scholarly journals Longitudinal urinary biomarkers of immunological activation in covid-19 patients without clinically apparent kidney disease versus acute and chronic failure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Krzysztof Laudanski ◽  
Tony Okeke ◽  
Hajj Jihane ◽  
Kumal Siddiq ◽  
Daniel J. Rader ◽  
...  
Keyword(s):  
Immune Response ◽  
Kidney Disease ◽  
Serum Level ◽  
Kidney Function ◽  
Immune Activation ◽  
Critical Role ◽  
Urinary Biomarkers ◽  
Activation Markers ◽  
Urine Biomarkers ◽  
Immune System Activation

AbstractKidney function is affected in COVID-19, while kidney itself modulates the immune response. Here, hypothesize if COVID-19 urine biomarkers level can assess immune activation vs. clinical trajectory. Considering the kidney’s critical role in modulating the immune response, we sought to analyze activation markers in patients with pre-existing dysfunction. This was a cross-sectional study of 68 patients. Blood and urine were collected within 48 h of hospital admission (H1), followed by 96 h (H2), seven days (H3), and up to 25 days (H4) from admission. Serum level ferritin, procalcitonin, IL-6 assessed immune activation overall, while the response to viral burden was gauged with serum level of spike protein and αspike IgM and IgG. 39 markers correlated highly between urine and blood. Age and race, and to a lesser extend gender, differentiated several urine markers. The burden of pre-existing conditions correlated with urine DCN, CAIX and PTN, but inversely with IL-5 or MCP-4. Higher urinary IL-12 and lower CAIX, CCL23, IL-15, IL-18, MCP-1, MCP-3, MUC-16, PD-L1, TNFRS12A, and TNFRS21 signified non-survivors. APACHE correlated with urine TNFRS12, PGF, CAIX, DCN, CXCL6, and EGF. Admission urine LAG-3 and IL-2 predicted death. Pre-existing kidney disease had a unique pattern of urinary inflammatory markers. Acute kidney injury was associated, and to a certain degree, predicted by IFNg, TWEAK, MMP7, and MUC-16. Remdesavir had a more profound effect on the urine biomarkers than steroids. Urinary biomarkers correlated with clinical status, kidney function, markers of the immune system activation, and probability of demise in COVID-19.

Abstract 161: Identification of Genetic Variants Associated with Kidney Injury That Leads to Increased Blood Pressure

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Ashlyn C Harmon ◽  
Ashley C Johnson ◽  
Santosh Atanur ◽  
Klio Maratou ◽  
Tim Aitman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Bone Marrow ◽  
Immune Response ◽  
Renal Function ◽  
Kidney Disease ◽  
Kidney Function ◽  
Genetic Variants ◽  
Kidney Injury ◽  
Chromosome 11 ◽  
Genomic Locus

Hypertension, diabetes and obesity, along with genetic predisposition, contribute to the growing number of chronic kidney disease patients. Our novel congenic model [S.SHR(11)] was developed through genetic modification of the Dahl salt-sensitive (S) rat, a model of hypertension related renal disease. The S.SHR(11) strain exhibits accelerated kidney injury compared to the already highly susceptible S rat. On either a low or high-salt diet, the S.SHR(11) model predominately exhibited more tubulointerstitial fibrosis compared to the S rat (17.1±1.29% vs. 12.9±1.22%). Increased α-SMA and macrophage infiltration was also observed. The S and S.SHR(11) had similar blood pressure (week 12), despite an early reduction in renal function in the S.SHR(11); however at an advanced age the S.SHR(11) demonstrated significantly higher blood pressure than the S (215±6.6 mm Hg vs. 183±5.9, respectively). This suggests that increased kidney injury is driving the development of hypertension later in life. Since these two animal models are identical with exception of chromosome 11, the causative genetic variants contributing to decreased renal function must reside within this region. The Dahl S and SHR genomes have been sequenced; this data provides a catalog of all the genetic variants between the two models. The 95% confidence interval of the genomic locus contains 28 non-synonymous SNP, with 15 of these SNP occurring within only three genes: Retnlg , Trat1 and Myh15. Two of these genes, Retnlg and Trat1, are known to play a role in immune response leading to our hypothesis that genetic variants in these genes alter protein function and lead to an increased immune response. Bone marrow transplant studies have been initiated to test our hypothesis and preliminary data shows that S rats who receive S.SHR(11) bone marrow have kidney function measurements similar to the S.SHR(11). The sequencing information has also lead to the development of nine new, more refined congenic strains. Through functional analysis of these new congenic animals, identification of the causative genetic variations will be expedited. In summary, we are employing a model of accelerated kidney disease to identify genes or genetic variants responsible for reduced kidney function and hypertension.

