bluuebunny/crossref_metadata_2025 huggingface dataset:
MO079SECURITY OF THERAPEUTIC APHERESIS IN PEDIATRICS. PROSPECTIVE STUDY DURING 2018 IN 171 APHERESIS SESSSIONS
Authors: López Baez Víctor , Arango Sancho Pedro , Calzada Baños Yolanda , Codina Sampera Elena , Vinuesa Jaca Ana , Hernández Zúñiga Lina , Madrid Aris Álvaro
Published: June 2020

Background and Aims

Identify hypocalcemia and hemodynamic disorders related to apheresis in pediatrics either complications in vascular access or related to anticoagulation and adverse reactions with replacement fluid.

Method

Prospective and descriptive study of 171 sessions for therapeutic apheresis in pediatrics during 2018. Inclusion criteria was based on the 2016 Clinical-Practice-of-Therapeutic-Apheresis-guidelines(ASFA). The apheresis technique was selected also based on the 2016 ASFA Guidelines and the expertise in our center.

Results

The 171 sessions were distributed as follows: 73% were immunoadsorption(IA), 12% were cytoapheresis, 10.5% were LDL-apheresis and 4.5% therapeutic plasma exchange(TPE). The average age was 9 years and 58% were women. 50, 33 and 17% were due to Nephrological, Neurological and Digestive pathology respectively. 83% of the nephrological indications correspond to a category I of the ASFA Guidelines, as well as 25% of the neurological indications and all indications of Digestive pathology correspond to a category II. 58, 25 and 17% used temporary catheter, permanent catheter and needles respectively. Only one patient is accidentally removed from the temporary jugular catheter and it has not been related to vascular access or by the apheresis technique itself. Sixty-six percent had individual anticoagulation with citrate/calcium plus heparin and the remaining 33%, only once. Any case of bleeding related to catheter or others. Only 3 sessions of IA in the hypocalcemia objective, being symptomatic in only one of them. Of all 8 sessions of TPE, we performed 6 with frozen fresh plasma as replacement fluid with no adverse reactions.

Conclusion

The apheresis techniques in pediatrics had been presented with few complications in our center, none derived from vascular access, anticoagulation, infections or adverse effects due to use of replacement fluid. The training of medical and nursing staff is essential to identify risk situations. The use of protocols and international guidelines ensure safety in pediatrics.
TO005OPERATIONAL TOLERANCE IN KIDNEY TRANSPLANT RECIPIENTS: TOMOGRAM TRANSCRIPTOMIC STUDY
Authors: Viklicky Ondrej , Klema Jiri , Mrazova Petra , Abramowicz Daniel , Abramowicz Marc , Massart Annick , Hruba Petra , Study Group TOMOGRAM
Published: June 2020

Background and Aims

TOMOGRAM, multicenter study founded by DESCARTES ERA/EDTA WG, aims to identify transcriptomic and genomic signatures of operational tolerance (OT) in recently identified cohort of OT kidney transplant recipients.

Method

RNA sequencing of peripheral blood was evaluated in 15 OT patients recently identified by TOMOGRAM consortium in 8 European countries, 23 stable patients (≥ 15 years on immunosuppression, STA), 14 CABMR patients (≥ 1 year, CR), 14 non-transplant CNI-treated patients and 14 healthy controls (HC). Differential expression was performed using DESEq2 and gene annotation analysis using Enrichr. Besides immunosuppression unadjusted model, robust negative-binomial regression model was created to adjust for immunosuppression intake. The models was trained on homogeneous group of STA patients.

Results

Using model unadjusted for immunosuppression, no differences in transcriptomic profiles between OT, STA and HC groups were identified. Nine transcripts were upregulated and 2 downregulated in OT compared CR group. The number of deregulated transcripts substantially increased when the model was adjusted for immunosuppression. Gene annotation analysis of top ranked deregulated 1109 transcripts (FC>2, adjusted p value <0.0001) showed deregulation of biological processes related to interferon-γ-mediated signaling pathway (p=1.4*10-5), response to cytokine (p=1.5*10-5), type I interferon signaling pathway (p=0.00036), regulation of I-kappaB kinase/NF-kappaB signaling (p=0.0021), cytokine-mediated signaling pathway (p=0.019) and neutrophil mediated immunity (p=0.033). While interferon-γ-mediated and type I interferon signaling were related to transcripts increased in CR, neutrophils associated transcripts were increased in OT. Analysis of cell types transcripts showed enrichment of CD19 B cells (p=1.6*10-9) in CR, while CD56NK cells (p=2.5*10-11) and CD8 T cells (p=1.6*10-11) transcripts predominated in OT. To reveal probability of operational tolerance inside STA group, 13 transcripts able to discriminate OT and CR cohorts with high AUC (>0.89) were used in PCA analysis (ADGRG3, ATG2A, GDPD5, IL16, MX2, SLA2, PRKD2, SLIRP, GNLY, SRCAP, ARGHAP9, IGHM, CD5). The high probability of OT signature was found in a single STA patient.

Conclusion

Contrary to previous reports which pointed out towards naïve B cell signatures, unique OT patients exhibit other specific immunosuppression-independent transcriptomic profiles.
TO012HOW DIFFERENT IS THE CLEARANCE OF LARGE MIDDLE MOLECULES AND INFLAMMATORY MARKERS FROM EXPANDED HEMODIALYSIS THERAPY COMPARED TO ONLINE HEMODIAFILTRATION?
Authors: Hadad Arrascue Fernando , Nilsson Lars-Göran , Bernardo Angelito , Rivera Angela , Guardiola Belmonte, Lourdes , Rosique Florentina , Andreu Muñoz Alberto , Perez Perez Antonio , Cabezuelo-Romero Juan
Published: June 2020

Background and Aims

Expanded hemodialysis (HDx) with a medium cut-off dialyzer, Theranova® 500, can achieve a middle molecule clearance but its efficacy or comparison with HDF is still unknown. It is still unknown on how large middle molecules and inflammation markers are affected over time with a medium cut-off dialyzer. This study compared the purifying effectiveness of Theranova® 500 dialyzer with respect to online Hemodiafiltration (OL-HDF).

