Effect of citrus-based products on urine profile: A systematic review and meta-analysis

Fakhri Rahman; Ponco Birowo; Indah S. Widyahening; Nur Rasyid

doi:10.12688/f1000research.10976.1

Home Browse Effect of citrus-based products on urine profile: A systematic review...

ALL Metrics

-

Views

-

Downloads

Get PDF

Get XML

Export

▬

✚

Systematic Review

Effect of citrus-based products on urine profile: A systematic review and meta-analysis

[version 1; peer review: 2 approved]

Fakhri Rahman¹, Ponco Birowo¹, Indah S. Widyahening^2,3, Nur Rasyid ¹

PUBLISHED 06 Mar 2017

Author details Author details

¹ Department of Urology, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta Pusat, 10430, Indonesia
² Department of Community Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta Pusat, 10310, Indonesia
³ Centre for Clinical Epidemiology & Evidence-based Medicine, Dr. Cipto Mangunkusumo National General Hospital - Faculty of Medicine, Universitas Indonesia, Jakarta Pusat, 10430, Indonesia

OPEN PEER REVIEW

REVIEWER STATUS

Abstract

Background. Urolithiasis is a disease with high recurrence rate, 30-50% within 5 years. The aim of the present study was to learn the effects of citrus-based products on the urine profile in healthy persons and people with urolithiasis compared to control diet and potassium citrate. Methods. A systematic review was performed, which included interventional, prospective observational and retrospective studies, comparing citrus-based therapy with standard diet therapy, mineral water, or potassium citrate. A literature search was conducted using PUBMED, COCHRANE, and Google Scholar with “citrus or lemonade or orange or grapefruit or lime or juice” and “urolithiasis” as search terms. For statistical analysis, a fixed-effects model was conducted when p > 0.05, and random-effects model was conducted when p < 0.05. Results. In total, 135 citations were found through database searching with 10 studies found to be consistent with our selection criteria. However, only 8 studies were included in quantitative analysis, due to data availability. The present study showed a higher increased in urine pH for citrus-based products (mean difference, 0.16; 95% CI 0.01-0.32) and urinary citrate (mean difference, 124.49; 95% CI 80.24-168.74) compared with a control group. However, no differences were found in urine volume, urinary calcium, urinary oxalate, and urinary uric acid. From subgroup analysis, we found that citrus-based products consistently increased urinary citrate level higher than controls in both healthy and urolithiasis populations. Furthermore, there was lower urinary calcium level among people with urolithiasis. Conclusions. Citrus-based products could increase urinary citrate level significantly higher than control. These results should encourage further research to explore citrus-based products as a urolithiasis treatment.

Keywords

Citrus, citrate, potassium citrate, urolithiasis, urine profile

Corresponding author: Nur Rasyid

Competing interests: No competing interests were disclosed.

Grant information: This study received grants from Directorate of Research and Community Service (DRPM), Universitas Indonesia in 2013 (2739/H.R12/HKT.05.00/2013).
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright: © 2017 Rahman F et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).

How to cite: Rahman F, Birowo P, Widyahening IS and Rasyid N. Effect of citrus-based products on urine profile: A systematic review and meta-analysis [version 1; peer review: 2 approved]. F1000Research 2017, 6:220 (https://doi.org/10.12688/f1000research.10976.1) First published: 06 Mar 2017, 6:220 (https://doi.org/10.12688/f1000research.10976.1) Latest published: 06 Mar 2017, 6:220 (https://doi.org/10.12688/f1000research.10976.1)

Introduction

Humans have suffered urinary tract stones for centuries¹. The incidence and prevalence of urolithiasis are different between geographic locations, depending on age and sex distribution, stone composition and stone location². Risk of stone development has been shown to be 5–10% with a higher prevalence in men than women³. Urolithiasis is a common disease with significant morbidity and cost worldwide^4–6. Based on National Health and Nutrition Examination survey, kidney stones affect 1 in 11 people in the United States, and an epidemiological increase was found in 2012 compared to 1994⁷. Additional data from Dr. Cipto Mangunkusumo National General Hospital, Indonesia’s national referral hospital, showed an increase in stone disease prevalence from 182 patients in 1997 to 847 patients in 2002⁸. Moreover, it is further worsen by its high recurrence rate reaching 30–50% within 5 years⁷.

Calcium-based urinary tract stone is the most common stone composition found in urolithiasis^9,10. Supersaturation is believed to be the mechanism behind calcium stone formation¹¹. One factor in determining urine stone formation or stone recurrence is urine profile, which is defined as urine volume and its composition. Hypercalciuria and hypocitraturia are the most common urine abnormalities found among calcium stone-formers¹². A high fluid intake could prevent stone formation by lowering supersaturation, whereas citrate could prevent stone formation by ionizing urinary calcium^13,14. Food that is rich of citrate is citrus. There are wide variety of citrus fruits and derivate products that can be easily obtained, such as lemonade, grapefruit, orange, lime, and citrus-based juice. Several studies had already been conducted to learn the effect of citrus-based products on urine profile. However, the results between those studies were contradictive. Therefore, our study aimed to systematically review and quantify the available studies regarding the effects of citrus-based products on urine profile and its comparison to a control diet and potassium citrate.

Methods

Eligibility criteria

We included both healthy people and patients with urolithiasis history in our selection criteria. Study subjects must have consumed citrus fruits, such as orange, lime, grapefruit, or juices made from the fruits. Study designs could be interventional, prospective observational, or retrospective with standard diet therapy (any kind of mineral water), or potassium citrate, as a control group therapy. We included studies with urine profile as the outcome. We only included articles written in English or Indonesian, and those with full text article available. We excluded non-systematic review articles. We did not limit studies based on their year conducted.

Search strategy

A literature search was conducted using PUBMED, COCHRANE, and Google Scholar as search engines on August 2016. The terms “citrus OR lemonade OR orange OR grapefruit OR lime OR juice” AND “urolithiasis” were used as search terms. We also searched the list of references in included studies. We did not use any limitation in study searching.

Study selection and data extraction

All studies were screened for duplication using EndNote X6 software. Duplication-free articles underwent title and abstract examination using predetermined inclusion and exclusion criteria mentioned above. Selection of studies was selected by two authors independently. Discrepancies of opinion were resolved by discussion. All studies, which fulfilled the inclusion and exclusion criteria, underwent full text review. For every eligible full text, we extracted the following data, if available: subjects specific condition, citrus-based product used in the study, number of patients consuming citrus-based product, citrate content or its concentration, control intervention, number of individuals under control intervention. For the outcomes, we extracted urine profile data as follows: volume, pH, calcium level, citrate level, oxalate level, and uric acid level. Measurement units used in this study are L/day for urine volume and mg/day for urinary calcium level, urinary citrate level, urinary oxalate level, and urinary uric acid level. All data in the form of numbers were extracted manually as mean and standard deviation for variable measurement.

Assessment of bias and statistical methods

This study used Cochrane Risk of Bias assessment tools¹⁵ and Newcastle-Ottawa scale¹⁶ to assess interventional and retrospective study’s quality, respectively. These assessments of study quality were done by two authors independently. Quantitative synthesis of included studies was analyzed using Review Manager (RevMan) 5.0 software and mean difference was used as its effects size measurement. Heterogeneity of studies was assessed using chi-square. A fixed-effects model was conducted when p > 0.05, whereas a random-effect model is conducted when p < 0.05. We also conducted subgroup analysis to differentiate between healthy and urolithiasis populations.

Studies which could not be included in quantitative analysis were described qualitatively.

Results

We found 135 citations through database searching. Literature searching from the list of references found similar studies that were all already included in this study. Ten studies were found to be consistent with our selection criteria (Figure 1).