scholarly journals Associations of Urine Biomarkers with Kidney Function Decline in HIV-Infected and Uninfected Men

2019 ◽  
Vol 50 (5) ◽  
pp. 401-410 ◽  
Author(s):  
Simon B. Ascher ◽  
Rebecca Scherzer ◽  
Michelle M. Estrella ◽  
Michael G. Shlipak ◽  
Derek K. Ng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kidney Disease ◽  
Kidney Function ◽  
Disease Risk ◽  
Kidney Injury ◽  
Procollagen Type ◽  
Urine Albumin ◽  
Urine Biomarkers ◽  
Increased Risk ◽  
Egfr Decline

Background: HIV-infected (HIV+) persons are at increased risk of chronic kidney disease, but serum creatinine does not detect early losses in kidney function. We hypothesized that urine biomarkers of kidney damage would be associated with subsequent changes in kidney function in a contemporary cohort of HIV+ and HIV-uninfected (HIV–) men. Methods: In the Multicenter AIDS Cohort Study, we measured baseline urine concentrations of 5 biomarkers from 2009 to 2011 in 860 HIV+ and 337 HIV– men: albumin, alpha-1-microglobulin (α1m), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and procollagen type III N-terminal propeptide (PIIINP). We evaluated associations of urine biomarker concentrations with annual changes in estimated glomerular filtration rate (eGFR) using multivariable linear mixed models adjusted for demographics, traditional kidney disease risk factors, HIV-related risk factors, and baseline eGFR. Results: Over a median follow-up of 4.8 years, the average annual eGFR decline was 1.42 mL/min/1.73 m2/year in HIV+ men and 1.22 mL/min/1.73 m2/year in HIV– men. Among HIV+ men, the highest vs. lowest tertiles of albumin (–1.78 mL/min/1.73 m2/year, 95% CI –3.47 to –0.09) and α1m (–2.43 mL/min/1.73 m2/year, 95% CI –4.14 to –0.73) were each associated with faster annual eGFR declines after multivariable adjustment. Among HIV– men, the highest vs. lowest tertile of α1m (–2.49 mL/min/1.73 m2/year, 95% CI –4.48 to –0.50) was independently associated with faster annual eGFR decline. Urine IL-18, KIM-1, and PIIINP showed no independent associations with eGFR decline, regardless of HIV serostatus. Conclusions: Among HIV+ men, higher urine albumin and α1m are associated with subsequent declines in kidney function, independent of eGFR.

scholarly journals Rapid Progression of Autosomal Dominant Polycystic Kidney Disease: Urinary Biomarkers as Predictors

2019 ◽  
Vol 50 (5) ◽  
pp. 375-385 ◽  
Author(s):  
A. Lianne Messchendorp ◽  
Esther Meijer ◽  
Folkert W. Visser ◽  
Gerwin E. Engels ◽  
Peter Kappert ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Function ◽  
Predictive Value ◽  
Progressive Disease ◽  
Autosomal Dominant ◽  
Urinary Biomarkers ◽  
Urinary Biomarker ◽  
Inflammation Markers ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

