A critical evaluation of the urinary inhibiting activity in idiopathic calcium oxalate nephrolithiasis

In order to obtain new insights into the relevance of inhibitors in whole urine by focusing on their reciprocal interactions, a statistical approach was followed in 35 controls and 27 calcium oxalate (CaOx) recurrent idiopathic stone formers. The inhibiting activity of CaOx crystal growth and the most widely accepted inhibitors (glycosaminoglycans, citrate, magnesium, pyrophosphate), stone constituents (calcium, oxalate, phosphate, urate) and other normal urinary substances were evaluated. It was seen that the inhibitors played a very small role in total inhibiting activity. On the other hand, considering other normal urinary constituents, almost all the inhibiting power of urine on crystal growth could be explained.     

Low urinary citrate excretion in nephrolithiasis

The urinary citrate excretion was examined in patients with nephrolithiasis who were categorized on the basis of different physiologic or metabolic abnormalities. A wide prevalence of low citrate excretion (hypocitraturia) was observed, with over one half of our patients with stones exhibiting it. Hypocitraturia was found in all patient categories except primary hyperparathyroidism and hyperuricosuric calcium oxalate nephrolithiasis. As expected, hypocitraturia was present in renal tubular acidosis and in enteric hyperoxaluria. However, urinary citrate was also low in absorptive and renal hypercalciurias, and in patients in whom an acid-base disturbance was clearly excluded.     

A single 24-hour urine collection is inadequate for the medical evaluation of nephrolithiasis

PURPOSE: We determined the adequacy of a single 24-hour urine sample for evaluating patients for medical renal stone prevention. MATERIALS AND METHODS: A total of 459 patients from a private urology practice specializing in the treatment of urolithiasis and 683 from a university stone research clinic provided 2 and 3, 24-hour urine samples, respectively. We used samples 1 and 2 from private practice patients, and 1 and 3 from university clinic patients for analysis, and compared each to the others by correlation coefficients and calculation of the mean difference plus or minus standard deviation (SD) of the difference. Urine risk factors were measured by standard methods. RESULTS: Although the correlation of urine values 1 and 2 was excellent for all stone risk factors, SD values for the differences were large enough that within 1 SD on either side of 0, which included 68.8% of cases, by chance urine 1 would depart from urine 2 by clinically important amounts. These departures would be more than sufficient to misdiagnose common metabolic disorders. CONCLUSIONS: A single 24-hour sample is not sufficient for evaluating patients before metabolic treatment for stone prevention because misdiagnosis is common, leading to inappropriate treatment.     

Total urinary protein in different types of nephrolithiasis

In 26 healthy individuals and 114 patients with urolithiasis, total urine protein levels were measured in a single sample by using the stain ponceau S. The findings were statistically analyzed. The levels of the protein were found to be 27-80 mg/l in the healthy individuals, while the distribution of the data was asymmetric as viewed from high values. The patients with urolithiasis exhibited their protein levels according to the type of nephrolithiasis. Proteinuria was demonstrated to be less pronounced in patients with oxalate and urate nephrolithiasis than in patients with coral phosphate calculi. There was a substantial asymmetry in the distribution of total urine protein for all the examined groups of urolithiasis patients, as well as great dispersion values, which fails to regard the parameter alone as a diagnostic criterion for the type of nephrolithiasis. At the same time it was noted that simultaneous examination of the levels of total protein, uric acid, potassium, and sodium enabled the type of a concrement (oxalate or phosphate) to be in vivo estimated with approximately 85% probability.     

