bluuebunny/crossref_metadata_2025 huggingface dataset:
P0130THE MORPHOMETRIC ANALYSIS OF GLOMERULI IN OBESE AND NON-OBESE PATIENTS WITH GLOMERULAR DISEASES
Authors: Jordanova Elena , Jankovic Radmila , Naumovic Radomir , Celic Dejan , Ljubicic Bojana , Pantic Igor , Simic-Ogrizovic Sanja , Jovanovic-Basta Gordana
Published: June 2020

Background and Aims

The aim of the study was to evaluate glomerular morphometry in obese and non-obese patients with glomerular diseases: FSGS, IgA nephropathy, membranous glomerulonephritis (MGN) and membranoproliferative glomerulonephritis (MPGN).

Method

The study included 125 patients with glomerular diseases (77 males, mean age 46± 15.2 years): obese (BMI> 27kg/m2- 63 patients) and non-obese (BMI< 27kg/m2-62 patients). The serum concentration of creatinine, proteins, albumin, cholesterol, trygliceride, daily proteinuria were measured at the time of kidney biopsy. Formula Cockcroft-Gault#(Cockcroft-Gault: non-obese) and Cockcroft-GaultLBW: obese) was calculated. Glomerular radius (GR), glomerular volume (GV) and glomerular density (GD) were compared morphometrically between two groups.

Results

At the time of kidney biopsy the obese had significantly lower eGFR, significantly higher creatinine, trygliceride, daily proteinuria compared to non-obese. Obese FSGS patients had significantly higher GR (109.44±6.03 μm vs 98.53±14.38 μm) and GV (3.13±0.49 x106 μm?vs 2.26±0.83 x106 μm?, only midly lower GD (1.91±0.39/mm2 vs 1.95±0.61/mm2) compared to non-obese. Obese IgA nephropathy patients had higher GR (110.69± 15.24 μm vs 107.77±14.53 μm), significantly higher GV(3.34±1.78 x106 μm?vs 2.31± 1.51 x106 μm? and significantly lower GD (1.21±0.29/mm2 vs 2.14±0.54/mm2) in comparation with non-obese. Significant positive association between GV and BMI (r=0.439; p<0.01) in FSGS patients was found. Significant positive correlation between GV and BMI (r=0.683; p< 0.01), but significant negative correlation between GD and BMI (r=-0.710; p< 0.01) in IgA nephropathy patients were found. Obese MGN patients had lower GR (112.82± 13.65 μm vs 118.39± 14.52 μm), GV (3.57± 1.19 x106 μm?vs 4.07± 1.28 x106 μm? and GD (1.89± 0.17/ mm2 vs 1.91± 0.92/mm2) but without significance compared to non-obese. Obese MPGN patients had higher GR(105.89± 12.24 μm vs 92.73± 30.01 μm), GV (2.94± 0.91 x106 μm?vs 2.31± 1.27 x106 μm? and GD (2.32± 0.63/ mm2 vs 2.03± 0.73/ mm2) but without significance in comparation with non-obese. Significant negative association between GD and daily proteinuria (r=-0.417; p<0.01) in MGN patients was found.

Conclusion

Obese FSGS patients had significantly higher GV, lower GD compared to non-obese. Obese IgA nephropathy patients had significantly higher GV and significantly lower GD. Obese MGN patients had lower and obese MPGN patients had higher morphometric parameters of glomeruli compared to non-obese. Significant positive correlation between GV and BMI in FSGS and IgA nephropathy patients were found.
P0131HIGH-DOSE URIC ACID ALTERS CELLULAR PROTEOME, INCREASES INTRACELLULAR ATP, ENHANCES TISSUE REPAIR CAPABILITY AND INCREASES CALCIUM OXALATE CRYSTAL-BINDING CAPABILITY OF RENAL TUBULAR CELLS: IMPLICATIONS TO HYPERURICOSURIA-INDUCED KIDNEY STONE DISEASE
Authors: Sutthimethakorn Suchitra , Thongboonkerd Visith
Published: June 2020

Background and Aims

Hyperuricosuria is well documented to get involved in the pathogenesis of kidney stone disease, especially uric acid (UA) and calcium oxalate (CaOx) types. Nevertheless, hyperuricosuria-induced alterations in renal tubular cells and cascade mechanisms that subsequently trigger kidney stone formation remained largely unknown. This study aimed to examine changes in cellular proteome and function in renal tubular cells after treatment with high-dose UA.

Method

MDCK cells were incubated with 3.5 mM uric acid for 48-h. Cellular proteins were extracted and subjected to quantitative proteomics analysis using 2-D PAGE followed by nanoLC-ESI-ETD MS/MS. The proteome data were confirmed by Western blotting, whereas functional analyses were performed using various assays.

Results

Quantitative proteomics analysis revealed significant changes in levels of 22 proteins in the UA-treated cells that were related to ATPase activity, mitochondrial transport, cell adhesion and molecule binding, cell projection organization and maintenance of location network, metabolic process, response to unfold proteins, and vesicle-mediated transport. Western blotting confirmed changes in levels of cellular proteins identified by quantitative proteomics. Functional assays revealed an increase in intracellular ATP level and enhancement of tissue repair capability in the UA-treated cells. Interestingly, isolation/purification of apical membranes followed by Western blotting showed the increased levels of HSP70 and HSP90 (the known receptors for CaOx crystals) on apical membranes of the UA-treated cells. CaOx crystal-cell adhesion assay revealed significant increase in CaOx-binding capability of the UA-treated cells, whereas neutralization of the surface HSP70 and HSP90 using their specific monoclonal antibodies caused significant reduction in such binding capability (even below the basal level).

Conclusion

These findings highlighted changes in renal tubular cells in response to high-dose UA that might be related to the pathogenic mechanisms of kidney stone disease associated with hyperuricosuria.
P0133INCREASED INTRA-ABDOMINAL PRESSURE DURING LAPARASCOPIC PNEUMOPERITONEUM ENHANCES ALBUMINURIA VIA RENAL VENOUS CONGESTION, ILLUSTRATING PATHOPHYSIOLOGICAL ASPECTS OF HIGH OUTPUT PREECLAMPSIA
Authors: Schoutteten Melanie , Pauline Dreesen , Vande Velde Nele , Heylen Line , Kaminski Iris , De Moor Bart , Malbrain Manu , Gyselaers Wilfried
Published: June 2020

Background and Aims

Intra-abdominal hypertension (IAH) causes severe organ dysfunction. Our aim is to evaluate the effect of increased intra-abdominal pressure (IAP) on renal function, hypothesizing that venous congestion may increase proteinuria and fluid retention without endothelial dysfunction.