Background: Markers currently used to predict the likelihood of rapid disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) are expensive and time consuming to assess and often have limited sensitivity. New, easy-to-measure markers are therefore needed that alone or in combination with conventional risk markers can predict the rate of disease progression. In the present study, we investigated the ability of tubular damage and inflammation markers to predict kidney function decline. Methods: At baseline, albumin, immunoglobulin G, kidney injury molecule 1, β2 microglobulin (β2MG), heart-type fatty acid-binding protein, neutrophil gelatinase-associated lipocalin, and monocyte chemotactic protein-1 ­(MCP-1) were measured in 24-h urine samples of patients participating in a study investigating the therapeutic efficacy of lanreotide in ADPKD. Individual change in estimated glomerular filtration rate (eGFR) during follow-up was calculated using mixed-model analysis taking into account 13 ­eGFRs (chronic kidney disease EPIdemiology) per patient. Logistic regression analysis was used to select urinary biomarkers that had the best association with rapidly progressive disease. The predictive value of these selected urinary biomarkers was compared to other risk scores using C-statistics. Results: Included were 302 patients of whom 53.3% were female, with an average age of 48 ± 7 years, eGFR of 52 ± 12 mL/min/1.73 m2, and a height-adjusted total kidney volume (htTKV) of 1,082 (736–1,669) mL/m. At baseline, all urinary damage and inflammation markers were associated with baseline eGFR, also after adjustment for age, sex and baseline htTKV. For longitudinal analyses only patients randomized to standard care were considered (n = 152). A stepwise backward analysis revealed that β2MG and MCP-1 showed the strongest association with rapidly progressive disease. A urinary biomarker score was created by summing the ranking of tertiles of β2MG and MCP-1 excretion. The predictive value of this urinary biomarker score was higher compared to that of the Mayo htTKV classification (area under the curve [AUC] 0.73 [0.64–0.82] vs. 0.61 [0.51–0.71], p = 0.04) and comparable to that of the predicting renal outcomes in ­ADPKD score (AUC 0.73 [0.64–0.82] vs. 0.65 [0.55–0.75], p = 0.18). In a second independent cohort with better kidney function, similar results were found for the urinary biomarker score. Conclusion: Measurement of urinary β2MG and MCP-1 excretion allows selection of ADPKD patients with rapidly progressive disease, with a predictive value comparable to or even higher than that of TKV or PKD mutation. Easy and inexpensive to measure urinary markers therefore hold promise to help predict prognosis in ADPKD.

scholarly journals Description of Serum Urea and Creatinine Levels Pre Hemodialysis and Post Hemodialysis at Royal Prima Hospital in Chronic Kidney Disease

2021 ◽  
Vol 2 (2) ◽  
pp. 118-123
Author(s):  
Raymond Nazimuddin Putra ◽  
Valentine Athania Br Perangin-angin ◽  
Sahna Ferdinand ◽  
Erny Tandanu
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Serum Level ◽  
Creatinine Level ◽  
Kidney Function ◽  
Kidney Failure ◽  
Chronic Kidney Failure ◽  
Serum Urea ◽  
Urea Level ◽  
Gradual Loss

Chronic Kidney Failure describes as the gradual loss of kidney functionand it is irreversible, to replace the loss of kidney function a therapy tokidney function is needed, which is hemodialysis. The objective of thisresearch is to know the levels of ureu and creatinine serum for prehemodialysis and post hemodialysis at RSU Royal Prima Medan. Themethods that are being used for this research is descriptive with 54 patientsas samples. The results of this research is loss of urea and creatinine serumlevel, with the average of urea level for pre hemodialysis is 128.11 mg/dL,and the average of urea level for post hemodialysis is 43.26 mg/dL with1,8% patient with low urea level, 50% with normal urea level, and 48.2%with high urea level. The average of creatine level for pre hemodialysis is11.56 mg/dL, and the average of creatine levels is 4.3 mg/dL, with all of thepatient still have a high creatinine levels. The conclusion is there is drop forboth urea and creatinen serum level, but the urea level for half of the patientdid not go down to normal, and for the creatinine level there is none of thepatient creatinine level that go down to normal.

