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- J Med Biochem
- v.43(4); 2024 Jun 15
- PMC11318902
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J Med Biochem. 2024 Jun 15; 43(4): 565-573.
Published online 2024 Jun 15. doi:10.5937/jomb0-45732
PMCID: PMC11318902
PMID: 39139181
Language: English | Serbian
Violeta Rabrenović,1 Milica Petrović,1 Milorad Rabrenović,3 and Nemanja Rančić4
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Abstract
Background
Metabolic syndrome (MetS) in patients with systemic lupus erythematosus (SLE) represents an additional burden and a poor prognostic factor for the onset or worsening of atherosclerosis and cardiovascular complications. In many patients with lupus nephritis (LN), MetS is often already manifested initially. Our work aimed to determine the frequency and characteristics of MetS in patients with LN, as well as the relationship components of MetS and characteristics of disease activity.
Methods
The clinical study included 67 patients with LN, 54 (80.59%) female and 13 (19.41%) male, with an average age of 42.86±14.46 years. Patients were divided into two groups: with MetS (35.82%) and without MetS (64.18%), active LN had (34 or 50.74%), and LN in remission (33 or 49.25%). We monitored clinical and biochemical parameters of interest.
Results
Comparing patients with LN collectively, as well as those with MetS and without MetS, we observed that patients with MetS were older (p=0.001), BMI (p<0.001), and systolic arterial pressure was higher (p=0.002), and smokers were more common in this group (p<0.001). In the analysis, increased triglycerides (p<0.001) and creatinine (p=0.027), and decreased albumin (p=0.050) and GFR (p=0.020) were observed in the group with MetS. MetS was present in 44.11% of patients with active LN and in 27.7% with LN in remission. The most common MetS parameter was arterial hypertension (76.6%), which correlated with GFR and creatinine; hypertriglyceridemia (47.8%), which is correlated with anti-ds-DNA Ab, erythrocyturia, proteinuria, and SLEDAI/r index; decreased HDL cholesterol (28.4%) which significantly correlated with albumin, C3 and anti-ds-DNA Ab.
Conclusions
In our patients with LN, MetS was associated with older age, impaired kidney function, and smoking. The most common parameter of MetS was arterial hypertension and dyslipidemia, which were significantly correlated with disease activity parameters, indicating an increased risk of cardiovascular complications in this group of patients.
Keywords: lupus nephritis, metabolic syndrome, dyslipidemia, activity
Abstract
Uvod
Metabolički sindrom (MetS) kod bolesnika sa SLE, predstavlja dodatno opterećenje i loš prognostički faktor za nastanak ili pogoršanje ateroskleroze i za kardiovaskularne komplikacije. MetS je često inicijalno već ispoljen kod mnogih bolesnika sa lupus nefritisom (LN). Cilj našeg rada je bio da utvrdimo učestalost i karakteristike MetS kod bolesnika sa LN, kao i odnos komponenti MetS i aktivnosti lupus nefritisa.
Metode
Kliničko ispitivanje je obuhvatilo grupu od 67 pacijenata sa LN, 54 (80,59%) ženskog pola i 13 (19,41%) muškaraca, prosečnih godina starosti 42,86±14,46. Pacijenti su podeljeni u dve grupe: prva sa MetS (35,82%) i druga bez MetS (64,18%), pacijenti su imali aktivan LN (34 ili 50,74%) i LN u remisiji (33 ili 49,25%). Pratili smo kliničke i biohemijske parametre od interesa.
Rezultati
Poredeći pacijente sa LN zbirno kao i one sa MetS i bez MetS, utvrdili smo da su pacijenti sa MetS bili stariji (p=0,001), BMI (p<0,001) i sistolni pritisak je bio viši (p=0,002) i pušači su bili zastupljeniji u ovoj grupi (p<0,001). U analizama su zapaženi povišeni trigliceridi (p<0,001) i kreatinin (p=0,027) i snižen albumin (p=0,050) i GFR (p=0,020) u grupi sa MetS. MetS je bio zastupljen kod 44,11% pacijenata sa aktivnim LN i kod 27,7% sa LN u remisiji. Najzastupljeniji parameter MetS je bila arterijska hipertenzija (76,6%) koja značajno korelirala sa GFR i kreatininom; hipertrigliceridemija (47,8%) koja je korelirala sa anti-ds-DNA At, eritrociturijom, proteinurijom i SLEDAI/r indeksom; snižen HDL holesterol (28,4%) koji je korelirao značajno sa albuminom, C3 i anti-ds-DNA At.
