bluuebunny/crossref_metadata_2025 huggingface dataset:
MO106: Circulating Neutrophil Count is Associated with Severity of Chronic Kidney Disease
Authors: Carrara Fabiola , Ruggenenti Piero , Parvanova Aneliya , Trillini Matias , Cugini Daniela , Stucchi Nadia , Ferrari Silvia , Remuzzi Giuseppe
Published: May 2022

BACKGROUND AND AIMS

Neutrophils (Ns) play a key role in inflammation and tissue injury, in particular in acute renal failure, by releasing a complex of cytotoxic products such as reactive oxygen intermediates, enzymes and microbicidal polypeptides. These effects are prevented or mitigated by Ns depletion [1, 2]. Here we investigated the relationships between Ns count and the severity of kidney dysfunction in patients with chronic kidney disease (CKD).

METHOD

In this cross-sectional study we evaluated the association between circulating Ns absolute number, CKD stage and measured glomerular filtration rate (mGFR) in 393 patients with renal disease from different causes. CKD stage was established on the basis of mGFR and K/DOQI guidelines [3]. The relationships of Ns count and other considered covariates with mGFR were evaluated by uni- and multi-variable linear regression models (Table 1). Variables considered in univariable models are listed in Table 1. Variables included in multivariable models were identified with forward selection. Circulating Ns were measured by Coulter LH 780 Hematology Analyzer (Beckman Coulter, Milan, Italy). The GFR was measured by the iohexol plasma clearance technique, a gold standard for direct GFR measurement [4]. P < .05 was considered as statistically significant.

RESULTS

The mean ± SD age and mGFR of the patients were 54.64 ± 13.75 years and 62.75 ± 22.52 mL/min/1.73 m2 (range: 15.53–131.79 mL/min/1.73 m2), respectively. Most patients had a kidney function in stage 2 and 3a (Figure 1A). The absolute number of Ns averaged 4.32 ± 1.77 × 103µL−1. Ns counts increased progressively in parallel with increasing CKD stage (P < .005, Figure 1A) and were negatively correlated with mGFR (P < .001, Figure 1B). At multivariable analysis, mGFR was associated negatively with Ns count and positively with basophils (Bs) count (Table 1).

CONCLUSION

In patients with CKD higher numbers of Ns and lower numbers of Bs, even within the normal range, were independently associated with more severe renal insufficiency. A major limitation of the study is the cross-sectional design that does not allow to establish a causal relationship between Ns count and severity of kidney dysfunction. These data provide the basis for studies to investigate mechanisms explaining these associations.
MO115: Cardiorenal Units as Management Strategy to Improve Outcomes in Cardiorenal Syndrome
Authors: Marques Maria , Cobo Marta , García Magallón Belen , Luisa Serrano Salazar Maria , Vazquez Lopez-Ibor Jorge , Lopez Paula , Janeiro Dario , Portoles Jose M
Published: May 2022

BACKGROUND AND AIMS

Cardiorenal syndrome (CRS), defined as the spectrum of disorders that acutely or chronically affect both heart and kidney function, is often a challenging condition with paucity of evidence-based therapy. The increasing burden of this entity has prompted the creation of cardiorenal units (CRU) as integrating programs intended to provide a combined multidisciplinary approach to maximize all chances for organ and patient recovery. Here we describe the early results of the creation of one CRU in a high complexity university hospital.

METHOD

This observational study included all patients diagnosed with CRS, who have been seen in the cardiorenal day care unit, formed by specific trained nephrologist, cardiologist and nurses. Assessment of cardiorenal function and volume status was performed by conventional cardiac ultrasound plus V-Scan, GFR estimation by CKD EPI, NT-proBNP determination and bioelectrical impedance when indicated.

RESULTS

Cardiorenal Unit of Puerta de Hierro University Hospital was created in January 2021. A total of 68 patients have been evaluated with a mean follow-up of 4 months (SD 3.2). Most frequent cardiologic diagnoses were 63.9% heart fellow with reduced function (HFrF) and 37.1% heart failure with preserved ejection fraction (HFpEF) and the presence on pulmonary hypertension or tricuspid regurgitation were 29.4% and 50.9%. 51.6% patients showed diuretic resistance.

Most frequent renal diagnosis were pure CRS 36.9%, and 27.7% and 24.6% CRS associated to diabetic kidney disease or nephroangioesclerosis, respectively. Mean FGe rate when patients were initially evaluated was 31.5 mL/min/1.73 m2 (SD 11.0) with demonstration of albuminuria in 48.5% of patients.

The integrated cardiorenal management of these patients included initiation or adjustment of specific cardio-nephroprotective drugs [SGLT2 inhibitors (46.8%), ARNi (25.8%), aldosterone receptor antagonists (4.8%)] or diuretic regime adjustment including iv administration (54.8%). Peritoneal dialysis was indicated in three patients and haemodialysis in one patient. Approximately 13.2% patients suffer new episodes of heart failure that needed hospitalization or unexpected medical attention at the day-care clinic. One patient died during follow-up (1.5%).

CONCLUSION

We conclude that this coordinated cardionephro approach of CRS was useful to optimize drug therapy aimed to mid-long term goals of cardionephro protection and to implement advanced therapies for fluid management in patients with diuretic resistance.
MO134: Follow-Up of Patients with Vasculitis: A 10-year retrospective study
Authors: Kozikopoulou Dimitra , Oikonomaki Theodora , Paikopoulou Angeliki , Choulitoudi Vasiliki , Nikolaos Liatsos Alexandros , Christodoulidou Christallenia
Published: May 2022

BACKGROUND AND AIMS

Vasculitis constitutes a systemic disease with renal involvement at almost 100% in microscopic polyangiitis, 70–80% in granulomatosis with polyangitiis, 25% in eosinophilic granulomatosis with polyangitiis and 40–50% appears as renal limited vasculitis. In order to describe our experience, we conducted a retrospective study of patients with vasculitis which we have been monitoring for the last 10 years.

