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Dysmetabolic markers predict outcomes in autosomal dominant polycystic kidney disease

Kocyigit, Ismail ; Ozturk, Fahir ; Eroglu, Eray ; Karaca, Zuleyha ; Kaynar, Ahmet Safa ; Cetin, Mustafa ; Tokgoz, Bulent ; Sipahioglu, Murat Hayri ; Bayramov, Ruslan and Sen, Ahmet , et al. (2019) In Clinical and Experimental Nephrology 23(9). p.1130-1140
Abstract

Background: Overweight and obesity were recently associated with a poor prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD). Whether the metabolic consequences of obesity as defined by the metabolic syndrome (MS) are also linked with disease progression remains untested. Methods: Eligible ADPKD patients with different stages of CKD (n = 105) and 105 non-diabetic controls matched for CKD stage were enrolled in the study. Groups were evaluated at baseline for presence of MS, blood markers of metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) score, and biochemical markers of inflammation (hs-CRP, IL-1β, IL-6, TNF-α and PON-1). MS was defined according to the National Cholesterol Education... (More)

Background: Overweight and obesity were recently associated with a poor prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD). Whether the metabolic consequences of obesity as defined by the metabolic syndrome (MS) are also linked with disease progression remains untested. Methods: Eligible ADPKD patients with different stages of CKD (n = 105) and 105 non-diabetic controls matched for CKD stage were enrolled in the study. Groups were evaluated at baseline for presence of MS, blood markers of metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) score, and biochemical markers of inflammation (hs-CRP, IL-1β, IL-6, TNF-α and PON-1). MS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Patients were followed for 12 months and progression defined as a decrease in baseline eGFR > 10%. Results: MS and hypertension were more prevalent amongst ADPKD patients than in the control group. Meanwhile, markers of inflammation such as hs-CRP (3.63 [3.45–5.17] vs. 4.2 [3.45–8.99] mg/dL; p = 0.014), IL-6 (21.65 [14.1–27.49] vs. 24.9 [16.23–39.4] pg/mL; p = 0.004) and IL-1β (21.33 [15.8–26.4] vs. 26.78 [18.22–35] pg/mL; p < 0.001) levels were all more elevated in ADPKD patients than in non-diabetic CKD subjects. In multivariate analysis having a truncating PKD1 mutation predicted (OR 1.25 [1.09–1.43]; p = 0.002) fulfilling the MS criteria. Finally, ADPKD patients fulfilling MS criteria had a significantly more rapid progression during 12 months of follow-up than did those that did not (OR 3.28 [1.09–9.87]; p = 0.035). Conclusions: Our data supports the notion that dysmetabolisms part of the ADPKD phenotype and associated with a poor outcome, especially in patients with a truncating PKD1 mutation.

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publication status
published
subject
keywords
Metabolic syndrome, Obesity, PKD1 mutation, Polycystic kidney disease, Renal progression
in
Clinical and Experimental Nephrology
volume
23
issue
9
pages
11 pages
publisher
Springer
external identifiers
  • scopus:85070371574
  • pmid:31134465
ISSN
1342-1751
DOI
10.1007/s10157-019-01748-z
language
English
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yes
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aee26ef6-3d1e-43ed-b070-039bc0a155b1
date added to LUP
2019-08-30 10:49:19
date last changed
2020-01-13 02:18:47
@article{aee26ef6-3d1e-43ed-b070-039bc0a155b1,
  abstract     = {<p>Background: Overweight and obesity were recently associated with a poor prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD). Whether the metabolic consequences of obesity as defined by the metabolic syndrome (MS) are also linked with disease progression remains untested. Methods: Eligible ADPKD patients with different stages of CKD (n = 105) and 105 non-diabetic controls matched for CKD stage were enrolled in the study. Groups were evaluated at baseline for presence of MS, blood markers of metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) score, and biochemical markers of inflammation (hs-CRP, IL-1β, IL-6, TNF-α and PON-1). MS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Patients were followed for 12 months and progression defined as a decrease in baseline eGFR &gt; 10%. Results: MS and hypertension were more prevalent amongst ADPKD patients than in the control group. Meanwhile, markers of inflammation such as hs-CRP (3.63 [3.45–5.17] vs. 4.2 [3.45–8.99] mg/dL; p = 0.014), IL-6 (21.65 [14.1–27.49] vs. 24.9 [16.23–39.4] pg/mL; p = 0.004) and IL-1β (21.33 [15.8–26.4] vs. 26.78 [18.22–35] pg/mL; p &lt; 0.001) levels were all more elevated in ADPKD patients than in non-diabetic CKD subjects. In multivariate analysis having a truncating PKD1 mutation predicted (OR 1.25 [1.09–1.43]; p = 0.002) fulfilling the MS criteria. Finally, ADPKD patients fulfilling MS criteria had a significantly more rapid progression during 12 months of follow-up than did those that did not (OR 3.28 [1.09–9.87]; p = 0.035). Conclusions: Our data supports the notion that dysmetabolisms part of the ADPKD phenotype and associated with a poor outcome, especially in patients with a truncating PKD1 mutation.</p>},
  author       = {Kocyigit, Ismail and Ozturk, Fahir and Eroglu, Eray and Karaca, Zuleyha and Kaynar, Ahmet Safa and Cetin, Mustafa and Tokgoz, Bulent and Sipahioglu, Murat Hayri and Bayramov, Ruslan and Sen, Ahmet and Oymak, Oktay and Ecder, Tevfik and Axelsson, Jonas},
  issn         = {1342-1751},
  language     = {eng},
  number       = {9},
  pages        = {1130--1140},
  publisher    = {Springer},
  series       = {Clinical and Experimental Nephrology},
  title        = {Dysmetabolic markers predict outcomes in autosomal dominant polycystic kidney disease},
  url          = {http://dx.doi.org/10.1007/s10157-019-01748-z},
  doi          = {10.1007/s10157-019-01748-z},
  volume       = {23},
  year         = {2019},
}