from Baja California to southern Oregon. Like other North American white pines, populations of sugar pine have been greatly reduced by the disease white pine blister rust (WPBR) caused by a fungal pathogen, Cronartium ribicola, that was introduced into North America early in the twentieth century. Major gene resistance to WPBR segregating in natural populations has been documented in sugar pine. Indeed, the dominant resistance gene in this species, Cr1, was genetically mapped, although not precisely. Genomic single nucleotide polymorphisms (SNPs) placed in a large scaffold were reported to be associated with the allele for this major gene resistance (Cr1R). Forest restoration efforts often include sugar pine seed derived from the rare resistant individuals (typically Cr1R/Cr1r) identified through an expensive 2-year phenotypic testing program. To validate and geographically characterize the variation in this association and investigate its potential to expedite genetic improvement in forest restoration, we developed a simple PCR-based, diploid genotyping of DNA from needle tissue. By applying this to range-wide samples of susceptible and resistant (Cr1R) trees, we show that the SNPs exhibit a strong, though not complete, association with Cr1R. Paralleling earlier studies of the geographic distribution of Cr1Rand the inferred demographic history of sugar pine, the resistance-associated SNPs are marginally more common in southern populations, as is the frequency of Cr1R. Although the strength of the association of the SNPs with Cr1Rand thus, their predictive value, also varies with geography, the potential value of this new tool in quickly and efficiently identifying candidate WPBR-resistant seed trees is clear.
The Apple Receptor-Like Kinase MdSRLK3 Positively Regulates Resistance Against Pathogenic Fungus Valsa mali by Affecting the Ca2+ Signaling Pathway
Authors: Han Pengliang , Li Rui , Yue Qianyu , Li Fudong , Nie Jiajun , Yin Zhiyuan , Xu Ming , Guan Qingmei , Huang Lili
Published: May 2022

Valsa mali is the main pathogenic fungus that causes the apple Valsa canker, a destructive disease severely threatening apple production in the world. However, the underlying key components involved in resistance against V. mali in apple trees remain largely unexplored. Here, we isolated and functionally characterized a G-type lectin S-receptor-like protein kinase MdSRLK3 from the cultivar Royal Gala derivative line GL-3. qRT-PCR showed that the relative expression of MdSRLK3 in apple branches reached its highest level at 24 h post V. mali inoculation, which was 13.42 times higher than without inoculation. Transient overexpression of MdSRLK3 enhanced apple resistance against V. mali, while transient silencing of MdSRLK3 reduced its resistance against the pathogen. More importantly, stable silencing of MdSRLK3 resulted in reduced resistance against this fungus. Furthermore, we demonstrated that MdSRLK3 positively regulated apple resistance by affecting the Ca2+ signaling pathway, and the regulation was also related to the H2O2 and callose signaling pathways. Overall, our data reveal that MdSRLK3 is a positive regulator of apple immunity.
Increased Residential Clustering of COVID-19 Cases Associated With SARS-CoV-2 Variant of Concern B.1.1.7
Authors: Flannagan Joe , Twohig Katherine A. , Carter Emma , Chudasama Dimple Y. , Lamagni Theresa , Dabrera Gavin
Published: May 2022

Background:

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in England in 2020 and subsequent global spread emphasized the need to understand epidemiologic characteristics of SARS-CoV-2 variants. A diagnostic proxy for this variant, referred to as S-gene target failure, provided a rich dataset to assess transmissibility of the variant in an analysis of clustering in residential settings.

Methods:

We used a pair-matched case–control study design to estimate odds of onward transmission within households with S-gene target failure index cases versus nontarget failure index cases. We defined cases as the index in a household cluster (clustered case) and controls as a case with no subsequent household cluster (sporadic). We matched clustered and sporadic cases one-to-one on specimen week, geography, and property type. We used conditional logistic regression, adjusting for age, sex, ethnicity, and symptom status, to assess odds of residential clustering.

Results:

Our study population comprised 57,244 individuals with specimen dates from 23 November 2020 to 4 January 2021. Crude analysis yielded 54% increased odds (odds ratio [OR] = 1.5; 95% confidence interval [CI] = 1.5, 1.6) of residential clustering associated with S-gene target failure; the association remained in the fully adjusted model (OR = 1.6, 95% CI = 1.5, 1.6). Stratified analyses by region showed increased odds of residential clustering associated with target failure in all regions apart from the Southwest, where we observed lower precision. Similar adjusted odds ratios with precise confidence intervals remained in stratified analyses by property category.

Conclusion:

We observed increased odds in all property types, consistent with greater transmissibility of the B.1.1.7 variant in this high-risk setting.