European Journal of Cardiovascular Medicine

Chronic kidney disease (CKD) is a growing health issue that poses both medical and financial challenges. For patients with CKD, kidney transplantation represents the best treatment option. Unfortunately, this option is often unattainable for many CKD patients, especially in developing countries like India. [1] Hemodialysis (HD) is a common alternative chosen by patients when kidney transplantation is not feasible. HD has been shown to prolong the lives of these individuals successfully. While HD effectively addresses metabolic issues, it also presents risks, including various infections, imbalances in electrolytes, sudden cardiac death, complications from HD such as dialysis disequilibrium syndrome, hypertension, cerebrovascular events, and oxidative stress.[2,3] Research indicates that CKD patients face an increased risk of heart disease, CKD-mineral bone disorders, electrolyte discrepancies, ongoing inflammation, and lipid metabolism abnormalities.[4] Individuals with end-stage renal disease (ESRD) undergoing HD have been found to have a significantly elevated risk of coronary atherosclerosis compared to healthy individuals.[5]

Elevated total cholesterol (TC), high levels of low-density lipoprotein (LDL) cholesterol, increased triglycerides (TG), and low levels of high-density lipoprotein cholesterol (HDL-C) are all recognized potential contributors to the development of cardiovascular disease (CVD) in the general population. Additionally, both mortality and morbidity are associated with lipid abnormalities, both qualitative and quantitative, in patients with chronic kidney disease (CKD), whether they are receiving hemodialysis or

have undergone transplantation.6-8 Typically, CKD patients exhibit increased TG levels, reduced serum HDL-C, and a higher proportion of lipoprotein-a (Lp-a).9 Nevertheless, patients undergoing maintenance hemodialysis (MHD) often show decreased cholesterol levels. It is crucial to note that there is an inverse relationship between cholesterol levels and mortality among CKD patients.10

Hypercholesterolaemia's connection to lower mortality rates and low total cholesterol (TC) levels being associated with higher mortality in patients undergoing maintenance hemodialysis (MHD) may be related to the interplay of malnutrition, inflammation, and arteriosclerosis.11,12 According to patient history, most individuals visiting the artificial kidney department (AKD) for hemodialysis in this tertiary care government facility come from lower socioeconomic backgrounds. Moreover, research is scarce regarding the serum lipid profile in chronic kidney disease (CKD) patients undergoing MHD, particularly from the western region of India. Given the cardiovascular disease (CVD)-related mortality among patients on hemodialysis, we aim to examine the serum lipid profile in CKD patients receiving long-term MHD treatment and assess the changes before and after hemodialysis.

This study aims to investigate lipid abnormalities in individuals with Chronic Kidney Disease, both those with diabetes and those without, as well as to emphasize the importance of early intervention to avert cardiovascular and other complications. 

OBJECTIVES

1. To estimate the prevalence of lipid abnormalities in chronic kidney disease patients.
2. To evaluate the Quantitative assessment of lipid abnormalities in chronic kidney disease patients.

Study Design:  Hospital-based, cross-sectional study.

Study area: The study was conducted in the Department of General Medicine at Narayana Medical College, Nellore.

Study period: 1 year.

Sample size: The study consisted of a total of 30 subjects and 30 controls.

Sampling Technique:  Simple Random technique.

Inclusion Criteria:  Patients with chronic kidney disease.

Exclusion criteria:  Patients with dyslipidemia due to other causes like Hypothyroidism, ethanol, liver diseases, AIDS, and genetic disorders of dyslipidemia are excluded from the study. 

Ethical consideration: Institutional Ethical Committee permission was obtained before the commencement of the study.

Study tools and Data collection procedure:

Diagnostic Criteria for Chronic Kidney Disease:

1. Clinical signs and symptoms of uremia.
2. Patients with serum creatinine >1.5 mg/dL.
3. Bilateral shrunken kidney/loss of corticomedullary differentiation on ultrasonography of the abdomen.

All the selected patients were subjected to detailed history and complete physical examination, and data collected was noted serially in a pre-designed proforma.

Estimation of Lipid Profile: The serum total cholesterol and triglyceride levels were measured by colorimetric test, and HDL cholesterol was measured by precipitation assay.

