Levels of Endocan, Angiopoietin-2, and Hypoxia-Inducible Factor-1a in Patients with Autosomal Dominant Polycystic Kidney Disease and Different Levels of Renal Function

2018 ◽  
Vol 47 (4) ◽  
pp. 231-238 ◽  
Author(s):  
Vassilios Raptis ◽  
Constantinos Bakogiannis ◽  
Charalampos Loutradis ◽  
Afroditi K. Boutou ◽  
Ioanna Lampropoulou ◽  
...  
Keyword(s):  
Renal Function ◽  
Autosomal Dominant ◽  
Hypoxia Inducible Factor ◽  
Polycystic Kidney ◽  
Group A ◽  
Function Group ◽  
Autosomal Dominant Polycystic Kidney ◽  
Group B ◽  
Angiopoietin 2 ◽  
Renal Function Group

Background: Endothelial dysfunction leading to unbalanced vasoconstriction and ischemia of renal parenchyma is increasingly proposed as an alternative pathway of renal damage in autosomal dominant polycystic kidney disease (ADPKD). However, human studies investigating the evolution of such phenomena are limited. This study investigated the levels of emerging biomarkers of endothelial function, angiogenesis and hypoxia, in ADPKD patients with different renal function. Methods: The study population consisted of three groups: 26 ADPKD patients with impaired renal function (Group A; estimated glomerular filtration rate [eGFR] 45–70 mL/min/1.73 m2), 26 ADPKD patients with preserved renal function (Group B; eGFR >70 mL/min/1.73 m2), and 26 age- and sex-matched controls with no history of renal disease. Circulating levels of endocan (endothelial cell-specific molecule-1) angiopoietin-2, and hypoxia-inducible factor-1a (HIF-1a) were determined by enzyme-linked immunosorbent assay techniques. Results: Patients in Group A had significantly higher levels of endocan (7.17 ± 0.43 ng/mL), angiopoietin-2 (5,595.43 ± 3,390), and HIF-1a (163.68 ± 37.84 pg/mL) compared to patients in Group B (6.86 ± 0.59 ng/mL, p = 0.017, 3,854.41 ± 3,014.30, p = 0.018, 136.84 ± 42.10 pg/mL, p = 0.019 respectively) or controls (4.83 ± 0.69 ng/mL, 1,069 ± 427.88 pg/mL, 70.20 ± 17.49 pg/mL, p < 0.001 for all comparisons). Of note, patients in Group B had also higher levels of all markers compared to controls (p < 0.001) despite having similar renal function. In correlation analyses within ADPKD patients, we noted strong correlations of all studied markers with asymmetric dimethylarginine (ADMA; endocan r = 0.908, p < 0.001, angiopoietin-2 r = 0.983, p < 0.001 and HIF-1a r = 0.998, p < 0.001), and only weak or modest correlations with eGFR. Conclusions: This study suggests that endothelial dysfunction causing microcirculatory changes, linked to angiogenesis and hypoxia, may come early in the course of ADPKD and could be a key regulator of renal injury progression.

Serum Copeptin, NLPR3, and suPAR Levels among Patients with Autosomal-Dominant Polycystic Kidney Disease with and without Impaired Renal Function

2020 ◽  
Vol 10 (6) ◽  
pp. 440-451
Author(s):  
Vasileios Raptis ◽  
Charalampos Loutradis ◽  
Afroditi K. Boutou ◽  
Danai Faitatzidou ◽  
Athanasios Sioulis ◽  
...  
Keyword(s):  
Renal Function ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Impaired Renal Function ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Group A ◽  
Autosomal Dominant Polycystic Kidney ◽  
Group B ◽  
Age And Sex

<b><i>Background:</i></b> The pathophysiology of renal disease progression in autosomal-dominant polycystic kidney disease (ADPKD) involves not only cystogenesis but also endothelial dysfunction, leading to the activation of inflammatory and fibrotic pathways. This study evaluated the levels of biomarkers related to osmoregulation, immune system activation, and tubular injury in ADPKD patients with impaired or preserved renal function. <b><i>Methods:</i></b> This study included 26 ADPKD patients with modestly impaired renal function (estimated glomerular filtration rate [eGFR] 45–70 mL/min/1.73 m<sup>2</sup>; Group A), 26 age- and sex-matched ADPKD patients with relatively preserved renal function (eGFR &#x3e;70 mL/min/1.73 m<sup>2</sup>; Group B), and 26 age- and sex-matched controls (Group C). Serum levels of copeptin, the inflammasome nucleotide-binding and oligomerization domain-like receptors pyrin domain-containing protein 3 (NLRP3), and soluble urokinase-type plasminogen activator receptor (suPAR) were measured with ELISA techniques. <b><i>Results:</i></b> Patients in Group A had higher levels of copeptin (median [interquartile range]: 50.44 [334.85] pg/mL), NLRP3 (5.86 [3.89] ng/mL), and suPAR (390.05 [476.53] pg/mL) compared to patients in Group B (32.38 [58.33], <i>p</i> = 0.042; 2.42 [1.96], <i>p</i> &#x3c; 0.001; and 313.78 [178.85], <i>p</i> = 0.035, respectively) and Group C (6.75 [6.43]; 1.09 [0.56]; and 198.30 [28.53], respectively; <i>p</i> &#x3c; 0.001 for all comparisons). Levels of all studied markers were also significantly higher in Group B patients compared to controls (<i>p</i> &#x3c; 0.001), despite having similar eGFR. In patients with ADPKD, all studied biomarkers were correlated positively with asymmetric-dimethylarginine (ADMA) and endocan levels, and negatively with eGFR. ADMA and endocan levels were the only parameters independently associated with increased copeptin levels. <b><i>Conclusions:</i></b> This study showed that ADPKD patients with impaired and preserved renal function had higher copeptin, NLRP3, and suPAR levels than controls. Such findings support that cystogenesis and inflammation are associated with endothelial dysfunction, even in the early stages of ADKPD.