Method

Three urine samples were collected from 32 non-pregnant women undergoing laparoscopic assisted vaginal hysterectomy (LAVH) and from 10 controls placed in Trendelenburg position for 60 minutes. Urine sampling was done before (PRE), during or immediately after (PER), and two hours after (POST) the procedure. Urinary albumin, protein and creatinine concentrations were measured in each sample, ratios were calculated and compared within and between groups.

Results

During LAVH, the albumin/creatinine ratio (ACR) increased and persisted POST-procedure, which was not observed in controls. A positive correlation existed between the LAVH duration and the relative change in both ACR and protein/creatinine ratio (PCR) PER- and POST-procedure.

Conclusion

Iatrogenic IAH increases urinary ACR and PCR in non-pregnant women via a process of venous congestion. This mechanism might explain the presentation of one specific subtype of late-onset preeclampsia, where no drop of maternal cardiac output is observed.
P0134PROTEINURIA IS NOT ALWAYS ASSOCIATED WITH PROGNOSIS IN IGA NEPHROPATHY
Authors: Cho Byoung-Soo , Yun Hyaejin , Jung Sungmin , Lee Hyun-soon
Published: June 2020

Background and Aims

To date the most widely well studied risk factor for progression to ESRD in patients with IgA nephropathy is proteinuria. Recent report suggests proteinuria reduction as a surrogate end point in trial of IgA nephropathy(2019,CJASN). Sensitivity of most biomarkers such as blood and urine gd-IgA1 level, IgG/IgA autoantibody, sCD89, sCD71, NGAL, KIM-1, Cystatin-C etc were compared with the amount of proteinuria. Most nephrologists do not performing kidney biopsy in patients without proteinuria or proteinuria less than than 500mg/day even though IgA nephropathy is suspected. However we recently experienced severe IgA nephropathy (HSD Lee, grade IV) in patients with normal urinalysis, and more than half the patients showed stationary or aggravated renal pathology at the follow up renal biopsy although urinalysis findings were normalized after methylprednisolone pulse therapy.

Method

In our center we performed 892 renal biopsies during last 6 years, we experienced 253 IgA nephropathy, of which 152 cases were done follow up renal biopsies to see the pathologic changes who showed normalized urinalysis findings after methylprednisolone pulse therapy.

Results

Of the 253 patients 241 patients showed initial abnormal urinalysis like hematuria and or proteinuria. However eleven patients showed normal urinalysis at the time of renal biopsy, of which 5 cases were diagnosed as essential hypertension and 6 cases were normal urinalysis associated with lowered GFR. Of the 152 follow up renal biopsies we evaluated 99 cases who showed normalized urinalysis findings after therapy, of which 65 cases(65.7%) showed stationary or aggravated renal pathology.

Conclusion

In conclusion further long term studies are needed, proteinuria could not be a surrogate marker for prognosis of the IgA nephropathy, Regardless of proteinuria if associated with hypertension and or lowered GFR, renal biopsy should be done. Follow up renal biopsy might be needed to confirm the healing of IgA nephropathy regardless of urinary findings to see the disappearance of IgA deposition, decreasing mesangial and endocapillary hypercellularity, disappearance of crescent formation, decreasing sclerosis, etc.
P0135EFFECT OF LYSOPHOSPHATIDIC ACID REGULATION ON THE AGING KIDNEY
Authors: JIN YONGJIE , Kim Eun Nim , Lim Ji Hee , Kim Hyung Duk , Kim Yaeni , Ban Tae Hyun , Park Cheol Whee , Choi Bum Soon
Published: June 2020

Background and Aims

Lysophosphatidic Acid (LPA) is a bioactive lysophospholipid that is present in all tissues. It has been reviewed that LPA could induce oxidative stress and inflammation. Oxidative stress is a major characteristic of aging which is a critical risk factor of renal dysfunction. Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that regulates the expression of antioxidants, which could improve cell viability by reducing oxidative stress, is found to be decreased in the aging kidney. Also, LPA regulates the expression of Nrf2 has been reported. In this study, we evaluate the effect of LPA in the aging kidney by elucidating the potential LPA-Nrf2 signaling pathway.

Method

Male 2- and 24-month-old C57/BL6 mice were used in this study. We measured histological change, oxidative stress, and aging-related protein expression in the kidneys.

Results

24-month-old mice displayed increased albuminuria. Creatinine clearance decreased with aging. There were increases in mesangial volume and tubulointerstitial fibrosis in 24-month-old mice. There were also increases in autotaxin, LPAR1, PI3K, Akt, GSK3β expression with aging and Nrf2, NQO1, HO1, SOD1, SOD2 were decreased in 24-month-old mice.

Conclusion

LPA signaling decreased antioxidants expression via down-regulating Nrf2. Targeting the LPA-Nrf2 pathway provides new evidence to decrease aging-related disease in the kidney.
P0143OPPOSING EFFECTS OF P38 MAPK IN PODOCYTES ON ALDOSTERONE-INDUCED GLOMERULAR INJURY IN POD-GC-A CKO MICE
Authors: SUGIOKA SAYAKA , Kato Yukiko , Ishii Akira , Mori Keita , Osaki Keisuke , Tokudome Takeshi , Matsusaka Taiji , Yanagita Motoko , Yokoi Hideki
Published: June 2020

Background and Aims

Previously, we demonstrated that uninephrectomized aldosterone-infused, high salt-fed podocyte-specific guanylyl cyclase-A (natriuretic peptide receptor 1) conditional KO (pod-GC-A cKO) mice exhibited glomerular injury and that pharmacological inhibition of p38 MAPK ameliorates podocyte damage. However, the effects of genetic deletion of p38 MAPK in podocytes of pod-GC-A cKO mice have been unclarified.

Method

We generated p38 MAPK(fl/fl);Nephrin-Cre (pod-p38 MAPK cKO) mice and p38 MAPK(fl/fl);GC-A(fl/fl);Nephrin-Cre (pod-p38MAPK/GC-A DKO) mice. For induction of glomerular injury, we treated them with aldosterone and high salt at 2 months of age for 3 weeks without nephrectomy (B-ALDO). In vitro, we examined the effect of p38 MAPK inhibitor in cultured human podocytes transfected with GC-A siRNA.

