bluuebunny/crossref_metadata_2025 huggingface dataset:
MO1025: Periostin as a Potential Biomarker of Renal and Arterial Damage in Children with Tuberous Sclerosis Complex
Authors: Skrzypczyk Piotr , Maria Wabik Anna , Szyszka Michał , Szmigielska Agnieszka , Krzemien Grazyna , Jozwiak Sergiusz , Brzewski Michal , Stelmaszczyk-Emmel Anna , Panczyk-Tomaszewska Malgorzata
Published: May 2022

BACKGROUND AND AIMS

Experimental data suggest that periostin is involved in the formation of renal cysts. Tuberous sclerosis complex (TSC) is a multisystem genetic disease characterized by the formation of lesions in virtually all organs, including the kidney—most commonly angiomyolipomas (AML) and cysts. There are no reliable markers of progression of renal lesions in patients with TSC. The study aimed to evaluate serum periostin levels in children with TSC and to assess the usefulness of periostin as a marker of renal lesion severity and arterial damage in this group of patients.

METHOD

In a group of 35 children with TSC (mean age 8.46 ± 5.64 years, 17 boys, 18 girls), serum periostin levels (ng/mL), anthropometric parameters, renal changes (by ultrasound and magnetic resonance imaging), blood pressure and biochemical parameters were evaluated. The control group consisted of 25 healthy children (mean age 8.72 ± 4.73 years, 14 boys, 11 girls). In addition, central pressure and parameters of arterial structure and function (cIMT, PWV, AIx75HR) were assessed in 20 children with TSC and 17 healthy children (age ≥ 4 years).

RESULTS

Arterial hypertension was found in two (5.7%) patients; AML was present in 20 (57.1%) children, including 9 (27.3%) atypical AML and 22 (62.8%) had cysts in the kidneys. Children with TSC did not differ in periostin levels compared with healthy children [67.46 ± 35.61 versus 68.14 ± 24.07 (ng/mL), P = .499]. In children with TSC, periostin concentration was negatively correlated with age (r = −0.614, P < .001), height (r = −0.634, P < .001), body weight (r = −0.658, P < .001), maximum cyst size (r = −0.481, P = .004) and office and ABPM systolic and diastolic blood pressure (r = −0.396 to −0.621, P < .050). There was no relationship between periostin levels and AML size or arterial damage parameters. In multivariate analysis, the only determinant of serum periostin levels in children with TSC was age [beta = −0.547, 95% confidence interval (95% CI) (−0.831 to −0.262)].

CONCLUSION

The usefulness of serum periostin determination as a marker of renal cystic lesions in children with tuberous sclerosis requires further study.
MO1027: Kidney Tubular Damage Associated with Early Sepsis and Longer Hospital Stay in Newborns with Neonatal Infection
Authors: Da Silva Barbosa Joycilene , Cavalcante Meneses Gdayllon , Rebouças Castelo Luan , Bezerra Da Silva Junior Geraldo , Maria Costa Martins Alice , De Francesco Daher Elizabeth , Lima Sampaio Tiago , Coelho Lopes Nicole , de Oliveira Gomes Amanda , Beatriz Timbó de Oliveira Ana , Daniel Alves Albuquerque Francisco , Pinheiro Gonçalves Lemes Romélia
Published: May 2022

BACKGROUND AND AIMS

The aim of the study was to evaluate the early association of urinary cystatin-C (uCysC) (proximal tubular injury biomarkers) with sepsis and longer hospital stay in premature newborns (NBs) with neonatal infection.

METHOD

This is a prospective study with NBs from Neonatal Intensive Care Unit (nUTI), between August 2019 and September 2020. Three groups were constructed: healthy NBs, NBs with neonatal infection without sepsis and NBs with sepsis. Premature newborns with kidney disease, renal malformation, insufficient data in the medical record, or samples with scarce volume were excluded. Urine samples were collected for biomarkers measurements. Urinary cystatin-C was quantified in the urine and expressed with or without ratio by urinary creatinine to investigate the urinary concentration bias.

RESULTS

In total, 62 NBs were included: 27 healthy, 24 with neonatal infection without sepsis and 11 with sepsis.  No acute kidney injury (AKI) was found in NBs and 22 (63%) had longer hospital stay (˃ 30 days). Higher levels of urinary cystatin-C, both adjusted for urinary creatinine, were elevated in NBs's sepsis group. Moreover, in NBs with a longer hospital stay, there was an elevated level of urinary cystatin-C, which was capable to predict the need for ˃ 30 days of hospital stay (AUC-ROC = 0.783, P = .01).

CONCLUSION

Our study demonstrated that kidney tubular damage biomarker, such as uCysC, was associated with early sepsis in premature NBs and was useful to prognosis evaluation.
MO1031: Burnout Syndrome Among Paediatric Nephrologists—Report on its Prevalence, Severity and Predisposing Factors
Authors: Pawlowicz-Szlarska Ewa , Skrzypczyk Piotr , Stańczyk Małgorzata , Pańczyk-Tomaszewska Małgorzata , Nowicki Michał
Published: May 2022

BACKGROUND AND AIMS

Burnout is an occupational-related syndrome comprising emotional exhaustion, depersonalization and reduced feelings of work-related personal accomplishments. Addressing and mitigating burnout is essential for avoiding high workforce turnover, patient dissatisfaction and a lower quality of care. There are some reports on burnout among adult nephrologists and general paediatricians, but little has been known about burnout among paediatric nephrologists. The aim of our study was to assess the prevalence and severity of burnout syndrome among Polish paediatric nephrologists.

METHOD

A 25-items online survey consisting of abbreviated Maslach Burnout Inventory and additional self-created questions about work-related factors was completed by 97 physicians affiliated with the Polish Society of Paediatric Nephrology. 75.3% of them were women, the median time of professional experience in the study group was 15 years.

