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JURNAL Impact of Food To Stone Formation
JURNAL Impact of Food To Stone Formation
To cite this article: Francesco Esperto, Roberto Miano, Martino Marangella & Alberto Trinchieri
(2018): Impact of food quantity and quality on the biochemical risk of renal stone formation,
Scandinavian Journal of Urology, DOI: 10.1080/21681805.2018.1453868
ARTICLE
CONTACT Alberto Trinchieri a.trinchieri@asst-lecco.it Urology Unit, Manzoni Hospital, via dell’Eremo 9/11, 23900 Lecco, Italy
ß 2018 Acta Chirurgica Scandinavica Society
2 F. ESPERTO ET AL.
by ion chromatography (Dionex ICS-1000; Thermo Scientific, potassium (r ¼ 0.261; p ¼ .000), sodium (r ¼ 0.309; p ¼ .000),
Sunnyvale, CA, USA). Sodium and potassium were deter- oxalate (r ¼ 0.244; p ¼ .000), urate (r ¼ 0.294; p ¼ .000), phos-
mined directly by ion-selective electrodes, and urine pH by a phate (r ¼ 0.303; p ¼ .000), sulfate (r ¼ 0.307; p ¼ .000), chloride
specific electrode (Hanna Instruments, Woonsocket, RI ,USA). (r ¼ 0.339; p ¼ .000) and US-UA (r ¼ 0.191; p ¼ .000), and
The original software LithoRisk [7] was used to compute the inversely related to urinary pH (r ¼ –0.149; p ¼ .002) and
relative supersaturation (beta) according to a scale where ammonium/sulfate ratio (r ¼ –0.205; p ¼ .000) (Table 2).
beta =1 is saturation, beta <1 undersaturation and beta >1 LAKE score was positively correlated with urate (r ¼ 0.114;
oversaturation. p ¼ .016), phosphate (r ¼ 0.109; p ¼ .022), sulfate (r ¼ 0.111;
The dietary patterns of the patients were evaluated by the p ¼ .019), US-CaOx (r ¼ 0.109; p ¼ .022) and US-CaP (r ¼ 0.171;
administration of a semi-quantitative questionnaire, which p ¼ .000), and inversely related to citrate (r ¼ –0.194;
made it possible to estimate the PRAL of the diet as the p ¼ .000), potassium (r ¼ –0.127; p ¼ .008) and ammonium/sul-
Load of Acid to Kidney Evaluation (LAKE) score [8]. The LAKE fate ratio (r ¼ –0.102; p ¼ .031) (Table 2).
score is a rapid food screener that assesses the potential acid Multiple linear regression analysis identified BMI
load of the diet by scoring the consumption of grains, meats, (p ¼ .009) and male gender (p ¼ .002) as independent predic-
cured meats, eggs, cheeses, legumes, potatoes, vegetables, tors of US-UA, and LAKE score (p ¼ .004) and age (p ¼ .001)
fruits, milk and other dairy products, and bread. as independent predictors of US-CaP. The ammonium/
The rates of overweight and obesity by gender and age sulfate ratio tended to decrease with the increase in
groups were calculated and compared. Linear correlations of BMI (p ¼ .007).
urinary risk factors with BMI and LAKE score were calculated. Supersaturation with respect to uric acid (beta >1) was
Multivariate analysis was performed by logistic regression, observed in the urine of 45 patients (10.2%), while supersat-
taking into account US-CaOx, US-CaP and Ca-UA as depend- uration with respect to calcium oxalate and calcium phos-
ent variables and age, gender, BMI and LAKE score as predic- phate was observed in the urine of 429 (97%) and 295
tors. Statistical analysis was performed using SPSS version (66.7%) patients, respectively.
11.5 (SPSS, Chicago, IL, USA). No difference in the percentage of urine with calcium
oxalate (100%, 96%, 97% and 93%, p ¼ .41) or calcium phos-
phate (57%, 69%, 62% and 74%, p ¼ .25) supersaturation was
Results observed in the four different BMI classes, whereas the rate
of patients with urine supersaturation with respect to uric
Of the 442 patients included in the study (240 male, 202
acid tended to increase progressively in the higher BMI
female), 14 (3.2%) had a BMI <18.5 kg/m2. The BMI was
classes (0%, 7%, 13% and 16%, p ¼ .05).
18.5–24.9 kg/m2 in 214 patients (48.5%), 25–29.9 kg/m2 in 156
patients (35.4%) and >30 kg/m2 in 57 patients (12.9%).