METHOD

We studied the time of the remission, the use of plasma exchange (PLEX), the biopsy results as well as the time between the first symptoms and the initiation of the therapy.

RESULTS

The total number of patients was 59, 28 (47.5%) females, with a mean age of 66.08 ± 13.95 years. The median follow-up time was 70 weeks with IQR [64, 76]. The patients with positive pANCA/MPO were 38 (64.4%), while those with positive cANCA/PR3 were 10 (16.9%). The remaining nine patients (15.3%) suffered from ANCA negative vasculitis. The mean value of the initial creatinine was 4.53 ± 2.3 mg/dL and the median value of the eGFR CKD-EPI was 11 mL/min/1.73 m2, IQR [7, 17]. The PLEX was implemented auxiliary in 16 patients (27.1%) and in 32 patients (54.2%) pulse cortisone along with intravenous cyclophosphamide was preferred. The remission was accomplished in 32 patients (54.2%) with median time of 8 weeks, IQR [0, 17]. At least one relapse episode was noted in 8 patients (13.6%), 19 patients (32.2%) ended up in ESRD and 15 patients (25.4%) deceased during the follow-up time. The major cause of death was sepsis with 10 demises (66.7%), while 5 patients (8.4%) suffered from malignancies in general. The remission time was found to be dependent on the initial value of creatinine (P-value.023). There was no statistical significance regarding the findings of the biopsy and the outcome, the relapse rate or the remission time. There was also no correlation marked between the first symptoms and the initiation of the therapy. The plasma exchange failed to reduce the time until the remission, unless the patient was cANCA positive (P-value.036). Although the sample was limited, the patients with positive cANCA/PR3 submitted to PLEX were able to achieve the remission in 5.25 weeks contrary to those who received solely methylprednisolone and cyclophosmamide. The latter achieved remission in 21 (mean) weeks (LogRank test, P-vaue .001. The vasculitis type has no effect over the renal outcome or the relapse rate. No statistical significance was found between the PLEX and the relapse rate or the outcome. Patients do not benefit from auxiliary treatment with the PLEX, unless they have positive cANCA/PR3. However, the initial serum creatinine seems to affect the time of the remission.

CONCLUSION

There is indisputable need for a larger patient sample in order to safely conduct further results.
MO149: Effect of Plasma Exchange on COVID-19 Associated Excess of Von Willebrand Factor and Inflammation in Critically Ill Patients
Authors: Seibert Felix S , Blazquez-Navarro Arturo , Hölzer Bodo , Doevelaar Adrian , Nusshag Christian , Merle Uta , Morath Christian , Zgoura Panagiota , Dittmer Rita , Schneppenheim Sonja , Babel Nina , Budde Ulrich , Henning Westhoff Timm
Published: May 2022

BACKGROUND AND AIMS

Ubiquitous microthromboses in the pulmonary vasculature play a crucial role in the pathogenesis of COVID-19 associated acute respiratory distress syndrome (ARDS). Excess of von Willebrand factor (vWf) with intravascular multimer formation was identified as a key driver of this finding. Plasma exchange (PLEX) might be a therapeutic option to restore the disbalance between vWf and ADAMTS13. We report the effects of PLEX on vWf, ADAMTS13, inflammatory cytokines and parameters of ventilation.

METHOD

We investigated 25 patients, who were on mechanical ventilation for COVID-19 pneumonia with ARDS at two German university hospitals. All patients received PLEX as an ultima ratio measure for refractory ARDS. VWf antigen (vWf: Ag), ADAMTS13 activity, a cytokine panel mirroring the inflammatory situation and clinical parameters were assessed before and after three to six PLEX therapies with fresh frozen plasma.

RESULTS

Before the PLEX sequence, there was an excessive release of vWf: Ag (425.4 ± 167.5%) and mildly reduced ADAMTS13 activity (49.7 ± 23.3%). After the PLEX series, there was a significant increase of ADAMTS13 activity to 62.4 ± 17.7% (P = .029) and a significant decrease of vWf: Ag to 336.1 ± 138.2% (P = .041) resulting in a 63% improvement of the ADAMT13/vWf: Ag ratio from 14.5 ± 10.0 to 23.7 ± 14.6  (P = .024). Comparison of parameters before and after individual PLEX sessions (n = 35) revealed a mean reduction of vWf from 387.8 ± 165.1% to 213.2 ± 62.3% (P = .001) and an increase of ADAMTS13 activity from 60.4 ± 20.1% to 70.5 ± 14.0% (P = .001). Parallelly, monocyte chemotactic protein-1 and interleukin-18 decreased significantly (P = .034 each). Along the PLEX sequence lactate dehydrogenase (P = .001), C-reactive protein (P = .001), and positive end expiratory pressure (P = .01) significantly decreased accompanied by an improvement of Horovitz index (P = .001).

CONCLUSION

PLEX restores the disbalance between ADAMTS13 and vWf: Ag, a driver of immunothrombosis. Moreover, it reduces the inflammatory state and is associated with a benefit of ventilation parameters. These findings render a further rationale to regard PLEX as a therapeutic option in severe COVID-19.
MO150: Serum Angiopoietin-Like Protein 3 Level is Negatively Associated with Vascular Reactivity Index by Digital Thermal Monitoring in Chronic Haemodialysis Patients
Authors: Wu Tzu-Chiang , Huang Hsiang-Jung , Lin Wei-Chen , Kuo Ch , Hsu Bang-Gee
Published: May 2022

BACKGROUND AND AIMS

Angiopoietin-like protein 3 (ANGPTL3) plays important roles in lipid and lipoprotein trafficking and metabolism and has demonstrated a positive correlation with cardiovascular risk assessment parameters of carotid and femoral artery intima-media thickness. We evaluated the association between serum ANGPTL3 levels and endothelial function in chronic haemodialysis (HD) patients.

METHOD

Blood samples were obtained from 116 chronic HD patients. We measured the endothelial function—represented by the vascular reactivity index (VRI)—via non-invasive digital thermal monitoring, and serum ANGPTL3 concentrations by using commercial enzyme-linked immunosorbent assay.

