Invest Clin 64(3): 329 - 337, 2023 https://doi.org/10.54817/IC.v64n3a6

Corresponding author: Hesong Ye. Jiangsu Second Chinese Medicine Hospital, The Second Affiliated Hospital of

Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China. Email: yehsjscmu@shu-edu.cn

Association of formation of urinary calculi

with blood lipid levels.

Longlong Tang, Hesong Ye, Yuan Qin, Ming Yang, Wentao Gong, Qi He, Yang Shen

and Qiyue Wang

Jiangsu Second Chinese Medicine Hospital, The Second Affiliated Hospital of Nanjing

University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China.

Keywords: urinary calculi; blood lipids; correlation.

Abstract. We aimed to analyze the composition of urinary calculi and its

correlations with blood lipids such as triglycerides (TG), total cholesterol (TC),

low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cho-

lesterol (HDL-C). Three hundred patients with urinary calculi treated from

January 2020 to July 2021 were selected retrospectively into a urinary calculi

group, while three hundred healthy individuals who received physical examina-

tion in our hospital during the same period were enrolled in a control group. Us-

ing the Spearman correlation analysis, we investigated the correlation between

the composition of urinary calculi and dyslipidemia and explored the factors

affecting urinary calculi through multivariate logistic regression analysis. The

serum levels of TG and TC were significantly higher (p<0.05), the serum HDL-

C level was significantly lower (p<0.05), while the serum LDL-C level displayed

no significant difference (p>0.05) in the urinary calculi group compared with

those in the control group. The proportion of uric acid calculi was significantly

higher in urinary calculi patients with dyslipidemia than that in those with

normal blood lipids (p<0.05). However, no significant difference was observed

in the proportions of infectious calculi and calcium calculi between urinary

calculi patients with dyslipidemia and those with normal blood lipids (p>0.05).

Dyslipidemia was positively correlated with uric acid calculi (p<0.05) but not

associated with infectious calculi or calcium calculi (p>0.05). TG was a risk

factor for urinary calculi (p<0.05). The formation of urinary calculi is closely

associated with blood lipid levels. Dyslipidemia, especially hypertriglyceride-

mia, can easily induce the formation of uric acid calculi.

330 Tang et al.

Investigación Clínica 64(3): 2023

Asociación de formación de cálculos urinarios con niveles

de lípidos en sangre.

Invest Clin 2023; 64 (3): 329 – 337

Palabras clave: cálculos urinarios, lípidos en sangre, correlación.

Resumen. Nuestro objetivo fue analizar la composición de los cálculos uri-

narios y sus correlaciones con los lípidos sanguíneos, como los triglicéridos

(TG), el colesterol total (CT), el colesterol de lipoproteínas de baja densidad

(LDL-C) y el colesterol de lipoproteínas de alta densidad (HDL-C). Trescien-

tos pacientes con cálculos urinarios tratados desde enero de 2020 hasta julio

de 2021 fueron seleccionados retrospectivamente e incluidos en el grupo de

cálculos urinarios, mientras que trescientas personas sanas que recibieron un

examen físico en nuestro hospital durante el mismo período se inscribieron en

el grupo control. La correlación entre la composición de los cálculos urinarios y

la dislipidemia se investigó mediante un análisis de correlación de Spearman, y

los factores que afectan a los cálculos urinarios se exploraron mediante un aná-

lisis de regresión logística multivariable. Los niveles séricos de TG y TC fueron

significativamente más altos (p<0,05), el nivel sérico de HDL-C fue significati-

vamente más bajo (p<0,05), mientras que el nivel sérico de LDL-C no mostró

diferencias significativas (p>0,05) en el grupo los cálculos urinarios en compa-

ración con los del grupo control. La proporción de cálculos de ácido úrico fue

significativamente mayor en los pacientes con cálculos urinarios y dislipidemia

que en aquellos con lípidos sanguíneos normales (p<0,05). Sin embargo, no se

observaron diferencias significativas en las proporciones de cálculos infecciosos

y cálculos de calcio entre los pacientes con cálculos urinarios con dislipidemia

y aquellos con lípidos sanguíneos normales (p>0,05). La dislipidemia se corre-

lacionó positivamente con cálculos de ácido úrico (p<0,05), pero no se asoció

con cálculos infecciosos o cálculos de calcio (p>0,05). TG fue un factor de ries-

go para cálculos urinarios (p<0,05). La formación de cálculos urinarios está

estrechamente relacionada con los niveles de lípidos en sangre. La dislipidemia,

especialmente la hipertrigliceridemia, puede inducir fácilmente la formación

de cálculos de ácido úrico.