Discussion
Overweight and obesity were present in 112 (46.7%) and 33
(13.8%) of the men, respectively, and in 44 (22%) and 24 Some previous studies have identified specific derangements
(11.9%) of the women. The occurrence of overweight and on 24 h urine from overweight and obese patients. All studies
obesity tended to be higher in men (p ¼ .000) and to agree that values of the excretion of oxalate, urate, phos-
increase with age in both genders, although there was a phate, sodium and creatinine are higher and urinary pH is
slight decrease in >65-year-old patients (p ¼ .000) (Table 1). lower in overweight or obese renal stone formers [9–13].
BMI was positively correlated with daily urinary excretion of Urinary ammonium, urinary sulfate and cystine were also
calcium (r ¼ 0.162; p ¼ .001), magnesium (r ¼ 0.206; p ¼ .000), reported by some authors to be higher in patients with
Table 1. Body mass index (BMI) categories by gender and age class in renal stone-forming patients.
BMI category (kg/m2)
Age (years), gender Underweight (<18.5) Normal (18.5–24.9) Overweight (25–29.9) Obesity (>30) Total
All
18–24 5 (15.6) 16 (50) 9 (28.1) 2 (6.2) 32
25–44 8 (4.5) 102 (57.3) 46 (25.8) 22 (12.3) 178
45–64 1 (0.5) 76 (41.1) 82 (43.8) 27 (14.6) 185
>65 0 20 (43.5) 20 (43.5) 6 (13) 46
Total 14 (3.2) 214 (48.5) 157 (35.4) 57 (12.9) 442
Males
18–24 1 (7.1) 7 (50) 4 (28.6) 2 (14.3) 14
25–44 1 (1) 43 (46.2) 39 (41.9) 10 (10.7) 93
45–64 0 35 (32.4) 56 (51.9) 17 (15.7) 108
>65 0 8 (32) 13 (52) 4 (16) 25
Total 2 (0.8) 93 (38.7) 112 (46.7) 33 (13.8) 240
Females
18–24 4 (22.2) 9 (50) 5 (27.8) 0 18
25–44 7 (8.2) 59 (69.4) 7 (8.2) 12 (14.1) 85
45–64 1 (1.2) 41 (52.6) 26 (33.3) 10 (12.8) 78
>65 0 12 (57.1) 7 (33.3) 2 (9.5) 21
Total 12 (5.9) 121 (59.9) 45 (22.3) 24 (11.9) 202
Data are shown as n (%).
SCANDINAVIAN JOURNAL OF UROLOGY 3
higher BMI [9,10]. However, data on calcium, magnesium and rich in animal protein [14]. However, the enlarged adipose
citrate excretion and urinary volume in obese renal stone for- tissue mass that defines obesity causes systemic insulin
mers are controversial. Urinary calcium excretion was found resistance, which is linked to a wide array of pathophysio-
to be increased [9], unchanged [13] or unchanged after cor- logical sequelae including an excessively acidic urine [15]. In
rection for sodium excretion [11], or increased only in obese patients with metabolic syndrome, differences in alkali con-
males and not in females [11]. Urinary volumes in obese sumption were considered not relevant to explain acidic
renal stone formers were reportedly either increased [9] or urine, and lower urinary pH persisted after adjustment for
unchanged [10]. Similarly, magnesium and citrate excretion urinary sulfate (as a marker of animal protein intake), sug-
were reported to be increased [9,13] or unchanged [10]. The gesting that dietary factors alone cannot account for the
present study confirmed that BMI was positively correlated overly acidic urine observed in those patients [16,17]. On the
with the major urinary risk factors for calcium stone formers, other hand, ammonia excretion is a major determinant of
i.e. calcium, oxalate, urate and phosphate, but also with an urinary pH by acting as a buffer in the urine, which tends to
inhibitor of calcium crystallization, i.e. magnesium, and be acidic when ammoniagenesis is affected, as in insu-
inversely related to urinary pH and to the ammonium/sulfate lin resistance.
ratio. The increased excretion of some urinary risk factors for In the present study, ammonium excretion tended to
stone formation in relation to increased BMI values can be increase with BMI, but less than the concomitant increase in
explained by the increased intake of nutrients and energy sulfate, so the ratio of urinary ammonium to urinary sulfate
that is associated with being overweight or obese. In this was inversely related to BMI. A similar finding has previously
study, sodium and sulfate excretion, which are reliable been observed in uric acid stone formers by Bobulescu et al.