RESULTS

A total of 17 (14.7%), 50 (43.1%) and 49 (42.2%) patients had poor (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0) and good (VRI ≥ 2.0) vascular reactivity. As the VRI decreased, the serum alkaline phosphatase (ALP, P = .025) and ANGPTL3 (P < .001) levels significantly increased. Serum log-transformed ALP (log-ALP, r = –0.187, P = .045) and log-ANGPTL3 (r = –0.319, P < .001) were negatively associated with VRI values by univariate linear regression analysis. After applying multivariate stepwise linear regression analysis adjustment, the significantly negative association of log-ANGPTL3 (standardized β = –0.319, adjusted R2 change = 0.094; P < .001) with VRI values in chronic HD patients remained.

CONCLUSION

Our study results indicated that ANGPTL3 concentration was negatively associated with VRI values and modulated endothelial function in chronic HD patients.
MO167: SAFETY OF SGLT2 INHIBITORS (SGLT2I) IN PEOPLE OVER 75 YEARS
Authors: Vidas Maria Marques , Domenech Ester , Testillano Lucía Martin , Maroto Alba , Lopez Paula , Portoles Jose' M
Published: May 2022

BACKGROUND AND AIMS

The use of iSGLT2 in people over 75 years was initially associated with a higher rate of adverse effects (AEs). Subsequent clinical trials have consistently demonstrated no increase of serious adverse effects in this group of patients, but the incidence of minor adverse events remains to be analysed in this group of patients

The objective of this study is to evaluate in real life the incidence of adverse effects attributable to this family of drugs in patients aged 75 years (75+) or more at the beginning of treatment with iSGLT2 taking as reference population patients aged less than 75 years (<75). The incidence of cardiovascular events and death was also analysed.

METHOD

Observational study, one-centre. We selected all the patients undergoing iSGLT2 treatment at our centre since 2015 till 2021, grouping them according to their age at the start (75 + versus <75 years).

RESULTS

A total of 153 patients started treatment with iSGLT2 in our centre, 33 (21.6%) were 75 or older. Follow-up time was 19.0 months, interquartile range [8.9–30.3]. Mean age 67.3 years (SD 10.5), m: f ratio was 3:1 and type of SGLT2i was dapagliflozin 49%, canagliflozin 29% and empagliflozin 22%.

A total of 28 patients (18.3%) had some side effect of the drug, without significant differences between + 75 and <75. The most frequent AEs in both groups were genitourinary (GU) infections (10.3%) and falls (9.2%), Eight patients discontinued treatment (five due to any AEs) with similar distribution in both groups. GU tract infections were more frequent in the first year of treatment treatment (100% during first year in 75+ and 46.7% in <75 years).  We did not found any difference in older patients in the rate of CV events or death (Log rank 0.6)

CONCLUSION

Side effects of iSGLT2 were uncommon in our population, and age above 75 years was not associated with a higher incidence of AEs. GU tract infections, which were the most prevalent AE, were more frequent in the first year of treatment indicating the need of a more careful monitoring in this period of time.
MO175: Association between Thrombotic Microangiopathy, ADAMTS13 Activity and Development of AKI, ARDS, AND Poor Outcomes in COVID-19 Patients (Pilot Study)
Authors: Vorobyev Eugene , Vorobyeva Snezhana , Galkina Olga , Zubina Irina , Bogdanova Evdokia , Levykina Elena , Kulikov Aleksander
Published: May 2022

BACKGROUND AND AIMS

Cases of microangiopathy associated with COVID-19 are not fully understood. We aimed to clarify in these patients the presence of thrombotic microangiopathy (TMA) and decreased ADAMTS13 activity, the possible influence of these factors on kidney and lung damage, and outcomes.

METHOD

The study involved 90 patients with COVID-19 and viral pneumonia, who were treated at the Pavlov First St. Petersburg State Medical University. Patients undergoing plasma transfusion were excluded. In addition to the standard examination, activity of ADAMTS13 was determined in admission (ELISA, normal range 30–160%).

RESULTS

Median level ADAMTS13 was 92%, IQR 27.9%. The presence of TMA took place in 26.7% of patients, in 41.5% patients with TMA the level of activity of ADAMTS13 was less than 60%. In patients with respiratory failure, the ADAMTS13 level was significantly lower–78.4%, IQR 32.1% versus 108.6%, IQR 26.7%. In patients with respiratory failure (P < .01),  the incidence of TMA was significantly higher–34.2% versus 19.3%, respectively (P < .01). The ADAMTS13 level neg. correlated with the risk of developing TMA (ρ = –0.486, P < .01),  AKI of any stage (KDIGO2012 criteria) (ρ = –0.288, P < .01),  acute respiratory distress syndrome (ARDS, ‘Berlin definition’) (ρ = –0.304, P < .01),  the duration of hospitalization (ρ = –0.342, P < .01) and the probability of death (ρ =–0.278, P < .01). In the case of five patients, an extremely low level of ADAMTS13 (less than 30%) was noted, which in all cases was accompanied by laboratory signs of TMA and the development of ARDS; two patients had a fatal outcome.

CONCLUSION

TMA and low ADAMTS13 activity are associated with progression to severe COVID-19 disease and development of AKI. Some of the cases of TMA in these patients may be due to low ADAMTS13 activity. Further research is needed to assess the potency of treating these patients with TMA associated with low ADAMTS activity.
MO223: Contribution of Interstitial CD138 + Plasma Cells on the Renal Outcome in Patients with Anca-Associated Vasculitis
Authors: Odler Balazs , Haefner Johannes M , Pollheimer Marion J , Schabhuettl Corinna , Krall Marcell , Rosenkranz Alexander , Eller Kathrin
Published: May 2022

BACKGROUND AND AIMS

Plasma cells (PC) are the most differentiated antibody and cytokine-producing B lineage cells and are thought to contribute to the perpetuation of inflammation in patients with ANCA-associated vasculitis (AAV). Agents targeting PCs are of interest in AAV, however, little is known about the role of interstitial CD138 + PCs in these patients. In this study, we aim to demonstrate the impact of this cell population in the prediction of renal outcomes in patients with AAV.

