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Year : 2016 | Volume : 4 | Issue : 1 | Page : 36 - 41  


Original Articles
Alteration in different lipoprotein fractions in chronic renal failure patients
  1. Ravi Kumar1, Ravindra Kumar2

1 Associate Professor, 2 Professor, Department of General Medicine, Malla Reddy Medical College for Women, Suraram, Hyderabad

 

Corresponding Author:

Dr. M. Ravi Kumar

Email: drmravikumar@gmail.com

 

Abstract:

 

Background: Chronic renal failure, which is an inevitable terminal pathway of any chronic renal parenchymal disease, is more known for its morbidity than for its mortality.

Objective: To note the alteration in different lipoprotein fractions among chronic renal failure patients.

Methods: 70 Cases of chronic renal failure were taken for study. These patients were divided into two groups of 35 each. One group consisting of 35 Patients who were on conservative treatment, and the other group of 35 patients were on regular short term hemodialysis (6 months – 2 years). Patients were selected from Kasturba Medical College Hospitals and from Wenlock Government Hospital, Mangalore, from April 2001 to December 2003.

Results: The HDL – cholesterol level was found to be significantly lower compared to control group. The total cholesterol and LDL was not raised significantly.

The HDL/TC ratio was significantly reduced.

Conclusion: Significant rise in triglyceride and VLDL concentration was seen in chronic renal failure patients.

Key words: lipoprotein fractions, chronic renal failure, VLDL

INTRODUCTION:

 

Chronic renal failure, which is an inevitable terminal pathway of any chronic renal parenchymal disease, is more known for its morbidity than for its mortality. The consequences of renal failure are reflected ultimately in every organ system in the body. The nature of severity of these consequences, however, has undergone profound changes since the advent of dialysis therapy. 1

Cardiovascular disease is a major cause of morbidity and mortality among patients with chronic renal failure1. More than 50% patients die from cardiovascular system complications. The growing recognition that dyslipidemia is a major risk factor for coronary heart disease has promoted interest in the identification and management of abnormalities in plasma lipids and lipoproteins. 2

Hence the present study was carried out to note the alteration in different lipoprotein fractions among chronic renal failure patients.

MATERIAL AND METHODS

 

70 Cases of chronic renal failure were taken for study. These patients were divided into two groups of 35 each. One group consisting of 35 Patients who were on conservative treatment, and the other group of 35 patients were on regular short term hemodialysis (6 months – 2 years). Patients were selected from Kasturba Medical College Hospitals and from Wenlock Government Hospital, Mangalore, from April 2001 to December 2003.

The control group was formed by 35 healthy persons which was age and sex matched to the study group.

Patients proven Diabetes Mellitus and Nephrotic syndrome with renal failure and patients on Lipid lowering drugs were excluded from the study.

For diagnosis of chronic renal failure, history, physical findings with supportive biochemical and sonological evidence are taken as criteria.  Renal biopsy was not considered for the fact that all kidney disease merge into a single pattern of end stage kidney.

Normal healthy individuals without any significant systemic medical illness, with normal biochemical profile and normal USG abdomen were included in the study; however individuals with hypertension, diabetes and significant systemic medical illness are excluded from this study.

For all patients the following investigations were done:

Urine: albumin, sugar, specific gravity, microscopy, 24 hours urinary protein.

Biochemical:

Blood Hb%, Peripheral smear, Blood urea, serum creatinine, serum total proteins, serum albumin, serum calcium, serum phosphorus, serum electrolytes, total cholesterol, triglycerides, HDL, LDL, VLDL. Chest x-ray, ECG, Ultrasound abdomen and ECHO was done.

FOR CHRONIC RENAL FAILURE:

CLINICAL CRITERIA:

The clinical criteria are not absolute and are non-specific, occur only in the later stage and are not dependable.  The features of uremia include fatigue, lethargy, somnolence, coma, anorexia, nausea, vomiting, hematemesis, gastric ulcers, diarrhea, dysentry, cardiac failure, pericarditis, cardiomyopathy, edema, hypertension, pleuritis, pulmonary edema, pulmonary hemorrhage, anemia, thrombasthenia, purpura, rickets, osteomalacia, osteitis fibrosa, pruritis, and peripheral neuropathy.

Patient was considered as anemic if facial pallor was associated with conjunctival and buccal mucous membrane pallor and nail pallor.  It was later confirmed by hemoglobin estimation.

Edema was considered as present when the pitting was demonstrated which persisted for more than 30 seconds.

Hypertension was considered when the blood pressure in the lying position was more than 160/90 mm of Hg.

Pleuritis and pericarditis were recognized by their accompanying pleural and pericardial rubs.

