ABSTRACT

Corresponding Author:
Dr. Ritesh Acharya,
Flat-404, Harihar Enclave, Goutam Nagar,
Bhubaneswar-751014,
Odisha, India.
E-mail: acharyaritesh1987@gmail.com
DOI: 10.14260/jemds/2018/301

ABSTRACT

BACKGROUND

Chronic kidney disease (CKD) is a significant global health problem with significant morbidity and mortality. Dyslipidaemia along with an abnormal apolipoprotein profile and composition is a common complication associated with the decline in eGFR in CKD. The association between abnormal lipid profile and severity of CKD has rarely been studied in a general population, especially in Indian setup and may have a future prognostic and management implication in patients with CKD.

Aims and Objectives- To study the pattern of lipid abnormalities in CKD patients and to correlate with severity of renal dysfunction.

MATERIALS AND METHODS

A descriptive comparative study was done using 50 cases of CKD of > 15 years age, along with 30 age and sex matched controls excluding confounding factors like diabetes, HTN, thyroid abnormalities, heart diseases, infection, inflammatory diseases, smoking, alcoholism etc. History, general and systemic examination, routine blood parameters, ECG, USG abdomen pelvis, serum total cholesterol, LDL, HDL, VLDL and triglycerides were done. The eGFR was calculated according to the CKD-EPI equation. Statistical analysis was done using student’s t-test, ANOVA, Bonferroni test, Mann-Whitney U test, Chi-square test and Pearson’s correlation. P value < 0.05 was considered as statistically significant.

RESULTS

The lipid profile in cases were TC: 184.96 ± 24.85 mg/dL; TGL: 148.10 ± 32.71 mg/dL; HDL: 32.38 ± 5.78 mg/dL; LDL: 122.82 ± 24.76 mg/dL; VLDL: 29.68 ± 6.54 mg/dL. Correlation between eGFR shows a significant negative correlation with TC (p= 0.007), TGL (p= 0.002), LDL (p= 0.000) and VLDL (p= 0.002) and positive correlation with HDL (p= 0.000). Comparison of lipid profile with grades of eGFR shows significant association with TGL (f= 3.804, p= 0.004), HDL (f= 18.099, p= 0.000), LDL (f= 3.793, p=0.004) and VLDL (f= 3.631, p= 0.005), but not with TC (f= 2.194, p= 0.064).

CONCLUSION

In CKD depending on severity there is a rise in TC, TGL, LDL, VLDL and a fall in HDL depending on severity.

KEYWORDS

Chronic Kidney Disease, Total Cholesterol, Triglyceride, Low Density Lipoprotein, High Density Lipoprotein, Very High Density Lipoprotein, Disease Severity.

BACKGROUND

CKD encompasses a spectrum of different pathophysiologic processes associated with abnormal kidney function and a progressive decline in GFR.¹ CKD is a significant global health problem. About 6% adult population in US have CKD stage 1 and 2, and 4.5% have CKD stage 3 and 4.¹ Its prevalence is high in India with a study showing 229/million population suffering from ESRD.² Most common causes of CKD include diabetic nephropathy, glomerulonephritis, HTN associated CKD, ADPKD and cystic and tubulointerstitial nephropathy.¹

Various complications of CKD include fluid electrolyte and acid base abnormalities, cardiovascular, neuromuscular, gastrointestinal, nutritional, endocrine and dermatological complications. Dyslipidaemia is a common complication of CKD and lipoprotein metabolism alteration and is associated with the decline in GFR; hence, lipid profile depends on the level of kidney function and the degree of proteinuria.^3,4 Disturbances in lipoprotein metabolism are evident even at the early stages of CKD and usually follow a downhill course that parallels the deterioration in renal function.⁵ Severe lipid metabolism disorders arise in patients with kidney failure and the lipid metabolism disorder peculiar to this patient group is known as uraemic dyslipidaemia,⁵ which may accelerate its progression.⁶ Abnormal lipid profile in CKD includes hypertriglyceridaemia, increase in triglyceride remnant Lp (a), increase in VLDL, decrease in HDL, total cholesterol and LDL usually within normal limits except in nephrotic syndrome patients.⁷ The association between lipid profile and severity of CKD has rarely been studied in a general population, especially in our part of the country and may have a future prognostic and management implication in patients with CKD.

The present study evaluates the type of dyslipidaemia in CKD patients and correlates with severity of renal dysfunction in CKD patients.

MATERIALS AND METHODS

This study is a descriptive comparative study and conducted in Department of Medicine of SCB Medical College and Hospital, Cuttack, from December 2016 to November 2017. After clearance from Institutional Ethics Committee (IEC), we included 50 CKD patients admitted to medicine wards. Thirty age and sex matched controls were taken excluding confounding factors like diabetes, HTN, thyroid abnormalities, heart diseases, infection, inflammatory diseases, smoking, alcoholism etc. Written consent was obtained from each individual participating in the study.

Patient Selection Criteria: Males and females > 15 years of age who were diagnosed as chronic kidney disease patients, attending PG Department of Medicine of SCB Medical College and Hospital were taken as cases.

