Obesidade e doença renal: aspectos fisiopatológicos
DOI:
https://doi.org/10.34019/1982-8047.2018.v44.13982Palavras-chave:
Obesidade, Doença Renal Crônica, Glomeruloesclerose Segmentar e Focal, Síndrome Metabólica, SobrepesoResumo
A epidemia de obesidade observada nas últimas décadas é acompanhada de aumento exponencial de doenças crônicas relacionadas, com destaque diabetes mellitus tipo 2, hipertensão arterial sistêmica, dislipidemia e doenças cardiovasculares. Do mesmo modo, a obesidade constitui fator de risco independente para o desenvolvimento de doença renal crônica, condição associada a elevados índices de morbidade e de mortalidade. A obesidade causa lesão renal de maneira indireta, por meio de sua estreita associação com hipertensão arterial sistêmica e com diabetes mellitus tipo 2 e de maneira direta, ao induzir adaptações glomerulares que culminam na glomerulopatia específica da obesidade. Além disso, o excesso de peso contribui para o agravamento de glomerulopatias pré-existentes. Múltiplos fatores explicam o desenvolvimento e o agravamento das lesões renais associadas à obesidade, em especial alterações hemodinâmicas, inflamatórias e metabólicas. Nesse contexto, a redução do peso corporal com ênfase nas alterações metabólicas e inflamatórias bem como o tratamento da hipertensão arterial e do diabetes mellitus constituem o primeiro passo para a prevenção primária e secundária do desenvolvimento de doença renal crônica. Nesta revisão serão apresentados os principais mecanismos fisiopatológicos da lesão renal associada à obesidade.
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ABRASS, C. K; SPICER, D.; RAUGI, G. J. Insulin induces a chance in extracellular matrix glycoproteins synthesized by rat mesangial cells in culture. Kidney International, v. 46, p. 613-620, sep. 1994.
BAUMANN, U.; EISENHAUER, T.; HARTMANN, H. Increase of glomerular filtration rate and renal plasma flow by insulin-like growth factor-1 during euglycaemic clamping in anaesthetized rats. European Journal of Clinical Investigation, v. 22, n.3, p. 204–209, mar. 1992.
BOLIGNANO, D.; ZOCCALI, C. Effects of weight loss on renal function in obese CKD patients: a systematic review. Nephrology Dialysis Transplantation, v.28, s. 4, p. 82-98, nov. 2013.
BONNET, F. et. al. Excessive body weight as a new independent risk factor for clinical and pathological progression in primary IgA nephritis. American Journal of Kidney Diseases, v. 37, n. 4, p. 720–727, apr. 2001.
BRENNER, B. M; LAWLER, E. V.; MACKENZIE, H. S. The hyperfiltration theory: a paradigm shift in nephrology. Kidney International. v. 49, n. 6, p. 1774-1777, jun. 1996.
BRIFFA, J. F. et al. Adipokines as a link between obesity and chronic kidney disease. American Journal of Physiology-Renal Physiology, v. 305, n. 12, p. 1629-1636, dec. 2013.
CHAGNAC, A. et al. Glomerular hemodynamics in severe obesity. American Journal of Physiology-Renal Physiology, v. 278, n. 5, p. 817-822, may. 2000.
COLE, B. K. et al. Valsartan protects pancreatic islets and adipose tissue from the inflammatory and metabolic consequences of a high-fat diet in mice. Hypertension, v. 55, n. 3, p. 715–721, mar. 2010.
D’AGATI, V. D. et al. Pathologic classification of focal segmental glomerulosclerosis: a working proposal. American Journal of Kidney Diseases, v. 43, n. 2, p. 368–382, feb. 2004.
D’AGATI, V. D.; et al. Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis. Nature Reviews Nephrology, v. 12, n. 8, p. 453–471, aug. 2016.
DE PAULA, R. B.; SILVA, A. A.; HALL, J. E. Aldosterone antagonism attenuates obesity-induced hypertension and glomerular hyperfiltration. Hypertension, v. 43, n. 1, p. 41-47, jan. 2004.
FAIN, J. N. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitamins & Hormones, v. 74, p. 443–477, 2006.
FOX, C. S. Predictors of new-onset kidney disease in a community-based population. Journal of American Medical Association. v. 291, n. 7, p. 844, feb. 2004.
