Implausible similarities in patient characteristics between two randomized controlled studies: a coincidence is unlikely
Authors: Yoshitsugu Obi, Hitomi Hama, Yoshiki Suzuki, Yoshitaka Isaka, Toshiki Moriyama
Journal: Kidney International (2012)

To the Editor: We have read the interesting article of the randomized controlled trial (RCT) by Goraya et al.1.Goraya N. Simoni J. Jo C. et al.Dietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathy.Kidney Int. 2012; 81: 86-93Abstract Full Text Full Text PDF PubMed Scopus (235) Google Scholar showing that 30-day dietary acid reduction with an aggressive intake of fruits and vegetables (F+V) has a renoprotective effect for stage 2 chronic kidney disease (CKD). Despite the small sample size, it clearly demonstrated the efficacy of F+V by both clinical and experimental surrogate markers. Its effect is almost the same with that of sodium bicarbonate, which had already been shown to attenuate the rate of decline of the glomerular filtration rate in a 5-year RCT by the same group of this study.2.Mahajan A. Simoni J. Sheather S.J. et al.Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy.Kidney Int. 2010; 78: 303-309Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar Thus, F+V without the increase in sodium intake may be more favorable than sodium bicarbonate for early CKD patients. However, the characteristics of the participants with stage 2 CKD between these two RCTs are implausibly similar (Table 1). These similarities are impossible for two separate RCTs with at least a 5-year interval. Even if these studies were conducted in parallel without a detailed description, the ‘NaCl’ groups should not be considered as the control, and ‘F+V’ seems like placebo with 5-year observation.Table 1Common patient characteristics quoted from the reports by Goraya et al.1.Goraya N. Simoni J. Jo C. et al.Dietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathy.Kidney Int. 2012; 81: 86-93Abstract Full Text Full Text PDF PubMed Scopus (235) Google Scholar and Mahajan et al.2.Mahajan A. Simoni J. Sheather S.J. et al.Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy.Kidney Int. 2010; 78: 303-309Abstract Full Text Full Text PDF PubMed Scopus (284) Google ScholarGoraya et al., CKD2 control (n=40)Mahajan et al., NaCl (n=40)Goraya et al., CKD2 and HCO3 (n=40)Mahajan et al., NaHCO3 (n=40)Goraya et al., CKD2 and F+V (n=40)Mahajan et al., placebo (n=40)Males (%)47.54847.54847.548Black/white/Hispanic (%)62.5/22.5/15.063/23/1562.5/20.0/17.563/20/1862.5/25.0/12.563/25/13Age (years)51.5±8.351.5±8.351.2±8.251.2±8.251.3±8.551.3±8.5Systolic BP (mm Hg)134.3±8.3152.6±14.7134.1±5.8155.3±12.6133.7±8.6155.2±12.9eGFR (ml/min)75.6±6.575.6±6.575.3±6.175.3±6.175.6±6.275.6±6.2Plasma total CO2 (mmol/l)26.0±0.826.4±0.825.9±0.626.2±0.725.9±0.826.0±0.9PRAL (mmol/day)59.3±21.159.3±21.164.3±17.764.3±17.760.4±19.460.4±19.48-h NAE (mEq)24.6±5.724.8±6.424.8±5.624.8±5.624.6±5.024.0±5.6Ualb (mg/g Cr)413.6±147.9413.6±147.9419.3±150.8419.3±150.8422.2±151.6422.2±151.6UNAG (U/g Cr)2.7±0.42.6±0.52.7±0.42.7±0.42.7±0.72.7±0.7UET-1 (ng/g Cr)5.5±1.15.7±0.85.7±1.05.7±1.05.5±1.25.5±1.2Urine Na+ excretion (mmol/g Cr)71.6±7.970.6±10.270.9±10.270.9±10.273.0±9.573.0±9.5Urine K+ excretion (mmol/g Cr)38.6±5.538.2±6.241.1±6.141.1±6.139.5±6.639.5±6.6Abbreviations: BP, blood pressure; CKD, chronic kidney disease; Cr, creatinine; eGFR, estimated glomerular filtration rate; F+V, fruits and vegetables; NAE, net acid excretion; PRAL, potential renal acid load; Ualb, urine albumin-to-creatinine ratio; UET-1, urine endothein-1-to-creatinine ratio; UNAG, urine N-acetyl-β-d-glucosaminidase-to-creatinine ratio.Values are expressed as number, percentage, or mean±SD as appropriate. Open table in a new tab Abbreviations: BP, blood pressure; CKD, chronic kidney disease; Cr, creatinine; eGFR, estimated glomerular filtration rate; F+V, fruits and vegetables; NAE, net acid excretion; PRAL, potential renal acid load; Ualb, urine albumin-to-creatinine ratio; UET-1, urine endothein-1-to-creatinine ratio; UNAG, urine N-acetyl-β-d-glucosaminidase-to-creatinine ratio. Values are expressed as number, percentage, or mean±SD as appropriate. The long-term follow-up of the MDRD study revealed the risk of the low-protein diet,3.Menon V. Kopple J.D. Wang X. et al.Effect of a very low-protein diet on outcomes: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study.Am J Kidney Dis. 2009; 53: 208-217Abstract Full Text Full Text PDF PubMed Scopus (177) Google Scholar which has been believed to be good for CKD by both patients and health professionals for a long time. The interesting hypothesis of Goraya et al. could have been an alternative dietary intervention for CKD patients if proven appropriately. Disappointingly, the serious suspicion of faking research has made a mess of the series of their RCTs.