Exclusion Criteria: Patients with history of alcoholism, chronic smokers, liver disease, hypothyroidism, metabolic syndrome, diabetes mellitus, hypertension, malignancy, coronary artery disease, history of lipid lowering drug intake and connective tissue disorders were excluded.

Investigations

All patients had undergone thorough clinical examination and laboratory investigations like complete blood counts, serum urea and creatinine, serum sodium and potassium, serum calcium, liver function tests, serum protein and albumin, blood glucose, arterial blood gases, lipid profiles, thyroid function tests and urine analysis. Electrocardiography and ultrasonography of abdomen were done on every patient. All blood samples were collected after 12 hours of fasting.

The eGFR was calculated according to the CKD- EPI (Chronic Kidney Disease Epidemiology Collaboration) equation, 2009. EGFR was graded G1, G2, G3, G4 and G5 as per the KDIGO 2012 guidelines.¹ Urine albumin was graded on basis of heat coagulation test as 0, trace (T) +, ++, +++ and ++++.

Statistical Analysis

The statistical analysis was done using the Statistical Package for Social Sciences (SPSS) version 21.0. Univariate analysis was used in description of demographic characteristics of the study population. Continuous variables were presented as means and standard deviation for unskewed data and median and interquartile range for skewed data. Student t-test was used to compare mean values (for two groups) and F test for Analysis of Variance (ANOVA) for more than two groups with unskewed data. Post hoc analysis was done using the Bonferroni test. Mann-Whitney U test was used to compare skewed data. Discrete variables were presented as frequency and percentages. Chi-square test was used to determine the significant associations between categorical variables. Pearson’s correlation was used to determine association between eGFR and other variables. P value < 0.05 was considered statistically significant and < 0.001 was considered as statistically highly significant.

RESULTS

The age and sex distribution of cases and controls shows both the study groups are age and sex matched.

Grading the cases in terms of severity showed 62% of the cases were in grade ‘g5’ and 34% were in grade ‘g4.’

The comparison between lipid profiles of cases and controls showed significant difference between total cholesterol (p= 0.001), triglyceride (p= 0.001), high density lipoprotein (p= 0.000), low density lipoprotein (p= 0.000) and very low density lipoprotein (p= 0.001).

Correlation between eGFR and lipid profile shows a significant negative correlation of eGFR with total cholesterol (p= 0.007), triglycerides (p= 0.002), low density lipoproteins (p= 0.000) and very low density lipoproteins (p= 0.002) and positive correlation with high density lipoproteins (p= 0.000).

There is a significant rise in total cholesterol (p= 0.043), triglycerides (p= 0.002), low density lipoproteins (p= 0.003) and very low density lipoproteins (p= 0.003) and fall in high density lipoproteins (p= 0.000) with decreasing eGFR grades.

                On comparing various parameters between cases and controls, there is a significant decrease in Hb (p= 0.000), S. Na (p= 0.000), S. Protein (p= 0.000), S. Albumin (p= 0.000) and a rise in B. Urea (p= 0.000) and S. Creatinine (p= 0.000).

                On correlating eGFR with various parameters, statistical significance was observed with Hb (r= 0.502, p= 0.000), S. Na (r= 0.414, p= 0.000), B. Urea (r= -0.683, p= 0.000), S. Creatinine (r= -0.682, p= 0.000), S. Protein (r= 0.526, p= 0.000) and S. Albumin (r= 0.619, p= 0.000).