Zaključak
Kod naših pacijenata sa LN, MetS je bio povezan sa starijim životnim dobom, poremećajem bubrežne funkcije i pušenjem. Najzastupljeniji parameter MetS kod pacijenata sa LN je bila arterijska hipertenzija i dislipidemija koja je značajno korelirala sa parametrima aktivnosti bolesti, što upućuje na povećan rizik od kardiovaskularnih komplikacija u ovoj grupi bolesnika.
Keywords: lupus nefritis, metabolički sindrom, dislipidemija, aktivnost
Introduction
Systemic lupus erythematosus (SLE) is a veryserious chronic immuno-inflammatory disease thatranks 20th on the list of causes of death in the femalepopulation [1]. An unfavorable outcome in SLE ismost often caused by infections, malignancies, kidneylesions, and cardiovascular diseases [2]. Compared tothe general population, patients with SLE have a 2-fold higher risk of developing nonfatal cardiovascularevents, and compared to diabetics of the same ageand gender, they have a 27% higher risk of developingcardiovascular disease [3]. The presence of metabolicsyndrome (MetS) (obesity, arterial hypertension,hyperglycemia, hypertriglyceridemia, reduction ofhigh-density lipoprotein cholesterol- HDL-cholesterol)in patients with SLE represents an additional burdenand a poor prognostic factor for the onset or worseningof atherosclerosis and cardiovascular events.MetS has been described with a frequency of 16–44%in patients with SLE [4][5][6]. Patients with lupus nephritis(LN) represent a group in which the activity of SLEhas led to kidney damage, which usually manifestsclinically in the form of nephrotic, nephritic syndrome,or rapidly progressive glomerulonephritis withconsequent arterial hypertension, all of whichincrease the risk of cardiovascular events. In patientswith LN, MetS is often already present, which representsan additional risk for the development of acceleratedatherosclerosis and cardiovascular complications[7][8]. Patients with LN have a 47% higherchance of developing coronary artery disease comparedto patients with SLE without LN [9].
Our work aimed to determine the frequency andcharacteristics of MetS in patients with LN, as well asthe relationship components of MetS and characteristicsof disease activity.
Materials and methods
In the clinical examination (approved by theEthics Committee and performed according to thetenets of the Declaration of Helsinki and conductedfrom 2012–2019), we included a group of 67 patientswith SLE and LN (54–80.59% female and 13 –19.41% male), the average age was 42.86±14.46years. The diagnosis was confirmed by the criteria of the European League Against Rheumatism (EULAR),and LN was confirmed by kidney biopsy and pathohistologicalverification (WHO classification, andInternational Society of Nephrology/Renal PathologySociety (ISN/RPS) classification) [10][11]. Kidney diseaseactivity was also classified according to the renaldisease activity index SLEDAI/r (renal (Systemic LupusErythematosus Disease Activity Index – rSLEDAI) [12].SLEDAI/r consists of 4 criteria that grade renal impairmentwithin the SLEDAI 2000 (Systemic LupusErythematosus Disease Activity Index- SLEDAI 2000)criteria of SLE activity [13]. The patients were dividedinto two groups: the first group consisted of patientswith MetS (35.82%), and the second group consistedof patients without MetS (64.18%). Patients had activedisease (34 patients – 50.74%) and disease in remission(33 patients – 49.25%). Active LN, according tostandard analysis, was defined as proteinuria ≥0.5g/24h; according to SLEDAI/r criteria (>4), hypocomplementemiaC3 and C4, positive anti-double-strandedDNA antibodies (anti-ds-DNA Ab) and pathohistologicalfindings of renal biopsy. Glomerular filtrationrate (GFR) was defined according to the ChronicKidney Disease Epidemiology Collaboration (CKDEPI)[14]. Complete remission was defined accordingto the criterion: proteinuria ≤0.5 g/24h.; SLEDAI/rindex (<4), negative anti-ds-DNA antibodies, complementC3 and C4 within the reference range, and GFR≥60 mL/min/1.73 m2). Excluding criteria were thesame for all groups: patients with infection, positiveurine culture, kidney failure (CKDeGFR< 60mil/min/1.73 m2), and those under 18.