Received: 28-09-2022 Accepted: 17-04-2023

INTRODUCTION

Urinary calculi is one of the common

urinary system diseases, with an annually

steadily increasing prevalence rate, espe-

cially in young people, and the first attack

rate is the highest among people aged 20-

30 years old

1,2

. From a global view, urinary

calculus presents a high prevalence rate in

countries such as the United States, China,

Thailand, and the United Kingdom, but is

rare in Central America, South America,

and Africa. Epidemiological data have man-

ifested that the incidence rate of urinary

calculi is 1-5% in China, and about 25% of

such patients need to be hospitalized

3,4

. As

Risk factors for urinary calculi 331

Vol. 64(3): 329 - 337, 2023

people’s working rhythm speeds up, their

diet structure changes and their living stan-

dards improve, the incidence rate of urinary

calculi is climbing each year. The formation

of urinary calculi is exceptionally compli-

cated and closely associated with abnor-

mal lipid metabolism, insulin resistance,

hyperglycemia, hypertension, obesity, etc.

Blood lipids are essential substances for the

primary metabolism of living cells, which

widely exist in human bodies and can take

part in energy metabolism

. According to

a study

, abnormal lipid metabolism is es-

sential in forming urinary calculi. However,

the correlations between blood lipids and

urinary calculi remain unclear. Therefore,

this study analyzed the composition of uri-

nary calculi, and the correlations of urinary

calculi with blood lipids were investigated

to provide a theoretical basis for the clini-

cal prevention and treatment of urinary cal-

culi.

PATIENTS AND METHODS

General data

Three hundred patients with urinary

calculi treated in our hospital from Janu-

ary 2020 to July 2021 were selected retro-

spectively into a urinary calculi group, while

three hundred healthy individuals who re-

ceived physical examination in our hospital

during the same period were enrolled in a

control group.

Inclusion criteria: 1) patients diag-

nosed as urinary calculi by B-ultrasound,

kidney ureter bladder X-ray, intravenous py-

elography, or computed tomography urog-

raphy, 2) those whose medical history was

complete, 3) those without blood diseases,

4) those without autoimmune diseases, 5)

those with no cardiovascular diseases, and 6)

those who were informed of this study and

signed the informed consent. Exclusion cri-

teria: 1) patients complicated with dysfunc-

tion of vital organs such as heart, liver, or

lung, 2) those pregnant or breastfeeding, 3)

those complicated with a malignant tumor,

hypertension, or diabetes mellitus, 4) those

with abnormal blood coagulation, 5) those

with hyperparathyroidism, or 6) those with

cognitive dysfunction.

Methods

Age, gender, BMI, smoking history,

drinking history, and other general data of

all the subjects were recorded after admis-

sion. Five ml of fasting peripheral venous

blood was collected in the morning and

placed in an aseptic vacuum blood collec-

tion tube. After centrifugation (Beijing Era

Beili Centrifuge Co., Ltd., model: DT4-6D)

at 3,000 rpm for 15 min to separate the se-

rum, the serum levels of low-density lipo-

protein cholesterol (LDL-C), triglyceride

(TG), high-density lipoprotein cholesterol

(HDL-C) and total cholesterol (TC) were

measured using an automatic biochemistry

analyzer (Beijing Beiruida Pharmaceutical

Technology Co., Ltd., model: SR95-SUN-

MATIK-9050). The criteria for dyslipidemia

were those referred to in the Chinese Guide-

lines for the Prevention and Treatment of

Dyslipidemia in Adults (2016 Revision)

Urinary calculi samples were collected on

the day of operation, which were washed

with distilled water and dried naturally. Lat-

er, the composition of urinary calculi was

analyzed using a LUMOS stand-alone FT-IR

spectroscopy analyzer (Bruker, Germany).