RESULTS

High level of emotional exhaustion, depersonalization and reduced feeling of personal accomplishments was observed in 39.2%, 38.1% and 21.6% of participants, respectively. 26.8% of participants presented at least a medium level of burnout in all three dimensions and 8.2% of them presented high three-dimensional burnout. No associations of burnout intensity and gender, job seniority and the use of holiday leave were found. 41.2% of participants stated, that they would like to take part in burnout prevention and support programme. According to the study participants, excessive bureaucracy in healthcare systems, rush and working overtime were the main job-related problems that can influence burnout intensity.

CONCLUSION

Burnout is an important factor in the professional landscape of paediatric nephrology. Actions aiming at reducing the risk of occupational burnout among paediatric nephrologists should be applied both at personal and institutional levels.
FC009: Women in Nephrology Leadership: A survey by the SFNDT
Authors: Karam Sabine , Hocine Aldjia , Hourmant Maryvonne
Published: May 2022

BACKGROUND AND AIMS

The percentage of women in nephrology has been increasing over the years but remains suboptimal.(1) Likewise, women are still under-represented at the leadership level. Multiple factors have been evoked to explain this gap such as the constraints of motherhood and the lack of adequate culture for women advancement.(2)

METHOD

A 13-question questionnaire was sent to all the members of the Societe Francophone De Dialyse et Transplantation (SFNDT) inquiring about their gender, country, setting of practice and assessing their views about the representation of women in nephrology in general and in leadership positions in particular. Participants were also asked to voice their opinion about the potential barriers impeding women advancement in nephrology and about potential solutions to remediate to the gap.

RESULTS

A total of 237 participants responded to the survey with 17.7% of men. About 45.6% practiced in a public setting and 29% in a university setting. About 52% of the participants deemed that the number of women in nephrology was sufficient and 6.75% also thought that this number was more than sufficient; however only 14.7% thought that the number of women occupying leadership positions was enough. Regarding potential factors limiting women advancement in nephrology, 56.17% thought that there was a lack of incentive from the society to promote women, 55.3% thought that there was a bias toward promoting men, 40.4% thought that the lack of adequate child support played a role and 35.7% thought that the lack of or an insufficient paternity leave had an impact. Regarding potential solutions that could be offered 90.7% of the participants agreed that there was need to encourage a life–work balance and 60% deemed necessary to establish an adequate support system for working women such as daycares, lactation rooms etc.

CONCLUSION

Despite the continuous increase in the number of women in nephrology, their involvement in leadership role remains minimal and needs to be improved by optimizing their work conditions and by providing adequate support for the right work–life balance.
FC012: Urinary Lithogenic Profile in Patients with Non-Alcoholic Fatty Liver Disease
Authors: Bargagli Matteo , Liguori Antonio , Baroni Silvia , D'amato Donato , Tomasello Lidia , Pizzolante Fabrizio , De Matthaeis Nicoletta , Miele Luca , Manuel Ferraro Pietro
Published: May 2022

BACKGROUND AND AIMS

Several epidemiological studies have observed an increased risk for nephrolithiasis in patients affected by non-alcoholic fatty liver disease (NAFLD). However, the urinary lithogenic risk profile for patients with NAFLD is currently unknown.

METHOD

We systematically analysed the urinary metabolic profile of patients affected by NAFLD and liver cirrhosis (LC), followed at the hepatology outpatient clinic of our institution, compared to healthy individuals. A complete metabolic work-up for kidney stone disease was performed in all subjects. Multivariable linear regression models adjusted for age, sex, body mass index, eGFR and diabetes, were applied to assess differences in urinary lithogenic risk factors between healthy individuals and patients affected by NAFLD and LC.

RESULTS

A total of 42 patients and 12 healthy individuals were included in the analysis. No differences in age, sex and BMI were found among patients affected by NAFLD and LC, whereas the latter were more diabetic (71.4% versus 14.3%). After adjusting for multiple confounders, patients with NAFLD and LC had lower urinary magnesium (−55 mg/24 h; 95% CI −104, −6; P = 0.03 and −63 mg/24 h; 95% CI −121, −6; P = 0.03, respectively) and borderline oxalate (−1.21 mg/24 h; 95% CI −2.42, −0.01; P = 0.05 and −1.42 mg/24 h; 95% CI −2.79, −0.04; P = 0.04, respectively) excretions, compared with healthy controls. Compared with LC patients, NAFLD patients showed higher urinary ammonia (539 mEq/24 h; 95% CI 245, 833; P < 0.01), ammonia/net acid excretion ratio (0.40; 95% CI 0.18, 0.62; P < 0.01), urine pH (1.16; 95% CI 0.44, 1.88; P = 0.05) and lower urinary uric acid excretion (−210 mg/24 h; 95% CI −419, −0.29; P < 0.01) and titratable acidity (−9.7 mEq/24 h; 95% CI −19.0, −0.4; P = 0.04).

CONCLUSION

Altered urinary ammonia and magnesium excretions seems to be involved in the higher risk for stone formation found in patients with NAFLD. More studies are needed to investigate stone phenotypes and renal handling of ammonia in this setting.
FC035: Exome Sequencing of the Israeli Dialysis-Treated Pediatric Population Reveals Monogenic Etiology in ∼44% of Cases
Authors: Kagan Maayan , Ben Moshe Yishay , Shlomovitz Omer , Atias-Varon Danit , Haskin Orly , Ben-Shalom Efrat , Magen Daniella , Schreiber Ruth , Volovelsky Oded , Shasha-Lavsky Hadas , Davidovits Miriam , Borovitz Yael , Mor Nofar , Khavkin Yulia , Tzvi Behr Shimrit , Pollack Shirley , Geylis Michael , Schnapp Aviad , Weissman Irith , Barel Ortal , Vivante Asaf
Published: May 2022

BACKGROUND

Chronic kidney disease in children is estimated to be secondary to a monogenic etiology in ∼20% of patients and can arise from mutations in a multitude of different single-gene causes. Still, data are lacking on the true prevalence of genetic etiologies dates from a large scale unbiased population screen of children with advanced kidney disease.

