Dysmetabolic markers predict outcomes in autosomal dominant polycystic kidney disease

• Published in: Clinical and experimental nephrology Vol. 23; no. 9; pp. 1130 - 1140
• Main Authors: Kocyigit, Ismail, Ozturk, Fahir, Eroglu, Eray, Karaca, Zuleyha, Kaynar, Ahmet Safa, Cetin, Mustafa, Tokgoz, Bulent, Sipahioglu, Murat Hayri, Bayramov, Ruslan, Sen, Ahmet, Oymak, Oktay, Ecder, Tevfik, Axelsson, Jonas
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.09.2019; Springer Nature B.V
• Subjects: Adult; Biochemical markers; Biomarkers - blood; Body weight; Case-Control Studies; Cholesterol; Clinical Medicine; Diabetes; Diabetes mellitus; Disease Progression; Energy Metabolism; Epidermal growth factor receptors; Female; Genetic Predisposition to Disease; Homeostasis; Humans; Hypertension - diagnosis; Hypertension - epidemiology; IL-1β; Inflammation Mediators - blood; Insulin; Interleukin 6; Kidney diseases; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Metabolic syndrome; Metabolic Syndrome - blood; Metabolic Syndrome - diagnosis; Metabolic Syndrome - epidemiology; Metabolic Syndrome - genetics; Metabolism; Middle Aged; Multivariate analysis; Mutation; Nephrology; Obesity; Original Article; Overweight; Phenotype; Phenotypes; Polycystic kidney; Polycystic Kidney, Autosomal Dominant - diagnosis; Polycystic Kidney, Autosomal Dominant - epidemiology; Polycystic Kidney, Autosomal Dominant - genetics; Prevalence; Renal Insufficiency, Chronic - diagnosis; Renal Insufficiency, Chronic - epidemiology; Renal Insufficiency, Chronic - genetics; Risk Factors; Time Factors; TRPP Cation Channels - genetics; Tumor necrosis factor-α; Turkey; Urology; Turkey; Obesity; PKD1 mutation; Metabolic syndrome; Renal progression; Polycystic kidney disease
• ISSN: 1342-1751; 1437-7799; 1437-7799
• DOI: 10.1007/s10157-019-01748-z

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.