The urinary tract and male reproductive system
C. Simon Herrington in Muir's Textbook of Pathology, 2020
The main types of urinary calculi are as follows: Calcium-containing stones, the calcium salt being predominantly oxalate with lesser amounts of calcium phosphate. These comprise more than 75% of all urinary calculi and are characteristically laid down in an acid urine.Complex triple phosphate stones including magnesium, ammonium, carbonate, and calcium components. These comprise 15% of urinary calculi and are laid down in alkaline urine. They may form an outer laminated deposit on other stones and are strongly associated with urinary tract infection.Uric acid and urate–uric acid stones comprise 5% of urinary calculi but affect up to 20% of patients with gout. Similar to calcium-containing stones they are typically laid down in an acid urine. Pure uric acid stones are radiolucent, rendering their detection on a plain abdominal radiograph virtually impossible.Cystine stones occur in primary cystinuria, a rare but important renal disease in childhood.
Parathyroid Hormone (Pth)
Fuad S. Ashkar, Lelio G. Colombetti in Radiobioassays, 2019
Cystine stones occur in patients with cystinuria. Uric acid and urate stones result from increased urinary uric acid concentration as in gout or in patients with abnormally acid urine. Apatite stones (phosphates of calcium) usually form in patients suffering from such disorders as hyperparathyroidism, renal tubular acidosis, Cushing’s syndrome, and other conditions associated with hypercalciuria. Oxalate stones, pure or in combination with apatite, may be found in patients with the same underlying conditions enumerated for apatite stones. Occasionally, they may be associated with primary hyperoxaluria, a congenital disease of metabolism. However, oxalate stones frequently occur in patients who are recurrent renal stone formers with no known underlying pathology. Magnesium ammonium phosphate stone formers are almost always found to have urinary tract infections.
The Nature of Renal Function
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
Amino acids are reabsorbed in the same general manner as glucose and phosphate. At least five transport proteins exist, some of which transport sodium and one of the major subclasses of amino acids with high specificity, while others operate as exchangers, transporting one group of amino acids out of the cell in exchange for entry of another (31). The normal plasma concentrations of all the amino acids are below threshold in health, so that normal urine contains virtually no amino acids of any kind. Several inherited defects of proximal tubular amino acid transport systems have been described. By far, the commonest is cystinuria. This is caused by mutations in an apical membrane system that operates as an amino acid exchanger. It transports cystine and the dibasic amino acids arginine, lysine, and ornithine into the cell in exchange for exit of neutral amino acids. This is another form of secondary active transport. The driving force for exchange is the steep cell-to-lumen gradient for neutral amino acids generated by sodium-coupled entry of the latter, also across the apical membrane. The exchanger is a heterodimer of two components, labeled rBAT and bo,+AT, respectively (32). The mutations that cause cystinuria affect rBAT, and numerous loss of function mutations have so far been identified in different families (33). The only clinical significance of cystinuria is the tendency to form cystine stones in the urinary tract: affected individuals are otherwise healthy.
What are the main challenges to the pharmacological management of cystinuria?
Published in Expert Opinion on Pharmacotherapy, 2020
Michael E. Rezaee, Andrew D. Rule, Vernon M. Pais
It is important to recognize inherent challenges in cystinuria management due to low medication compliance. Prior research has shown that less than 20% of cystinuria patients achieve and maintain urinary cystine levels low enough to prevent stone formation [16]. Other chronic conditions, such as hypertension, have higher documented medication compliance rates ranging from 35–60% [17]. Cystinuria is a genetic, chronic disease with an early average age of onset between 20 and 30 years of age. Thus, it can be difficult for patients to comply with long-term medication use that requires taking multiple pills 3 to 4 times a day, especially given occasionally intolerable side effects of many of the medications. However, these patients are also often highly motivated due to frequent debilitating episodes of renal colic. As such, cystinuria patients should be managed in comprehensive multidisciplinary metabolic stone clinics, comprised of nephrologists, urologists, and dietitians to achieve the best possible outcomes for these patients [18]. This is an especially important management strategy given that 25% of cystinuria patients are known to develop non-cystine stones during their lifetime [19].
Safety profile of D-penicillamine: a comprehensive pharmacovigilance analysis by FDA adverse event reporting system
Published in Expert Opinion on Drug Safety, 2021
Vijay Kumar, Anand Prakash Singh, Nicholas Wheeler, Cristi L. Galindo, Jong-Joo Kim
D-pen is also used to treat cystinuria, an inherited autosomal recessive disease caused by mutations in SLC3A1 and SLC7A9 genes. These mutations manifest high concentrations of the amino acid cystine in the urine, which enhances the formation of cystine stones in the kidneys, ureter, and bladder [20,21]. Cystinuria patients cannot properly reabsorb cystine into their bloodstream, leading to the accumulation of cystine in their urine. The excess cystine forms crystals and becomes stones that can create blockages in the urinary tract and provide sites for bacterial infections [20,21]. D-pen is used to reduce urine levels of cystine. D-pen combines and forms disulfide bonds with cysteine, resulting in the formation of a D-pen-cysteine disulfide compound that is more soluble than cystine and thereby facilitates the excretion in urine [22,23].
Alpha lipoic acid as a novel therapeutic approach to cystinuria
Published in Expert Opinion on Orphan Drugs, 2018
Scott V. Wiener, Thomas Chi, Marshall L Stoller
Cystinuria is a rare genetic disorder that results in recurrent, debilitating kidney stone episodes. Cystine is a dimer of two cysteine molecules that is poorly soluble at typical urinary pH (5–7) and rapidly crystalizes. Traditional management strategies rely on extremely high fluid intake (up to 5L daily), dietary management, altering urine pH to increase cystine solubility and competitive binding of cysteine molecules to form more soluble dimers. These treatments are poorly tolerated and require significant lifestyle modification for affected patients. Surgical treatments tend to be more frequent, more invasive, and less effective for affected patients due to the radiographic (poorly visible) and physical characteristics (difficult to break) of cystine stones.
Related Knowledge Centers
- Aminoaciduria
- Bladder
- Cystine
- Dimerization
- Hematuria
- Sodium Nitroprusside
- Urine
- Ureter
- Kidney
- Kidney Stone Disease