Glomerular nephritis

Long-term lithium therapy is associated with a 10% to 20% risk of morphologic renal changes (e.g., glomerular sclerosis, tubular atrophy, and interstitial nephritis). 

In all forms of glomerular nephritis in tropical populations in Africa, there was increased protein in the urine. In the selective proteinuria of the nephrotic syndrome most of the protein was mainly albumin and transferrin, with lower concentrations of IgG and other globulins. On the other hand, the urine of the nonselective proteinuria of the nephrotic syndrome is characterized by much higher concentrations of IgG, IgA, a2-macroglobulins, and some IgM. Differential protein clearance to establish selectivity of proteinuria has been discussed above. 

The author has observed a marked hypogammaglobulinemia in patients with the nephrotic syndrome in both the West Indies and Nigeria. In these patients the serum IgG level may be less than 500 mg/100 ml, and the urine electrophoretic pattern may resemble that of a normal serum. The striking hypogammaglobulinemia which so frequently accompanies chronic glomerular nephritis is responsible for the superimposed infection that may occur in this condition. 

Rare reactions with long-term use include peptic ulcer disease, G1 bleeding, gastritis, severe hepatic reactions (cholestasis, jaundice), nephrotoxicity (glomerular nephritis, interstitial nephritis, nephrotic syndrome), and an acute hypersensitivity reaction (includingfever, chills, and join pain). 

Extensive literature has accumulated concerning other forms of renal dysfunction during long-term lithium therapy, including chronic interstitial nephritis and minimal-change glomerulopathy with nephrotic syndrome. Some instances of decreased glomerular filtration rate have been encountered but no instances of marked azotemia or renal failure. 

There are many other reports arguing against this mechanism as the major pathogenetic pathway of lupus nephritis. The presence of circulating DNA/anti-DNA immune complexes is difficult to detect (B25,13). Moreover, recent studies demonstrated that the levels of circulating DNA (nucleosome) immune complexes were low (B28, F8, L14). Data also suggest that DNA/anti-DNA complexes are rapidly cleared by the liver (E5) and bind poorly to glomerular basement membrane (GBM) (12). 

Schmiedeke, T. M., Stockl, F. W., Weber, R., Sugisaki, Y., Batsford, S. R., and Vogt, A., Histones have high affinity for the glomerular basement membrane. Relevance for immune complex formation in lupus nephritis. J. Exp. Med. 169,1879—1894 (1989). 

R6. Remuzzi, A., Monaci, N., Bonassi, M. E., Coma, D., Zoja, C., Mohammed, E. I., and Remuzzi, G., Angiotensin-converting enzyme inhibition prevents loss of glomerular hydraulic permeability in passive Heymann nephritis. Lab. Invest. 79, 1501—1510 (1999). 

Y2. Yang, D. H., Goyal, M., Sharif, K., Kershaw, D., Thomas, P., Dysko, R., and Wiggins, R., Glomerular epithelial protein 1 and podocalysin-like protein 1 in inflammatory glomerular disease (crescentic nephritis) in rabbit and man. Lab. Invest. 74, 571-584 (1996). 

Glomerular lesions, such as those found in diabetes and glomerular nephritis, are characterized by basement membrane thickening and an increase in collagen-like substances within the mesangial regions that ultimately lead to proteinuria. Protease inhibitors prevent thickening of the basement membrane and reduce proteinuria. 

Various experimental procedures were described as models for glomerulonephritis in human beings. Most of them were developed in rats and rabbits. They involve the reactions of antibodies against renal components, such as Masugi nephritis (Masugi and Sato 1934), Heymann nephritis (Heymann 1959), nephrotoxic serum nephritis (Unanue and Dixon 1967), crescentic type anti-glomerular membrane nephritis (Nagoe et al. 1994, 1998), anti-Thyl nephritis (Chen etal. 1999). 

Nagamatsu et al. (1999) found beneficial effects of an angiotensin II type I receptor antagonist in anti-glomerular basement membrane antibody-associated nephritis in rats. 

Hara M, Batsford SR, Mihatsch MJ et al. (1991) Complement and monocytes are essential for provoking glomerular injury in passive Heymann nephritis in rats. Terminal complement components are not the sole mediators of proteinuria. Labor Invest 65 168-179... 

Nagamatsu T, Hayashi K, Oka T, Suzuki Y (1999) Angiotensinll typel receptor antagonist suppresses proteinuria and glomerular lesions in experimental nephritis. Eur J Pharmacol 374 93-101... 

A prerenal mechanism secondary to the vascular leak syndrome is commonly involved in the pathophysiology of acute renal insufficiency. In addition it has been suggested that a direct intrinsic intrarenal effect of aldesleukin with a higher than expected reduction in glomerular filtration rate or tubular dysfunction (85,89) is involved. Several isolated cases of acute interstitial or tubulointerstitial nephritis with predominant T lymphocjde infiltration of the kidneys (90-92) and the exacerbation of a subchnical IgA glomerulonephritis (93) suggested altered cell-mediated immunity. 

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