Figure 1. Study flow diagram.

Two of ten studies had to be excluded from quantitative analysis because of the following reasons: (1) Penniston et al.¹⁷ only published baseline data and its maximal change following intervention; and (2) Tosukhowong et al.¹⁹ used medians as their outcome measurement, and due to its non-uniform distribution, we were unable to convert these to means. Therefore, eight studies were analyzed to find the effect of citrus-based products on urine profile compared to controls. However, not all of the eight studies were included in urine profile outcome measurement, due to data availability. Characteristics of the included studies and their risk of bias assessment can be seen in Table 1 and Figure 2/Supplementary Table 1, respectively.

Table 1. Characteristic of included studies.

Study author and year	Type of study	Subject condition	Intervention	n	Control	n
*Study included in qualitative synthesis only*
Penniston et al (2007)¹⁷	RS	Subjects with calcium oxalate stone	Lemonade (5.9 gr citrate)	63	Lemonade (5.9 gr citric acid) plus potassium citrate	37
Tosukhowong et al (2008)¹⁹	RCT	Post-operative subjects with nephrolithiasis	• Lime powder (4.4 gr citrate) • Potassium citrate	13 11	Placebo	7
*Study included in qualitative and quantitative synthesis*
Aras et al (2008)²⁰*	RCT	Subjects with hypocitraturic calcium stone	• Lemon juice (4.2 gr citrate) • Potassium citrate	10 10	Water 3 L/day	10
Goldfarb and Asplin (2001)²¹	CBAS	Healthy subjects	Grapefruit juice	10	Tap water 240 ml, 3 times a day	10
Honow et al (2003)²²	CBAS	Healthy subjects	• Orange juice • Grapefruit juice • Apple juice	3 3 3	Mineral water	3
Koff et al (2007)²³	CS	Subjects with history of nephrolithiasis	Lemon juice (4.5 gr citrate)	21	Fluid except lemonade or citrus drink	21
Odvina (2006)²⁴	CS	Healthy and stone former subjects	• Orange juice (2.3 gr citrate) • Lemonade (2.3 gr citrate)	14 14	Distilled water 400 ml	14
Seltzer et al (1996)²⁵	CBAS	History of hypocitraturic calcium nephrolithiasis	• Lemonade (5.9 gr citrate)	12	Fluid maintaining 2 L urine	12
Sumorok et al (2011)¹⁸	CS	Healthy subjects	• Sunkist orange soda (3 cans)	12	Water 1.06 L/day	12
Trinchieri et al (2002)²⁶	CS	Healthy subjects	• Grapefruit juice (1.4 gr citrate)	7	Water	7

RS – retrospective study; RCT – randomized controlled trial; CBAS – controlled before-after study; CS – crossover study. *Also included in qualitative synthesis for comparison between citrus-based product and potassium citrate.

Figure 2. Risk of bias assessment summary.

Effect of citrus-based products on urine profile

Data shows that citrus-based products increased urine pH (mean difference, 0.16; 95% confidence interval [CI] 0.01-0.32) and urinary citrate (mean difference 124.49; 95% CI 80.24-168.74) to a higher extent than control treatment (Figure 3).

Figure 3. Urine pH and urinary citrate levels represented by a forest plot.

However, there was no statistically significant difference in urine volume (mean difference -0.09; 95% CI -0.20-0.02), urinary calcium (mean difference -5.45; 95% CI -18.89-7.98), urinary oxalate (mean difference 0.76; 95% CI -0.47-1.98) and urinary uric acid (mean difference 2.15; 95% CI -23.96-28.27) between the two groups (Figure 4).

Figure 4. Urine volume, urinary calcium, urinary oxalate, and urinary uric acid levels represented by a forest plot.

Subgroup analysis showed a significantly higher urinary citrate level in both the healthy population and the population with history of urolithiasis who received citrus-based therapy compared to control. However, urine pH, which showed a statistically significant increase in urine pH compared to controls, did not demonstrate any differences in a subgroup analysis. On the other hand, urinary calcium was lower after consumption of citrus-based products compared to controls in the urolithiasis population. Furthermore, this study demonstrated that there was a lower urine volume in the healthy population after drinking citrus-based products compared to controls (Figure 5). We did not find any differences in other urine profile variables, either in the healthy population or the population with history of urolithiasis (Supplementary Figure 1 and Supplementary Figure 2).

Figure 5. Subgroup analysis of urine profiles represented by forest plot.

We tried to conduct further analysis by excluding Aras et al.²⁰ from quantitative analysis, due to its different study method (RCT). We still found a significant increase in urine citrate level in both mixed population (mean difference 132.46; 95% CI 70.48-194.44) and the population with a history of urolithiasis (mean difference 159.22; 95% CI 47.05-271.40]), as well as no statistically significant difference in urine pH (mean difference 0.16; 95% CI -0.02-0.33). Furthermore, other variables still demonstrate similar outcomes after exclusion of Aras et al.

Comparison between citrus-based products and potassium citrate in urine profile

Due to the reasons stated above, we decided to discuss the comparisons between citrus-based product and potassium citrate in a qualitative manner.

Three studies showed both citrus-based products (lemon juice and lime powder) and potassium citrate increased the level of urinary citrate significantly^17,19,20. Even though no significant difference in post treatment urine profile was found between citrus-based products and potassium citrate, post-treatment citrate level in the potassium citrate group showed a 3.5 times increase from pre-treatment level, while it was only 2.5 times in the lemon juice group²⁰. Furthermore, Penniston et al. exhibited a greater maximum increase of urinary citrate level in lemonade therapy combined with potassium citrate compared to lemonade therapy alone¹⁷.

Two studies also showed significant increase in urine pH in both treatment arms^17,19. However, a study by Aras et al. only exhibit a significant increase in urine pH for the potassium citrate group²⁰. In terms of side effects, patients in the potassium citrate group suffered gastric and oropharyngeal discomfort, although they did not require drug discontinuation²⁰. Furthermore, potassium citrate had lower compliance compared to citrus-based therapy¹⁹.

Study Author	Year	Type of Study	Risk of Bias Assessment							Intervention	n	Mean/Mean Difference	Standard Deviation	Control	n	Mean/Mean Difference	Standard Deviation
			Random Sequence Generation	Allocation Concealment	Blinding of Participants and Personnel	Blinding of Outcome Assessment	Incomplete Outcome Data	Selective Reporting	Other Bias
Aras et al	2008	Randomized controlled trial	?	?	-	?	?	+	-	Lemon juice (4.2 gr citrate)	10	6	0.3	Water 3 L/day	10	5.8	0.3
Goldfarb et al	2001	Controlled before-after study	-	-	-	?	+	+	+	Grapefruit juice	10	6.47	0.42	Tap water 240 ml, 3 times a day	10	6.28	0.25
Honow et al	2003	Controlled before-after study	-	-	-	?	?	+	+	Orange juice 0.5 L	3	6.32	0.21	Mineral water	3	6.29	0.17
										Orange juice 1 L	3	6.42	0.17	Mineral water	3	6.29	0.17
										Grapefruit juice 0.5 L	3	6.42	0.14	Mineral water	3	6.08	0.16
										Grapefruit juice 1 L	3	6.66	0.14	Mineral water	3	6.08	0.16
Koff et al	2007	Crossover study	+	-	-	+	+	+	-	Lemon juice (4.5 gr citrate)	21	5.63	0.47	Fluid except lemonade or citrus drink	21	5.51	0.4
Sumonok et al	2011	Crossover study	+	?	?	+	-	+	-	Sunkist orange soda (3 cans)	12	6.21	0.18	Water 1.06 L/day	12	6.29	0.18
Trinchieri et al	2002	Crossover study	?	?	?	?	?	+	+	Grapefruit juice (1.4 gr citrate)	7	5.8	0.3	Water	7	5.9	0.4

Dataset 1.Characteristics of studies included for urine pH.