Results

B-ALDO-treated pod-p38 MAPK/GC-A DKO mice resulted in significant elevation of serum Cr (0.29 ± 0.04 mg/dl), massive albuminuria (42,660 ± 20,200 μg/mgCr) and severe foot process effacement in addition to intracapillary fibrin thrombi which indicated endothelial damage. Vehicle-treated DKO mice, B-ALDO-treated pod-GC-A cKO mice, and B-ALDO-treated pod-p38 MAPK cKO showed normal serum Cr levels (0.14 ± 0.01, 0.18 ± 0.02, 0.20 ± 0.01 mg/dl, respectively), mild increase of albuminuria (223 ± 6.5, 1,496 ± 592, 649 ± 303 μg/mgCr, respectively) and only segmental foot process effacement. Blood pressure was not elevated in either mutant mice compared with that of B-ALDO control mice. Furthermore, glomerular mRNA expressions of MCP-1, PAI-1, and FN were upregulated and that of VEGF-A was downregulated in DKO mice. In vitro, suppression of GC-A mRNA by siRNA in combination with p38 MAPK inhibitor downregulated VEGF mRNA in human cultured podocytes. Our previous works showed that pharmacological inhibition of p38 MAPK in the whole body ameliorated podocyte damage, whereas our current result showed that genetic deletion of p38 MAPK in podocytes aggravated renal injury. In order to explain the discrepancy in these results, we added an analysis of podocyte specific GC-A fl/fl p38 fl/+ cKO mice. Pod GC-A fl/fl p38 fl/+ cKO mice exhibited considerably milder renal damage than pod GC-A fl/fl p38 fl/fl double cKO mice.

Conclusion

Genetic complete p38 MAPK deletion in GC-A-nul podocytes exacerbated aldosterone-induced glomerular endothelial cell injury as well as podocytes, and resulted in renal dysfunction, probably through VEGF downregulation, whereas partial p38 MAPK inhibition in podocytes ameliorated aldosterone-induced glomerular injury in pod-GC-A cKO mice. These results suggest a certain level of p38 MAPK in podocytes is necessary to protect endothelial and epithelial cells from aldosterone-induced renal injury.
P0144LOW-ENERGY SHOCKWAVE TREATMENT PROMOTES ENDOTHELIAL PROGENITOR CELL HOMING TO THE STENOTIC PIG KIDNEY
Authors: Zhao Yu , Zhang Xiao liang , Liu Bicheng , Lerman Lilach
Published: June 2020

Background and Aims

Endothelial progenitor cells (EPCs) patrol the circulation and contribute to endothelial cell regeneration and tissue revascularization. Atherosclerotic renal artery stenosis (ARAS) induces microvascular loss in the stenotic kidney. A regimen of low–energy shockwave therapy (SW) induces angiogenesis and reduces chronic ischemia, but the mechanism remains unclear. This study tested the hypothesis that SW increases EPCs homing to the stenotic kidney and increases renal capillary regeneration in a unilateral ARAS swine model.

Method

Domestic pigs were randomized to normal control or unilateral ARAS (induced by a local irritant coil in the renal artery and a high-fat diet). ARAS pigs were treated with low-energy SW (0.1 mJ/mm2) or sham (n=6 each group), bi-weekly for 3 consecutive weeks, starting after 3 weeks of ARAS. Blood samples for EPCs (CD34+ and KDR+ by flow cytometry) and the homing factor SDF-1 were collected 4 weeks after completion of SW treatment from the inferior vena cava (IVC) and the stenotic kidney (STK) vein and artery. Urine was collected from the urinary bladder. Kidneys were studied ex vivo for morphology and expression of an endothelial cell marker (CD31) and the pro- angiogenic growth factor angiopoietin (Ang)-1.

Results

In ARAS, tubulointerstitial fibrosis, tubular score, urinary protein, serum creatinine and mean arterial pressure were significantly increased and capillary count (Fig. 1A) decreased (P<0.05 vs. control), but all markedly improved in ARAS+SW (P<0.05 vs. ARAS). EPC number was decreased in the IVC and renal artery of ARAS pigs (Fig. 1B), but improved in ARAS+SW. SDF-1 levels in the IVC, STK vein and artery, and Ang-1 expression in the kidney of ARAS+SW, were all increased (P<0.05 vs. ARAS).

Conclusion

Low-energy shockwave improves ischemic kidney capillary density, which is associated with and may be at least in part mediated by promoting EPC mobilization and homing to the stenotic kidney.
P0145MESENCHYMAL STEM CELLS PROTECT RENAL TUBULAR CELLS VIA TSG-6 REGULATED MACROPHAGE FUNCTION AND PHENOTYPE SWITCHING
Authors: Zhao Yu , Zhang Xiao liang , Liu Bicheng , Lerman Lilach
Published: June 2020

Background and Aims

Tumor necrosis factor-α-induced gene/protein (TSG)-6 is a key factor influencing mesenchymal stem cells (MSCs) immunomodulatory properties, but its renoprotective efficacy is unknown. Using a novel swine model of renal artery stenosis (RAS) complicated by metabolic syndrome (Mets), we assessed the therapeutic effects of adipose tissue-derived MSCs-produced TSG-6 and mechanisms underlying the immunomodulatory properties of MSCs.

Method

Five groups of pigs (n=6 each) were studied after 16 weeks of diet-induced Mets and unilateral RAS (Mets+RAS), either untreated or treated 4 weeks earlier with a single intra-renal delivery of autologous posrcine adipose tissue-derived MSCs (pMSC). Lean, Mets, and RAS shams served as controls. We studied renal function in vivo (using CT imaging) and kidney histopathology and macrophage phenotype ex vivo. In vitro, TSG-6 levels were measured in conditioned media of human MSCs (hMSCs) incubated with or without TNF-α. Additionally, levels of the tubular injury marker LDH were measured in conditioned media after co-culturing macrophages with injured HK-2 cells (achieved by TNF-α and antimycin-A, AMA) with or without addition of TSG-6. The effects of TSG-6 on macrophage phenotype (M1/M2), adhesion, and migration capability were determined.

