Intratubular crystallization of calcium oxalate in the presence of membrane vesicles: An in vitro study (original) (raw)

2001, Kidney International

Intratubular crystallization of calcium oxalate in the presence Exactly where and how urinary stones originate are of membrane vesicles: An in vitro study. still unclear. Most urinary stones are located in the Background. Since urine spends only a few minutes in the kidneys. Some are seen attached to the renal papillae. renal tubules and has a low supersaturation with respect to Others demonstrate signs of earlier attachment to the calcium oxalate (CaOx), nucleation of CaOx crystals in the kidneys, such as remains of renal tubules in small depreskidneys is most probably heterogeneous. We have proposed sions on stone surface [1]. Kidneys of many stone patients that membranes of cellular degradation products are the main substrate for crystal nucleation. The purpose of our study was contain subepithelial plaques on their papillae [2]. These to determine the site of membrane-mediated crystal nucleation plaques are suggested to be the sites of stone developwithin the renal tubules and the required lag time, factors ment. Obviously, for a stone to form, crystallization must that determine whether crystallization results in crystalluria or occur, and crystals must be retained in the kidneys. Since nephrolithiasis. urine spends only three to five minutes in the renal tu-Methods. Nucleation of CaOx was allowed to occur in five different artificial urine solutions with ionic concentrations sim-bules and is generally undersaturated for CaOx before ulating urine in proximal tubules (PTs), descending (DLH) reaching the collecting ducts (CDs), it is suggested that and ascending (ALH) limbs of the loop of Henle, distal tubules nucleation of CaOx crystals within the renal tubules is (DTs), and collecting ducts (CDs). A constant composition most probably heterogeneous [3]. Investigations of the crystallization system was used. Experiments were run for two ionic conditions within different segments of the nephron hours with or without the renal tubular brush border membrane and application of the data to in vitro studies have shown (BBM) vesicles. Results. The addition of BBM significantly reduced the nuthat urine of the loop of Henle can support calcium cleation lag time and increased the rate of crystallization. The phosphate (CaP) nucleation [4-10]. It was proposed that average nucleation lag time decreased from 84.6 Ϯ 43.4 minutes CaP crystals formed in the loops could promote nucleto 24.5 Ϯ 19 minutes in PTs, from 143.6 Ϯ 29 to 70.2 Ϯ 53.4 ation of CaOx further along the nephron in the CDs. minutes in DLH, from 17.6 Ϯ 8.6 minutes to 0.625 Ϯ 0.65 min-The results of most in vitro crystallization studies showed utes in DTs and from 9.54 Ϯ 3.03 minutes to 0.625 Ϯ 0.65 that it took hours for the precipitation of CaP in solutions minutes in CDs. There was no nucleation in the ALH solution without BBM for two hours. CaOx dihydrate (COD) was comsimulating urine in the loop; however, urine spends only mon in most solutions. Calcium phosphate (CaP) also nucleminutes in the tubules and seconds in various segments ated in the DLH and CD solutions. [7, 8]. Since crystallization must occur in moving urine, Conclusions. In the absence of membrane vesicles, there studies in one laboratory utilized a dynamic crystallizawas no crystallization in any of the solutions within the time tion system [7, 8]. The solution composition simulated urine spends in the renal tubules. As a result, homogeneous changing conditions existing in the proximal tubule (PT), nucleation of crystals anywhere within the nephron appears unlikely. However, BBM-supported nucleation is possible in the descending limb of the loop of Henle (DLH), the the DTs as well as CDs. A high crystallization rate in CDs ascending limb of the loop of Henle (ALH), the distal would promote rapid crystal growth and aggregation, resulting tubule (DT), and finally to the conditions existing in the in crystal retention within the kidneys and development of CD. When the solution conditions became similar to nephrolithiasis. those in the DLH, precipitation of CaP required less than three seconds. The CaP precipitate, however, began to dissolve in the ascending limb conditions (ALH) and