bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO622IMPAIRED PROTEIN-BOUND UREMIC TOXIN EXCRETION SUGGESTS TUBULAR DYSFUNCTION IN DIABETIC NEPHROPATHY
Authors: Gerritsen Karin , Ahmed Sabbir , Sparidans Rolf , Mihaila Silvia , Broekhuizen Roel , Goldschmeding Roel , Nguyen Tri , Masereeuw Rosalinde 
Published: May 2021

Abstract

Background and Aims
Kidney tubular damage is an important prognostic determinant in diabetic nephropathy (DN) (1). Proximal tubular secretion is a vital homeostatic function that is responsible for excretion of waste, such as protein bound uremic toxins (PBUTs) that are minimally eliminated via glomerular filtration. PBUTs are potentially harmful waste products of endogenous metabolism that are efficiently excreted by tubular secretion via organic anion transporters (OATs). Currently available diagnostic methods cannot accurately detect tubular dysfunction. We hypothesize that renal PBUT clearance may be a sensitive tubular function marker. Here, we measured PBUTs in long-term streptozotocin (STZ)-induced murine diabetic nephropathy (DN), which was characterized by severe tubular atrophy and interstitial fibrosis (2).

Method
Diabetes mellitus was induced in C57Bl/6 mice by a single intraperitoneal injection of 200 mg/kg STZ which resulted in substantial kidney damage after 6 months evaluated by histopathology and conventional markers (2). Indoxyl sulfate (IS), hippuric acid (HA), kynurenic acid (KA), kynurenine (Kyn), p-cresol glucuronide (pCG), p-cresol sulfate (pCS) and indole acetic acid (IAA) were measured in plasma and urine after 6 and 8 months by LC-MS/MS.

Results
Among the PBUTs with the highest OAT affinity, viz. IS, HA and KA, plasma concentrations were 2.2-, 2.3- and 1.5-fold higher (p=0.005, 0.0006, 0.03; Fig 1A-C) after 6 months and 1.9-, 2.1- and 2-fold higher (p=0.008, 0.0005, 0.001; Fig 2A-C) after 8 in DN, and urinary excretions (normalized for plasma concentrations) were 3.3-, 2.3- and 3.0-fold lower (p=0.012, 0.16, 0.03; Fig 1G-I) after 6 months and 2.5-, 1.6-, 2.3-fold lower (p=0.028, 0.046, 0.0005; Fig 2G-I) after 8 months in DN. Other PBUTS, viz. IAA, Kyn, pCS and pCG, were not significantly affected.

Conclusion
Our findings suggest that OAT function is compromised in murine long-term DN. Renal clearance of IS, HA and KA may be a marker of tubular function in DN. Future studies should focus on correlations with histology and validation in other species.
MO626EFFECTS OF RAMIPRIL IN LUNG AND KIDNEY ANGIOTENSIN CONVERTING ENZYME 2 (ACE2) EXPRESSION IN A TYPE 2 DIABETIC MURINE MODEL: LESSONS FOR COVID-19 INFECTION
Authors: Vergara Arana Ander , Jacobs Cachá Conxita , Molina Mireia , Dominguez Pamela , Benito Begoña , Bermejo Sheila , Seron Micas Daniel , Soler Romeo Maria Jose 
Published: May 2021

Abstract

Background and Aims
Angiotensin converting enzyme 2 (ACE2) is one of the components of the renin-angiotensin system (RAS) that mainly degrades angiotensin II to angiotensin-(1-7). ACE2 is predominantly expressed in the kidney and the heart, but it has been evidenced in type 2 alveolar lung cells, where it acts as a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, a controversy arose as to whether the use of RAS blockers could increase ACE2 lung expression and the risk infection by COVID-19. This study aimed to investigate the effect of an ACE inhibitor (Ramipril) on ACE2 expression in experimental diabetes.