MetS was defined as present if three or more ofthe following five criteria were present: (1) obesity(BMI >30 kg/m2 used as a surrogate marker ofabdominal obesity consistent with the definition ofabdominal obesity in the National Institutes of Healthobesity guidelines; (2) elevated triglycerides ≥1.7mmol/L, or medication; (3) reduced high-densitylipoprotein (HDL) cholesterol (HDL-cholesterol) lessthan 40 mg/dL (1.04 mmol/L) in men, or less than 50mg/dL (1.3 mmol/L) in women; (4); increased bloodpressure ≥130/ 85 mmHg, or using medication forhypertension; (5) elevated fasting glucose (>5.6mmol/L) or using antidiabetic medication [15].
All laboratory parameters for the group withactive LN were determined before the immunosupressive treatment started (in this way, the effect of thetherapy on the laboratory analyses was prevented).The group with LN in remission received maintenancetherapy: 5–10 mg of corticosteroids and 50–75 mg ofazathioprine per day. The authors had access to informationthat identified participants in the study.
Blood specimens were collected after anovernight fasting. The parameters we monitored wereclinical parameters: BMI (kg/m2), arterial blood pressure(measured in millimeters of mercury: mmHg),standard laboratory parameters: C reactive protein(CRP), complete blood count (CBC), glucose, albumin,cholesterol, triglycerides, high-density lipoproteincholesterol (HDL-cholesterol), low-density lipo proteincholesterol (LDL-cholesterol), and kidney functionparameters: serum creatinine levels and GFR.Regarding immune parameters, complement C3 (C3)and complement C4 (C4), anti-antinuclear antibodies(ANA), and anti-double stranded DNA antibodies(anti-ds-DNA Ab) were monitored. Complete urineanalysis for urinary casts, erythrocyturia, pyuria, andproteinuria 24-hour and urine culture were monitored.
Statistical analysis
The data were analysed using the StatisticalPackage for the Social Sciences IBM-SPSS, version26.0. Categorical variables were presented as frequencyand were analysed using the Chi-square test.All continuous variables are presented as median(interquartile range: 25–75th percentile) or mean±standard deviation for the data that are not normallyor normally distributed, respectively. The Kolmogorov-Smirnov test was used to test the normality ofdata distribution. For intergroup comparisons, theMann-Whitney test for non-parametric variables wasused. Spearmen’s coefficient correlation tested therelationship between variables. Statistical significancewas defined as p<0.05 for all comparisons.
Results
Basic demographic, clinical, and laboratoryparameters of patients with LN, as well as with andwithout MetS, are shown in Table 1.
Table 1
Basic characteristics of our patients with LN collectively and divided according to the presence of MetS.
* Chi-square test; # Mann-Whitney test (bold values are significant)<br>MetS – metabolical syndrome; nMetS – non-metabolical syndrome
| Parameters | LN 67 | MetS 24 | nMetS 43 | p-value |
|---|---|---|---|---|
| Sex: male/ female N, % | 13 (19.4)/54 (80.6) | 8 (33.3)/16 (66.7) | 5 (11.6)/38 (88.4) | 0.031* |
| Age (years) | 41 (31–55) | 54 (43–59) | 36 (30–43) | 0.001# |