METHOD

Forty AAV patients with glomerulonephritis, diagnosed between 2014 and 2018 at the Division of Nephrology of the Medical University of Graz were included and followed for 36 months. Histological assessments using the kidney allograft Banff classification were performed to describe the tubulointerstitial (TI) damages. Immunohistochemistry analysis was performed in 29 patients to assess the renal interstitial CD138 + cell expression. More than ten CD138 + cells per high power field were stated as high expression (excluding CD138 staining of renal tubular epithelial cells). Changes in kidney function, the incidence of renal relapses (RR), and end-stage renal disease (ESRD) were analyzed.

RESULTS

In the kidney biopsies, N = 21 (72%) patients had a high expression of CD138 + plasma cells. No significant difference was observed in PR3 and MPO serotypes in the group of patients with high CD138 + cell expression (43% versus 57%, P = .793). In addition, no significant difference was seen in the changes in kidney function and the incidence of RR or ESRD between the groups with high and low expression of CD138 + cells during the follow-up period. However, patients with more severe TI damage had more severe proteinuria {urinary albumin/creatinine ratio: 51 [interquartile range (IQR) 42–123] versus 360 (IQR 202–1112) mg/g Creatinine; P = .016} at 3-year follow-up, and tended to have a higher rate of RR and ESRD [i0/i1: N = 2/18 (11%) versus i2/i3: N = 6/22 (27%), P = .258 and i0/i1: N = 2/18 (11%) versus i2/i3: N = 6/22 (27%), P = .258, respectively].

CONCLUSION

Our data indicate a significant proportion of CD138 + PCs in kidney specimens of patients with AAV. Despite the lack of association between this cell population and our cohort’s renal outcome, these results provide additional insights on the renal B-cell clusters in patients with AAV. In addition, our findings go along with already existing data on the association between extended TI damage and worse renal outcome.
MO228: Clinical Features and Obesity Impact on Chronic Kidney Disease Progression in Patients with Glomerular Diseases
Authors: Jordanova Elena , Jankovic Radmila , Pantic Igor , Celic Dejan , Ljubicic Bojana , Simic-Ogrizovic Sanja , Jovanovic-Basta Gordana
Published: May 2022

BACKGROUND AND AIMS

The kidney disease secondary to obesity is obesity-related glomerulopathy characterized by the following: glomerulomegalia, progressive glomerulosclerosis, proteinuria and progression of renal failure. The aims of the present study were to evaluate the clinical features and 2 years outcome in obese and non-obese patients with glomerular diseases.

METHOD

This study included 125 patients with renal biopsy-proven glomerular diseases: minimal change disease, FSGS, IgA nephropathy, membranous glomerulonephritis, membranoproliferative glomerulonephritis (mean age 46.93 ± 15.10 years). There were 63 obese (BMI ≥ 27 kg/m2) and 62 non-obese (BMI <27 kg/m2) patients. The serum concentration of protein, albumin, cholesterol, trygliceride, creatinine and daily proteinuria were measured at the time of kidney biopsy, 6, 12 and 24 months after the biopsy. The estimated glomerular filtration rate (eGFR) was calculated according to the equations: Cockcroft–Gault#(Cockcroft–Gault–BMI < 27 kg/m2 Cockcroft–GaultLBW-BMI ≥27kg/m2) and Chronic Kidney Disease Epidemiology Collaboration Equation (CKD–EPI).

RESULTS

At the time of kidney biopsy, the obese had significantly lower eGFR calculated by formulas: Cockcroft–Gault# (62.29 ± 27.53 versus 96.30 ± 38.80 mL/min) and CKD–EPI (71.52 ± 31.15 versus 86.36 ± 27.63 mL/min/1.73 m2), significantly higher daily proteinuria (6.11 ± 4.94 versus 4.47 ± 4.95 g/day), creatinine (122.14 ± 87.56 versus 93.66 ± 41.40 μmol/L), trygliceride (2.76 ± 1.39 versus 2.20 ± 1.30 mmol/L) in comparison with non-obese. There was statistically significant difference in eGFR calculated by Cockcroft-Gault# 6 months (t = 5.353, P < .01), 12 (t = 5.234, P < .01) and 24 months (t = 2.329, P < .05) after the kidney biopsy between obese and non-obese. The reduction in eGFR Cockcroft–Gault# after 24 months compared with baseline in obese was 14.7%, in non-obese 13.7% (P > 0.05). After 12 months follow-up significantly higher percentage of non-obese patients reached complete remission (59.4% versus 35.3%) compared with obese (χ2 = 4.548), but after 24 months there were no significant difference.

CONCLUSION

Obese patients at the time of kidney biopsy, 6, 12 and 24 months later had the significant lower eGFR compared to non-obese. After 24 months follow-up there was no significant difference in percentage of patients with complete remission between two groups, although after 12 months follow-up a significantly smaller number of obese were in complete remission.
MO234: Ubiquitin C-Terminal Hydrolase L1 (UCHL1) Antibody Production in Nephrotic Syndrome
Authors: Chebotareva Natalia , Vinogradov Anatoliy , Cao Wenjing
Published: May 2022

BACKGROUND AND AIMS

Recently, evidence has emerged that the ubiquitin system, which is involved in extracellular protein degradation, is most susceptible to damage in podocytes in cases of severe nephritis. We studied anti-ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) antibodies in patients with glomerulonephritis and proteinuria.

METHOD

Sixty-five patients with CGN were included in our study. Forty-two patients had nephrotic syndrome, and twenty-three did not. Serum levels of anti-UCHL1 antibodies were measured by ELISA.

