The value of currently available urine biomarkers that identify those at risk for diabetic nephropathy is increasingly called into question. The development of new urine and plasma biomarkers to predict diabetic nephropathy may shed light on disease mechanisms. Also, rational clinical trial design will be made possible by such markers.
While the mouse has many advantages, the human diabetic nephropathy phenotype has been difficult to faithfully replicate in the mouse using candidate gene approaches. Future work should focus on developing "humanized mice," in which loci associated with human diabetic complications are knock-in to the mouse. These animals could then be used to study mechanisms and therapeutics using systems biology approaches.
Non-mammalian model organisms have been underutilized to understand diabetic nephropathy pathogenesis. These simple model organism systems that permit ease of genetic manipulation, rapid throughput and precise measurement of phenotypes. Work published earlier this year (PNAS 107: 775, 2010) demonstrated that type 2 DM risk loci could be characterized in zebrafish. Interestingly, this study demonstrated this study shows ...more »
Hyperglycemia could cause albuminuria. Should we find out with certainty that either high FBS and/or high 2 hrs PP sugar be treated aggresively before a clinical diagnosis of DM is made
The primary focus of the pathophysiology of diabetic renal disease has been on the glomerulus. Albuminuria has been shown to be a very sensitive biomarker of proximal tubule injury. Early changes in the proximal tubule may lead to secondary pathology which is typical for diabetic nephropathy. Thus the tubule may represent a therapeutic target for early diabetes.
What are the regulators of glomerular basement membranes? Can we target glomerular endothelium and podocytes to restore normal barrier components and functions?
Failure of ACE inhibitors in advanced diabetic nephropathy is an increasing problem. Studies suggest that it is due to aldosterone breakthrough. The mechanism for this escape mechanism is unclear.
At the current time, we only have RAAS blockade and hypertension control to slow progression to ESRD. What mechanisms should be targeted to slow progression (loss of GFR) in diabetic nephropathy?