Statistical analysis

The IBM SPSS 26.0 software was uti-

lized for statistical analysis. The numerical

data were expressed as n (%) and compared

by the χ

test between groups. The measure-

ment data were expressed as (`χ ± s) and

compared by t-test between groups. Spear-

man’s analysis was employed to analyze the

correlation between urinary calculi compo-

sition and dyslipidemia. Besides, multivari-

ate logistic regression analysis was adopted

to explore the factors affecting urinary cal-

culi. p<0.05 indicated that the difference

was statistically significant.

332 Tang et al.

Investigación Clínica 64(3): 2023

RESULTS

Baseline clinical data

In the urinary calculi group, there were

190 males and 110 females, aged 18-67

years old, with an average age of 45.56±5.23

years old and a body mass index (BMI) of

24.51±3.34 kg/m

. Two hundred of the pa-

tients had a smoking history, while 210 of

them had a drinking history. In terms of uri-

nary calculi type, there were 100 cases of

kidney calculi, 190 cases of ureteral calculi,

and ten cases of bladder calculi. In the con-

trol group, there were 189 males and 111

females, aged 18-68 years old, with a mean

age of 45.51±5.45 years old and a BMI of

24.57±3.17 kg/m

. Among them, 202 pa-

tients had a smoking history, while 209 had

a drinking history. No significant differences

were found in the age, gender, smoking his-

tory, BMI, drinking history and other general

data between the two groups (p>0.05).

Composition of urinary calculi

The composition analysis results of the

300 patients with urinary calculi indicated

260 cases of calcium calculi (including 102

cases of calcium oxalate - calcium oxalate

monohydrate/calcium oxalate dihydrate),

32 cases of calcium oxalate + calcium phos-

phate, 54 cases of calcium oxalate + hydroxy-

apatite, 54 cases of calcium oxalate + uric

acid, and 18 cases of calcium oxalate + uric

acid + calcium phosphate, 51 cases of infec-

tious calculi (including 23 cases of hydroxy-

apatite + calcium oxalate, 14 cases of mag-

nesium ammonium phosphate + calcium

oxalate, four cases of hydroxyapatite + mag-

nesium ammonium phosphate, two cases of

ammonium urate, and eight cases of magne-

sium ammonium phosphate + uric acid), and

28 cases of uric acid calculi (including ten

cases of uric acid calculi and 18 cases of uric

acid + magnesium ammonium phosphate).

Serum levels of TG, HDL-C, TC and LDL-C

The serum levels of TG and TC were

significantly higher, while the serum HDL-

C levels were significantly lower in urinary

calculus group than those in control group,

showing statistically significant differences

(p<0.05). However, the serum LDL-C lev-

els in the urinary calculus group displayed

no statistically significant differences in

comparison with those in control group

(p>0.05) (Fig. 1).

Multivariate logistic regression analysis

results of factors affecting formation

of urinary calculi

Multivariate logistic regression analysis

was performed by incorporating the factors

with significant differences above, revealing

that TG was a risk factor for the formation of

urinary calculi (p<0.05) (Table 1).

Composition of calculi in urinary calculi

patients with normal blood lipids

and dyslipidemia

The proportion of uric acid calculi in

urinary calculi patients with dyslipidemia

was significantly higher than in those with

normal blood lipids, showing a statistically

significant difference (p<0.05). However,

there were no statistically significant differ-

ences in the proportions of infectious calculi

and calcium calculi between urinary calculi

patients with dyslipidemia and those with

normal blood lipids (p>0.05) (Table 2).

Correlation between the composition

of urinary calculi and dyslipidemia

Dyslipidemia was positively correlated

with uric acid calculi (p<0.05), but not as-

sociated with infectious calculi or calcium

calculi (p>0.05) (Table 3).

