Nephrotic Syndrome and Associated Renal Lesions

Nephrotic syndrome may occur in any type of primary or secondary glomerulonephritis. Around two dozen histopathological categories or subcategories of glomerulonephritis are now recognized and etiological factors are largely determined. However, prevention and treatment of glomerulonephritis needs momentum to curb the development of irreversible renal failure. The main diagnostic feature of nephrotic syndrome is massive proteinuria (excretion of protein in urine) exceeding 3 g/24 hour. The other features of nephrotic syndrome, such as, hypoproteinemia (decreased level of proteins in blood), edema (swelling) and hyperlipidemia (elevated levels of lipids in blood) are consequential due to excretion of proteins in urine. Clinically the patient does not bother to consult a nephrologist or general physician until edema becomes evident. With the fall in the plasma osmotic pressure due to loss of the plasma proteins in urine the fluid from blood would leak into the interstitial space resulting in a reduction in circulating blood volume, but the kidneys try to maintain blood volume by retaining salts and water.

In children around 80% cases of nephrotic syndrome are due to minimal change disease(MCD) and in adults the dominance of MCD is lost. In adults the cause of nephrotic syndrome may be minimal change disease, membranous glomerulonephritis (MGN), focal glomerulosclerosis, mesangial proliferative glomerulonephritis or membranoproliferative glomerulonephritis (MPGN). Metabolic disorders like diabetes mellitus could also be a cause of nephrotic syndrome. Secondary amyloidosis is also known to cause renal lesions associated with nephrotic syndrome. Immunological disorders like systemic lupus erythematosis and vasculitis may also be a cause of glomerulonephritis. Renal biopsy evaluation by light microscopy (LM), immunofluorescence microscopy (IFM) and electron microscopy (EM) is must for an accurate diagnosis of type of glomerulonephritis in a patient of nephrotic syndrome. Minimal change disease, membranous glomerulonephritis (MGN), focal glomerulosclerosis, mesangial proliferative glomerulonephritis, membranoproliferative glomerulonephritis (MPGN) and diffuse endocapillary glomerulonephritis are the common and primary causes of nephrotic syndrome. Focal segmental proliferative glomerulonephritis and diffuse proliferative glomerulonephritis with crescents are considered as uncommon-primary causes of nephrotic syndrome. Glomerulonephritis due to metabolic disorders, immunological disorders, toxemia of pregnancy or malignant conditions of kidney are labeled as secondary causes of nephrotic syndrome.

Bacterial Endocarditis and Associated Kidney Disease

There is very strong association between bacterial endocarditis or heart valve infection and kidney disease. Prior to the discovery, development and active use of antibiotics, the majority of the patients developed renal disease (kidney disease) as a consequence of subacute valvular infection. The incidence of clinical renal involvement has dropped significantly with the introduction of effective treatment of bacterial endocarditis with antibiotics. The assessment of renal involvement in bacterial endocarditis is quite difficult as transient changes in urine sediment are generally observed. There may be focal and segmental lesions with normal creatinine clearance. Intravenous drug users are at greater risk of developing bacterial endocarditis.

Staphylococcus aureus infection as the cause of bacterial endocarditis has been reported in majority of the cases that lead to a higher frequency of diffuse glomerular disease. The renal lesions associated with endocarditis involved embolization and infection. The renal lesions could also have immunological basis as immune complex deposits within glomeruli have been detected in majority of the cases. The involvement of complement (an immune response modulator protein in our blood) system during active disease (bacterial endocarditis) in association with immune complexes complicates the severity of intra-glomerular lesions. The two major categories of renal lesions found in patients affected by bacterial endocarditis are: (1) Focal segmental abnormality due to subacute infection and (2) Diffuse glomerular lesions in the patients with acute bacterial endocarditis mimicking the pattern of post-streptococcal glomerulonephritis. The electron micrograph (Fig-1) from the kidney biopsy of a patient with acute glomerulonephritis and acute bacterial endocarditis illustrates the subepithelial immune complex deposits.

Fig-1: Electron micrograph illustrating the hump shaped subepithelial immune complex deposits (D) alongside the glomerular basement membrane (GBM) and urinary space (US), during acute glomerulonephritis. Uranyl acetate and Lead citrate stain.

The assessment of renal involvement in endocarditis may be difficult diagnostic entity as only minor and transient changes are observed in urinary deposit with variable changes in blood biochemistry. The clinician must recognize the status of impaired cardiac output in the first stage and later workout the potential risk of treatment associated antibiotic nephrotoxicity. The assessment of renal function at the time of presentation of case could be helpful to rule out endocarditis associate renal disease or treatment associated antibiotic nephrotoxicity.