Study Author	Year	Type of Study	Risk of Bias Assessment							Intervention	n	Mean/Mean Difference	Standard Deviation	Control	n	Mean/Mean Difference	Standard Deviation
			Random Sequence Generation	Allocation Concealment	Blinding of Participants and Personnel	Blinding of Outcome Assessment	Incomplete Outcome Data	Selective Reporting	Other Bias
Aras et al	2008	Randomized controlled trial	?	?	-	?	?	+	-	Lemon juice (4.2 gr citrate)	10	302.7	75.14	Water 3 L/day	10	186.5	68.92
Goldfarb et al	2001	Controlled before-after study	-	-	-	?	+	+	+	Grapefruit juice	10	591	220	Tap water 240 ml, 3 times a day	10	505	226
Honow et al	2003	Controlled before-after study	-	-	-	?	?	+	+	Orange juice 0.5 L	3	670.1	160.7	Mineral water	3	557.97	152.77
										Orange juice 1 L	3	820.5	197.97	Mineral water	3	557.97	152.77
										Grapefruit juice 0.5 L	3	775.5	168.7	Mineral water	3	618.3	144.28
										Grapefruit juice 1 L	3	869.32	186.9	Mineral water	3	618.3	144.28
Koff et al	2007	Crossover study	+	-	-	+	+	+	-	Lemon juice (4.5 gr citrate)	21	446	376	Fluid except lemonade or citrus drink	21	476	467
Seltzer et al	1996	Controlled before-after study	-	-	-	?	-	+	-	Lemonade	12	346	197	Fluid maintaining 2 L urine	12	142	99
Sumonok et al	2011	Crossover study	+	?	?	+	-	+	-	Sunkist orange soda (3 cans)	12	613	148.18	Water 1.06 L/day	12	554	148.18

Dataset 2.Characteristics of studies included for urinary citrate.

Study Author	Year	Type of Study	Risk of Bias Assessment							Intervention	n	Mean/Mean Difference	Standard Deviation	Control	n	Mean/Mean Difference	Standard Deviation
			Random Sequence Generation	Allocation Concealment	Blinding of Participants and Personnel	Blinding of Outcome Assessment	Incomplete Outcome Data	Selective Reporting	Other Bias
Aras et al	2008	Randomized controlled trial	?	?	-	?	?	+	-	Lemon juice (4.2 gr citrate)	10	2.014	0.944	Water 3 L/day	10	2.188	0.688
Goldfarb et al	2001	Controlled before-after study	-	-	-	?	+	+	+	Grapefruit juice	10	1.6	0.8	Tap water 240 ml, 3 times a day	10	1.7	1
Honow et al	2003	Controlled before-after study	-	-	-	?	?	+	+	Orange juice 0.5 L	3	2.633	0.19	Mineral water	3	2.767	0.275
										Orange juice 1 L	3	2.716	0.095	Mineral water	3	2.767	0.275
										Grapefruit juice 0.5 L	3	2.638	0.192	Mineral water	3	2.805	0.126
										Grapefruit juice 1 L	3	2.606	0.195	Mineral water	3	2.805	0.126
Koff et al	2007	Crossover study	+	-	-	+	+	+	-	Lemon juice (4.5 gr citrate)	21	1.9	0.7	Fluid except lemonade or citrus drink	21	1.8	0.6
Odvina	2006	Crossover study	+	?	+	?	-	+	+	Lemonade (2.3 gr citrate)	14	2.61	0.31	Distilled water 400 ml	14	2.55	0.54
										Orange juice (2.3 gr citrate)	14	2.51	0.35	Distilled water 400 ml	14	2.55	0.54
Seltzer et al	1996	Controlled before-after study	-	-	-	?	-	+	-	Lemonade	12	2.7	2.5	Fluid maintaining 2 L urine	12	2.9	2.4

Dataset 3.Characteristics of studies included for urine volume.

Study Author	Year	Type of Study	Risk of Bias Assessment							Intervention	n	Mean/Mean Difference	Standard Deviation	Control	n	Mean/Mean Difference	Standard Deviation
			Random Sequence Generation	Allocation Concealment	Blinding of Participants and Personnel	Blinding of Outcome Assessment	Incomplete Outcome Data	Selective Reporting	Other Bias
Aras et al	2008	Randomized controlled trial	?	?	-	?	?	+	-	Lemon juice (4.2 gr citrate)	10	118.3	86.16	Water 3 L/day	10	185.6	61.63
Goldfarb et al	2001	Controlled before-after study	-	-	-	?	+	+	+	Grapefruit juice	10	104	83	Tap water 240 ml, 3 times a day	10	122	102
Honow et al	2003	Controlled before-after study	-	-	-	?	?	+	+	Orange juice 0.5 L	3	126	22.86	Mineral water	3	149.2	29.79
										Orange juice 1 L	3	144.8	22.25	Mineral water	3	149.2	29.79
										Grapefruit juice 0.5 L	3	143.2	27.02	Mineral water	3	161.6	33.26
										Grapefruit juice 1 L	3	148	27.71	Mineral water	3	161.6	33.26
Odvina	2006	Crossover study	+	?	+	?	-	+	+	Lemonade (2.3 gr citrate)	14	154	58	Distilled water 400 ml	14	159	42
										Orange juice (2.3 gr citrate)	14	146	52	Distilled water 400 ml	14	159	42
Seltzer et al	1996	Controlled before-after study	-	-	-	?	-	+	-	Lemonade	12	92	78	Fluid maintaining 2 L urine	12	131	119
Sumonok et al	2011	Crossover study	+	?	?	+	-	+	-	Sunkist orange soda (3 cans)	12	148	33.61	Water 1.06 L/day	12	129	33.61

Dataset 4.Characteristics of studies included for urinary calcium.

Study Author	Year	Type of Study	Risk of Bias Assessment							Intervention	n	Mean/Mean Difference	Standard Deviation	Control	n	Mean/Mean Difference	Standard Deviation
			Random Sequence Generation	Allocation Concealment	Blinding of Participants and Personnel	Blinding of Outcome Assessment	Incomplete Outcome Data	Selective Reporting	Other Bias
Aras et al	2008	Randomized controlled trial	?	?	-	?	?	+	-	Lemon juice (4.2 gr citrate)	10	26.45	19.98	Water 3 L/day	10	22.6	12.43
Goldfarb et al	2001	Controlled before-after study	-	-	-	?	+	+	+	Grapefruit juice	10	52	13	Tap water 240 ml, 3 times a day	10	41	9
Honow et al	2003	Controlled before-after study	-	-	-	?	?	+	+	Orange juice 0.5 L	3	15.9	1.25	Mineral water	3	15.5	1.39
										Orange juice 1 L	3	16.21	1.25	Mineral water	3	15.5	1.39
										Grapefruit juice 0.5 L	3	17.74	3.12	Mineral water	3	16.2	2.18
										Grapefruit juice 1 L	3	17	2.94	Mineral water	3	16.2	2.18
Odvina	2006	Crossover study	+	?	+	?	-	+	+	Lemonade (2.3 gr citrate)	14	30	7	Distilled water 400 ml	14	31	10
										Orange juice (2.3 gr citrate)	14	35	6	Distilled water 400 ml	14	31	10
Seltzer et al	1996	Controlled before-after study	-	-	-	?	-	+	-	Lemonade	12	42	12	Fluid maintaining 2 L urine	12	53	33
Sumonok et al	2011	Crossover study	+	?	?	+	-	+	-	Sunkist orange soda (3 cans)	12	30.1	7.17	Water 1.06 L/day	12	31.7	7.17

Dataset 5.Characteristics of studies included for urinary oxalate.

