BACKGROUND: Our preliminary studies indicate that chronic caffeine consumption has adverse renal effects in nephropathy associated with high blood pressure and insulin resistance. The purpose of this study was to investigate the effects of early (beginning at 8 weeks of age) and long-term (30 weeks) caffeine treatment (0.1% solution) on renal function and structure in obese, diabetic ZSF1 rats. METHODS: Metabolic and renal function measurements were performed at six-week intervals and in a subset of animals (N = 6 per group) heart rate (HR) and mean arterial blood pressure (MABP) were monitored by a radiotelemetric technique. At the end of the study acute, measurements of renal hemodynamics and excretory function were conducted in anesthetized animals. RESULTS: Caffeine produced a very mild increase (4 to 5%) of MABP and HR, but greatly augmented proteinuria (P < 0.001), reduced creatinine clearance (P < 0.05) and had a mixed effect on metabolic status in obese ZSF1 rats. Caffeine significantly reduced body weight, glycosuria, fasting glucose and insulin levels and improved glucose tolerance, had no effect on elevated plasma triglycerides levels and significantly increased plasma cholesterol level (P < 0.001). Acute measurements of renal function revealed increased renal vascular resistance (95.1 +/- 11 vs. 50.7 +/- 2.4 mm Hg/mL/min/g kidney, P < 0.01) and decreased inulin clearance (0.37 +/- 0.11 vs. 0.97 +/- 0.13 mL/min/g kidney, P < 0.002) in caffeine-treated versus control animals, respectively. Caffeine potentiated the development of more severe tubulointerstitial changes (P < 0.05) and increased focal glomerulosclerosis (14.7 +/- 1.7 vs. 6.5 +/- 0.9%, caffeine vs. control, P < 0.002). CONCLUSION: The present study provides the first evidence that caffeine (despite improving insulin sensitivity) exacerbates renal failure in obese, diabetic ZSF1 rats. Further mechanistic studies of adverse renal effects of caffeine in chronic renal failure associated with metabolic syndrome are warranted.
BACKGROUND: Our preliminary studies indicate that chronic caffeine consumption has adverse renal effects in nephropathy associated with high blood pressure and insulin resistance. The purpose of this study was to investigate the effects of early (beginning at 8 weeks of age) and long-term (30 weeks) caffeine treatment (0.1% solution) on renal function and structure in obese, diabetic ZSF1 rats. METHODS: Metabolic and renal function measurements were performed at six-week intervals and in a subset of animals (N = 6 per group) heart rate (HR) and mean arterial blood pressure (MABP) were monitored by a radiotelemetric technique. At the end of the study acute, measurements of renal hemodynamics and excretory function were conducted in anesthetized animals. RESULTS:Caffeine produced a very mild increase (4 to 5%) of MABP and HR, but greatly augmented proteinuria (P < 0.001), reduced creatinine clearance (P < 0.05) and had a mixed effect on metabolic status in obese ZSF1 rats. Caffeine significantly reduced body weight, glycosuria, fasting glucose and insulin levels and improved glucose tolerance, had no effect on elevated plasma triglycerides levels and significantly increased plasma cholesterol level (P < 0.001). Acute measurements of renal function revealed increased renal vascular resistance (95.1 +/- 11 vs. 50.7 +/- 2.4 mm Hg/mL/min/g kidney, P < 0.01) and decreased inulin clearance (0.37 +/- 0.11 vs. 0.97 +/- 0.13 mL/min/g kidney, P < 0.002) in caffeine-treated versus control animals, respectively. Caffeine potentiated the development of more severe tubulointerstitial changes (P < 0.05) and increased focal glomerulosclerosis (14.7 +/- 1.7 vs. 6.5 +/- 0.9%, caffeine vs. control, P < 0.002). CONCLUSION: The present study provides the first evidence that caffeine (despite improving insulin sensitivity) exacerbates renal failure in obese, diabetic ZSF1 rats. Further mechanistic studies of adverse renal effects of caffeine in chronic renal failure associated with metabolic syndrome are warranted.
Authors: Andrés Díaz-López; Indira Paz-Graniel; Verónica Ruiz; Estefanía Toledo; Nerea Becerra-Tomás; Dolores Corella; Olga Castañer; J Alfredo Martínez; Ángel M Alonso-Gómez; Julia Wärnberg; Jesús Vioque; Dora Romaguera; José López-Miranda; Ramon Estruch; Francisco J Tinahones; José Lapetra; Luís Serra-Majem; Aurora Bueno-Cavanillas; Josep A Tur; Vicente Martín Sánchez; Xavier Pintó; Miguel Delgado-Rodríguez; Pilar Matía-Martín; Josep Vidal; Clotilde Vázquez; Lidia Daimiel; Tania Fernandez Villa; Emilio Ros; Sonia Eguaras; Nancy Babio; Jose V Sorlí; Albert Goday; Itziar Abete; Lucas Tojal Sierra; Francisco Javier Barón-López; Laura Torres-Collado; Marga Morey; Antonio Garcia-Rios; Rosa Casas; María Rosa Bernal-López; José Manuel Santos-Lozano; Adela Navarro; Jose I Gonzalez; María Dolores Zomeño; Maria Angeles Zulet; Jessica Vaquero Luna; Raul Ramallal; Montse Fitó; Jordi Salas-Salvadó Journal: Sci Rep Date: 2021-04-22 Impact factor: 4.379
Authors: Md Abdul Hye Khan; Lauren Kolb; Melissa Skibba; Markus Hartmann; René Blöcher; Ewgenij Proschak; John D Imig Journal: Diabetologia Date: 2018-07-21 Impact factor: 10.122
Authors: Ken Dower; Shanrong Zhao; Franklin J Schlerman; Leigh Savary; Gabriela Campanholle; Bryce G Johnson; Li Xi; Vuong Nguyen; Yutian Zhan; Matthew P Lech; Ju Wang; Qing Nie; Morten A Karsdal; Federica Genovese; Germaine Boucher; Thomas P Brown; Baohong Zhang; Bruce L Homer; Robert V Martinez Journal: PLoS One Date: 2017-07-26 Impact factor: 3.240
Authors: Md Abdul Hye Khan; Sung Hee Hwang; Scott D Barnett; Anna Stavniichuk; Wojciech K Jankiewicz; Bruce D Hammock; John D Imig Journal: Br J Pharmacol Date: 2021-08-12 Impact factor: 8.739