| BMI (kg/m2) | 24.6 (22.9–28.6) | 29.75 (25.22–32.92) | 23.40 (21.50–24.80) | <0.001# |
| Systolic blood pressure | 130 (120–135) | 135 (130–140) | 120 (110–130) | 0.002# |
| Diastolic blood pressure | 80 (70–85) | 80 (72.5–90.0) | 80 (70–85) | 0.181# |
| Smoking | 20 (29.8) | 14 (58.3) | 6 (14.0) | <0.001* |
| CRP (mg/L) | 3.45 (3.10–4.90) | 3.45 (3.11–4.77) | 3.45 (2.97–5.10) | 0.699# |
| RBC (109 g/L) | 4.12 (3.70–4.55) | 3.93 (3.51–4.59) | 4.15 (3.94–4.53) | 0.224# |
| Hb (g/L) | 118 (107–126) | 115.50 (98.50–130.50) | 120 (112–125) | 0.534# |
| WBC (109 g/L) | 6.24 (4.87–7.94) | 6.55 (5.19–7.88) | 5.52 (4.43–8.05) | 0.221# |
| PLT (109 g/L) | 202 (178–254) | 206.50 (174.25–252.00) | 199 (180–256) | 0.880# |
| Triglyceride (mmol/L) | 1.62 (1.32–2.11) | 1.94 (1.73–2.73) | 1.48 (1.20–1.64) | <0.001# |
| Cholesterole (mmol/L) | 5.61 (4.80–6.51) | 6.25 (4.43–6.91) | 5.60 (4.88–6.23) | 0.855# |
| HDL-cholesterol (mmol/L) | 1.70 (1.40–1.96) | 1.62 (1.05–1.91) | 1.80 (1.50–1.99) | 0.131# |
| LDL cholesterol (mmol/L) | 3.50 (2.81–4.12) | 3.74 (2.50–4.20) | 3.50 (2.89–3.99) | 0.917# |
| Glucose (mmol/L) | 4.60 (4.40–5.20) | 5.10 (4.40–5.77) | 4.60 (4.40–5.00) | 0.067# |
| Creatinine (μmol/L) | 79 (67–109) | 95.50 (72.25–123.25) | 77.00 (64.00–94.00) | 0.027# |
| Albumin (g/L) | 38 (32–41) | 34.00 (28.25–40.00) | 39.00 (35.00–41.00) | 0.050# |
| GFR (mL/min/1,73 m2) | 78.42 (60.10–102.51) | 66.30 (51.15–89.91) | 83.01 (68.90–109.76) | 0.020# |
| Proteinuria (g/24h) | 1.04 (0.25–3.60) | 1.68 (0.37–6.00) | 0.41 (0.24–3.20) | 0.055# |
| SLEDAI/r | 1 (0–6) | 3.50 (0–6.75) | 1 (0–5) | 0.093# |
| C3 complement (g/L) | 0.81 (0.65–0.90) | 0.76 (0.63–0.97) | 0.81 (0.65–0.85) | 0.979# |
| C4 complement (g/L) | 0.13 (0.09–0.17) | 0.14 (0.11–0.17) | 0.12 (0.08–0.17) | 0.192# |
| ANA (IU/mL) | 2 (0–3) | 2.00 (1.00–3.00) | 1.00 (0.00–13.00) | 0.968# |
| Anti ds DNA Ab (IU/mL) | 40 (15–100) | 47.50 (20.00–100.00) | 15.00 (15.00–100.00) | 0.195# |
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Comparing patients with LN collectively as wellas those with and without MetS, we found statisticalsignificance for age. Patients with MetS were older(p=0.001). BMI was significantly higher (p<0.001)in the group with MetS; the average BMI was29.89±4.85 kg/m2 (in the group without MetS23.35±2.70 kg/m2), while for the collective group ofpatients, it was 24.69±4.77 kg/m2. A statistically significantdifference was obtained with smokers in thegroup with MetS (p<0.001). Also, in the group withMetS, systolic blood pressure was statistically significantlyelevated (p=0.002). Comparing laboratory analyses, a statistically significant difference wasobserved for triglycerides (p<0.001), albumin(p=0.050), and renal function parameters: creatinine(p=0.027) and GFR (p=0.020). Proteinuria wasincreased in the group with MetS, but in the comparison,a value at the limit of significance was obtained(p=0.055). MetS was present in 15 (44.11%)patients with active LN and in patients with LN inremission in 9 (27.27%). Table 2 and Table 3 showbasic clinical and laboratory parameters in patientswith active LN and LN in remission.
Table 2
Characteristic clinical and laboratory parameters of patients with active LN according to the prevalence of MetS.