METHOD

In order to provide comprehensive real-world evidence for monogenic etiologies of childhood end-stage kidney disease—on a national level—we initiated a nation-wide multicenter study of all pediatric Israeli dialysis units. Specifically, between 2020 and 2021, we recruited ∼90% (n = 66) of children on dialysis from all six dialysis units treating children in Israel. We conducted exome sequencing and diagnostic analysis for all patients. We assessed the diagnostic yield of genetic analysis and its relation to baseline clinical phenotypes.

RESULTS

Overall, the cohort comprises 66 individuals from different families with a first-degree consanguinity rate of 47%. Participants' mean age at renal replacement therapy initiation was 8.1 years (range 1-month to 20-years). Using exome sequencing we identified a genetic etiology in 29 out of 66 (44%) participants. The most common subgroup of diagnostic variants was in genes causing renal cystic ciliopathies (e.g. NPHP1, NPHP4, PKHD1 and BBS9), which together explain 31% of all monogenic etiologies. This was followed by mutations in genes causing CAKUT (e.g. EYA1, HNF1B, PAX2, COL4A1 and GREB1L), steroid-resistant nephrotic syndrome (e.g. LAGE3, NPHS1, NPHS2, LMX1B, SMARCAL1 and CRB2) and tubulopathies (e.g. CTNS, AQP2), which explain 21%, 21% and 17% of all genetic etiologies, respectively. The yield of exome sequencing was higher among non-Jewish compared with Jewish individuals (52% versus 29%) and in children from consanguineous families compared with non-consanguineous families (56% versus 31%). The final molecular diagnosis did not correspond with the pre-exome clinical diagnosis in 17% of cases.

CONCLUSION

Exome sequencing in an unbiased pediatric cohort with end-stage kidney disease yields a genetic diagnosis in 44% of cases and reveals many underappreciated monogenic etiologies. Surprisingly, renal cystic ciliopathies causing-genes were more common than CAKUT genes in our cohort. These results emphasize the importance of genetic testing among children with advanced chronic kidney disease and validate the role of exome sequencing as a standard routine diagnostic tool.
FC038: Efficacy of Levamisole for Maintaining Remission after the First Flare of Steroid Sensitive Nephrotic Syndrome in Children: The Nephrovir-3 Randomized Controlled Trial
Authors: Dossier Claire , Kwon Theresa , Nekrouf Celia , Bensaid Philippe , Parmentier Cyrielle , Galerne Aurelien , Chace Anne , Gobet Sophie , Nathanson Sylvie , Mahdi Fouad , Zenkhri Ferielle , Rouget Sebastien , Boyer Olivia , Berard Laurence , Rousseau Alexandra , Hogan Julien , Deschenes Georges
Published: May 2022

BACKGROUND AND AIMS

In children with Steroid Sensitive Nephrotic Syndrome (SSNS), relapse after the first flare occurs in 80% of cases, whatever the dosage or duration of initial steroid therapy. Therefore, there is an unmet need for early interventions to reduce the incidence of relapse and subsequent steroids and immunosuppressive drug exposure. Levamisole is an antihelmintic drug with an immunomodulatory action that reduces relapses in children with frequent relapses or steroid-dependant NS. NEPHROVIR-3 is the first trial to assess the efficacy of levamisole in increasing duration of initial remission after the diagnosis of INS.

METHOD

NEPHROVIR-3 is a multicentric placebo-controlled randomized trial (1:1), in 38 centres of the Paris area, France. Patients were included at INS diagnosis and randomized, when steroid sensitive within 4 weeks, to receive either levamisole 2.5 mg/kg/48 h or placebo for 6 months, in addition to the French steroid protocol (18 weeks-3990 mg/m2). Primary outcome was the relapse-free survival at 1 year. The effect of the study drug was analysed by a Cox proportional hazard model stratified on centre.

RESULTS

Between September 2017 and February 2020, 86 patients were included, median age at INS onset was 5 years (IQ 3–7), with 69% of boys. At 4 weeks, 68 of them were randomized. Median time to remission was 8.5 days (IQ 6–12). Relapse-free survival at 12 months was 53.8% [95 confidence interval (95% CI) 34.7–69.5] in the levamisole group versus 20.9% (7.2–39.4) in the placebo group (P = .007). The risk of relapse associated with levamisole was HR = 0.37 (95% CI 0.15–0.89).

CONCLUSION

Early treatment with levamisole at the first flare of childhood SSNS significantly improves relapse-free survival at 1 year.
FC044: Heterozygous Variants in Kinase Domain of NEK8 cause an Autosomal-Dominant Ciliopathy
Authors: Claus Laura , Stallworth Jennifer , van Jaarsveld Richard , Turner Joshu , Hawks Alexandra , May Melanie , Flanagan-Steet Heather , Louie Raymond , Silver Josh , Lerner-Ellise Jordan , Morel Chantal , Mighton Chloe , Ziegler Alban , Barakat Stefan , Dahan Karin , Demoulin Nathalie , Jean Goffin Eric , Larsen Martin , Michael Hertz Jens , Lilien Marc , Olinger Eric , Sayer John , Obeidová Lena , Seeman Tomas , Senum Sarah , Hanna Christian , Rogers Curtis , Duran Karen , Peters Edith , Harris Peter , Mason Jennifer , van Haaften Gijs , M. Van Eerde Albertien , Steet Richard
Published: May 2022

BACKGROUND AND AIMS

NEK8/NPHP9 encodes a protein that localizes to the primary cilium. Biallelic NEK8 variants are known to cause multiorgan developmental defects, including kidney cystic dysplasia and extensive extra-renal defects, with heterozygous carrier parents being asymptomatic [1]. This autosomal recessive inheritance is the most common inheritance mode for ciliopathies. Complementary to this, we now propose a dominant negative effect for specific heterozygous NEK8 missense variants in the kinase domain resulting in an autosomal-dominant ciliopathy.

