Rhubarb and Angiotensin Converting Enzyme Inhibitor

Use of angiotensin converting enzyme inhibitors (ACEI) in diabetic nephropathy has been shown
to be beneficial in slowing progression of disease. This would include use of ACEI,
aggressive blood pressure and blood sugar control as well as other possible interventions.
Experimental studies in chronic kidney disease (CKD) patients in China has suggested that
rhubarb extract when used alone is equivalent to the protection afforded by ACEI. Furthermore
when used in combination with ACEI, the renoprotective effect of rhubarb appears to be
additive.

Rhubarb extract is a chinese herbal preparation that is used extensively in china and other
asian countries to treat constipation and CKD. Its mechanism of action in preventing
progression of CKD is uncertain but perhaps related to TGF beta and TNF alpha inhibition.

The specific aim is to determine the combined effect of rhubarb plus enalapril slowing the
rate of decline of CKD (using Iothalamate GFRs) in patients in diabetes. A secondary aim
would be to measure serum TGF beta concentrations over time and see if any observed decrease
in the rate of decline of CKD is related to changes in TGF beta levels.

Inclusion Criteria:

1. Male or female patients >18 years

2. Patients with diabetic nephropathy (history of type 1 or type 2 diabetes for > 7
years, no other cause for proteinuria listed in their medical chart). This is the
definition used in most peer-reviewed trials44,45 of diabetic nephropathy. We do
recognize that their proteinuria could be due to some other concomitant kidney disease
but the only way to confirm that is to do a kidney biopsy which is not clinically
justified.

3. Proteinuria ≥ 0.5 g/day

4. Ability to sign consent form

Exclusion Criteria:

1. Pre study GFR (see section 10.7) < 20 ml/min

2. Renal disease of etiologies other than diabetes

3. Uncontrolled hypertension (Systolic BP >180 mmHg and Diastolic BP >110mm Hg)

4. Patients with history of kidney stones in past 10 years

5. Patients with active chronic liver disease (Liver enzymes ALT, AST >2.5 times normal)

6. Patients with primary small bowel disease with malabsorption, blind loop syndrome, or
jejunoileal bypass surgery (may cause unabsorbed fatty acids to combine with calcium
which in turn causes too much absorption of oxalate)

7. Patients with current alcohol, illicit drug use or any other condition (eg. Psychiatry
disorder) that in the opinion of the investigator may interfere with the patient's
ability to comply with the study

8. Pregnant women or women of child bearing potential who are unwilling to use an
adequate form of contraceptive during the course of the study (ACEI may be fetotoxic)

9. Patients with significant unstable cardiovascular disease (NYHA class III and IV)

10. Patients with active malignancy

11. Uncontrolled infections.

12. Patients with a known sensitivity to the study medications (including enalapril)

13. Patients on angiotensin II receptor blockers (ARBs)

14. Microscopic or macroscopic hematuria (to rule out kidney disease other than diabetic
nephropathy)

15. Patients on any herbal supplements unwilling to discontinue them

16. Severe malnutrition (serum albumin <2.6mg/dL)

17. Hyperkalemia at baseline, defined as serum potassium ≥ 5.5 mg/dL

18. Iodine allergy.