Method

Sixty-three patients who were already receiving HDF were evaluated and 43 were randomized by residual renal function. Twenty-one patients received treatment with HDx using Theranova® 500 and 22 patients remained in HDF in post-dilution mode, using a high-flux dialyzer, Polyflux® 170H, for up to 24 weeks. The dialysis time and the adequacy parameters for both arms were the same. Large middle molecules were measured (kappa immunoglobulin free light chains [κ-FLC], lambda immunoglobulin free light chains [λ-FLC], chitinase-3-like protein 1 [YKL-40], fibroblast growth factor 23 [FGF-23] and serum beta-2 microglobulin [β2M]), ; and inflammatory markers (high sensitivity C-reactive protein [hs-CRP], pentraxin - 3 [PTX-3], interleukin-6 [IL-6], interleukin-10 [IL-10]) at 12 weeks of treatment; and its change from baseline to weeks 12 and 24 in mid-week pre-dialysis. The method of measurement was the immunoassay. Siemens immunoassay was used for FLCs.

Results

HDx with Theranova® 500 demonstrated comparable results to OL-HDF with convective volume 24.4±3.2 L in terms of reduction rate (RR) of middle molecules (κ-FLC, λ-FLC, FGF-23 and β2M) at 12 weeks of treatment. HDx demonstrated similar performance to HDF in mid-week pre-dialysis plasma levels of middle molecules from baseline, at 12 and 24 weeks of treatment. Greater RR of YKL-40 at 12 weeks of treatment was seen in HDx group when compared to HDF (58.1% vs 42.4%; p≤0.0001), and there was a difference in the pre-dialysis β2M change from Baseline values between the groups (-0.60 for HDx arm and +3.28 for HDF arm, p=0.46). HDx with Theranova® 500 demonstrated comparable results to HDF in terms of reduction rate (RR) of inflammatory markers (hs-CRP, PTX-3, IL-6 and IL-10) at 12 weeks of treatment.

There were no differences in the parameters of adequacy of dialysis between both arms. Both treatments were effective in maintaining pre-dialysis albumin and fibrinogen levels throughout the study. There were no significant adverse events related to the safety of Theranova.

Conclusion

HDx with Theranova® 500 is an emergent, effective and safe hemodialysis therapy that showed a purifying efficacy at least comparable to OL-HDF.
TO015INTRADIALYTIC ON-LINE MULTICOMPONENT TOTAL REMOVED SOLUTE MONITORING IN SPENT DIALYSATE BY A NOVEL MINIATURIZED OPTICAL SENSOR
Authors: Adoberg Annika , Paats Joosep , Arund Jürgen , Leis Liisi , Pilt Kristjan , Fridolin Ivo , Luman Merike
Published: June 2020

Background and Aims

Urea is the most commonly exploited marker of dialysis adequacy. Plenty of other uremic retention solutes with a deleterious effect on morbidity and mortality of uremic patients accumulate in ESKD patients [1]. Commonly, the uremic solutes are divided into three physicochemical types [2] with the representative markers urea, uric acid (UA),indoxyl sulfate (IS), and β2-Microglobulin (B2M). Optical monitoring of the uremic marker molecules has been proposed [3]. Despite being cumbersome as a clinical routine, direct dialysis quantification from total dialysate collection (TDC) is as the ‘gold standard’ for measuring the total amount of uremic solutes removed [4]. A robust and compact optical on-line dialysis monitoring device is a step closer to automatic assessment of removal of uremic toxins in dialysis.

The aim of this study was to evaluate intradialytic on-line multicomponent Total Removed Solute (TRS) monitoring in the spent dialysate by a novel miniaturized optical sensor during hemodialysis (HD) and hemodiafiltration (HDF) with different settings.

Method

Ten ESKD patients (6 male and 4 female, 60.2±16.8 years) on chronic HDF were enrolled into the study (fistula N=9, graft N=1). For each patient 5 midweek dialysis sessions (length 240min, HD: N=1, Qb=200ml/min, Qd=300ml/min, 1,5m2; HDF: N=4, Qb≥300ml/min, Qd≥500ml/min, Vsubst≥15l, 1,8m2 and 2,2m2) were included. Spent dialysate from the drain was monitored on-line by a miniaturized sensor prototype (Optofluid Technologies OÜ, Estonia). For the reference, the samples from the spent dialysate drain tube of the HD machine were taken as 7, 60, 120 and 180min after the start and at the end of the session (240min). The concentrations of urea and B2M in dialysate were determined in the clinical laboratory. Concentration of IS and UA was determined utilizing the HPLC. TRS values were calculated using the tank weight and the lab or optical tank solute concentrations. t-test was used to determine significant differences between the methods (P≤0.05).

Results

The laboratory and optical TRS values were 489±112mM and 512±87mM for urea (R2=0.870), 4232±712µM and 4331±756µM for UA (R2=0.985), 230±47mg and 231±40mg for B2M (R2=0.906), 606±339µM and 616±321µM for IS (R2=0.969) (Fig. 1), being not statistically different for any uremic solutes. The reason for higher correlation for UA and IS is direct measurements of UA and IS by the optical sensor whereas urea and B2M are estimated indirectly.