Evaluation of immune activation following neoadjuvant sipuleucel-T in subjects with localized prostate cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2563-2563
Author(s):  
Nadeem A. Sheikh ◽  
Johnna D. Wesley ◽  
Nikole Perdue ◽  
Frances P. Stewart ◽  
Lawrence Fong
Keyword(s):  
Prostate Cancer ◽  
T Cell ◽  
B Cells ◽  
T Cell Activation ◽  
Immune Activation ◽  
Cell Activation ◽  
Localized Prostate Cancer ◽  
Cellular Immunotherapy ◽  
Activation Markers ◽  
Immune System Activation

2563 Background: Sipuleucel-T is an FDA-approved autologous cellular immunotherapy for men with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC). NeoACT (Study P07-1) was undertaken to investigate neoadjuvant sipuleucel-T treatment in subjects with localized prostate cancer. Methods: In this open-label, phase 2 study (NCT00715104), subjects with localized prostate cancer received 3 infusions of sipuleucel-T at approximately 2-week intervals, beginning 6–7 weeks prior to radical prostatectomy (RP). Following RP, subjects were randomized 1:1 to receive / not receive a sipuleucel-T booster infusion 12 weeks post-RP. Cellular composition, antigen presenting cell (APC) activation, cytokines, and T and B cell activation were profiled before and after each culture with PA2024, the fusion protein containing prostatic acid phosphatase used to generate sipuleucel-T. Results: Of the 42 enrolled subjects (median age: 61 years; 98% Caucasian), 38 received all 3 infusions of sipuleucel-T, and 15 subjects received a booster infusion. Consistent with sipuleucel-T in mCRPC, CD54 upregulation (APC activation) was greater at the second and third infusions relative to the first (p<0.001). The expression of early T cell activation markers (CD134, CD137, CD278 and CD279) were increased in pre-culture cells obtained after the first infusion, and further increased after culture. Activated mature B cells (CD20+CD27+IgD+CD86+) increased following culture in all 3 products (p<0.01); memory B cells (CD20+CD27+IgD-CD86+) were progressively increased following the first infusion (p<0.05 third vs. first product). TNF-α, IFN-γ, IL-2 were secreted at higher levels during culture of the second and third products (all p<0.001). The observed increases in CD54 upregulation, early T cell activation markers, and memory and activated mature B cells were maintained at booster treatment. Conclusions: Neoadjuvant sipuleucel-T resulted in robust immune system activation that was consistent with boosting of an immune response primed with the first infusion. Immune activation was maintained at the booster infusion 3 months following initial sipuleucel-T treatment.

Abstract MP072: Association of Urinary Kidney Injury Biomarkers with Kidney Function Decline: A Case-Control Study from the Multi-Ethnic Study of Atherosclerosis (MESA)

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Carmen A Peralta ◽  
Ronit Katz ◽  
Joseph V Bonventre ◽  
Venkata Sabbisetti ◽  
David Siscovick ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Function ◽  
Case Control Study ◽  
Kidney Injury ◽  
Case Control ◽  
Urinary Biomarkers ◽  
Tubular Injury ◽  
Future Risk ◽  
Kidney Function Decline ◽  
Control Study

Background: The urinary biomarkers of tubular injury ((urine neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1)) can indicate acute kidney injury before reductions in estimated glomerular filtration rate (eGFR) are clinically detectable. Whether elevations of these markers are associated with future risk of kidney disease has not been investigated. Methods: We studied the association of urinary NGAL and KIM-1 with kidney function decline in a 1:1 ratio case-control study among 686 MESA participants. NGAL and KIM-1 were measured at baseline (standardized for urinary creatinine) and expressed both as continuous and in deciles. eGFR was estimated by cystatin C. Cases were defined as persons with eGFR>60 ml/min/1.73m 2 who subsequently developed incident CKD (defined as eGFR<60 plus eGFR decline > 1ml/min/year) and/or had rapid kidney function decline (RKFD, ≥3ml/min/1.73m 2 /year) by the MESA year 5 visit. Of the 343 cases, 145 had incident CKD, 141 had RKFD and 57 had both. Controls were matched for age, gender, race, diabetes, and baseline eGFR. We adjusted for age, hypertension and presence of albuminuria (ACR ≥30 mg/g). Results: Higher levels of KIM-1 were significantly associated with kidney function decline, and these associations were strongest for the top decile compared to lowest decile. Presence of albuminuria only minimally attenuated the findings. NGAL levels were not associated with kidney function decline. (Table) Model OR (95%CI) for Incident CKD and/or Rapid Kidney Function Decline KIM-1 (pg/ml) * KIM-1-Cr Ratio * (pg/mg) KIM-1 ≥ 927 pg/ml (Top Decile) NGAL (ng/ml) * NGAL-Cr Ratio * (ng/mg) NGAL ≥ 36 ng/ml (Top Decile) Age Adjusted 1.15 (1.02, 1.29) 1.17 (1.02, 1.34) 2.09 (1.21, 3.62) 1.04 (0.99, 1.10) 1.03 (0.98, 1.09) 1.63 (0.96, 2.78) Age + HTN Adjusted 1.15 (1.03, 1.29) 1.16 (1.01, 1.33) 2.13 (1.22, 3.70) 1.04 (0.99, 1.10) 1.03 (0.98, 1.09) 1.58 (0.93, 2.71) + ACR ≥ 30mg/g 1.15 (1.02, 1.29) 1.13 (0.98, 1.30) 2.02 (1.15, 3.56) 1.04 (0.99, 1.10) 1.03 (0.97, 1.08) 1.55 (0.89, 2.70) * Per doubling. Top decile is compared to lowest decile Conclusions: KIM-1, a marker of tubular injury, is associated with future risk of kidney disease independent of albuminuria. Our findings suggest that urinary biomarkers of tubular injury are a promising tool for identifying persons at risk for CKD.