RESULTS

The levels of anti-UCHL1 antibodies were significantly higher in FSGS patients than in MCD, IgA nephropathy, membranous nephropathy or membranoproliferative glomerulonephritis patients and healthy people. The levels of UCHL1 antibodies in serum did not correlate with 24-h proteinuria, eGFR, blood pressure, glomerulosclerosis percentage or area of tubulointerstitial fibrosis. During the development of the ROC curve {[AUC = 0.839 [95% confidence interval (CI) 0.740–0.937]} for FSGS versus other forms of nephritides, a readjustment of the sensitivity of 81.3% and specificity of 72.7% were established (Fig. 1). A former increase in anti-UCHL1 antibody levels above 0.749 ng/mL may be a marker of FSGS (Fig. 1).

CONCLUSION

An increase in the level of anti-UCHL1 antibodies in the serum was noted in FSGS, which suggests that these antibodies could be a potential biomarker for FSGS patients.
MO235: TGF-Β1/PSMAD3 Dependent Signaling in Glomerulonephritis and Its Association With Renal Injury and Progression
Authors: Chalkia Aglaia , Gakiopoulou Harikleia , Giannou Panagiota , Kourniotis Dimitrios , Kapota Athanasia , Mpora Margarita , Vasilopoulos Dimitrios , Petras Dimitrios
Published: May 2022

BACKGROUND AND AIMS

Transforming growth factor-β1 (TGF-β1) has long been considered as a potent, multifunctional cytokine that is involved in the pathogenesis of fibrosis and inflammation, which acts through Smad signaling in renal pathology. We intended to investigate the expression of TGF-β1/Smad3 signaling in glomerulonephritis (GN) and to assess its role as risk factor for progression to chronic kidney disease (CKD).

METHOD

We evaluated the immunohistochemical expression of TGF-β1, phosphorylated Smad3 (pSmad3) and Smad7 semiquantitatively and quantitatively using computerized image analysis program in different compartments of 50 renal biopsies with GN and the results were statistically analyzed with clinicopathological parameters. We also examined the associations among their expressions, the impact of their co-expression and their role in progression to CKD.

RESULTS

TGF-β1 expression correlated positively with segmental glomerulosclerosis (P = .025) and creatinine level at diagnosis (p = .002), while pSmad3 expression with interstitial inflammation (P = .024). In glomerulus, we recorded different expression patterns of pSmad3 in crescents, while concomitant expressions of strong Smad7 and moderate pSmad3 were observed to be correlated with renal inflammation, such as cellular crescent (P = .011), intense interstitial inflammation (P = .029) and lower serum complement 3 (P = .028) and complement 4 (P = .029). We also reported a significant preferable expression between pSmad3 and glomerular endothelial cells of proliferative GN (P = .045) and podocytes of non-proliferative GN (P = .005). Finally, on multivariate Cox-regression analysis, TGF-β1 expression (HR = 5.08; 95% CI 1.133–22.78; P = .034) was emerged as independent predictor for CKD.

CONCLUSION

TGF-β1/Smad3 dependent signaling is upregulated, especially in proliferative GN, with specific characteristics in different forms of GN. TGF-β1 expression is indicated as independent risk factor for progression to CKD, while specific co-expression pattern of pSmad3 and Smad7 in glomerulus is correlated with renal inflammation.
MO238: Erythroid ACKR1 Expression has a Protective Effect on the Development of Experimental Glomerulonephritis
Authors: Artinger Katharina , Novitzky-Basso Igor , Kirsch Alexander H , Schabhuettl Corinna , Hub Elin , Eller Philipp , Rosenkranz Alexander , Eller Kathrin , Rot Antal
Published: May 2022

BACKGROUND AND AIMS

The overwhelming majority of individuals of West African ancestry carry an ‘erythroid silent’ FyB(ES) SNP in the promoter region of ACKR1 that causes a selective loss of ACKR1 in erythroid cells but does not affect its expression in endothelial cells. The FyB(ES) polymorphism is of a special interest for understanding human kidney disease as individuals of West African ancestry have higher incidence of chronic kidney disease. Moreover, multiple chemokine ligands of ACKR1 are known to contribute to the inflammatory pathology in experimental nephrotoxic serum nephritis (NTS), a murine model of immune complex glomerulonephritis.

METHOD

We developed two humanized transgenic mouse strains that are genetically deficient for mouse ACKR1 but instead carry either West African FyB(ES) or Caucasian FyB human polymorphic ACKR1 variants. These strains as well as ACKR1-deficient and WT mice were subjected to NTS. The parameters of immunopathogenesis and kidney disease were evaluated after 14 days after the induction of NTS.

RESULTS

Albuminuria, PAS and tubular injury scores were significantly increased in FyB(ES)tg and ACKR1-deficient mice as compared with their respective control strains. While monocytes were unchanged in peripheral blood, we found significantly increased numbers of macrophages and neutrophils infiltrating the kidneys of FyB(ES)tg and ACKR1-deficient mice. Interestingly, T cell numbers in the draining lymph nodes were comparable between FyB(ES)tg and ACKR1-deficient mice and their respective controls.

CONCLUSION

We found that NTS was more severe in ACKR1-deficient and FyB(ES) mice as compared with their respective controls. Our results show that ACKR1 expression in the erythroid compartment has a significant impact on the development of kidney disease. These findings have important implications for the pathomechanisms of glomerulonephritis in individuals of West African ancestry who lack ACKR1 selectively in the erythroid lineage.
MO244: PCSK9 Inhibitors are Efficient in Treatment of Resistant Hypercholesterolemia in Nephrotic Syndrome
Authors: Vukovic Brinar Ivana , Ivandic Ema , Gellineo Lana , Jelakovic Ana , Fistrek Prlic Margareta , Jelakovic Bojan
Published: May 2022

BACKGROUND AND AIMS

Hypercholesterolemia in nephrotic syndrome is commonly resistant to statin therapy and represents an important clinical challenge both for cardiovascular risk prevention and to eliminate lipotoxic effect on podocytes. Serum PCSK9 level is elevated in nephrotic syndrome and has a key pathophysiologic role in development and persistance of hyperlipidemia. Thus, we aimed to investigate the role of PCSK9 inhibitors in control of hypercholesterolemia in patients with neprotic syndrome.