METHOD

We performed genetic testing in patients from several medical centers. To explore the consequences of the identified NEK8 variants, we are performing cilia staining assays in patients' skin fibroblast and kidney cells, as well as in mIMCD3 cells overexpressing the identified variants. Furthermore, we are examining the impact of the NEK8 variants on replication stress response.

RESULTS

We identified three distinct heterozygous NEK8 variants in 12 families (Table 1), all leading to missense alterations in the kinase domain. Interestingly the p.Arg45Trp variant is a recurrent variant we detected in 10 unrelated families. All patients have a kidney phenotype that varies from mild focal segmental glomerulosclerosis to prenatal presentation with polycystic kidneys. Most patients have kidney failure needing kidney replacement therapy at varying ages of onset. In all patients, we thoroughly checked whether a second variant could be found. Furthermore, the large symptomatic family and de novo occurrences favor a dominant inheritance mode. Our preliminary results from functional studies show abnormal primary cilia formation in serum-starved cells as well as increased replication stress.

CONCLUSION

We present the first evidence for a pathogenic effect of heterozygous NEK8 variants. Remarkably our patients present with a kidney limited phenotype as compared to the multiorgan defects found in patients with biallelic variants. This reveals a new mode of inheritance for NEK8 variants and expands genotype-phenotype correlations for this gene.
FC068: Association of PLA2R Antibody Exposure and EGFR Slope in PLA2R-Related Membranous Nephrology: Results from a Cohort of 3982 Adult Chinese Patients
Authors: Le Wei-Bo , Shi Jingsong , Hu Weixin , Zhi-Hong Liu
Published: May 2022

BACKGROUND AND AIMS

PLA2R antibody level could be used in the risk stratification for patients with Membranous Nephrology (MN). However, the association of PLA2R antibody level and glomerular filtration rate slope in PLA2R-related MN and what specific PLA2R antibody level should be used to predict the risk of disease progression remains unclear.

METHOD

A total of 11 628 patients who had at least one positive serum PLA2R antibody test (>20 RU/mL) were screened from July 2016 through June 2021 in our kidney center. The baseline was defined as the first time of PLA2R antibody test. PLA2R exposure level was defined as area under the curve of the antibodies divided by the time of follow-up. The eGFR slope for each individual was calculated using mixed-effects models. The association between PLA2R exposure level and eGFR slope was analyzed using locally weighted linear regression. The candidate cutoff level of PLA2R antibody used to predict the risk of disease progression were defined as the value corresponding to the lower quartile (25th percentile) of the eGFR slope.

RESULTS

A total of 3982 PLA2R-related MN patients were finally included in this study. The median follow-up (IQR) was 3.7 (2.7–4.6) years. The participants had a median (IQR) proteinuria exposure of 1.7 (0.94–3.4) g/24 h and a median (IQR) PLA2R antibodies exposure level of 27.7 (11.9–67.0) RU/mL during follow-up. The median eGFR slope (IQR) was –1.5 (–5.2 to –0.02) mL/min/1.73 m2 per year in the mixed model. The relationship between eGFR slope and PLA2R antibody exposure is linear in the square root scale of PLA2R antibodies, but is obvious non-linear in the linear scale and in the log scale of PLA2R antibodies. One unit increase of PLA2R antibodies exposure in square root scale is associated with a –0.61 ± 0.02 mL/min/1.73 m2 per year faster decline in eGFR (P < 0.001). The level of PLA2R antibody exposure corresponding to the lower quartile of the eGFR slope (–5.2 ml/min/1.73 m2 per year) is 8.7 RU/mL in square root scale (75 RU/mL in linear scale).

CONCLUSION

A linear relationship was observed between eGFR slope and PLA2R antibodies exposure in square root scale. It would be more helpful to report PLA2R antibodies test in square root scale than in linear scale. Our data suggest that 8.7 RU/mL in square root scale (75 RU/mL in linear scale) could be used as one of the candidate cutoff values of PLA2R antibody level to predict the risk of MN progression.
FC082: Effects of Dapagliflozin in Patients with Chronic Kidney Disease According to Background Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Dose
Authors: Lambers Heerspink Hiddo , Jong Niels , Stefansson Bergur , Chertow Glenn , Maria Langkilde Anna , Mcmurray John , Correa-Rotter Ricardo , Rossing Peter , Toto Robert , Wheeler David
Published: May 2022

BACKGROUND AND AIMS

Treatment guidelines for patients with chronic kidney disease (CKD) recommend renin–angiotensin system inhibition (RASi) with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) to reduce the risk of kidney failure. However, patients with more advanced CKD do not always tolerate RASi. The sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of kidney failure in patients with CKD in the DAPA-CKD trial. We performed a post hoc analysis of this trial to assess the efficacy of dapagliflozin by baseline dose level of ACEi or ARB.

METHOD

Participants with CKD [estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2; urinary albumin-to-creatinine ratio (UACR) 200–5000 mg/g), with or without type 2 diabetes, were randomized 1:1 to dapagliflozin 10 mg or placebo, once daily. Participants were to be treated with the recommended target dose, or a stable tolerated dose of ACEi or ARB, unless medically contraindicated, for ≥4 weeks prior to inclusion. The primary outcome was a composite of sustained ≥50% eGFR decline, end-stage kidney disease or death from a kidney or cardiovascular cause. A prespecified kidney-specific secondary outcome was the same as the primary endpoint, but without cardiovascular death. A composite cardiovascular outcome (heart failure hospitalization or cardiovascular death), and all-cause mortality were other secondary endpoints. Time-to-event analyses were performed to assess the effects of dapagliflozin versus placebo according to baseline prescription and dose of ACEi or ARB treatment.