The cholesterol ratios then were calculated by using the total cholesterol / HDL cholesterol and LDL cholesterol / HDL cholesterol ratios. All the blood samples were 12-hour fasting samples.

Estimation of LDL Cholesterol: The LDL fraction was mathematically derived using the Friedewald formula as follows:

Estimation of VLDL:

STATISTICAL ANALYSIS:

Continuous variables were expressed as the mean ± standard deviation (SD), and the categoric variables were expressed as a percentage. The student‘s t-test was used to compare lipid values and ratios. A two-tailed P ‘value of < 0.05 was considered to be significant.  

TABLE NO 1: AGE AND SEX DISTRIBUTION

In the present study,50 patients with Chronic Kidney Disease were included, out of which 37 patients (74%) are males and 13 patients (26%) are females. On decade-wise grouping, we found a maximum number of patients are between 41-50 years (36%) followed by between 51-60 years (22%). The mean age for the total number of patients was 48.7±13.6. The mean age for male patients is 48.243±13.367. The mean age for female patients is 49.923±14.801.

TABLE NO.2: AETIOLOGY OF CKD

Type 2 DM is found to be the most common etiology (38%) for CKD both in male patients (63.15%) as well as female patients (36.8%). HTN follows diabetes as a common etiology for CKD (32%).

The number of cases about duration of CKD, from its initial detection, we found, in our study, maximum number of cases were of <1 Year duration (56%), followed between 1 -2 years of duration (22%) and of > 2 years of duration (22%).

In this table, we found in our study that the maximum number of Patients with type 2 DM (52.6%) with a duration of 5-15 years developed CKD. In hypertensive patients, the maximum number of patients with a duration between 5 -15 years (75%) developed CKD. Patients with less than 5 years of duration of chronic glomerulonephritis, obstructive uropathy and chronic pyelonephritis developed CKD. The aetiology for CKD was not known in 8 number of Patients.

Mean hemoglobin percentage was 7.82±1.40              when serum creatinine was <4 mg/dl, 7.335±1.20 when serum creatinine was 4 – 8mg/dl, and 7.27±1.27 when serum creatinine was >8 mg/dl. A maximum number of patients (40%) had serum creatinine between 4 – 8mg/dl with mean Hb% of 7.335±1.20 and >8 mg/dl with mean Hb of 7.27±1.27. We found out of 50 patients, 5 patients (10%) had coronary artery disease (CAD) and 1patients (2%) had cerebrovascular disease (CVD) as the commonest vascular complications.

We found that,    out of     50 patients, 31 patients (62%) had normal ECG.11 patients (22%) had LVH as thecommonest ECG changes, followed by IHD in 6 patients (12%) and hyperkalamia in 2 patients (4%).  We found that 34% of           patients had DR, 14% had HR, and 2% of patients had both DR and HR.

TABLE NO.3: BIOCHEMICAL INVESTIGATIONS IN CHRONIC KIDNEY DISEASE PATIENTS

TABLE NO.4: LIPID PROFILE AMONG CKD PATIENTS

TABLE NO.5: LIPID ABNORMALITIES DIFFERENCE IN TOTAL CHOLESTEROL

In this study, 23 patients (46%) had serum cholesterol in the desirable range,10 patients (20%) had borderline high and 7 patients(14%) were in high range i.e,> 240 mg/dl.

Mean total cholesterol is as follows:

Mean (total)         =             196.3 + 45.46

Mean (males)      =             214.70  59.34

Mean (females)   =             227.53  35.01

As compared to desirable and borderline among males,t=10.63 P<0.001 is statistically high significant. Compared to borderline and high among males,t=6.82 P<0.001 is statistically highly significant. As compared to desirable       and border line. Females, t=0.030, p>0.05 statistically insignificant. Compared to borderline high and high among females, t=5.69, P<0.001 is statistically highly significant. As compared to males and females in the desirable range, there is Statistical significance, t=4.554,p<0.05. As compared to males and females in the borderline group, there is no statistical significance, t=0.20, p>0.05, hence statistically insignificant. As compared to males and females in the high group, t=0.378, p value>0.05, which is statistically insignificant.

