Recurrent Stone Formers Research Articles

Long-term effects of potassium citrate therapy on the formation of new stones in groups of recurrent stone formers with hypocitraturia.

To compare stone formation rates before (as total rates and during remote periods) and after therapy with potassium citrate in patients with hypocitraturia. The study comprised 15 patients with hypocitraturia only (Group I) and 12 patients with hypocitraturia associated with other abnormalities (Group II), all of whom were recurrent stone formers. Their urine chemistry, including citrate, was measured before and after treatment. In both groups, the urinary citrate concentration increased significantly to within normal limits during therapy with potassium citrate (P < 0.005). The rate of total stone formation in patients in Group I decreased significantly from 0.7/year before to 0.13/year after treatment (P < 0.005). The corresponding remote stone formation rate before (0.88/year) was significantly greater than the rate after treatment (0.13/year; P < 0.005; follow-up 4.6 +/- 1.9 years). Patients in Group II showed a similar striking decrease in total stone formation rate, from 1.2/year to 0.08/year after treatment (P < 0.005). The corresponding remote stone formation rate (1.66/year) before was significantly greater than that after treatment (0.08/year; P < 0.005; follow-up 4.1 +/- 1.6 years). There was a remission rate of 93% for stone formation over the complete follow-up. Potassium citrate appears to be the drug of choice in the long-term treatment of patients with hypocitraturia as it not only decreases the rate of stone formation but also maintains normal citrate levels in the urine.

Isoelectric focusing of Tamm-Horsfall glycoproteins: a simple tool for recognizing recurrent calcium oxalate renal stone formers

Tamm-Horsfall glycoproteins (THPs) from healthy probands and a majority of recurrent calcium oxalate renal stone formers reveal different physicochemical properties when analyzed using isoelectric focusing (IEF). The pI values of THPs from healthy probands are approximately 3.5 while THPs from recurrent renal stone formers have pI values of between 4.5 and 6. The two groups of THPs exhibit completely different protein patterns. The differences in IEF analysis allow differentiation between THPs from healthy probands and recurrent calcium oxalate stone formers and may possibly be used as a simple diagnostic method for the recognition of recurrent calcium oxalate renal stone formers.

Recurrent stone formation: Pathophysiology and prevention

Recurrent stone formation: Pathophysiology and prevention

Evaluation of the risk of stone formation: study on crystalluria in patients with recurrent calcium oxalate urolithiasis.

The aim of this study was to determine the usefulness of the morning calcium oxalate crystalluria in detecting stone formers particularly prone to recurrence. Over a 24-hour period of urine collection, the morning calcium oxalate crystalluria was evaluated as well as the risk of stone formation, established with Tiselius and Parks indices, for 25 recurrent stone formers (group 1) and 25 normal controls (group 2). Morning crystalluria (type, size, number/ml and state of aggregate) and the Tiselius index were comparable in the two groups. Conversely, calciuria as well as the citrate/ calcium ratio and the Parks index varied significantly for stone formers and normal controls. No particular correlation appeared between crystalluria and indices of Tiselius and Parks, calciuria, calcium-oxalate product or calcium/ oxalate and citrate/calcium ratios. Morning calcium oxalate crystalluria does not enable an efficient characterization of recurrent stone formers. Its discordance with others potential indicators of the risk of stone formation poses the problem of their respective validity and evokes the prevalence of still unknown inhibiting agents in the phenomenon of crystallization.

Experience with augmentation cystoplasty. A review.

Good experience with clam cystoplasty is reported for 28 patients (14 female), 89% of whom had a neuropathic bladder. Prolonged conservative treatment had failed in all cases. The efficacy of the operation in terms of continence, increased bladder compliance, and bladder capacity was confirmed. Complications were common and included inability to void (70%) requiring clean intermittent catheterisation (CIC), recurrent urinary tract infection (59%) and stone formation (22%). Due to these complications, further surgery was required for 44% of the patients. Although clam enterocystoplasty is an efficient way to reconstruct a functionally disturbed urinary tract, careful patient selection is essential. Lifetime follow-up and recognition of the most frequent complications is mandatory.

