Evaluation of Coffee Therapy for Improvement of Renal Oxygenation

Over 1.25 million Americans have Type 1 Diabetes (T1D), increasing risk for early death from
cardiovascular disease (CVD). Despite advances in glycemic and blood pressure control, a
child diagnosed with T1D is expected to live up to 17 years less than non-diabetic peers. The
strongest risk factor for CVD and mortality in T1D is diabetic kidney disease (DKD). Current
treatments, such as control of hyperglycemia and hypertension, are beneficial, but only
partially protect against DKD. This limited progress may relate to a narrow focus on clinical
manifestations of disease, rather than on the initial metabolic derangements underlying the
initiation of DKD. Renal hypoxia, stemming from a potential metabolic mismatch between
increased renal energy expenditure and impaired substrate utilization, is increasingly
proposed as a unifying early pathway in the development of DKD. T1D is impacted by several
mechanisms which increase renal ATP consumption and decrease ATP generation.

Caffeine, a methylxanthine, is known to alter kidney function by several mechanisms including
natriuresis, hemodynamics and renin-angiotensin-aldosterone system. In contrast, to other
natriuretic agents, caffeine is thought to fully inhibit the local tubuloglomerular feedback
(TGF) response to increased distal sodium delivery. This observation has broad-ranging
implications as caffeine can reduce renal oxygen (O2) consumption without impairing effective
renal plasma flow (ERPF) and glomerular filtration rate (GFR).

There are also data suggesting that chemicals in coffee besides caffeine may provide
important cardio-renal protection. Yet, there are no data examining the impact of
coffee-induced natriuresis on intrarenal hemodynamic function and renal energetics in
youth-onset T1D. Our overarching hypothesis in the proposed pilot and feasibility trial is
that coffee drinking improves renal oxygenation by reducing renal O2 consumption without
impairing GFR and ERPF. To address these hypotheses, we will measure GFR, ERPF, renal
perfusion and oxygenation in response to 7 days of cold brew coffee (one Starbucks® Cold brew
325ml bottle daily [205mg caffeine]) in an open-label pilot and feasibility trial in 10
adolescents with T1D already enrolled in the CASPER Study (PI: Bjornstad).