bluuebunny/crossref_metadata_2025 huggingface dataset:
P0095MOLECULAR MECHANISMS OF THE CARDIOVASCULAR EFFECTS OF LANTHIONINE, A NEW UREMIC TOXIN, AND ITS INTERACTIONS WITH THE REDOX MICROENVIRONMENT
Authors: Vigorito Carmela , Anishchenko Eugenia , Coppola Annapaola , Lombari Patrizia , Ingrosso Diego , Perna Alessandra
Published: June 2020

Background and Aims

The non-proteinogenic amino acid lanthionine is a byproduct of the biosynthesis of hydrogen sulfide (H2S), an endogenously produced gas with cardiovascular properties). Lanthionine concentration is increased in uremia and it has been proposed as a new uremic toxin. In the zebrafish model, lanthionine induces effects on cardiac embriogenesis, arrhythmia, and locomotor alterations. Some effects are counteracted by glutathione, the well known antioxidant. In a human endothelial cell model, lanthionine significantly reduces H2S release, both protein content and glutathionylation of cystathione beta-synthase (CBS), one of the main H2S-producing enzymes, miR-200c and miR-423 levels, as well as vascular endothelial growth factor expression, while it also increases intracellular calcium levels. We investigated in the present abstract the actions of glutathione on some of lanthionine effects on zebrafish and endothelial cells. We utilized what is considered to be a more stable form of glutathione, acetylglutathione (AcGSH).

Method

Zebrafish behavior and heart size were analyzed by the Danio Vision system and confocal microscopy, respectively. Gene and protein expression were analyzed usimg qPCR and Western Blot, respectively. CBS glutathionylation has been assessed by immunoprecipitation with a magnetic beads-coated anti-GSH. Interleukins levels were evaluated by ELISA. Lanthionine acetylation was evaluated by LC/MS.

Results

In zebrafish, we demonstrated that AcGSH significantly increases heart size and the expression of atrium specific proteins. Increased heart rate and heart rhythm plasticity determined by AcGSH were partially counteracted by lanthionine. Monitoring of larval movements showed that this behavior was affected by AcGSH supplementation. In endothelial cells, AcGSH increased H2S release, and, utilized in combination with lanthionine, it was able to partially counteract its effects on H2S release. AcGSH was able to increase CBS glutathionylation and to offset lanthionine effects on glutathionylation. In addition, it increased tubulin, histone, and NFKB acetylation and IL-8 and IL-13 levels. We also demonstrated with mass spectrometry that lanthionine was non-enzymatically acetylated by AcGSH, suggesting a possible mechanism.

Conclusion

In conclusion, our findings support the notion that lanthionine is a uremic toxin, which is strongly modified in its effects by the redox microenvironment.
P0096RENAL EXPRESSION AND CIRCULATING LEVELS OF CANONICAL WNT PATHWAY INHIBITORS IN THE EXPERIMENTAL MODEL OF EARLY CHRONIC KIDNEY DISEASE
Authors: Bogdanova Evdokia , Beresneva Olga , Galkina Olga , Zubina Irina , Ivanova Galina , Parastaeva Marina , Dobronravov Vladimir
Published: June 2020

Background and Aims

Molecular mechanisms implicated in the initial stages of inorganic phosphate (Pi) imbalance in chronic kidney disease (CKD) remain poorly understood.

The aim of the study was to evaluate whether canonical Wnt pathway inhibitors (iWnt) involved in early response to Pi retention in CKD.

Method

Mild CKD was induced by 3/4 nephrectomy (NE, n=10) in spontaneously hypertensive rats (SHR) fed rat chow diet containing 0.8 % phosphate. Controls were sham operated SHR (SO, n=9). Duration of experimental exposure (NE or SO) was 4 months. Creatinine (Cr), albumin/ creatinine ratio (Alb/Cr), inorganic phosphate (Pi), fractional (FEPi) and daily Pi excretion (uPi24), intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), Klotho protein, sclerostin (SOST) and Dickkopf-1 (DKK1), SOST and DKK1 mRNA expression in kidney, renal interstitial fibrosis (RF) were analyzed.

Results

Levels of Alb/Cr, serum Cr, RF and indices of Pi exchange in the experimental model corresponded to mild CKD with Pi retention (Table). No differences were observed in serum levels of Klotho, FGF23 and PTH in experimental group vs controls (Table). Serum SOST and DKK1 concentrations were significantly higher in NE group while the kidney expression of SOST and DKK1 mRNAs decreased compared to SO (Table).

Conclusion

Early stages of experimental CKD are characterized by increased serum concentrations of sclerostin and Dickkopf-1 in the absence of Klotho, FGF23 or PTH levels alterations. The increase of circulating iWnt levels seems not to be associated with their renal biosynthesis and likely have a bone origin.
P0099CALCINEURIN INHIBITION, BUT NOT DEHYDRATION, IN RATS MIMICS HUMAN RENAL HISTOPATHOLOGY OF PATIENTS WITH CHRONIC INTERSTITIAL NEPHRITIS IN AGRICULTURAL COMMUNITIES (CINAC)
Authors: Schreurs Gerd , Nast Cynthia , Maudsley Stuart , D'Haese Patrick , De Broe Marc , Vervaet Benjamin
Published: June 2020

Background and Aims

CINAC patients present a newly discovered constellation of proximal tubular lysosomal lesions which is also observed in patients experiencing calcineurin inhibitor (CNI) nephrotoxicity, suggesting that CINAC is a toxin-induced nephropathy involving calcineurin inhibition. An alternate hypothesis advocates chronic heat stress/dehydration as the major etiological factor for CINAC. Here, we evaluated in rats to what extent heat stress/dehydration versus CNI exposure reflects proximal tubular CINAC histopathology.

