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Lipoprotein(a) A Marker for Early Diabetic Nephropathy in Chronic Type II Diabetes Mellitus in Indians

 

JG Saluja*, MS Ajinkya**, SS Khanna***, Leroy Rebello****, Gurpreet Saluja+

 

Lipoprotein(a) [Lp(a)] is an LDL like particle which has apoB-100 and apo(a) covalently linked to each other by at least one disulphide bond.16,17 It can inhibit the activation of plasminogen to plasmin by tissue plasminogen activator and hence prevents lysis of fibrin clot. This is because of its structural similarity to plasminogen. It competes with endothelial binding sites forming Lp(a)-fibrin complex which is deposited in arterial intima. It is a known fact that Asian Indians have Lp(a) levels twice as high as Caucasians hence they are 3 fold prone to metabolic disorders and Coronary artery disease (CAD). Lp(a) levels and microalbuminuria levels were studied in 50 patients having Type II Diabetes mellitus with varying stage of diabetic nephropathy. It was found that Lp(a) levels are good marker for early cases of diabetes nephropathy.

Introduction
Abnormalities in plasma lipid and lipoprotein metabolism are common in Diabetes Mellitus. This dyslipidaemia is a major risk factor for the development of atherosclerosis and results in a wide variety of complications.

Established chronic renal failure is a progressive condition, which leads to a state of metabolic syndrome.1,2 Protecting the kidney, implies slowing the development of renal failure. The important factor that can help in protecting the kidney include the treatment of the underlying disease, like hypertension and diabetes mellitus, avoiding the abuse of drugs and regular medical checkups. The kidneys play a major role in the clearance of apolipoprotein A-1 (apo-A1)3 and high density lipoprotein (HDL) from the blood stream. Proximal tubules and epithelial cells of the kidney prevent the loss of these proteins in the urine by reabsorbing them from the urinary filtrates.

Aim
The aim was to study the serum levels of Lp(a) in type II diabetes mellitus with and without nephropathy and to determine correlation between serum Lp(a) and the severity of diabetic nephropathy.


Fig.1 :

Fig.2 :

Methodology
The study was conducted on 100 patients diagnosed to have type II Diabetes Mellitus of five years or more duration. 50 patients with no nephropathy served as the control group and another 50 patients with nephropathy formed the study group. The patients involved in this study had been diagnosed to have type II Diabetes Mellitus as per the UKPDS criteria5 (1999). The cases were matched with respect to sex, age, body mass index (BMI) waist and hip ratio with control. Study subjects had signs of nephropathy and raised value of Lp(a) Creatinine and Microalbumin controls were normal. The mean age of the study group was 35.85 1.80 years (20-52 yrs). The BMI was 28 ± 1.57 in study group vs 26.99 ± 1.54 years. In the control group the two groups were also similar as regards measurements of waist, hip, waist-hip ratio (WHR) and basal blood pressure.

The following group of patients were excluded from the study : Patients with diabetes and less than five years duration, patients on hypolipidaemic drugs, smokers and alcoholics. Fasting venous samples of blood were drawn for the estimation of levels of serum lipoprotein (a) [Lp(a)] and creatinine, Microalbumin was measured in urine. They were quantitatively measured by immuno-turbidometry methods etc using the commercially available kits.

Discussion
Diabetic nephropathy is one of the most serious complications in both type I and II diabetes mellitus. The duration of diabetes and glycaemic control are the most crucial factors in the pathogenesis of nephropathy. However these above mentioned factors alone do not explain the development of progressive nephropathy.6 It may be absent in some with poor control of diabetes, while others may show manifestation of nephropathy in a relatively short duration of time despite effecting good metabolic control. These facts, raise possibilities of other factors playing a role in the pathogenesis of diabetic nephropathy. Therefore, the above study was undertaken to evaluate the possible role of Lp(a), a counterpart of LDL cholesterol in the occurrence and development of diabetic nephropathy.

The presence of microalbuminuria in urine is an early sign of local and systemic endothelial dysfunction leading to vasculopathy which in turn is associated with pathological evidence of target organ damage to the kidneys.7,8

Microalbuminuria is an independent risk factor for progessive renal disease in patients with diabetes mellitus. Microalbuminuria is also has been shown to be an associated risk factor for vascular disease similar to dysplipidaemia and physical inactivity.9,10

In our study, the average serum Lp(a) levels in patients with diabetic nephropathy are significantly higher than those of control. High serum Lp(a) is an independent risk factor for atherogenesis and thromboembolism in types I and II diabetes.11 Since capillary occlusion can be a finding in diabetic nephropathy, Lp(a) may play an important role in the development and progression of diabetic nephropathy.12 Vasculopathy may enhance chronic ischaemia leading to the production of Reactive Oxidative Species (ROS) which act as free radicals causing increased lipid peroxidation. This causes the subfraction of LDL to be high [Lp(a)]. This is a marker for nephropathy.13

Kuboyma14 et al showed definite use of Lp(a) levels in chronic renal failure, and revealed a significant relationship of Lp(a) with high molecular weight. Apo(a) and creatinine level. Our study proves that the Lp(a) levels definitely have a relation with creatinine and microalbumin. Hence Lp(a) alone can be used as an important marker for detecting early nephropathy which can be prevented by metabolically controlling diabetes mellitus thereby reducing morbidity and mortality.