FRIGOLET, M. E.; TORRES, N.; TOVAR, A. R. The renin–angiotensin system in adipose tissue and its metabolic consequences during obesity. The Journal of Nutritional Biochemistry, v. 24 n. 12, p. 2003–2015, dec. 2013.
FUKUDA, A.; et al. Growth-dependent podocyte failure causes glomerulosclerosis. Journal of the American Society of Nephrology, v. 23, n. 8, p. 1351–1363, aug. 2012.
GULER, H. P.; et al. Insulin-like growth factor-1 increases glomerular filtration rate and renal plasma flow in man. Acta Endocrinology. v. 121, n. 1, p 101-106, jul. 1989.
GUO, H.; et al. Protective effects of glucagon-like peptide-1 analog on renal tubular injury in mice on high-fat diet. Cellular Physiology and Biochemistry, v. 41, n. 3, p.1113–1124, feb. 2017.
GUO, C.; et al. Mineralocorticoid receptor blockade reverses obesity-related changes in expression of adiponectin, peroxisome proliferator-activated receptor-gamma, and proinflammatory adipokines. Circulation. V. 117, n. 17, p. 2253-2261, apr. 2008.
GUO, X.; et al. Adiponectin retards the progression of diabetic nephropathy in db/db mice by counteracting angiotensin II. Physiological Reports, v. 2, n. 2, e. 00230, feb. 2014.
HALBERG, N.; et al. Systemic fate of the adipocyte-derived factor adiponectin. Diabetes, v. 58, n. 9, p. 1961–1970, set. 2009.
HALL, J. E. The kidney, hypertension and obesity. Hypertension. v. 41, n. 3, p. 625-633, jan. 2003.
HALL, J. E.; et al. Obesity-induced hypertension. Renal function and systemic hemodynamics. Hypertension, v. 22, n. 3, p. 292-299, sep. 1993.
HENEGAR, J. R.; et al. Functional and structural changes in the kidney in the early stages of obesity. Journal of American Society of Nephrology. v.12, n. 6, p. 1211-1217, jun. 2001.
HIRATA, A.; et al. Contribution of glucocorticoid-mineralocorticoid receptor pathway on the obesity-related adipocyte dysfunction. Biochemical and Biophysical Research Communications. v. 419, n. 12, p. 182-187, mar. 2012.
HTAY, H.; et al. Predictors of residual renal function decline in peritoneal dialysis patients: the bal ANZ trial . Peritoneal Dialysis International, v. 37 n. 3, p. 283–289, may./jun. 2016.
IZQUIERDO-LAHUERTA, A.; MARTÍNEZ-GARCÍA, C.; MEDINA-GÓMEZ, G. Lipotoxicity as a trigger factor of renal disease. Journal of Nephrology, v. 29, n. 5, p. 603–610, oct. 2016.
KALANTAR-ZADEH, K.; et. al. The obesity paradox in kidney disease: how to reconcile it with obesity management. Kidney International Reports, v. 2, n. 2, p. 271–281, mar. 2017.
KAMBHAM, N.; et al. Obesity-related glomerulopathy: an emerging epidemic. Kidney International, v. 59, n. 4, p. 1498–1509, abr. 2001.
LEMARIÉ, C.A.; SCHIFFRIN, E. L. The angiotensin II type 2 receptor in cardiovascular disease. Journal of Renin Angiotensin Aldosterone System, v. 11, n. 1, p. 19–31, mar. 2010.
MA, L.; et al. Angiotensin type 1 receptor modulates macrophage polarization and renal injury in obesity. American Journal of Physiology-Renal Physiology, v. 300, n. 5, p. 1203–1213, may. 2011.
MARK, A. L.; et al. Selective leptin resistance: a new concept in leptin physiology with cardiovascular implications. Journal of Hypertension, v. 20, n. 7, p. 1245–1250, jun. 2002.
MASSIERA, F. et al. Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. The FASEB Journal, v. 15, n. 14, p. 2727–2729, dec. 2001.