Effect of oral calcium loading on intact PTH and calcitriol in idiopathic renal calcium stone formers and healthy controls

The calciuric response after an oral calcium load (1000 mg elemental calcium together with a standard breakfast) was studied in 13 healthy male controls and 21 recurrent idiopathic renal calcium stone formers, 12 with hypercalciuria (UCa x V > 7.50 mmol/24 h) and nine with normocalciuria. In controls, serum 1,25(OH)2 vitamin D3 (calcitriol) remained unchanged 6 h after oral calcium load (50.6 +/- 5.1 versus 50.9 +/- 5.0 pg/ml), whereas it tended to increase in hypercalciuric (from 53.6 +/- 3.2 to 60.6 +/- 5.4 pg/ml, P = 0.182) and fell in normocalciuric stone formers (from 45.9 +/- 2.6 to 38.1 +/- 3.3 pg/ml, P = 0.011). The total amount of urinary calcium excreted after OCL was 2.50 +/- 0.20 mmol in controls, 2.27 +/- 0.27 mmol in normocalciuric and 3.62 +/- 0.32 mmol in hypercalciuric stone formers (P = 0.005 versus controls and normocalciuric stone formers respectively); it positively correlated with serum calcitriol 6 h after calcium load (r = 0.392, P = 0.024). Maximum increase in urinary calcium excretion rate, delta Ca-Emax, was inversely related to intact PTH levels in the first 4 h after calcium load, i.e. more pronounced PTH suppression predicted a steeper increase in urinary calcium excretion rate. Twenty-four-hour urine calcium excretion rate was inversely related to the ratio of delta calcitriol/deltaPTHmax after calcium load (r = -0.653, P = 0.0001), indicating that an abnormally up-regulated synthesis of calcitriol and consecutive relative PTH suppression induce hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential analysis of recurrent calcium calculi by infrared spectroscopy.

While the incidence of calcium urolithiasis increases, the precise mechanism of calcium oxalate stone formation is still controversial. Is the composition of a recurrent calcium oxalate stones always the same as previous ones? There are few reports that specifically address the question by study of sequential changes of the composition of recurrent calcium calculi. From our medical records 70 patients with a history of two or more recurrent episodes of calcium oxalate stone disease were selected and the analyses of 190 stones were reviewed. Infrared spectroscopic analysis was done using a Perkin Elmer 1740 spectrophotometer. Calcium oxalate monohydrate were detected in 63 stones, calcium oxalate dihydrate in 12, calcium oxalate monohydrate mixed with dihydrate in 28, calcium oxalate monohydrate mixed with calcium phosphate in 30, calcium oxalate dihydrate mixed with calcium phosphate in 20, calcium oxalate monohydrate mixed with dihydrate and calcium phosphate in 20, calcium oxalate monohydrate mixed with dihydrate and calcium phosphate in 37. Alterations of stone components during follow-up were found in 43 stones from 40 patients. The shift of a main composition from calcium oxalate monohydrate to calcium oxalate dihydrate was found in 24 stones and vice versa in 19 stones. Sequential changes of the compositions of recurrent calcium calculi are highly likely to occur with time in individual recurrent calcium stone formers. Calcium oxalate monohydrate was a most common component of the studied recurrent calcium stones.

A study of recurrent stone formers with special reference to renal tubular acidosis.

Forty-five patients with recurrent renal stone were examined for distal renal tubular acidosis (dRTA) defects by acid challenge test (150 mg ammonium chloride/kg body weight). Their 24-h urine samples were analysed for creatinine, calcium, oxalic acid, inorganic phosphorus, uric acid, magnesium and citric acid. One-hour urine samples before acid load and hourly samples for the 7 h following acid challenge test were collected and analysed for creatinine, calcium, citric acid, inorganic phosphorus, titratable acidity, and ammonium. The incidence of distal RTA defect was 22.2% in the patients examined. The major biochemical characteristics in RTA patients compared with patients without RTA were: (a) significantly higher urinary pH, (b) significantly lower excretion of citric acid, (c) no significant difference in calcium excretion and (d) a tendency toward lower titratable acidity and ammonium excretion.

Renal mass and serum calcitriol in male idiopathic calcium renal stone formers: role of protein intake.