Association of urinary pH with body weight in nephrolithiasis

BACKGROUND: The prevalence of kidney stone disease in the United States is progressively increasing, paralleling the growing rate of obesity. Uric acid nephrolithiasis, a condition associated with a low urinary pH, has been linked to obesity and insulin resistance. Based on these observations, we hypothesized that urinary pH may be inversely associated to body weight in nephrolithiasis. METHODS: Data were retrieved from 4883 patients with nephrolithiasis who underwent ambulatory evaluation at two established stone clinics in Dallas and Chicago. The patients collected 24-hour urine samples on an outpatient basis, while avoiding any drug that could alter urinary pH. Patients were divided in increasing sextiles of body weight, and urinary pH was adjusted for urinary creatinine and for age. RESULTS: Urinary pH had a strong, graded inverse association with body weight. Urinary creatinine and age were both found to be significant covariates of urinary pH, while gender was not a significant independent variable after adjustment for urinary creatinine. Mean 24-hour urinary pH, adjusted for age and urinary creatinine, were 6.09, 6.04, 6.01, 5.99, 5.97, and 5.91 for sextiles of body weight in increasing order from Dallas (P for linear trend <0.0001), and 6.18, 6.10, 6.04, 6.02, 5.97, and 5.88 for the sextiles from Chicago (P for linear trend <0.0001). CONCLUSION: We conclude that urinary pH is inversely related to body weight among patients with stones. The results confirm the previously proposed scheme that obesity may sometimes cause uric acid nephrolithiasis by producing excessively acid urine due to insulin resistance.     

A simplified urinary incontinence score for the evaluation of treatment outcomes

There are no standardized definitions for anti-incontinence therapy outcomes. The present study was conducted to evaluate whether the incorporation of several non-invasive outcome measures into a new score may serve as a meaningful outcome instrument. Ninety-four consecutive sphincteric incontinent women who underwent a pubovaginal sling by a single surgeon were enrolled. All patients underwent a full clinical evaluation, including pre- and post-operative questionnaires, 24-hour voiding diary, and 24-hour pad test. Surgery outcomes were classified twice: First, by analyzing the patient questionnaire, voiding diary, and pad test separately, according to previously published criteria, and second, by combining the three outcome tools into a new response score. The new score was constructed in a simple, easy-to-remember format and divided into five categories: cure, good response, fair response, poor response, and failure. All patients were evaluated at least 1 year post-operatively. Comparison of the old and new classifications suggests that the new response score provides a more accurate evaluation of the surgical outcomes. Although 64 to 69% of the patients were originally classified as cure according to the old classification, only 44.7% were re-classified as cure by the strict criteria employed in the new score. Furthermore, the response score also differentiates between various degrees of clinical improvement (i.e., good, fair, or poor response). Twenty-five (26.6%) patients, most of whom were previously classified as cure, were re-classified as good response, whereas 20 others were re-classified as fair (13. 9%), or poor (7.4%) response. Seven (7.4%) patients were re-classified as surgical failures. All were diagnosed pre-operatively as having complex sphincteric incontinence. Specific failure rates were therefore 11.3% for complex and 0% for simple cases. In conclusion, the suggested post-operative response score incorporates in a user-friendly format three popular outcome tools (i.e., 24-hour diary, 24-hour pad test, and patient questionnaire) and seems to reflect the surgical results more accurately. Further studies are needed to assess its validity and reproducibility in other treatment modalities. Neurourol Urodynam. 19:127-135, 2000.     

