The use of green tea polyphenols for treating residual albuminuria in diabetic nephropathy: A double-blind randomised clinical trial

Abstract

Prior research has shown that in experimental diabetes mellitus, green tea reduces albuminuria by decreasing podocyte apoptosis through activation of the WNT pathway. We investigated the effect of green tea polyphenols (GTP) on residual albuminuria of diabetic subjects with nephropathy. We conducted a randomised, double-blind study in 42 diabetic subjects with a urinary albumin-creatinine ratio (UACR) >30 mg/g, despite administration of the maximum recommended dose of renin-angiotensin (RAS) inhibition. Patients were randomly assigned to two equal groups to receive either GTP (containing 800 mg of epigallocatechin gallate, 17 with type 2 diabetes and 4 with type 1 diabetes) or placebo (21 with type 2 diabetes) for 12 weeks. Treatment with GTP reduced UACR by 41%, while the placebo group saw a 2% increase in UACR (p = 0.019). Podocyte apoptosis (p = 0.001) and in vitro albumin permeability (p < 0.001) were higher in immortalized human podocytes exposed to plasma from diabetic subjects compared to podocytes treated with plasma from normal individuals. In conclusion, GTP administration reduces albuminuria in diabetic patients receiving the maximum recommended dose of RAS. Reduction in podocyte apoptosis by activation of the WNT pathway may have contributed to this effect.

Figure 1. Flow diagram of the trial.

eGFR, estimated glomerular filtration rate; HIV, human immunodeficiency virus; NYHA, New York Heart Association; HbA1c, glycated hemoglobin; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker.

Figure 2. Patients in the green tea polyphenol group (n = 21) experienced a significant reduction in UACR, while patients in the placebo (n = 21) group experienced a small increase.

Geometric mean of % change in urinary albumin-creatinine ratio from baseline to the end of the study. Vertical bars represent the 95% confidence intervals. P value is for comparison between the green tea polyphenol and the placebo groups.

Figure 3. Analysis of the filtration barrier function of the podocyte monolayer by an albumin efflux assay.

Differentiated iHPs were incubated with plasma from each healthy controls (n = 3) and plasma from each diabetic subjects before (n = 3) or after 12 weeks treatment with GTP (n = 3) and albumin influx through podocyte monolayer was assessed after 6 hours, as described in methods. Data are presented as mean and vertical bars represent the standard deviation. *P < 0.001 vs. control, ^#P = 0.003 vs. diabetic, ^$P < 0.001 vs. diabetic GTP, ^&P = 0.01 vs. diabetic. GTP, green tea polyphenol; DKK-1, dickkopf 1, EGCG, epigallocatechin gallate.

Figure 4. Analysis of podocyte apoptosis.

(A,B) TUNEL assay, scale bars 50 μm. Bars in B represent the median of three human plasma samples derived from an average of ten fields. Vertical bars represent the standard deviation. N = 3 for each condition. *P = 0.01 vs. control, ^#P = 0.01 vs. diabetic, ^$P < 0.001 vs. diabetic GTP, ^&P < 0.001 vs. diabetic. (C) Caspase-3 activity. Data are presented as mean ± SD; N = 3 for each condition. *P < 0.001 vs. control, ^#P < 0.001 vs. diabetic, ^$P < 0.001 vs. diabetic GTP, ^&P = 0.007 vs. diabetic. GTP, green tea polyphenol; DKK-1, dickkopf 1, EGCG, epigallocatechin gallate.