Conclusion

Novel miniaturized optical sensor successfully carried out intradialytic on-line multicomponent TRS monitoring for the uremic solutes urea, UA, B2M and IS in the spent dialysate.
P0005TIME-VARYING DIALYSATE BICARBONATE CONCENTRATIONS CAN REDUCE PEAK INTRADIALTIC SERUM BICARBONATE CONCENTRATIONS
Authors: Ebinger Anna , Waniewski Jacek , Malyszko Jolanta , Wieliczko Monika , Mauro Pietribiasi , Leypoldt John (Ken)
Published: June 2020

Background and Aims

Hemodialysis (HD) treatments using bicarbonate-containing dialysis solutions can result in large intradialytic increases in serum bicarbonate concentration, potentially inducing intradialytic alkalemia. It has been suggested that a time-varying, compared with a constant, dialysate bicarbonate concentration may limit the intradialytic increase in serum bicarbonate concentration (Tobvin & Sherman, Semin Dial 2016). We tested this hypothesis using a mathematical model of bicarbonate transport during HD.

Method

We used the H+ mobilization model describing bicarbonate transport during HD (Sargent et al, Semin Dial 2018) to compare intradialytic serum bicarbonate concentrations when using constant or time-varying dialysate bicarbonate concentrations that deliver the same total amount of buffer base to the patient during the HD treatment. We employed this model to evaluate different time-varying dialysate bicarbonate concentration profiles that started at a high value and then decreased as a step function with a 10-minute timing resolution. Dialysis time was 210 minutes, dialysis solutions were assumed to contain acetate at 3 mEq/L, and all kinetic parameters were assumed to be identical to those reported by Sargent et al (Semin Dial 2018). All results with time-varying dialysate bicarbonate concentrations were compared to a constant dialysate concentration of 32 mEq/L.

Results

Example results comparing time-varying (36.0 mEq/L for the initial 40 min, 31.2 mEq/L thereafter) and constant (32 mEq/L) dialysate bicarbonate concentrations are shown in the figure. The time-varying dialysate bicarbonate concentration lowered the peak intradialytic serum bicarbonate by 0.4 mEq/L for approximately one-half of the treatment. Similar reductions in the peak intradialytic serum bicarbonate concentration could be achieved if the initial high dialysate bicarbonate concentration was 37.6 mEq/L for 30 min or 40.8 for 20 min. The optimal initial high dialysate bicarbonate concentrations and the reduction in the peak intradialytic serum bicarbonate concentrations were somewhat dependent on the assumed patient-dependent H+ mobilization coefficient.

Conclusion

We conclude that a time-varying dialysate bicarbonate concentration can lower the peak intradialytic serum bicarbonate concentrations while delivering the same total amount of buffer base to the patient. Whether this approach will yield improved patient outcomes requires further evaluation.
P0011THE ROLE OF AQUAPORIN-11 (AQP11) IN THE THYMUS DEVELOPMENT
Authors: Masaka Kei , Tanaka Yasuko , Ishibashi Kenichi
Published: June 2020

Background and Aims

Some aquaporins transport not only water but also small non-ionic molecules such as glycerol. In fact, aquaporin-9 (AQP9) has been shown to transport glycerol which is critical to support memory T cell survival through metabolic fitness (Cui G et al. Cell. 161:750, 2015). As AQP11 is widely expressed and transport glycerol as well as water, AQP11 may also play a role in immunological system, which will expand the repertoire of the aquaporin research field.

Method

The AQP11 expression in the thymus was examined by RT-PCR, Western blot and immunohistochemistry in mice. Phenotypic analysis and microarray analysis of the thymus were conducted in wild and AQP11 null mice at 21 day old before the development of uremia due to polycystic kidneys.

Results

Both mRNA and protein expressions of AQP11 in the thymus were higher than those of the kidney by RT-PCR and Western blot. Interestingly, the size of the thymus from AQP11 null mice was smaller than that of the wild mice: 28mg vs. 56mg, even after the correction by the body weight: 0.59 % vs. 0.82 %, as the body size of AQP11 null mice was smaller. The vacuolated medullary epithelial cells were observed in the thymus of AQP11 null mice with narrowed cortex. The immunohistochemical analysis revealed the AQP11 expression at the stromal-epithelial cells in the thymus. The microarray analysis of the gene expression in the thymus was compared between the wild and AQP11 null thymus by the annotation analysis based on the David Bioinformatics Resources 6.8 (beta). The up-regulated 66 genes more than 1.5 folds in AQP11 null thymus are mainly related to the PI3K/Akt signaling pathway to promote metabolism, proliferation, cell survival, growth and angiogenesis. On the other hand, the down-regulated 55 genes less than half in AQP11 null thymus are related to energy production and the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Further RT-qPCR analysis confirmed the enhanced expression of Egfr (Epidermal Growth Factor Receptor), Itgb4 (Integrin beta-4) and Il2ra (interleukin 2 receptor alpha) and the diminished expression of aquaglyceroporin AQP7, Pck1 (Phosphoenolpyruvate carboxy-kinase 1) and Ucp1 (Mitochondrial uncoupling protein 1). The up-regulated genes for growth signaling was unexpected with the smaller thymus but may support the survival of the hypoplastic thymus as a compensation. On the other hand, the down-regulated genes may compromise fat-glucose-energy metabolism in the thymus leading to the smaller thymus, which may be aggravated by the decreased expression of AQP7, another glycerol channel.

Conclusion

AQP11 may play an important role in the metabolic control of the developing thymus possibly through its glycerol transport. The smaller thymus with narrower cortex in AQP11 null mice may lead to immunological dysfunction, which is currently under study.
P0014MYELOID-SPECIFIC TARGETING OF NOTCH AMELIORATES RENAL FIBOSIS VIA REDUCED INFILTRATION AND ACTIVATION OF BONE MARROW-DERIVED MACROPHAGE
Authors: Jiang Yali
Published: June 2020

Background and Aims

Macrophages play critical roles in renal fibrosis. However, macrophages exhibit ontogenic and functional heterogeneities, and which population of macrophages contributes to renal fibrosis and the underlying mechanisms remain unclear.