Results

Mets+RAS pigs showed increased renal M1 macrophages and renal vein TNF-α levels. After p-MSCs delivery, renal vein TSG-6 increased and TNF-α decreased, M1 macrophage switched to M2 (Fig. A),, renal function improved, and fibrosis alleviated. In vitro, TNF-α increased TSG-6 secretion by h-MSCs. TSG-6 decreased LDH release from injured HK-2, induced a macrophage phenotypic switch from M1 to M2 (Fig. B), and reduced M1 macrophage adhesion and migration (Fig. C).

Conclusion

TNF-α-induced TSG-6 release from MSCs in vivo and in vitro may decrease renal tubular cells injury, which is associated with and may be at least in part mediated by regulating macrophage function and phenotype.
P0146MESENCHYMAL STEM CELLS AND THEIR EXTRACELLULAR VESICLES PROGENY DECREASE RENAL INJURY IN EXPERIMENTAL SWINE RENAL ARTERY STENOSIS THROUGH DIFFERENT MECHANISMS
Authors: Zhao Yu , Zhang Xiao liang , Liu Bicheng , Lerman Lilach
Published: June 2020

Background and Aims

Novel therapies are needed to address the increasing prevalence of chronic kidney disease. Mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) augment tissue repair. EVs have practical benefits, but their efficacy relative to MSCs is incompletely understood. We tested the hypothesis that EVs are as effective as MSCs in protecting the stenotic kidney but target different injury pathways.

Method

Pigs were studied after 16 weeks of renal injury achieved by diet-induced metabolic syndrome (Mets) and renal artery stenosis (RAS). Pigs were untreated or treated four weeks earlier with a single intrarenal delivery of autologous adipose tissue-derived MSCs (1 × 107) or EVs (1 × 1010). Lean pigs and sham RAS served as controls (n=6 each). Stenotic kidney function was studied in-vivo using CT. Histopathology and expression of necroptosis markers (RIPK-1 and RIPK-3), inflammatory and growth factors (angiopoeitin-1 and VEGF) was studied ex-vivo.

Results

Stenotic-kidney glomerular filtration rate and blood flow in Mets+RAS were both lower than Mets, increased in Mets+RAS+MSCs, and further improved in Mets+RAS+EV. Both MSCs and EVs improved renal function, hypoxia, and decreased renal fibrosis and apoptosis. MSC were slightly more effective in preserving microvascular density (0.02-0.2mm in diameter), and prominently attenuated renal inflammation. However, EVs more significantly upregulated growth-factor expression and decreased necropotosis.

Conclusion: Adipose tissue-derived MSCs and their EVs both improve stenotic kidney function and decrease tissue injury in Mets+RAS. MSCs more effectively preserve the microcirculation, while EVs bestow better preservation of renal cellular integrity. These findings encourage further exploration of this novel approach to attenuate renal injury.
P0157GENETICALLY DETERMINED HYPOALBUMINEMIA AND THE RISK OF HYPERTENSION: GWAS-BASED INSTRUMENTAL VARIABLE ANALYSIS
Authors: Han Sang-Woong , Yu Mi-yeon , Choi Jong Wook , Yi Joo-Hark , Lee Chang Hwa , Park Joon-Sung
Published: June 2020

Background and Aims

Hypoalbuminemia is a clinical indicator of vascular endothelial dysfunction. However, the genetic association of hypoalbuminemia with hypertension has not yet been clarified. We investigated whether genetic variation(s) associated with decreased serum albumin level is deeply related with increased risk of hypertension.

Method

Mild hypoalbuminemia was defined as a serum albumin concentration of less than 4.0 g/dL. We performed GWAS-based instrumental variable analysis using the population-based cohort data collected from KoGES. Eligible as cases were all native Koreans without significant medical illness and a total 4326 participants were divided in into control (n = 3157) and hypoalbuminemic (n = 1168) according to their serum albumin level.

Results

Our GWAS revealed that 71 susceptibility loci were associated with mild hypoalbuminemia and subsequent two-stage least squares estimation analysis showed that both genetic variations at rs2894536 in LOC107986598 gene and rs10972486 in the ATP8B5P gene were related with systolic blood pressure. In subsequent Cox-proportional hazards model, we found that not only low serum albumin (HR = 0.654, 95% CI = 0.521-0.820), but also polymorphisms of rs2894536 (HR = 1.176, 95% CI = 1.015-1.361) and rs10972486 (HR = 1.152, 95% CI = 1.009-1.316) were significant predictor of hypertension. Our two-stage residual inclusion analysis indicated that candidate genetic variation attenuated the association between serum albumin and hypertension, showing hazard ratios of hypoalbuminemia on development of hypertension were 0.762 (0.659-0.882) for rs2894536 and 0.759 (0.656-0.878) for rs10972486.

Conclusion

These findings support a causal relationship between hypoalbuminemia-associated genetic variation, hypoalbuminemia and development of hypertension.
P0162HEMODIALYSIS AND PERITONEAL DIALYSIS PATIENTS HAVE SEVERELY IMPAIRED ENDOTHELIAL POST-OCCLUSIVE FOREARM VASODILATORY RESPONSE ASSESSED WITH LASER SPECKLE CONTRAST IMAGING
Authors: Alexandrou Maria Eleni , Gkaliagkousi Eugenia , Loutradis Charalampos , Dimitriadis Chrysostomos , Mitsopoulos Eustathios , Lazaridis Antonios , Nikolaidou Varvara , Dolgiras Panagiotis , Papadopoulou Dorothea , Douma Stella , Papagianni Aikaterini , Sarafidis Panteleimon
Published: June 2020

Background and Aims

Endothelial dysfunction is associated with cardiovascular events and mortality in various disease states, including end-stage-renal-disease (ESRD). Novel technological approaches have emerged for real-time assessment of endothelial reactivity. This study examined forearm skin microcirculation using Laser Speckle Contrast Imaging (LSCi) before and after arterial occlusion in ESRD patients undergoing hemodialysis (HD) or peritoneal dialysis (PD)

Method

38 patients undergoing HD were matched in a 1:1 ratio with 38 PD patients (for age, sex and dialysis vintage) and 38 controls (for age and sex). Skin microvascular reactivity parameters assessed with LSCI included baseline perfusion, occlusion perfusion, and peak perfusion during post-occlusive reactive hyperemia (PORH); time to peak perfusion; proportional change from baseline to peak perfusion; baseline and peak cutaneous vascular conductance (CVC); proportional change from baseline to peak CVC; and the amplitude of the PORH response (calculated as the difference between peak and baseline CVC).

