Inhibiting the renin angiotensin (RAS) system has been the cornerstone of therapy for patients with proteinuric CKD for almost 2 decades, to slow the decline in renal function, delay the presence of dialysis and reduce cardiovascular events and death.~There is evidence in both the cardiac and renal literature that suggests that maximising the dose of RAS therapy leads to improved outcomes over smaller doses of RAS therapy.~Indeed, many of the studies on which we base our care use doses which are higher than what the majority of our patients are taking. Thus patients are being systemically undertreated by therapies which have been shown to have robust reno protection. With up to 80% of patients on RASi therapy are not on maximal RASi therapy , putting them at risk of a more rapid progression and poorer outcomes and increased healthcare costs.~An important reason for this is the presence or fear around hyperkalaemia. With reports of significantly increased rate of hyperkalaemia seen following increases in prescribing of RASi therapy. These concerns have lead NICE to recommend not starting patients on RASi therapy if their potassium is >5mmol/l, and KDOQI guidelines recommending consideration of stopping RASi therapy if serum potassium is >5.5mmol/l.~ACE inhibitors and angiotensin receptor blockers are thought to confer long term renal protection through reduction of proteinuria. The reduction in glomerular pressure is a major mechanism leading to a reduction in proteinuria, and hence renal protection, however as a consequence there will also an acute fall in eGFR. Therefore, when starting/up titrating ACEi/ARB it is expected that there will be an acute fall in eGFR, which is expected to be more than compensated for due to the subsequent long term renal protection. Indeed, current NICE guidelines do not suggest any alteration in management until the drop in eGFR is >25%.~There is a currently huge unmet need to optimise RASi therapy in those patients with hyperkalaemia.~There have been recent advances in novel therapeutics which can lower potassium in patients. One such agent is Sodium zirconium cyclosilicate (SZC).~SZC is a highly selective inorganic cation exchanger designed to entrap potassium in the intestine.~It has been shown to effective in lowering potassium in patients with heart failure, Diabetes, CKD and RASi therapy. With around a 1mmol/l fall in the serum potassium on those treated with SZC, compared to placebo.~In the 5-large clinical trials it appears efficacious, well tolerated and safe.
The hypothesis is that 3 months' treatment with SZC versus placebo will enable RASi (Irbesartan) maximisation in a cohort of patients with diabetic kidney disease.