Study Author	Year	Type of Study	Risk of Bias Assessment							Intervention	n	Mean/Mean Difference	Standard Deviation	Control	n	Mean/Mean Difference	Standard Deviation
			Random Sequence Generation	Allocation Concealment	Blinding of Participants and Personnel	Blinding of Outcome Assessment	Incomplete Outcome Data	Selective Reporting	Other Bias
Aras et al	2008	Randomized controlled trial	?	?	-	?	?	+	-	Lemon juice (4.2 gr citrate)	10	311	156.7	Water 3 L/day	10	472.2	194.69
Goldfarb et al	2001	Controlled before-after study	-	-	-	?	+	+	+	Grapefruit juice	10	544	103	Tap water 240 ml, 3 times a day	10	562	123
Honow et al	2003	Controlled before-after study	-	-	-	?	?	+	+	Orange juice 0.5 L	3	548.08	29.12	Mineral water	3	531.27	46.59
										Orange juice 1 L	3	548.08	34.94	Mineral water	3	531.27	46.59
										Grapefruit juice 0.5 L	3	566.58	49.5	Mineral water	3	532.95	32
										Grapefruit juice 1 L	3	522.86	58.23	Mineral water	3	532.95	32
Odvina	2006	Crossover study	+	?	+	?	-	+	+	Lemonade (2.3 gr citrate)	14	523	291	Distilled water 400 ml	14	585	345
										Orange juice (2.3 gr citrate)	14	491	81	Distilled water 400 ml	14	527	123
Seltzer et al	1996	Controlled before-after study	-	-	-	?	-	+	-	Lemonade	12	533	116	Fluid maintaining 2 L urine	12	527	123
Sumonok et al	2011	Crossover study	+	?	?	+	-	+	-	Sunkist orange soda (3 cans)	12	436	128	Water 1.06 L/day	12	420	153

Dataset 6.Characteristics of studies included for urinary uric acid.

Discussion

This study showed that citrus-based products, such as lemonade, orange juice and grapefruit juice, could increase urinary citrate levels and urine pH. Low citrate excretion, as in type I tubular acidosis, shows an increase in nephrolithiasis incidence²⁷. Therefore, existence of citrate in urine is important since it is a well-known preventive factor in calcium stone formation, with an increase in calcium salt solubility and calcium oxalate crystal growth inhibition as its primary mechanism. It also can reduce bone resorption and increase calcium reabsorption in kidneys. Furthermore, citrate fixes the inhibitory properties of Tamm-Horsfall protein²⁸. Citrate and Tamm-Horsfall protein are related to inhibition of calcium oxalate agglomeration²⁹. An increase in urine pH is due to metabolism of citrate into bicarbonate¹³. Moreover, an increase in urine pH could reduce reabsorption of citrate³⁰. Thus, it could induce more citrate excretion. A study conducted by Curhan et al.³¹ found an increased risk of stone formation associated with grapefruit juice consumption; although, the exact mechanism is still unclear. One theory suggests that grapefruit juice contains sugar, which can increase calcium excretion³¹. However, this study proved that citrus-based products could increase urinary citrate level, which could be a protective factor for urinary tract stone formation.

Potassium citrate has been used as urolithiasis stone treatment for more than two decades. Its effectiveness in urolithiasis treatment has been established from several studies^32,33. From one meta-analysis conducted by Phillip et al., potassium citrate significantly reduced stone size, reduced new stone formation, and increased citrate levels³⁴. The stone prevention mechanism of potassium citrate is thought to be due to alkali loading and its citrate-uric effect³⁵. In this study, potassium citrate showed a significant increase in urinary citrate and is superior to citrus-based products in elevating urinary citrate. However, the use of potassium citrate has a limitation due to its side effect if used for a long term period, such as epigastric discomfort and frequent large bowel movement, and it requires the consumption of many tablets daily to reach sufficient therapeutic doses, which could dramatically decrease patient compliance³⁶. Therefore, citrus-based products could be an alternative therapy with lower cost and better urinary citrate level than control therapy.

This is the first systematic review and meta-analysis that focuses on citrus-based product and its effect towards urine profile compared to standard therapy. However, this study only searched for published article which could lead into publication bias. Moreover, most of the included studies were not conducted using the best method for interventional studies, which is randomized controlled trials. Therefore, from the positive results this study has shown, we encourage other researchers to conduct randomized controlled trials to provide stronger evidence the beneficial effects of citrus-based products on urinary stone disease.

Conclusions

Citrus-based products increase urinary citrate and urine pH significantly compared to control treatments. Compared to standard potassium citrate therapy, there was a smaller increase in urine pH and urine citrate using citrus-based products. However, due to potassium citrate side effects and patient’s poor compliance, citrus-based products could be alternative therapy in preventing stone formation. These study’s results should encourage further research to explore citrus-based product as a urolithiasis treatment.

Data availability

Dataset 1: Characteristics of studies included for urine pH. doi, 10.5256/f1000research.10976.d153056³⁷

Dataset 2: Characteristics of studies included for urinary citrate. doi, 10.5256/f1000research.10976.d153057³⁸

Dataset 3: Characteristics of studies included for urine volume. doi, 10.5256/f1000research.10976.d153058³⁹

Dataset 4: Characteristics of studies included for urinary calcium. doi, 10.5256/f1000research.10976.d153059⁴⁰

Dataset 5: Characteristics of studies included for urinary oxalate. doi, 10.5256/f1000research.10976.d153060⁴¹

Dataset 6: Characteristics of studies included for urinary uric acid. doi, 10.5256/f1000research.10976.d153061⁴²

Author contributions

PB and NR developed the concept of this study. IW designed the research methodology. FR did the literature searching. FR and PB did the selection of studies. FR prepared the draft of manuscript. All author contributed in the revision of the draft manuscript and have agreed to the final content.

Competing interests

No competing interests were disclosed.

Grant information

This study received grants from Directorate of Research and Community Service (DRPM), Universitas Indonesia in 2013 (2739/H.R12/HKT.05.00/2013).

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Supplementary material

Supplementary Table 1. Newcastle-Ottawa scale for retrospective study’s risk of bias assessment.

Click here to access the data.

Supplementary Table 2: PRISMA checklist.

Click here to access the data.

Supplementary Figure 1. Urine pH, urinary calcium, urinary oxalate, and urinary uric acid in healthy subject population.

Click here to access the data.

Supplementary Figure 2. Urine volume, urine pH, urinary oxalate, and urinary uric acid in population with a history of urolithiasis.

Click here to access the data.