Method

Wistar rats were divided in 3 groups. Group 1 (n=6) was given water ad libitum (control group). Group 2 (n=8) was water deprived for 10 hours per 24h, 5 days/week and were placed in an incubator (37°C) for 30 min/hr of water deprivation. Group 3 (n=8) underwent daily oral gavage with cyclosporine (50mg/kg body weight). Animals were weighed daily and urine was collected at day 3, 17 and 28. After 28 days, rats were sacrificed. Kidneys were collected for light (LM) and electron microscopic (EM) histopathological analysis as well as for cortical renal tissue proteomics.

Results

Cyclosporine rats developed focal cortical lesions mimicking those of CINAC patients: i.e. atrophic proximal tubuli with thickened basement membranes and associated tubulo-interstitial fibrosis, PASM staining demonstrating enlarged argyrophyllic granules in the affected proximal tubuli, LAMP1 immunofluorescent staining identifying a subset of these granules as lysosomes, and EM confirming the presence of enlarged lysosomes, some dysmorphic approaching CINAC lysosomes. In dehydrated rats, confirmed by urinary osmolality and fluctuating body weight associated with water deprivation, none of the cyclosporine features were observed. Proteomic analysis confirmed cellular toxicity by cyclosporine, whereas the dehydration group lacked any markers of such.

Conclusion

The histopathological analogy between CNI nephrotoxicity in rats and humans and CINAC suggests a toxicological etiology for CINAC. In rats, dehydration/heat stress alone does not lead to the constellation of proximal tubular lesions as observed in CINAC patients.
P0122THE MECHANISM OF DNA INJURY INDUCED COLLAGEN TYPE VI EXCRETION IN GLOMERULAR ENDOTHERIAL CELLS
Authors: Ai Fujii , Sunatani Yumi , Kengo Furuichi , Fujimoto Keiji , ADACHI HIROKI , Iwabushi Kuniyoshi , Yokoyama Hitoshi
Published: June 2020

Background and Aims

Collagen deposition is observed in various part of kidney tissue and is serious pathological damage in kidney. Nodular glomerulosclerosis is one of a phenotype of collagen deposition in glomerular lesion, which affects the prognosis of renal function, but there is no effective treatment at present. Recently, we identified that glomerular endothelial cells with DNA double-strand breaks (DSB) are involved in the long-term accumulation of ECM molecules, especially collagen type VI(COL6). However, the mechanism of glomerular COL6 accumulation is still unclear.

Method

We examined the phospho-histone H2AX (γ-H2AX) of the DSB marker and COL6 accumulation in biopsied human kidneys to investigate their association. In addition, we investigated in vitro the relationship between DSB and COL6 excretion and the intracellular signal pathways in human glomerular endothelial cells (HRGEc) using mitomycin C (MMc)-induced DNA damage. In this study, we focused on the expression of DSB response signal pathways, i.e. ATM, ATR and DNA-PK using their specific kinase inhibitors (KU55933, VE-821, Nu7441).

Results

COL6 deposits and γ-H2AX expression in nuclei were detected in human glomerular capillary loop and glomerular nodular lesions. The multiple regression analysis showed that γ-H2AX positive area is the most independent factor for COL6 accumulation in glomeruli (β: 0.539, t=2.668, p=0.014). Furthermore, COL6 was the independent factor of nodular lesion in various pathologic diseases such as diabetic nephropathy, hypertensive glomerulosclerosis and the long-term transplanted allografts (β: 0.373, t=2.268, p=0.032).

In vitro study, COL6 excretion detected by the decrease of COL6 positive cells was suppressed only in the ATR-inhibited group (control vs. kinase inhibitors; 2 h, 40.1 ± 23.5 vs. 59.0 ± 23.2%, p <0.01; 24 h, 18.8 ± 23.6 vs. 56.3 ± 16.5%, p <0.001).

Conclusion

This study suggested that nodular glomerulosclerosis is induced by DNA damage and COL6 deposition through ATR pathway in glomerular capillary endothelial cells. These findings will provide great insights into the development of new therapies that would suppress glomerularsclerosis in various kidney diseases.
P0129DIET INDUCED ACCELERATION OF RENAL INJURY IN THE BTBROB/OB MOUSE MODEL OF DIABETIC KIDNEY DISEASE
Authors: William-Olsson Lena , Tonelius Pernilla , Tesan Tomic Tajana , Söderberg Magnus , Björnson Granqvist Anna
Published: June 2020

Background and Aims

There is a need of disease relevant models for efficient evaluation of new drug targets in the renal field. The obese diabetic BTBRob/ob mouse model have features resembling important aspects of human diabetic kidney disease and is extensively used in pharmacological studies. Since diet composition plays a role in diabetic- and renal disease it is important to have detailed control of nutritional intake in our pre-clinical models, especially since many studies use in-diet drug administration. In this study we compared disease progression in obese diabetic mice on non-defined chow diet (R3) with the defined control diet D12450B (Research Diets).

Method

BTBRob/ob mice were fed either regular laboratory rodent chow (R3) or the defined control diet D12450B containing 35% sucrose from 6 weeks of age. The animals were studied for 14 to 20 weeks of age and both physical parameters, urine and blood parameters, histology and gene expression was examined. (R3 group n=14, D12450B group n=8).

Results

Mice on the defined D12450B diet displayed increased calorie- and water intake, but gained less weight compared to R3 group. Blood glucose and HbA1c was higher at all timepoints, and urinary albumin-to-creatinine ratio was highly elevated compared to mice on R3 diet. Mice fed D12450B also displayed lower levels of plasma insulin and increased plasma b-hydroxybutyrate levels. Histopathological evaluation revealed that the defined D12450B diet increased induction both of mesangial injury score and gene expression of tubular injury markers NGAL and Kim-1.

Conclusion

: In summary, the choice of diet composition will have a huge impact on the disease progression in diabetic leptin-deficient overeating mouse models. These finding underline the importance of describing the diet composition in detail and take precaution on diet selection for preclinical studies.
P0138THE ROLE OF TREFOIL FACTOR 3 IN THE EVALUATION OF RENAL ALTERATION IN PATIENTS WITH ANKILOSING SPONDYLITIS
Authors: Plenkina Lidia , Simonova Olga
Published: June 2020

Background and Aims

Kidney damage in ankylosing spondylitis (AS) has one of the leading positions. The diagnostic value of traditional markers of renal damage is not high, which often leads to delayed diagnosis. Therefore, an active research for alternative methods is conducted. The Aim was to evaluate urinary excretion of Trefoil factor-3 (TFF-3) in patients with AS.