scholarly journals Innate immune responses in patients treated with SBRT irradiation enhances prostate cancer remissions

2022 ◽  
Author(s):  
Amrita Cheema ◽  
Yaoxiang Li ◽  
Sean Collins ◽  
Simeng Suy ◽  
Mary Ventimiglia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Response ◽  
Radiation Therapy ◽  
Immune Responses ◽  
Immune Activation ◽  
Biomarker Discovery ◽  
Critical Role ◽  
Innate Immune ◽  
Therapeutic Modality ◽  
Innate Immune Activation

Stereotactic body radiation therapy (SBRT) is a curative therapeutic modality employing large fractional doses of highly conformal radiation therapy for cancer treatment. To understand the mechanisms underlying clinical responses to radiation therapy, SBRT offers a unique window for high-throughput analysis of post-radiation molecular events to inform predictive biomarker discovery and strategies for multi-disciplinary therapeutics. We performed a longitudinal analysis of plasma proteins and metabolites from patients treated with prostate SBRT, comparing cohorts of patients in clinical remission to cohorts experiencing PSA-determined cancer progression. We observed the onset of post-SBRT DNA Damage Response (DDR), cell cycle arrest, and immune response signaling in patients within one hour of treatment and innate immune response signaling that persisted for up to three months following treatment. Furthermore, patients in remission experienced more robust immune responses and metabolite elevations consistent with a pro-inflammatory, M1-mediated innate immune activation in the short-term following SBRT, whereas patients with disease progression had less robust immune responses and M2-mediated metabolite elevations. We interpret these data to support a critical role for innate immune activation in the clinical outcomes of patients receiving radiation therapy for prostate cancer potentially improving future multidisciplinary therapeutic strategies.

scholarly journals Development of Bio-Artificial Micro-Vessels with Immunosuppressive Capacities: A Hope for Future Transplantations and Organoids

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3610-3610 ◽  
Author(s):  
Sina Naserian ◽  
Mohamed Essameldin Abdelgawad ◽  
Julie Lachaux ◽  
Nassim Arouche ◽  
Fanny Loisel ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Endothelial Cells ◽  
Cord Blood ◽  
Progenitor Cells ◽  
Conflicts Of Interest ◽  
Critical Role ◽  
Artificial Organs ◽  
Activation Markers ◽  
First Time

