Diabetic Nephropathy

Diabetic Nephropathy

It is easier to find genes in DN for T1D than T2D?

It has been difficult to identify SNPs with even modest effects in studies of type 2 diabetic nephropathy. One possible explanation is that patients with kidney disease who have type 2 diabetes may not have a single disease. Indeed the old biopsy data suggest that there is a diversity of diseases in this population. Should gene finding efforts focus exclusively on type 1 diabetic nephropathy for the short term?

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Diabetic Nephropathy

What is the best way to collect patient samples?

Identifying robust association between genetic variation and severe human CKD phenotypes has been hindered by lack of collections of patient sample collection of sufficient size to use effectively in GWAS. The community could address this issue by developing reproducible but simple clinical phenotyping criteria and collecting samples from ESRD patients in dialysis units. Contrast can be made to publicly available datasets ...more »

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Diabetic Nephropathy

What are the key genetic and epigenetic determinants of DN?

Metabolic control alone does not predict an individual’s risk for diabetic complications. Family studies suggest that genetic factors play an important role in the predisposition for a specific type of complication and its progression. In addition to more classic genetics, research in this area has expanded to epigenetics and non-coding RNA. Epigenetic marks include modifications to the DNA or chromatin that do not ...more »

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Will systems biology discover new pathways and targets for DN?

There has been an explosion of new genetic, biochemical, and cell biologic techniques. Appropriate systems biology tools are needed to facilitate integration of genotyping information, mRNA expression, microRNA expression, promoter analysis, proteome expression, and metabolome profiles in order to identify key biological processes and their interactions. In addition to better computational tools, a deeper understanding ...more »

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Diabetic Nephropathy

What next after RAAS blockade?

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?

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Diabetic Nephropathy

Does aldosterone breakthrough occur in DN?

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.

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Can we restore GBM function in DN?

What are the regulators of glomerular basement membranes? Can we target glomerular endothelium and podocytes to restore normal barrier components and functions?

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What is the role of the tubule in early DN?

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.

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Will aggressive treatment of blood sugar slow progression?

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

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A role for the study of non-mammalian model systems in DN?

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 »

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Can we develop "humanized mice" for the study of DN?

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.

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Can biomarkers predict type 2 diabetic nephropathy

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.

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