Results

Baseline perfusion [HD: 46.97±14.6; PD: 49.32±18.07; controls: 42.02±11.94 Laser-Specle-Perfusion-Units (LSPU), p=0.097] and peak post-occlusion perfusion (104.77±28.68 vs 109.04±40.77 vs 116.96±30.96 LSPU, p=0.238) did not differ between groups. However, the post-occlusive vascular response was completely different, since time to peak response (HD: 7.24±6.99; PD: 10.68±9.45; controls: 11.11±5.1 sec, p=0.003) and the (%) increase from baseline to peak perfusion (HD: 133%±66; PD: 149%±125; controls: 187%±61, p=0.001) was significantly lower in ESRD patients.

ESRD patients had also lower levels of peak CVC, indicating the maximum capillary recruitment (HD: 1.05±0.3; PD: 1.07±0.44; controls: 1.57±0.52 LSPU/mmHg, p<0.001), lower % increase of CVC at peak (p=0.001), and lower amplitude of the PORH response (p=0.001) (a measure of the difference between baseline and maximum capillary recruitment).

Conclusion

Using this novel non-invasive technology endothelial post-occlusive skin vasodilatory response was found to be similar between HD and PD patients and significantly impaired compared to controls. Future studies are needed to assess the prognostic implications of this microcirculatory functional defect.
P0180U-SHAPED RELATIONSHIP BETWEEN SERUM URIC ACID LEVEL AND THE RISK OF END STAGE RENAL DISEASE AND ALL-CAUSE MORTALITY IN MEN
Authors: Go Su-Ryeong , Lee, Hajeong , Heo Nam Ju , CHIN HO JUN , Na Ki Young
Published: June 2020

Background and Aims

High uric acid level was known as a risk factor to incident chronic kidney disease, mortality, or cardiovascular mortality. However, it is obscure which level of uric acid (UA) is safe to prevent end stage renal disease (ESRD) and mortality. We searched the optimal range of UA level to escape the incident ESRD and death in a large cohort of general population.

Method

We enrolled 143,762 adult subjects participated in voluntary health check-up program from three referral hospitals in Korea between 1995 and 2009. We defined 48,147 control subjects (CONTROL) without risk factors of high UA level, to calculate 5, 20, 80, and 95 percentiles of UA level and allocated whole participants into five groups (G1, G2, G3, G4, G5) according to the criteria in each gender. We merged the incident data of ESRD from the Korean ESRD registry by December 2017 and the mortality data from the Ministry of the Interior and Safety by May 2018 based on the identifier of Koreans. This project was approved by institutional review boards of the three hospitals.

Results

The UA levels of 5, 20, 80, 95 percentiles in CONTROL were 2.9 mg/dL, 3.5 mg/dL, 4.9 mg/dL, and 5.7 mg/dL in females, and 4.1 mg/dL, 5.0 mg/dL, 6.8 mg/dL, and 7.8 mg/dL in males. There were 76,784 (53.4%) males and 66,978 (46.6%) females. The age was 50.5 ± 12.2 years and the level of GFR by CKD-EPI equation was 94.3 ± 15.2 ml/min/1.73 m2 at enrollment. Among females, ESRD was developed in 110 subjects (0.2%) and 1,922 subjects (2.9%) were dead during more than 12 years. The level of UA and groups of UA were not independent risk factors to mortality or incident ESRD in females. Among males, there were 162 subjects with ESRD (0.2%) and 4293 subjects (5.6%) were dead. Compared to G3 group (5.0 mg/dL ≤ UA<6.8 mg/dL), other groups showed higher risk of incident ESRD adjusted with related factors by Cox’s hazard proportional model in males (p=0.016). The Hazard ratios (HRs) for incident ESRD in G1 group (<4.1 mg/dL), G4 group (6.8 mg/dL ≤ UA< 7.8 mg/dL), and G5 group (7.8 mg/dL ≤ UA) were 2.409 (95% CI, 1.312-4.423, P=0.005), 1.710 (95% CI, 1.080-2.707, P=0.022), and 1.742 (95% CI, 1.098-2.762, P=0.018), respectively. The HRs for all-cause mortality in G1, G4, and G5 group were 1.203 (95% CI, 1.017-1.346, P=0.001), 1.099 (95% CI, 1.006-1.201, P=0.037), and 1.137 (95% CI, 1.015-1.272, P=0.026), respectively. We found there were 591 subjects died from cardiovascular disease (CVD) among 3,352 deaths with valid cause of death. G1 and G5 group showed higher risk for CVD-mortality compared to G3 group in men (p<0.001).

Conclusion

Serum uric acid level showed U-shaped pattern of HRs for incident ESRD and all-cause mortality in men, only. The appropriate uric acid level might be 4.1-6.7 mg/dL in men.
P0188TOTAL CHOLESTEROL EXCESS DOESN'T AFFECT CORONARY ARTERY CALCIFICATION INDEPENDENTLY OF RENAL FUNCTION
Authors: Kuryata Olexandr , Shatailo Viktor , Nikolaichyk Alina , Semenov Viktor
Published: June 2020

Background and Aims

Coronary artery calcium score (CACS) allows to improve significantly predictive value of traditional tools for cardiovascular risk estimation. Reduced renal function is associated with increase of rates of cardiovascular events. Dyslipidemia is an important factor of cardiovascular system injury in chronic kidney disease. The Aim. To investigate association between glomerular filtration rate (GFR), total cholesterol and CACS.

Method

We performed the study on 170 patients (77 males and 93 females, aged 56 [52;63] years) who underwent CACS at Dnipropetrovsk Mechnikov Regional Hospital, Dnipro, Ukraine, from December 2017 till March 2019. Patients in the study were free of known cardiovascular disease and required reclassification of cardiovascular risk. Patients were subdivided by total cholesterol (TC) level (<5.2 mmol/l, n=83; ≥5.2 mmol/l, n=87) and by GFR (≥90 ml/min, n=64; 60-89 ml/min, n=90; 30-59 ml/min, n=16). CACS was presented in Agatston units (AU).

Results

Median age in groups by TC was comparable (56 [53;63] vs 56 [51;64] years, p=0.51) and elevated significantly with decline of GFR (54 [49;59], 57 [53;65] and 70 [59;77] years for patients with GFR≥90, 60-89 and 30-59 ml/min respectively, p for trend <0.001). We didn’t observe any statistically significant differences of CACS after patients subdivision, though it was higher in TC≥5.2 mmol/l group.