Faculty Opinions recommended

References

1. Eknoyan G: History of urolithiasis. Clinical Reviews in Bone and Mineral Metabolism. 2004; 2(3): 177–85. Publisher Full Text
2. Trinchieri A: Epidemiology of urolithiasis. Arch Ital Urol Androl. 1996; 68(4): 203–49. PubMed Abstract
3. Türk C, Knoll T, Petrik A, et al.: Pocket Guidelines on urolithiasis. Eur Urol. 2014; 40(4): 362–71.
4. Fukuhara H, Ichiyanagi O, Kakizaki H, et al.: Clinical relevance of seasonal changes in the prevalence of ureterolithiasis in the diagnosis of renal colic. Urolithiasis. 2016; 44(6): 529–537. PubMed Abstract | Publisher Full Text | Free Full Text
5. Muslumanoglu AY, Binbay M, Yuruk E, et al.: Updated epidemiologic study of urolithiasis in Turkey. I: Changing characteristics of urolithiasis. Urol Res. 2011; 39(4): 309–14. PubMed Abstract | Publisher Full Text
6. Edvardsson VO, Indridason OS, Haraldsson G, et al.: Temporal trends in the incidence of kidney stone disease. Kidney Int. 2013; 83(1): 146–52. PubMed Abstract | Publisher Full Text
7. Scales CD Jr, Smith AC, Hanley JM, et al.: Prevalence of kidney stones in the United States. Eur Urol. 2012; 62(1): 160–5. PubMed Abstract | Publisher Full Text | Free Full Text
8. Indonesia IAU: Tatalaksana Batu Saluran Kemih. 2007.
9. Singh P, Enders FT, Vaughan LE, et al.: Stone Composition Among First-Time Symptomatic Kidney Stone Formers in the Community. Mayo Clin Proc. 2015; 90(10): 1356–65. PubMed Abstract | Publisher Full Text | Free Full Text
10. Moses R, Pais VM Jr, Ursiny M, et al.: Changes in stone composition over two decades: evaluation of over 10,000 stone analyses. Urolithiasis. 2015; 43(2): 135–9. PubMed Abstract | Publisher Full Text
11. Park S, Pearle MS: Pathophysiology and management of calcium stones. Urol Clin North Am. 2007; 34(3): 323–34. PubMed Abstract | Publisher Full Text
12. Maalouf N: Approach to the adult kidney stone former. Clin Rev Bone Min Metab. 2012; 10(1): 38–49. PubMed Abstract | Publisher Full Text | Free Full Text
13. Tracy CR, Pearle MS: Update on the medical management of stone disease. Curr Opin Urol. 2009; 19(2): 200–4. PubMed Abstract | Publisher Full Text
14. Siener R: Can the manipulation of urinary pH by beverages assist with the prevention of stone recurrence? Urolithiasis. 2016; 44(1): 51–6. PubMed Abstract | Publisher Full Text
15. Higgins JP, Altman DG, Gøtzsche PC, et al.: The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011; 343: d5928. PubMed Abstract | Publisher Full Text | Free Full Text
16. Wells GA, Shea B, O’Connell D, et al.: The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa, ON: Ottawa Hospital Research Institute; [Accessed September 1, 2016]. 2011. Reference Source
17. Penniston KL, Steele TH, Nakada SY: Lemonade therapy increases urinary citrate and urine volumes in patients with recurrent calcium oxalate stone formation. Urology. 2007; 70(5): 856–60. PubMed Abstract | Publisher Full Text
18. Sumorok NT, Asplin JR, Eisner BH, et al.: Effect of diet orange soda on urinary lithogenicity. Urol Res. 2012; 40(3): 237–41. PubMed Abstract | Publisher Full Text
19. Tosukhowong P, Yachantha C, Sasivongsbhakdi T, et al.: Citraturic, alkalinizing and antioxidative effects of limeade-based regimen in nephrolithiasis patients. Urol Res. 2008; 36(3–4): 149–55. PubMed Abstract | Publisher Full Text
20. Aras B, Kalfazade N, Tuğcu V, et al.: Can lemon juice be an alternative to potassium citrate in the treatment of urinary calcium stones in patients with hypocitraturia? A prospective randomized study. Urol Res. 2008; 36(6): 313–7. PubMed Abstract | Publisher Full Text
21. Goldfarb DS, Asplin JR: Effect of grapefruit juice on urinary lithogenicity. J Urol. 2001; 166(1): 263–7. PubMed Abstract | Publisher Full Text
22. Hönow R, Laube N, Schneider A, et al.: Influence of grapefruit-, orange- and apple-juice consumption on urinary variables and risk of crystallization. Br J Nutr. 2003; 90(2): 295–300. PubMed Abstract | Publisher Full Text
23. Koff SG, Paquette EL, Cullen J, et al.: Comparison between lemonade and potassium citrate and impact on urine pH and 24-hour urine parameters in patients with kidney stone formation. Urology. 2007; 69(6): 1013–6. PubMed Abstract | Publisher Full Text
24. Odvina CV: Comparative value of orange juice versus lemonade in reducing stone-forming risk. Clin J Am Soc Nephrol. 2006; 1(6): 1269–74. PubMed Abstract | Publisher Full Text
25. Seltzer MA, Low RK, McDonald M, et al.: Dietary manipulation with lemonade to treat hypocitraturic calcium nephrolithiasis. J Urol. 1996; 156(3): 907–9. PubMed Abstract | Publisher Full Text
26. Trinchieri A, Lizzano R, Bernardini P, et al.: Effect of acute load of grapefruit juice on urinary excretion of citrate and urinary risk factors for renal stone formation. Dig Liver Dis. 2002; 34(Suppl 2): S160–3. PubMed Abstract | Publisher Full Text
27. Khanniazi MK, Khanam A, Naqvi SA, et al.: Study of potassium citrate treatment of crystalluric nephrolithiasis. Biomed Pharmacother. 1993; 47(1): 25–8. PubMed Abstract | Publisher Full Text
28. Fuselier HA, Ward DM, Lindberg JS, et al.: Urinary Tamm-Horsfall protein increased after potassium citrate therapy in calcium stone formers. Urology. 1995; 45(6): 942–6. PubMed Abstract | Publisher Full Text
29. Laube N, Jansen B, Hesse A: Citric acid or citrates in urine: which should we focus on in the prevention of calcium oxalate crystals and stones? Urol Res. 2002; 30(5): 336–41. PubMed Abstract | Publisher Full Text
30. Heilberg IP, Goldfarb DS: Optimum nutrition for kidney stone disease. Adv Chronic Kidney Dis. 2013; 20(2): 165–74. PubMed Abstract | Publisher Full Text
31. Curhan GC, Willett WC, Rimm EB, et al.: Prospective study of beverage use and the risk of kidney stones. Am J Epidemiol. 1996; 143(3): 240–7. PubMed Abstract | Publisher Full Text
32. Robinson MR, Leitao VA, Haleblian GE, et al.: Impact of long-term potassium citrate therapy on urinary profiles and recurrent stone formation. J Urol. 2009; 181(3): 1145–50. PubMed Abstract | Publisher Full Text
33. Allie-Hamdulay S, Rodgers AL: Prophylactic and therapeutic properties of a sodium citrate preparation in the management of calcium oxalate urolithiasis: randomized, placebo-controlled trial. Urol Res. 2005; 33(2): 116–24. PubMed Abstract | Publisher Full Text
34. Phillips R, Hanchanale VS, Myatt A, et al.: Citrate salts for preventing and treating calcium containing kidney stones in adults. Cochrane Database Syst Rev. 2015; 10(10): CD010057. PubMed Abstract | Publisher Full Text
35. Ettinger B, Pak CY, Citron JT, et al.: Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J Urol. 1997; 158(6): 2069–73. PubMed Abstract | Publisher Full Text
36. Lee YH, Huang WC, Tsai JY, et al.: The efficacy of potassium citrate based medical prophylaxis for preventing upper urinary tract calculi: a midterm followup study. J Urol. 1999; 161(5): 1453–7. PubMed Abstract | Publisher Full Text
37. Rahman F, Birowo P, Widyahening IS, et al.: Dataset 1 in: Effect of citrus-based products on urine profile: A systematic review and meta-analysis. F1000Research. 2017. Data Source
38. Rahman F, Birowo P, Widyahening IS, et al.: Dataset 2 in: Effect of citrus-based products on urine profile: A systematic review and meta-analysis. F1000Research. 2017. Data Source
39. Rahman F, Birowo P, Widyahening IS, et al.: Dataset 3 in: Effect of citrus-based products on urine profile: A systematic review and meta-analysis. F1000Research. 2017. Data Source
40. Rahman F, Birowo P, Widyahening IS, et al.: Dataset 4 in: Effect of citrus-based products on urine profile: A systematic review and meta-analysis. F1000Research. 2017. Data Source
41. Rahman F, Birowo P, Widyahening IS, et al.: Dataset 5 in: Effect of citrus-based products on urine profile: A systematic review and meta-analysis. F1000Research. 2017. Data Source
42. Rahman F, Birowo P, Widyahening IS, et al.: Dataset 6 in: Effect of citrus-based products on urine profile: A systematic review and meta-analysis. F1000Research. 2017. Data Source

