ORIGINAL RESEARCH

published: 20 June 2022

doi: 10.3389/fendo.2022.877794

Prognostic Value of Triglyceride

to High-Density Lipoprotein
Cholesterol Ratio (TG/HDL-C)
in IgA Nephropathy Patients
Gaiqin Pei 1,2†, Aiya Qin 1,3†, Lingqiu Dong 1,3, Siqing Wang 1,3, Xiang Liu 1,3,
Dandan Yang 1,3, Jiaxing Tan 3, Xiaoyuan Zhou 4, Yi Tang 3* and Wei Qin 3*
1 West China School of Medicine, Sichuan University, Chengdu, Sichuan, China, 2 Department of Rehabilitation Medicine

Center, West China Hospital, Sichuan University, Sichuan, China, 3 Department of Nephrology, West China Hospital of
Sichuan University, Chengdu, Sichuan, China, 4 West China School of Public Health, West China Forth Hospital of Sichuan
University, Chengdu, China

Edited by: Background: The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio is
Nehal Mohsen Elsherbiny,
Mansoura University, Egypt
an easy-to-use atherogenic and prognostic marker which has attracted increasing attention
Reviewed by:
these days. However, whether TG/HDL-C correlate with outcomes in IgA nephropathy
Elena Rampanelli, (IgAN) patients remains unknown. To clarify these issues, we conducted this study.
Amsterdam University Medical Center,
Netherlands Methods: A total of 1146 patients from West China Hospital of Sichuan University were
Enrique Rodilla, retrospectively analysed between 2008 and 2018.The demographic, clinical and
Hospital de Sagunto, Spain
pathological data of all patients at the time of biopsy were collected. Then, patients
*Correspondence:
Yi Tang
were divided into the high TG/HDL group (TG/HDL ≥ 1.495, N=382) and the low TG/HDL
tmka1986@163.com group (TG/HDL-C < 1.495, N=764) based on the optimal cut-off value of the TG/HDL-C
Wei Qin using receive operating curve. Cox proportional hazard models and Kaplan–Meier curves
qinweihx@scu.edu.cn
†
were used to evaluate the renal outcomes of IgAN.
These authors have contributed
equally to this work Results: The median age of the patients was 33 (26-42) years, and 44.5% were men. By
correlation analysis, we found that the TG/HDL-C ratio was negatively correlated with the
Specialty section:
This article was submitted to
eGFR (r = 0.250, P < 0.001) but positively correlated with proteinuria (r = 0.230, P< 0.001),
Renal Endocrinology, BMI (r=0.380, P<0.001) and serum uric (r =0.308, P< 0.001). Patients with a higher TG/
a section of the journal
HDL-C ratio tended to have hypertension [odds ratio (OR), 1.987; 95% CI, 1.527-2.587;
Frontiers in Endocrinology
P<0.001] and more severe pathologic lesions with tubular atrophy/interstitial fibrosis (OR,
Received: 17 February 2022
Accepted: 17 May 2022 1.610; 95% CI, 1.203-2.154; P=0.001). During a median follow-up period of 54.1 (35.6-
Published: 20 June 2022 73.2) months, a high TG/HDL ratio was strongly associated with worse renal survival in
Citation: IgAN patients (log-rank: P <0.001). Multivariate Cox analysis demonstrated that a high TG/
Pei G, Qin A, Dong L, Wang S, Liu X,
Yang D, Tan J, Zhou X, Tang Y and
HDL-C ratio (HR 1.775, 95% CI 1.056-2.798; P=0.029) was an independent predictive
Qin W (2022) Prognostic Value of marker to ESRD.
Triglyceride to High-Density
Lipoprotein Cholesterol Ratio (TG/ Conclusion: In this study, we addressed the importance of TG/HDL-C ratio as a
HDL-C) in IgA Nephropathy Patients. predictive marker for IgAN progression.
Front. Endocrinol. 13:877794.
doi: 10.3389/fendo.2022.877794 Keywords: triglyceride, high-density lipoprotein cholesterol, IgA nephropathy, prognosis, TG/HDL-C ratio

Frontiers in Endocrinology | www.frontiersin.org 1 June 2022 | Volume 13 | Article 877794