Seasonal variations in urinary risk factors among patients with nephrolithiasis

Twenty-four hour urine specimens from 5,677 stone-forming patients throughout the United States were analyzed for seasonal variations in urinary risk factors for nephrolithiasis. Determinations were performed for urine volume, pH, calcium, oxalate, phosphorus, sodium, magnesium, citrate, sulfate, uric acid, and the relative supersaturation (RS) of calcium oxalate, brushite, monosodium urate, and uric acid. Criteria for significant seasonal variation included a significant difference in monthly means of risk factors, seasonal grouping of the data by the Student-Newman-Keuls multiple range test, consistent year-to-year trends and a physiologically significant range. Minimum urine volume of 1.54 +/- 0.70 SD L/day occurred in October while a maximum urine volume of 1.76 +/- 0.78 SD L/day was observed during February. Minimum urine pH of 5.94 +/- 0.64 SD was observed during July and August while a maximum pH of 6.18 +/- 0.61 SD was observed during February. Daily urinary excretion of sodium was lowest during August, 158 +/- 74 SD mEq/day and highest during February 177 +/- 70 SD mEq/day. The RS of brushite and uric acid were found to display significant pH-dependent seasonal variation with a maximum RS of uric acid 2.26 +/- 1.98 SD in June and a low of 1.48 +/- 1.30 SD in February. Maximum RS of brushite 2.75 +/- 2.58 was observed during February. Minimum RS of brushite 1.93 +/- 1.70 SD was observed in June. Phosphorus excretion displayed seasonal variation about a spring-fall axis with a maximum value 1042 +/- 373 SD mg/day in April and a minimum value of 895 +/- 289 SD mg/day. Urine volume, sodium, and pH were significantly lower during the summer (June, July, August) than in the winter (December, January, February). The RS of uric acid was higher, but that of brushite and monosodium urate was lower in the summer than in the winter. The seasonal changes observed in urine volume, pH, sodium, and the RS of brushite and uric acid are consistent with summertime sweating and increased physical activity. Seasonal variations in phosphorus excretion are probably dietary in origin. The summertime was characterized by an increased propensity for the crystallization of uric acid but not of calcium oxalate or calcium phosphate.     

Gestational urinary hyperthiosulfaturia protects hypercalciuric normal pregnant women from nephrolithiasis

Urinary calcium excretion increases by 1–2-fold during gestation in normal, uncomplicated pregnant women. Hypercalciuria occurs in all trimesters and elevates urine supersaturation with regards to calcium oxalate. However, crystalluria has not been a frequent clinical finding and stone formation is not a common complication of pregnancy. To elucidate this discrepancy we measured various chemical entities (i.e. calcium, oxalate, uric acid, phosphorous, magnesium, citrate, sulfate and thiosulfate) in urine at the end of each trimester of 25 pregnant women. Twenty-five healthy women served as controls. Our observations show that endogenous thiosulfate, a natural component of urine, increased considerably during pregnancy to approximately 36, 38 and 40 M/24 hour at the end of each three trimesters. One month after delivery, endogenous thiosulfaturia and hypercalciuria, in parallel, returned to initial normal values. Consequently, it seems that gestational hyperthiosulfaturia protects hypercalciuric normal pregnant women from the risk of nephrolithiasis.     

Increased urinary excretion of renal enzymes in idiopathic calcium oxalate nephrolithiasis

Urinary excretion of gamma-glutamyl transpeptidase, angiotensin I converting enzyme, beta-galactosidase and N-acetyl-beta-glucosaminidase was evaluated in 30 patients with idiopathic calcium oxalate urolithiasis. Higher than normal values were observed and the excretory enzyme pattern suggested tubular damage in patients with stones. A parallel study in the rat showed that an oxalate surcharge can promote increased urinary excretion of these enzymes. It is known that urothelium injury may enhance crystal adhesion. If the damage is primary it may be viewed as a promoting factor. If it is secondary it may be considered a factor capable of increasing salt precipitation.     

Fasting versus 24-h urine pH in the evaluation of nephrolithiasis

An abnormal urinary pH (UpH) represents an important risk factor for nephrolithiasis. In some stone formers, a fasting urine specimen is obtained instead of a 24-h urine collection for stone risk evaluation. We examined the relationship between 24-h and fasting UpH in non-stone forming individuals and stone formers with various etiologies and a wide range of urine pH to test the validity of fasting UpH. Data from 159 subjects was examined in this retrospective study. We included non-stone forming subjects and stone formers with hypercalciuria, distal renal tubular acidosis, idiopathic uric acid nephrolithiasis, or chronic diarrhea. Participants collected a 24-h urine followed by a 2-h fasting urine. For the entire cohort, a significant correlation was seen between fasting and 24-h UpH (r ² = 0.49, p < 0.001). Fasting pH was significantly higher than 24-h UpH for the entire cohort (6.02 ± 0.63 vs. 5.89 ± 0.51; p < 0.001), and in the subgroups of non-stone formers and stone formers with hypercalciuria or distal renal tubular acidosis. Fasting UpH was >0.2 pH units different from 24-h UpH in 58% of participants. The difference between fasting and 24-h UpH did not correlate with net gastrointestinal alkali absorption or urine sulfate, suggesting that dietary factors alone cannot explain this difference in UpH. Fasting urine pH correlates moderately with 24-h urine pH in a large cohort of individuals. Significant variability between these two parameters is seen in individual patients, emphasizing the cardinal role of 24-h urine collection for evaluating UpH in nephrolithiasis.     