Lp(a) also has an antifibrinolytic effect,15 so it may contribute to the occlusion of small vessels and therefore can be considered as an independent risk factor in the development of diabetic nephropathy.

Conclusion
From the above study it is concluded that Lipoprotein(a) is considered to be an important marker for detection of early diabetic nephropathy.

Acknowledgements
We thank Miss Deepti Panicker for helping us in the preparation of the graphs and the technical data.

References

  1. Chen J, Muntner P, et al. The metabolic syndrome and chronic kidney disease in US adults. Ann Intern Med 2004; 140 (3) : 139.
  2. Butler R, Macdonald TM, et al. The clinical implications of diabetic heart disease. Eur Heart 1998; 19 : 1617-27.
  3. Lberopoulos E, Elisaf M, et al. Apolipoprotein E and Renal disease. Ann J Kidney Dis 2004; 43 (2) : 223-33.
  4. Breznan D, Sparks DL, et al. The lipid composition of high density lipoprotein affects its reabsorption in the kidney by proximal tubule epithelial cells. Biochemistry Journal 2004; 379 (Pt2) : 343-49.
  5. Clinical Recommendations from the United Kingdom prospective diabetic study (UKPDS). Endocrine Practice 1999;157-58.
  6. Grune T, Jakstadt M, et al. Elevated serum concentrations of cardiotoxic lipid peroxidation products in chronic renal failure in relation to severity of anaemia. Cli Nephrol 2002; (suppl1) : 520-25.
  7. Meittinen H, Pyolora K, et al. Proteinuria predicts stroke and other atherosclerotic vascular disease events in nondiabetic and non insulin dependent diabetic subjects. Stroke 1996;27:2033-39.
  8. Vaeth M, Schmitz A. Microalbuminuria : A major risk factor in non insulin dependent diabetes. A 10 year follow up study of 503 patients. Diabet Med 1988; 5 : 126-34.
  9. Epstein M, et al. Diabetes, hypertension and cardiovascular disease. An update. Hypertension 2001; 37 : 1053-59.
  10. National Kidney Foundation, KDOQI clinical practice guidelines for managing dyslipidemia in chronic kidney disease. Am J Kidney Dis 2003;41:51-592.
  11. Scott J. Thrombogenesis is linked to atherogenesis at last? Nature 1989; 341 : 22-23.
  12. Ballard D, et al. Chronic renal failuer in non insulin dependent diabetes mellitus : A population based study in Rochester, Minnesota. Ann Intern Med 1989; 111 : 788-96.
  13. Kaysen GA, Eiserich JP. The role of oxidative stress altered lipoprotein structure and function and microinflammation on cardiovascular risk in patients with minor renal dysfunction. Am Soc Nephrol 2004; 15 (3) : 538-48.
  14. Kuboyama M, Aqeta M, et al. Serum lipoprotein (a) concentrations and Apo (a) isoform under conditions of renal dysfunction. J Atheroscler Thromb 2003; 10 (5) : 238-39.
  15. Gavish D Breslow, et al. Lipoprotein (a) modulations of endothelial cell surface of fibrinolysis and its potential role in antherosclerosis. Nature 1989; 339 : 303-5.
  16. Narayanan S. Current perceptives on laboratory markers for the assessment of cardiovascular disease and myocardial damage. Indian J Clin Biochem 1999; 14 (2) : 117-28.
  17. Schaefer EJ, Iman-fava S, Jenner, et al. Lipoprotein(a) levels and risk of coronary heart disease in men. The lipid research clinics coronary primary preventives trial. JAMA 1994; 271 : 99-103.
  18. Mc Cully KS. Homocysteine folate, Vitamin B6 and Cardiovascular disease. JAMA 1998; 279 : 392-93.
  19. Enas EA, Yusufs Garg, et al. Lipoprotein(a) levels in Indian Physicians : comparison with black and white Physician in USA. Indian Heart J 1994; 46 : 1 (Abstract).
  20. Vasisht S, Wasir HS. Srivastava LM. Association between incidence of lipoprotein (a) and coronary heart disease. Indian Heart J 1992; 44 : 23-26.

*Professor and Head of Pathology Department and Professor of Immunology at Mumbai University of PG Student. **Hon Professor of Pathology; ***Hon. Physician; ****Intern at CMPH Med College and Shree Mumbadevi Homeopathic Hospital, Vile Parle (West), Mumbai 56. +PG Student, Bio Analytical Science.

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