Conclusion

We didn’t find convincing data supporting significant impact of TC excess on coronary artery calcification.
P0192RELATIONSHIP BETWEEN SERUM HEPCIDIN AND THE PROGRESSION OF CHRONIC KIDNEY DISEASE: KOREAN COHORT STUDY FOR OUTCOME IN PATIENTS WITH CHRONIC KIDNEY DISEASE (KNOW-CKD)
Authors: Sung Su Ah , Han Kum Hyun , Lee Jien , Lee Taehee
Published: June 2020

Background and Aims

Hepcidin plays a central role in iron metabolism. However, few studies have evaluated the relationship between serum hepcidin and the progression of chronic kidney disease (CKD). This study aimed to determine the relationship between serum hepcidin levels and the progression of renal diseases in patients with CKD.

Method

We reviewed data of 2,016 patients from a large-scale multicenter, prospective study enrolled between 2011 and 2016, who had data regarding the serum hepcidin level, hemoglobin level, iron indices, usage of erythopoiesis-stimulating agents (ESA) or iron, and follow-up of renal events. Renal events were defined as a >50% decrease in kidney function from the baseline values, doubling of the serum creatinine level, or initiation of renal-replacement treatment.

Results

During a mean 3.6 years, 556 patients developed renal events (27.6%). In multivariate Cox proportional hazard regression analysis adjusted for confounders including kidney function, the hemoglobin level, conventional iron indices, usage of ESA or iron, and other chronic diseases, the hazard of serum hepcidin for renal events was evident in the comparison between only the first and fourth quartiles (hazard ratio 1.603, 95% confidence interval, 1.187-2.163, P = 0.002). In the multivariate penalized spline curve analysis, the relationship between serum hepcidin and renal events was J-shaped, and the renal hazard was particularly evident at a serum hepcidin level ≥60 ng/ml.

Conclusion

Increased serum hepcidin levels independently predict the progression of CKD in non-dialysis patients with CKD. The potential direct renal hazard of serum hepcidin needs to be confirmed in future randomized controlled trials.
P0199ASSESMENT OF FILTRATION RATE IN ONCOLOGICAL PATIENTS
Authors: Klimek Kamila , ALONSO GARCIA FABIOLA , Lara Ruiz Alfonso , AGUDO MARTINEZ ANA , Almenara Tejederas Marina , SALGUIERA LAZO MERCEDES
Published: June 2020

Background and Aims

Accuracy in the estimation of the glomerular filtration rate (GFR) in oncological patients is essential in order to adjust chemotherapy doses accordingly. Finding an appropriate formula for this subgroup of patients is a subject of ongoing debate. The present study introduces a cohort of the aforementioned patients followed in the Onconephrology outpatients clinic, in which different formulas were applied for the calculation of the GFR.

Method

A retrospective study with a cohort of 17 onconephrological patients was conducted. The following variables were evaluated: age, sex, height, weight, body mass index, body surface area and type of tumor. Renal function was estimated with the Cockcroft Gault, the Janowitz-Williams, the CKD-EPI, the adjusted by body surface-CKD-EPI, the MDRD, the adjusted by body surface-MDRD, the CKD-EPI Cystatin C, the adjusted by body surface-CKD-EPI Cystatin C formulas and 24-hour urine creatinine clearance. Every equation was compared with the Cr EDTA clearance which is considered the gold standard. The statistical analysis was carried out by means of the IBM SPSS Statistics software. Concordance between chromatography and the remaining formulas was assessed with the Wilcoxon (null hypothesis of no difference between medians) and Bland-Altman tests.

Results

6 women and 11 men were included in the study, with a mean age of 64.24 years (SD 9.9), a mean BMI of 28.25kg/m2 (SD 7.98), and a mean Cr EDTA clearance was 37.07ml/min (SD 15.45). 15 patients suffered from solid malignancies, whereas the remaining 2 patients suffered from hematological tumors. The most common solid tumor was lung cancer (n=5), followed by rectal carcinoma (n=2).

The null hypothesis was accepted for the adjusted for body surface-CKD-EPI Cystatin C equation (p-0,089) and 24-hour urine creatinine clearance (p 0.955), when compared to 51Cr EDTA clearance. The Bland-Altman test revealed the smallest differences between the 24-hour urine creatinine clearance and 51Cr EDTA clearance (-0.09867), with 95% concordance limits of -36.14 and 34.17, and a non-significant linear regression coefficient (p 0.915).

Conclusion

This study revealed that the 24-hour urine creatinine clearance is the closest formula to the gold standard for the assessment of the GFR in patients with malignancies. However, the small sample size hinders the generalization of these results. Larger sample size studies are mandatory to confirm these findings.
P0207PLASMA CHEMOKINE CXC MOTIF-LIGAND 16 AS A PREDICTOR OF RENAL PROGNOSIS IN IMMUNOGLOBULIN A NEPHROPATHY
Authors: Luo Ran , Yang Yi , Chang Dan , Liu Tingting , Li Yue-Qiang , Dai Wei , Zuo Mei-Ying , Xu Yu-lin , Zhang Chun-Xiu , Xu Gang , Ge Shu-wang
Published: June 2020

Background and Aims

A recognized non-invasive biomarker to improve risk stratification of IgA nephropathy (IgAN) patients is scarce. CXCL16 has been shown to play a key role in inflammatory disease as chemoattractant, adhesion and fibrosis factor. This study assessed the possibility of plasma CXCL16 as a potential biomarker in IgAN patients.

Method

Plasma CXCL16 was measured in 230 patients with renal biopsied IgAN from 2012 to 2014. The patients were followed for 41.3 months with 50% reduction in eGFR or ESRD as end-points.

Results

The plasma CXCL16 levels in IgAN patients were significantly correlated with the uric acid, estimated glomerular filtration rate and tubular atrophy/interstitial fibrosis score in multivariate analysis. In addition, the counts of CD4+ T cells, CD8+ T cells and CD20+ B cells in renal biopsies of IgAN patients were significantly correlated with the plasma CXCL16 levels, but not CD68+ macrophage. Finally, we concluded that patients with higher plasma CXCL16 levels had a higher risk of poor renal outcome compared with those with lower. No association was observed between the CXCL16 polymorphisms and clinical parameters including plasma CXCL16 levels and prognosis.