Mann-Whitney test (bold values are significant)<br>MetS – metabolical syndrome; nMetS – non-metabolical syndrome
| LN – active | |||
|---|---|---|---|
| Parameters | MetS (15/34) | nMetS (19/34) | p |
| BMI (kg/m2) | 29.80 (24.60–33.50) | 23.20 (21.50–24.70) | <0.001 |
| Glucose (mmol/L) | 5.10 (4.30–5.80) | 4.60 (4.40–4.80) | 0.302 |
| Triglyceride (mmol/L) | 2.29 (1.72–3.11) | 1.50 (1.30–1.70) | 0.001 |
| HDL-cholesterol (mmol/L) | 1.69 (1.04–1.96) | 1.70 (1.50–1.96) | 0.336 |
| Systolic blood pressure (mmHg) | 135 (130–140) | 120 (110–130) | 0.027 |
| Diastolic blood pressure (mmHg) | 80 (80–90) | 80 (70–80) | 0.202 |
| CRP (mg/L) | 3.48 (2.97–5.29) | 3.47 (0.96–5.80) | 0.732 |
| Creatinine (μmol/L) | 111 (70–137) | 71 (64–87) | 0.096 |
| C3 (g/L) | 0.72 (0.45–0.77) | 0.72 (0.52–0.76) | 0.973 |
| C4 (g/L) | 0.13 (0.10–0.19) | 0.08 (0.05–0.12) | 0.043 |
| Proteinuria (g/24h) | 3.72 (1.90–9.70) | 3.20 (1.75–4.10) | 0.179 |
| SLEDAI/r | 6 (4–7) | 6 (3–6) | 0.179 |
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Table 3
Characteristic clinical and laboratory parameters of patients with LN in remission according to the presence of MetS.
Mann-Whitney test (bold values are significant)<br>MetS – metabolical syndrome; nMetS – non-metabolical syndrome
| LN – in remission | |||
|---|---|---|---|
| Parameters | MetS (9/33) | nMetS ( 24/33) | p |
| BMI (kg/m2) | 29.60 (25.60–32.30) | 23.60 (21.60–26.22) | <0.001 |
| Glucose (mmol/L) | 5.20 (4.40–6.60) | 4.65 (4.32–5.00) | 0.121 |
| Triglyceride (mmol/L) | 1.82 (1.73–2.25) | 1.39 (1.09–1.61) | 0.016 |
| HDL-cholesterol (mmol/L) | 1.60 (1.23–1.87) | 1.80 (1.50–2.08) | 0.272 |
| Systolic blood pressure (mmHg) | 135 (130–140) | 120 (116.25–133.75) | 0.029 |
| Diastolic blood pressure (mmHg) | 80 (70–90) | 80 (70–85) | 0.592 |
| CRP (mg/L) | 3.20 (3.13–4.10) | 3.43 (3.00–4.25) | 0.921 |
| Creatinine (μmol/L) | 79 (73.5–110.5) | 78.50 (64.75–102.25) | 0.414 |
| C3 (g/L) | 0.98 (0.87–1.08) | 0.84 (0.81–1.00) | 0.207 |
| C4 (g/L) | 0.15 (0.13–0.16) | 0.14 (0.12–0.19) | 0.921 |
| Proteinuria (g/24h) | 0.28 (0.14–0.78) | 0.25 (0.15–0.36) | 0.677 |
| SLEDAI/ r | 0 (0–0.5) | 0 (0–1) | 0.766 |
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We obtained a statistically significant differencefor MetS parameters (BMI, triglycerides, systolic bloodpressure) in LN with active disease and LN in remission.Table 4 shows the prevalence of certain MetSparameters in our patients.
Table 4
The frequency of certain parameters of MetS in thegroup with LN.
| LN (n=67) | |
|---|---|
| MetS, n (%) | 24 (35.8) |
| BMI>30, n (%) | 14 (20.9) |
| BMI, median (IQR) | 24.60 (22.90–28.60) |
| Hypertriglyceridiemia, n (%) | 32 (47.8) |
| Triglyceride, median (IQR) | 1.62 (1.32–2.11) |
| Low HDL-cholesterol, n (%) | 19 (28.4) |
| HDL-cholesterol, median (IQR) | 1.70 (1.40–1.96) |
| Arterial hypertension, n (%) | 50 (74.6) |
| Systolic blood pressure, median<br>(IQR) | 130 (120–135) |
| Diastolic blood pressure, median<br>(IQR) | 80 (70–85) |
| Hyperglycemia, n (%) | 9 (13.4) |
| Glucose, median (IQR) | 4.60 (4.40–5.20) |
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In Table 4, we have shown the prevalence ofcertain MetS parameters in our patients with LN. Themost prevalent was arterial hypertension (74.6%),dyslipidemia: increased triglycerides (47.8%), decreased HDL-cholesterol (28.4%), BMI in 20.9%, andhyperglycemia was observed in 13.4% of patients.