Metabolic evaluation of patients with recurrent idiopathic calcium nephrolithiasis

BACKGROUND: Metabolic evaluation in recurrent idiopathic calcium renal stone-formers (RCSF) was analysed with respect to the following questions: (1) do three 24-h urines provide more diagnostic accuracy in the metabolic evaluation of RCSF than 1 or 2 urines?; (2) does time after stone event influence the diagnostic yield?; (3) is urine composition at weekends different from that at mid-week?; (4) what are the prevalences of the most important risk factors (RF) of idiopathic calcium nephrolithiasis, i.e. low volume (LV), hypercalciuria (HC), hyperoxaluria (HO), hyperuricosuria (HU), hypocitraturia (Hypo-Cit), and hypomagnesiuria (Hypo-Mg)?; and (5) do male RCSF differ from females with respect to urinary RFs? METHODS: Seventy-five RCSF (59 men, 16 women) collected three 24-h urines (U1-3) while on free-choice diet. To account for possible variations in lifestyle and diet, U1 and U3 had to be collected midweek and U2 at a weekend. RESULTS: When considering all three urines together (U1 + U2 + U3), the number of RF abnormalities/patient was 2.8 +/- 0.1, higher than numbers of any combination of two urines or of any single urine (P = 0.0001 for all comparisons). The number of RF abnormalities also rose with time after stone event, from 0.8 +/- 0.1 (range 0-4) in U1 to 1.1 +/- 0.1 (range 0- 4) in U3 (P = 0.011 vs U1). Whereas all other RF did not change between collections, urine volume was lower in U2 (1793 +/- 90 ml) than in U1 (2071 +/- 97 ml, P = 0.0001 vs U2) and U3 (1946 +/- 97 ml, P = 0.046 vs U2). At least 1 abnormality was found in 85.3% of all RCSF, and multiple abnormalities occurred in 47%. The most frequent RF was HC (39%), followed by HO and LV (32% each), Hypo-Cit (29%), HU (23%) and Hypo-Mg (19%). Males more often had Hypo-Cit (P < 0.001) and Hypo-Mg (P < 0.01) than females, whereas HO was more frequent in female RCSF (P < 0.025 vs males). CONCLUSIONS: Diagnostic accuracy of metabolic evaluation in RCSF increases both with the number of urines collected and the time passing after a stone event. Urines collected at weekends differ from those of the week only by their lower volumes. Abnormalities of RF for calcium nephrolithiasis can be detected in 85.3% of RCSF, and HC is the most common RF both in male and female RCSF.      

Diagnostic value of urinary cyclic AMP measurement in patients with calcium nephrolithiasis

One hundred patients with recurrent calcium nephrolithiasis were submitted to the Pak test. At fasting state hypercalciuria was found in 27 cases, while a group of 16 further patients became hypercalciuric after oral calcium load. Only measurement of urinary cAMP excretion in both conditions made it possible to diagnose renal hypercalciuria in 9 out of 27 patients in the former group; according to test results 4 patients were expected to have primary hyperparathyroidism, but afterwards the disease was identified in only one case.     

Role of linear tomography in evaluation of patients with nephrolithiasis

One hundred twenty-four consecutive patients with suspected or known nephrolithiasis were referred for evaluation by linear tomography. Renal calculi were detected in 98 patients (79%). Linear tomography revealed more renal calculi than did preliminary KUB films in 46 patients (37%), although in only 10 cases (8%) was the tomogram positive if the KUB was negative. Exact quantification of the numbers and locations of renal stones is important in patients to be managed metabolically, and in those being evaluated in advance of or following percutaneous or extracorporeal lithotripsy.