DYNAMic Renal Assessment: NOvel Methods to Assess KIDNEY Functional Reserve

Quantification of glomerular filtration rate (GFR) over time is the standard assessment of kidney function. In clinical practice, the endogenous marker, 'serum creatinine' concentration, is used as a static assessment of kidney function to estimate GFR. However, serum creatinine fails to increase until at least 50% of kidney tissue is lost,[2] thus is an inadequate indicator of early CKD.

GFR like many other physiological processes is not static and augments temporarily to stimuli such as exercise and protein intake, by up to 25% from baseline in healthy individuals.[3] Similar to cardiac function stress tests which predict adverse outcomes, inability to respond to renal stressors or 'reduced renal reserve' has been demonstrated to occur prior to development of CKD (e.g. in patients with diabetes and previous acute kidney injury (AKI)) and is associated with vulnerability to future AKI, despite the presence of apparently normal kidney function measured by serum creatinine concentration.[4] Renal reserve is lost with progressive CKD,[4] and has also been demonstrated to relate to severity of histological lesions.[5]

Current measurements of renal reserve (stimulated increase in GFR due to augmented renal blood flow above basal fasting values) involve administration of a compound that is freely filtered by the glomerulus, unaffected by tubular function and is physiologically inert, with assessment before and after an oral protein load or amino acid infusion which induces arterial vasodilation, increasing renal blood flow and GFR

The study proposes a comparison of two novel methods of 'dynamic renal function testing' with renal reserve testing.

Inclusion:

• Patients with sickle cell nephropathy, diagnosed clinically or histologically. Sickle Cell patients will be confirmed Hb SS and eGFR (CKD-EPI) ≥ 135 ml/min/1.73m2 OR
• Previous living kidney donation
• Age ≥ 4No contraindication or known allergy to any trial medications.
• Willing and able to provide written informed consent

Exclusion:

• Aged < 40
• Unable or unwilling to provide informed consent
• Breastfeeding or pregnant women
• Patients involved in other interventional research studies.