To determine whether chronic overconsumption of protein might increase renal mass and cause up-regulation of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D] production, 57 male recurrent idiopathic calcium stone formers (RCSF), 29 with hypercalciuria (HCSF; urinary calcium x V, > 7.50 mmol/day) and 28 with normocalciuria (NCSF), were compared with 15 healthy male controls (C) while consuming a free choice diet. Renal mass in RCSF was measured by the sum of the surface areas of right and left kidneys (square centimeters) on plain films of the abdomen by a computer-assisted sonic stylus; in C, renal mass was assessed sonographically. Serum intact PTH and 1,25-(OH)2D were measured radioimmunometrically. In HCSF, urinary phosphate x V (35.9 +/- 1.2 mmol/day) was higher than that in NCSF (29.3 +/- 1.3 mmol/day; P = 0.0009) or C (28.7 +/- 1.8 mmol/day; P = 0.005); urinary creatinine x V (16.5 +/- 0.5 mmol/day) was also higher in HCSF than in NCSF (15.0 +/- 0.5 mmol/day; P = 0.024) or C (13.8 +/- 0.6 mmol/day; P = 0.002). For identical blood levels of ionized calcium and phosphate, the 1,25-(OH)2D/PTH concentration ratio (an index of regulation of 1,25-(OH)2D production) was higher in HCSF (6.5 +/- 1.0) than in NCSF (4.0 +/- 0.3; P = 0.005). In addition, the sum of the surface areas of right and left kidneys was increased in HCSF (163.4 +/- 2.9 cm2) compared with that in NCSF (140.5 +/- 3.1 cm2; P = 0.0001), and it positively correlated with urinary phosphate x V (r = 0.429; P = 0.001) as well as with urinary creatinine x V (r = 0.294; P = 0.026); no such correlation was noted in C. Calcitriol levels were positively related to renal mass in RCSF (r = 0.316; P = 0.018), but not in C. Finally, urinary calcium x V positively correlated with the serum calcitriol/PTH concentration ratio only in RCSF (r = 0.388; P = 0.003). These findings suggest that protein overconsumption may cause an increase in renal mass and up-regulate calcitriol production in some male RCSF, an effect that would subsequently cause "idiopathic" hypercalciuria.

Urinary tamm-horsfall protein increased after potassium citrate therapy in calcium stone formers

Objectives To evaluate the effect of oral potassium citrate therapy on urinary excretion rates of citrate, Tamm-Horsfall protein (THP), and on calcium oxalate monohydrate crystal agglomeration inhibition [tm], in patients with recurrent calcium stone formation. Methods To evaluate the effect of oral therapy with potassium citrate on urinary citrate, THP, and [tm], 24-hour urine samples were collected before and at least 2 months after initiation of oral potassium citrate therapy in 33 calcium stone-forming patients who had no dietary restrictions. The citrate concentration was measured by an adaptation of a citrate lyase method. Urinary disaggregated THP concentration was determined with a quantitative enzyme-linked immunosorbent assay. The [tm] was determined by observing the effects of patients' urine, before and after oral potassium citrate therapy, on the uptake of 45Ca 2+ onto the surfaces of added preformed calcium oxalate crystals in a supersaturated solution of calcium oxalate, using the in vitro kinetic method described by other investigators. Results We observed an increased urinary excretion rate of citrate from a mean of 1.9 mmol/24 h prealkali to 2.6 mmol/24 h postalkali ( P < 0.0004) and of THP from a mean of 94.0 mg/24 h prealkali to 199.3 mg/24 h postalkali ( P <0.0016). A corresponding increase in [tm] from a mean of 177.1 minutes prealkali to 221.0 minutes postalkali ( P < 0.024) was also observed. Conclusions To our knowledge this is the first report correlating increased urinary citrate with THP excretion rate following oral alkalinization with potassium citrate in calcium stone formers. Of clinical importance is the corresponding increase in [tm], which was previously shown to be inversely related to stone-forming activity. Moreover, urinary citrate and THP are known to have a synergistic effect on [tm]. Our data suggest that the effectiveness of potassium citrate therapy in calcium stone-forming patients may, at least in part, be due to increased levels of THP.