Method
12 weeks old diabetic db/db mice (n=7) were given ramipril (8 mg/Kg/day) during 8 weeks or the respective vehicle. db/m (n=7) vehicle-treated non-diabetic mice were included as controls. ACE2 mRNA expression and enzymatic activity were studied in kidney, heart and lung samples of these animals to identify if the diabetic condition or treatment with ramipril modulated ACE2 expression.

Results
In vehicle-treated diabetic db/db animals, ACE2 mRNA expression was significantly increased in the kidney (p&lt;0.001) and ramipril treatment reversed this effect (p=0.026). In the heart, ACE2 expression decreased in db/db when compared to db/m littermates (p=0.035) and ramipril had no effect. We found no differences in ACE2 gene expression in the lung. Besides, ACE2 enzymatic activity was increased in the kidney (29%) and also in the lung (16%) of db/db mice when compared to controls. Ramipril treatment decreased ACE2 activity a 19% in the lung and had no effect in the kidney when compared to untreated db/db (see figure). In the heart, ACE2 activity tended to decrease in db/db mice (29%) when compared to db/m and ramipril increased ACE2 activity (18%) but did not exceed the cardiac ACE2 activity of the db/m.

Conclusion
ACE2 is increased in the kidney and the lung, and decreased in the heart of diabetic mice. Ramipril treatment restores ACE2 levels. The results suggest that ACE inhibitors do not increase ACE2 expression and the activity decrease exerted in the lung may be protective against COVID-19 infection.
MO645BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN WITH TYPE 2 DIABETES MELLITUS WITH AND WITHOUT DIABETIC NEPHROPATHY
Authors: Valentinova Monova Daniela , Shumnalieva Russka , Monov Simeon 
Published: May 2021

Abstract

Background and Aims
Diabetes mellitus and osteoporosis are both common human diseases. Diabetic nephropathy is characterized by the presence of pathological quantities of urine albumin excretion, diabetic glomerular lesions, and loss of glomerular filtration rate in diabetics. Little evidence has been reported on relationships between BMD and albuminuria.
The aim of this study is to compare the bone mineral density (BMD) in postmenopausal women with type 2 diabetes mellitus (T2DM) with and without diabetic nephropathy.

Method
We retrospectively analyze the BMD of the lumbar spine and femur using dual-energy X-ray absorptiometry in 84 postmenopausal women with T2DM with (39) and without (45) diabetic nephropathy. The serum levels of calcium, phosphorus, total alkaline phosphatase, and urine albumin excretion were measured in all participants. Diagnosis of albuminuria was based on albumin-creatinine ratio (ACR).

Results
Age, body mass index (BMI) and time since menopause were not significantly different between the two groups. The T-scores of basal BMD at L4 were significantly lower in patients with diabetic nephropathy (-0,94 ± 0,40) compared to patients without nephropathy. No significant differences in serum creatinine were detected between two groups of patients. Our data suggest that ACR was negatively associated with lumbar spine and femoral neck BMD.

Conclusion
Our results suggest that postmenopausal women with diabetic nephropathy have a lower BMD and are at increased risk of osteoporosis in the lumbar spine compared with postmenopausal women without diabetic nephropathy. ACR was negatively associated with lumbar spine and femur neck BMD. One of the explanations that has been proposed for the association between albuminuria and osteoporosis is that albuminuria is associated with reduced bone blood flow, resulting in a decreased rate of bone remodeling and the development of osteoporosis.
MO646PATHOLOGICAL PROGNOSTIC FACTORS IN DIABETIC NEPHROPATHY: A RETROSPECTIVE STUDY
Authors: Sannier Aurélie , Maisons Valentin , Bobot Mickael , Vrtovsnik Francois , Jourde-Chiche Noemie , Barba Christophe , Daniel Laurent , Rioux-Leclercq Nathalie , Vigneau Cécile , Halimi Jean-Michel , Chemouny Jonathan 
Published: May 2021

Abstract

Background and Aims
Kidney Biopsies (KB) performed in patients with Type-2 diabetes (T2D) usually aim at differentiating diabetic nephropathy (DN) from other kidney diseases. However, KB could also help refining patients’ prognosis, both in terms of renal survival, and in terms of patient survival. In 2010, the Renal Pathology Society developed a pathological classification of DN, but the prognostic value of the described items , is still imperfectly documented. We aimed to assess the prognostic performances of these items to predict renal and patient survival.

