Kidney disease cystinuria

In 54 patients, a kidney biopsy was performed 13.2 8.9 days after onset (n = 32). In all patients, the findings suggested either acute tubular necrosis or its recovery phase. The underlying diseases included kidney diseases such as IgA nephropathy [138], minimal change nephrotic syndrome [139], autosomal dominant polycystic kidney disease (ADPKD) [140], and cystinuria [67]. 

Diseases of the kidney that are discussed in this section include (1) the uremic syndrome, (2) chronic kidney disease, (3) end-stage renal disease, (4) diabetic nephropathy, (5) hypertensive nephropathy, (6) glomerular diseases, (7) interstitial nephritis, (8) polycystic Iddney disease, (9) polycystic kidney disease, (10) toxic nephropathy, (11) obstructive uropathy, (12) tubular diseases, (13) renal calculi, and (14) cystinuria. In addition, this section also includes discussions on (1) prostaglandins and NS AIDS in kidney disease, (2) monoclonal light chains and kidney disease, and (3) urinary osmolality. 

Other conditions Porphyrias, pregnancy, cystinosis, cystinuria, kidney disease, smoking, alcohol consumption, gout... 

Free cysteine occurs only in very low amounts in the blood. Most of the potential free cysteine occurs as cystine where the two SH groups are oxidized to a disulfide bond. This compound can be reduced to cysteine where and when needed. Normally, the kidney reabsorbs both cysteine and cystine. In the disease cystinuria, the transport of cystine into many cells is defective. This causes an increase in plasma cystine, resulting in a spillage of cystine in the urine. Cystine is rather insoluble and forms stones in the kidney, bladder, and ureter, which can be extremely painful. Cystine has a lower solubility as pH decreases. 

Cysteine and cystine are relatively insoluble and are toxic in excess.450 Excretion is usually controlled carefully. However, in cystinuria, a disease recognized in the medical literature since 1810,451 there is a greatly increased excretion of cystine and also of the dibasic amino acids.451 452 As a consequence, stones of cystine develop in the kidneys and bladder. Patients may excrete more than 1 g of cystine in 24 h compared to a normal of 0.05 g, as well as excessive amounts of lysine, arginine, and ornithine. The defect can be fatal, but some persons with the condition remain healthy indefinitely. Cystinuria is one of several human diseases with altered membrane transport and faulty reabsorption of materials from kidney tubules or from the small intestine. Substances are taken up on one side of a cell (e.g., at the bottom of the cell in Fig. 1-6) and discharged into the bloodstream from the other side of the cell. In another rare hereditary condition, cystinosis, free cystine accumulates within lyso-somes.453... 

Understanding and mimicking of the cellular transport processes are both challenging and rewarding from scientific and technological point of view. For example in certain inherited diseases (such as cystinuria), specific transport systems are either defective or missing [1]. Cystinuria is a human disease characterized by the absence of a transport system that carries cystine and other amino acids into kidney cells. Kidney cells normally reabsorb these amino acids from the urine and return them to the blood, but a person inflicted with cystinuria develops painful stones from amino acids that accumulate and crystallize in the kidneys. Similarly, there are many technological applications of these transport processes, e.g., bioseparations, bioextractions, and synthetic nano-bioreactors. 

Inherited defects in amino acid transport affect epithelial cells of the gastrointestinal tract and renal tubules. Some affect transport of neutral amino acids Hartnup disease), others that of basic amino acids and ornithine and cystine (cystinuria), or of glycine and proline (Chapter 12). Cystinosis is an intracellular transport defect characterized by high intralysosomal content of free cystine in the reticuloendothelial system, bone marrow, kidney, and eye. After degradation of endocytosed protein to amino acids within lysosomes, the amino acids normally are transported to the cytosol. The defect in cystinosis may reside in the ATP-dependent efflux system for cystine transport, and particularly in the carrier protein. 

Transport of molecules across plasma membranes is a critical function of all organisms. A single genetic mutation in a transport protein can give rise to disease. In cystinuria, for example, dietary cysteine can be taken up in the intestine in the form of small polypeptides and subsequently released into the bloodstream as the free amino acid which would normally be taken up by the tissues. In cystinuria, however, the import of cystine into cells cannot occur due to a genetic defect in the transport protein and the cystine in the blood is passed into the kidney where renal reabsorption is defective and the cystine precipitates as kidney stones. 

Kidney stones are a major symptom of cystinuria. What is the basis of this disease ... 

Hartnup disease Is another genetically determined and relatively rare autosomal recessive disorder. It is caused by a defect in the transport of neutral amino acids across both intestinal and renal epithelial cells. The signs and symptoms are, in part, caused by a deficiency of essential amino acids (see Clinical Comments). Cystinuria and Hartnup disease involve defects in two different transport proteins. In each case, the defect is present both in intestinal cells, causing malabsorption of the amino acids from the digestive products in the intestinal lumen and in kidney tubular cells, causing a decreased resorption of these amino acids from the glomerular filtrate. 

Patients with cystinuria and Hart- I nup disease have defective transport proteins in both the intestine and the kidney. These patients do not absorb the affected amino acids at a normal rate from the digestive products in the intestinal lumen. They also do not readily resorb these amino acids from the glomerular filtrate into the blood. Therefore, they do not have a hyperaminoacidemia (a high concentration in the blood). Normally, only a few percent of the amino acids that enter the glomerular filtrate are excreted in the urine most are resorbed. In these diseases, much larger amounts of the affected amino acids are excreted in the urine, resulting in a hyperaminoaciduria. 

Two human genetic diseases are known which involve this disulphide amino acid. In one, cystinuria , there is a transport defect in the intestine and kidney. This results in abnormally high levels of cystine in the urine and can result in the precipitation of cystine crystals and kidney stone formation. In cystinosis, cystine crystals form within cells and eventually cause severe kidney damage. The nature of the primary biochemical lesion is unknown all known cystine reduction systems of the cell appear to be normal. 

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