Lipoprotein Glomerulopathy - A Rare Glomerular Disorder

Introduction

Lipoprotein glomerulopathy is a condition in which lipid accumulation occurs in the glomerular capillaries of the kidneys. It is a rare condition that is characterized by proteinuria (high protein level in the urine), disturbance in lipoprotein metabolism, and renal insufficiency. This article gives insight into the clinical and laboratory features of lipoprotein glomerulopathy, the mechanisms causing this disorder, and the therapeutic options that are available.

What Is Glomerulopathy?

Glomerulopathy refers to a group of diseases that affect the glomeruli (filtering unit) of the kidneys. Such diseases can be inflammatory or noninflammatory diseases, but inflammatory conditions refer to glomerulitis. Hence, glomerulopathy usually refers to a non-inflammatory disease of the glomeruli of the kidneys.

What Is Lipoprotein Glomerulopathy?

Lipoprotein glomerulopathy is a rare condition that usually occurs in adulthood, and males are affected predominantly. It is caused by a rare mutation in the apolipoprotein E gene, which causes the accumulation of lipoproteins as intracapillary thrombi in the glomerular capillaries of the kidneys. Lipoprotein glomerulopathy is characterized by the presence of proteinuria, disturbances in lipid metabolism, and renal insufficiency. The disturbances in lipid metabolism closely resemble those observed in type III hyperlipidemia disorder. It is commonly observed in East Asian countries and also in Europe and America.

What Causes Lipoprotein Glomerulopathy?

Lipoprotein glomerulopathy is an autosomal dominant disease. It is caused by mutations in the apolipoprotein E (ApoE) gene that encodes apolipoprotein E. Apolipoprotein E is a component of lipoproteins such as high-density lipoproteins (HDLs), very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDLs), and triglycerides. The mutations commonly associated with lipoprotein glomerulopathy are the Sendai and Kyoto variants. Other variants, like Osaka or Kurashiki variants, have also been reported.

What Are the Effects of Lipoprotein Glomerulopathy?

• Lipoprotein glomerulopathy causes disturbance in the remnant lipoprotein catabolism due to the alterations in the ApoE molecule and intravascular deposition of lipoprotein-containing thrombi in the glomerular capillaries. Structural abnormalities in the ApoE molecule reduce its ability to bind low-density lipoproteins (LDL) and intermediate-density lipoproteins (IDL).

• Abnormalities in apolipoprotein E cause alterations in the mesangial and basement membrane. This is associated with an increase in glomerular permeability and nephrotic syndrome with increased levels of LDL, VLDL, and apolipoprotein B. This impairs catabolism and lipoprotein plasma clearance and increases its ability to bind other molecules like heparin, which results in specific renal diseases like ApoE homozygote glomerulopathy, lipoprotein glomerulopathy, and membranous nephropathy-like apolipoprotein E deposition disease.

• The abnormality increases the lipoprotein plasma levels and results in the formation of apolipoprotein and lipoprotein glomerular deposition.

• Lipoprotein glomerulopathy resembles type III hyperlipidemia which is characterized by an increase in LDL and triglyceride levels. Increased levels of plasma apolipoproteins, proteinuria, microhematuria, and nephrotic syndrome.

• It also results in progressive loss of renal function. It causes focal segmental sclerosis, mild glomerulomegalia, mesangial proliferation, and reduplication of the capillary basement membrane with mesangial interposition in some patients.

• The renal function is compromised, and glomerulosclerosis and glomerular loss can be observed.

What Are the Signs and Symptoms of Lipoprotein Glomerulopathy?

Lipoprotein glomerulopathy is associated with proteinuria, dyslipidemia (lipid imbalance), and an increase in serum apolipoprotein levels. Patients with lipoprotein glomerulopathy that resemble type III hyperlipidemia present with severe dyslipidemia, cutaneous xanthomas (fat deposition under the skin surface), apoprotein E homozygosity, and atherosclerosis (plaque deposition inside the arteries). Renal involvement in type III hyperlipidemia is rare and is characterized by the accumulation of mesangial and interstitial foam cells.

What Are the Complications of Lipoprotein Glomerulopathy?

• Lipoprotein glomerulopathy results in complications like chronic renal failure.

• Abnormalities in the lipoproteins cause the development of accelerated atherosclerotic lesions and stimulate the progression of the disease. Impairment in enzyme pathways and proteins involved in lipoprotein metabolism causes chronic kidney disease.

• Lipoprotein glomerulopathy progresses to cause a nephrotic syndrome that is characterized by excessive excretion of protein in the urine. This damages the glomerular capillaries and increases the risk of infections and the formation of blood clots.

• The disease progresses to cause nephritic syndrome (inflammation of the glomerulus causing blood in the urine, increased blood pressure and reduced urine output) in some patients.

How Is Lipoprotein Glomerulopathy Diagnosed?

The diagnosis of lipoprotein glomerulopathy is based on renal biopsy and histopathological examination. Histopathological examination shows the presence of capillary ectasia, which is accompanied by mesangiolysis. The histopathological examination determines the nature of the intraluminal deposits. The interstitium shows the presence of diffuse fibroedema and tubular atrophy. The lumina of the glomerular tufts show the presence of thrombi that is finely vacuolated. All these histopathological features suggest the presence of lipoprotein glomerulopathy.

How Is Lipoprotein Glomerulopathy Treated?

• A specific treatment protocol for lipoprotein glomerulopathy has not been established. Lipid-lowering drugs are given with LDL aphaeresis to reduce the plasma lipids and lipid thrombi formation. The treatment with lipid-lowering drugs did not cause remission of proteinuria, but it was accompanied by a slow and progressive worsening of kidney function with persistent capillary lipid thrombi, interstitial fibrosis, and glomerulosclerosis.

• However, lipoprotein glomerulopathy is successfully managed with more aggressive hypolipidemic and antihypertensive drugs with LDL aphaeresis. This showed a significant improvement in the recovery of renal function and the complete remission of proteinuria.

• Recent studies showed that immunoadsorption onto protein A showed a significant response. It demonstrated reduced proteinuria, a decrease in apo E, and resolved intraglomerular thrombi.

• Fenofibrate drugs can induce the remission of this disease. However, the fibrate effects are dependent on the degree of lipid control and baseline proteinuria. Normalizing the serum apo E and triglycerides can help in judging the efficacy of lipid-lowering drugs.

Conclusion

Lipoprotein glomerulopathy is a rare disorder that affects the glomerular capillaries of the kidneys. It causes the accumulation of lipoproteins in the form of lipid thrombi in the glomeruli. It causes disturbances in lipoprotein metabolism and reduces lipoprotein plasma clearance. It is also characterized by the presence of proteinuria and renal insufficiency. It also causes progressive loss of renal function. A specific treatment protocol is not available for treating this disorder. However, lipoprotein glomerulopathy is successfully managed with more aggressive hypolipidemic and antihypertensive drugs with LDL aphaeresis, which showed a significant improvement in lipoprotein plasma clearance and the recovery of renal function.