METHOD

Consecutive patients with nephrotic syndrome and elevated atherogenic Lp (a) (n = 4) and patients with resistant secondary glomerulonephritis with nephrotic proteinuria (n = 2) were included. In all patients, in addition to full dose statin therapy, evolocumab 420 mg s.c. monthly was introduced. Lipid levels were measured after a median of 4 (range 2–9) months after starting evolocumab.

RESULTS

Nephrotic syndrome was caused by focal segmental glomerulosclerosis in four patients (66.7%) and membranous nepropathy was the cause in two patients (33.3%). Median age of included patients was 49.5 (range 24–70) years. Four patients with primary cause of glomerulonephritis received specific imunosupressive treatment. During follow-up, we observed descrease in glomerular filtration rate (eGFR median 58.5 interquartile range (IQR) [46.7–98.7] mL/min/1.73 m2 versus median 47 IQR [38.25–89.25] mL/min/1.73 m2; P = .046) and persistence of proteinuria [median 11 970 IQR (3862–13 765) mg/dU versus median 10 847 (5407–14 340) mg/dU; P = .753]. However, despite persistent proteinuria and decrease in eGFR, significant decrease in total cholesterol [median 9.10 IQR (6.92–10.87) mmol/L versus median 6.81 (5.4–8.45) mmol/L; P = .028] and LDL cholesterol [median 5.40 IQR (4.12–7.25) versus median 4.04 IQR (2.70–4.60); P = .046] was observed. There was no significant difference in Lp (a) and triglyceride levels.

CONCLUSION

PCSK9 inhibitors are a promising new therapeutic option for hyperlipidemia in patients with nephrotic syndrome. Further research, including a larger number of patients, is needed to correctly position PCSK9 inhibitors in treatment of hyperlipidemia in patients with nephrotic syndrome.
MO251: Renal Glucocorticoid Receptor Expression and Clinical Course in Patients with IGA Nephropathy
Authors: Tekin Ala Bilge , Paydas Saime , Kaya Bülent , Eren Ateş Kıvılcım , Gönlüşen Gülfiliz , Sertdemİr Yaşar
Published: May 2022

BACKGROUND AND AIMS

Glucocorticoids are used as primary treatment in IgA nephropathy (IgAN), and they manifest their effects by binding to intracellular glucocorticoid receptors. Studies have shown that GCR expression correlates with the degree of steroid response in various diseases. Therefore, we aimed to evaluate renal GCR expression, Oxford MEST score in clinical course of IgAN patients.

METHOD

This study included 110 patients with biopsy-proven IgAN. Patients were treated with ACEI/ARB, methylprednisolon (80% patients). In renal biopsies, Oxford-MEST score was calculated and GCR expression was determined immunohistochemically. KDIGO criteria (2020) were accepted for remission. Clinical course, eGFR, proteinuria and other biochemical tests test were recorded during 1-year follow-up period.

RESULTS

Demographic and laboratory data did not correlate with renal GCR staining rate. İn patients with M1 of the MEST score, GCR staining was more prominent than those with M0. GFR values were higher and proteinuria was lower in patients with T0 compared with patients with T1 and T2 (P < .05 for all) . Patients with E1 had significantly higher systolic blood pressure (BP), increased proteinuria and lower eGFR than patients with E0. Poor prognostic factors for achieving remission were higher systolic/diastolic BP, increased levels of white blood cell (WBC) count/neutrophil count, PTH, BUN, creatinine, uric acid, potassium, magnesium, MCV, Mentzer index, total cholesterol, LDL and higher sclerosis in biopsy at baseline during follow up period for 1 year.

CONCLUSION

Clinical presentation and outcome at 1 year in IgAN patients were well predicted by the Oxford-MEST score, but not by renal GCR expression. GCR staining intensity was only correlated with M1 score. Baseline higher BP, increased serum creatinine, uric acid and PTH were poor prognostic factors. Interestingly higher WBC and neutrophils counts, increased serum LDL and Mentzer index at baseline were also correlated with clinical course.
MO259: Maintenance Therapies for Anti-Neutrophil Cytoplasmic Antibody Small-Vessel Vasculitis: A Network Meta-Analysis
Authors: Bellos Ioannis , Boletis Ioannis , Karagiannis Minas , Lionaki Sophia
Published: May 2022

BACKGROUNDS AND AIMS

Over the past two decades, considerable progress has been made in maintaining remission in patients with anti-neutrophil cytoplasmic antibody (ANCA) vasculitis using a variety of medications, including rituximab, azathioprine, mycophenolate, methotrexate, and glucocorticoids. However, although survival has improved dramatically over the last decades, relapse rates remain significant for certain patients, stressing the need for advocation of new therapeutic strategies. The aim of this study was to compare the efficacy and safety of different regimens used for maintenance of remission in patients with ANCA-vasculitis.

METHOD

This network meta-analysis studied adult patients with ANCA-vasculitis in complete remission, who were maintained with various regimens, excluding patients with eosinophilic granulomatosis with polyangiitis, and those who have ended up in end-stage kidney disease. Outcomes of interest included relapse (any/major), relapse-free survival and adverse effects. PubMed, Scopus, Web of Science, CENTRAL, Clinicaltrials.gov and Google Scholar were systematically searched from inception.

RESULTS

Overall, the meta-analysis was based on 10 reports, describing the outcomes of 7 RCTs including 752 patients with ANCA-vasculitis. Compared with rituximab, relapse-free survival was significantly worse with the use of azathioprine {HR 2.11 [95% confidence interval (CI) 1.19–3.74]}, methotrexate [HR 2.51 (95% CI 1.24–5.08)] and mycophenolate mofetil [HR 3.57 (95% CI 1.70–7.46)]. Compared with mycophenolate mofetil, better outcomes were estimated for azathioprine [HR 0.59 (95% CI 0.37–0.94)], cyclophosphamide [HR 0.39 (95% CI 0.20–0.75)] and leflunomide [HR 0.30 (95% CI 0.11–0.84)]. Compared with rituximab a higher relapse risk was estimated for azathioprine [OR 2.15 (95% CI 1.00–4.59)] and mycophenolate mofetil [OR 4.42 (95% CI 1.63–11.94)]. A higher risk of major relapse was calculated for azathioprine [OR 2.39 (95% CI 1.10–5.19)], methotrexate [OR 3.18 (95% CI 1.14–8.89)] and mycophenolate mofetil [OR 5.20 (95% CI 1.65–16.37)] compared with rituximab. The rates of serious adverse effects did not differ significantly among interventions.

