Diabetic Uropathy

Follow up from Urologic Complications of Diabetes Meeting

Rough drafts of Breakout Group Reports

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Diabetic Complications (General)

How does diabetes affect regeneration and repair?

Tissue injury in diabetes results from cell damage and death, impaired communication among cells, dysfunction of nerves and blood vessels, and detrimental responses to systemic signals, such as inflammation. The development of the clinical manifestations depends on tissue-specific responses to injury and impairments in repair and regenerative processes. The knowledge base of the pathologic process in different tissues ...more »

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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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Diabetic Nephropathy

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 Neuropathy

Pipeline fracture

1001 drugs fix NCV slowing in diabetic rodents but none have translated to clinical use. Does NCV slowing in short term rodents have a different pathogenesis to that in humans?

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Diabetic Neuropathy

Demyelination

Demyelination is a prominent feature of clinical neuropathy, but absent from rodent models of diabetes (barring occasional reports of fixation artifact). Some markers of Schwann cell fidelity are disrupted, but myelin remains resplendently unchanged in the face of long periods of excess glucose exposure. Do we have to resort to the usual handwaving of "absoute duration of diabetes" being an explanatory factor when the ...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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Diabetic Nephropathy

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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Diabetic Nephropathy

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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