Long-term caffeine consumption exacerbates renal failure in obese, diabetic, ZSF1 (fa-fa(cp)) rats.
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).


CONCLUSIONS
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.
Tofovic
Stevan P
SP
Center for Clinical Pharmacology, Department of Medicine, University of Pittsburgh School of Medicine, Pennsylavania 15213-2582, USA. tofovic@msx.dept-med.pitt.edu
Kost
Curtis K
CK
Jackson
Edwin K
EK
Bastacky
Sheldon I
SI
D000818:Animals; D002110:Caffeine / Q000008:administration & dosage* / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000503:physiopathology*; D004334:Drug Administration Schedule; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009765:Obesity; D051381:Rats; D011922:Rats, Mutant Strains; D012079:Renal Circulation / Q000187:drug effects; D051437:Renal Insufficiency / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D002110:Caffeine