Insulin Resistance and Kidney Disease, some thoughts.

Insulin molecule courtesy wikipedia.

Insulin resistance is a term many doctors and scientists are already familiar with. However not that many patients have a concept of exactly what is meant by resistance to insulin. Other than its role in the causation of type 2 diabetes, Ginsberg considers insulin resistance a major underlying abnormality driving cardiovascular disease, the major cause of morbidity and mortality in much of the world.

Although most of the research produced thus far focused on the role of insulin resistance in diabetics, it is now apparent that insulin resistance is important in its own right.

Insulin resistance is a syndrome that has been linked to increased risk for cardiovascular disease. However its effect is believed to act via promoting dyslipidemia, hypertension, hypercoagulability, and atherosclerosis.

In terms of kidney disease it has been shown by other authors that insulin resistance correlated linearly with decline in renal function. Independent variables related to insulin resistance were bicarbonate and Apo A-1/B levels in patients with chronic kidney disease. Low serum bicarbonate has been implicated in increased bone disease of renal failure and poor cardiac function as well increasing the pace of progression to end stage renal disease an effect that can be ameliorated in part by the prescription of bicarbonate. It would therefore not surprise me if insulin resistance were associated in some future study with increased progression to end stage renal disease. The Treatment of insulin resistance will likely then be a significant issue for patients with kidney disease.

Rosiglitazone is an oral drug that reduces the amount of sugar (glucose) in the blood. It is used for treating patients with type 2 diabetes. It is one of the few drugs currently available capable of reducing insulin resistance. The drug itself is not without side effects, there have been warnings issued regarding a propensity for the development of heart failure in some patients on this drug.

Type 2 diabetic patients on dialysis may derive benefits from this drug both in terms of glucose control as well as reduced insulin resistance. While the question of the safety of rosiglitazone among patients on dialysis still remains to be fully answered, a study of 24 patients on CAPD treated with rosiglitazone has revealed interesting evidence that the drug has no long term negative effects on cardiac function in CAPD patients. Although the study was small, it is somewhat reassuring that the drug may also be safe in patients with lesser degrees of kidney failure.

Once the drug is deemed safe in patients with kidney disease it would be interesting to see a randomized control trial sufficiently powered to determine if rosiglitazone has any impact on the progression of renal disease. If the answer is no then insulin resistance may just be another marker of the inflammatory state that is uremia instead of a driver of progression in and of itself.