Method
Native KBs with diabetic and/or hypertensive nephropathy (DN/HN) performed in patients with T2D in four French centers were analyzed and scored according to the classification developed by the Renal Pathology Society. Clinical and biological data was collected from the patients’ records. Survival analyses were performed for renal survival (time to first dialysis or preemptive transplantation) and death after dichotomization of continuous data). For each of the analyses, we first established a model comprising clinical data only. We then assessed the benefit of adding each of the pathological item to the clinical model. Finally, we performed a backward stepwise analysis to identify items predictive of renal and/or patient survival.

Results
We analyzed 165 biopsies with DN/HN from patients with T2D and with at least 12 months of follow-up (unless they reached an endpoint during the first year). Among them, 73 (44%) were male, 155 (94%) had hypertension, 53 (34%) hematuria, 22 (15%) had proliferative diabetic retinopathy (DR), 33 (23%) had non-proliferative DR, 90 (62%) had no DR (20 had missing data). Mean (SD) age was 63 (11), median [IQR] eGFRCKD-EPI was 29 [18;45] ml/min/1.73m², urinary protein-to-creatinine ratio was 0.38 [0.14;0.83] g/mmol, HbA1c was 7 [6.2;8.2] % and diabetes duration before KB was 10 [5;19] years. The median [IQR] follow-up was 33 months[18;57]. During the follow-up, 43 (26%) patients died and 69 (42%) required renal replacement therapy (RRT). The percentage of ischemic glomeruli, and presence of more than one area of arteriolar hyalinosis (ah=2), were predictive of renal survival and improved the predictive value of the model when added to clinical parameters. Presence of at least one convincing Kimmelstiel–Wilson lesion (nodular glomerulosclerosis or Class III DN) was predictive of death and similarly improved the predictive model (See figure).

Conclusion
Pathological findings on KB, as classified by the Renal Pathology Society, carry significant prognostic value in patients with T2D and DN/HN. Vascular lesions (presence of arteriolar hyalinosis and less than 7% of ischemic glomeruli) predicted the need for RRT, while nodular glomerulosclerosis was predictive of death.
MO648SERUM SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR IN PATIENTS WITH DIABETIC KIDNEY DISEASE
Authors: Lupusoru Gabriela Elena , Ailincai Ioana-Georgiana , Sorohan Bogdan Marian , Andronesi Andreea Gabriella , Lupusoru Mircea , Andronesi Danut , Manda Dana , Caragheorgheopol Andra , Ismail Gener 
Published: May 2021

Abstract

Background and Aims
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide, associated with significant cardiovascular morbidity and mortality. Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker associated with inflammation, endothelial dysfunction and kidney disease. There is a lack of studies that investigate the role of suPAR in patients with DKD. Our aim was to assess the level of serum suPAR and to evaluate its association with kidney function, proteinuria and histological lesions in patients with DKD.

Method
We performed a cross-sectional study on 75 patients with DKD evaluated in our department between 2019 and 2020. Inclusion criteria were: age&gt; 18 years, diagnosis of type 1 or type 2 diabetes mellitus, DKD and absence of malignancy, autoimmune disease, infectious disease and liver disease. Demographical, clinical and laboratory parameters were collected at the time of admission. A subset analysis was performed on 28 patients with biopsy- proven diabetic nephropathy (DN) to investigate the association of serum suPAR with histological lesions. Kidney function was evaluated based on serum creatinine and estimated with CKD-EPI formula, proteinuria was reported as 24h proteinuria and albumin/creatinine ratio (ACR) and serum suPAR levels were measured with a solid-phase ELISA kit. The detection range of the kit was 12 -360 pg/ml (7.8- 500).