Pei et al. TG/HDL-C and IgA Nephropathy

BACKGROUND TG/HDL-C ratio was obtained by dividing the serum triglyceride

level by the plasma high-density lipoprotein cholesterol level.
Immunoglobulin A (IgA) nephropathy (IgAN), characterized by Anemia, hypertension and hyperuricaemia was defined as
diffusely deposited IgA in the kidneys, is the most prevalent described previously (12, 13). eGFR was calculated using the
primary glomerulonephritis and a leading cause of end-stage CKD-EPI equation (14). Renal biopsy samples were evaluated by
renal disease (ESRD), in which 20–40% of IgAN patients reach an experienced pathologist and a nephrologist according to the
ESRD 10–20 years after the initial diagnosis (1). Recognizing risk Oxford classification (15)
factors of ESRD would be beneficial for to slowing the
progression of IgAN. Treatments
Abnormal lipoprotein metabolism, which could lead to All patients received optimal support treatment, including a full
impaired renal function and accelerated atherosclerosis (2), is dose of angiotensin-converting-enzyme inhibitor (ACEI) or
often characterized by the presence of high TG and low HDL-C angiotensin receptor blockers (ARBs). Glucocorticoids and
in chronic kidney disease (CKD) (3). It is well known TG usually immunosuppressant therapy included cyclophosphamide
increases in the early stages of CKD and is associated with (2 mg/kg daily for 3 months), mycophenolate mofetil (1-2 g
delayed catabolism. However, TG levels fluctuate substantially daily for 6-8 months), tacrolimus (0.03-0.05 mg/kg daily for 6-8
based on feeding status, thus limiting its utility as a predictive months) or cyclosporin was used based on pathological
biomarker (4). The single HDL-C, despite the functions of anti- classification and clinical severity according to the guidelines.
inflammatory and antithrombotic, remains controversial in
predicting cardiovascular disease (CVD) or mortality (5). The Outcome Definition
combination of TG and HDL-C, which is the TG/HDL-C ratio, The renal outcome was progression to ESRD, defined by
could therefore overcome the problem and has been proposed as commencement of renal replacement therapy or an eGFR <15
a more practical atherogenic and insulin resistance marker (6, 7). mL/min/1.73 m2.
It has attracted increasing attention for the better predictive
value for CVD (6, 8) and disease prognosis such as peritoneal Statistical Analysis
dialysis (7), coronavirus disease 2019 (9), type 2 diabetes (10), Continuous variables are expressed as the means ± SDs or
and CKD (11). However, whether the TG/HDL-C ratio could be medians (interquartile ranges). Categorical variables were
another predictor of IgAN progression remains unknown. To expressed as numbers and percentages (%). Student’s t test or
clarify these issues, we conducted this study. the Mann–Whitney U test was used for continuous variables,
and the c2 test was used for categorical variables. The optimal
thresholds of the TG/HDL ratio were obtained according to the
MATERIALS AND METHODS highest Youden’s index using receiver operating curve (ROC)
analyses. Kidney survival in each group was estimated by the
Patients Kaplan–Meier method. Univariate and multivariate Cox
A total of 1449 patients from West China Hospital of Sichuan proportional hazard models were used to evaluate renal
University between 2008 and 2018 were initially enrolled. progression of IgAN. Three statistical models were used in
patients with systemic disease, such as systemic lupus analysis: model 1 (demographics + pathological features + TG/
erythematosus, diabetes, Henoch-Schönlein purpura, liver HDL-C), model 2 (demographics + clinical features +TG/HDL-
cirrhosis or disorder of liver function, malignancy, etc., and C) and model 3 (demographics + clinical+ pathological
without complete clinical and pathologic data were excluded in features +TG/HDL-C). All the data were analysed by the
this study. Patients were followed up for at least 12 months or software package SPSS 23.0 software package (SPSS, Chicago,
until study-defined endpoints were reached. Finally, 1146 adult IL, USA) and GraphPad Prism 8.0. Two-tailed P<0.05 was
biopsy-proven IgAN patients (age > 14 years) were enrolled. The considered statistically significant.
research was in compliance with the Declaration of Helsinki and
was approved by the ethical committees of West China Hospital
of Sichuan University (2019-33). Informed consent was obtained RESULTS
from each patient or their legal guardians prior to treatment.
Demographic and Clinicopathological
Clinical Data Characteristics
Patient information, including age, sex, clinical manifestations, A total of 1146 biopsy-proven IgA nephropathy patients from
laboratory indexes, renal pathology reports, and treatment West China Hospital of Sichuan University were finally enrolled
strategies, systolic/diastolic blood pressure (SBP/DBP), body in this retrospective study (Figure 1). The demographic, clinical,
mass index (BMI) was obtained from electronic medical and pathologic characteristics of the included patients are shown
records. Laboratory values included 24-h proteinuria (UPRO), in Table 1. The median age of the patients was 33 (26-42) years,
hematuria level (URBC), hemoglobin (Hb), serum albumin and 44.5% were men. The median follow-up period was 54.1(35.6-
(ALB), serum creatinine (Cr), estimated glomerular filtration 73.2) months. ROC analysis revealed that the optimal cut-off TG/
rate (eGFR), uric acid (UA), triglycerides (TG), total cholesterol HDL-C ratio with which to predict the progression of ESRD
(TC), and high-density lipoprotein cholesterol (HDL-C). The in patients with IgAN was 1.495 (Supplementary Figure 1).

