Proteinuria low-molecular weight

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). 

High-molecular weight proteinuria Low-molecular weight proteinuria... 

At any level, the proteinuria may be nonselective in that it contains the spectrum of molecular sizes. For example, when microalbuminuria is observed in the absence of low molecular weight proteinuria, it may... 

Kabanda A, Jadoul M, Lauwerys R, Bernard A, van Ypersele de Strihou C. Low molecular weight proteinuria in Chinese herbs nephropathy. Kidney Int 1995 48 1571-1576... 

Wrong OM, Norden AGW, Feest TG. Denfs disease a fanuhal proximal renal tubular syndrome with low molecular weight proteinuria, hypercalciuria, nephro-calcinosis, metabohc bone disease, progressive renal failure, and a marked male predominance. Q ) Med 1994 87 473-93. 

Despite the technical problems associated with its measurement, the experience with P2-m far exceeds that of all other low molecular weight proteinuria assays [79]. 

Denfs disease is a familial renal tubular syndrome characterized by low molecular-weight proteinuria, hypercalciuria, nephrolithiasis and eventual renal failure. Mutations in the CLC-5 chloride channel are the basis for this disease. In humans, this channel is expressed mainly in the kidney, and mutations in the human CLCN5 promoter region might be the cause of Denf s disease (Devuyst et al. 1999, Hayama et al. 2000). 

Dent s disease a familial renal tubular syndrome, characterized by low molecular weight proteinuria, hypercalciuria, nephrolithiasis, and eventual renal failure dermatitis inflammation of the skin dermographism over-sensihve reaction of the skin in which pressure or friction gives rise to a wheat so that a word traced is visible... 

Several studies indicate that the onset of low-molecular weight proteinuria is a sign of irreversible kidney damage (Friberg et a ., 1974 Roels et al., 1982 Piscator 1984 Elinderet al., 1985 Smith et al., 1986). Above specific levels of ( 2-M associated with cadmium exposure it is unlikely that P2-M levels return to normal even when cadmium exposure is eliminated by removal of the individual from the cadmium work environment (Friberg, Ex. 29, 1990). 

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 urine frequently contains casts and amorphous debris, but rarely any considerable number of red blood corpuscles. Proteinuria and aminoaciduria are found in nearly all untreated patients from a very early age. The proteinuria is usually reported as albuminuria in the literature, but in some cases the urinary protein has been shown by electrophoresis to consist largely of a-globulin and other relatively low-molecular-weight proteins (B21). A similar urinary pattern occurs in a number of diseases of the renal tubule. The proteinuria is often only moderate in degree, e.g., < 50 to 150 mg protein per 100 ml of urine, but is easily detected by the conventional tests for protein, such as salicylsulfonic acid. Excretion of protein can rise to nearly 1 g/100 ml in some cases (H8, L7). 

A 72-year-old man was treated with ceftriaxone (2 g bd) and gentamicin (80 mg tds) for a severe urinary tract infection (75). On day 5 his serum potassium concentration was 3 mmol/1 with a normal serum creatinine and urine examination. Despite treatment with oral potassium chloride plus a high potassium diet, his serum potassium fell to 2.3 mmol/1 4 days later, accompanied by inappropriate kaliuresis, hypouricemia with inappropriate uri-cosuria, and hypophosphatemia with inappropriate phosphaturia. There was no bicarbonate wasting, but there was proteinuria 1.2 g/day, with a predominance of low molecular weight proteins in contrast, serum creatinine was normal and creatinine clearance was 78 ml/minute. The aminoglycoside was withdrawn with subsequent progressive improvement in renal proximal tubular function, which normalized 9 days later. 

Madalena L, Facio ML, Angerosa M, Pandolfo M, Bresciani P, Alejandre M, Pizzolato M,Toblli JE. Urinary excretion of low molecular weight proteins in patients with pure monoclonal light chain proteinuria. J Nephrol. 2007 Nov-Dec 20(6) 683-8. 

PIscator M. Proteinuria In chronic cadmium poisoning. III. Electrophoretic and Immuno-electrophoretic studies on urinary proteins from cadmium workers, with special reference to the excretion of low molecular weight proteins. Arch Environ Health 1966 12 335-344. 

The tubular reabsorptive process is saturable. Any increase in the filtered load (because of glomerular damage, increased glomerular vascular permeability [e.g., inflammatory response], or increased circulating concentration of low molecular weight proteins) or decrease in reabsorptive capacity (because of tubular damage) can result in increased urinary protein excretion proteinuria). The pattern of urinary protein excretion can be used to identify the cause and to classify the proteinuria, of which there are three main types (Table 45-5). Diagnostic approaches to the characterization of proteinuria are considered in Chapter 24. 

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