MetS correlated with parameters of renal function:GFR and creatinine and with albumin, erythrocyturia,and borderline significance for proteinuria(p=0.054) were also noted, as shown in Table 5. Ifwe look at the correlations between individual elementsof MetS with parameters that are significant fordisease activity in our patients with LN, we note thatBMI correlates significantly with GFR, creatinine, anderythrocyturia. The level of serum triglycerides correlatesstatistically significantly with anti-ds-DNA Ab,and urinary parameters: erythrocyturia, proteinuria,and SLEDAI/r index, and HDL cholesterol with albumins,complement C3, and anti-ds-DNA Ab. Arterialhypertension correlates significantly with renal functionparameters GFR and creatinine.
Table 5
Correlation of MetS and significant LN parameters.
Spearman’s correlation rank (bold values are significant)
| MetS | GFR | Creatinine | Albumin | C3 | ANA | ds DNA<br>Ab | Er/u | Protein/<br>u 24h | SLEDAI/r | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| MetS | r | 1.000 | -0.286 | 0.273 | -0.241 | -0.00, | 0.005 | 0.162 | 0.258 | 0.237 | 0.206 |
| p | 0.019 | 0.025 | 0.049 | 0.979 | 0.968 | 0.197 | 0.035 | 0.054 | 0.094 | ||
| BMI | r | 0.656 | -0.307 | 0.281 | -0.099 | 0.025 | -0.042 | 0.019 | 0.251 | 0.065 | 0.072 |
| p | 0.000 | 0.011 | 0.021 | 0.426 | 0.839 | 0.734 | 0.879 | 0.040 | 0.603 | 0.564 | |
| Trygliceride | r | 0.533 | -0.156 | 0.195 | -0.233 | -0.211 | 0.111 | 0.256 | 0.295 | 0.308 | 0.253 |
| p | 0.000 | 0.208 | 0.144 | 0.058 | 0.086 | 0.370 | 0.040 | 0.015 | 0.011 | 0.039 | |
| HDL-cholesterol | r | -0.186 | -0.115 | 0.041 | 0.334 | 0.290 | -0.111 | -0.246 | -0.068 | -0.223 | -0.168 |
| p | 0.132 | 0.355 | 0.740 | 0.006 | 0.017 | 0.371 | 0.048 | 0.583 | 0.070 | 0.174 | |
| Glucose | r | 0.225 | -0.206 | 0.184 | -0.041 | 0.033 | 0.040 | -0.028 | 0.077 | 0.013 | 0.022 |
| p | 0.067 | 0.095 | 0.136 | 0.741 | 0.793 | 0.749 | 0.828 | 0.538 | 0.916 | 0.860 | |
| Arter.<br>hypertension | r | 0.247 | -0.250 | 0.280 | -0.217 | 0.012 | -0.003 | -0.011 | 0.064 | 0.124 | 0.073 |
| p | 0.044 | 0.041 | 0.022 | 0.077 | 0.922 | 0.984 | 0.928 | 0.605 | 0.319 | 0.558 |
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Discussion
MetS and LN, as the renal manifestation of SLE,represent two causally related entities. Patients withactive LN have a higher frequency of MetS than thosewith LN in remission. MetS further aggravates LNwith its components, damaging many organs and systems.Previous studies mainly described patients withSLE as a target group and indicated the severity ofMetS, while much fewer described the associationbetween MetS and LN [7][8][9].