Evidence for the Presence of Abnormal Proteins in the Urine of Recurrent Stone Formers

Two-thirds of matrix of all urinary stones consists of proteins. Despite intense research, their relationship to calculogenesis remains controversial. In an attempt to study excretion of proteins in stone formers, their urinary profiles were analyzed and compared with those of healthy subjects. Two-dimensional gel electrophoresis was employed to obtain high resolution separation of proteins. The urine of patients with histories of idiopathic calcium oxalate (CaOx) calculi contained 7 unique proteins, and 2 others that appeared to be overexpressed. Except for alpha 1 -acid glycoprotein, the remaining 8 proteins are previously unknown constituents of urine with molecular weights of approximately 43, 39.5, 29, 26, 25.5, 26.5, 27 and 18.5 kD. Their isoelectric points range from 5.5 to 8.0. Coelectrophoresis of pooled urinary proteins of male and female stone formers disclosed that all 9 proteins had identical charges and molecular weights, regardless of the donors' sex. Analyses of urines of idiopathic recurrent CaOx stone formers who had no radiologically detectable calculi also revealed the presence of these proteins. This excludes the possibility that the proteins might be a consequence of abrasion of urothelial lining by the developing stone(s). Recently defective Tamm-Horsfall mucoprotein (THM) has been implicated in urinary stone formation. Coelectrophoresis of pooled urinary proteins of healthy subjects and stone formers denoted that it had an identical charge and molecular weight in both groups. This suggested that stone formation could not be ascribed to a difference in composition of THM. Whether this is attributable to a dissimilar amino acid sequence of this mucoprotein, remains to be probed.

Evidence for the Presence of Abnormal Proteins in the Urine of Recurrent Stone Formers

Evidence for the Presence of Abnormal Proteins in the Urine of Recurrent Stone Formers

Effect of Medical Management and Residual Fragments on Recurrent Stone Formation Following Shock Wave Lithotripsy

Minimal emphasis has been placed on the clinical sequelae of residual stone fragments following shock wave lithotripsy. Moreover, there are no studies investigating the role of medical therapy on the course of stone disease in patients with residual fragments. In this retrospective, nonrandomized review, we evaluated 80 patients who had undergone shock wave lithotripsy at various institutions in Texas and were referred to our mineral metabolism clinic for metabolic evaluation and medical management of the stone disease. Of the patients 31 were determined to be stone-free following lithotripsy, while 49 had residual stone fragments. All patients were contacted an average of 43.2 months (range 9 to 79) following shock wave lithotripsy and the radiographs were reviewed. Patients were placed into 4 groups after shock wave lithotripsy: stone-free or residual fragments on or off medical therapy. In the stone-free group (19 patients), medical treatment produced a significant decrease in stone formation from a median of 0.67 to 0.0 stones per patient per year (p < 0.001). In 36 patients with residual fragments stone formation before shock wave lithotripsy was higher than in the stone-free group but there was also a significant decrease in the stone formation rate from a median of 2.47 to 0.00 stones per patient per year while on medical therapy (p < 0.001). Of the 12 stone-free patients who did not remain on medical therapy there was a slight decrease in the stone formation rate from a mean of 0.83 to 0.40 stones per patient per year, although this decrease was not significant (p = 0.07). In 13 patients with residual fragments not on medical treatment there was only a minimal decrease in the stone formation rate from a median of 1.33 to 0.77 stones per patient per year (p = 0.06). We also assessed the significance of so-called clinically insignificant residual fragments (smaller than 5 mm.) following shock wave lithotripsy in 26 of the 36 patients with residual fragments. More than half of the 26 patients with clinically insignificant fragments in the group that did not continue on medical therapy demonstrated significant stone growth during followup, suggesting that these fragments were not insignificant. Moreover, only 16% of the patients with fragments smaller than 5 mm. demonstrated an increase in fragment size while on medical therapy, again suggesting that appropriate medical treatment can decrease the risk of recurrent stone formation or growth (p < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Renal morphology and urodynamic factors for renal stone formation