MINISTÉRIO DA SAÚDE. Vigitel Brasil 2016: Vigilância de fatores de risco e proteção para doenças crônicas por inquérito telefônico. Ministério da Saúde, Secretaria de Vigilância em saúde, Secretaria de Gestão Estratégica e Participativa. Brasília, 2016. Disponível em: http://portalms.saude.gov.br/images/pdf/2018/marco/02/vigitel-brasil-2016.pdf. E http://portalarquivos.saude.gov.br/images/pdf/2017/abril/17/Vigitel.pdf. Acesso em 28/09/2018, 17:43.
MIRANDA, L. S. P.; DE PAULA, R.B.; COSTA, M. B. Fatores dietéticos de risco e de proteção para condições crônicas de saúde em município da zona da mata de Minas Gerais. 113f. Dissertação (Mestrado em Saúde Brasileira). Programa de pós-graduação da Universidade Federal de Juiz de Fora, Juiz de Fora, 2017.
MITSNEFES, M. et al. Ceramides and cardiac function in children with chronic kidney disease. Pediatric Nephrology, v. 29, n. 3, p. 415–422, mar. 2014.
MUNIYAPPA, R.; SOWERS, J. R. Endothelial insulin and IGF-1 receptors: when yes means no. Diabetes, v. 61, n. 9, p. 2225–2227, sep. 2012.
NADERI, N. et al. Obesity paradox in advanced kidney disease: from bedside to the bench. Progress in Cardiovascular Diseases, v. 61, n. 2, p. 168-181, jul./ago. 2018.
NAKAMAKI, S. et al. Adiponectin reduces proteinuria in streptozotocin-induced diabetic Wistar rats. Experimental Biology and Medicine, v. 236, n. 5, p. 614–620, may. 2011.
NAUMNIK, B.; MYSLIWIEC, M. Renal consequences of obesity. Medical Science Monitor. V. 16, n.8, p. 163-170, aug. 2010.
NGUYEN, A.; CAT, D.; TOUYZ, R.M. A new look at the renin–angiotensin system — focusing on the vascular system. Peptides, v. 32, n. 10, p. 2141–2150, oct. 2011.
PANDEY, A. et al. H2AK119 monoubiquitination regulates angiotensin II receptor mediated macrophage infiltration and renal fibrosis in type 2 diabetic rats. Biochimie, v. 131, p. 68–76, dec. 2016.
PANDURU, N. M. et al. Urinary adiponectin is an independent predictor of progression to end-stage renal disease in patients with type 1 diabetes and diabetic nephropathy. Diabetes Care, v. 38, n. 5, p. 883–890, may. 2015.
PARK, J. et al. Obesity Paradox in End-Stage Kidney Disease Patients. Progress in Cardiovascular Diseases, v. 56, n. 4, p. 415–425, jan./fev. 2014.
PIETILÄINEN, K. H. et al. Acquired obesity increases CD68 and tumor necrosis factor-α and decreases adiponectin gene expression in adipose tissue: A study in monozygotic twins. The Journal of Clinical Endocrinology & Metabolism, v. 91, n. 7, p. 2776–2781, jul. 2006.
PRAGA, M. et al. Nephrotic proteinuria without hypoalbuminemia: clinical characteristics and response to angiotensin-converting enzyme inhibition. American Journal of Kidney Diseases, v. 17, n. 3, p. 330–338, mar. 1991.
PRAGA, M. et al. Influence of obesity on the appearance of proteinuria and renal insufficiency after unilateral nephrectomy. Kidney International, v. 58, n. 5, p. 2111–2118, nov. 2000.
PRAGA, M.; MORALES, E. The fatty kidney: obesity and renal disease. Nephron, v. 136, n. 4, p. 273–276, jul. 2016.
REDDY, M. A. et al. Losartan reverses permissive epigenetic changes in renal glomeruli of diabetic db/db mice. Kidney International, v. 85, n. 2, p. 362–373, fev. 2014.
REMUZZI, G.; CATTANEO, D.; PERICO, N. The aggravating mechanisms of aldosterone on kidney fibrosis. Journal of the American Society of Nephrology, n. 19, v. 8, p. 1459–1462, aug. 2008.
REYNOLDS, L. J., et al. Obesity, type 2 diabetes, and impaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1. Journal of Applied Physiology, v. 122, n. 1, p. 38–47, jan. 2017.
RHEE, C. M.; AHMADI, S. F.; KALANTAR-ZADEH, K. The dual roles of obesity in chronic kidney disease. Current Opinion in Nephrology and Hypertension, v. 25, n. 3, p. 208–216, may. 2016.