Patients with SLE and LN have accelerateddevelopment of atherosclerosis, which is conditionedby the action of traditional risk factors (smoking, dyslipidemia,arterial hypertension, diabetes mellitus,increased BMI) and the immuno-inflammatory effectof the disease, while the mechanism of this processhas not yet been fully clarified [16][12]. The treatmentof SLE involves not only the treatment of theimmune process but also the prevention of cardiovascularcomplications and atherosclerosis. According tomany findings, endothelial dysfunction is the basis ofthe development of atherosclerosis, and SLE is anindependent factor of endothelial dysfunction [17][18]. The results of a multicenter study by Parker et al.,[8]. which included 1150 patients with SLE, describea prevalence of MetS of 38.2% and also indicate thatlupus nephritis and active disease are significant factorsin the development of MetS, where the early useof antimalarials had a protective effect. A meta-analysisby Lu et al. [19], which included the results of 20studies, shows that patients with LN have twice therisk of developing cardiovascular diseases (atherosclerosis,myocardial infarction, stroke, peripheral vasculardisease, heart failure) compared to patients withSLE (who have a 2–10 times higher risk compared tothe general population).
Sharma et al. investigated subclinical atherosclerosisin patients with SLE and LN by measuringthe thickening of the intima-media of the carotidartery complex and showed that patients with LNhave a higher risk of developing atheroscleroticchanges in the carotid arteries [20].
In our group of patients with LN, MetS wasobserved in a similar percentage (35.82%) as in otherauthors [8]. We observed that in 44.1% of patientswith active LN, MetS was manifested initially, while inpatients with LN in remission, MetS was observed in27.2% of cases. According to the age distribution,patients with LN and MetS were significantly older,and, quite expectedly, BMI, arterial hypertension, andsmoking were significantly more prevalent in thisgroup.
The prevalence of obesity in SLE was 28–50%and was associated with dyslipidemia and atherosclerosis,with older age, lupus nephritis, arterial hypertension,duration of the underlying disease, and corticosteroidtherapy [21][22]. Obesity was statistically significantly associated with the development of LNduring the follow-up of patients with SLE, accordingto a study by Kang et al. [23]. Elevated BMI in ourpatients with LN was represented in a slightly lowerpercentage of 20.9% for BMI >30 kg/m2, and 41.7%for BMI 25–29 kg/m2. Sun et al. described arterialhypertension in 91% of patients with LN, where theaverage values of systolic blood pressure of theirpatients were 130.7±15.5 mmHg and diastolicblood pressure 78.2±10.3 mmHg [9]. Arterial hypertension,as an important predictor of adverse cardiovascularoutcomes in the general population, waspresent in 91.6% of our patients with LN and MetS,and in the total number of patients with LN, arterialhypertension was present in 74.6% of patients.
In our patients with LN, the systolic blood pressurewas higher than that described by other authorsand was 140.93±11.42 mmHg, as well as the diastolicblood pressure (84.61±7.40 mmHg). Theseelevated arterial pressure values were associated withactive kidney lesions in LN and elevated immuneparameters. Patients with SLE had arterial hypertensionin 58.2% and obesity in 12.4%, according to thestudy by Katz et al. [24], and a similar percentage of58.4% was described by Hanly et al. [25] in an internationalcohort study [25], in contrast to our patients,who had a higher percentage of arterial hypertension.
The difference between the subjects explainssuch a high percentage of arterial hypertension in ourpatients. Katz et al. [24] described a group of patientswith SLE, while our group was represented by patientswith LN, which was the most severe manifestation ofSLE. In the study by Hanly et al., a group of patientswith LN was described who had elevated BMI on average5.9% of patients, in contrast to ours (20.9%),which resulted in higher arterial hypertension.
One of the important characteristics of the MetSin SLE is atherogenic dyslipidemia, most oftenreduced HDL-cholesterol, elevated triglycerides, andLDL-cholesterol is usually within reference limits. It isconsidered that the role of HDL-cholesterol in SLE isvery important from the aspect of the anti-inflammatoryresponse, and some studies have shown that theinfusion of HDL-cholesterol reduces atheroscleroticplaque in an animal model [26][27]. Sun et al. [9]describe dyslipidemia in LN in 45.5% of patients.Dyslipidemia is also very common in our patients:hypertriglyceridemia 47.8%, hypercholesterolemia59.7%, and lowered HDL-cholesterol (28.4%). Ourpatients with LN also had elevated LDL cholesterol,which further increased the risk of developing cardiovascularcomplications.