Method

In this study, we genetically targeted Notch signaling by disrupting the transcription factor recombination signal binding protein-Jκ (RBP-J), to reveal its role in regulation of macrophages during the unilateral ureteral obstruction (UUO)-induced murine renal fibrosis.

Results

Myeloid-specific disruption of RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and myofibroblast activation, as well as attenuated epithelial-mesenchymal transition, likely owing to the reduced expression of TGF-β. Meanwhile, RBP-J deletion significantly hampered macrophage infiltration and activation in fibrotic kidney, although their proliferation appeared unaltered. By using macrophage clearance experiment, we found that kidney resident macrophages made negligible contribution, but bone marrow (BM)-derived macrophages played a major role in renal fibrogenesis. Further mechanistic analyses showed that Notch blockade reduced monocyte emigration from BM by down-regulating CCR2 expression. Finally, we found that myeloid-specific Notch activation aggravated renal fibrosis, which was mediated by CCR2+ macrophages infiltration.

Conclusion

In summary, our data have unveiled that myeloid-specific targeting of Notch could ameliorate renal fibrosis by regulating BM-derived macrophages recruitment and activation, providing a novel strategy for intervention of this disease.
P0015SIRT2 REGULATES CISPLATIN-INDUCED ENDOPLASMIC RETICULUM STRESS THROUGH HEAT SHOCK FACTOR 1 DEACETYLATION
Authors: Park Woong , Kim Hyeongwan , Jung Yujin , Kang Kyung Pyo , Kim Won
Published: June 2020

Background and Aims

Nephrotoxicity is an important cisplatin-induced adverse reaction and restricts the use of cisplatin to treat malignant tumors. Endoplasmic reticulum (ER) stress is caused by the accumulation of misfolded proteins, and is induced by cisplatin in kidneys. SIRT2 nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase is a member of the sirtuin family, but its role in cisplatin-induced ER stress remains unclear.

Method

To investigate the effect of SIRT2 on cisplatin-induced ER stress using SIRT2 knockout mice and human proximal tubular epithelial cells (HK-2 cells). We treated cisplatin (20 µg/mL) or induced by intraperitoneal injection of cisplatin (20 mg/kg) and evaluated the changes of ER stress and its signal mechanism.

Results

Cisplatin administration was found to significantly increase the expressions of PRKR-like ER kinase (PERK), phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), and the C/EBP homologous protein (CHOP) and caspase-12 in the kidneys of SIRT2-wild type mice. However, cisplatin-induced increases in the expressions of p-PERK, p-eIF2α, CHOP and, caspase-12 were diminished in kidneys of SIRT2 knockout mice. In vitro, cisplatin significantly increased the expressions of p-PERK, p-eIF2α, CHOP, and caspase-12 in HK-2 cells. When the effect of SIRT2 on cisplatin-induced ER stress was evaluated using SIRT2-siRNA (ON-TARGET plus human SIRT2 siRNA) or the SIRT2 inhibitors, AGK2 and AK1, knockdown or inhibition of SIRT2 significantly attenuated the cisplatin-induced protein expression of p-PERK, p-eIF2α, CHOP, and caspase-12. Immunoprecipitation studies showed SIRT2 bound physically to heat shock factor (HSF)1 and that HSF1 acetylation was significantly increased by cisplatin. In addition, knockdown of SIRT2 increased cisplatin-induced HSF1 acetylation and increased the expression of heat shock protein (HSP)70.

Conclusion

These observations suggest that suppression of SIRT2 ameliorates cisplatin-induced ER stress by increasing HSF1 acetylation and HSP expression.
P0018GLOMERULAR ENDOTHELIAL CELL SENESCENCE DRIVES AGE-RELATED KIDNEY DISEASE THROUGH PAI-1
Authors: Cohen Camille , Oceanc Legoff , Soysouvanh Frederic , Tanou Marine , Vasseur Florence , Nguyen Clement , Amrouche Lucile , Meunier Tanguy , Rabant Marion , Nochy Dominique , Legendre Christophe , Anglicheau Dany , Milliat Fabien , Terzi Fabiola
Published: June 2020

Background and Aims

In age-related chronic kidney disease (CKD), the most frequent histological lesion observed is glomerulosclerosis. The molecular mechanisms involved in this deterioration process are unclear, but cellular senescence might play a role.

Method

By combining several murine models of physiological and accelerated aging with transgenic animals and in vitro models, we discovered the role of endothelial senescence in the development of glomerular lesions.

Results

These senescent glomerular endothelial cells secreted several molecules, grouped under the senescence associated secretory phenotype (SASP) including the plasminogen activator inhibitor 1 (PAI-1). Specific deletion of PAI-1 in endothelial cells prevented the development of glomerulosclerosis during physiological and accelerated aging, by decreasing podocyte loss. In addition, we showed that PAI-1 mediates a detrimental endothelial-podocyte crosstalk, as incubation of podocytes by supernatant of senescent glomerular endothelial cells led to their detachment. Consistently, preincubation of the senescent supernatant with tiplaxtinin, a PAI-1 inhibitor, preserved podocytes. More importantly, we demonstrated that these data are relevant to humans. In fact, PAI-1 staining the day of the transplantation was predictive of kidney allograft dysfunction 12 months after transplantation from elderly donors.

Conclusion

In conclusion, our study uncovers the critical role played by endothelial senescence in the development of glomerulosclerosis during aging and identified PAI-1 as a novel promising biomarker for predicting kidney dysfunction in patients receiving a kidney from elderly donors.
P0024TRIPARTITE MOTIF-CONTAINING 55 (TRIM55) PARTICIPATES IN THE IMMUNE RESPONSE IN THE EXPERIMENTAL ANTI-THY1 GLOMERULONEPHRITIS
Authors: Chen Lei , Jiang Hongli
Published: June 2020

Background and Aims

Mesangial proliferative glomerulonephritis (MsPGN) is considered as an immune- related disease. In the previous study, tripartite motif family was reported to be closely related to immune regulation. Therefore, we performed a series of experiments in vivo and vitro to investigate the role of tripartite motif-containing 55 (TRIM55), a member of tripartite motif family, in the progression of MsPGN.