Method

Urine samples of 50 patients (male/female =37/13) were evaluated. The requrentments for patients providing samples were: confirmed diagnosis of AS, age 18 and over and and absence of intercurrent diseases. Median age of patients was 39 [34; 56] years, duration of articular syndrome was 10 [7;18] years, glomerular filtration rate (GFR) - 105 [83;119] ml/min/1.73 m? Patients received nonsteroidal anti-inflammatory drugs (NSAIDs) and tumor necrosis factor alpha inhibitors (TNFα inhibitors). TFF-3 level was measured by enzyme-linked immunosorbent assay. Urinary excretion was expressed as nanograms per millimol of urinary creatinine. The results were compared with the results of the control group.

Results

The level of TFF-3 in patients without chronic kidney disease (CKD) was higher than in the control group: 53.4 [20.8;105.7] and 23.3[1.9;62.9] ng/mmol respectively, (p=0.02). A correlation with disease activity was found for BASDAI (rs=0.3, p<0.05) and ASDAS (rs=0.3, p<0,05). Marker values in patients receiving NSAIDs were higher compared with TNFα inhibitors: 89,5 [39.8;118.9] and 32,6 [13.5; 88.2] ng/mmol respectively, (p=0.04). The level of TFF-3 did not depend on sex, age and AS duration. It did not correlate with GFR and albuminuria.

Conclusion

TFF-3 urinary excretion is higher in patients with AS compared with healthy individuals, as well as in patients receiving NSAIDs compared with TNFα inhibitors. Thus, the marker may be of interest for diagnosis in patients with pre-clinical tubulointerstitial damage, including those associated with the NSAIDs toxicity.
P0150APREECLAMPSIA ABOUT 252 PATIENTS
Authors: Akli Boubchir , Akli Boubchir , Kichou Brahim , ALI MADIOU
Published: June 2020

Background and Aims

The main objective was to estimate the prevalence of pre-eclampsia (PE) in pregnant women in Tizi-ouzou (Algeria). Secondary objectives were to estimate the frequency of PE risk factors, and the incidence of maternal and fetal complications.

Methods

Our study was observational, prospective and descriptive, including all pregnant women at the prenatal appointment in the 2 maternity units of Tizi-ouzou, between January 2012 and June 2013. PE was diagnosed if gestational hypertension was associated with proteinuria > 300mg/24h, after 20 weeks of gestation.

Results

We had 252 cases of PE on 3225 pregnant women. The prevalence of PE was 7.8% (CI 95%: 6.9%–8.7%). The most frequent PE risk factors were nulliparity (56%), age >40 years (27%), obesity (26%) and PE in any previous pregnancy (21%). The incidence of maternal adverse events was 28.7% (CI 95%: 23.1%–34.3%), including 5 deaths. The rates of prematurity, small for gestational age infant and fetal death were 58.2%, 49.7% and 6.7%, respectively.

Conclusion

The prevalence of PE in pregnant women in Tizi-ouzou is around 8%. The incidence of maternal and fetal adverse outcomes remains high. Only earlier diagnosis and closer monitoring could improve the prognosis of our patients, since the treatment of PE remains currently childbirth.
P0158RENAL DENERVATION VERSUS SPIRONOLACTONE IN THE TREATMENT OF RESISTANT HYPERTENSION: A META-ANALYSIS
Authors: Edding Sherida , Cabral Brian Michael , Cating-Cabral Monica Therese
Published: June 2020

Background and Aims

Resistant hypertension (RH) is defined as blood pressure that remains above guideline-directed goal despite the concurrent use of at least three antihypertensive agents of different classes, one of which is a diuretic. Treatment of RH is focused on the addition of fourth-line therapy. Several studies revealed impressive blood pressure reductions when spironolactone was added to the therapeutic regimen. In the recent years, there has been a growing perception that controlling blood pressure in resistant hypertension is beyond the reach of existing drug therapies, leading to the emergence of device-based therapies, such as renal denervation. Our aim is to do a systematic review of randomized controlled trials that compares the use of Spironolactone and Renal Denervation in patients with RH.

Method

A comprehensive literature search from the PubMed, Embase, Cochrane Library, and Ovid was performed with the following search terms: Resistant Hypertension, Spironolactone, Renal Denervation. The search was limited to randomized-controlled trials that compared Spironolactone to Renal Denervation in patients with Resistant Hypertension. Three prospective clinical trials were selected and analyzed using Cochrane Revman v5.3. Primary outcome were mean changes in 24-hour Ambulatory Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP). Secondary outcomes include mean changes in Office SBP and DBP. Safety was assessed by changes in eGFR and potassium levels.

Results

Two trials comprising 130 patients were selected - 63 patients treated with RDN and 67 patients with Spironolactone. Pooled analysis of the 2 trials for 24H SBP and DBP showed an adjusted standardized mean difference of 0.55 mmHg (CI -0.72, 1.82; P = 0.39) and 0.32 mmHg (CI -0.72, 1.35; P = 0.55) with significant heterogeneity. No significant differences were also noted in terms of decline in eGFR (p = 0.07) and changes in serum potassium (p = 0.29) from baseline to 6 months.

Conclusion

Based on our results, RD appears to be safe and effective treatment for RH. However, additional larger studies should be done including a cost-benefit analysis to explore that possibility of RD as treatment alternative for those intolerant of spironolactone or as a possible 5th line of treatment for those already taking spironolactone.
P0161TO EVALUATE THE TH PROFILE (TH1/TH2/TH17 ) AMONG GESTATIONAL DIABETES AND NORMAL PREGNANCY
Authors: Kaul Anupma , Pandey Amita , Aggrwal Vikas
Published: June 2020

Background and Aims

Gestational diabetes mellitus (GDM) is a common pregnancy complication, characterized by insulin resistance and low-grade systemic inflammation with a pro-inflammatory immune system response. Our objective was to study the peripheral Th1, Th2, Th17 and Treg response in GDM compared to normal pregnancy.