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Pei et al. TG/HDL-C and IgA Nephropathy

Thus, according to their TG/HDL-C ratio at the time of renal

biopsy, patients were divided into two groups: a high TG/HDL-C
group (TG/HDL ≥ 1.495, N=382) and a low TG/HDL group
(TG/HDL-C < 1.495, N=764). The median eGFR in the high TG/
HDL-C and low TG/HDL-C groups was 9100.0 and 81.5 mL/
min/1.73 m2, respectively. Interestingly, higher SBP, DBP and
BMI levels were shown in the high TG/HDL-C group. Compared
with the low TG/HDL-C group, patients in the high TG/HDL-C
group had a higher incidence of anemia, hyperuricemia and
hypertension (all P <0.001), a higher proportion of males (P
<0.001), and worse renal function (P<0.001). Moreover, higher
levels of TG (P<0.001), TC (P=0.003), UPRO (P<0.001), and Cr
(P<0.001) and lower HDL-C (P<0.001) and URBC (P=0.009)
levels were observed in the high TG/HDL-C group. Regarding
pathological lesions, patients with a high TG/HDL-C always had
mesangial hypercellularity (P=0.06), segmental
glomerulosclerosis (P=0.053) and tubular atrophy/interstitial
FIGURE 1 | Flow diagram.
fibrosis (P=0.002).

TABLE 1 | Demographic and clinicopathological characteristics of 1146 IgAN patients.

Parameters Total N=1146 Group 1 (TG/HDL<1.495) N=764 Group 2 (TG/HDL ≥ 1.495) N=382 P

