Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Pediatric Nephrology
Published in: Pediatric Nephrology 3/2011

01-03-2011 | Review

PPARγ and chronic kidney disease

Author: Agnes B. Fogo

Published in: Pediatric Nephrology | Issue 3/2011

Login to get access

Abstract

Peroxisome proliferator-activated receptor-γ (PPARγ) agonists, exemplified by the thiazolidinediones (TZDs), have been used extensively for their beneficial effects to improve insulin sensitivity and lipid metabolism in type 2 diabetic patients. PPARγ receptors are part of the steroid hormone nuclear receptor family and, when activated by agonist binding, can affect numerous target genes expressing PPAR response elements. Results from experimental studies and a limited number of studies in humans suggest that PPARγ agonists have manifold effects beyond those on dysmetabolic syndrome. These potentially beneficial actions are mediated via renal parenchymal and infiltrating cells and modulate fibrotic, inflammatory, immune, proliferative, reactive oxygen and mitochondrial injury pathways. Thus, the potential benefits of TZDs in chronic kidney disease impact numerous pathogenic pathways. This review will focus on evidence of the effects of TZDs in nondiabetic chronic kidney disease in experimental and human disease settings.
Literature
1.
Sarafidis PA, Bakris GL (2006) Protection of the kidney by thiazolidinediones: an assessment from bench to bedside. Kidney Int 70:1223–1233PubMedCrossRef
2.
Szeto C-C, Li PK (2008) Antiproteinuric and anti-inflammatory effects of thiazolidinediones. Nephrology (Carlton) 13:53–57CrossRef
3.
Iglesias P, Diez JJ (2006) Peroxisome proliferator-activated receptor gamma agonists in renal disease. Eur J Endocrinol 154:613–621PubMedCrossRef
4.
Tontonoz P, Nagy L, Alvarez JG, Thomazy VA, Evans RM (1998) PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 93:241–252PubMedCrossRef
5.
Anderson S, Meyer TW, Rennke HG, Brenner BM (1985) Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J Clin Invest 76:612–619PubMedCrossRef
6.
Ma LJ, Marcantoni C, Linton MF, Fazio S, Fogo AB (2001) Peroxisome proliferator-activated receptor-gamma agonist troglitazone protects against nondiabetic glomerulosclerosis in rats. Kidney Int 59:1899–1910PubMedCrossRef
7.
Yoshida K, Kohzuki M, Xu HL, Wu XM, Kamimoto M, Sato T (2001) Effects of troglitazone and temocapril in spontaneously hypertensive rats with chronic renal failure. J Hypertens 19:503–510PubMedCrossRef
8.
Marx N, Schönbeck U, Lazar MA, Libby P, Plutzky J (1998) Peroxisome proliferator-activated receptor gamma activators inhibit gene expression and migration in human vascular smooth muscle cells. Circ Res 83:1097–1103PubMed
9.
Marx N, Bourcier T, Sukhova GK, Libby P, Plutzky J (1999) PPARgamma activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPARgamma as a potential mediator in vascular disease. Arterioscler Thromb Vasc 19:546–551
10.
Ohga S, Shikata K, Yozai K, Okada S, Ogawa D, Usui H, Wada J, Shikata Y, Makino H (2007) Thiazolidinedione ameliorates renal injury in experimental diabetic rats through anti-inflammatory effects mediated by inhibition of NF-kappaB activation. Am J Physiol Renal Physiol 292:F1141–F1150PubMedCrossRef
11.
Yang HC, Ma LJ, Ma J, Fogo AB (2006) Peroxisome proliferator-activated receptor-gamma agonist is protective in podocyte injury-associated sclerosis. Kidney Int 69:1756–1764PubMedCrossRef
12.
Kanjanabuch T, Ma LJ, Chen J, Pozzi A, Guan Y, Mundel P, Fogo AB (2007) PPAR-gamma agonist protects podocytes from injury. Kidney Int 71:1232–1239PubMedCrossRef
