The Relationship Between Dyslipidemia and Lupus Nephritis in Systemic Lupus Erythematosus Patients Attending a Saudi Rheumatic Center, Tabuk

Background: There is an increasing awareness of the role of dyslipidemia in lupus nephritis patients, no researchers have studied dyslipidemia in systemic lupus erythematosus (SLE) in Tabuk. In this study, we aimed to investigate the association between dyslipidemia and lupus nephritis in Tabuk, Saudi Arabia. Methods: This cross-sectional comparative longitudinal hospital-based study was conducted at a rheumatic clinic in the North West Armed Force Hospital (NWAFH) during the period April 2014–June 2015. Seventy-three patients diagnosed with SLE were invited to participate in the study. All participants were required to sign a written informed consent, following which they were interviewed using a structured questionnaire. Data collected include demographic data, clinical characteristics, fasting lipid proﬁle, renal function tests, urine analysis, antinuclear antibody, anti-double-stranded antibodies, complement levels, serum albumin, anticardiolipin, ant bodies, and antiphospholipid antibodies. Lupus nephritis was ascertained by renal biopsy. The research was approved by the ethical committees of both the University of Tabuk and the NWAFH and data were analyzed using the Statistical Package for Social Sciences (SPSS). Results: Out of 73 patients with SLE, 86.3% were females with a mean age of 34 ± 6.4 years. Lupus nephritis was evident in 26% of the patients, proteinuria in 44.1%, high total cholesterol in 17.8%, high low-density lipoprotein in 15.1%, high triglycerides in 27.3%, and low high-density lipoproteins in 52.1%. Patients with lupus nephritis had high total cholesterol, high LDL, high TG, and low HDL than those without lupus nephritis p < 0.05. Conclusion : Dyslipidemia was more common among patients with SLE nephritis, and an aggressive treatment is recommended to reduce this serious complication. The relatively small size of the study group and the fact that the study was conducted at a single tertiary center are the limitations of this study. A structured sociodemographic data and clinical characteristics including lupus nephritis based on renal biopsy ﬁndings, myocardial infarction, stroke, infections, hypertension, pre-hypertension, and hypotension. All patients were in remission at the time of lipid measurements as indicated by serological markers. Patients with active disease were excluded from the study as well as those on steroid dose >10 mg/day, diabetic patients, patients with nephrotic range proteinuria, those with chronic liver disease or active malignancy, patients diagnosed with familial dyslipidemias, active thyroid disorders, and patients on oral contraceptive pills. The following investigations were undertaken:


Introduction
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease found in women in their childbearing age; nearly one-fifth of the cases occur in the first two decades of a woman's life. The disease runs a remitting-relapsing course with breakout difficult to control. Cardiovascular disease is the most common cause of death among patients that acquire the disease for more than five years [1].
Accelerated atherosclerosis and premature ischemic heart disease are common causes of mortality and morbidity among patients with SLE. Increasing age is a risk factor for coronary heart disease but unlike the general population, young women with SLE are more affected. The potential for cardiovascular disease including myocardial infarction, cerebrovascular and peripheral arterial disease in young women with SLE is approximately double than that in the general population [2,3].
Several pathophysiological mechanisms mediate coronary heart disease including atherosclerosis, arteritis, thrombosis, spasm, embolization, and abnormal coronary flow [4]. It is strongly suggested by epidemiological studies that in addition to conventional coronary risk factors, there are non-classical risks in SLE patients, in fact, SLE is considered an independent risk factor for atherosclerosis [5,6].
A recently published research concluded that regardless of food intake and nutritional status, preserved kidney function, low disease activity, and low steroid dose, adolescent females with SLE have proatherogenic lipid biomarkers that may contribute to atherosclerosis risks [7].
In this regard, dyslipidemia was found to be prevalent in SLE patients (55-77%), especially among those with active disease, heavy proteinuria, and concomitant medications. Furthermore, cardiovascular complications are the leading cause of death among SLE patients with renal failure, and renal impairment was found to be associated with dyslipidemia [8].
No researcher has studied dyslipidemia in SLE patients in Tabuk, Saudi Arabia. Thus, the present study was conducted to investigate the relationship of dyslipidemia among patients with SLE in Tabuk.