Results
Among the 75 patients, mean age was 57.9±12.2 years, male was the dominant gender (65.3%), mean BMI was 30.7±5.5 kg/m2, most patients had hypertension (97.3%) and 22.7% were active smokers. Sixty six out of 75 patients (88%) had type 2 diabetes and the median duration of diabetes was 180 months (120- 240). Median values of estimated glomerular filtration rate (eGFR), 24h proteinuria and ACR were 24.3 ml/min (15- 36), 4.8 g/24h (1.9- 7.1) and 2000 mg/g, respectively. Median serum level of suPAR at the time of evaluation was 2857.2 pg/ml (1916.4- 3700.1). Its level was positively correlated with duration of diabetes (r= 0.278, p= 0.01), eGFR (r= 0.634, p&lt; 0.001), 24h proteinuria (r= 0.490, p&lt; 0.001), ACR (r= 0.524, p&lt; 0.001) and negatively correlated with urine specific gravity (r= -0.284, p= 0.01). In the subset analysis on 28 patients with biopsy-proven DN, median suPAR level was 2474 pg/ml (1782-3745) and was positively correlated with DN class (r= 0.493, p=0.008) and interstitial fibrosis and tubular atrophy (IFTA) score (r= 506, p=0.006), but not with interstitial inflammation, arteriolar hyalinosis or arteriolosclerosis.

Conclusion
Our study showed a high serum level of suPAR in patients with DKD and its association with duration of diabetes, urinary specific gravity, kidney function and proteinuria. We also found a positive correlation with severity of glomerular lesions and IFTA.
MO649DIAGNOSTIC TESTS OF NOVEL URINARY BIOMARKERS TO IDENTIFY EARLY STAGES OF NEPHROPATHY IN NON HYPERTENSIVE TYPE 2 DIABETIC MELLITUS
Authors: Mahapatra Himansu , Kulshreshtha Bindu , Goyal Dr Parul , Chirkara Anubhuti , Khanna Tripti , Singh Anamika , Arora Arpita , Prasad Gupta Yadunandan , Sekhar Venkatesan 
Published: May 2021

Abstract

Background and Aims
Activation of RAS and tubulointerstitial damage might be seen in pre-albuminuria stage of diabetic nephropathy. Here, diagnostic tests of urinary Angiotensinogen, Cystatin C, Neutrophil gelatinase associated lipocalin and IL 18 have been studied in pre-microalbuminuria diabetic patients.

Method
Total 952 Diabetic screened for Nephropathy (e-GFR ≥120&ACR≥30), among them 120 cases were followed up for one year. At one year they were classified in to Hyperfiltration43, Normoalbuminuria29 and Microalbuminuria48 groups. Another 63 Diabetes without nephropathy were included as controls. Hypertension, on ACEI/ARB, e-GFR&lt;60ml/min/1.73m2 and all Macroalbuminuria conditions were excluded. All were subjected to urine protein, ACR, HbA1c,e-GFR, along with urinary bio markers(IL-18, Cystatin-C, NGAL and Angiotensinogen). Comparative analysis of all groups, Diagnostic tests, correlation and logistic regression were analysed.

Results
Urinary IL18/Cr, Cystatin /Cr. and Angiotensiogen /Cr. levels were higher in groups of hyper filtration (13.47, 12.11 & 8.43mg/g), Normoalbuminuria (9.24,11.74&9.15mg/g) and microalbuminuria(11.59,14.48&10.24mg/g) than controls(7.38,8.39&1.26mg/g) but not NGAL/Cr. in all groups. High levels were significant in all except Cystatin/Cr. & IL18/Cr. in normoalbuminuria group. The AUC, sensitivity and specificity of Angiotensinogen (0.9, 90% and 80%) ACR (0.69, 40% and 100%) and e-GFR (0.6,37 and 100%)respectively. AUC of other biomarkers viz, IL 18/cr. Cystatin/Cr and NGAL/Cr. were 0.65, 0.64 and 0.51 respectively. Angiotensinogen/Cr and IL18/Cr showed correlation with log albuminuria r-0.3 p 0.00 and r-0.28 p 0.00 respectively; NGAL with log e-GFR (r-0.28 p0.00).Multivariate logistic analysis showed Odds of contracting nephropathy is 7.5 times having higher values of Log Angio/Cr.