Lin et al. indicate that patients with newly diagnosedSLE have a 22% higher risk compared to thecontrol group for the development of diabetes mellitusin the next three years, whereby insulin resistanceis influenced by diseases and applied therapy (corticosteroids,calcineurin inhibitors), genetic factors, race and other factors [28]. All this indicates that inpatients with SLE, regular controls are necessary –fasting plasma glucose level and glycated hemoglobin,control of the therapeutic level of calcineurininhibitors in the blood, reduction of the maintenancedose of corticosteroids, as well as adherence to adietary regime of nutrition.
A study by Salmasi et al. [29], which included1498 patients with SLE, showed a protective effect ofantimalarial drugs that reduced the risk of diabetesmellitus in these patients by 39%, mainly by reducingthe need for high doses of corticosteroids at the sametime.
Our patients had manifested hyperglycemia in13.4% of cases, which is a lower percentage than thatdescribed by other authors [29][30]. We believe manyfactors contributed to this: our patients were younger,their BMI was lower, and they might have been morecareful with the recommended diet.
Many studies indicate an association betweenrenal function parameters and MetS, i.e., anincreased cardiovascular risk that is accompanied byelevated creatinine and MetS. In a study by Bultinik etal. [31] multivariate analysis of the metabolic syndromescore and clinical and therapeutic variableswas used to obtain statistical significance for age,ESR, complement C3, creatinine, and intravenouscorticosteroid therapy. These authors note that corticosteroidtherapy affects the worsening of arterialhypertension, dyslipidemia, obesity in patients withSLE, and especially in patients with lupus nephritisand lupus CNS, as the most severe manifestations ofSLE, bearing in mind that intravenous doses of corticosteroidsare applied much more often [31].
In our patients, we observe a statistically significantcorrelation of MetS with kidney function parameters(creatinine and GFR), but also with albumin anderythrocyturia, which is similar to the results of otherstudies [31].
Kidney failure, which represents poor prognosticparameters in LN, was more pronounced in the groupof patients with active LN and MetS. It confirms thatthis is a group of patients with an increased risk for apoor outcome. A decrease in serum albumin andmanifested erythrocyturia were also observed, whichare important parameters for LN activity, and their significantcorrelation with MetS indicates the connectionof these unfavorable factors and the necessity ofcareful monitoring of these patients and implementationof timely treatment.
Also, when correlating the individual parametersof MetS with parameters significant for LN activity, wenotice that dyslipidemia (elevated triglycerides anddecreased HDL-cholesterol level) significantly correlates with many parameters for disease activity.Triglycerides are statistically significantly correlatedwith anti-ds-DNA Ab and urinary parameters: erythrocyturia,proteinuria, SLEDAI/r index, and HDL-cholesterolcorrelated with albumin, C3, and anti-ds-DNA Ab. In our group, arterial hypertension as aparameter of MetS shows a significant correlationwith parameters of renal function: creatinine andGFR.
The results of our study indicate the necessity ofa multidisciplinary approach to patients with LN, so inaddition to achieving remission of glomerulonephritis,we could also influence other adverse conditions(MetS) and ensure a favorable course of the diseaseand better survival of our patients.
However, in our opinion, a limitation of ourstudy was related to the presented number of patientswho had LN and MetS. The sample size most likelylimited the statistical significance of the correlationbetween MetS elements and certain parameters ofactive renal lesions (complement level, proteinuria,SLEDAI/r index), but individual MetS parameters(triglyceride and HDL cholesterol levels) showed thatsignificance. This is also why we believe that futurestudies with more patients with active LN and manifestedMetS could better define this relationship.
Conclusions
The presence of MetS in our LN patients wasassociated with age, more severe impairment of renalfunction, and smoking. The most common parametersof MetS were arterial hypertension and dyslipidemia,which are significantly correlated with diseaseactivity parameters, indicating an increased risk ofcardiovascular complications in this group of patients.
This is also the reason to highlight the need fortimely detection and treatment of MetS componentsin patients with LN. Bearing in mind that LN activityand cardiovascular complications are very significantpredictors of an unfavorable outcome, detailed follow-up of these patients could influence a more favorablecourse and delay the progression of the disease.
Dodatak
Statement of ethics
Our institution’s Ethics Committee approved thestudy, and oral informed consent was obtained fromall patients.
Conflict of interest statement
All the authors declare that they have no conflictof interest in this work.
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