Renal defects

Trisomy 13 (Patau syndrome, 47,XY,+13 47,XX,H 13) is seen in approximately 1 in 10,000 live births. More than 90% of conceptions are lost prenatally, and more than 90% of those who survive to term do not survive to 1 year of age. Common disease features include oral-facial clefts, microphthalmia (small eyes), renal defects, and polydactyly (extra fingers). Central nervous system malformations and heart defects are common and contribute to mortality. 

Approximately two thirds of all renal stones contain calcium phosphate or calcium oxalate. Many patients with such stones exhibit a renal defect in calcium reabsorption that causes hypercalciuria. This can be treated with thiazide diuretics, which enhance calcium reabsorption in the distal convoluted tubule and thus reduce the urinary calcium concentration. Salt intake must be reduced in this setting, as excess dietary NaCl will overwhelm the hypocalciuric effect of thiazides. Calcium stones may also be caused by increased intestinal absorption of calcium, or they may be idiopathic. In these situations, thiazides are also effective, but should be used as adjunctive therapy with decreased calcium intake and other measures. 

Abnormalities in renal or tissue autoregulatory systems could cause hypertension. It is possible that a renal defect in sodium excretion may develop first, which can then cause resetting of tissue autoregulatory processes, resulting in a higher arterial BP. 

A combination of suturing with synthetic thread in an atraumatic needle and the use of KL-3 adhesive was employed to dose lesions of the kidneys. The renal defect in nephrolithotomy was treated with a continuous suture before application of KL-3 adhesive to the wall of the renal parenchyma. The hgation of large intraorgan vessels (more than 7 mm in diameter) has been performed and appeared to be beneficial when the adhesive joining the renal tissue was followed with suturing of the defect of the renal fibrous capsule, which allowed the wound to be sealed and isolated the adhesive from adjacent tissues. 

Under the general conditions of balance techniques, identical outflow and constant pool size at the time of measurement mean identical inflow into the pool. Thus, there is no difference in purine absorption between normal and hyperuricemic persons. However, under the experimental conditions used, hyperuricemic persons clearly show a lower than normal renal elimination of uric acid at any given level of plasma uric acid. This is further evidence in favor of a renal defect as the... 

The vitamin D3 metabolite la,25-dihydroxycholecalciferol is a lifesaving drug in treatment of defective bone formation due to renal failure. Retrosynthetic analysis (E.G. Baggjolint, 1982) revealed the obvious precursors shown below, a (2-cyclohexylideneethyl)diphenylphosphine oxide (A) and an octahydro-4f/-inden-4-one (B), to be connected in a Wittig-Homer reaction (cf. section 1.5). 

Our attention is focus on the biochemical defects of kynurenine pathway. The concentration of metabolites changes under various diseases, such as neurodegenerative disease, memory loss, chronical renal failure, eyes disease. 

Humans lacking AQP1 do not suffer from any severe symptoms. The only phenotype that can be observed in these individuals is a mild renal concentration defect. 

Polycystic kidney disease (Polycyst in-1 activates canonical Wnt signaling pathway) Injury-induced renal fibrosis Heart failure Ulcerative colitis Osteoporosis-Pseudoglioma Syndrome (genetic syndrome of defective bone formation) Ulcerative colitis Familial Alzheimer s disease (through interaction with Presenilin-1) Familial Alzheimer s disease (through interaction with Presenilin-1)... 

Fatal hereditary disorder that typically presents in the neonatal period. Clinical features include an array of hepatic, renal and neurological dysfunctions. Patients with Zellweger syndrome rarely survive the first year of life. The disease is caused by mutations in the Pex proteins leading to an defective import of peroxisomal matrix proteins and consequently to a loss of most peroxisomal metabolic pathways. 

This complex contains 11 polypeptide subunits of which only one is encoded by mtDNA. Defects of complex III are relatively uncommon and clinical presentations vary. Fatal infantile encephalomyopathies have been described in which severe neonatal lactic acidosis and hypotonia are present along with generalized amino aciduria, a Fanconi syndrome of renal insufficiency and eventual coma and death. Muscle biopsy findings may be uninformative since abnormal mitochondrial distribution is not seen, i.e., there are no ragged-red fibers. Other patients present with pure myopathy in later life and the existence of tissue-specific subunits in complex III has been suggested since one of these patients was shown to have normal complex 111 activity in lymphocytes and fibroblasts. 

Hyperargininemia. This defect is characterized by elevated blood and cerebrospinal fluid arginine levels, low erythrocyte levels of arginase (reaction 5, Figure 29-9), and a urinary amino acid pattern resembling that of lysine-cystinuria. This pattern may reflect competition by arginine with lysine and cystine for reabsorption in the renal tubule. A low-protein diet lowers plasma ammonia levels and abolishes lysine-cystinuria. 

Glycinuria results from a defect in renal tubular reabsorption. The defect in primary hyperoxaluria is the failure to catabolize glyoxylate formed by deamination of glycine. Subsequent oxidation of glyoxylate to oxalate results in urohthiasis, nephrocalcinosis, and early mortality from renal failure or hypertension. 

There are numerous abnormalities of cysteine metabolism. Cystine, lysine, arginine, and ornithine are excreted in cystine-lysinuria (cystinuria), a defect in renal reabsorption. Apart from cystine calculi, cystinuria is benign. The mixed disulfide of L-cysteine and L-homocysteine (Figure 30-9) excreted by cystinuric patients is more soluble than cystine and reduces formation of cystine calculi. Several metabolic defects result in vitamin Bg-responsive or -unresponsive ho-mocystinurias. Defective carrier-mediated transport of cystine results in cystinosis (cystine storage disease) with deposition of cystine crystals in tissues and early mortality from acute renal failure. Despite... 

A number of genetic diseases that result in defects of tryptophan metabolism are associated with the development of pellagra despite an apparently adequate intake of both tryptophan and niacin. Hartnup disease is a rare genetic condition in which there is a defect of the membrane transport mechanism for tryptophan, resulting in large losses due to intestinal malabsorption and failure of the renal resorption mechanism. In carcinoid syndrome there is metastasis of a primary liver tumor of enterochromaffin cells which synthesize 5-hydroxy-tryptamine. Overproduction of 5-hydroxytryptamine may account for as much as 60% of the body s tryptophan metabolism, causing pellagra because of the diversion away from NAD synthesis. 

Glutaric acidurias Type I Primary defect of glutarate oxidation Type II Defect of electron transfer flavoprotein Type I Severe basal ganglia/cerebellar disease with macrocephaly. Onset 1-2 years Type II Fulminant neurological syndrome of the neonate. Often with renal/hepatic cysts. Usually fatal Diet low in lysine and tryptophan Supplementation with coenzyme Q, riboflavin, carnitine... 

Coenzyme Q10 (CoQlO) deficiency. This mitochondrial encephalomyopathy has three main clinical presentations. A predominantly myopathic form is characterized by the triad of exercise intolerance, recurrent myoglobinuria, and CNS involvement. A more frequent ataxic form is dominated by ataxia and cerebellar atrophy, variously associated with weakness, developmental delay, seizures, pyramidal signs, and peripheral neuropathy, often simulating spinocerebellar atrophy. A third presentation with fatal infantile encephalomyopathy and renal involvement, has been described in two families. The biochemical defect (or defects) presumably involve different steps in the biosynthesis of CoQlO, but are still unknown, as are the molecular defects. Diagnosis, however, is important because all patients - and especially those with the myopathic and infantile forms - benefit from CoQlO supplementation [13,14]. 

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