Conclusion
Urinary Angiotensinogen has higher diagnostic value than ACR and e-GFR followed by IL 18 and Cystatin to diagnose DN at the pre-albuminuric stages but not urinary NGAL.
MO651DIABETES CARE IN HAEMODIALYSIS TREATMENT : ADVANCES IN 2020
Authors: Dillmann Clementine , Tollard Clemence , Chantrel Yoann-Francois , Mountassir Hanane , Brokhes-Lecalvez Sophie , Fall-Mostaine Fatema , Takla Zafer , Fickl Rocsana , BABICI Daniela , Serb Liviu , Kessler Laurence , Chantrel Francois 
Published: May 2021

Abstract

Background and Aims
Management of diabetes and follow-up of haemodialysis patients are still poorly standardized. The objective of this study is to establish a descriptive inventory of all routine parameters for monitoring diabetes and glycemic control by Continuous Glucose Monitoring (CGM).

Method
The study recruited 32 diabetic patients in a medical dialysis unit. Glycemic control was assessed using CGM (FreeStyle Free Pro®) over at least 11 days with measurement of: mean blood glucose level, percentage of blood glucose level: &lt; 70 mg/dl (TBR), between 70 and 180 mg/dl (TIR), and &gt; 180 mg/dl (TAR). The results are expressed in average or median [25-75 percentiles]. SPSS® statistical analyses compared extra and per dialytic periods.

Results
Patients’ mean age was 71±8 years, diabetes duration was 21±6.5 years (87.5% T2DM), mean weight was 77±13kg, HbA1c was 7±0.98%, 98% had a high risk of foot injury (Grade 2 and 3) . Only 46.8% of the patients were followed by a diabetes specialist and 84.3% were treated with insulin and 18.75% received oral medication while only 50% performed self blood glucose-monitoring. The average blood glucose level was 133±13 mg/dl (∼1000 measurements). CGM results for 32 patients over the total period were: TIR at 70% [58-76], TAR at 15% [4.6-29], and TBR at 9.6% [3.7-20].Per-dialytic TIR (84%; [76-93]) was significantly higher (p=0.02) than extra-dialytic TIR (68%; [56-75]). Per-dialytic TAR (5.5%; [0.0-10.7]) was significantly lower (p&lt;0.01) than extra-dialytic TAR (14%; [3.6-29]). TBR did not vary significantly.

Conclusion
The majority of patients were treated with insulin but only 50% performed self- of blood glucose. Hypoglycaemia was lower during dialysis period. 98% of patients had a high risk of foot injury. CGM could be a usefull tool for the evaluation of glycemic profile of haemodialysis patients, and allows a better adjustment of their treatment.
MO655PROTEINURIA DECREASE AFTER SGLT2I : WHAT CAN WE EXPECT?
Authors: Moliz Candela , Casillas Esther , Lopes Martín Vanessa , Martin Irene , Viera Elizabeth , Fernandez Lucas Milagros , Villacorta Javier 
Published: May 2021

Abstract

Background and Aims
The effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in reducing proteinuria secondary to type II diabetic nephropathy is well known. However, in daily practice we might have the impression that those patients who present with a higher proteinuria at the beginning of SGLT2i treatment might not reach an equal decrease of proteinuria compared to those with lower initial proteinuria (under 1g/24h). To verify this hypothesis we analysed the evolution of our patients depending on the initial proteinuria.