Method

Th1, Th2, Th17 and Treg subsets was determined by flow cytometry based on staining for specific intracellular cytokines levels and their CRP levels were also assessed.. The health status of all offspring was also assessed 6 months post-delivery.

Results

Α total of 32 adult pregnant women were enrolled into a GDM (n=18) and Control (n=14) group. At the third trimester of pregnancy, the GDM group had a higher proportion of Th2, Th17 and Treg cells compared to control. Contrary to the control group, the GDM group exhibited no significant change in the Th1/Th2/Th17/Treg profile postpartum. A higher circulating CRP were noted in the GDM group compared to controls. At the 6-month post-delivery assessment, 23.6% of the offspring from the GDM group were found to have developed atopic dermatitis or food allergy compared to none from the control group.

Conclusion

Compared to an uncomplicated pregnancy, GDM exhibits a significantly different peripheral T-cell profile at the third pregnancy trimester characterized by higher proportion of Th2, Th17 and Treg cells which persist six months post-delivery, while the increased high sensitivity CRP (hsCRP) levels stressed the low-grade inflammatory profile of this disease
P0166ADDITIVE INTERACTION OF HIGH SODIUM INTAKE AND INCREASED SERUM TRIGLYCERIDE ON HYPERTENSION
Authors: Yi Joo-Hark , Yu Mi-yeon , Choi Jong Wook , Han Sang-Woong , Lee Chang Hwa , Park Joon-Sung
Published: June 2020

Background and Aims

Both high salt diet and abnormal lipid metabolism are critical risks of vascular endothelial dysfunction. This study investigated the interactive effects of increased sodium intake and elevated serum triglyceride (TG) on elevated blood pressure (BP).

Method

We conducted nation-wide, population-based interaction analysis using Kawasaki method for estimating 24-h urinary sodium excretion (e24hUNaEKawasaki) as a candidate indicator of dietary sodium intake. Eligible as cases were all native Koreans aged 20 years or older without significant medical illness.

Results: A total of 16936 participants were divided into quintiles according to their e24hUNaEKawasaki results. Participants in the highest quintile were more obese and hypertensive and had increased white blood cell count, decreased hemoglobin, greater glycemic exposure, and poor lipid profiles as compared to lower quintiles. Linear regression showed that e24UNaEKawasaki was closely related with dietary sodium intake, systolic BP, diastolic BP, and TG. Multiple logistic regression, adjusted for dietary sodium intake and various conventional risk factors of hypertension, demonstrated that both e24UNaEKawasaki and TG were significant predictors of hypertension. Our interaction analysis revealed that high sodium intake had a bigger effect on the risk of hypertension in participants with elevated TG than those without (adjusted RERI = 0.022, 95% CI = 0.017-0.027; adjusted AP = 0.017, 95% CI = 0.006-0.028; adjusted SI = 1.010, 95% CI = 1.007-1.014).

Conclusion

Our findings indicate that the interaction of high salt diet and abnormal lipid metabolism may exert synergistic biologic effect on the increased arterial BP.
P0182SAFETY AND EFFICACY OF INTRA-RENAL ARTERIAL AUTOLOGOUS CD34+ CELL TRANSFUSION IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A RANDOMIZED, OPEN-LABEL, CONTROLLED PHASE II CLINICAL TRIAL
Authors: Yang Chihchao , Li Yi-Chen , Yip Honkan
Published: June 2020

Background and Aims

This was a randomized, open-label, controlled phase II clinical trial to investigate the safety, efficacy and the outcomes of intra-renal artery (RA) infusion of autologous peripheral-blood-derived CD34+ cells for chronic kidney disease (CKD) (i.e., stage III or IV) patients.

Method

Between December 2016 and November 2018, 52 consecutive patients with CKD at stage III or IV were randomly allocated into treatment group (TG) (2.5 × 107 cells for each RA; n=26) and control group (CG) (standardized pharmacotherapy only; n=26). The primary endpoints included safety and change of creatinine level/creatinine clearance (Ccr). The secondary endpoints were 12-month combined unfavorable clinical outcomes (defined as dialysis or death), improvement in proteinuria, and CD34+cell-related adverse events.

Results

All patients were uneventfully discharged after CD34+ cell therapy. Flow cytometric analysis showed increases in circulating EPC (i.e., CD34+KDR+CD45dim/CD34+CD133+ CD45dim/CD31+CD133+CD45dim/CD34+CD133+KDR+/CD133+) and hematopoietic stem cell (HSC) (CD34+) populations after G-CSF treatment. Besides, Matrigel assay of angiogenesis was also significantly enhanced (all p<0.001). Renal vein blood samplings (i.e., at 0/5/10/30 min after CD34+ cell infusion) demonstrated significant progressive increases in EPC level (p for trend<0.001) among the TG patients. The baseline EPC populations did not differ between TG and CG (p>0.5). One-year combined unfavorable clinical outcomes were significantly lower in TG than those in CG [0% (0) vs. 13.3% (4), p=0.038](Figure). By 12-month after CD34+ cell therapy, circulating creatinine level, ratio of urine protein to urine creatinine, and creatinine clearance did not differ between TG and CG (all p>0.1).

