Renal disorders involve an alteration in the normal physiology and function of the kidney. Renal disorders can result from a wide range of acute and chronic conditions and events, including physical, chemical, or biological injury, insult or trauma, disease such as, for example, hypertension, diabetes, congestive heart failure, lupus, sickle cell anemia, and various inflammatory and autoimmune diseases, HIV-associated nephropathies, etc. Renal disorders can lead to reduced kidney function, hypertension, and renal failure, seriously compromising quality of life, sometimes requiring dialysis and in certain circumstances, kidney transplantation.
Diabetic nephropathy also known as Kimmelstiel-Wilson syndrome and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nodular glomerulosclerosis due to longstanding diabetes mellitus and is a prime cause for dialysis in many Western countries. The syndrome can be seen in patients with chronic diabetes. The disease is progressive and may cause death two or three years after the initial lesions and is more frequent in women. Diabetic nephropathy is the most common cause of chronic kidney failure and end-stage kidney disease in the United States. People with both type 1 and type 2 diabetes are at risk. The risk is higher if blood-glucose levels are poorly controlled. However, once nephropathy develops, the greatest rate of progression is seen in patients with poor control of their blood pressure.
Diabetic nephropathy is clinically well defined and is characterized by proteinuria, hypertension, edema and renal insufficiency. There are limited treatment options for diabetic nephropathy. Current treatments are primarily directed to improving complications of the diseases as follows: 1) control of blood-pressure (ACE-inhibitors inhibitors or Angiotensin receptor blockers (ARBs); 2) Control of glycemic values; and 3) lipoproteic diet, exercise or other life styles modifications. However, there is an important need for better drugs and treatments since current treatment may have limited impact on the progressive decline in kidney function and patients still progress to renal replacement therapy, either dialysis or renal transplantation.
Hyperlipidemia is a major complication of diabetic nephropathy and is a determinant of progression of renal disorder in diabetes. Hyperlipidemia is a pathogenic factor for diabetic nephropathy and clinical studies involving therapeutic interventions for hyperlipidemia suggest the importance of this approach in at least slowing the progression of diabetic renal disorder (Rosario and Prabhakar (2006), Current Diabetes Reports, 6:455-462). Therefore, there is a need for methods and compounds for modulating blood lipids levels, and more particularly reducing levels of harmful serum lipid levels, especially cholesterol and triglycerides in diabetic patients.