Age (year) 33 (26-42) 31 (25-41) 36 (27-44) < 0.001

Gender (male, %) 510 (44.5) 303 (39.7) 207 (54.2) < 0.001
HTN (%) 335 (29.2) 186 (24.5) 149 (39.2) < 0.001
SBP (mmHg) 125 (115-138) 124 (115-137) 128 (117-139) 0.012
DBP (mmHg) 82 (75-90) 80 (74-90) 84 (76-92) 0.004
BMI (kg/m2) 23.1 (20.2-25.6) 22.0 (19.6-24.7) 24.9 (22.3-27.6) < 0.001
CKD stages (%) < 0.001
Stage 1 615 (53.7) 455 (59.6) 160 (41.9)
Stage 2 290 (25.3) 178 (23.3) 112 (29.3)
Stage 3 202 (17.6) 118 (15.4) 84 (22.0)
Stage 4 39 (3.4) 13 (1.7) 26 (6.8)
Pathologic
M1 (%) 860 (75.1) 560 (73.3) 300 (78.5) 0.06
E1 (%) 52 (4.5) 35 (4.6) 17 (4.5) 1.00
S1 (%) 704 (61.4) 454 (59.4) 250 (65.4) 0.053
T1-2/T0 (%) 243 (21.2) 141 (18.5) 102 (26.7) 0.002
C1-2/C0 (%) 244 (21.3) 162 (21.2) 82 (21.5) 0.939
Clinical
Cr (umol/L) 83.3 (65.2-109.0) 79.0 (62.0-102.0) 93.8 (72.0-126.0) < 0.001
eGFR (mL/min/1.73 m2) 93.6 (66.0-117.7) 100.0 (71.8-120.1) 81.5 (54.9-105.5) < 0.001
ALB (g/L) 40.0 (36.0-43.1) 40.1 (36.0-43.2) 40.0 (35.8-43.0) 0.694
HDL (mmol/L) 1.39 (1.11-1.73) 1.54 (1.31-1.87) 1.07 (0.89-1.26) < 0.001
TG (mmol/L) 1.5 (1.1-2.1) 1.2 (0.9-1.5) 2.5 (2.0-3.4) < 0.001
TC (mmol/L) 4.8 (4.1-5.7) 4.7 (4.1-5.5) 5.0 (4.2-5.8) 0.003
UPRO (g/d) 1.5 (0.8-3.0) 1.3 (0.7-2.7) 2.0 (1.0-3.5) < 0.001
URBC (/HP) 18.0 (6.0-61.0) 19.5 (6.3-68.0) 15.0 (5.0-47.5) 0.009
Anemia (%) 161 (14.1) 88 (11.5) 73 (19.1) < 0.001
Hyperuricemia 466 (40.7) 262 (34.3) 204 (53.4) < 0.001
Treatment (%) 0.039
SC 438 (38.2) 307 (40.2) 131 (34.3)
GC only 432 (37.7) 289 (37.8) 143 (37.4)
IT and/or GC 276 (24.1) 168 (22.0) 109 (28.3)
Follow-up
Duration (months) 54.1 (35.6-73.2) 56.4 (36.3-75.1) 48.3 (34.7-67.6) < 0.001
ESRD 78 (6.8) 32 (4.2) 46 (12.0) < 0.001

Data presented as median (first-third interquartile range) or number (percentage).

SBP, Systolic Blood Pressure; DBP, diastolic blood pressure; BMI, body mass index; CKD, chronic kidney disease; M, mesangial proliferation; E, endocapillary proliferation; S, segmental
sclerosis; T, tubular atrophy/interstitial fibrosis; C, crescents; Cr, creatinine; eGFR, estimated glomerular filtration rate; ALB, albumin; HDL, high-density lipoprotein cholesterol; TG,
triglycerides; TC, total cholesterol; UPRO, 24 h urine protein; URBC, urinary red blood cell counts; SC, supportive care; GC, corticosteroids; IT, immunosuppressive therapy; ESRD, end
stage renal disease.

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Pei et al. TG/HDL-C and IgA Nephropathy

Correlation of the TG/HDL-C

Ratio With Clinical Parameters and
Pathological Lesions
The correlations between the TG/HDL-C levels and
clinicopathological findings are illustrated in Tables 2, 3. Our
results showed that TG/HDL-C was significantly negatively
correlated with the eGFR (r = -0.250, P < 0.001) but positively
correlated with proteinuria (r = 0.230, P < 0.001), BMI (r=0.380,
P < 0.001) and serum uric (r =0.308, P< 0.001). Logistic
regression analysis was conducted to analyse the relationship
between TG/HDL and clinicopathologic features. The high TG/
HDL-C group IgAN patients were more likely to have
hypertension [odds ratio (OR), 1.987; 95% CI, 1.527-2.587;
P<0.001] and pathologic lesions with tubular atrophy/
interstitial fibrosis (OR, 1.610; 95% CI, 1.203-2.154; P<0.001)
and segmental sclerosis (OR, 1.293; 95% CI, 1.002-
1.670; P=0.049)