RESULTS

Of 4296 (99.9%) participants with available data on ACEi/ARB doses, 1231 (28.7%) were using the target dose, 1867 (43.5%) a dose ≥50% to <100% of target, 1068 (24.9%) a dose 0 to <50% of target and 130 (3.0%) were not using an ACEi/ARB. In the placebo group, the event rate for the primary outcome was highest among participants not using ACEi/ARBs compared to the other subgroups (figure 1). The benefit of dapagliflozin on the primary composite outcome was consistent regardless of use or non-use of the target dose of ACEi/ARBs. This consistency was maintained for the secondary outcomes (Figure 1). Dapagliflozin compared to placebo reduced the rate of eGFR decline over the study by –0.93 [95% confidence interval (95% CI) 0.61–1.25] mL/min/1.73 m2. This effect was present regardless of the use or non-use of target doses of ACEi/ARBs (P for interaction 0.877).

CONCLUSION

Dapagliflozin was similarly efficacious in reducing major adverse kidney and cardiovascular outcomes in participants with CKD regardless of the use or dose of ACEi/ARB.
FC086: Improved Immunologic Response to COVID-19 Vaccine with Prolonged Dosing Interval in Hemodialysis Patients
Authors: Haarhaus Mathias , Duhanes Monica , Lesevic Natasa , Matei Bogdan , Ramsauer Bernd , Da Silva Rodrigues Rui , Su Jun , Haase Michael , Santos Carla , Macário Fernando
Published: May 2022

BACKGROUND AND AIMS

Vaccination against coronavirus disease 2019 (COVID-19) can reduce disease incidence and severity. Dialysis patients demonstrate a delayed immunologic response to vaccines. We determined factors affecting the immunologic response to COVID-19 vaccines in hemodialysis patients.

METHOD

All patients within a Swedish hemodialysis network, vaccinated with two doses of COVID-19 vaccine 2–8 weeks before inclusion, were eligible for this cross-sectional study. Severe adult respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein antibody levels were determined by the EliA SARS-CoV-2-Sp1 IgG test (Thermo Fisher Scientific, Phadia AB) and related to clinical and demographic parameters. Eighty-nine patients were included.

RESULTS

Patients were vaccinated with two doses of Comirnaty (BNT162b2, 73%) or Spikevax (mRNA-1273, 23.6%). Three patients received combinations of different vaccines. Response rate (antibody titres >7 U/mL) was 89.9%, while 39.3% developed high antibody titres (>204 U/mL), 47 (43–50) days after the second dose. A previous COVID-19 infection associated with higher antibody titres [median (25th–75th percentile) 1558.5 (814.5–3763.8) U/mL versus 87 (26–268) U/mL; P = 0.002], while the time between vaccine doses did not differ between groups (P = 0.7). Increasing SARS-CoV-2 antibody titres were independently associated with increasing time between vaccine doses, decreasing serum calcium levels and previous COVID-19 (Table 1).

CONCLUSION

In conclusion, a longer interval between COVID-19 mRNA vaccine doses, lower calcium and a previous COVID-19 infection were independently associated with a stronger immunologic vaccination response in hemodialysis patients. While the response rate was good, only a minority developed high antibody titres 47 (43–50) days after the second vaccine dose.
FC 106: Validation of the Optimal Torque Teno Virus Range for Risk Stratification of Graft Rejection and Infection in Kidney Transplant Recipients by TTV R-GENE®
Authors: Görzer Irene , Gelas Fanny , Haupenthal Frederik , Kulifaj Dorian , Puchhammer-Stöckl Elisabeth , Bond Gregor
Published: May 2022

BACKGROUND AND AIMS

The nonpathogenic and ubiquitous Torque Teno virus (TTV) plasma load is associated with immunosuppression in solid organ transplant recipients. An optimal TTV range has been defined for risk stratification of graft rejection and infection in the first year post kidney transplant applying an in-house PCR. Recently, a commercial PCR—the TTV R-GENE® kit—has been CE certified for clinical use. The present study was designed to validate and refine the optimal TTV range applying the TTV R-GENE® kit.

METHOD

Patients and events were selected from the prospective TTV-POET trial, including all 628 consecutive adult recipients of a kidney allograft transplanted at the Medical University of Vienna, between January 2016 and July 2020. Patients were followed for 12 months post-transplant or until drop-out. TTV was quantified longitudinally by the TTV R-GENE® kit. The primary outcome was biopsy proven graft rejection and the secondary end-point was infection.

RESULTS

A total of 78 patients with 85 graft biopsies (rejection, n = 18) and 274 patients with 80 infectious events following TTV quantification after reaching steady state in month 3 post-transplantation were selected. TTV was quantified at a median of 17 days before rejection was diagnosed and 63 days before onset of infection. The risk for rejection decreased by 25% with every log level increase in TTV load [RR 0.75, 95% confidence interval (95% CI) 0.67–0.85; < 0.001]. For TTV loads < 5log10 c/mL a high specificity of 90% for rejection was calculated. The risk for an infection increased by 6% with every log level increase of TTV load (RR 1.06, IQR 1.00–0.12;  = 0.047). For TTV loads > 7log10 c/mL a high specificity of 91% for infection was calculated. Multivariate modelling revealed an independent associated between TTV and rejection and infection, respectively.