Conclusion

Plasma CXCL16 levels were associated with clinical parameters, pathological damage, the CD4+ T cells, CD8+ T cells and CD20+ B cells infiltration in renal tissue and renal outcome in IgAN patients. Plasma CXCL16 might be a potential prognosis predictor in Chinese IgAN patients.
P0212IMMUNOSUPPRESSIVE TREATMENT OF PATIENTS WITH ANCA ASSOCIATED VASCULITIS (AAV) IN CHRONIC DIALYSIS PROGRAM
Authors: File Ibolya , Ujhelyi László , Balla Jozsef , Bidiga László , Csilla Trinn , Markóth Csilla , Gabriella Szűcs , Mátyus János
Published: June 2020

Background and Aims

There are numerous studies on AAV, however, data describing the use of immunosuppressive treatment in AAV patients (pts) on chronic dialysis are limited. Most studies found that the incidence of infection is much higher than that of relapses (0.05-0.1 pt per year), suggesting that immunosuppression should be stopped after 3 months in pts with end-stage renal failure.

Material, Method

Retrospective analysis of immunosuppressive treatment in pts on chronic dialysis due to AAV. From 1995 to 2019 139 pts were diagnosed with AAV. Among them 38 patients (26 female, 12 male, mean age 58 years) needed chronic dialysis (>90 days) due to severe renal AAV (29), relapsing renal disease (6) or progressive CKD without active vasculitis (3).

Results

Microscopic polyangiitis was diagnosed in 20, granulomatosis with polyangiitis in 14, eosinophilic granulomatosis with polyangiitis in 4 cases. MPO-ANCA was more frequent than PR3-ANCA (23 vs 12), in one case both ANCAs were positive, and in two cases both were negative. The mean dialysis duration was 55 months (4–180 months). 18 pts (47%) had at least one relapse during the observation period. The mean age, the clinical diagnosis, the type of ANCA did not cause any difference, the dialysis time was longer in the relapsed pts group (72+/-38 vs. 40+/-29 months) compared to pts without relapse. High relapse rate was seen in 6 cases. Three patient had continuously high level of PR3-ANCA without relapse or any sign of disease. Relapses were treated mostly with combined therapy of corticosteroids and oral/intravenous cyclophosphamide followed by azathioprin maintenance therapy. Cortocosteroid alone was used in 7 pts, rituximab in five pts as maintenance therapy. Serious infection (needing hospital care) rate during any immunosuppressive treatment was 0.12 per patient-years. There were 12 deaths on dialysis, the median time to death was 61 months (range 3–132). The deaths rate was higher (9/18 vs. 4/20) in relapsed pts, 4 occurring during immunosuppressive treatment. Causes of deaths were cardiovascular (8), sepsis (3), malignancy (2 pts). Seven pts received kidney grafts, 15 pts remained on dialysis, but in three case dialysis could be discontinued after 16, 35 and 36 months.

Conclusion

Our study points to higher relapse rate and lower serious infection rate in AAV pts on chronic dialysis compared to previous studies. It seems reasonable to continue immunosuppression above 3 months in pts remaining on chronic dialysis. This approach may decrease the relapse rate preventing damage of other organs, allowing transplantation and in some pts recovery of renal function could be achieved.
P0215EXCESSIVE TISSUE SODIUM STORAGE IN PATIENTS WITH NON-DIALYSIS DEPENDENT CARDIO-RENAL SYNDROME IS COMPARABLE TO HEMODIALYSIS PATIENTS
Authors: Lemoine Sandrine , Salerno Fabio , Akbari Alireza , McIntyre Christopher
Published: June 2020

Background and Aims

Both CKD and heart failure (HF) are characterized by a propensity to retain sodium. Renal dysfunction worsens the progression of heart failure and is associated with worse outcomes. This may be a result of synergistic aggravation of sodium retention by the two conditions. We aimed to compare tissue Na storage in skin and muscle between cardiorenal (CR) patients and patients with a range of renal dysfunction, including those requiring hemodialysis (HD).

Method

Proton and 23Na images of the lower limb were acquired on a 3T MRI. We studied 9 CR patients, 7 matched CKD 2-5 patients (without HF) and 31 established HD patients. Regions of interest including skin and soleus were drawn on images to provide a quantitative sodium measurement and these tissue concentrations compared between groups. Blood samples were drawn at each scan in all patients. Spot urine samples were collected for CR patients.

Results

For CR patients, mean age was 66 ± 8 years, 78% of male, mean estimated glomerular filtration rate (eGFR) was 52 ± 18 mL/min/1.73m2, urea was 11 ± 6 mmol/L. For HD patients, mean age was 66 ± 8.7 years, 68% of male and mean dialysis vintage was 38 ± 37 months for HD patients. Mean age was 63 ± 8, 71 % of male, eGFR 45 ± 29 mL/min/1.73m2 for CKD patients. CR patients displayed an increased amount of salt in skin (32.5 ± 13 mmol/L) and muscle (26 ±4 mmol/L) with levels significantly higher than that seen in GFR matched controls (without HF) and comparable to HD patients (31 ±12 and 28 ± 6 mmol/L p=0.9 and p=0.3 respectively) without meaningful residual renal function.

Conclusion

The combination of HF and CKD is associated with intense tissue Na storage; resulting in tissue Na accumulation in CR patients (with reasonably well-preserved renal function) similar to CKD patients requiring HD.
P0221SOLUBLE UROKINASE RECEPTOR (SUPAR) IS A PREDICTOR OF DISEASE STATE AND RENAL PROGNOSIS IN PRIMARY NEPHROTIC SYNDROME
Authors: Fujimoto Keiji , Kagaya Yu , Fujii Ai , Kumano Syo , ADACHI HIROKI , Kengo Furuichi , Yokoyama Hitoshi
Published: June 2020

Background and Aims

A hypothesis has been proposed that serum (s-) soluble urokinase receptor (suPAR) activates glomerular podocyte β3 integrin to cause podocyte injury and onset of proteinuria in primary nephrotic syndrome (pNS). However, s-suPAR has been questioned as a disease marker for pNS because it did not correlate with urinary protein (UP). Furthermore, there are a few reports that suggested a correlation between urinary (u-) suPAR and UP by univariate analysis, but the correlation between the two has not been studied by multivariate analysis taking confounding factors into account. In addition, it is unclear how u-suPAR is involved in the pathogenesis of pNS.