13.
Maeda A, Horikoshi S, Gohda T, Tsuge T, Maeda K, Tomino Y (2005) Pioglitazone attenuates TGF-beta(1)-induction of fibronectin synthesis and its splicing variant in human mesangial cells via activation of peroxisome proliferator-activated receptor (PPAR)gamma. Cell Biol Int 29:422–428PubMedCrossRef
14.
Nicholas SB, Kawano Y, Wakino S, Collins AR, Hsueh WA (2001) Expression and function of peroxisome proliferator-activated receptor-gamma in mesangial cells. Hypertension 37:722–727PubMed
15.
Zafiriou S, Stanners SR, Saad S, Polhill TS, Poronnik P, Pollock CA (2005) Pioglitazone inhibits cell growth and reduces matrix production in human kidney fibroblasts. J Am Soc Nephrol 16:638–645PubMedCrossRef
16.
Li Y, Wen X, Spataro BC, Hu K, Dai C, Liu Y (2006) Hepatocyte growth factor is a downstream effector that mediates the antifibrotic action of peroxisome proliferator-activated receptor-gamma agonists. J Am Soc Nephrol 17:54–65PubMedCrossRef
17.
Harte A, McTernan P, Chetty R, Coppack S, Katz J, Smith S, Kumar S (2005) Insulin-mediated upregulation of the renin angiotensin system in human subcutaneous adipocytes is reduced by rosiglitazone. Circulation 111:1954–1961PubMedCrossRef
18.
Takeda K, Ichiki T, Tokunou T, Funakoshi Y, Iino N, Hirano K, Kanaide H, Takeshita A (2000) Peroxisome proliferator-activated receptor gamma activators downregulate angiotensin II type 1 receptor in vascular smooth muscle cells. Circulation 102:1834–1839PubMed
19.
Sugawara A, Takeuchi K, Uruno A, Ikeda Y, Arima S, Sato K, Kudo M, Taniyama Y, Ito S (2001) Differential effects among thiazolidinediones on the transcription of thromboxane receptor and angiotensin II type 1 receptor genes. Hypertens Res 24:229–233PubMedCrossRef
20.
Erbe DV, Gartrell K, Zhang YL, Suri V, Kirincich SJ, Will S, Perreault M, Wang S, Tobin JF (2006) Molecular activation of PPARgamma by angiotensin II type 1-receptor antagonists. Vascul Pharmacol 45:154–162PubMedCrossRef
21.
Suganuma E, Babaev VR, Motojima M, Zuo Y, Ayabe N, Fogo AB, Ichikawa I, Linton MF, Fazio S, Kon V (2007) Angiotensin inhibition decreases progression of advanced atherosclerosis and stabilizes established atherosclerotic plaques. J Am Soc Nephrol 18:2311–2319PubMedCrossRef
22.
Nakamura T, Ushiyama C, Shimada N, Hayashi K, Ebihara I, Koide H (2000) Comparative effects of pioglitazone, glibenclamide, and voglibose on urinary endothelin-1 and albumin excretion in diabetes patients. J Diabetes Complications 14:250–254PubMedCrossRef
23.
Dong FQ, Li H, Cai WM, Tao J, Li Q, Ruan Y, Zheng FP, Zhang Z (2004) Effects of pioglitazone on expressions of matrix metalloproteinases 2 and 9 in kidneys of diabetic rats. Chin Med J (Engl) 117:1040–1044
24.
Zafiriou S, Stanners SR, Polhill TS, Poronnik P, Pollock CA (2004) Pioglitazone increases renal tubular cell albumin uptake but limits proinflammatory and fibrotic responses. Kidney Int 65:1647–1653PubMedCrossRef
25.
Kiss E, Popovic ZV, Bedke J, Adams J, Bonrouhi M, Babelova A, Schmidt C, Edenhofer F, Zschiedrich I, Domhan S, Abdollahi A, Schäfer L, Gretz N, Porubsky S, Gröne HJ (2010) Peroxisome proliferator-activated receptor (PPAR)gamma can inhibit chronic renal allograft damage. Am J Pathol 176:2150–2162PubMedCrossRef
26.
Nencioni A, Grünebach F, Zobywlaski A, Denzlinger C, Brugger W, Brossart P (2002) Dendritic cell immunogenicity is regulated by peroxisome proliferator-activated receptor gamma. J Immunol 169:1228–1235PubMed
27.