CONCLUSION

These data support the value of TTV quantified by TTV R-GENE® for risk stratification of graft rejection and infection in the first year post kidney transplantation. The optimal TTV range defined within this study will be applied in an interventional randomized controlled trial to assess the safety of TTV-guided immunosuppression: the TTVguideIT trial.
FC 107: Development and Validation of a Machine Learning-Based Virtual Biopsy System in Kidney Transplant Patients
Authors: Yoo Daniel , Divard Gillian , Raynaud Marc , Naesens Maarten , Kamar Nassim , Bouquegneau Antoine , Oppenheimer Federico , De Sousa Erika , Kuypers Dirk , Durrbach Antoine , Seron Micas Daniel , Rabant Marion , Duong Van Huyen Jean-Paul , Bestard Oriol , Basic-Jukic Nikolina , Jurić Ivana , Legendre Christophe , Lefaucheur Carmen , Aubert Olivier , Loupy Alexandre
Published: May 2022

BACKGROUND AND AIMS

Graphical Abstract

In kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate lesions inherited from the donor or acquired after transplantation. However, many centres worldwide do not perform those biopsies which remain invasive, costly and may delay the transplant procedure. We aimed to develop and validate a noninvasive virtual biopsy system.

METHOD

A total of 17 centres were included from Europe, North America and Australia from 2000 to 2019. Candidate predictors were assessed following a prespecified protocol. Outcome measures were the day-zero biopsy lesions (Banff classification) including CV, AH, IFTA scores and % of sclerotic glomeruli. Six machine learning models were developed and their performances were assessed.

RESULTS

A total of 12 992 day-zero biopsies were included. Eleven parameters were used to build the classifiers, including donor age, kidney function, hypertension, BMI, proteinuria, diabetes, sex, donor type, cause of death and Hep-C status. The ensemble models (random forests, neural networks, gradient boosting, extreme gradient boosting tree, linear discriminant analysis, and naive Bayes) showed multi-AUC of 0.738, 0.817 and 0.788 for prediction of CV, AH and IFTA scores, and a good performance for predicting glomerulosclerosis (mean absolute error, MAE = 4.766). We confirmed the robustness and generalizability in multiple clinical scenarios and subpopulations and built an online interface for clinicians: https://transplant-pred/Virtual_Biopsy.

CONCLUSION

We developed and validated the first virtual biopsy system that enables the prediction of day-zero biopsy, based on routinely collected parameters. This can assist clinicians in assessing allograft quality, discrimination of donor derived versus acquired lesions after transplantation and prevent overdiagnosis of calcineurin inhibitor (CNI) toxicity.
FC 113: Development and Validation of an Integrative DD-CFDNA System to Predict Allograft Rejection: A Population Based Study
Authors: Aubert Olivier , Brousse Romain , Gueguen Juliette , Ursule-Dufait Cindy , Yoo Daniel , Anglicheau Dany , Lefaucheur Carmen , Loupy Alexandre
Published: May 2022

BACKGROUND AND AIMS

Post-transplantation patient care requires development and validation of noninvasive biomarkers to improve allograft monitoring and prevention from unnecessary biopsies. Preliminary reports have suggested the association of donor derived cell-free DNA (dd-cfDNA) with allograft rejection. However, there is no proof of its added value beyond standard of care patient management in large and deep phenotyped cohorts.

METHOD

A total of 1210 concomitant evaluations of allograft histology, anti-HLA DSA and functional parameters between 2013 and 2018 were included corresponding to 637 evaluations in the derivation cohort and 573 in the validation cohort. dd-cfDNA was measured in plasma at the time of the evaluation. Diagnoses were assessed using Banff 2019 criteria. Parameters associated with kidney allograft rejection were assessed using uni- and multivariable logistic regression. We developed a risk model using the variables that were independently associated with rejection.

RESULTS

Higher levels of dd-cfDNA were observed for AMR and TCMR or both compared to other diagnoses (Figure 1A). We found incremental dd-cfDNA levels with increasing Banff lesion scores for g, ptc, i, t, cg and C4d (Figure 1B). There was no association of dd-cfDNA levels with allograft inactive lesions. In multivariable analysis, dd-cfDNA (P < 0.0001) was associated with kidney allograft rejection independently of DSA (P < 0.0001), eGFR (P = 0.018), kidney allograft instability (P = 0.013) and previous rejection (P < 0.0001). Based on these parameters, we built an integrative idd-cfDNA model that showed good discrimination (AUC: 0.83), good calibration and added value beyond a model without dd-cfDNA (AUC of the model without dd-cfDNA: 0.77 versus 0.83 for the integrative model; P < 0.0001). We confirmed our results in the validation cohort with a good discrimination (AUC: 0.82) and a good calibration. This integrative score, including the dd-cfDNA, is being validated in Belgium and in the USA.

CONCLUSION

We demonstrate the independent and added value of dd-cfDNA in addition to conventional features to predict rejection. This first integrative system shows improved performance for patient monitoring and could help physicians in decision-making process.
FC 116: SGLT2 Inhibitors in Kidney Transplantation: A Multicenter Study
Authors: García Carro Clara , Bedia Raba Andrea , Banegas Deras Eduardo J , Alberto Vigara Luis , Valero San Cecilio Rosalía , Cruzado Vega Leónidas , Gavela Eva , Elena González García M , Pérez-Flores Isabel , Sanchez-Bielsa Francisco
Published: May 2022

BACKGROUND AND AIMS

SGLT2 inhibitors (SGLT2i) are the first-line therapy in patients with type 2 diabetes mellitus (DM2) and CKD, together with metformin according to most recent published guidelines. They are related to better renal and cardiovascular outcomes. SGLT2i could be potentially benefitial in terms of renal function preservation and cardiovascular outcomes in kidney transplantion (KT). Despite published data about SGLT2i in KT patients with DM2 or new-onset diabetes after transplantation are limited, their use seems to be common in everyday clinical practice. Our aim is to investigate if SGLT2i are safe and well tolerated in a cohort of KT recipients, as well as to analyze clinical and laboratory data at 6 months after SGLT2i initiation.