Congestive cardiac failure was considered by the presence of cardiomegaly, presence of S3, pulmonary basal rales, raised jugular venous pressure, tender hepatomegaly and edema.

Pulmonary edema was diagnosed by tachypnea, cyanosis, lung crepitations (bilateral) with or without x-ray evidence of bilateral non-homogenous coarse infiltrate shadow spreading from hilar regions.

Hypertensive retinopathy on fundus examination was graded accordingly:

Grade I: was considered in the presence of narrowing of vessels.

Grade II: was diagnosed by the marked variation in the caliber of the vessels and AV nipping.

Grade III: was diagnosed when flame shaped hemorrhages or round        retinal hemorrhages and cotton wool exudates were noticed. 

Grade IV: changes show the addition of papilloedema along with the above feature.

Papilloedema was made out by the presence of swelling of the optic disc, blurring of the margins and engorgement of veins and apparent disappearance of blood vessels as they amount to the elevated disc.

Urine output below 400 ml was considered as Oliguria and more than 2000ml was considered as Polyuria.  Nocturia was suspected if the patient got up atleast two times in the night to pass the urine.

URINE FINDINGS:

Urine specific gravity done on fresh voided specimen early in the morning less than 1012 was considered as Isosthenuria.  Proteinuria was considered as present when the heat test showed a definite cloud which did not get dissolved on addition of glacial acetic acid.  Urine white cells or pus cells more than 4-5 per HP particularly noticed in Clumps was considered as abnormal.

BIOCHEMICAL FINDINGS:

Elevated blood urea above 50 mg% was considered as abnormal.  Serum creatinine more than 2 mg% was considered abnormal.

ULTRASOUND ABDOMEN:

Bilaterally contracted and small kidneys with loss of corticomedullary junction were taken as indicative of chronic renal failure kidney. 

Thus in general the criteria that were used to establish chronic renal failure are:

  1. Clinical features of uremia.
  2. Anemia less than 11 gm% for women, less than 13 gm% men.
  3. Elevated blood urea and serum creatinine levels.
  4. Glomerular filtration rate estimation.
  5. Small sized contracted kidneys on ultrasound studies.

 

In the two study groups the parameters studied were: Hb%, Blood urea, serum creatinine, total proteins, serum albumin, serum electrolytes and total lipid profile were estimated in K.M.C.Hospital laboratory.

BLOOD SAMPLING AND PREPARATION OF SERUM:

Blood samples were drawn from all the patients after a minimum of 8-12 hours of fasting.  The subjects were asked to have a light, fat free diet on the day prior to the sampling.  The venupuncture was done in the cubital fossa. About 12ml of blood was drawn using perfectly dry and sterile syringe.  About 10ml of blood was transfused to dried glass vials.

Serum was separated within 2 hours after collection to prevent artifactal change in concentration of HDL.  After the clot retraction occurred, the serum was transferred out to a centrifuge tube and centrifuged at 5000 rpm for 10 minutes.  The supernant clear serum was then pipetted out using dry piston pipettes with disposable tips and stored in dry thin walled vials at 4°C.  The samples were analysed on the same day or within 48 hours.

PHYSICAL EXAMINATION OF SERA:

The sera of each patient were examined soon after seperation for its appearance to know whether it is clear or lipemic (opalascent). Then the sera was again inspected after overnight refrigeration at 4°C and noted down any creamy layering on the top (chylotest) or turbidity of the intranatant (VLDL test).  The turbid serum was graded into three grades (T1, T2 and T3), depending upon degree of turbidity.  This was done to implement it as a bedside test for hyperlipidemia.

 

 

 

 

RESULTS

Seventy patients of chronic renal failure and 35 normal subjects (control) were taken for the present study.

Lipid levels like TC, TG, HDL, LDL and VLDL were estimated in controls and patients were compared.

Table 1: Bio chemical data in control and renal failure patients

Parameters

Group

N

Mean

SD

t

P value

Blood urea

Patients

70

159.42

59.85

13.85

0.001

 

Controls

35

18.57

5.63

 

 

  1. creatinine

Patients

70

9.1

3.21

15.03

0.001

 

Controls

35

0.92

0.23

 

 

Total proteins

Patients

70

6.28

0.49

6.19

0.001

 

Controls

35

6.82

0.23

 

 

  1. albumin

Patients

70

3.33

0.35

10.08

0.001

 

Controls

35

4.06

0.33

 

 

*t = Student t-test (unpaired), vhs = very highly significant

Mean and standard values for urea in controls and patients showed a considerable difference which was found to be highly significant (P=0.001).

Creatinine levels in patients were very high as compared to controls. This difference was statistically significant (P=0.001).

Mean total protein was significantly reduced as compared to controls (P=0.001). This was found to be highly significant.