Renal Survival
During a median follow-up period of 54.1 (35.6-73.2) months, a
total of 78 (6.8%) patients developed ESRD. For renal survival,
our results reveal that TG/HDL-C ≥1.495 was significantly
associated with ESRD (Figure 2, P < 0.001). Subgroup analysis FIGURE 2 | Kaplan-Meier analysis for the endpoint of ESRD stratified by the
cutoff point of the TG/HDL-C.
of mesangial hypercellularity and tubular atrophy/interstitial
fibrosis, CKD stages and proteinuria for ESRD by Kaplan–
Meier analysis is shown in Figure 3. Our results indicated that
tubular atrophy/interstitial fibrosis (Figures 3E, F) in
a high TG/HDL-C ratio was a risk factor for ESRD in patients
pathologic lesions.
with IgAN, especially patients with eGFR<60 mL/min/1.73 m2
(P<0.001) (Figures 3A–C), 24-hour urine protein ≥1 g/day
(P< 0.001) (Figure 3D), or mesangial hypercellularity and TG/HDL-C as an Independent Risk Factor
for Progression of IgAN to ESRD
We performed Cox regression analyses to evaluate risk factors
TABLE 2 | Correlation between related variables and TG/HDL-C. for ESRD in patients with IgAN, which showed that a high TG/
HDL-C ratio was significantly associated with a higher risk of
Variables Correlation coefficient (r) P value
ESRD (HR=3.290, 95% CI: 2.093-5.173, P<0.001) in univariate
TG/HDL-C UPRO 0.230 < 0.001** analysis. Then, three models were used for multivariate Cox
Hb 0.034 0.254 regression (Table 4 and Supplementary Tables 1, 2), which
UA 0.308 < 0.001**
BMI 0.380 < 0.001**
indicated that high TG/HDL-C was an independent risk factor of
ALB -0.035 0.242 renal endpoints (model 1: HR 4.158, 95% CI 1.970-8.775,
eGFR -0.250 < 0.001** P<0.001; model 2: HR 3.944, 95% CI 1.825-8.523, P<0.001;
**stands for P < 0.01.
model 3: HR 1.775, 95% CI 1.056-2.798, P=0.029). Moreover,
UPRO, 24 h urine protein; Hb, hemoglobin; UA, uric acid; BMI, body mass index; ALB, when stratified by the quartiles of baseline level of TG/HDL-C as
albumin; eGFR, estimated glomerular filtration rate. Q1, Q2, Q3 and Q4 group (Supplementary Figure 2), significant
difference were also shown between Q4 (highest quartiles) and
TABLE 3 | Logistics regression models for the relationship between TG/HDL-C
other groups (Q1, Q2, and Q3)
and kidney pathologic lesion.

OR 95%CI P value
DISCUSSION
M 1.333 0.995-1.785 0.054
E 0.970 0.536-1.755 0.920 Dyslipidemia is common in China, with a prevalence of 41.9 %,
S 1.293 1.002-1.670 0.049*
and is commonly characterized by the presence of high TG and
T1-2/T0 1.610 1.203-2.154 0.001**
C1-2/C0 1.016 0.753-1.370 0.919
low HDL-C in CKD (16). Recently, the combination of TG and
HTN 1.987 1.527-2.587 < 0.001** HDL-C, the TG/HDL-C ratio, has attracted increasing attention
for its better predictive power for cardiovascular events and
*stands for P < 0.05, **stands for P < 0.01.
M, mesangial proliferation; E, endocapillary proliferation; S, segmental sclerosis; T, tubular insulin resistance than the lonely combination (17, 18).
atrophy/interstitial fibrosis; C, crescents; HTN, hypertension. Noticeably, several studies have shown a positively relationship

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Pei et al. TG/HDL-C and IgA Nephropathy

A B C

D E F

FIGURE 3 | Subgroup Kaplan-Meier analysis for endpoint of ESRD; eGFR (A–C), UPRO (D), M (E), T (F); eGFR, estimated glomerular filtration rate; UPRO, 24 h
urine protein; M, mesangial proliferation; T, tubular atrophy/interstitial fibrosis.

TABLE 4 | Analysis of factors associated with renal outcomes in model 3 (demographics+ clinical indicators+ pathological features+ TG/HDL-C).