DISCUSSION

Fifty cases of CKD were taken in the study, eliminating those which fell under the exclusion criteria. Thirty age and sex category matched healthy individuals were taken as controls. The age of the study population ranged from 25 to 75 years. Mean age of cases was 49.06 ± 12.52 years and controls was 49.6 ± 12.07 years. This was similar to that of CKD Registry of India 2007,⁸ where the mean age of cases was 48.3 ± 16.6 years and in the studies by Patel and Sirajwala⁹ and by Adejumo, Okaka and Ojogwu.¹⁰ As depicted in Table 1, the age group with maximum percentage of study population was 46-60 years’ group with 48% of cases and 36.7% of controls in the same. In CKD Registry of India 2007⁸, 71.2% of the cases belonged to age group 19 - 60 years. As depicted in Table 2, the sex distribution showed 58% of cases were males and 42% were females. Among controls, 60% were males and 40% were females. The majority of our patients belonged to male gender. In CKD Registry of India 2007⁸, the percentages of male cases were 68.9 and female cases were 31.1. Similar results to current study were seen in studies by Abraham et al¹¹ and Ganta et al.¹² The mean eGFR calculated by the CKD-EPI equation¹ was found to be 13.12 ± 8.67 in cases and 88.44 ± 23.9 in controls. There was a significant fall in eGFR in CKD cases. The mean eGFR of study by Sumanth and Shobharani¹³ was 22.22 ± 8.70 and that by Adejumo et al¹⁴ was 30.19 showing results similar to our study. On basis of severity grades 62% of cases were in G5 grade and 34% of cases were in G4 grade as shown in Table 3. Most CKD cases belonged to grade G5 followed by G4. In CKD Registry India 2007, 50.3% cases were in G5 and 24% were in G4. In study by Ganta et al,¹² 45.71% cases were in G5 and 37.14 % were in G4. These findings were similar to that in our study. As shown in Table 4, the study of various lipid parameters showed the Mean ± S.D. of serum total cholesterol to be 184.96 ± 24.85 in cases and 166.90 ± 19.81 in controls, and the difference was statistically significant with a ‘p’ value of 0.001. The Mean ± S.D. of serum triglycerides, high density lipoprotein, low density lipoprotein and very low density lipoprotein for cases were 148.10 ± 32.71, 32.38 ± 5.78, 122.82 ± 24.76 and 29.68 ± 6.54 and for controls were 124.33 ± 21.98, 42.50 ± 4.25, 100.33 ± 16.71 and 25.06 ± 4.44 respectively. The differences were statistically significant with ‘p’ values of 0.001, 0.000, 0.000 and 0.001 respectively for serum triglycerides, high density lipoprotein, low density lipoprotein and very low density lipoprotein. The correlation between eGFR and various lipid parameters depicted in Table 5 showed a statistically significant correlation between eGFR and serum total cholesterol (r= -0.299, p= 0.007), serum triglycerides (r= -0.347, p= 0.002), serum high density lipoprotein (r= 0.696, p= 0.000), low density lipoprotein (r= -0.408, p= 0.000) and serum very low density lipoprotein (r= -0.336, p= 0.002 ). As shown in Table 6 on comparing the various lipid parameters with grades of eGFR, serum triglycerides (F= 3.804, p= 0.004), high density lipoproteins (F= 18.099, p= 0.000), low density lipoproteins (F= 3.793, p= 0.004) and very low density lipoproteins (F= 3.631, p= 0.005) showed statistical significance, but no such significance was observed for serum total cholesterol (F= 2.194, p= 0.064). These findings indicate a rise in serum total cholesterol, triglycerides, low density lipoproteins, very low density lipoproteins and a fall in high density lipoproteins in CKD with fall in eGFR. Similar changes in lipid profile were seen by Machnur and Chandrashekar,¹⁵ Patel and Sirajwala,⁹ Ganta V et al,¹² Attman, Samuelsson and Alaupovic,¹⁶ Mannangi et al and Wang et al,¹⁷ Paul and Kurien¹⁸ in separate studies showed significant inverse correlation between triglyceride and GFR and significant positive correlation between high density lipoprotein and GFR (p= < 0.001).

Table 7 depicted that comparing Mean ± S.D. of haemoglobin levels of case and controls showed a value of 8.782 ± 1.705 in cases and 11.046 ± 1.617 in controls with a ‘p’ value of 0.000. This shows a fall in haemoglobin with CKD. Similar reports have been given by studies of Chonchol                   et al¹⁹ and Ortega et al.²⁰ For BMI, it was 19.97 ± 3.13 for cases and 20.46 ± 3.48 for controls. The values were not statistically significant with a ‘p’ value of 0.513. The CKD Registry of India 2007⁸ had majority of patients between BMI range of 18.5 and 24.9. For serum sodium, the Mean ± S.D. of cases was 130.64 ± 11.82 and controls was 140.36 ± 6.49. The values were statistically significant with a ‘p’ value of 0.000. This indicates the presence of significant hyponatraemia in CKD patients. For potassium, it was found to be 3.98 ± 0.70 and 3.96 ± 0.50 for cases and controls respectively with no statistical significance (p= 0.871). The median of blood urea and serum creatinine were 75 (IQR= 38 - 128.25) and 3.25 (IQR= 1.025 - 5.725) respectively. The values were statistically significant with ‘p’ values of 0.000 for both. This indicates a significant rise in blood urea and serum creatinine in CKD patients. Similar results have been reported by Lakshmi, Subhashini and Swami.²¹ The Mean ± S.D. of serum protein and serum albumin were 6.53 ± 0.55 and 3.49 ± 0.46 for cases, and 7.28 ± 0.45 and 4.29 ± 0.42 for controls respectively. The values were statistically significant with ‘p’ values of 0.000 for both. This indicates a fall in serum protein and albumin in CKD. Similar report has been submitted by the study of Adejumo et al.¹⁰ As shown in Table 8, statistically significant correlation was found between eGFR and haemoglobin, serum sodium, serum protein, serum albumin, blood urea and serum creatinine with r= 0.502, 0.414, 0.526, 0.619, -0.683 and -0.682 respectively with ‘p’ value of 0.000 in all. Values of BMI and serum potassium did not show any statistical significance.

CONCLUSION

Our study revealed that there was significant dyslipidaemia in CKD patients. There was rise in total cholesterol, triglycerides, low density lipoproteins, very low density lipoproteins and a fall in high density lipoproteins in CKD. These changes in lipid profile varied significantly when correlated with fall in eGFR. There is significant change in all lipid parameters when compared with grades of eGFR.