Materials and Methods
This cross-sectional descriptive, longitudinal, hospital-based study was conducted between June 2014 and April 2015 among patients attending the rheumatic outpatients' For the purpose of this research, the following definitions were adopted: • Hypertension: self-reported, on antihypertensive therapy, history of systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg. The ethical committee of the University of Tabuk and the local committee approved the research, and the Statistical Package for Social Sciences was used for data analysis.
The Chi-square test was used to compare categorical data, and data were presented as a mean ± SD and percentages unless otherwise specified with a p < 0.05 considered as significant.

Results
Female dominance (86.3%) was obvious in the 73 studied patients, their age ranged from 20 to 50 years with a mean age of 34 ± 6.4 years. Lupus nephritis was found in 26% of the patients, stroke was evident in 8.2%, while myocardial infarction was concluded in 1.4% of the SLE patients. Other clinical characteristics are shown in Table 1.  Table 3).  Table 5 shows the relationship between lipid profile and neuropsychiatric manifestations. The relationship between the serum albumin and lipid profile are shown in Table 7 in which the total cholesterol was 4.86 ± 1.38 mmol/l in patients with low serum albumin vs 4.48 ± 0.46 mmol/l in patients with normal serum albumin with no statistically significant difference of p = 0.337; TG was 1.26 ± 0.59 mmol/l vs 1.87 ± 1.30 in patients with low and normal serum albumin, respectively, with p = 0.114; LDL was 2.91 ± 0.71 mmol/l among patients with low albumin vs 2.78 ± 0.48 in normal serum albumin patients with p = 0.583; while HDL level was 1.14 ± 0.27 mmol/l and 1.14 ± 0.23 among patients with low and normal serum albumin, respectively, with p = 0.933.

Discussion
Advances in immunosuppressive therapy and supportive care have improved the survival and short-term clinical outcomes of SLE patients, with a substantial improvement in the cardiovascular morbidity and mortality, there is an increasing awareness of dyslipidemia as a major vascular risk among these patients [11].
The present data showed high total cholesterol in 17.8%, high LDL in 15.1%, high triglycerides in 27.3%, and low HDL in 52.1% of SLE patients, hypercholesterolemia was higher than in an epidemiological study conducted among Saudi patients [12] and hypercholesterolemia was found in 8.5%. A study published in Jakarta found high total cholesterol, high LDL, high triglycerides, and low HDL in 43%, 26.4%, 44.2%, and 26% of SLE patients, respectively [13]. The difference in the percentages of the lipid profile can be attributed to genetic and dietary factors and the level of exercise in the two studies.
Formiga et al. [14] reported that 55% of young premenopausal SLE women with In the current study the total serum cholesterol in SLE patients with lupus nephropathy was 5.4 ± 1.4 mmol/l and was positively correlated with proteinuria and lupus nephritis; similarly, Tisseverasinghe et al. found that the serum cholesterol exceeds 5.2 mmol/l in SLE patients and was associated with mortality and adverse renal outcomes [17].
Previous literature concluded that hyperlipidemia will enhance renal immune complex-mediated complement activation and development of nephritis, in the current study, hyperlipidemia was positively correlated with proteinuria and lupus nephritis confirming the aforementioned observation [18]. In the present study, a correlation was found between hypocomplementemia and dyslipidemia that can be explained by the small size of our study.
In the present study, low-density lipoprotein was high in 14.8% and was in positive correlation with proteinuria and SLE nephropathy, in accordance with Olusi and George who concluded a prevalence of atherogenic LDL in 52% of SLE patients [19].

Limitations:
The study limitation was the small size of the study group, also we could not control for the therapy taken for SLE treatment like hydroxychloroquine which can decrease the lipids through various mechanisms.

Conclusion
Dyslipidemia was found to be higher among patients with SLE compared to the Saudi general population and was positively correlated with SLE nephropathy and proteinuria.
Aggressive treatment of dyslipidemia could decrease nephropathy and overall cardiovascular risk.