Method

36 male SD rats were randomly divided into 6 groups to induce anti-Thy1 nephritis. Specimens of the negative control group were collected at 0d after the injection, while those of other groups were collected at 1d, 2d, 3d, 4d, 5d after the injection, respectively. Renal cortex slices were obtained for histological and immunohistochemistry assessmen of CD68. qPCR analysis of glomerulus was performed to examine the expression of TRIM55 . Primary RMCs with overexpression of TRIM55 were obtained through plasmid transfection. In addition, si-RNA tranfection was used to knock down the expression of TRIM55 in primary RMCs. qPCR analysis was conducted to detect the level of cytokines, such as TNF-α, CCL2, CXCL6, CXCL10, and IL-6.

Results

PAS staining results indicated mesangial dissolution occurred since 1d, followed by inflammatory cell infiltration. CD68 immunohistochemical staining results showed that macrophages infiltration peaked at 1d and then decreased gradually. The expression of TRIM55 mRNA also peaked at 1d and decreased gradually, which was consistent with the trend of macrophages infiltration. In primary RMCs, knockdown of TRIM55 led to down-regulation of the expression of cytokines (TNF-α, CCL2, CXCL6, CXCL10 and IL-6). On the other hand, the expression of those cytokines(TNF-α, CCL2, CXCL6, CXCL10 and IL-6) significantly increased in TRIM55-overexpressed primary RMCs.

Conclusion

The above results indicate that TRIM55 participates in the immune response in experimental anti-Thy1 glomerulonephritis by regulating the production of cytokines. We duce TRIM55 may be a promising therapeutic intervention to ameliorate leukocyte infiltration in MsPGN.
P0025BARIATRIC SURGERY MAY REDUCE UPREGULATED EXPRESSION OF FIBROBLAST GROWTH FACTOR 21 AND ANGIOTENSIN-CONVERTING ENZYME 2 IN OBESE PATIENTS
Authors: Yu Byung Chul , Kim Hyoungnae , Park Mooyong , Kwon Soon hyo
Published: June 2020

Background and Aims

Recent studies showed that the fibroblast growth factor 21 (FGF21) and angiotensin-converting enzyme 2 (ACE2)/Angiotensin 1-7 (Ang (1-7))/MAS axis of the renin-angiotensin system counteract to the negative role of Ang II in various disease. In this study, we examed FGF21 and ACE2/Ang (1-7) in obesity and its change after bariatric surgery.

Method

We prospectively enrolled obese patient who performed bariatric surgery and age-sex matched healthy volunteers (HV) (n=12 each). We obtained their clinical information and serum samples. Serum FGF-21, Ang II, ACE2, and Ang (1-7) levels were measured by enzyme-linked immunosorbent assay kits. We measured also FGF-21, Ang II, ACE2, and Ang (1-7) 6 months after bariatric surgery in obese patients (n=12).

Results

FGF21, Ang II, and ACE2 levels were significantly higher in obese patients compared with HV (p= 0.045, < 0.001, and 0.020, respectively). FGF21, Ang II, and ACE2 levels were significantly decreased after bariatric surgery (p = 0.002, 0.005, and 0.023, respectively). There was no significant difference in Ang (1-7) levels between obese patients and HV (p = 0.887) (Figure 1). Although Ang (1-7) levels did not change after bariatric surgery (p = 0.480), changes in Ang (1-7) levels were positively correlated with changes in body mass index (BMI) (R2 = 0.580, p = 0.048) (Figure 2).

Conclusion

FGF21 and ACE2 were upregulated in obese patients and they are reduced after bariatric surgery. A decrease in BMI after bariatric surgery could lead to decrease in Ang (1-7).
P0031IS OXIDATIVE STRESS ASSOCIATED WITH TOTAL KIDNEY VOLUME IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE?
Authors: Dogan Ibrahim , Eser Baris , Aydemir Nihal , Kayadibi Huseyin , Ozcan Oguzhan , Fidan Nurdan , Ozkurt Sultan
Published: June 2020

Background and Aims

Ischemia Modified Albumin (IMA) is a marker of cardiovascular risk factor associated with oxidative stress. In this study, our aim was to determine oxidative stress status in autosomal dominant polycystic kidney disease (ADPKD) and to evaluate its relationship with total renal volume.

Method

Seventy-two ADPKD (mean age 52 (41-64) years) and 33 healthy controls (mean age 54 (42-62) years) (P= 0.372) were included in the study. Total Oxidant Level (TOS) and Total Antioxidant Level (TAS) were measured using the colorimetric method. Oxidative Stress Index (OSI) was calculated. IMA level was measured by ELISA. Total renal volume was assessed by magnetic resonance imaging. The relationship between oxidative stress, inflammation and renal volume was evaluated by correlation analysis. P values <0.05 were considered significant for statistical analyses.

Results

Serum IMA level was higher in the patient group (158.46 ng/ml (85.98-246.70)) than in the control group (70.04 ng/ml (50.40-80.02); (P< 0.001). TOS level and OSI rate were significantly higher in the patient group compared to the control group, and TAS level was not different between the two groups (P< 0.001, P< 0.001, P= 0.576, respectively).Correlation analysis was performed between IMA, TAS and TOS levels, OSI rate and kidney volume. IMA level correlated with TOS level and OSI positively (P< 0.001), but there was no correlation between IMA level and TAS level and renal volume (P= 0.550, P= 0.286, respectively). IMA level was negatively correlated with GFR and positively correlated with proteinuria (P= 0.040, P< 0.001, respectively). There was no correlation between total renal volume and IMA, TAS, CRP and proteinuria. The correlation between volume and GFR and TOS level was borderline negative (P= 0.054, P= 0.051, respectively).