Conclusion

CD34+ cell therapy was safe and improved one-year outcome.
P0230IMMUNOSUPPRESSIVE TREATMENT DOES NOT IMPROVE KIDNEY SURVIVAL IN PATIENTS WITH HCV CRYOGLOBULINAEMIA TREATED WITH DIRECT-ACTING ANTIVIRALS
Authors: Ana Pérez de José , Carbayo Javier , Pocurull Anna , Huerta Ana , Cases Corona Clara Maria , Bada Bosch Teresa , Shabaka Amir , Ramos Terrada Natalia , Martinez Valenzuela Laura , Goicoechea Marian
Published: June 2020

Background and Aims

Since the introduction of direct-acting antivirals (DAAs), few data have been published about kidney outcome in hepatitis C virus related mixed cryoglobulinaemia (HCV-MC) patients treated with combined DAAs and rituximab.

We aimed to asses if combined treatment with DAAs and rituximab in patients with HCV-MC improves kidney survival and immunological response.

Method

Observational, multicentre, cohort study of 100 patients with HCV-MC from 14 Spanish centres treated with DAAs. Patients were followed up for a median duration of 138 months (11.5 years).

Long-term kidney survival and immunological response were evaluated based on immunosuppressive treatment received. Kidney event was defined as duplication of creatinine level or 50% decrease in glomerular filtration rate, dependence on renal replacement therapy or non-reduction of proteinuria by 50% compared to baseline. Immunological response was defined as the decrease in cryocrit ≤1%.

Results

Sustained virological response was attained in 98 (98%) patients. 49 patients were treated with immunosuppressive treatment associated with DAAs, 26 with rituximab and the rest (23) with steroids and/or cyclophosphamide. Patients receiving immunosuppressive treatment had higher basal cryocrit (6.3±4.5 vs 3.8±3.9%, p=0.011), lower glomerular filtration rate (55±27 vs 68±25 ml/min/1.73 m2) and more haematuria (p=0.001). The 26 patients treated with rituximab had more severe disease: higher viral load (p=0.001), cryocrit (p=0.011), proteinuria (p=0.004), microhaematuria (p=0.012) and hypertension (p=0.012) and lower glomerular filtration rate (p=0.001). 15 patients had a kidney event at the end of follow-up. Predictive variables of kidney events were lower age (HR 0.94, 95%CI 0.89-0.99; P= 0.038) and lower glomerular filtrate rate (HR 0.97, 95%CI 0.94-0.99; p=0.026), in a model adjusted to proteinuria and microhaematuria. Immunosuppressive treatment with or without rituximab did not change kidney survival.

Regarding the immunological response, only 19 patients had a cryocrit >1% at the end of follow-up. There were no differences in age, viral load, proteinuria and basal glomerular filtration rate between these patients with no immunological response and those who had a sustained immunological response over time. The only differences between these two groups were a higher basal cryocrit and a minor C4 levels. Immunosuppressive treatment with or without rituximab did not changed the immunological response.

Conclusion

Patients with more severe HCV-MC are those receiving immunosuppressive treatment. However, immunosuppressive treatment does not change kidney survival nor immunological response of these patients in the long term.
P0238LONG-TERM OUTCOME OF CHILDHOOD IDIOPATHIC NEPHROTIC SYNDROME
Authors: Dao Myriam , Hummel Aurélie , Boyer Olivia , Charbit Marina , Joly Dominique , Dessaix Kathleen , Salomon Rémi , Knebelmann Bertrand , Servais Aude
Published: June 2020

Background and Aims

Little is known about the long-term outcome of childhood idiopathic nephrotic syndrome (INS), in particular long-term complications, rate of relapses, frequency of prolonged steroid (S) and immunosuppressive treatment (IS). The choice of immunosuppressive drug remains discussed. Our aim was to study the long-term outcome in adulthood of patients with INS diagnosed during childhood.

Method

In this monocentric retrospective study, we included all adult patients (>18 years) admitted in our nephrology department between 2013 and 2019 with INS diagnosed during childhood. Patients who reached ESRD during childhood were excluded. Data regarding the outcome in adulthood were obtained through clinical database and medical charts.

Results

Eighty-two patients (M/F = 2/1) were included. Sixty-height patients had steroid-sensitive nephrotic syndrome (SSNS), including 52 with steroid-dependant nephrotic syndrome (SDNS). The other 14 patients had steroid-resistant nephrotic syndrome (SRNS). The median age at diagnosis was 3.9 years (1.2-16.5). The median number of relapses during childhood was 12 (0-52), 0.9/patient/year. 89% of patients received IS therapy in addition to S during childhood: median number of successive therapeutic lines was 3 (0-10) per child.

Median follow-up during adulthood was 4.6 (0.1-25) years. 67% of patients experienced at least one relapse during adulthood, with a median number of relapses of 0.53 (0-3.7)/patient/year. Risk of relapse during adulthood was significantly associated with the total number of relapses during childhood (p=0.015) and with the number of relapses per year during childhood (p=0.007). 45% of patients received IS in addition to S during adulthood, mainly mycophenolate mofetil (23/82), calcineurin inhibitors (21/82) and rituximab (12/82). High blood pressure was observed in 22% of patients.

At last follow-up, median eGFR was 90 (64-117) mL/min/1.73m in SSNS patients, 86 (57-126) mL/min/1.73m in SDNS patients and 70 (23-113) mL/min/1.73m in SRNS patients. Only 4/82 patients presented with eGFR lower than 60 mL/min/1.73m. Among them, 3 had SRNS. Only 1 thrombo-embolic event and 3 severe infections were reported.

Bone densitometry was performed in 26 adult patients and osteopenia was found in 19 of them (73%).

Conclusion

The incidence of relapses in adulthood was relatively high in our study. However bias related to inclusion criteria could play a role. Whereas renal function remained normal in most patients, high blood pressure and osteopenia were frequent but major complications were rarely reported.
P0255THE SHORT TERM MATERNAL OUTCOME OF PREGNANT CHRONIC KIDNEY DISEASE PATIENTS
Authors: Lim Christopher thiam seong , Ong Yun Jin , Yong Shao Wei , Weeven94@hotmail.com Wee Ven Hing , Bidin Mohammad Zulkarnain , Goh Bak leong
Published: June 2020

Background and Aims

Pregnancy in chronic kidney disease (CKD) is associated with increased risk of adverse maternal outcomes and fetal outcomes. The risks are noticeable even in early stages of CKD. Despite the rising concern, there are few follow-up studies in this high-risk group.

