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 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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References
Gabow PA. Autosomal dominant polycystic kidney disease. N Engl J Med. 1993;5:332–42.
Torres VE, Harris PC. Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int. 2009;2:149–68.
Ecder T, Schrier RW. Cardiovascular abnormalities in autosomal-dominant polycystic kidney disease. Nat Rev Nephrol. 2009;4:221–8.
Ecder T, Schrier RW. Hypertension in autosomal-dominant polycystic kidney disease: early occurrence and unique aspects. J Am Soc Nephrol. 2001;1:194–200.
Lin CC, Kurashige M, Liu Y, Terabayashi T, Ishimoto Y, Wang T, et al. A cleavage product of Polycystin-1 is a mitochondrial matrix protein that affects mitochondrial morphology and function when heterologously expressed. Sci Rep. 2018;8(1):2743.
Nowak KL, You Z, Gitomer B, Brosnahan G, Torres VE, Chapman AB, et al. Overweight and obesity are predictors of progression in early autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2018;29(2):571–8.
Ducloux D, Motte G, Vautrin P, Bresson-Vautrin C, Rebibou JM, Chalopin JM. Polycystic kidney disease as a risk factor for post-transplant diabetes mellitus. Nephrol Dial Transplant. 1999;5:1244–6.
Merta M, Tesar V, Zima T, Jirsa M, Rysava R, Zabka J. Cytokine profile in autosomal dominant polycystic kidney disease. Biochem Mol Biol Int. 1997;41:619–24.
Pei Y, Obaji J, Dupuis A, Paterson AD, Magistroni R, Dicks E, et al. Unified criteria fo rultrasonographic diagnosis of ADPKD. J Am Soc Nephrol. 2009;20(1):205–12.
James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507–20.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.
Crutchlow MF, Robinson B, Pappachen B, Wimmer N, Cucchiara AJ, Cohen D, et al. Validation of steady-state insülin sensitivity indices in chronic kidney disease. Diabetes Care. 2007;30(7):1813–8.
National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation. 2002;25:3143–421.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration), et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12.
Bae KT, Tao C, Wang J, Kaya D, Wu Z, Bae JT, Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP), et al. Novel approach to estimate kidney and cyst volumes using mid-slice magnetic resonance images in polycystic kidney disease. Am J Nephrol. 2013;38(4):333–41.
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, ACMG Laboratory Quality Assurance Committee, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–24.
Rowe I, Chiaravalli M, Mannella V, Ulisse V, Quilici G, Pema M, et al. Defective glucose metabolism in polycystic kidney disease identifies a new therapeutic strategy. Nat Med. 2013;19(4):488–93.
Riwanto M, Kapoor S, Rodriguez D, Edenhofer I, Segerer S, Wüthrich RP. Inhibition of aerobic glycolysis attenuates disease progression in polycystic kidney disease. PLoS ONE. 2016;11(1):e0146654.
Warner G, Hein KZ, Nin V, Edwards M, Chini CC, Hopp K, et al. Food restriction ameliorates the development of polycystic kidney disease. J Am Soc Nephrol. 2016;27(5):1437–47.
Kipp KR, Rezaei M, Lin L, Dewey EC, Weimbs T. A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease. Am J Physiol Renal Physiol. 2016;310(8):F726–31.
Pietrzak-Nowacka M, Safranow K, Byra E, Bińczak-Kuleta A, Ciechanowicz A, Ciechanowski K. Metabolic syndrome components in patients with autosomal-dominant polycystic kidney disease. Kidney Blood Press Res. 2009;32(6):405–10.
Fox CS, Larson MG, Leip EP, Culleton B, Wilson PW, Levy D. Predictors of new-onset kidney disease in a community-based population. JAMA. 2004;7:844–50.
Iseki K, Ikemiya Y, Kinjo K, Inoue T, Iseki C, Takishita S. Body mass index and the risk of development of end-stage renal disease in a screened cohort. Kidney Int. 2004;5:1870–6.
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We thank all study participants who enrolled to the study
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IK, EE, and FO conceived of the study and designed the protocol which was implemented by IK, JA, TE and EE. These authors also recruited the participants. BT, MHS, OO and ZK helped with the study design. AS set up and validated the inflammatory markers assay and helped to interpret the results. RB performed the tests for determining PKD mutation. IK, EE and FO coordinated the study. FO and MC collected the data of the study. IK, EE and ASK wrote the paper. JA reviewed the draft and provided expertise for revision. All authors participated in data analysis and interpretation, and also read and approved the final manuscript.
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Kocyigit, I., Ozturk, F., Eroglu, E. et al. Dysmetabolic markers predict outcomes in autosomal dominant polycystic kidney disease. Clin Exp Nephrol 23, 1130–1140 (2019). https://doi.org/10.1007/s10157-019-01748-z
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DOI: https://doi.org/10.1007/s10157-019-01748-z