Conclusion

There is an increased level of oxidative stress in ADPKD. Increased IMA level may show oxidative stress in this population. Total renal volume in ADPKD is associated with loss of renal function but not sufficient to show oxidative stress.
P0038WATER RESTRICTION INDUCES THE SHORTENING OF PRIMARY CILIA IN KIDNEY TUBULAR CELLS
Authors: Park Kwon Moo , Kong Min Jung
Published: June 2020

Background and Aims

The primary cilia play a key role in the maintenance of cell homeostasis by sensing and transducing extracellular signals into the cell and are associated with several kidney diseases including ADPKD. Here, we investigated whether water restriction affects the length of primary cilia of kidney tubule cells and its underlying mechanisms.

Method

Some mice were not supplied with water for 2 days and then the length of primary cilia were determined by immunostaining using acetylated-α-tubulin (ac-α-tubulin) antibody. Madin-Darby canine kidney (MDCK) cells were exposed to high concentration of NaCl or mannitol and the lengths of primary cilia were determined under microscope.

Results

Water restriction shortened primary cilia length in kidney tubular cells along with the increase of urine osmolality. Water restriction lowered the expression of acetylated-α-tubulin (ac-α-tubulin), EXOC5, one of the components of exocyst complex, and α-tubulin transferase in the kidney. In MDCK cells, high concentration of NaCl or mannitol treatments shortened primary cilia length and decreased the expression of ac-α-tubulin, EXOC5, and α-tubulin transferase.

Conclusion

These findings demonstrate that water restriction induces the shortening of primary ciliua in kidney tubule cells along with increased urine osmolality, suggesting that primary cilia are involved in the urine concentric process.
P0039IS A NEPHRECTOMY POLYCYSTIC KIDNEY DISEASE NECESSARY FOR PATIENTS WITH END-STAGE CHRONIC KIDNEY DISEASE?
Authors: Perlin Dmitriy , Dymkov Ivan
Published: June 2020

Background and Aims

In the structure of end-stage CKD polycystic kidney disease is about 8-10 %. These patients often required preparation for transplantation. In addition, enlarged kidneys are reducing the volume of the abdominal cavity, negative impact on the peritoneal dialysis (PD).

Method

In 2005-2019 41 nephrectomies were performed in patients with end-stage CKD with polycystic kidney disease: 11 patients have undergone open nephrectomy, 13 patients laparoscopic nephrectomy and 17 retroperitoneoscopic nephrectomy. We analyzed postoperative period and complications, method of treatment end-stage CKD selected in future. In particular, we evaluated the effectiveness of peritoneal dialysis depending on the operating access.

Results

Complications: intraoperative bleeding was in 3 cases, damage of the spleen was in one. The significantly lower blood loss was in the group of operations performed endoscopic access. Subsequently, 16 patients were treated with hemodialysis (HD), 25 patients PD. The effectiveness of PD was estimated by 3 months and 1 year after start treatment by kt/v. In the group of patients with open nephrectomy, the effectiveness on average was 1.61 and 1.44 respectively. Patients underwent laparoscopic nephrectomy the efficiency is in average of 1.72, and 1.60, retroperitoneoscopic nephrectomy 1.88, 1.72 respectively. The conversion method of PD-treatment to the HD within 6 months after surgery was required in 5 patients (open nephrectomy technique), 2 patients (laparoscopic technique), no one patient (retroperitoneoscopic technique) was not required for the conversion PD to HD.

Conclusion

Our experience of nephrectomies in patient with end-stage CKD indicate the safety and effectivity of the endoscopic technique and its applicability to patients on PD. Retroperitoneoscopic access has less impact on the effective area of the peritoneum, which is reflected in the subsequent course of PD.
P0077A NEW MUTATION OF DNAJB11 AS A CAUSE OF CYSTIC KYDNEY DISEASE: THE FOURTH GENE OF ADPKD
Authors: Pisani Isabella , Allinovi Marco , Palazzo Viviana , Gentile Micaela , Giglio Sabrina , Fiaccadori Enrico , Manenti Lucio
Published: June 2020

Background and Aims

Monogenic inherited diseases are an underestimated but important cause of chronic kidney disease (CKD). Despite the increasing knowledge about their inheritance, they are identified in fewer than 10% of CKD patients. Among monogenic causes of CKD, polycystic kidney diseases (PKD) represent a group of disorders with a clinical and genetic heterogeneity and a variable phenotype (from early manifestations during pregnancy or childhood to the absence of clinical manifestations until adulthood). We here present a PKD family with 5 members displaying the disease (Figure 1).

Method

We revised patients clinical history, laboratory data and imaging exams. An accurate family history was recovered. Blood samples were collected from living patients to perform an exome analysis using next generation sequencing to analyze all possible genes involved in PKD.

Results

Each patient presented a clinical history of nephrolithiasis, a variable degree of CKD (from normal kidney function to renal transplant), urinary and blood parameters compatible with distal renal tubular acidosis (hypercalciuria, low urinary citrate excretion and hypokalemia). Imaging exams showed several renal cysts in the medulla or at the cortico-medullary junction with intracystic calcifications (Figure 2). Some patients displayed also large cortical renal cysts and also hepatic and pancreatic cysts. The genetic analysis performed using next generation sequencing in four patients showed a new mutation on the gene DNAJB11; the mutation introduced a stop codon and was identified as pathogenic by prediction programs. It was present in heterozygosity in all subjects and had an autosomal dominant pattern of inheritance.