Klotz L, Dani I, Edenhofer F, Nolden L, Evert B, Paul B, Kolanus W, Klockgether T, Knolle P, Diehl L (2007) Peroxisome proliferator-activated receptor gamma control of dendritic cell function contributes to development of CD4+ T cell anergy. J Immunol 178:2122–2131PubMed
28.
Marx N, Mach F, Sauty A, Leung JH, Sarafi MN, Ransohoff RM, Libby P, Plutzky J, Luster AD (2000) Peroxisome proliferator-activated receptor-gamma activators inhibit IFN-gamma-induced expression of the T cell-active CXC chemokines IP-10, Mig, and I-TAC in human endothelial cells. J Immunol 164:6503–6508PubMed
29.
Revelo MP, Federspiel C, Helderman H, Fogo AB (2005) Chronic allograft nephropathy:expression and localization of PAI-1 and PPAR-gamma. Nephrol Dial Transplant 20:2812–2819PubMedCrossRef
30.
Paueksakon P, Revelo MP, Ma LJ, Marcantoni C, Fogo AB (2002) Microangiopathic injury and augmented PAI-1 in human diabetic nephropathy. Kidney Int 61:2142–2148PubMedCrossRef
31.
Eddy AA, Fogo AB (2006) Plasminogen activator inhibitor-1 in chronic kidney disease: evidence and mechanisms of action. J Am Soc Nephrol 17:2999–3012PubMedCrossRef
32.
Guan Y, Hao C, Cha DR, Rao R, Lu W, Kohan DE, Magnuson MA, Redha R, Zhang Y, Breyer MD (2005) Thiazolidinediones expand body fluid volume through PPARgamma stimulation of ENaC-mediated renal salt absorption. Nat Med 11:861–866PubMedCrossRef
33.
Yang HC, Deleuze S, Zuo Y, Potthoff SA, Ma LJ, Fogo AB (2009) The PPARgamma agonist pioglitazone ameliorates aging-related progressive renal injury. J Am Soc Nephrol 20:2380–2388PubMedCrossRef
34.
Pistrosch F, Herbrig K, Kindel B, Passauer J, Fischer S, Gross P (2005) Rosiglitazone improves glomerular hyperfiltration, renal endothelial dysfunction, and microalbuminuria of incipient diabetic nephropathy in patients. Diabetes 54:2206–2211PubMedCrossRef
35.
Pistrosch F, Herbrig K, Oelschlaegel U, Richter S, Passauer J, Fischer S, Gross P (2005) PPARgamma-agonist rosiglitazone increases number and migratory activity of cultured endothelial progenitor cells. Atherosclerosis 183:163–167PubMedCrossRef
36.
Sidhu JS, Cowan D, Kaski JC (2003) The effects of rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, on markers of endothelial cell activation, C-reactive protein, and fibrinogen levels in non-diabetic coronary artery disease patients. J Am Coll Cardiol 42:1757–1763PubMedCrossRef
37.
Kincaid-Smith P, Fairley KF, Farish S, Best JD, Proietto J (2008) Reduction of proteinuria by rosiglitazone in non-diabetic renal disease. Nephrology (Carlton) 13:58–62CrossRef
38.
Joy MS, Gipson DS, Dike M, Powell L, Thompson A, Vento S, Eddy A, Fogo AB, Kopp JB, Cattran D, Trachtman H (2009) Phase I trial of rosiglitazone in FSGS: I. Report of the FONT Study Group. Clin J Am Soc Nephrol 4:39–47PubMedCrossRef
Metadata
Title
PPARγ and chronic kidney disease
Author
Agnes B. Fogo
Publication date
01-03-2011
Publisher
Springer-Verlag
Published in
Pediatric Nephrology / Issue 3/2011
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-010-1602-2

Other articles of this Issue 3/2011

Pediatric Nephrology 3/2011 Go to the issue

Review

Genetics of congenital anomalies of the kidney and urinary tract

Editorial

World Kidney Day 2011: Protect your kidneys, save your heart

Educational Review

Microvascular disease in children and adolescents with type 1 diabetes and obesity

Original Article

Markers of childhood lupus nephritis indicating disease activity

Original Article

Hepatic and pulmonary nodular lesions in pediatric urinary tract infections

Original Article

Expression and function of the Ets transcription factor pea3 during formation of zebrafish pronephros