DISCUSSION

The reasons for the formation of urinary

calculi are complicated, and are associated

with various factors. According to a study

hyperglycemia, hypertension and abnormal

lipid metabolism are risk factors for the for-

mation of urinary calculi, and abnormal lipid

metabolism is an important contributor to

Risk factors for urinary calculi 333

Vol. 64(3): 329 - 337, 2023

Fig. 1. Serum levels of TG, HDL-C, TC and LDL-C.

Table 1

Composition of calculi in urinary calculi patients with normal blood lipids and dyslipidemia (n(%)).

Group n Infectious calculi Calcium calculi Uric acid calculi

Normal blood lipids 210 39 (18.57) 180 (85.71) 8 (3.81)

Dyslipidemia 90 12 (13.33) 80 (88.89) 20 (22.22)

1.225 0.550 25.241

P 0.268 0.459 <0.001

Tabla 2

Correlation between composition of urinary

calculi and dyslipidemia.

Composition of urinary

calculi

Dyslipidemia

r p

Infectious calculi 0.082 0.647

Calcium calculi 0.056 0.834

Uric acid calculi 0.678 <0.001

334 Tang et al.

Investigación Clínica 64(3): 2023

the formation of urinary calculi, which can

increase the risk of urinary calculi by 25-

30%. A previous study

suggested that el-

evated blood lipid levels will induce rising

blood viscosity, leading to atherosclerosis

(AS), affecting renal blood flow, and thereby

facilitating the deposition of lithogenic sub-

stances in the blood to form calculi. The re-

sults of this study manifested that the serum

levels of TG and TC were remarkably higher.

In contrast, serum HDL-C level was dramati-

cally lower in the urinary calculus group than

those in the control group. Still, the serum

LDL-C levels were not significantly different

between the two groups, which was consis-

tent with the study results of Besiroglu et al.

. These findings suggest that the formation

of urinary calculi is associated with dyslipid-

emia. Moreover, the results of multivariate

logistic regression analysis demonstrated

that TG was a risk factor for urinary calculi,

implying that dyslipidemia, especially hyper-

triglyceridemia, is more prone to the forma-

tion of urinary calculi. Hence, controlling

blood lipids has important clinical signifi-

cance for the prevention of urinary calculi.

For the 300 urinary calculi patients en-

rolled in this study, the high incidence age

was 40-50 years old, with more males than

females (the male-to-female ratio was 1.73).

By analyzing the composition of urinary cal-

culi, it was found that there were 260 cases

of calcium calculi, 51 cases of infectious

calculi, and 28 cases of uric acid calculi. It

can be inferred that calcium calculi were

the major components of calculi in the 300

patients. It is probably because the dietary

structure of residents in this area is dominat-

ed by seafood, meat, and other high-protein

and high-cholesterol foods. Excessive intake

of such foods can result in the elevation of

blood lipids and increased endogenous acid

metabolites in urine, which boosts the ex-

cretion of urinary calcium, calcium oxalate,

and uric acid, reduces citrate excretion, and

lowers the reabsorption of calcium in urine,

thereby inducing more calcium oxalate cal-

culi. Among the 300 patients with urinary

calculi in this study, the proportion of pa-

tients with infectious calculi was next only

to those with calcium calculi; most were

female. Infectious calculi are the results of

infection caused by urease-producing bac-

teria in urine, and the major components

include magnesium ammonium phosphate,

apatite and so on

. It has been pointed out

in a study

that urinary tract infection is

one of the most common pathogenic fac-

tors of female urinary calculi, and the inci-

dence rate of upper urinary tract infectious

calculi in female is three times that in men.

In the present study, uric acid calculi were

Table 3

Logistic regression analysis results of factors affecting urinary calculi.