Method
A retrospective analysis of 40 patients who had initiated treatment with SGLT2i was carried out. At the beginning of treatment, 23 patients presented proteinuria over 1 gram/24h and the other 17 presented less than 1g/24h. The decrease of proteinuria after 6 months of follow-up was analysed in each group. The variations in serum creatinine, haemoglobin and glycosylated haemoglobin were also examined.
A second analysis depending on initial glomerular filtration rate (Under and over 60 ml/min) was also performed.

Results
In table 1 the basal characteristics of this population are shown. Analysis of the complete population showed a significant decrease of proteinuria (Initial mean proteinuria was 1636+/-1513 mg/24h vs final mean proteinuria of 1320+/-1480mg/24h, p=0.015).
Furthermore, the analysis by groups depending on initial proteinuria revealed that both groups had a significant reduction of proteinuria after 6 months:
A second exam depending on initial GFR was carried out, proving that those with lower initial GFR maintained a significant decreased of proteinuria after 6 months of treatment.

Conclusion
In our cohort, against our hypothesis, we didn´t observe lower reduction of proteinuria when we started the treatment with proteinuria above 1 g/24h. We can consider that the effect of SGLT2i doesn’t decreased in patients with higher initial proteinuria. Therefore, we should always consider and offer this therapeutic option to our ND patients.
MO639THE ASSOCICATION BETWEEN SERUM INTERLEUKIN 1 BETA AND HEPARAN SULFATE IN DIABETIC NEPHROPATHY PATIENTS
Authors: Jiang Liqiong 
Published: May 2021

Abstract

Background and Aims
The global diabetes mellitus (DM) prevalence in 2019 is estimated to be 9.3%. Approximately 20% to 40% of patients with DM develop diabetic nephropathy (DN). DN is the leading cause of end stage renal disease (ESRD). Inflammation is considered to be an important mechanism in the development of DM and persists for a long time before the occurrence of DN. Many studies demonstrated that decrease of endothelium glycocalyx (EG) was negatively correlated with proteinuria. Whether EG damage induced by inflammasome in DM patients leads to the occurrence of micro albuminuria (MA) and accelerating the progress of DKD is rarely studied.

Method:
This prospective, observational cohort study screened 300 diagnosed diabetic patients from departments of nephrology and endocrinology of our hospital. The exclusion criteria were: type 1 diabetes; acute infections; usage antibiotics within 3 months; kidney disease before; heart failure; malignancy. Finally 70 patients were invited to this study and were divided into type 2 DM (T2DM) group and type 2 diabetic nephropathy (T2DN) group. T2DM group were defined as patients with normal MA and without diabetic retinopathy (n=35). T2DN group were defined as patients with increased MA and diabetic retinopathy (n=35). Laboratory data were measured via routine laboratory methods. Heparan sulfate (HS) and interleukin 1 beta (IL-1β) were noted as EG biomarker and inflammasome biomarker respectively. Serum samples of patients were collected, and serum IL-1β and HS were measured by ELISA. SPSS 18.0 was used for all statistical analyses.

Results:
T2DN patients had higher serum IL-1β (27.85 vs. 21.35 pg/ml), higher HS (2.17 vs. 1.47 ng/ml), higher urea nitrogen (6.30 vs. 5.33 umol/L), higher CRP (2.03 vs. 0.81 mg/L), higher hemoglobin (128 vs. 141 g/L), higher neutrophil (4.1 vs. 3.4 × 109/L) and higher neutrophilic granulocyte percentage (63% vs. 56%) compared with T2DM patients (all P&lt;0.05). Logistic regression analyses demonstrated serum HS was independently associated with T2DN. Furthermore in T2DN patients, serum IL-1β was positively correlated with HS (r = 0.6, P&lt;0.01) and was and independent associated factor. The relationship of HS and IL-1β was not significant in T2DM patients.

Conclusion
T2DN patients had higher serum IL-1β and HS than T2DM patients in our study. In T2DN patients IL-1β was an independent associated factor of HS. The results suggested that the inflammasome may damage the EG in diabetic patients, which induced the occurrence of MA and accelerating the progress of DN.