Method

We followed up and analysed 538 pregnancies in 173 women with pre-existing of primary renal disease who were seen at a tertiary nephrology centre from January 2007 until December 2015. We sought to investigate the changes in laboratory and clinical parameters, maternal and fetal outcomes.

Results

Figure 1 showed the changes of parameters intra and post-partum period. Increase in weight (p=0.034, OR 1.135, 95% CI 1.01-1.276), antibiotics consumption (p=0.022, OR 0.088, 95% CI 0.011-0.0703), pregnancy-related hypertension (p=0.056, OR 0.161, 95% CI 0.025-1.05) and gromerulonephritis (p=0.049, OR 14.22, 95% CI 1.009- 200.52) were associated with worsening of proteinuria intra-pregnancy and post-pregnancy period. Age more than 30-year-old (p=0.024, OR 0.644, 95% CI 0.439-0.945), multiple pregnancies (p = 0.032, OR 14.4, 95% CI 1.25-165 , antibiotics usage (p=0.033, OR 27.59, 95% CI 1.302-585.169), diuretic usage (p=0.034, OR 0.003, 95% CI 1.26-0.646), pregnancy-related hypertension (p=0.06, OR 21.838, 95% CI 0.878-543.376) and proteinuria (> 1.5g/d) (p=0.025, OR 0.235 95% CI 0.067-0.717) and fetal complications such as fetal death (p=0.013, OR 3.608 95% CI 1.311-9.930) was associated with rapid renal function decline of 25-50% . Elevation of serum uric acid is associated with a higher risk of adverse fetal outcome (r=0.845 p=0.004).

Conclusion

Multiple pregnancies, antibiotic usage, pregnancy-related hypertension are strong predictors of rapid maternal rapid function decline. Pre-conception counselling, minimization of antibiotic usage and aggressive blood pressure monitoring and treatment should be part of the standard treatment for this high-risk population.
P0258EVALUATION OF ACUTE - PHASE REACTANTS IN MONITORING DISEASE ACTIVITY AND RESPONSE TO IMMUNOSUPPRESSIVE THERAPY IN IDIOPATHIC RETROPERITONEAL FIBROSIS
Authors: Obrencevic Katarina , Petroviä‡ Marijana , Rancic Nemanja , Tadiä‡ Jelena , Vavic Neven , Nikolic Bojan , Radojevic Milorad , Rabrenovic Violeta , Mijuskovic Mirjana
Published: June 2020

Background and Aims

Idiopathic retroperitoneal fibrosis (IRF) is a rare disease characterized by fibroinflammatory periaortic tissue that affects the ureters, causing obstructive nephropathy and impairment of renal function. Findings strongly suggest an autoimmune etiology. Medical treatment includes immunosuppressive drugs, but the optimal treatment has not been established. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) represent markers of active inflammation in the early phase of the disease, and hence could be sensitive predictors of the treatment response.

Method

This retrospective case series study includes patients with IRF treated with two different protocols: corticosteroids in combination with mycophenolate mofetil (MMF) and corticosteroids combined with azathioprine (AZA). The total number of 28 patients (13 in the first group and 15 in the second group) were treated and followed in the Clinic of nephrology in Military Medical Academy.

Results

At presentation 92.3% of patients had elevated levels of ESR and CRP, and 67.8% of them had acute renal insufficiency. Systemic symptoms resolved after four weeks in all patients. The kidney function improved significantly in both groups after first moth of treatment, although the creatinine level was higher in the MMF group because of the disease recurrence in 23% of the patients. In MMF group was observed faster reduction in the periaortic mass after six months and 53.8% of patients achieve 100% of the mass reduction at the end of the treatment while 33.3% in AZA group. The levels of ESR and CRP after one month of treatment in AZA group correlated with the fibrotic mass reduction after six months and after one year. In MMF group, only the CRP level after one month correlated with the fibrotic mass reduction achieved after one year.

Conclusion

MMF had more rapid and complete effect in hydrnephrosis withdrawal and total reduction of the fibrotic tissue, comparing with AZA whose effect was slower and without complete mass reduction. CRP strongly correlated with the remission of the disease in both therapeutic protocols.
P0264ASSESSMENT OF GFR IN MORBIDLY OBESE PATIENTS USING DIFFERENT EQUATIONS: WHICH IS THE BEST?
Authors: Sabry Alaa , Basiony Amir , Kamal Mohamed
Published: June 2020

Background and Aims

Obesity is a potent risk factor for the development of kidney disease. The prevalence of abdominal obesity in Egyptians based upon the European cut-off points was 30.2% for men and 70.9% for women.

To detect the best formula for estimation of glomerular filtration rates in morbidly obese individuals.

Method: In this prospective study 82 morbidly obese patients were included, Age: 15 to 65 years, Morbidly obese patient (BMI > 40 Kg/m2), Creatinine clearance calculated from a 24-h urine was done, Estimated glomerular filtration rate (eGFR): It was assessed to be correlated with creatinine clearance and detect the most suitable formula for morbidly obese patients.

Cockcroft-Gault formula:  Cockcroft-Gault formula (for total body weight): ockcroft-Gault formula (for adjusted body weight): Cockcroft-Gault formula (for lean body weight), MDRD-eGFR (Modification of Diet in Renal Disease equation) (Shahbaz & Gupta, 2019), CKD-epidemiology (CKD-EPI): (Levey, et al, 2009)

Results

Demogrphic criteria of the studdied patients

Conclusion: The equations that had the nearest values to creatinine clearance were CG-TBW-GFR and CGAjBW- GFR, both of them had a moderate reliability with more agreement for the CG-TBW-GFR equation . The CG-TBW-GFR formula was the most reliable one to measure GFR, followed by the CG-AjBW-GFR formula, while the CG-IBW, CG-LBW, MDRD-GFR and CKD-EPI-GFR formulae were not reliable at all .
P0266PREDICTIVE FACTORS OF COMPLETE RENAL RESPONSE IN PROLIFERATIVE LUPUS NEPHRITIS: A COLLABORATIVE STUDY
Authors: Sanchez Alamo Beatriz , Cases Corona Clara Maria , Gatius Serena , Dominguez Torres Patricia , Valdes Elena , Shabaka Amir , Fernandez Juarez Gema Maria
Published: June 2020

Background and Aims

Proliferative lupus nephritis (class III and IV) is the most severe form of lupus nephritis and requires prompt diagnosis and treatment with immunosuppressive therapy. Since it represents the most serious entity and has the greatest functional consequences there is a need to determine which factors in proliferative lupus nephritis are most predictive of good long-term renal function.