Studies on the pathogenesis of urolithiasis have mainly focused on metabolic disorders. However, metabolic disorders alone are not sufficient to explain the problem. In the present study, morphological and urodynamic differences of the upper urinary tract on both the stone and normal side were examined. There were 35 cases of those who had experienced unilateral, recurrent, and/or multiple stone formation. 1. Morphologic study. Study of the pelvic-caliceal system (PCS) revealed significant differences in the following parameters on the stone side as compared with the normal side. The findings were: 1) the number of minor calices (papillaes), Np, was higher; 2) the number of major calices, Nm, was higher; 3) the number of branches, Nb, was higher; 4) the lower calyx radius, 1(2), was longer; 5) the total calyx area, Ac, was larger; 6) the renal pelvic area, Ar, was larger; 7) and the total area, At, was larger. 2. Urodynamic study. Additional study of the urodynamic factors revealed significant differences in the following parameters on the stone side as compared with the normal side. These findings include: 1) the peristaltic frequency in the upper third of the ureter was less; 2) the difference in peristaltic interval was longer and the rhythm of the peristaltic discharge was irregular. However, no significant difference in the contraction pressure was found except in the pelviureteral junction. After furosemide had been administered, the contraction pressure decreased while the peristaltic frequency increased on both sides. Furthermore, it was found that on the stone side the peristaltic interval decreased significantly as well as the rhythm of the peristaltic discharge becoming regular. The results of the two studies indicate that in the same individual the urine flow in the stone side as compared to the of the normal side is either stagnant or inconstant, thereby creating conditions conductive to the formation and growth of stones which become difficult to discharge owing to these same conditions. Therefore, morphological and urodynamic disorders of the upper urinary tract may be considered as factors contributing to stone formation. It appears that the diuretic action is an effective method for preventing stone recurrence and facilitating stone passage.

Tamm-Horsfall glycoprotein: role in inhibition and promotion of renal calcium oxalate stone formation studied with Fourier-transform infrared spectroscopy

Tamm-Horsfall glycoprotein (THP) from healthy probands inhibits the precipitation of calcium oxalate, whereas THP from individuals who repeatedly develop calcium oxalate stones has no effect or even promotes precipitation. Using Fourier-transform infrared spectroscopy, we found a structural differentiation between these functionally different THPs: a decisive difference in sialic acid content. Quantitative analysis for sialic acid showed the same results. THP from healthy probands had a high sialic acid content (51 +/- 9 g/kg), whereas THP from recurrent stone formers had a decreased sialic acid content (21 +/- 4 g/kg). This explains the dual role of THP in the precipitation of calcium oxalate and the formation of renal stones and shows the importance of glycosylation in the function of this glycoprotein.

Serum super oxide dismutase (SOD), malondialdehyde (MDA) levels in urinary disorders

Evaluation of serum SOD and MDA level was done in 21 first episode renal stone formers, 9 recurrent stone formers, 20 patients with obstructive uropathy other than urolithiasis and 12 patients with urinary infection. Twenty-two healthy volunteers were taken as controls. The level of SOD in respective groups was 2.12±0.84, 2.78±0.85, 1.42±0.31, 1.98±0.70 and 2.32±0.62 units/ml and of MDA was 2.61±1.07, 2.69±1.15, 1.65±0.33, 1.33±0.34 and 1.55±0.48 n mol/ml respectively. The results indicate increased peroxidative stressin nephrolithiasis only. Since SOD level was normal in all groups, this increased peroxidative stress in nephrolithiasis should be due to factors other than this one.

Circadian variations in the risk of urinary calcium oxalate stone formation.

To evaluate the circadian fluctuations in the risk of urinary calcium oxalate stone formation with regard to critical periods of crystallization. Over a given time period, the Tiselius index depends on urine volume and urinary excretion of oxalate, calcium, citrate and magnesium. This crystallization potential was evaluated during three successive periods spread over 24 h for 25 recurrent stone-formers aged 16-76 years (mean 50) and 25 control subjects aged 27-71 years (mean 44). There was no significant difference in the value of the Tiselius index for all equivalent time periods in both groups of patients. The minimum value was recorded in the afternoon and the circadian pattern of the index illustrated the predominant importance of urinary output in its determination. Morning urinary concentrations and excretions of citrate, and nocturnal levels of magnesium were significantly higher in the stone-formers when compared with the control subjects. The lithogenic risk for calcium oxalate stones was maximal at the end of the night or during the early morning, when urinary output was minimal. This circadian study revealed abnormalities that are not apparent from non-fractionated 24 h urine samples, and which were potentially relevant to therapy.