So also albumin levels are reduced in patients as compared to control (p=0.001). The difference was found to be highly significant.

The value of various fractions of lipid in patients and controls were studied.

Table 2: Lipid profile data in controls and renal failure patients 

Lipid profile

Group

N

Mean

Std.  Deviation

t

P value

  1. cholesterol

Patients

70

201.45

46.95

1.81

P=.073

ns

Controls

35

185.85

27.45

Triglycerides

Patients

70

168.80

66.25

5.11

p=.001

vhs

Controls

35

106.74

38.62

HDLc

Patients

70

36.60

6.80

6.36

p=.001

vhs

Controls

35

47.56

10.75

LDLc

Patients

70

131.09

45.27

1.70

P= .092

ns

Controls

35

116.92

27.24

VLDLc

Patients

70

33.76

13.25

1.98

P=.05

sig

Controls

35

25.95

27.23

HDL/TC

Patients

70

0.19

6.56E-02

5.52

p=.001

vhs

Controls

35

0.27

8.24E-02

ns = Not significant     sig= significant

Total cholesterol value in controls and patients are 185.85 ± 27.45 mg/dl and 201.45 ± 46.95 mg/dl respectively (p= 0.073). However this difference was not significant. 

Triglycerides mean value in patients with CRF was significantly high as compared to controls 168.80 ± 66.25 and 106.74 ±38.62 mg/dl respectively. This is statistically highly significant. (P = 0.001)

HDL values in chronic renal failure patients are decreased compared to controls 36.60 ± 6.80 and 47.56  ± 10.75 respectively (p<0.001). This was statistically highly significant. (P=0.001)

LDL values were increased in chronic renal failure patients   compared to controls 131.09 ± 45.27 and 116.92 ± 27.24 respectively. However this difference was not significant. (P=0.092)

Significant increase in VLDL were found in patients as compared to controls 33.76± 13.25 and 25.95 ± 27.23 respectively. This was statistically significant. (P = 0.05).

There is a significant reduction in HDL/TC ratio in patients as compared to controls, 0.19±6.56 E-02 and 0.27±8.24 E-02 respectively. This was statistically significant (P=0.001).

Among the total 70 patients included in the study 41 patients showed abnormal lipid profile and 29 patients showed normal lipid profile.

DISCUSSION

The results of the study on the lipid profile in patients with chronic renal failure shows that there are significant deviations in the lipid profiles of these patients as compared to controls.

In this study triglycerides were markedly elevated compared to control group and statistically highly significant. (P = 0.001)

Attman P.O., Alaupovic P., stated, hypertriglyceridemia is the most common plasma lipid abnormality in adult patients and children with renal failure. 3

The cause for hypertriglyceridemia in chronic renal failure patients has not been delineated. Available data derived from kinetic studies with intra lipid administration have demonstrated that reduced catabolism of triglyceride is the predominant defect due to deficiency of lipoprotein lipase 4 or hepatic triglyceride lipase 5 or both. These enzymes are the primary mediation of the process, reason for decrease in activity of these enzymes is not clear.

Possibly due to:

  • Presence of circulatory inhibitor of lipolytic enzymes in the serum 1
  • Changes in apoprotein concentrations which can effect lipoprotein lipase activity. 6
  • Insulin resistance seen in renal insufficiency 3
  • Alteration of lipoprotein substrate 3

The relationship between hypertriglyceridemia and atherosclerotic heart diseases is for less clear, some found to be a risk factor but others not. 7, 8

Cholesterol values were raised in patients as compared to controls but this value was statistically not significant. (P=0.073)

Gerald Appel found low values of cholesterol in CRF patients. 9

Anderson et al found hypercholesterolemia in 20% of patients. 10 Hypercholesterolemia has long been recognized as a significant risk factor for coronary heart disease.

LIPID ABNORMALITIES IN UREMIA: 10

  1. Triglycerides markedly elevated.
  2. Mild increase in cholesterol
  3. HDL values decreased in significant number of patients.
  4. Increase in levels of LDL & VLDL.

There was decrease in HDL cholesterol seen in patients compared to controls, which was statistically significant (P=0.001).