markers of sodium and protein intake, tended to increase [18], who demonstrated a blunted urine ammonium excre-
with BMI. tion in response to an acute acid load. No relation between
The increased intake of nutrients can influence the excre- BMI and US-CaOx or US-CaP was found in the present study,
whereas US-UA tended to increase with BMI. US-CaOx and
tion of urinary risk factors either directly or indirectly through
US-CaP are not influenced by the increase in BMI because it
alteration of their metabolism. Uric acid, oxalate and phos-
implies an increase in the risk factors for stone formation
phate seem to be strictly dependent on dietary intake,
that is counteracted by the concomitant increase in inhibitors
whereas this relationship is weaker for other nutrients, such
of calcium crystallization. In contrast, overweight or obese
as calcium and citrate, which are more affected by metabolic
patients tend to have higher mean levels of US-UA, although
alterations or variations in renal handling. Calcium urinary
in this population only 13% of the overweight patients and
excretion depends on the dietary intake of sodium and cal-
16% of the obese patients presented with supersaturated
cium, but in stone-forming subjects it is also strongly influ-
urine for uric acid. Accordingly, the rate of uric acid stones in
enced by a number of heterogeneous pathophysiological
obese patients has been previously found to be higher than
anomalies that may be stronger than the effect of diet. The
in the general population of renal stone formers. Daudon
influence of dietary citrate on urinary citrate is limited
et al. showed that the proportion of uric acid stones grad-
because citrate excretion is much more dependent on the ually increased with the BMI of patients, from 7.1% in normal
intracellular pH of the proximal tubular cells, which may be BMI to 28.7% in obese male subjects and from 6.1% in nor-
influenced by the acid load of the urine. Urinary pH depends mal BMI to 17.1% in female obese patients [19]. Although
on a complex interplay of dietary and metabolic factors. The metabolic syndrome, which includes the presence of obesity
acid load of the diet has an effect on urinary pH, as demon- in its definition, has also been associated with calcium stone
strated by the finding of higher urinary pH value in people formation [20], renal stone formers with metabolic syndrome
consuming a vegetarian diet than in those who eat a diet have a higher prevalence of uric acid stones than patients
without metabolic syndrome [21,22]. Therefore, the tendency
Table 2. Correlation of urinary risk factors and urinary saturations by body for overweight and obese patients to have an increased risk
mass index (BMI) and Load of Acid to Kidney Evaluation (LAKE) score values.
of stone formation seems to be limited to patients who form
BMI LAKE score
uric acid stones or mixed calcium oxalate/uric acid stones.
r p r p However, in the present study population, levels of US-CaOx
Urinary calcium (mg/24 h) 0.162 .001 –0.045 NS and US-CaP seem to be more dependent on other nutritional
Urinary phosphate (mmol/24 h) 0.303 .000 0.109 .022
Urinary urate (mg/24 h) 0.294 .000 0.114 .016 patterns. A previous study demonstrated that PRAL in renal
Urinary oxalate (mmol/24 h) 0.244 .000 0.027 NS calcium stone formers was higher than in gender- and age-
Urinary citrate (mg/24 h) 0.034 NS –0.194 .000 matched controls [5], and found an inverse relationship
Urinary magnesium (mg/24 h) 0.206 .000 –0.090 NS
Urinary potassium (mEq/24 h) 0.261 .000 –0.127 .008 between urinary citrate and PRAL [23]. In multiple linear
Urinary sodium (mEq/24 h) 0.309 .000 0.020 NS regression analysis of the data, BMI, together with male gen-
Urinary chloride (mEq/24 h) 0.339 .000 0.038 NS der, was an independent predictor of US-UA, but not of US-
Urinary sulfate (mmol/24 h) 0.307 .000 0.111 .019
Urinary ammonium (mmol/24 h) 0.046 NS 0.002 NS CaOx or US-CaP. In contrast, US-CaP was predicted by LAKE
Urinary volume (ml/24 h) 0.073 NS –0.045 NS score, a measure of dietary PRAL, owing to its inverse correl-
Urinary pH –0.149 .002 –0.028 NS ation with the urinary excretion of citrate.
Urinary saturation CaOx 0.060 NS 0.109 .022
Urinary saturation CaP 0.014 NS 0.171 .000 This study has some possible limitations. First, the risk of
Urinary saturation UA 0.191 .000 0.004 NS stone formation was measured by the levels of urinary satur-
NS: not significant. ation in 24 h samples. A more robust approach could be the
4 F. ESPERTO ET AL.
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