CONCLUSION

Rituximab appears predominant in maintaining remission in patients with ANCA-vasculitis with no cost in adverse events.
MO268: Use of Corticosteroids in a Norwegian Cohort of Patients with IGA Nephropathy and Rapid Progression to End-Stage Renal Disease
Authors: Lunde Haaskjold Yngvar , Rivedal Mariell , Gjærde Lura Njål , Bjorneklett Rune , Knoop Thomas
Published: May 2022

BACKGROUND AND AIMS

Despite several clinical trials, treatment with corticosteroids in patients with Immunoglobulin A nephropathy (IgAN) remains controversial [1, 2]. The recently updated KDIGO guidelines suggests that treatment with corticosteroids could be considered in patients with persistent proteinuria above 0.75 to 1.0 g per day in patients with estimated glomerular filtration rate (eGFR) above 30 mL/min/1.73 m2 despite intensive supportive care [3]. This is a more liberal approach compared with the 2012 guidelines, which suggested that patients selected for treatment with steroids should have eGFR above 50 mL/min/1.73 m2 [4]. It could be valuable to identify clinicians decision on when to initiate immunosuppressive treatment, since this could have implication on how future therapeutics might be used in patients with IgAN [5]. Our aim is to describe the use of corticosteroids and evaluate the effect of this treatment using a Norwegian cohort of patients with IgAN.

METHOD

We identified patients with biopsy-proven IgAN from the Norwegian Kidney Biopsy Registry and the Norwegian Renal Registry, who all had progressed to end-stage renal disease (ESRD) and collected clinical, treatment and biochemical data from patient records.

RESULTS

A total of 151 patients with a diagnostic kidney biopsy performed between 1988 and 2010 were included. The median time from biopsy to ESRD was 5 years. A majority of 94% of the patients received supportive treatment with Renin–Angiotensin–Aldosterone System blockade. A total of 40 patients (27%) received treatment with corticosteroids, with a median eGFR and proteinuria at time of biopsy at 49.5 mL/min/1.73 m2 and 5.1 g per day, respectively. Median time from biopsy to steroid treatment was 12 months. Patients treated with corticosteroids had a significant decrease in proteinuria from 5.6 to 3 g per day (P = .02), but there was no difference in time to progression to ESRD between the two groups (P = .58). The vast majority (87.5%) of the patients treated with corticosteroids reported on adverse events.

CONCLUSION

We found that the use of corticosteroids had significant impact on proteinuria but did not delay progression to ESRD. Adverse events were common in patients treated with corticosteroids. The patients were treated according to the current guidelines
MO284: Dipeptidyl-Peptidase-4 Inhibitor, Teneligliptin, Ameliorates Folic Acid-Induced Acute Kidney Injury in Mice
Authors: Ema Chiemi , Iwakura Takamasa , Tsuchida Miyuu , Fujikura Tomoyuki , Yasuda Hideo
Published: May 2022

BACKGROUND AND AIMS

Acute kidney injury (AKI) is histologically characterized by tubular cell death and inflammation. It has demonstrated that cell death in renal tubule cells on AKI could be introduced by regulated necrosis or apoptosis, but the molecular mechanisms are reported to be different between AKI models [1]. Recently, Dipeptidyl -peptidase-4(DPP4) inhibitors have been reported to ameliorate cisplatin-induced AKI and ischemia-reperfusion-induced AKI [2, 3]. In this study, we examined the effect of teneligliptin, a DPP4 inhibitor, on folic acid (FA)-induced AKI(FA-AKI) model in mice, which is reported to be mainly induced by ferroptosis, one of the regulated necrotic pathways [4].

METHOD

C57BL/6J mice (12–14 weeks old) received a single intraperitoneal injection of FA of 250 mg/kg in 0.3 mol/L sodium bicarbonate, and were euthanized 48 h later. Teneligliptin or vehicle were orally administered just before and 24 h after FA infusion, respectively. Blood samples and renal tissue samples were collected at the time of euthanasia for evaluation.

RESULTS

The increase of serum creatinine (mean 0.297 mg/dL in teneligliptin-treated mice versus 0.833 mg/dL in vehicle-treated mice; P < 0.01) and blood urea nitrogen (mean 72.22mg/dL in teneligliptin-treated mice versus 177.7mg/dL in teneligliptin-treated mice; P = 0.016) were suppressed in teneligliptin-treated mice, compared to vehicle-treated mice (Fig. 1A and B). Histologically, teneligliptin treatment reduced tubular injury score, tubular cell death evaluated with the terminal uridine nick-end labeling (TUNEL) and kidney injury molecule-1 (kim-1) expression in the kidney (Fig. 2A-C). In addition, number of infiltrating Ly6G + neutrophil and number of infiltrating F4/80 + macrophages were decreased in the kidney of teneligliptin-treated mice, compared with that of vehicle-treated mice (Fig. 2D and E).

CONCLUSION

We found that teneligliptin ameliorated FA-AKI in mice by suppressing necroinflammation in the kidney. Further studies are needed to clarify the underlying mechanisms of the renoprotection.
MO305: COVID-19 in Elderly Patients with Acute Kidney Injury
Authors: Ayar Yavuz , Deniz Olgun , Doner Baris , Kilic İsa , Demir Canan , Sahin Abdulkadir
Published: May 2022

BACKGROUND AND AIMS

Coronavirus disease 2019 (COVID-19), which started in China in December 2019 and spread all over the world, is more progressive in patients who are elderly and with chronic diseases. Especially, kidney involvement affects the survival of patients. In this study, we analysed COVID-19 patients who developed acute kidney injury treated in our unit, retrospectively.

