Anti-inflammatory effects of rosiglitazone in patients with stage 4 and 5 chronic kidney disease

Patients with renal disease are characterized by high morbidity and mortality
due to complications of premature cardiovascular disease (CVD). The
pathophysiological background of this excessive cardiovascular risk is not
completely understood but multiple factors seem to be important. Classic risk
factors such as dyslipidemia, hypertension and smoking are prevalent in
patients with chronic kidney disease but are not sufficient alone to account
for the high prevalence of CVD in this condition. It has been postulated that
non-traditional risk factors, such as volume overload, inflammation and insulin
resistance are important.
Thiazolidinediones (TZDs) or glitazones constitute a relatively new class of
antihyperglycemic agents that improve insulin action in skeletal muscles, liver
and adipose tissue, and thus decrease insulin resistance through activation of
a nuclear receptor, the peroxisome proliferator-activated receptor gamma
(PPARγ), which regulates the expression of genes controlling the synthesis of
proteins that take part in glucose and lipid metabolism. TZDs are therefore
currently used as antidiabetic drugs. Glucose intolerance is a nearly universal
finding in patients with chronic renal failure and in animal models of uremia.
The glucose intolerance results from impaired insulin-mediated glucose disposal
by muscle, adipose, and liver tissue. In type 2 diabetes patients,
rosiglitazone appears to be effective in reducing pulse wave velocity (PWV).
Whether these changes occur in advanced chronic kidney disease non-diabetic
patients is currently unknown.

The primary aim of this study will be to determine the effect of rosiglitazone
on intima media thickness and calcification in patients with stage 4 and 5
CKD. The secondary end points are the effects on pulse wave velocity, blood
pressure, the lipid profile, insulin resistance and inflammation.

This is a double blinded placebo controlled study in patients with stage 4 and
5 chronic kidney disease. Eligible patients in the outpatient kidney clinic
will be informed by their treating physician about the study and they will be
asked to join the study. Following informed consent the eligible patients will
undergo baseline evaluation and will then be followed for a period of 48 weeks.
A total of 200 non-diabetic stage 4 and 5 CKD patients will be evaluated at
baseline..
The original medication will be continued. Fifteen patients will receive
rosiglitazone 4 mg once per day for the initial 8 weeks and, after checking
serum transaminases, the doses will be doubled for the remaining 4 weeks of
the study. The other 15 patients form the control group. The total follow-up
will be 48 weeks.

100 patients will receive rosiglitazone 4 mg once per day for the initial 8
weeks and, after checking serum transaminases, the doses will be doubled for
the remaining 4 weeks of the study. The other 100 patients form the control
group

In clinical practice when rosiglitazone is administered to patients with
diabetes the most commonly side effects (1-10%) are: edema,anemia and
hypercholesteolemia. There are other side effects but this are relatively rare.
In this study, it we closely monitor potential side effects.