Parameter Univariate Multivariate

HR 95%CI P value HR 95%CI P value

high TG/HDL-C 3.290 2.093-5.173 < 0.001 1.775 1.056-2.798 0.029

male 1.902 1.213-2.982 0.005 – – –
Age (per year) 0.991 0.971-1.012 0.410 0.951 0.928-0.976 < 0.001
BMI (kg/m2) 1.048 0.956-1.149 0.319 – – –
SBP (mmHg) 1.033 1.022-1.044 < 0.001 – – –
DBP (mmHg) 1.049 1.034-1.063 < 0.001 – – –
M1 8.806 2.776-27.937 < 0.001 4.320 1.348-13.847 0.014
E1 2.232 1.073-4.642 0.032 – – –
S1 1.614 1.001-2.602 0.049 – – –
T1-2/T0 11.811 7.154-19.499 < 0.001 2.475 1.398-13.847 0.002
C1-2/C0 1.290 0.786-2.115 0.314 – – –
UPRO>1.0g 3.310 1.823-6.007 < 0.001 – – –
URBC>5/HP 0.947 0.559-1.605 0.840 – – –
Anemia 3.717 2.339-5.908 < 0.001 – – –
Hyperuricemia 4.457 2.778-7.573 < 0.001 – – –
hypoalbuminemia 2.255 1.302-3.907 0.004 – – –
CKD stages
CKD 2 vs 1 6.993 2.260-21.268 0.001 6.800 2.147-21.538 0.001
CKD 3 vs 1 30.497 10.970-85.394 < 0.001 23.898 7.714-74.031 < 0.001
CKD 4 vs 1 136.066 46.960-394.247 < 0.001 63.129 19.189-207.689 < 0.001
Treatment 0.010 0.036
GC/SC 0.738 0.414-1.317 0.304 1.191 0.705-2.011 0.514
IT/SC 1.710 1.019-2.869 0.042 0.563 0.319-0.992 0.047

SBP, Systolic Blood Pressure; DBP, diastolic blood pressure; BMI, body mass index; M, mesangial proliferation; E, endocapillary proliferation; S, segmental sclerosis; T, tubular atrophy/
interstitial fibrosis; C, crescents; UPRO, 24 h urine protein; URBC, urinary red blood cell counts; SC, supportive care; GC, corticosteroids; IT, immunosuppressive therapy.

between the TG/HDL-C ratio and renal function decline in CKD patients with IgAN was associated with more severe clinical
patients (16, 18–20). However, whether TG/HDL-C has a role in features and pathologic lesions. Our further analysis revealed a
IgAN progression remains unknown. higher serum TG/HDL-C level was an independent risk factor
In this study, 78 (6.8%) patients developed ESRD in our 1146 for the progression to ESRD (HR 1.775, 95% CI 1.056-
biopsy-proven IgAN patients. A higher TG/HDL-C ratio in 2.798, P=0.029).

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Pei et al. TG/HDL-C and IgA Nephropathy

