Lipoprotein (a) risk factor and potential target for Chronic Kidney Disease, unravels study

Chronic Kidney Disease (CKD) is one of the most common diseases globally. Impaired kidney disease is one of the common causes of CKD and individuals with CKD have an increased risk of atherosclerotic cardiovascular disease and early death. Previous statements from the European Society have found that individuals with chronic kidney disease and impaired kidney function have increased levels of plasma lipoproteins. Increased levels of plasma lipoproteins cause stenosis of various arteries in the body like coronary, carotid, and renal. However, there was ambiguity on whether impaired kidney disease causes increased plasma lipoproteins or vice versa. Hence, researchers conducted a 1-sample Mendelian randomization study to test if high plasma lipoprotein(a) is genetically associated with an increased risk of chronic kidney disease.

The study was conducted by drawing blood samples involving individuals from the Copenhagen General Population Study. The study's primary endpoint was patients with estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m² at baseline or who died of chronic kidney insufficiency. Restricted cubic splines were used to evaluate the relationship between lipoprotein(a) levels and the risk of chronic kidney disease. Multivariable-adjusted logistic regressions were used to find the odds of chronic kidney disease.

Findings:

• Higher lipoprotein levels were associated with a higher risk of chronic kidney disease
• Multivariable adjusted logistic regression models found that a stepwise higher risk of CKD was associated with stepwise higher lipoprotein levels
• On a continuous scale, lower KIV-2 repeats were associated with an increased risk of chronic kidney disease.
• The observational analysis found that for every 50 mg/dL (105 nmol/L) higher lipoprotein level, the multivariable-adjusted OR for chronic kidney disease was 1.25
• Variable analysis showed that, for people with genetically increased levels of lipoproteins by 50mg/dl, the genetic causal risk of chronic kidney disease was 1.30.

Thus, the Mendelian randomization study strongly emphasizes the association between high plasma lipoprotein(a) levels and impaired kidney function as observed in general studies and genetic analysis. The authors also suggested lipoprotein lowering therapies which can play a protective role in preventing CKD.

Further reading: High Lipoprotein(a) as a Cause of Kidney Disease: A Population-Based Mendelian Randomization Study. Doi: https://doi.org/10.1016/j.jacc.2024.08.059.

Take home points:

• Chronic kidney diseases are common global diseases
• Impaired kidney disease is one of the causes of CKD
• High lipoproteins are observationally and genetically associated with an increased risk of CKD