Conclusion

DNAJB11 mutations were reported as a cause of PKD for the first time in 2018 by Cornec-Le-Gall and colleagues. The nephropathy derived from these mutations need to be differentiated from ADPKD (autosomal dominant polycystic kidney disease), from ADTKD (autosomal dominant tubulointerstitial kidney disease) and from medullary sponge kidney. DNAJB11 encodes a co-chaperone of the endoplasmic reticulum (ER) also called ERdj3. It is part of the HSP40 protein family and plays a central role in both intracellular and extracellular proteomic homeostasis (proteostasis). In the intracellular compartment it acts as a co-chaperone in the pathway of the unfolded protein response (UPR) in which it binds misfolded proteins which have to be secreted and activates BiP an HSP70 of ER whose function is to correct the misfolding. In the kidney it is mainly expressed in the thick ascending limb of Henle’s loop, in the distal tubule and in the collecting duct justifying the clinical presentation of nephropathy and differentiating the disease from ADPKD (Figure 3).
P0093IMPROVED INTEROBSERVER AGREEMENT IN BANFF SCORING OF RENAL ALLOGRAFT BIOPSIES WHEN ROUTINELY USING CD3/PAS STAIN
Authors: Abrahams Neil , Abrahams Lauren , Freeman-Costin Katherine , Obregon Cecilia , Ziadie Mandolin
Published: June 2020

Background and Aims

The BANFF Classification of renal allograft rejection consists of scores for cellular and antibody mediated rejection. The scores for tubulitis (t), interstitial inflammation (i), glomerulitis (g), total inflammation (ti), and endotheliatis (v) have direct prognostic and therapeutic significance as they contribute to a diagnosis of renal allograft rejection. The original BANFF scoring was developed using hematoxylin and eosin (H&E) stain only. This study examines the level of interobserver agreement using H&E and a combination CD3/PAS stain that highlights T lymphocytes and basement membranes.

Method

50 consecutive renal allograft biopsies were retrieved and on each case H&E and CD3/PAS stains (Ventana/Roche Tissue Diagnostics clone 2GV6 for CD3) were performed. CD3/PAS and H&E slides were matched and blinded for two reviewers [reviewer (R1) and reviewer 2 (R2)]. Each case was graded in an identical manner following criteria designated for (t),(i),(g) and (ti) as previously described in the Banff Classification for Renal Allograft Biopsies. Cases were not graded for (v) as there were too few cases with endothelialitis to allow for statistical evaluation. The matched scores were analyzed using weighted Kappa statistics for interobserver agreement within each group. Agreement levels were characterized using Landis and Koch descriptions for level of agreement. All p values were two-tailed, values of <0.05 were considered statistically significant. Statistical analyses was performed using SAS Version 9.4, Cary NC.

Results

Mean age was 44 years with a range of 9 -75 years. Standard deviation (SD) for age was 18 years. Gender distribution was 20% female and 80% male. Agreement between R1 and R2 for (t) scores was moderate (Weighted Kappa 0.5276) as opposed to fair for H&E group (Weighted Kappa 0.4189). Similarly, interobserver agreement was moderate for scores of (i) and (ti) in the CD3/PAS group and fair in the H&E group. For both CD3/PAS and H&E interrater evaluations, agreement was fair to poor for (g) with weighted Kappa of 0.3928 and 0.3559 respectively.

Conclusion

This study showed increased levels of interobserver agreement when using a CD3/PAS combination stain to score allograft biopsies for (t), (i) and (ti). Since (t), (i) and (ti) scores directly affect a diagnosis of rejection, we propose routine use of CD3/PAS in addition to H&E when reviewing renal allograft biopsies. Glomerulitis (g) shows poor interobserver agreement regardless of the stain used and further studies to refine the criteria for (g) in Banff revisions of the classification may be of value.
P0120FEATURES OF ULTRASTRUCTURAL CHANGES IN KIDNEY TISSUE IN THE PATIENTS WHO HAVE PASSED AWAY AS A RESULT OF SEPSIS
Authors: Agayev Mehman , Ismayilova Shalala , Ibishova Arzu
Published: June 2020

Background and Aims

It is believed that septicemia and septicopyemia can lead to functional failure of many organs, including the kidneys. In this regard, it is important to study the morphological features of ultrastructural changes in kidney tissue.

Method

Structural changes in renal tissue of 30 patients who died as a result of sepsis were investigated by electron-microscopy. The burial was carried out at an early stage (1-6 hours after death). The sections obtained for ultrasonic examination were examined on “James 100 S ” electron microscope after contrasting with uranyl acetate and lead citrate solution.

Results

An ultrastructural study of the cells of the cortical and medial layers of the kidneys revealed that there are changes in extracellular contacts and cell fragmentation as a result of lysis of the cytoplasmic membrane of cells. The integrity of the basal membrane of epithelial cells of the proximal and distal tubules are preserved.

However, the basal layer did not have a homogeneous structure, intersected and transparent in certain areas. Numerous vacuoles, lipid supplements and fragments of lysed intracellular proteins in the cytoplasm have been identified in the cytoplasm of cells. Most of the nucleus was in the collapse phase. The lumen of tubules is narrow and most of the microvilli of the brush border are destructed. It was revealed that in sepsis renal failure and severe destructive changes and the formation of necrosis sites in the structural elements of the nephron as a result of bacterial toxins were mainly observed in areas where bacteria were localized.

Conclusion

Abnormalities of podocytes, of endothelial cells, disruption of the basal membrane layers as a result of abnormal damage of organelles especially mitochondria, changes of proximal and distal tubules may be caused by severe renal failure due to sepsis.
P0121KIDNEY BIOPSY FINDINGS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Authors: Ahbap Dal Elbis , Basturk Taner , Sakaci Tamer , Hasbal Nuri Baris , Sevinç Mustafa , Ozagari Ayse Aysim , Eken Kamile Gulcin , Unsal Abdulkadir
Published: June 2020

Background and Aims

The aim of the study is to evaluate kidney biopsy findings other than renal diabetic changes in patients with type 2 diabetes mellitus.