Variable Partial regression

coefficient

Standard

error

Wald P 95% CI OR

Gender -0.242 0.179 1.562 0.983 0.431-0.902 0.872

Age 0.243 0.154 1.872 0.871 0.672-1.325 1.128

BMI -0.319 0.147 4.234 0.643 0.542-0.927 0.743

Smoking history 0.156 0.182 1.784 0.743 0.783-1.221 1.209

Drinking history 0.257 0.211 1.673 0.683 1.092-2.532 1.392

TG 0.811 0.305 12.298 0.004 1.547-5.092 2.345

LDL-C 0.041 0.098 0.345 0.823 0.811-1.243 1.112

HDL-C 0.209 0.174 1.205 0.645 0.745-1.562 1.532

TC 0.227 0.172 1.782 0.711 0.943-2.093 1.342

Risk factors for urinary calculi 335

Vol. 64(3): 329 - 337, 2023

the least common among the 300 patients

with urinary calculi. Uric acid is not only the

major composition of uric acid calculi, but

also involved in the formation of calculi com-

posed of other elements. Hyperuricemia-in-

duced calculi are co-formed by a variety of

components under different internal envi-

ronments

. It has been revealed in a study

that patients with uric acid calculi have

higher incidence rates of diabetes mellitus,

poor glucose tolerance, and hypertriglyc-

eridemia than normal people. The results of

this study also demonstrated that the pro-

portion of uric acid calculi in urinary calculi

patients with dyslipidemia was dramatically

higher than that in those with normal blood

lipids. Still, there was no significant differ-

ence in the proportions of infectious calculi

and calcium calculi between urinary calculi

patients with dyslipidemia and those with

normal blood lipids.

This suggested that dyslipidemia can

easily lead to the formation of urinary calcu-

li, especially uric acid calculi, which was fur-

ther confirmed by the Spearman correlation

analysis in this study. It is because elevated

blood lipid levels can lead to lipid deposi-

tion, which damages the tubular excretory

function, thus resulting in rising uric acid

levels. Meanwhile, increased uric acid levels

reduce lipoprotein esterase activity and TG

decomposition. As a result, the blood TG lev-

el rises. In addition, high uric acid can cause

increased excretion of urine, rising uric acid

concentration in urine, and decreased urine

PH, so it is more likely to induce the forma-

tion of uric acid calculi under the action of

multiple factors

16-18

. Uric acid can reduce

the protective activity of inhibitors against

calcium oxalate crystal formation in urine,

allowing the formation of calcium oxalate

crystals and aggregation into stones. There-

fore, hyperuricemia is related to uric acid-in-

duced heterogeneous nucleation of calcium

oxalate crystals

Hence, in clinical treatment of urinary

calculi, besides calculus treatment, atten-

tion should be paid to regulating the me-

tabolism level in the body, effective control

of blood lipids, reasonable diet, and more

exercise, so as to lower the risk of recurrent

urinary calculi.

In summary, the formation of urinary

calculi is closely associated with blood lipid

levels. Dyslipidemia, especially hypertriglyc-

eridemia, can easily lead to the formation of

uric acid calculi. Controlling blood lipids has

important clinical significance for the pre-

vention of urinary calculi. Regardless, this

study is limited. This is a single-center ret-

rospective study with a small sample size, so

the results may be biased. In the future, we

will perform multicenter prospective studies

with larger sample sizes to clarify the spe-

cific mechanism.

Funding

None.

Conflicts of interest

The authors reported no potential con-

flict of interest.

ORCID numbers

• Longlong Tang (LT):

0000-0002-9951-3257

• Hesong Ye (HY):

0000-0002-8303-6468

• Yuan Qin (YQ):

0000-0003-1257-3984

• Ming Yang (MY):

0000-0002-8688-3611

• Wentao Gong (WG):

0000-0002-8891-0476

• Qi He (QH):

0000-0003-1987-0949

• Yang Shen (YS):

0000-0002-6329-9826

• Qiyue Wang (QW):

0000-0002-6593-9145

336 Tang et al.

Investigación Clínica 64(3): 2023

Authors’ contribution

LT and HY designed the study; YQ, MY

and WG conceived and supervised the study;

QH and YS performed and analyzed the ex-

periments; QW drafted the paper. All authors

read and approved the final manuscript.

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