Background: From creating artificial organs to transplantation and cancer, newly formed vessels are playing a critical role. Endothelial progenitor cells (EPCs) are non-differentiated endothelial cells which are present in circulation and are applied in neovascularization and correction of damaged endothelial sites. In culture, EPCs generate endothelial colony forming cells (ECFCs) that have endothelial features but still retain properties of stem/progenitor cells. However, these cells which are recognized as CD31+CD144+KDR+ are very rare in blood stream. Therefore, it is necessary to be ex-vivo expanded for further applications. Since EPCs from patients are proved to be impaired and inefficient, allogenic sources either from adult or cord blood are considered as good alternatives. Due to the reaction of immune response to allogenic cells which usually leads to increased immune response and inflammation and finally elimination of injected cells, we have focused on the exact role of EPCs on immune cells, particularly, T cells which are the most important cells applied in immune rejection. Aims: First we sought to design and produce a biomimetic micro-vessel device and to endothelialize it in static and under flow conditions. Second, we wanted to investigate the interaction between EPCs and T cells to further understand their potential immunogenicity. Results: For the first part of the study we have been able to produce a biomimetic micro-vessel device that is porous, biocompatible, soft and transparent for high-resolution microscopy techniques. We have developed a multi-scale microfluidic chips with a conventional design of successive branching for fluid injection into the capillaries following Murray's laws (Figure 1A). Furthermore, we have successfully endothelialized this artificial micro-vessel using cord blood derived EPCs both in static and under flow condition and kept them in an acceptable situation up to 2 weeks after the first seeding (Figure 1B and C). For the second part of our study, we have shown for the first time that in contrary to already differentiated endothelial cells, EPCs while co-cultured with T cells, not only do not increase T cell proliferation but also are extremely immunosuppressant (Figure 1D). Moreover, we have shown that EPCs could also reduce the activation markers expressed by both CD4+ and CD8+ conventional T cells. Conclusion: We have demonstrated for the first time the possibility of producing an endothelialized vessel-like micro chamber with remarkable immunosuppressive and immunomodulatory properties. This proves the importance of using EPCs for future bio-artificial organs since these cells not only do not increase allo-response but also can regulate it. In case of transplantation, our findings could open a door for ameliorating the transplant acceptance through faster endothelialization and suppression of alloreactive T cells aiming to reject the transplant. Disclosures No relevant conflicts of interest to declare.

Description of Serum Urea and Creatinine Levels Pre Hemodialysis and Post Hemodialysis at Royal Prima Hospital in Chronic Kidney Disease

2021 ◽  
Vol 2 (1) ◽  
pp. 119-124
Author(s):  
Raymond Nazimuddin Putra ◽  
Valentine Athania Br Perangin-angin ◽  
Sahna Ferdinand ◽  
Erny Tandanu
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Serum Level ◽  
Creatinine Level ◽  
Kidney Function ◽  
Kidney Failure ◽  
Serum Urea ◽  
Urea Level ◽  
Gradual Loss

A B S T R A C TChronic Kidney Failure describes as the gradual loss of kidney function and it isirreversible, to replace the loss of kidney function a therapy to kidney function isneeded, which is hemodialysis. The objective of this research is to know the levels ofureu and creatinine serum for pre hemodialysis and post hemodialysis at RSU RoyalPrima Medan. The methods that are being used for this research is descriptive with54 patients as samples. The results of this research is loss of urea and creatinineserum level, with the average of urea level for pre hemodialysis is 128.11 mg/dL, andthe average of urea level for post hemodialysis is 43.26 mg/dL with 1,8% patient withlow urea level, 50% with normal urea level, and 48.2% with high urea level. Theaverage of creatine level for pre hemodialysis is 11.56 mg/dL, and the average ofcreatine levels is 4.3 mg/dL, with all of the patient still have a high creatinine levels.The conclusion is there is drop for both urea and creatinen serum level, but the urealevel for half of the patient did not go down to normal, and for the creatinine levelthere is none of the patient creatinine level that go down to normal.

scholarly journals MO648SERUM SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR IN PATIENTS WITH DIABETIC KIDNEY DISEASE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Gabriela Elena Lupusoru ◽  
Ioana-Georgiana Ailincai ◽  
Bogdan Marian Sorohan ◽  
Andreea Gabriella Andronesi ◽  
Mircea Lupusoru ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Serum Level ◽  
Specific Gravity ◽  
Kidney Function ◽  
Diabetic Kidney Disease ◽  
Urokinase Plasminogen Activator Receptor ◽  
Duration Of Diabetes ◽  
Plasminogen Activator Receptor

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.

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