Urolithiasis
Manit Arya, Taimur T. Shah, Jas S. Kalsi, Herman S. Fernando, Iqbal S. Shergill, Asif Muneer, Hashim U. Ahmed in MCQs for the FRCS(Urol) and Postgraduate Urology Examinations, 2020
The most important factor in uric acid stone formation is low urinary pH as most patients have normal urinary uric acid levels. Uric acid solubility is significantly reduced when urinary pH is <5.5. Other important factors include low urine volume and a hyperuricosuria. Low urinary volume can more commonly occur in patients with chronic diarrhoeal conditions, ileostomies, excessive sweating or poor oral intake. Hyperuricosuria occurs in addition to hyperuricaemia in patients with primary gout, myeloproliferative conditions and Lesch-Nyhan syndrome. Hyperuricosuria occurs in patients without raised serum urate levels due to some medications (thiazides or salicylates) and excessive intake of dietary meats.
The Scientific Basis of Urinary Stone Formation
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
Uric acid is the end-product of purine metabolism and is normally excreted in urine in the range 2 to 5 mmol/day (75,76). Patients with urinary excretions above this range are prone to form uric acid stones, but hyperuricosuria per se is not the sole cause or even the most important factor in uric acid lithiasis (77). Dehydration is as important as hyperuricosuria, and a low urine pH is more critical than both of these factors (78,79). The main causes of hyperuricosuria are listed in Table 2. The most recent addition to this list is fructose, which has been shown to increase the urinary excretion of uric acid following the breakdown of fructose by fructokinase (80).
Cholelithiasis and Nephrolithiasis
John K. DiBaise, Carol Rees Parrish, Jon S. Thompson in Short Bowel Syndrome Practical Approach to Management, 2017
For patients with hyperuricosuria refractory to diet modification, xanthine oxidase inhibitors such as allopurinol should be considered. The potential side effects of allopurinol, including rash, gastrointestinal upset, and transaminitis, may limit its use [96]. The novel xanthine oxidase inhibitor febuxostat has a more favorable safety profile and improved bioavailability and is more potent than allopurinol [97]. Further study of its use in SBS is warranted.
Established and recent developments in the pharmacological management of urolithiasis: an overview of the current treatment armamentarium
Published in Expert Opinion on Pharmacotherapy, 2020
Mohamed Abou Chakra, Athanasios E. Dellis, Athanasios G. Papatsoris, Mohamad Moussa
There is a global diversity in the prevalence of uric acid (UA) nephrolithiasis. UA stone comprises 8–10% of all kidney stones in the United States. However, its prevalence is higher in patients with type 2 diabetes mellitus and those with obesity. Three significant urinary abnormalities have been described as the main etiologic factors for the development of UA nephrolithiasis; low urinary pH, hyperuricosuria and low urinary volume [108]. Patients with medical conditions that promote profound hyperuricosuria are at high risk of developing uric acid calculi. These conditions include myeloproliferative disorders, and monogenic metabolic disorders, such as Lesch-Nyhan syndrome [109]. In idiopathic UA nephrolithiasis, the urinary pH and the fractional excretion of urate are significantly lower than in control subjects. Since these impairments are believed to be associated with primary gout, the underlying disturbance in idiopathic UA nephrolithiasis may be primary gout. Some but not all patients with primary gout suffer from uric acid stones or display hyperuricemia at a given time [110].
Current understanding of Lesch-Nyhan disease and potential therapeutic targets
Published in Expert Opinion on Orphan Drugs, 2019
Human HPRT is encoded by the HPRT1 gene located on the long arm of the X chromosome [21] and HPRT deficiency is inherited as a recessive X-linked trait. Thus, males are generally affected and women are generally asymptomatic carriers. Several women with LND due to a variety of molecular mechanisms have been described in the literature [22–26]. HPRT1 mutations, accounting for HPRT deficiency, are very heterogeneous in type and localization [27-30]. The diagnosis of HPRT deficiency must be supported by clinical, biochemical, enzymatic and molecular data. Hyperuricemia with hyperuricosuria is the biochemical hallmark that prompts an enzymatic diagnosis [29]. Patients present low or undetectable HPRT activity in hemolysates, with increased adenine phosphoribosyltransferase (APRT) activity. To better characterize the HPRT deficiency, in order to find a possible residual activity, enzyme activity can be measured in intact cells (erythrocytes or fibroblasts) [4,10,30]. Although LND variants are designated as partial HPRT deficiency, only HRH patients exhibit a residual HPRT activity in hemolysates, while it is extremely unusual in HND patients [30]. Some residual HPRT activity has been described in fibroblasts from patients with HND [3].
Kidney stone proteomics: an update and perspectives
Published in Expert Review of Proteomics, 2021
Paleerath Peerapen, Visith Thongboonkerd
The association of hyperuricosuria and CaOx kidney stone formation was investigated by studying the alteration in renal epithelial cellular proteome in response to high-dose uric acid [84]. Levels of 22 proteins were changed after the cells were incubated in 3.5 mM uric acid-containing medium. The protein alterations caused by uric acid treatment were accompanied by the increases of COM crystal-cell adhesion, cell migration activity, and intracellular ATP production [84]. Interestingly, uric acid-induced up-regulation of heat shock protein (HSP) 70 kDa (HSP70) and HSP90 at apical membrane fraction led to the increment of COM crystal-binding capacity of the cells that could be blocked by specific antibodies to HSP70 and HSP90 [84]. These data strengthened the relationship between hyperuricosuria and CaOx kidney stone formation and might explain the underlying mechanisms of such related disorders.
Related Knowledge Centers
- Allopurinol
- Bladder
- DNA
- Purine
- Rna
- Uric Acid
- Uricosuric
- Urine
- Kidney
- Hyperuricemia