TABLE NO. 6: DIFFERENCE IN SERUM TRIGLYCERIDES

As compared to <150 and 150-199 among males, t= 9.241, P<0.001 is statistically highly significant. As compared to borderline high and high among males, t=5.047 P<0.001 is statistically highly significant. As compared to <150 and 150 – 199 among females, t=4.268, P<0.05 is statistically significant. As compared to borderline high and high among females, t=2.857, p<0.05 is statistically significant. As compared to <150 mg/dl, among males and females, t=1.812, p>0.05 is statistically insignificant. As compared to the borderline high between male and females, t=0.583, p>0.05 is statistically insignificant. As compared to high values between males and females, t=0.649 P>0.05 is statistically insignificant.

Table No. 7: Difference in Serum HDL Cholesterol levels

As compared to Serum HDL-C between 50 – 60 and 41 – 50 mg/dl among males, t=2.894, p<0.05 statistically significant. As compared to Serum HDL-C between 41 – 50 and < 40 mg/dl among males, t=3.990, p<0.001 is statistically highly significant.

The maximum number of patients (56%) were found in near optimal range, followed by borderline high (16%) and an equal number of patients (10%) were found in levels <100 mg/dl and very high levels.

Table No.8: Lipid Profile among diabetic and non-diabetic CKD patients

As compared to T.cholesterol levels among diabetic and non-diabetic patients, t=0.74,p>0.05 is statistically insignificant. As compared to triglyceride levels among diabetic and non- diabetic patients, t=1.814, p>0.05 is statistically insignificant. As compared to HDL-C levels among diabetic and non-diabetic Patients, t=0.131 p>0.05 is statistically insignificant. As compared to LDL-C levels among diabetic and non-diabetic Patients, t=1.503, p>0.05 is statistically insignificant. As compared to VLDL-C levels among diabetic and non-diabetic Patients, t=0.998, p>0.05 is statistically insignificant.

The study was conducted on 50 chronic kidney disease patients. There were 37 male patients and 13 female patients with a mean age of 48.7 years. The mean age for male patients was 48.23 and for female patients was 49.92

years. The overall male to female ratio in our study was 2.84:1. Feast TG et al and Smith SR¹³ analyzed age, sex and racial difference in the incidence and progression of renal disease in American population and found lowest incidence in children (10/year) and highest in the elderly (>400/year). The incidence is slightly higher in males than in females. In our study, we found that 74% were males and 26% were females, and the maximum number of patients was between 41-50 years (36%), followed by 51-60 years (22%) and then 61-70 years (16%). 

The majority of patients with CKD are hypertensive, with the prevalence increasing with the increasing severity of CKD such that in the most severe stages of CKD (eGFR < 30 mL/min), over 90% of patients are hypertensive.¹⁴ Studies have clearly shown a significant reduction in the rate of progression of CKD when hypertension is treated. Particularly, this has been demonstrated in major studies investigating the blockade of the RAS with ACEI in both proteinuric and nonproteinuric^15-17 CKD and with angiotensin II receptor blockers.

As a potentially modifiable risk factor, the impact of hypertension on cardiovascular disease in patients with CKD is of great interest. As kidney impairment progresses, there is increasing activation of the RAS in response to glomerular sclerosis and interstitial disease, as well as fluid overload and increased arterial stiffness, all of which contribute to hypertension. Essential hypertension itself causes microvascular damage in the renal vascular bed, causing kidney damage and, hence, through RAS activation, exacerbating essential hypertension. Hypertension is known to alter renal physiological function with increased filtration fraction of sodium and increased renovascular resistance seen in hypertensive patients.¹⁸  

In our study, we found that there is a decline in hemoglobin with increasing duration of CKD. Anemia exerts a large influence over the pathogenesis of LVH, and correction with erythropoietin has been shown to reduce LVH. CKD is associated with an increased prevalence of concomitant CHF, ischemic heart disease, cardiac arrhythmias (most commonly atrial fibrillation), and valvular calcification.¹⁹  

PAD is common in CKD patients. Among adults aged >40 years with estimated GFR<60 ml/min per 1.73 m2, National Health and Nutrition Examination Survey data from 1999 to 2000 report prevalence of 24%²⁰ The Chronic

Renal Insufficiency Cohort study data show PAD in 7% of adult CKD ND patients;²¹ prevalence in CKD 5D patients is 17–48%. CKD is an independent risk factor for PAD events.²² The relative risk of stroke in CKD 5D patients was estimated to be 5–10 times that of the age-matched general population119 with an overall stroke risk of 4 %. In our study, we found out of 50 patients, 5 patients (10%) had coronary artery disease (CAD), and 1 patient (2%) had cerebrovascular disease (CVD) as the commonest vascular complications.

