Chronic Kidney Disease
Chronic kidney disease, CKD, is a complication that occurs with some people with diabetes. CKD, characterized by the gradual loss of kidney function, is most common among people with Type 2 diabetes and hypertension and affects 26 million American adults. Diabetes has become the primary cause of kidney disease in the United States and the associated incidence of diabetic nephropathy is also on the rise. The following summarizes the size of the CKD market:
- 5-10 million people in the U.S. with DKD1
- 120 million people in China with DKD2
- 40 percent of all diabetics will develop DKD3
- $11.7 billion chronic kidney disease potential market
Clinically, CKD is characterized by a progressive increase in urine albumin/albuminuria and a decline in glomerular filtration rate (“GFR”), hypertension, and a high risk of cardiovascular morbidity and mortality.
Management of CKD includes treatment of the underlying Type 2 diabetes and/or hypertension. Blood pressure medications, such as angiotensin converting enzyme (“ACE”) inhibitors and angiotensin receptor blockers (“ARBs”), are commonly prescribed to control hypertension and slow the progression of CKD. Nevertheless, most patients continue to have a decline in kidney function. About 20 percent of patients eventually progress to end-stage renal disease (“ESRD”) and require hemodialysis, peritoneal dialysis, or renal transplant. CKD is a serious medical condition and needs treatments with new mechanisms of action that target pathways other than the renin-angiotensin-aldosterone system (“RAAS”) in order to slow or reverse the progression of the disease.
DM199 activates the bradykinin receptors and via the kallikrein-kinin system counter-balances the renin-angiotensin system, triggering kinin-dependent mechanisms that mitigate and/or repair damages caused by diabetic nephropathy and potentially improving vasodilation, anti-fibrosis, anti-inflammation, anti-oxidative stress, anti-thrombosis and improved insulin sensitization. DiaMedica believes that DM199 could improve kidney function without increasing the risks of increased hyperkalemia as seen with ACEi and ARBs. Hyperkalemia is the result of elevated blood potassium (K+) levels which increases the risk of abnormal heart rhythms and sudden death. The risk of hyperkalemia results in potentially suboptimal dosing and discontinuation of ACEi and ARB treatment for CKD patients. There is an estimated 2.5 million patients in the U.S. that have CKD and hyperkalemia.
Numerous clinical papers have been published demonstrating the positive effects of the KLK1 protein combined with valsartan, an ARB. These studies have ranged from one to six months in length and demonstrated a time dependent improvement in kidney disease based on urinary albumin excretion rate and other clinical endpoints of kidney disease. A potential differentiation between DM199 and ACEi and ARB treatments is that with DM199, hyperkalemia might be avoidable with a bradykinin receptor-specific agonists.
DiaMedica is preparing for an upcoming clinical trial in patients with moderate chronic kidney disease.
- Centers for Disease Control. National Chronic Kidney Disease Fact Sheet. 2014.
- Zhang, L., et al. Prevalence of Chronic Kidney Disease in China: A Cross-Sectional Survey. Lancet. 2012 Mar 3; 379(9818):815-22.
- Reutens, AT. Epidemiology of Diabetic Kidney Disease. The Medical Clinics of North America. 2013 Jan; 97(1):1-18.