METHOD

The clinical and laboratory data of 610 patients who were hospitalized due to COVID-19 pandemic between 1 June 2020 and 30 June 2021 in the intensive care and other clinics of our hospital were evaluated from the records, retrospectively. A total of 140 patients were diagnosed with AKI according to the criteria of Kidney Disease Global Outcomes (KDIGO). The patients were divided into two groups as KDIGO stages 1 and 2 and 3.

RESULTS

The median age in both groups was 70 (35–92) and 73 (35–90) years. Approximately 70% of them were >65 years old. Almost all of the patients had hypertension. Most of the patients were using angiotensin converting enzyme inhibitors (ACE inh) or angiotensin receptor blockers (ARB) (84%). AKI was present at the time of admission (61.9%) in the KDIGO 1 group and at the time of hospitalization (64.3%) in the KDIGO 2, 3 groups. The mortality rate was higher in stage 2–3 AKI patients (35.7%). Ferritin and fibrinogen levels were high in the KDIGO 2, 3 group, while lymphocyte levels were low.

CONCLUSION

AKI can be seen at the time of admission and during treatment in patients who are hospitalized and treated due to COVID-19. COVID-19 is more mortal in patients with advanced AKI.
MO308: Urinary Biomarkers to Predict Acute Kidney Damage and Mortality In COVID-19
Authors: Racovitan Diana , Hogeweg Maximilian , Doevelaar Adrian , Seidel Maximilian , Rohn Benjamin , Bettag Sebastian , Rieckmann Sonja , Babel Nina , Henning Westhoff Timm , Seibert Felix S
Published: May 2022

BACKGROUND AND AIMS

Acute kidney injury (AK) is a frequent condition in patients hospitalized for COVID-19. There are only few reports on the use of urinary biomarkers in COVID-19 and no data comparing the prognostic use of individual biomarkers in the prediction of adverse outcome so far.

METHOD

We performed a prospective monocentric study on the value of urinary biomarkers to predict the composite endpoint of a transfer to the intensive care unit (ICU), the need for renal replacement therapy (RRT), mechanical ventilation and in-hospital mortality. A total of 41 patients hospitalized for COVID-19 were enrolled in this study. Urine samples were obtained shortly after admission in order to assess neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), calprotectin and vanin-1.

RESULTS

We identified calprotectin as a predictor of a severe course of the disease, requiring intensive care treatment (AUC 0.728, P = .016). Positive and negative predictive values were 78.6% and 76.9%, respectively, using a cut-off concentration of 127.8 ng/mL. NGAL tended to predict COVID-19 associated AKI without reaching statistical significance (AUC 0.669, P = .053). The best parameter in the prediction of in-hospital mortality was NGAL as well (AUC 0.674, P = .077). KIM-1 and vanin-1 did not reach significance for any of the investigated endpoints.

CONCLUSION

While KIM-1 and vanin-1 did not provide prognostic clinical information in the context of COVID-19, this study shows that urinary calprotectin and NGAL concentrations are independent predictors of an adverse course of the disease. Calprotectin and NGAL may thereby constitute helpful adjuncts in the identification of patients at increased risk who may benefit from upcoming antiviral agents to SARS-CoV-2.
MO314: Oliguria as a Strong Predictor of Mortality in Leptospirosis
Authors: Rista Elvana , Cadri Vilma , Saliaj Kristi , Akshija Ilir , Duraku Ahmet , Puca Edmond , Abazaj Erjona , Thereska Nestor , Harxhi Arjan
Published: May 2022

BACKGROUND AND AIMS

Leptospirosis is an endemic, globally widespread zoonotic disease caused by pathogenic spirochetes of the genus Leptospira. It presents with high clinical variability, with a constellation of symptoms ranging from a mild, nonspecific, self-limiting febrile syndrome to acute liver failure, acute kidney injury, coagulopathy and respiratory involvement. Acute kidney injury (AKI) is a common complication and generally presents as nonoliguric and hypokalemic. The aim of this study was to delineate potential predictors of mortality in Leptospirosis.

METHOD

We conducted a prospective, observational, single-center study in the span of 5 years, from 2010 to 2015. Patients enrolled in the study had an age at presentation >14 years and were hospitalized for longer than 24 h with a conclusive diagnosis of Leptospirosis. Baseline patient characteristics, including demographic, clinical and laboratory data were collected. Definitive diagnosis was established through serology assay, using the indirect-ELISA test to detect positive Leptospira IgM and IgG. Fisher's exact test was used to identify predictors of mortality during the course of the infection.

RESULTS

A total of 119 consecutive patients diagnosed with Leptospirosis were enrolled during a 5-year period, 92% were males. Mean age at presentation was 48.8 ± 14.9 and 41.5 ± 19.8 years for males and females, respectively. Mortality in our cohort was estimated to be 9% (10 patients). Urine output and bilirubin levels were found to be the most significant predictors of mortality. Fischer's exact test determined urine output at a cut-off value of 400 mL/24 h as the strongest predictor of mortality (P < 0.001) in Leptospirosis. Bilirubin levels showed an equivalent statistical significance at a cut-off value of 19 mg/dL (P < .001). Creatinine levels on admission, at a cut-off value of 3 mg/dL, proved to be the third strongest predictor of mortality, followed by nadir platelet count and age at a cut-off value of 70 × 103/µL and 49 years, respectively.

CONCLUSION

Our study defined oliguria as the most significant predictor of mortality in patients with severe Leptospirosis, closely followed by bilirubin levels on admission. Other predictors to consider include creatinine levels on admission, nadir platelet count and age at presentation. Incorporating predictors of mortality, from the outset, in treatment algorithms of Leptospirosis, will promote a more timely diagnosis and the development of more specific management guidelines, enabling clinicians to provide personalized treatment plans, potentially impacting the prognosis, morbidity and mortality rates in these patients.