The lipid profiles of 50 chronic kidney disease patients were analyzed irrespective of their etiology and modality of treatment. Cuxart M, Sans Ret al.²³ showed in their study that hypertriglyceridemia was detected in 34% of the hemodialysis patients and in none of the controls (p<0.001), also a significant reduction of HDL-C level was found in hemodyalysis group as compared with controls (p<0.001). Shah B and Nair S et al.²⁴ also showed that significant hypertriglyceridemia does develop in a majority of chronic kidney disease patients (p<0.05). Attman PO, Samuelsson O et al.²⁵ suggested that it is the elevated concentration of Apo B-containing lipoproteins that contribute to the progression of renal disease. Permell P et al.²⁶, Waltus BA et al study showed that in chronic kidney disease dyslipidemia is highly prevalent with predominence of atherogenic triad (hypertriglyceredimia, elevated LDL and reduce HDL. in their study there was elevation in triglycerides (52%) decreased HDL by (51%) with elevation of LDL (40 %) with total cholesterol of 24 %.

In our study, the mean triglyceride level was found to be 179.2 mg /dl that is 64 % above normal, mean cholesterol 196.3 mg /dl that is 54 % above normal, LDL 127 mg/dl that is 82 % above normal but HDL 38 mg/dl that is 70 % below normal. There was an elevation in triglycerides, chlolesterol, and LDL except HDL which was decreased in this study. Epidemiological studies have shown that HDL-cholesterol levels are inversely related to future cardiovascular risk.²⁷ HDL particles possess multiple antiatherogenic activities including reverse cholesterol transport (transport of surplus cholesterol from the arterial wall to the liver for excretion) as well as antioxidative, anti-inflammatory and antithrombotic functions, which are attributed to HDL- associated apolipoproteins (mainly apolipoprotein AI) and enzymes (paraoxonase-1, platelet-activating factor acetylhydrolase and lecithin-cholesterol acyltransferase (LCAT)).²⁸ Studies in patients or laboratory animals with predialysis renal failure consistently reveal decreased concentrations of HDL-cholesterol compared to individuals with normal renal function. ^29,30

Muntner et al.³¹ studied the relationship of plasma lipids to a rise in serum creatinine of 0.4 mg/dL or greater in 12728 participants with baseline serum creatinine that was less than 2.0 mg/dL in men and less than 1.8 mg/dL in women. They found that individuals with higher baseline triglyceride and lower HDL- cholesterol levels were at increased risk for a rise in creatinine.  Diabetic retinopathy was also more common and more severe in renal failure. Patients with undiagnosed diabetes and unrecognized proliferative retinopathy were identified among the patients with CKD stages 3 to 5. The increased severity of retinal complications in diabetic renal failure emphasizes the need for regular monitoring because the retinopathy is asymptomatic, may progress rapidly if untreated, and visual loss can be prevented or limited with treatment. The presence of diabetic retinopathy is also a marker of increased risk of cardiac disease and death. In our study, we found that 50 % of the patients had retinopathy changes on fundus examination, of which 34% of the patients had diabetic retinopathy changes, 14 % had hypertensive retinopathy changes, and 2 % had both.

In conclusion, this study of 50 CKD patients revealed that Type 2 diabetes (38%) and hypertension (32%) were the leading causes, with most patients aged 41-50 years. A significant proportion of diabetic (52.6%) and hypertensive (75%) patients with 5-15 years of disease duration developed CKD. Hemoglobin levels declined with rising serum creatinine and longer CKD duration. Common complications included CAD (10%), CVD (2%), and LVH (22%). Diabetic retinopathy (34%) and hypertensive retinopathy (14%) were notable findings. Lipid profile abnormalities were prevalent, with 70% having low HDL (<40 mg/dl) and 34% showing atherogenic changes, highlighting the increased cardiovascular risk in CKD patients.

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