Comments on this article Comments (0)

Version 1

VERSION 1 PUBLISHED 06 Mar 2017

Author details Author details

¹ Department of Urology, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta Pusat, 10430, Indonesia
² Department of Community Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta Pusat, 10310, Indonesia
³ Centre for Clinical Epidemiology & Evidence-based Medicine, Dr. Cipto Mangunkusumo National General Hospital - Faculty of Medicine, Universitas Indonesia, Jakarta Pusat, 10430, Indonesia

Competing interests

No competing interests were disclosed.

Grant information

This study received grants from Directorate of Research and Community Service (DRPM), Universitas Indonesia in 2013 (2739/H.R12/HKT.05.00/2013).
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Article Versions (1)

version 1

Published: 06 Mar 2017, 6:220

https://doi.org/10.12688/f1000research.10976.1

Copyright

© 2017 Rahman F et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).

Download

Export To

metrics

	Views	Downloads
F1000Research	-	-
PubMed Central Data from PMC are received and updated monthly.	-	-

Citations

0

SEE MORE DETAILS

CITE

how to cite this article

Rahman F, Birowo P, Widyahening IS and Rasyid N. Effect of citrus-based products on urine profile: A systematic review and meta-analysis [version 1; peer review: 2 approved]. F1000Research 2017, 6:220 (https://doi.org/10.12688/f1000research.10976.1)

NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.

track

receive updates on this article

Track an article to receive email alerts on any updates to this article.

Open Peer Review

Version 1

VERSION 1

PUBLISHED 06 Mar 2017

Views

8

Reviewer Report 08 May 2017

Bhaskar Somani, University Hospitals Southampton NHS Trust, Urology, Southampton, SO16 6YD., UK

Approved

https://doi.org/10.5256/f1000research.11834.r22426

The authors present a comprehensive systematic review and meta-analysis of the effect of citrus-based products on urine profile. The paper is supplemented by the PRISMA flow chart and forest plot charts to present their results.

Although their ... Continue reading

The authors present a comprehensive systematic review and meta-analysis of the effect of citrus-based products on urine profile. The paper is supplemented by the PRISMA flow chart and forest plot charts to present their results.

Although their search strategy is good, they should have used other terms such as 'kidney stones', 'stones', 'ureteric stones' and 'calculi' too. They have only used the term 'Urolithiasis' which could potentially miss on other relevant studies.

As a limitation of any systematic review the authors are correct in acknowledging that their is likely to be a publication bias. Similarly, the long term effect of the use of citrate-based products in not know from this study and whether their results translate into a reduction in stone recurrences remain unknown.

A recent cochrane review on the use of citrate salts on prevention and treatment of calcium containing kidney stones in adults showed a reduction in new stone formation and stone recurrences in these patients¹.

Overall the paper reads well and is a nice summary on the use of citrate based products on urine profile.

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Yes
Are sufficient details of the methods and analysis provided to allow replication by others?

Yes
Is the statistical analysis and its interpretation appropriate?

Yes
Are the conclusions drawn adequately supported by the results presented in the review?

Yes

References

1. Phillips R, Hanchanale VS, Myatt A, Somani B, et al.: Citrate salts for preventing and treating calcium containing kidney stones in adults.Cochrane Database Syst Rev. 2015. CD010057 PubMed Abstract | Publisher Full Text

Competing Interests: No competing interests were disclosed.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

CITE

Report a concern

Respond or Comment

Views

9

Reviewer Report 02 May 2017

David S Goldfarb, NYU Langone Medical Center and NYU School of Medicine, New York, NY, USA

Approved

https://doi.org/10.5256/f1000research.11834.r21950

1. The authors are correct in stating that no previous meta-analysis of the effects of citrus fruits has been performed. The results are not surprising as stone clinicians consider citrus supplementation (or potassium citrate) of important utility. However, the meta-analysis is ... Continue reading

1. The authors are correct in stating that no previous meta-analysis of the effects of citrus fruits has been performed. The results are not surprising as stone clinicians consider citrus supplementation (or potassium citrate) of important utility. However, the meta-analysis is reasonable to perform as the intervention is commonly administered.
2.The studies are similar enough to consider a meta-analysis worth doing. One study used diet orange soda which is not citrus juice (I am the senior author of that study). There is otherwise an appropriate selection of studies, based on availability of the requisite data which the authors explain in detail.
3. The limitations of the data include the relatively small sample size, so that the meta-analysis is also underpowered but shows the expected increase in urine citrate and the increase in urine pH only in stone formers and not in non-stone forming controls. No studies actually assess stone formation as an outcome, addressing only urinary chemistry.
4. The conclusions appear reasonable, and are well-stated, if not surprising.
5. Table 1 could be improved by including the dose of juice for all the interventions.
6. I did not find a legend for figure 2 about bias assessment. The figure is hazy, not of perfect resolution. There is no interpretation of the bias assessment in the manuscript. It is worth noting that it is probably not possible to blind participants to citrus juice vs water. The other criteria, such as blinding to sequence allocation may also not be critical to a study of urine chemistry and not of kidney stone outcomes.
7. Regarding Curhan’s finding that grapefruit juice was associated with higher risk for stones, mentioned in the discussion, that finding was not confirmed in a later study¹.
8. In the introduction, the authors state “whereas citrate could prevent stone formation by ionizing urinary calcium”: this is not quite correct. Citrate binds to ionic calcium and prevents it from binding to oxalate or phosphate.

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Yes
Are sufficient details of the methods and analysis provided to allow replication by others?

Yes
Is the statistical analysis and its interpretation appropriate?

Yes
Are the conclusions drawn adequately supported by the results presented in the review?

Yes

References

1. Ferraro PM, Taylor EN, Gambaro G, Curhan GC: Soda and other beverages and the risk of kidney stones.Clin J Am Soc Nephrol. 2013; 8 (8): 1389-95 PubMed Abstract | Publisher Full Text

Competing Interests: Owner of the Ravine Group, see http://www.filamentbiosolutions.com/Press-releases/filament-announces-licensing-agreement.html. Disclosure: I am an author of 2 of the papers included in the study: Goldfarb, and Sumorok.

Reviewer Expertise: Nephrolithiasis, kidney stones, calculi, renal, chronic kidney disease, end stage renal disease, electrolytes and acid-base balance, gout

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

CITE

Report a concern

Respond or Comment

Comments on this article Comments (0)

Version 1

VERSION 1 PUBLISHED 06 Mar 2017

Open Peer Review

Reviewer Status

Reviewer Reports

	Invited Reviewers
	1	2
Version 1 06 Mar 17	read	read

David S Goldfarb, NYU Langone Medical Center and NYU School of Medicine, New York, USA
Bhaskar Somani, University Hospitals Southampton NHS Trust, Urology, Southampton, UK

Comments on this article

All Comments(0)

Add a comment

Sign up for content alerts

Browse by related subjects

Back to all reports

Reviewer Report

8 Views

08 May 2017 | for Version 1

Bhaskar Somani, University Hospitals Southampton NHS Trust, Urology, Southampton, SO16 6YD., UK

8 Views Cite this report Responses(0)

Approved

The authors present a comprehensive systematic review and meta-analysis of the effect of citrus-based products on urine profile. The paper is supplemented by the PRISMA flow chart and forest plot charts to present their results.