Method

Methods We analysed the data of 49 biopsy-proven proliferative lupus nephritis (18,4% class III and 81,6% class IV) of three different Spanish hospitals to find prognostic factors for complete renal response (CRR), defined as loss of <25% of eGFR and the absence of proteinuria and microhematuria at the end of the follow up. Sociodemographic, clinical, laboratory, and treatment-related data at the time of kidney biopsy and during follow-up were obtained. We performed univariate analysis and logistic regression to identify independent risk factors.

Results

The median follow-up was 8 years (IQR: 3-12,5), during which time 18 patients (36,7 %) achieved CRR. In the univariate analysis complete renal response was related to: (1) at the diagnosis to: age [40,52 (11,29) years vs 29,92 (11,93) p=0,004]; (2) in kidney biopsy to less leukocyte infiltration (42,3% p=0,05); (3) during the follow up to: less comorbities (27,8% vs 64,3% p=0,02), less infections (27,8% vs 58,6% p=0,04) and less hospitalizations due to infections (0% vs 33,3% p=0,010), less prevalence of high BP (22,2% vs 60,7% p=0,01), (4) at the end of follow up to : serum albumin [3,97 (0,59) vs 4,31(0,19) mg/dL p=0,03].

In the logistic regression comorbidies (HR : 5,71 95%IC: 1,56-20,93 p=0,008) and age at the moment of diagnosis (HR : 1,046 95%IC:1,001-1,071 p=0,04) were related to complete renal response. We didn´t find any differences concerning treatments.

Conclusion

Proliferative lupus nephritis is one of the most severe manifestations of lupus nephritis, resulting in increased morbidity and mortality. Traditionally it has been thought that older patients have a worst prognosis, however we demonstrated that they achieved more frequently CRR. In the management of the patients traditional reno protective measures like strict control of BP must be considered since it is a predictive factor of CRR. We shouldn´t forget about the implications of an aggressive immunosuppressive treatment such as hospitalizations due to infections and comorbities.
P0275SCOPE AND CONSISTENCY OF OUTCOME MEASURES FOR PHYSICAL FITNESS IN TRIALS IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A SYSTEMATIC REVIEW
Authors: Jegatheesan Dev , Modderman Richard , Krishnasamy Rathika , Tong Allison , Coombes Jeff , Viecelli Andrea , Johnson David W , Isbel Nicole M
Published: June 2020

Background and Aims

Impaired physical fitness is prevalent across the spectrum of kidney disease and is associated with an increased risk of mortality, progression to end-stage kidney disease, falls and hospitalisation. Physical fitness outcomes have been extensively reported in randomised trials involving patients with kidney disease. This study aimed to assess the scope and consistency of physical fitness outcomes and outcome measures reported in kidney disease trials.

Method

A systematic review of randomised trials reporting physical fitness outcomes in adults with chronic kidney disease not requiring kidney replacement therapy, receiving maintenance haemodialysis or peritoneal dialysis, and kidney transplant recipients was conducted. The scope, frequency and characteristics of physical fitness outcome measures were categorised and analysed. Trials were identified from MEDLINE, Embase and the Cochrane Library from March 2000 to March 2019.

Results

From 115 relevant trials, 171 outcome measures for 32 outcomes were identified and categorised into five domains of physical fitness: exercise capacity (reported in 83% of trials), physiological-metabolic (57%), neuromuscular fitness (52%), body composition (45%) and cardiorespiratory fitness (19%). Exercise capacity had 53 different outcome measures and at 15 separate time points. The most common outcome measures were the 6-minute walk test (29%), peak oxygen uptake (20%), 1-repetition maximum (19%) and hand-grip strength (11%), with marked inconsistency in the reporting of outcomes between trials. Outcomes were assessed by field-based tests (65%), lab-based tests (31%) and patient-reported measures (4%).

Conclusion

There is large heterogeneity in the reporting of physical fitness outcomes, with inconsistencies in the use of validated, relevant and patient-important outcome measures.
P0283LONG-TERM FOLLOW-UP OF CRYOGLOBULINEMIC SYNDROME WITH RENAL INVOLVEMENT AFTER DAA
Authors: Affatato Stefania , Pollastri Ester , Belotti Elena , Zani Roberta , Zaltron Serena , Spinetti Angiola , Castelli Francesco , Scolari Francesco
Published: June 2020

Background and Aims

To date, the literature shows that HCV eradication with DAA leads to remission from HCV-related cryoglobulinemic syndrome (CS). The goal of our study is to evaluate the effect of DAA treatment on cryoglobulinemic kidney disease.

Method

Since 2015, 58 patients (pts) have been treated in our Centre; among them we have selected 12 pts with active kidney disease at the time of treatment. Clinical manifestations, renal function and immunological tests were monitored during follow-up (range 6-48 months).

Results

General characteristics of the population are shown in Table 1.

At the time of treatment 6 pts had nephritic syndrome (sdr), 1 had nephrotic sdr and 5 pts had mixed nephritic-nephrotic sdr.

It should be noted that 8/12 pts had been treated with Rituximab (RTX) in the 6 months preceding the DAA; despite that they had active disease at baseline.