Method

In 36 patients with pNS including minimal change (n=18), focal segmental glomerulosclerosis (n=7), membranous nephropathy (n=9) and membranoproliferative glomerulonephritis (n=2), the relationship between u-suPAR (pg/mgCr) and UP (g/gCr) was examined by cross-sectional analysis of baseline values before treatment and longitudinal analysis of changes during the first 2 months of treatment (⊿). In addition, the localization and staining intensity of activated β3 integrin in renal tissue were examined by immuno-histochemistry methods. We also examined whether s-suPAR (pg/ml) or u-suPAR is useful for predicting renal prognosis (1.5-fold increase from baseline in s-Cr) using Cox proportional hazard analysis.

Results

In cross-sectional analysis, u-suPAR was a UP predictor independent of s-suPAR, eGFR and selectivity index (S.I.) [standardized partial regression coefficient (stdβ) = 0.879, p <0.00001]. Also in the longitudinal analysis, ⊿u-suPAR was a ⊿UP predictor independent of ⊿s-suPAR, ⊿eGFR and S.I. (stdβ = 0.574, p = 0.003). Furthermore, there were significant correlations between u-suPAR and u-L-FABP (r = 0.522, p = 0.001), and between ⊿u-suPAR and ⊿u-L-FABP (r = 0.395, p = 0.017). Activated β3 integrin was mainly detected on proximal tubular brush-border (PTBB), but not glomerular capillaries, moderate to strongly positive in pNS. ⊿s-suPAR was the only predictor of 1.5-fold increase from baseline in s-Cr (Hazard Ratio: 1.361 per 500 pg/ml increase of s-suPAR, p=0.006).

Conclusion

In pNS, u-suPAR was a proteinuria predictor independent of s-suPAR, suggesting the possibility of the mechanisms of proteinuria through β3 integrin activation in PTBB by u-suPAR. In addition, s-suPAR was useful in predicting renal prognosis.
P0225THE PRESENCE OF SIMPLE RENAL CYST IS ASSOCIATED WITH INCREASED RISK OF ALBUMINURIA IN YOUNG ADULTS
Authors: Boo Hyo Jin , SONG SEUNGMIN , Lee Jung Eun , Jang Hye Ryoun , Huh Wooseong , Kim Dae Joong , Kim Yoon-Goo
Published: June 2020

Background and Aims

It is well-known that the prevalence of simple renal cyst increases with age. However, simple cysts are occasionally found in adults younger than 40 years of age. This cross-sectional study evaluated the clinical significance of simple renal cysts in young adults, focusing on the associations with hematuria and albuminuria.

Method

Adults younger than 40 years who received a comprehensive medical checkup from January 2005 to December 2013 were included. Simple renal cysts were identified by ultrasonography.

Results

Among 5832 subjects, renal cysts were found in 276 (4.7%). Subjects diagnosed with polycystic kidney disease (n=5) or medullary sponge kidney (n=1) were excluded from the analyses. A single cyst and multiple cysts were found in 234 (4.0%) and 42 (0.7%) subjects, respectively. The locations of single cyst were cortex in 187, medulla in 26, and parapelvic region in 21. Age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.02-1.12 per 1-year increment, P = 0.002), systolic BP (OR, 1.01; 95% CI, 1.00-1.02 per 1-mmHg increment, P = 0.006), and hypertension (OR, 1.85; 95% CI, 1.24-2.76, P = 0.003) were independent predictors of the presence of simple cyst. The presence of cysts was not associated with increased prevalence of hematuria. While, the subjects with cysts had higher prevalence of albuminuria than those without cysts (11.3% vs. 4.5%, P <0.001). Multivariate analyses of albuminuria revealed that the presence of simple renal cyst was associated with a 2.30-fold increase in the prevalence of albuminuria (95% CI 1.512-3.519, P <0.001) independently of other risk factors. The location of the cysts was not related to the prevalence of albuminuria.

Conclusion

The presence of simple renal cysts was independently associated with increased prevalence of albuminuria. The causal relationship between renal cysts and albuminuria needs to be elucidated in further studies.
P0226CONSEQUENCES OF SUPRAPHYSIOLOGICAL DYALYSATE MAGNESIUM CONCENTRATION ON ARTERIAL STIFFNESS, HEMODYNAMIC PROFILE AND ENDOTHELIAL FUNCTION IN HEMODIALYSIS: A RANDOMIZED CROSS-OVER STUDY AND FOLLOW-UP
Authors: Del Giorno Rosaria , Lavorato Soraya , Stefanelli Kevyn , Allegra Giampiero , Zapparoli Claudia , Lazarevic Pedrag , Berwert Lorenzo , Gabutti Luca
Published: June 2020

Background and Aims

Increasing dialysate magnesium improves vascular stiffness in subjects undergoing maintenance hemodialysis. The present findings merit a larger trial to evaluate the effects of a 0.75 mmol/L D-Mg2+ on major clinical outcomes.

Method

A randomized 4-week cross-over study aimed at investigating the consequences of increasing D-Mg2+ from 0.50 to 0.75 mmol/L on arterial stiffness, hemodynamic profile, and endothelial function in subjects undergoing hemodialysis. The long-term effect of higher D-Mg2+ on mineral metabolism markers was investigated in a six-month follow-up. Data were analysed by linear mixed models for repeated measures.

Results

Pulse wave velocity and pulse pressure significantly decreased on the higher D-Mg2+ compared with the standard one by -0.91 m/sec (95% confidence interval: -1.52 to -0.29; p=0.01) and -9.61 mmHg (-18.89 to -0.33, p=0.04), respectively. A significant reduction in systolic blood pressure of -12.96 mmHg (-24.71 to -1.22, p=0.03) was also observed. No period or carryover effects were observed. During the long-term follow-up the higher D-Mg2+ significantly increased total serum and ionized Mg (mean percentage change from baseline to follow-up +21%; and + 27%; p≤0.001 for both), while parathormone (PTH) decreased significantly (-11%, p=0.03).

Conclusion

Increasing dialysate magnesium improves vascular stiffness in subjects undergoing maintenance hemodialysis. The present findings merit a larger trial to evaluate the effects of a 0.75 mmol/L D-Mg2+ on major clinical outcomes.