Although their search strategy is good, they should have used other terms such as 'kidney stones', 'stones', 'ureteric stones' and 'calculi' too. They have only used the term 'Urolithiasis' which could potentially miss on other relevant studies.

As a limitation of any systematic review the authors are correct in acknowledging that their is likely to be a publication bias. Similarly, the long term effect of the use of citrate-based products in not know from this study and whether their results translate into a reduction in stone recurrences remain unknown.

A recent cochrane review on the use of citrate salts on prevention and treatment of calcium containing kidney stones in adults showed a reduction in new stone formation and stone recurrences in these patients¹.

Overall the paper reads well and is a nice summary on the use of citrate based products on urine profile.

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Yes
Are sufficient details of the methods and analysis provided to allow replication by others?

Yes
Is the statistical analysis and its interpretation appropriate?

Yes
Are the conclusions drawn adequately supported by the results presented in the review?

Yes

References

1. Phillips R, Hanchanale VS, Myatt A, Somani B, et al.: Citrate salts for preventing and treating calcium containing kidney stones in adults.Cochrane Database Syst Rev. 2015. CD010057 PubMed Abstract | Publisher Full Text

Competing Interests

No competing interests were disclosed.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Respond to this report

Responses (0)

Back to all reports

Reviewer Report

9 Views

02 May 2017 | for Version 1

David S Goldfarb, NYU Langone Medical Center and NYU School of Medicine, New York, NY, USA

9 Views Cite this report Responses(0)

Approved

1. The authors are correct in stating that no previous meta-analysis of the effects of citrus fruits has been performed. The results are not surprising as stone clinicians consider citrus supplementation (or potassium citrate) of important utility. However, the meta-analysis is reasonable to perform as the intervention is commonly administered.
2.The studies are similar enough to consider a meta-analysis worth doing. One study used diet orange soda which is not citrus juice (I am the senior author of that study). There is otherwise an appropriate selection of studies, based on availability of the requisite data which the authors explain in detail.
3. The limitations of the data include the relatively small sample size, so that the meta-analysis is also underpowered but shows the expected increase in urine citrate and the increase in urine pH only in stone formers and not in non-stone forming controls. No studies actually assess stone formation as an outcome, addressing only urinary chemistry.
4. The conclusions appear reasonable, and are well-stated, if not surprising.
5. Table 1 could be improved by including the dose of juice for all the interventions.
6. I did not find a legend for figure 2 about bias assessment. The figure is hazy, not of perfect resolution. There is no interpretation of the bias assessment in the manuscript. It is worth noting that it is probably not possible to blind participants to citrus juice vs water. The other criteria, such as blinding to sequence allocation may also not be critical to a study of urine chemistry and not of kidney stone outcomes.
7. Regarding Curhan’s finding that grapefruit juice was associated with higher risk for stones, mentioned in the discussion, that finding was not confirmed in a later study¹.
8. In the introduction, the authors state “whereas citrate could prevent stone formation by ionizing urinary calcium”: this is not quite correct. Citrate binds to ionic calcium and prevents it from binding to oxalate or phosphate.

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Yes
Are sufficient details of the methods and analysis provided to allow replication by others?

Yes
Is the statistical analysis and its interpretation appropriate?

Yes
Are the conclusions drawn adequately supported by the results presented in the review?

Yes

References

1. Ferraro PM, Taylor EN, Gambaro G, Curhan GC: Soda and other beverages and the risk of kidney stones.Clin J Am Soc Nephrol. 2013; 8 (8): 1389-95 PubMed Abstract | Publisher Full Text

Competing Interests

Owner of the Ravine Group, see http://www.filamentbiosolutions.com/Press-releases/filament-announces-licensing-agreement.html. Disclosure: I am an author of 2 of the papers included in the study: Goldfarb, and Sumorok.

Reviewer Expertise

Nephrolithiasis, kidney stones, calculi, renal, chronic kidney disease, end stage renal disease, electrolytes and acid-base balance, gout

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Respond to this report

Responses (0)

[1] 1. Eknoyan G: History of urolithiasis. Clinical Reviews in Bone and Mineral Metabolism. 2004; 2(3): 177–85. Publisher Full Text

[2] 2. Trinchieri A: Epidemiology of urolithiasis. Arch Ital Urol Androl. 1996; 68(4): 203–49. PubMed Abstract

[3] 3. Türk C, Knoll T, Petrik A, et al.: Pocket Guidelines on urolithiasis. Eur Urol. 2014; 40(4): 362–71.

[4] 4. Fukuhara H, Ichiyanagi O, Kakizaki H, et al.: Clinical relevance of seasonal changes in the prevalence of ureterolithiasis in the diagnosis of renal colic. Urolithiasis. 2016; 44(6): 529–537. PubMed Abstract | Publisher Full Text | Free Full Text

[5] 5. Muslumanoglu AY, Binbay M, Yuruk E, et al.: Updated epidemiologic study of urolithiasis in Turkey. I: Changing characteristics of urolithiasis. Urol Res. 2011; 39(4): 309–14. PubMed Abstract | Publisher Full Text

[6] 6. Edvardsson VO, Indridason OS, Haraldsson G, et al.: Temporal trends in the incidence of kidney stone disease. Kidney Int. 2013; 83(1): 146–52. PubMed Abstract | Publisher Full Text

[7] 7. Scales CD Jr, Smith AC, Hanley JM, et al.: Prevalence of kidney stones in the United States. Eur Urol. 2012; 62(1): 160–5. PubMed Abstract | Publisher Full Text | Free Full Text

[8] 8. Indonesia IAU: Tatalaksana Batu Saluran Kemih. 2007.

[9] 9. Singh P, Enders FT, Vaughan LE, et al.: Stone Composition Among First-Time Symptomatic Kidney Stone Formers in the Community. Mayo Clin Proc. 2015; 90(10): 1356–65. PubMed Abstract | Publisher Full Text | Free Full Text

[10] 10. Moses R, Pais VM Jr, Ursiny M, et al.: Changes in stone composition over two decades: evaluation of over 10,000 stone analyses. Urolithiasis. 2015; 43(2): 135–9. PubMed Abstract | Publisher Full Text

[11] 11. Park S, Pearle MS: Pathophysiology and management of calcium stones. Urol Clin North Am. 2007; 34(3): 323–34. PubMed Abstract | Publisher Full Text

[12] 12. Maalouf N: Approach to the adult kidney stone former. Clin Rev Bone Min Metab. 2012; 10(1): 38–49. PubMed Abstract | Publisher Full Text | Free Full Text

[13] 13. Tracy CR, Pearle MS: Update on the medical management of stone disease. Curr Opin Urol. 2009; 19(2): 200–4. PubMed Abstract | Publisher Full Text

[14] 14. Siener R: Can the manipulation of urinary pH by beverages assist with the prevention of stone recurrence? Urolithiasis. 2016; 44(1): 51–6. PubMed Abstract | Publisher Full Text

[15] 15. Higgins JP, Altman DG, Gøtzsche PC, et al.: The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011; 343: d5928. PubMed Abstract | Publisher Full Text | Free Full Text