Ten out of 12 pts went into complete remission after HCV-eradication, 1 went into partial remission. One pt, never treated, did not respond clinically to HCV eradication and therefore underwent RTX therapy.

Other 2 pt with a recent diagnosis of cryoglobulinemic syndrome came to our attention with a clinical picture of nephritic sdr: they’d never been treated with immunosuppressive therapy and get remission only whit HCV eradication.

One pt, although complete CS remission, started hemodialysis for ESRD secondary to ADPKD.

During follow-up 3 pts underwent CS relapse: 2 pts, one with lymphoma, were retreated with RTX after 12 and 48 months respectively; 1 pt, with type I cryoglobulinemia and clinical manifestation of vasculitis, died of acute disease reactivation in Cameroon after 9 months from the end of DAA.

By evaluating the overall population there is a rapid and prolonged clinical response to DAA therapy, in particular a complete resolution of skin ulcers (Tab 2).

Cryocrit decreases and C3 and C4 increase early and persistently after treatment; vice versa the rheumatoid factor does not undergo significant variations.

Proteinuria is reduced at the end of the treatment (EOT) and shows a decreasing trend also afterwards; urinary sediment is drastically reduced at EOT and further decreases during follow-up up to the presence of only isolated urinary anomalies in almost all patients (Tab 3).

Conclusion

The eradication of HCV, and therefore the removal of the immunological stimulus underlying the cryogloblinemic syndrome, appears to be crucial in the control of cryoglobulinemic glomerulonephritis, also after failure of RTX treatment.

However, relapses at variable interval from DAA therapy do not allow us to lose these patients to follow-up even after several years from disease remission.
P0292CONSTIPATION IN CHINESE ELDERLY: A HIDDEN CAUSE OF CHRONIC KIDNEY DISEASE AND THE RISK OF RAPID RENAL FUNCTION DECLINE
Authors: Jian Guihua , Cheng Dongsheng , Wang Zhi , Li Junhui , Yang Qi , Chen Huan , Wang Niansong
Published: June 2020

Background and Aims

Both constipation and chronic kidney disease (CKD) are common among seniors. However, the association between constipation and CKD remain unclear. This study investigates the correlation between the two to provide a new basis for clinical treatment.

Method

Data from Shanghai community elderly physical examination database (2010-2018) were used to conduct a cross-sectional study and a retrospective cohort to evaluate the relationship between constipation and the prevalence of CKD and rapid renal function decline in the elderly community.

Results

The cross-sectional study covered 16,177 participants, with an average age of 71.3. Comparing to no constipation group, seniors with constipation have a higher proportion of suffering from CKD stage 3. Constipation is an independent risk factor contributing to the high prevalence of CKD stage 3 (OR:1.238,95% CI,1.045-1.466). This finding was further tested through a retrospective cohort study that included 4,203 participants with a medium following time of 6.1 years. As a result, 9.5% (n=401) reported to have rapid progression of renal function. After adjustment of confounding factors, the logistic regression analysis indicates that, constipation is an independent predictive variable of rapid renal function decline among aged population.

Conclusion

Constipation is an independent risk factor for the prevalence of CKD and an independent predictor of rapid renal function decline among seniors in the community. Prevention and treatment for constipation should be taken at an early stage, which may reduce the incidence of CKD and delay the progression of CKD.
P0295IMPROVED LEFT VENTRICULAR FUNCTION EVALUATION AFTER KIDNEY TRANSPLANT
Authors: Flores Fonseca Milagros Melissa , Rodriguez Ugarte Viridiana , Villalvazo Osoria Priscila Berenice , Ruiz Cruz Norma Cecilia , Velasco Ramirez Sandra Fabiola , Ramirez Anguiano Ana Cristina , Gomez Navarro Benjamin
Published: June 2020

Background and Aims

Chronic kidney disease (CKD) represents a major risk factor for cardiovascular (CV) disease. CKD pro inflammatory state evokes structural and functional cardiac and vascular changes, such as chronic dysregulation of nitric oxide in vascular muscle, results in left ventricular hypertrophy (LVH), LV dilatation, LV systolic and diastolic dysfunction, endothelial dysfunction and atherosclerosis. Recent advances in echocardiographic methods allows to evaluate changes in cardiac structure and function after KT. The aim of this study was to assess changes in LV structure and function after renal transplantation in patients with end-stage renal disease (ESRD).

Method

All subjects were prospectively recruited prior to kidney transplantation in our center at Centro Medico Nacional de Occidente, Jalisco, Mexico. Demographics, echocardiographic evaluation, clinical and biochemical studies were performed before and after KT. Patients with transplant failure after KT were excluded. Thirty patients were included in the final analysis. Statistical analysis: Results are expressed as means and standard deviation (SD). Accordingly, paired T test or Wilcoxon test were used for comparison of paired observations. Categorical variables were compared using chi-square test or Fisher’s exact probability test, as appropriate. Multivariate logistic regression models including the variables changes in LVEF, LV systolic and diastolic function and LV mass index. Statistical analyses were performed using SPSS v26.0 (IBM Corporation, NY, USA); p < 0.05 was considered statistically significant.

Results

Mean age was 31.99 ± 11.28 years, and 65% were women. Before transplant, LVEF was 58% and pulmonary arterial pressure was 32 mmHg. Ventricular dysfunction was associated with unclamping donor renal vessels at 107.8 ± 7.96mmHg, and lower perioperative hemodynamics values. The LVEF group increased from 25% to 72.5%, and serum creatinine decrease from 2.25 ± 3.76 mg/dl to 1.98± 2.65 mg/dl (p<0.001) by 6 months after kidney transplant. The best set of predictors in multiple regression analysis of renal function were the onset of diuresis and the use of diuretics (R2 = 0.4; p < 0.001).

Conclusion

We observed a significant reversal of LV dysfunction. This was accompanied by a significant improvement on kidney graft function. These findings highlight the dynamics between cardiac and renal function, and support the application of adequate echocardiographic evaluation on CKD patients with low LVEF undergoing KT.