Glomerular injury

Cadmium is effectively accumulated in the kidneys. When the cadmium concentration exceeds 200 gg/g in the kidney cortex, tubular damage will occur in 10% of the population, and proteins begin to leak into urine (proteinuria). When the concentration of cadmium in the kidney cortex exceeds 300 pg/g, the effect is seen in 50% of the exposed population. Typically, excretion of low-molecular weight proteins, such as beta-microglobulin, is increased, due to dysfunction of proximal tubular cells of the kidney. The existence of albumin or other high-molecular weight proteins in the urine indicates that a glomerular injury has also taken place. The excretion of protein-bound cadmium will also be increased. 

Among the various primary and secondary glomerular diseases, diabetic nephropathy represents the most common cause of stage 5 chronic kidney disease accounting for about 44% of all patients on dialysis. One important mediator of glomerular injury in diabetic... 

Johnson R, Couser W, Alpers C, Vissers M, Schulze M. The human neutrophils serine proteinases, elastase and cathespin G can mediate glomerular injury in vivo. J Exp Med 1988 168 1169-1174. 

Excretion of markedly elevated levels of protein is indicative of glomerular disease, whereas low-level proteinuria indicates tubular damage or very early/lowgrade glomerular injury (Peterson et al. 1969 Finco 1997). Further determination of the severity and... 

Small numbers of lipid droplets (representing neutral lipid, lipoprotein or phospholipid) are considered normal in dogs, cats, mice and humans (Gross et al. 1991 Streather et al. 1993 Finco 1997). Increased excretion of lipid droplets (which may cause increased urine turbidity) may indicate glomerular injury (de Mendoza et al. 1976 Gherardi and Calandra 1982). Increased urinary phospholipid excretion (confirmed by thin layer chromatography) may indicate early papillary injury/renal papillary necrosis in rodents (Thanh etal. 2001). 

Increased albumin usually indicates glomerular injury, although it is not a specific marker for any one nephron site (Guder and Hofmann 1992 Price et al. 1996 Finn and Porter 1998). High levels of albumin in urine are invariably the result of glomerular malfunction. Low level increases in urine albumin, especially in circumstances where total urine protein excretion is not elevated ( microalbuminuria ) can result either from increased glomerular filtration or decreased tubular reabsorption, and albumin values... 

Due to size limitations, most enzymes present in plasma are not filtered into the urine but there are some exceptions (e.g., lysozyme) these will be increased in the urine if tubular function (and uptake of filtered protein) is decreased. In addition, if glomerular injury accompanies tubular injury leakage of larger molecular weight proteins may occur and plasma source enzymes that ordinarily would not be filtered may appear in urine. AST, LDH and IALP may thus appear in urine. 

Tolins JP, Raij L (1990) Comparison of converting enzyme inhibitor and calcium channel blocker in hypertensive glomerular injury. Hypertension 10 452-461 Tonshoff B, Powell DR, Zhao D et al. (1997) Decreased hepatic insulin-like growth factor (IGF)-I and increased IGF binding protein-1 and -2 gene expression in experimental uremia. Endocrinology 138 938-946... 

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... 

Kimura et al. (1993) described strain specificity in the susceptibility of mice to daunomycin-induced glomerular injury. Klahr and Morrissey (1997) described the effects of ACE inhibitors and angiotensin II receptor antagonists on various parameters associated with renal interstitial fibrosis induced by unilateral ureteral obstruction in rats. 

Milner LS, Wei SH, Houser MT (1991) Amelioration of glomerular injury in doxorubicin hydrochloride nephrosis by dimethylthiourea. J Lab Clin Med 118 427 134 Milner LS, Wei S, Kazakoff P et al. (1994) Synergistic effect of fish oil diet and dimethylurea in acute adriamycin nephrosis. AM J Med Sci 308 266-270 Mizuno S, Mizuno-Horikawa Y, Yue BF et al. (1999) Nephrotic mice (ICGN strain) A model of diffuse mesangial sclerosis in infantile nephrotic syndrome. Am J Nephrol 19 73-82... 

In rare cases penicillamine can cause extracapillary glomerulonephritis with more extensive and serious glomerular injury leading to progressive and persistent renal insufficiency. One such patient has been described with a review of 26 similar published cases (233). 

Peltier J, Bellocq A, Perez J,DoublierS, Dubois YC, Haymann JP,CamusslG,and Baud L.Calpain activation and secretion promote glomerular injury in experimental glomerulonephritis evidence from calpastatin-transgenic mice. J Am Soc Nephrol 17 3415-3423, 2006. 

Tomosugi N, Cashman S, Hay H, Pusey C, Evans D, Shaw A, Rees A. Modulation of antibodiy-mediated glomerular injury nv Vo by bacterial llpopolysaccharide, tumor necrosis factor, and IL-I. J Immunol 1989 142 3083-3090. 

Tipping PG, Huang XR, Berndt MC, Holdsworth SR. A role for P selectin In complement-independent neutrophil-mediated glomerular Injury. Kidney Int. 1994 46 79-88. 

KagamI S, Kondo S. Betal-integrins and glomerular injury. J Med Invest. 2004 51 1-13. 

Jennette JC, Falk RJ Acute renal failure secondary to leukocyte-mediated acute glomerular injury. Ren Fail. 14 395-399,1992... 

Jocks T, Zahner G, Freudenberg J, Wolf G, Thaiss F, Helmchen U, Stahl RA Prostaglandin El reduces the glomerular mRNA expression of monocyte- chemoattractant protein 1 in anti-thymocyte antibody-induced glomerular injury. J Am Soc Nephrol... 

Saunders JR, Aminian A, McRae JL, O Farrell KA, Adam WR, Murphy BF Clusterin depletion enhances immune glomerular injury in the isolated perfused kidney. Kidney Int 45 817-27,1994... 

BertanIT, FerrazzI P, Schleppatl A, RuggenentI P,Gamba A, Parenzan L, Mecca G, Perico N, ImbertI O, RemuzzI A, RemuzzI G. Nature and extent of glomerular Injury Induced by cyclosporine In heart transplant patients. Kidney Int 1991 40 243-250. 

Allen AR, McHale J, Smith J, Cook HT, Karkar A, et al. 1999. Endothelial expression of VCAM-1 in experimental crescentic nephritis and effect of antibodies to very late antigen-4 or VCAM-1 on glomerular injury. J Immunol. 162 5519— 27... 

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