NEPHROTIC SYNDROME COMPLICATIONS

• Nephrotic Syndrome
• Symptoms of Nephrotic Syndrome
• Treatment of Nephrotic Syndrome
• Complications of Nephrotic Syndrome

Complications of the nephrotic syndrome

A number of complications are recognized in patients with the nephrotic syndrome: these result from the metabolic consequences of prolonged protein loss.
 

Infections

The incidence of infections, particularly bacterial, is increased in the nephrotic syndrome. Peritonitis is well recognized in children and is an important cause of mortality. Cellulitis, particularly streptococcal, is common and may spread rapidly. The cause of the increased susceptibility to infections is a combination of physical factors such as the accumulation of fluid in the interstitial space, the peritoneal and/or pleural space, and the impairment of defence mechanisms, such as the reduction in immunoglobulin concentration and impaired white cell function.

Prompt induction of remission of oedema and proteinuria is the best method of preventing infection. When this cannot be achieved, good skin care is important, and there is a good case for using prophylactic penicillin to prevent pneumococcal infection in oedematous children.  

Antipneumococcal vaccines against capsular antigens induce an adequate response when given to patients in remission. Any suspicion of infection should be treated aggressively in those with the nephrotic syndrome, with a low threshold for starting a parenteral antibiotic regimen, including benzylpenicillin in children, as soon as necessary cultures have been taken.

Thromboembolism

There is an increase in both arterial and venous thromboses in patients with the nephrotic syndrome. The increased thrombotic tendency is manifest by an increased risk of deep leg vein thromboses and pulmonary embolism and an increase in arterial thrombotic episodes. Deep leg vein thrombosis is clinically evident in about 6 per cent of nephrotic adults and can be detected in about 25 per cent if Doppler ultrasonography is used. Likewise, after any thromboembolic event they would advise anticoagulation for as long as the nephrotic state persisted.

Renal vein thrombosis may occur, presenting acutely with loin pain, haematuria, deterioration in renal function, and with swelling of the kidney detectable on imaging (usually by ultrasonography). It can also present with a significant increase in urinary protein excretion and a gradual reduction in renal function. Some are associated with pulmonary embolism. Renal vein thrombosis can be associated with all causes of the nephrotic syndrome, most common in membranous glomerulonephritis, when it is clinically apparent in 6 to 8 per cent of cases and detectable on imaging in 10 to 45 per cent.

Treatment of symptomatic renal vein thrombosis is by anticoagulation with full-dose therapeutic intravenous heparin or low molecular weight heparin (although there is little experience of using the latter in this condition) followed by warfarinization. Thrombolysis has also been used, although the indications for this are not well defined. The prognosis is usually benign, with recanalization of the veins and recovery of renal function.
 

Alterations in lipid metabolism

Alterations in lipid metabolism are well recognized in patients with nephrotic syndrome. There is concern that these changes might lead to atheromatous vascular disease and also be an adverse factor with respect to the development of progressive renal function impairment.

Patients with the nephrotic syndrome have an increased concentration of both free cholesterol and cholesterol esters, which have an inverse correlation with plasma albumin concentration. There is an increase in phospholipids, and in severe cases fasting triglycerides are elevated. Plasma free fatty acid concentrations are reduced.

There are alterations in lipoproteins: very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) are increased, whilst high-density lipoprotein (HDL) concentrations are less predictably affected.

There is an increase in the hepatic production of VLDL and LDL. In addition there is evidence for the diminished removal of LDL, possibly due to a reduction in the activity of lipoprotein lipase. The changes in HDL concentrations are probably related to the reduction in lecithin cholesterol acyl transferase (LCAT) activity that occurs in nephrotic patients.

Proteinuria and the progression of renal disease

It is well recognized that proteinuria is associated with glomerulonephritis. In experimental studies proteinuria is associated with interstitial damage, tubular injury, and glomerulosclerosis. Heavy proteinuria is associated with progressive glomerular scarring, and intervention to reduce proteinuria is accompanied by reduction in sclerosis. It is possible that the prolonged and heavy proteinuria has an adverse effect on mesangial cells leading to mesangial sclerosis and eventually global sclerosis, but it is likely that proteinuria is only one of many factors responsible for progressive renal disease.