ROVIN, B. H.; et al. Plasma, urine, and renal expression of adiponectin in human systemic lupus erythematosus. Kidney International, v. 68, n. 4, p. 1825–1833, oct. 2005.
SABOIA, Z. M. R. M. et al. Association between syndecan-1 and renal function in adolescents with excess weight: evidence of subclinical kidney disease and endothelial dysfunction. Brazilian Journal of Medical Biology and Research. v. 51, n. 3, p. 71-71, jan. 2018.
SARAFIDIS, P. A.; RUILOPE, L. M. Insulin resistance, hyperinsulinemia, and renal injury: mechanisms and implications. American Journal of Nephrology, v. 26, n. ?, p. 232-244, may. 2006.
SAS, K. M. et al. Targeted lipidomic and transcriptomic analysis identifies dysregulated renal ceramide metabolism in a mouse model of diabetic kidney disease. Journal of Proteomics & Bioinformatics, s. 14:002, may. 2015.
SCHIMIDT, M. I.; et al. Cohort Profile: Longitudinal Study of Adult Health (ELSA-Brasil). International Journal of Epidemiology. v. 44, n. 1, p. 68-75, feb. 2015.
SCHWENK, M. H.; HIRSCH, J. S.; BOMBACK, A. S. Aldosterone blockade in CKD: emphasis on pharmacology. Advances in Chronic Kidney Disease, v. 22, n. 2, p. 123–132, mar. 2005.
SHANKAR, A.; et al. Relationship between plasma leptin level and chronic kidney disease. International Journal of Nephrology. v. 2012, p. 1-6, may. 2012.
SILVA JUNIOR, et al. Obesity and kidney disease. Jornal Brasileiro de Nefrologia. v. 39, n. 1, p. 65-69, mar. 2017.
TIROSH, A.; GARG, R.; ADLER, G. K. Mineralocorticoid receptor antagonists and the metabolic syndrome. Current Hypertension Reports. v. 12, n. 4, p. 252-257, aug. 2010.
TOZAWA, M. et al. Influence of smoking and obesity on the development of proteinuria. Kidney International, v. 62, n. 3, p. 956–962, sep. 2002.
TRAYHURN, P.; BEATTIE, J. H. Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proceedings of the Nutrition Society, v. 60, n. 03, p. 329–339, aug. 2001.
UNGER, R. H. Lipotoxic diseases. Annual Review of Medicine, v. 53, n. 1, p. 319–336, feb. 2002.
VIRTUE, S.; VIDAL-PUIG, A. Adipose tissue expandability, lipotoxicity and the metabolic syndrome — an allostatic perspective. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, v. 1801, n. 3, p. 338–349, mar. 2010.
VON EYNATTEN, M. et al. (2009). Urinary adiponectin excretion: a novel marker for vascular damage in type 2 diabetes. Diabetes, v. 58, n. 9, p. 2093–2099, sep. 2009.
WHALEY-CONNELL, A.; SOWERS, J. R. Obesity and kidney disease: from population to basic science and the search for new therapeutic targets. Kidney International, v. 92, n. 2, p. 313–323, aug. 2017.
WING, R. et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. New England Journal of Medicine, v. 369, n. 2, p. 145–154, jul. 2013.
YIANNIKOURIS, F. et al. Adipocyte-specific deficiency of angiotensinogen decreases plasma angiotensinogen concentration and systolic blood pressure in mice. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. v. 302, n. 2, p. 244–251, jan. 2012.
YONEKURA, Y. et al. The influences of larger physical constitutions including obesity on the amount of urine protein excretion in primary glomerulonephritis: research of the Japan Renal Biopsy Registry. Clinical and Experimental Nephrology, v. 19, n. 3, p. 359–370, jun. 2014.
ZHU, Q.; SCHERER, P. E. Immunologic and endocrine functions of adipose tissue: implications for kidney disease. Nature Reviews Nephrology, v. 14, n. 2, p. 105–120, feb. 2018.
ZICHA, J. et al. Renoprotective effects of ETA receptor antagonists therapy in experimental non-diabetic chronic kidney disease: is there still hope for the future?. Physiological Research, v. 67, s. 1, p. 55-67, jun. 2018.
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