METHOD

Multicentre observational study in KT recipients with diabetes under SGLT2i treatment.

RESULTS

A total of 323 patients were included, and 284 completed a 6-month follow-up. Mean age was 61.2 ± 10.3 years old, 74.4% were men and 41% presented DM2. Previous antidiabetic therapies: insulin (48.1%), DPP4 inhibitors (36.1%) and metformin (33.1%). Empagliflozine was started in 55.8%, dapagliflozine in 23.2% and canagliflozin in 20.6%. After SGLT2i initiation, body weight reduction, an improvement in blood pressure and glycaemic control, higher haemoglobin levels and a decrease in cholesterol levels were observed. Also, a mild decrease in eGFR was detected while albuminuria was lower. These differences were statistically significant (Table 1). In 34 patients (10.5%), SGLT2i was stopped: 2.78% presented urinary tract infection (UTI), 1.5% balanitis and 1.2% important eGFR decreasing slope. During the study period, six patients presented a graft loss (one related to SLGT2) and six patients died (deaths not related to SGLT2i).

CONCLUSION

SGLT2i have a safe security profile in KT, and are related to a better glycaemic and blood pressure control, as well as to a decrease in albuminuria, and to an improvement in cardiovascular risk factors. Thus, SGLT2i should be prescribed in KT recipients with DM2 or NODAT with adequate eGFR. UTI surveillance is essential in these patients.
FC 129: Stopping versus Continuing Renin–Angiotensin System Inhibitors After Acute Kidney Injury and Adverse Clinical Outcomes: An Observational Study From Routine Care Data
Authors: Janse Roemer , Fu Edouard , Clase Catherine M , Tomlinson Laurie , Lindholm Bengt , Van Diepen Merel , Dekker Friedo W , Jesus Carrero Juan
Published: May 2022

BACKGROUND AND AIMS

The risk–benefit ratio of continuing with renin–angiotensin system inhibitors (RASi) after an episode of acute kidney injury (AKI) is unclear. While stopping RASi may prevent recurrent AKI or hyperkalaemia, it may deprive patients of the cardiovascular benefits of using RASi.

METHOD

We analysed outcomes of long-term RASi users experiencing AKI (stage 2 or 3, or clinically coded) during hospitalization in Stockholm, Sweden, during 2007–2018. We compared stopping RASi within 3 months after discharge with continuing. The primary study outcome was the composite of all-cause mortality, myocardial infarction and stroke. Recurrent AKI was our secondary outcome, and we considered hyperkalaemia as a positive control outcome. Propensity score overlap weighted Cox models were used to estimate hazard ratios, balancing 75 confounders. Weighted absolute risk differences (ARD) were also determined.

RESULTS

We included 10 165 individuals, of whom 4429 stopped and 5736 continued RASi, with a median follow-up of 2.3 years. Median age was 78 years, 45% were women, and median kidney function before the index episode of AKI was 55 mL/min/1.73 m2. After weighting, those who stopped had an increased risk [HR, 95% confidence interval (95% CI)] of the composite of death, myocardial infarction and stroke (1.13, 1.07–1.19; ARD 3.7, 95% CI 2.6–4.8) compared with those who continued, a similar risk of recurrent AKI (0.94, 0.84–1.05), and a decreased risk of hyperkalaemia (0.79, 0.71–0.88).

CONCLUSION

Stopping RASi use among survivors of moderate-to-severe AKI was associated with a similar risk of recurrent AKI, but higher risk of the composite of death, myocardial infarction and stroke.
MO087: Ambulatory Blood Pressure Trajectories and Blood Pressure Variability in Kidney Transplant Recipients: A Comparative Study Against Hemodialysis Patients
Authors: Korogiannou Maria , Sarafidis Pantelis , Eleni Alexandrou Maria , Theodorakopoulou Marieta , Pella Eva , Efstathios Xagas , Argyris Antonis , Protogerou Athanase , Papagianni Aikaterini , Boletis Ioannis , Marinaki Smaragdi
Published: May 2022

BACKGROUND AND AIMS

Hypertension is the most prevalent cardiovascular risk factor in kidney transplant recipients (KTRs). Preliminary data suggest similar ambulatory blood pressure (ΒP) levels in KTRs and hemodialysis (HD) patients. This is the first study evaluating in comparison the full ambulatory BP profile and short-term BP variability (BPV) in KTRs versus HD patients.

METHOD

Two hundred four KTRs were matched (2:1 ratio) with 102 HD patients for age and gender. BP levels, BP trajectories and BPV indices over a 24-h ambulatory BP monitoring (ABPM) in KTRs were compared against both the first and second 24-h period of a standard 48-h ABPM in HD. To evaluate the effect of renal replacement treatment and time on ambulatory BP levels, two-way-ANOVA for repeated-measurements was performed.

RESULTS

KTRs had significantly lower SBP and pulse-pressure (PP) levels compared with HD during all periods studied (24-h SBP: KTR: 126.5 ± 12.1 mmHg; HD first 24-h: 132.0 ± 18.1 mmHg, P = 0.006; second 24-h: 134.3 ± 17.7 mmHg, P < 0.001); no significant differences were noted for DBP levels with the exception of second nighttime. Repeated-measurements-ANOVA showed a significant effect of RRT modality and time on ambulatory SBP levels during all periods studied, and a significant interaction between-them; the greatest between-group difference in BP (KTRs—HD in mmHg) was observed at the end of the second 24-h (−13.9 mmHg, 95%CI: −21.5 to −6.2, P < 0.001). Ambulatory systolic and diastolic BPV indices were significantly lower in KTRs than in HD during all periods studied (24-h SBP-ARV: KTRs: 9.6 ± 2.3 mmHg; HD first 24-h: 10.3 ± 3.0 mmHg, P = 0.032; second 24-h: 11.5 ± 3.0 mmHg, P < 0.001). No differences were noted in dipping pattern between the two groups.