[16] 16. Wells GA, Shea B, O’Connell D, et al.: The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa, ON: Ottawa Hospital Research Institute; [Accessed September 1, 2016]. 2011. Reference Source

[17] 17. Penniston KL, Steele TH, Nakada SY: Lemonade therapy increases urinary citrate and urine volumes in patients with recurrent calcium oxalate stone formation. Urology. 2007; 70(5): 856–60. PubMed Abstract | Publisher Full Text

[18] 18. Sumorok NT, Asplin JR, Eisner BH, et al.: Effect of diet orange soda on urinary lithogenicity. Urol Res. 2012; 40(3): 237–41. PubMed Abstract | Publisher Full Text

[19] 19. Tosukhowong P, Yachantha C, Sasivongsbhakdi T, et al.: Citraturic, alkalinizing and antioxidative effects of limeade-based regimen in nephrolithiasis patients. Urol Res. 2008; 36(3–4): 149–55. PubMed Abstract | Publisher Full Text

[20] 20. Aras B, Kalfazade N, Tuğcu V, et al.: Can lemon juice be an alternative to potassium citrate in the treatment of urinary calcium stones in patients with hypocitraturia? A prospective randomized study. Urol Res. 2008; 36(6): 313–7. PubMed Abstract | Publisher Full Text

[21] 21. Goldfarb DS, Asplin JR: Effect of grapefruit juice on urinary lithogenicity. J Urol. 2001; 166(1): 263–7. PubMed Abstract | Publisher Full Text

[22] 22. Hönow R, Laube N, Schneider A, et al.: Influence of grapefruit-, orange- and apple-juice consumption on urinary variables and risk of crystallization. Br J Nutr. 2003; 90(2): 295–300. PubMed Abstract | Publisher Full Text

[23] 23. Koff SG, Paquette EL, Cullen J, et al.: Comparison between lemonade and potassium citrate and impact on urine pH and 24-hour urine parameters in patients with kidney stone formation. Urology. 2007; 69(6): 1013–6. PubMed Abstract | Publisher Full Text

[24] 24. Odvina CV: Comparative value of orange juice versus lemonade in reducing stone-forming risk. Clin J Am Soc Nephrol. 2006; 1(6): 1269–74. PubMed Abstract | Publisher Full Text

[25] 25. Seltzer MA, Low RK, McDonald M, et al.: Dietary manipulation with lemonade to treat hypocitraturic calcium nephrolithiasis. J Urol. 1996; 156(3): 907–9. PubMed Abstract | Publisher Full Text

[26] 26. Trinchieri A, Lizzano R, Bernardini P, et al.: Effect of acute load of grapefruit juice on urinary excretion of citrate and urinary risk factors for renal stone formation. Dig Liver Dis. 2002; 34(Suppl 2): S160–3. PubMed Abstract | Publisher Full Text

[27] 27. Khanniazi MK, Khanam A, Naqvi SA, et al.: Study of potassium citrate treatment of crystalluric nephrolithiasis. Biomed Pharmacother. 1993; 47(1): 25–8. PubMed Abstract | Publisher Full Text

[28] 28. Fuselier HA, Ward DM, Lindberg JS, et al.: Urinary Tamm-Horsfall protein increased after potassium citrate therapy in calcium stone formers. Urology. 1995; 45(6): 942–6. PubMed Abstract | Publisher Full Text

[29] 29. Laube N, Jansen B, Hesse A: Citric acid or citrates in urine: which should we focus on in the prevention of calcium oxalate crystals and stones? Urol Res. 2002; 30(5): 336–41. PubMed Abstract | Publisher Full Text

[30] 30. Heilberg IP, Goldfarb DS: Optimum nutrition for kidney stone disease. Adv Chronic Kidney Dis. 2013; 20(2): 165–74. PubMed Abstract | Publisher Full Text

[31] 31. Curhan GC, Willett WC, Rimm EB, et al.: Prospective study of beverage use and the risk of kidney stones. Am J Epidemiol. 1996; 143(3): 240–7. PubMed Abstract | Publisher Full Text

[32] 32. Robinson MR, Leitao VA, Haleblian GE, et al.: Impact of long-term potassium citrate therapy on urinary profiles and recurrent stone formation. J Urol. 2009; 181(3): 1145–50. PubMed Abstract | Publisher Full Text

[33] 33. Allie-Hamdulay S, Rodgers AL: Prophylactic and therapeutic properties of a sodium citrate preparation in the management of calcium oxalate urolithiasis: randomized, placebo-controlled trial. Urol Res. 2005; 33(2): 116–24. PubMed Abstract | Publisher Full Text

[34] 34. Phillips R, Hanchanale VS, Myatt A, et al.: Citrate salts for preventing and treating calcium containing kidney stones in adults. Cochrane Database Syst Rev. 2015; 10(10): CD010057. PubMed Abstract | Publisher Full Text

[35] 35. Ettinger B, Pak CY, Citron JT, et al.: Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J Urol. 1997; 158(6): 2069–73. PubMed Abstract | Publisher Full Text

[36] 36. Lee YH, Huang WC, Tsai JY, et al.: The efficacy of potassium citrate based medical prophylaxis for preventing upper urinary tract calculi: a midterm followup study. J Urol. 1999; 161(5): 1453–7. PubMed Abstract | Publisher Full Text

[37] 37. Rahman F, Birowo P, Widyahening IS, et al.: Dataset 1 in: Effect of citrus-based products on urine profile: A systematic review and meta-analysis. F1000Research. 2017. Data Source

[38] 38. Rahman F, Birowo P, Widyahening IS, et al.: Dataset 2 in: Effect of citrus-based products on urine profile: A systematic review and meta-analysis. F1000Research. 2017. Data Source

[39] 39. Rahman F, Birowo P, Widyahening IS, et al.: Dataset 3 in: Effect of citrus-based products on urine profile: A systematic review and meta-analysis. F1000Research. 2017. Data Source

[40] 40. Rahman F, Birowo P, Widyahening IS, et al.: Dataset 4 in: Effect of citrus-based products on urine profile: A systematic review and meta-analysis. F1000Research. 2017. Data Source

[41] 41. Rahman F, Birowo P, Widyahening IS, et al.: Dataset 5 in: Effect of citrus-based products on urine profile: A systematic review and meta-analysis. F1000Research. 2017. Data Source

[42] 42. Rahman F, Birowo P, Widyahening IS, et al.: Dataset 6 in: Effect of citrus-based products on urine profile: A systematic review and meta-analysis. F1000Research. 2017. Data Source

Effect of citrus-based products on urine profile: A systematic review and meta-analysis

Abstract

Keywords

Introduction

Methods

Eligibility criteria

Search strategy

Study selection and data extraction

Assessment of bias and statistical methods

Results

Figure 1. Study flow diagram.

Table 1. Characteristic of included studies.

Figure 2. Risk of bias assessment summary.

Effect of citrus-based products on urine profile

Figure 3. Urine pH and urinary citrate levels represented by a forest plot.

Figure 4. Urine volume, urinary calcium, urinary oxalate, and urinary uric acid levels represented by a forest plot.

Figure 5. Subgroup analysis of urine profiles represented by forest plot.

Comparison between citrus-based products and potassium citrate in urine profile

Discussion

Conclusions

Data availability

Author contributions

Competing interests

Grant information

Supplementary material

References

Comments on this article Comments (0)

Open Peer Review

Comments on this article Comments (0)

Open Peer Review

Reviewer Status

Reviewer Reports

Comments on this article

Browse by related subjects

The problem

How to fix it

The problem

How to fix it

The problem

How to fix it

The problem

How to fix it

The problem

How to fix it

The problem

How to fix it

Competing Interests Policy

Stay Updated