Value of repeated analyses of 24-hoururine in recurrent calcium urolithiasis

Objectives. The value of repeated analyses of 24-hour urine collectionsfor daily excretion of calcium, uric acid, citrate, phosphorus, and creatinine and for volume and pH performed to detect and classify metabolic disorders in a selected group of calcium stone formers with striking recurrence rates was assessed in a retrospective study. Methods. A total of 441 urinalyses made over a mean period of 80.4 months of samples obtained from 49 patients were reviewed. Fifty-nine percent of patients were initially found to have metabolic disorders (absorptive hypercalciuria types I and II, hyperuricuria, hypocitraturia) and therefore received specific drug therapy (allopurinol, thiazide, alkali citrate, orthophosphate) for a mean of 45.7 months (group I). The remaining patients were classified as metabolically inactive and were given general metaphylactic instructions (group II) Results. In 73% of patients recurrent stones developed, with no statistically significantdifference between the two groups (79% vs 65%). In 55% of group I patients, urinalyses continued to yield abnormal findings during follow-up; however, subsequent abnormal findings were also seen in 40% of the metabolically inactive group II patients. Overall, metabolic disorders were observed at some point in 75% of patients. Only 27% remained recurrence free, and 62% thereof also had pathologic urinary findings. Conclusions. It does not appear that drug treatment in recurrent calcium urolithiasisbased on urinary findings is superior to simple general metaphylactic recommendations, nor that repeated analyses of 24-hour urine collections furnish additional information on the risk of recurrent stone formation or on the presence of risk factors leading to recurrence in the long-term course of disease.

Increased Calcium Absorption in Nephrolithiasis Explained by Uptake Studies in Ileal Brush Border Membrane Vesicles

We previously showed that recurrent calcium renal stone formers have enhanced urinary excretions of calcium and oxalate resulting from malabsorption of citrate. In the present investigation, the mechanism of the citrate-induced increased calcium uptake was studied using guinea pig ileal brush border membrane vesicles. In this model, calcium is absorbed in a concentration dependent, single mechanism uptake with a Km of 275 +/- 30 umol/liter (SD) and a Vmax of 4.0 +/- 0.5 nmol/min.mg protein. Under conditions of maximal calcium uptake, both citrate and phosphate inhibited calcium absorption into brush border membrane vesicles (BBMVs). In contrast, when phosphate and citrate were added together, calcium absorption normalized. Citrate inhibition of calcium absorption appeared to be due to free citrate ions, and phosphate ions overcame this inhibition. Phosphate inhibition was mostly due to decreased concentrations of ionized calcium and partly to precipitation of insoluble calcium phosphate. These studies confirm that the effects of citrate in humans in enhancing calcium absorption occur in the lumen of the gut and are not related to further biochemical conversions of citrate by the gut cells, to effects of citrate on calcium-related hormones, or to the renal handling of calcium. Also, the effects of citrate on increasing calcium absorption should be increased or attenuated in patients who malabsorb citrate, and this explains the increased urinary calcium and oxalate excretions reported for recurrent calcium stone formers.

Dietary management of urolithiasis

Within the United States, 5% to 15% of the population will have a symptomatic episode of a stone within the urinary tract by the age of 70. At least 50% of these individuals will have recurrent stone formation if left untreated. The composition of urine from which these stones are formed and in which they grow is, in part, dependent on diet, including fluid intake. The volume of urine is an important determinant of solute concentration. Ionic strength, pH, and the concentration of the major ionic species present in urine determine the level of saturation for any crystal system that could be precipitating. There are many conditions that can be complicated by the formation of calculi within the urinary tract. Identifying the dietary factors that are contributing to the problem and correcting these abnormalities are the foundations for good medical management. This review identifies dietary components that need to be considered in the management of affected patients and considers specific medical problems that may be especially influenced by diet and fluid intake.