Soy-based renoprotection

Table 3 Human studies with soy protein and renal isoflavone metabolism

Ref.	Study design	Kidney function	Subjects/group	Amount of soy protein used	Control/comparator protein	Duration of intervention	Outcomes	Notes
Fanti et al[115], Franke et al[192]	3 separate protocols:	ESRD patients on HD and normal healthy subjects	23 HD subjects and 10 healthy subjects for baseline IF measures	20 g soy protein	Baseline diet is self-selected standard renal diet	Single meal interventions	55%-65% of HD patients had undetectable serum IFs and 35%-45% had concentrations > 200 nM on standard renal diet	First study to report blood levels of genistein and daidzein in ESRD patients
	Assessment of baseline serum concentrations of IFs		7 HD patients and 8 healthy subjects for meal intervention study (8 h only); 2 healthy subjects and 3 HD subjects had multiple serum and urine timepts collected				Serum concentrations of IFs greater post-soy protein ingestion compared to baseline for both groups (P < 0.001); concentrations in HD subjects after 8 h of soy protein consumption were greater than those in healthy subjects (P < 0.05)	Daidzein metabolites equol and O-DMA were not detected in sera of any of the subjects
	Post-ingestion concentrations of IFs		5 HD patients for pre- and post-dialysis IF measures				Half-lives of genistein and daidzein averaged 3.5 and 6 h in healthy subjects, respectively but were increased to an average of 47 and 58 h in HD patients
	Effects of hemodialysis on IF concentrations						HD did not effectively remove IFs from serum since (due to higher molecular weight of conjugates and large proportion of unconjugated IFs are bound to albumin)
Fanti et al[116]	Observational	Randomly selected HD patients residing in the United States, Japan or Thailand	Subjects from:	Habitual dietary intake of soy was assessed by questionnaires developed by their renal replacement therapy programme dieticians	Study aim was to compare habitual dietary intake of soy in 3 countries	N/A	Serum IF concentrations significantly higher in HD patients from Japan compared to United States or Thailand (P < 0.0001)
			United States = 20				Significant correlation between soya intake and genistein (P < 0.0001), daidzein (P < 0.0001), glycitein (P < 0.001) and O-DMA (P < 0.01) in subjects from all 3 countries
			Japan = 20				ESRD HD patients displayed consistently higher concentrations of daidzein compared to genistein, while the reverse occurs in healthy subjects
			Thailand = 17				Concentrations of sulphated and unconjugated compounds in HD subjects (Japan only studied) are comparable to those detected in healthy subjects
Locati et al[117]	Single arm intervention study	Renal transplant patients	16 subjects (11 M, 5 F)	25 g soy protein substituted for 25 g animal protein	25 g animal protein (as habitual diet)	5 wk	Serum IFs were measured and 5 different groups were identified on the basis of the IF profiles: (1) 4 subjects had no detectable IFs; (2) only genistein was quantifiable in 7 patients; (3) 3 patients had only detectable genistein and daidzein; (4) 2 subjects only had detectable genistein and equol; and (5) 1 subject had the highest observed genistein and daidzein with detectable dihydrogenistein and equol	Concentrations of serum IFs in the renal transplant patients were similar to those observed in healthy subjects

F: Female; HD: Hemodialysis; IF: Isoflavones; M: Male; O-DMA: O-desmethylangolensin; ESRD: End-stage renal disease; N/A: Not available.