Previous studies have reported that the reduction in renal process (25, 26). Additionally, further tissue injury is contributed
function in patients is related to high TG/HDL-C levels (11, 16), owing to impaired HDL-mediated reverse cholesterol transport by
but no study has focused on IgAN patients. To our knowledge, limiting the unloading of the excess cellular cholesterol and
this is the first study assessing the correlation between the TG/ phospholipid burden (25). Thus, in the future, recognizing the
HDL-C ratio and ESRD in IgAN patients. Moreover, the TG/ TG/HDL-C ratio as a potentially modifiable risk factor for patients
HDL-C ratio has a greater influence in advanced IgAN patients may allow the utilization of preventative strategies to optimize both
(eGFR< 60 mL/min/1.73 m2) or these with 24-hour urine protein treatment and survival outcomes.
of ≥1 g/day in our study. This might be due to the slow Some limitations warrant consideration. First, this was a
progression of mild renal disease, especially within a limited retrospective study based on a single-center database. Second,
follow-up period (12). the median follow-up time of 54 months was relatively short.
Here, higher SBP, DBP and BMI levels were shown in the high Further multicenter validation in different ethnic populations
TG/HDL-C group. Further analysis showed TG/HDL was with longer follow-ups was needed.
positively correlated with BMI (r=0.380, P < 0.001). In our
multivariate Cox regression analyses, BMI was not independent
risk factor for renal progression. It is well known obesity often
result in excessive accumulation of energy, accompanied by CONCLUSION
abnormalities in lipid parameter levels. Some studies showed it
The TG/HDL-C ratio may be considered as a prognostic
was associated with the early development of hypertension and
biomarker in IgAN patients.
CKD progression (21). However, emerging epidemiologic
evidence indicated that obesity was not a direct and
independent risk factor for IgAN (22). It was possible that high
BMI indirectly accelerated the progression of IgAN by inducing DATA AVAILABILITY STATEMENT
metabolic syndrome on patients, in which TG/HDL-C is strongly
associated with it (23). Additionally, we would like to stress that The raw data supporting the conclusions of this article will be
high TG/HDL-C patients tend to have hypertension and more made available by the authors, without undue reservation.
severe renal pathologic lesions of segmental glomerulosclerosis
and tubular atrophy/interstitial fibrosis. Considering that
abnormalities in lipid parameter levels could accelerated ETHICS STATEMENT
atherosclerosis is plausible to believe that pathology of IgAN
patients with a high TG/HDL-C level. The studies involving human participants were reviewed and
Abnormalities in lipid parameter levels could lead to impaired approved by the ethical committees of West China Hospital of
renal function and accelerated atherosclerosis (2). TG usually Sichuan University (2019-33). The patients/participants
increases in the early stages of CKD and is associated with provided their written informed consent to participate in
delayed catabolism and decreased activity of hepatic TG lipase this study.
and peripheral lipoprotein lipase. However, based on feeding
status, TG levels could fluctuate substantially, thus limiting its
utility as a predictive biomarker (4). HDL-C, inversely associated
with outcomes, decreases in patients with CKD (11). The
AUTHOR CONTRIBUTIONS
combination of these two markers could therefore overcome this GP, AQ, SW, LD, XL, and DY collected and analysed the data.
problem and lead to a far more consistent, stable, fasting GP and AQ wrote the main manuscript text. YT, XZ and JT
measurement of dyslipidaemia, which has indeed attracted much reviewed and edited the manuscript. WQ supervised all the work
more attention in disease prognosis, including cardiovascular and revised the manuscript. All authors contributed to the article
disease (6), diabetes (10), and peritoneal dialysis (7). Here, the and approved the submitted version.
potential mechanisms by which the TG/HDL-C ratio serves as a
prognostic biomarker in IgAN patients may be as follows. TG/
HDL-C is a reliable indicator of insulin resistance, which induces
oxidative stress. Oxidative stress impairs the activation of nuclear FUNDING
factor erythroid-2-related factor-2, which protects against kidney
tissue injury (16). The filtered proteins, such as fatty acids, This study is partly supported by the National Key R&D
phospholipids, and cholesterol contained in the filtered proteins Program of China (2020YFC2006503) &(2020YFC2006500).
(albumin and lipoproteins), could include direct toxic effects of
lipids on glomerular cells and promote matrix production (3, 24).
Moreover, these materials act as damage-associated molecular ACKNOWLEDGMENTS
patterns (DAMPs) and are recognized by Toll-like receptors
(TLR2 and TLR4), which can activate inflammatory responses, We are indebted to all the people who kindly participated in
causing tubulointerstitial fibrosis and injury in the reabsorption this study.

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Pei et al. TG/HDL-C and IgA Nephropathy

Supplementary Figure 1 | ROC curves (AUC) of TG/HDL-C for prediction of

SUPPLEMENTARY MATERIAL ESRD.

The Supplementary Material for this article can be found online

Supplementary Figure 2 | Kaplan-Meier analysis for the endpoint of ESRD
at: https://www.frontiersin.org/articles/10.3389/fendo.2022. stratified by quartile: Q1, first quartile; Q2, median; Q3, third quartile, Q4, fourth
877794/full#supplementary-material quartile.

(CHARLS). Lipids Health Dis (2021) 20:110. doi: 10.1186/s12944-021-

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fimmu.2021.700224 absence of any commercial or financial relationships that could be construed as a
13. Al-Makki A, DiPette D, Whelton PK, Murad MH, Mustafa RA, Acharya S, potential conflict of interest.
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Frontiers in Endocrinology | www.frontiersin.org 7 June 2022 | Volume 13 | Article 877794