Method

Diabetic patients with kidney biopsy between January 2003 and January 2020 were enrolled to the study. Kidney biopsy was performed to patients with suspicion of kidney disease other than diabetic nephropathy. The suspicious cases were patients without diabetic retinopathy, diabetes mellitus history less than 5 years, creatinine increase faster than expected course and hematuria. Demographic features, biopsy finding were all noted.

Results

Totally, 135 patients’ data were evaluated in which 54.1% was male. Demographic characteristics of the patients and laboratory data are given in Table 1. Mean age was 55.4±11 years and mean diabetes duration was 6.9±6.3 years. Mean duration of diabetes was 5.3±5.5 years in patients with nondiabetic nephropathy whereas it was 10.2±6.4 and 11.2±7.6 years in patients with diabetic and/or nondiabetic pathologies respectively (p<0.05). Serum creatinine and proteinuria level were lower, and hemoglobin levels were higher in patients with nondiabetic nephropathy (p <0.05).C3 was low in 3.7% of patients. ANA and ANCA positivity were seen in 8.1% and 3.7% of the patients, respectively. Patients without diabetic retinopathy was 81.7% of the total cohort. Biopsy indications were renal insufficiency (8.9%), nephrotic syndrome (24.4%), non-nephrotic proteinuria (16.4%), renal insufficiency with nephrotic range proteinuria (25.9%), renal insufficiency with non-nephrotic proteinuria (24.4%). Mean glomeruli number was 19.3±11.1. Ten patients had macroscopic hematuria in which all resolved with conservative care. Early diabetic changes, diffuse and/or nodular glomerulosclerosis were present in 3.1% and 96.9% of diabetic patients, respectively. Biopsies with diabetic changes with other nondiabetic pathologies were 3% of the biopsies. Isolated nondiabetic nephropathy was found in 23.7% of patients. Pathologic findings other then diabetic changes were as follows in patients without diabetic nephropathy: focal segmental glomerulosclerosis (FSGS) 49.5%, membranous glomerulonephritis 14,1%, Ig A nephropathy 12,1%, membranoproliferative glomerulonephritis 5 %, crescentic glomerulonephritis 4,1%, acute tubular necrosis 4,1%, amyloidosis 3%, tubulointerstitial damage 2%, others 6,1%.

Conclusion

Biopsy in diabetic patients is beneficial to show both diabetic nephropathy and other kidney pathologies. Kidney biopsy may be performed if there is suspicion of other glomerular pathologies. Focal segmental sclerosis was the most common pathology in our patients without diabetic nephropathy
P0125ELECTRON MICROSCOPIC DESCRIPTION OF A SENSITIVE DIAGNOSTIC PROXIMAL EPITHELIAL LYSOSOMAL LESION IN PATIENTS WITH CINAC/CKDU/MEN AND CNI NEPHROTOXICITY
Authors: Vervaet Benjamin , Nast Cynthia , Jayasumana Channa , Schreurs Gerd , Roels Frank , Herath Chula , Kojc Nika , Samaee Vahid , Rodrigo Sonali , Gowrishankar Swarnalata , Mousson Christiane , Dassanayake Rajeewa , Orantes Carlos , Vuiblet Vincent , Rigothier Claire , D'Haese Patrick , De Broe Marc
Published: June 2020

Background and Aims

In CINAC patients from Sri Lanka, we recently observed a sensitive constellation of proximal tubular cell findings including cellular/tubular atrophy, cell fragment shedding and, by electron microscopy (EM), the presence of an increased number of enlarged lysosomes. Here we focused on precisely defining the EM lysosomal phenotype and evaluating its presence in CINAC/MeN/CKDu cases and controls from other countries.

Method

Thirthy-two renal biopsies (18 Sri Lanka, 10 El Salvador, 1 India, 3 France) of patients with a diagnosis of CINAC (CKD 1-3A, 3B) were examined by electron microscopy (EM) in comparison to renal biopsies of normal kidneys at implantation, patients with calcineurin inhibitor (CNI) toxicity (n=17), proteinuric nephropathies (n=15), light chain disease (n=4), several cases on nephrotoxic drugs (lomustine, clomiphene, lithium, tenofovir, cisplatinum) and patients with reduced renal function of various causes (n=20).

Results

The aberrant lysosomal phenotypes can be defined as enlarged (>1.2µm) and dysmorphic with a light-medium electron-dense matrix containing dispersed dark electron-dense non-membrane bound round to irregular shaped “aggregates”. In addition, indicative clusters of 4-6 smaller lysosomes with the same features could be observed. No cristae or other features of mitochondria, autophagic vacuoles, lipofuscin/ceroid droplets, peroxisomes (marginal plate), lysosomal myeloid bodies (aminoglycoside nephropathy) or electron dense laminated lysosomal inclusions (Fabry disease) were observed. Patients with calcineurin inhibitor nephrotoxicity and several cases on nephrotoxic drugs (lomustine, clomiphene, lithium) and a subset of patients with light chain disease, all conditions that can either directly or indirectly be linked to calcineurin inhibition, presented the same lesions. We present an image set demonstrating the phenotypical consistency of the diagnostic lysosomal lesion versus similar features that are non-diagnostic.

Conclusion

A rather sensitive constellation of lysosomal lesions in renal proximal tubular cells was detected associated with CINAC/CKDu/MeN and CNI nephrotoxicity in several countries, suggesting a common new pathomechanistic paradigm where CINAC patients are experiencing a tubulotoxic mechanism similar to CNI nephrotoxicity.