CONCLUSION

SBP and PP levels and trajectories, and BPV were significantly lower in KTRs compared to age- and gender-matched HD patients during all periods studied. These findings suggest a more favorable ambulatory BP profile in KTRs, in contrast with previous observations.
MO090: Diagnostic Performance of Pre-Dialysis And Ambulatory Blood Pressure Levels in Men and Women Hemodialysis Patients
Authors: Karagiannidis Artemios , Theodorakopoulou Marieta , Eleni Alexandrou Maria , Faitatzidou Danai , Baksiova Afroditi , Giamalis Panagiotis , Papagianni Aikaterini , Sarafidis Pantelis
Published: May 2022

BACKGROUND AND AIMS

Ambulatory blood pressure (BP) control is worse in men than in women with chronic kidney disease or kidney transplantation. So far no study assessed in parallel possible effects of sex differences on the prevalence, control and BP phenotypes according to pre-dialysis and 48-h ABPM in hemodialysis patients. Further, no study has evaluated the diagnostic accuracy of pre-dialysis BP levels in men and women hemodialysis patients.

METHOD

129 male and 91 female hemodialysis patients that underwent 48-h ABPM with Mobil-O-Graph-NG were included in this analysis. Hypertension was defined as follows: (1) pre-dialysis BP ≥ 140/90 mmHg or use of antihypertensive agents, (2) 48-h BP ≥ 130/80 mmHg or use of antihypertensive agents.

RESULTS

The prevalence of hypertension was not different between men and women with the use of pre-dialysis BP (92.2% versus 92.3%, P = 0.987, respectively) or 48-h ABPM (92.2% versus 89%, P = 0.411). With the use of pre-dialysis BP men had significantly lower control rates than women (18.5% versus 32.1%, P = 0.025); a similar pattern of worse control in men was apparent with the use of ABPM, but the difference was not statistically significant (22.7% versus 28.4%, P = 0.360). The rate of patients with concordant lack of control by pre-dialysis and ABPM readings was significantly higher in men than women (65.3% versus 49.4%, P = 0.023); white-coat (14.9% versus 17.6%, P = 0.593) and masked hypertension (10.7% versus 18.8%, P = 0.101) did not differ between groups. However, the misclassifation rate with the use of pre-dialysis BP was lower in men than women. There was moderate or at best fair agreement between pre-dialysis and ambulatory BP with regards to the prevalence (men: κ-statistics = 0.39, P < 0.001 and women: 0.27, P = 0.011) and control rates (κ-statistics = 0.25, P = 0.005 and 0.17, P = 0.124, respectively). Pre-dialysis BP ≥ 140/90 mmHg had sensitivity/specificity of 85.9%/51.4% in men and 72.4%/54.5% in women for the diagnosis of 48-h BP ≥ 130/80 mmHg. Receiver-operating-curve analyses confirmed this poor diagnostic performance.

CONCLUSION

The prevalence of hypertension is similar between men and women hemodialysis patients, but men have worse rates of office BP control. The diagnostic accuracy of pre-dialysis BP levels was equally poor in men and women hemodialysis patients.
MO094: Intensive Blood Pressure Lowering and Myocardial Fibrosis Biomarkers in Individuals With and Without CKD: Results From the Systolic Blood Pressure Intervention Trial (Sprint)
Authors: Aparna Fnu , Pajewski Nicholas , Kitzman Dalane , Upadhya Bharathi , Killeen Anthony , Rajagopalan Sanjay , Wright Jackson , Rahman Mahboob , Dobre Mirela
Published: May 2022

BACKGROUND AND AIMS

Circulating cardiac biomarkers implicated in the pathogenesis of heart disease may provide a non-invasive, more precise assessment of cardiovascular risk. In the Systolic Blood Pressure Intervention Trial (SPRINT), intensive blood pressure lowering was associated with a 25% reduction in cardiovascular events and a 27% reduction in all-cause mortality. We sought to assess whether the beneficial effect of lowering systolic blood pressure on clinical outcomes was accompanied by a reduction in serum biomarkers of myocardial fibrosis.

METHOD

SPRINT, a multicenter randomized controlled trial conducted in the United States, enrolled participants aged ≥ 50 years, at increased risk for cardiovascular disease and randomized them to intensive systolic blood pressure lowering (target < 120 mmHg) or standard blood pressure lowering (target < 140 mmHg). In a randomly selected subgroup of SPRINT participants, myocardial fibrosis was assessed by two collagen-derived serum peptides, C-terminal propeptide of procollagen type I (CICP) and N-terminal propeptide of procollagen type 3 (P3NP) and Galectin 3 measured at study baseline and at 24 months follow-up. Chronic kidney disease was defined as eGFR < 60 mL/min/1.73 m2. Analyses were based on linear mixed models including clinic site as a random effect, with adjustments for treatment group and baseline level of each respective biomarker.

RESULTS

A total of 742 SPRINT participants with and without CKD with available measurements of myocardial fibrosis biomarkers at study baseline and 24 months were included in the study. The median (IQR) Galectin 3, CICP and P3NP levels at study baseline and 24 months follow-up in the intensive versus standard group are presented in the Table 1. Intensive blood pressure lowering was not associated with longitudinal changes in CICP or P3NP (Table 1 and Figure 1). Intensive blood pressure lowering was associated with a statistically significant increase in Galectin 3 level [between group mean difference 0.47 (IQR: 0.03–0.92) ng/mL, P = 0.04]. All of the findings were generally consistent across participants with and without CKD (Table 1).

CONCLUSION

In a random sample of SPRINT participants, intensive versus standard blood pressure lowering was not associated with a reduction in circulating myocardial fibrosis biomarkers overtime in hypertensive individuals with and without CKD.