Goldberg et al found decrease in HDL concentration in patients compared to controls. 11

Rapoport, Aviram, study showed there is no decrease in HDL concentration in chronic renal failure patients. 12

Fuh MMT et al 13 found decrease in plasma HDL cholesterol concentration seen in patients with chronic renal failure is associated with decrease in both the fractional catabolic rate and the total synthetic rate of APOAI/HDL. The worse the renal function is the slower the fractional catabolic rate and the lower the APOAI/HDL. The changes in lipoprotein lipase activity, the enzyme those are responsible for VLDL-triglyceride hydrolysis may play a major role in this regard. For example lipoprotein lipase activity is decreased in patients with chronic renal failure. The lower the lipoprotein lipase activity is the lower the plasma HDL concentration. There is also evidence that patients with chronic renal failure have a factor in the plasma which inhibits lipoprotein lipase. Thus there are several possible mechanisms involving an abnormality in VLDL – triglyceride hydrolysis which could result in abnormal HDL metabolism and HDL concentration in patients with chronic renal failure. Alternatively the slow fractional catabolic rate of APOAI in patients with chronic renal failure could be a primary event resulting from a decrease in the synthesis or secretion of APOAI. APOAI is synthesized and secreted by Intestine, liver and it is certainly possible that these functions could be suppressed in patients with chronic renal failure.

There is marginal rise of serum total cholesterol in chronic renal failure patients, compared to controls but this rise was not statistically significant (P=0.73). Shah et al in their study showed no significant change in levels of total cholesterol. 14                                    

There is significant raise in VLDL levels in chronic renal failure patients compared to controls (P= 0.05). Cheung showed increase in very low density lipoproteins. 15

The LDL levels were marginally raised in patients as compared to controls and this was not statistically significant (P=0.092).

Anderson et al showed increase in LDL levels. 10

Gerald Appel et al showed normal or decrease in LDL levels. 9

The concentration of the most atherogenic lipoprotein LDL is usually normal or only marginally increased. In uremia LDL lipoproteins qualitatively altered. In-vitro studies have shown that LDL isolated from uremic patients is a poor ligand for the LDL apo B/E receptors.

 

CONCLUSION:

In this study alterations in different lipoprotein fractions in chronic renal failure patients were studied and also difference in lipid profile in chronic renal failure patients on conservative treatment and hemodialysis were also studied.

Significant rise in triglyceride and VLDL concentration was seen in chronic renal failure patients.

The HDL – cholesterol level was found to be significantly lower compared to control group.

The total cholesterol and LDL was not raised significantly.

The HDL/TC ratio was significantly reduced.

 

REFERENCES:

 

  1. King W., Greene E.L, Raij L., 1992 “Cardiovascular risk factors in chronic renal failure and hemodialysis populations”. Am J of Kidney Diseases, 19(6) : 505-515.
  2. Grundy SM, 1986 “Cholesterol and coronary heart disease: A new era”. JAMA, 256 : 2849 – 2858.
  3. Attman PO., Alaupovic P., 1991 “Lipid abnormalities in chronic renal insufficiency”. Kidney Int, 39(S-31): S16-S23.
  4. Staprans I., et al., 1979 “Apoprotein composition of plasma lipoprotein in uremic patients on hemodialysis”. Clin Chem Acta, 93: 135-143.
  5. Mordasini R., et al, 1977 “Selective deficiency of hepatic triglyceride lipase in uremic patients”. N Engl. J. Med, 297: 1362-1366.
  6. Staprans I., et al., 1979 “Apoprotein composition of plasma lipoprotein in uremic patients on hemodialysis”. Clin Chem Acta, 93: 135-143.
  7. Hully SB., Roseman RH., et al, 1980 “Epidemiology as a guide to clinical decisions – The association between triglyceride and coronary heart disease”. N Eng J Med, 302: 1382-1389.
  8. Rosenman RH., Brond RI., 1975 “Coronary heart disease in Western collaborative group study”. JAMA, 233:L 872-877.
  9. Gerald Appel., 1991 “Lipid abnormalities in renal disease” Kidney Int, 39: 169-183.
  10. Anderson Sharon, Garcia, Diego L and Brenner B.M., “Renal and systemic manifestations and glomerular disease”. Chapter –38 Text book of Kidney, Vol. 2, Edn. 4, W.B. Saunders Company, Philadephia, 1991: 1852-1860 pp.
  11. Goldberg AP., Appletaum Bondan DM., 1979 “Increase lipase during clofibrate treatment of hypertriglyceridemia in patients on hemodialysis”. New Eng J Med, 301 : 1073-76.
  12. Rapport J., Aviram M., 1978 “Defective high density lipoprotein composition in patients on chronic hemodialysis”. New Eng J Med, 299: 1326-1329.
  13. Fuh mmt, Lee C, Jeng C, 1990 “Effect of CRF on HDL Kinetics:. Kidney Int, 37: 1259-1300.
  14. Shah BV., et al, 1994 “Dyslipidemia in patients with chronic renal failure and renal transplant patients”. J. Post-grad Med, 40 (2) : 52-54.
  15. Cheung AK., Wull Kablitz., 1993 “Atherogenic lipids and lipoproteins in hemodialysis patients”. A. J. Kidney diseases, 22: 271.

 

 

 





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