Tubular proteinuria

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. 

The presence of protein in the urine is a marker of glomerular and tubular dysfunction and is recognized as an independent risk factor for the progression of CKD.8 Furthermore, the degree of proteinuria correlates with the risk for progression of CKD. An increase of 1 g of protein excretion per day is associated with a five-fold increase in the risk of progression of CKD, regardless of the cause of CKD.9 The mechanisms by which proteinuria potentiates CKD are discussed later. Microalbuminuria is also linked with vascular injury and increased cardiovascular mortality.10... 

Genitourinary Renal papillary necrosis, hematuria, hyposthenuria, proteinuria, nephritic syndrome, tubular dysfunction,... 

In those patients who survive more than a few weeks, the effects of renal tubular dysfunction become more severe. Acidosis and hypo-phosphatemic rickets are prominent features. The urine is alkaline and gives a strong Rothera reaction. However, the ability to concentrate the urine is never lost and there is neither polydipsia nor polyuria. Aminoaciduria, hydroxyphenyluria, glucosuria, fructosuria, and proteinuria continue. The liver remains large and cirrhotic. Death finally occurs in liver failure, sometimes after several years. There is evidence that some children recover with no residual signs other than a large firm liver. 

Proteinuria (including albuminuria indicative of increases in the permeability of the glomerular capillary wall fi-2 microglobulin indicative of an impairment in tubular reabsorption)... 

Targeting of anti-inflammatory and anti-fibrotic drugs to the proximal tubular cell may prevent tubulointerstitial inflammation and scarring secondary to systemic and glomerular infection and proteinuria. Furthermore, tubular drug dehvery may be beneficial during shock, renal transplantation, ureter obstruction, diabetes, proteinuria, renal carcinoma and some tubular defect diseases such as Fanconi and Bartter s s5mdrome. 

Targeting of nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen could be of interest for the treatment of proteinuria and tubular defects such as Fanconi syndrome and Bartter s syndrome [73,74]. Although a conjugate with an ester spacer is preferred to a conjugate with a direct peptide hnkage [66,67], we continued our research using naproxen di-... 

The LC50 in mice was 2236ppm for 10 minutes signs of exposure were irritation of eyes and nose, delayed-onset pulmonary edema, and renal tubular damage with proteinuria, hemamria, and elevated blood urea nitrogen. In other exposed animals, a decrease in the white blood cell count and a depression of all blood elements have also been observed. ... 

Mis-localisation of annexin 2 has recently been implicated in the pathogenesis of Dent s disease. This term is now used collectively to describe what was previously four conditions that affect kidney function X-linked recessive nephrolithiasis with renal failure, X-linked recessive hypophosphatemic rickets, idiopathic low molecular weight proteinuria with hypercalciuria and nephrocalcinosis and Dent s disease. Patients with this condition present with low molecular weight proteinuria and hypercalciuria. Renal stones, nephrocalcinosis and renal failure are common late-stage developments. The condition has been attributed to abnormal acidification within endosomes of the proximal tubular cells. It is very rare and is usually caused by mutations in the voltage-dependent Cl /H+ chloride antiporter CLCN5, but occasionally in the PI4,5P2 5-phosphatase, OCRL1 (oculocerebrorenal syndrome of Lowe protein 1). 

Hypoalbuminemia is a consequence of increased glomerular filtration of albumin. Loss of albumin is caused both by the loss of albumin into the urine (albuminuria) and by the reabsorption of albumin in the proximal tubule, which is mostly accompanied by its degradation. Increased tubular degradation of albumin may explain severe hypoalbuminemia in patients with only relatively moderate proteinuria, ca 3.5-4 g/day. Synthesis of albumin in the liver of nephrotic patients... 

Direct tubular toxicity of proteinuria or interaction of tubular cells (or renal interstitium) with some specific components of the proteinuric urine, for example, albumin, transferrin, immunoglobulins and their fragments, components of complement, and chemotactic or growth factors, has been suggested (R7). 

The relative contributions of different proteins and their ligands to proteinuria-mediated tubular damage remain to be established. 

Renal Effects. Acute nephritis with albuminuria and oliguria, polyuria, and nitrogen retention were observed in individuals after application of a salve that contained potassium chromate. These effects disappeared in individuals who survived. Autopsy of people who died revealed hyperemia and tubular necrosis (Brieger 1920). Acute nephritis with polyuria and proteinuria were also described in a man who was admitted to a hospital with skin ulcers on both hands due to dermal exposure to ammonium dichromate in a planographic printing establishment where he had worked for a few months (Smith 1931). A 49-year-old man with an inoperable carcinoma of the face was treated with chromic acid crystals. Severe nephritis occurred after treatment with the chromium(VI) compound. Urinalysis revealed marked protein in the urine. Death resulted 4 weeks after exposure. A postmortem examination of the kidneys revealed extensive destruction of the tubular epithelium (Major 1922). 

Wedeen RP, Haque S, Udasin I, et al. 1996. Absence of tubular proteinuria following environmental exposure to chromium. Arch Environ Health 51(4) 321-323. 

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