scholarly journals FP058LEVELS OF ENDOCAN, ANGIOPOIETIN-2 AND HIF-1A IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE AND DIFFERENT LEVELS OF RENAL FUNCTION

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i67-i67
Author(s):  
Vasilios Raptis ◽  
Charalampos Loutradis ◽  
Constantinos Bakogiannis ◽  
Afroditi Boutou ◽  
Marilena Alexandrou ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Angiopoietin 2 ◽  
Different Levels

scholarly journals Genetic Characteristics of Korean Patients with Autosomal Dominant Polycystic Kidney Disease by Targeted Exome Sequencing

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hyunsuk Kim ◽  
Hayne Cho Park ◽  
Hyunjin Ryu ◽  
Hyunho Kim ◽  
Hyun-Seob Lee ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Exome Sequencing ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Kidney Volume ◽  
Polycystic Kidney ◽  
Genetic Characteristics ◽  
Targeted Exome Sequencing ◽  
Autosomal Dominant Polycystic Kidney

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is one of the main causes of end-stage renal disease (ESRD). Genetic information is of the utmost importance in understanding pathogenesis of ADPKD. Therefore, this study aimed to demonstrate the genetic characteristics of ADPKD and their effects on renal function in 749 Korean ADPKD subjects from 524 unrelated families. Genetic studies of PKD1/2 were performed using targeted exome sequencing combined with Sanger sequencing in exon 1 of the PKD1 gene and a multiple ligation probe assay. The mutation detection rate was 80.7% (423/524 families, 331 mutations) and 70.7% was novel. PKD1 protein-truncating (PKD1-PT) genotype was associated with younger age at diagnosis, larger kidney volume, lower renal function compared to PKD1 non-truncating and PKD2 genotypes. The PKD1 genotype showed earlier onset of ESRD compared to PKD2 genotype (64.9 vs. 72.9 years old, P < 0.001). In frailty model controlled for age, gender, and familial clustering effect, PKD2 genotype had 0.2 times lower risk for reaching ESRD than PKD1-PT genotype (p = 0.037). In conclusion, our results suggest that genotyping can contribute to selecting rapid progressors for new emerging therapeutic interventions among Koreans.

scholarly journals Angiotensin-converting enzyme gene polymorphism in autosomal dominant polycystic kidney disease

2014 ◽  
Vol 03 (02) ◽  
pp. 057-063 ◽  
Author(s):  
Sanjeev Nair ◽  
Praveen Kumar Kolla ◽  
Madhav Desai ◽  
Pathapati Rama Mohan ◽  
Ramalingam K. ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Genotype Distribution ◽  
Polycystic Kidney ◽  
Ace Genotype ◽  
Autosomal Dominant Polycystic Kidney ◽  
Rate Of Decline ◽  
The One

Abstract Background and aim : Autosomal dominant polycystic kidney disease shows considerable variability in clinical features, including differences in severity of hypertension, rate of decline of renal function and variability in rate of cystogenesis, which are not fully explained by the genetic heterogeneity of this disease. Many different modifier variables have been proposed to explain this variability. This study aims to look at the role played by polymorphism of the ACE gene as a possible modifier in the clinical course and rapidity of progression. Material and Methods : Thirty seven patients diagnosed as ADPKD were recruited to the study. Clinical data were provided by questionnaires. Blood was collected for the determination of the ACE Insertion/Deletion (I/D) polymorphism genotype. The ACE genotype was also determined in a general control population (n = 40). The data was analyzed using the SPSS software. ACE genotype polymorphism frequencies were compared across groups using the one-way ANOVA tests. λ2 cross tabulation statistics was used to test for difference between frequency data. Results: The ACE genotype distribution showed no differences between the study (II 29.7%, ID 43.2%, DD 27.1%) and the control (II 35%, ID 45%, DD 20%) populations. Although patients on hemodialysis had a significantly higher Blood Pressure levels (p = 0.004) when compared to non-dialysis patients, no significant differences were demonstrated between genotypes of the study population. No difference was also demonstrated between the genotypes for rate of decline in renal function. Conclusion : No relationship between the ACE I/D polymorphism in ADPKD patients and severity of hypertension or progression towards ESRD was demonstrated.

scholarly journals SP201EFFECTS OF FASTING ON RENAL FUNCTION OF PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

2016 ◽  
Vol 31 (suppl_1) ◽  
pp. i153-i153
Author(s):  
Iskender Ekinci ◽  
Rumeyza Kazancıoglu ◽  
Reha Erkoç ◽  
Elif Kılıç ◽  
Elif Ece Dogan ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney
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