The relationship between total urinary testosterone and renal calculi

Summary It is generally known that age and sex are risk factors of urolithiasis. Therefore the total urinary testosterone concentrations of persons with and without renal stones were investigated by means of radioimmunoassay. The total testosterone level of the first morning midstream urine was comparable with 24 h urine samples of 16 healthy persons (r_s=0.9618). Investigation of the total urinary testosterone confirmed that the concentration is age dependent. A distinct decrease in total testosterone was observed in elderly persons. Therefore the total testosterone concentrations of the two groups, with and without stones, were studied within the same age interval (P=0.8292). The total testosterone level differed significantly for these two groups (P=0.0006). In general, the testosterone level of the kidney stone patients was lower than that of their healthy counterparts. In order to determine whether this variation in testosterone concentration would affect the urinary urokinase activity, a correlation study was undertaken. A positive correlation was found between the total urinary testosterone concentrations and the activity of urokinase (r_s=0.7305). It therefore seems that the total urinary testosterone concentrations may play a role in the pathogenesis of the multifactorial disease, urolithiasis.     

Clinical and biochemical profile of patients with “pure” uric acid nephrolithiasis compared with “pure” calcium oxalate stone formers

The purpose of the present study was to compare the clinical characteristics of “pure” uric acid (UA) stone formers with that of “pure” calcium oxalate (CaOx) stone formers and to determine whether renal handling of UA, urinary pH, and urinary excretion of promoters and inhibitors of stone formation were different between the two groups. Study subjects comprised 59 patients identified by records of stone analysis: 30 of them had “pure” UA stones and 29 had “pure” CaOx nephrolithiasis. Both groups underwent full outpatient evaluation of stone risk analysis that included renal handling of UA and urinary pH. Compared to CaOx stone formers, UA stone formers were older (53.3 ± 11.8 years vs. 44.5 ± 10.0 years; P = 0.003); they had higher mean weight (88.6 ± 12.5 kg vs. 78.0 ± 11.0 kg; P = 0.001) and body mass index (29.5 ± 4.2 kg/m² vs. 26.3 ± 3.5 kg/m²; P = 0.002) with a greater proportion of obese subjects (43.3% vs. 16.1%; P = 0.01). Patients with “pure” UA lithiasis had significantly lower UA clearance, UA fractional excretion, and UA/creatinine ratio, with significantly higher serum UA. The mean urinary pH was significantly lower in UA stone formers compared to CaOx stone formers (5.17 ± 0.20 vs. 5.93 ± 0.42; P < 0.0001). Patients with CaOx stones were a decade younger, having higher 24-h urinary calcium excretion (218.5 ± 56.3 mg/24 h vs. 181.3 ± 57.1 mg/24 h; P = 0.01) and a higher activity product index for CaOx [AP (CaOx) index]. Overweight/obesity and older age associated with low urine pH were the principal characteristic of “pure” UA stone formers. Impairment in urate excretion associated with increased serum UA was also another characteristic of UA stone formers that resembles patients with primary gout. Patients with pure CaOx stones were younger; they had a low proportion of obese subjects, a higher urinary calcium excretion, and a higher AP index for CaOx.     

Pathophysiology of incomplete renal tubular acidosis in recurrent renal stone formers: evidence of disturbed calcium,bone and citrate metabolism

Summary Urinary acidification, bone metabolism and urinary excretion of calcium and citrate were evaluated in 10 recurrent stone formers with incomplete renal tubular acidosis (RTA), 10 recurrent stone formers with normal urinary acidification (NUA) and 10 normal controls (NC). Patients with iRTA had lower plasma standard bicarbonate after fasting (P<0.01) and lower urinary excretion of titratable acid (P<0.05) and citrate (P<0.01) compared with NUA patients and NC, and higher urinary excretion of ammonia (P<0.05) compared with NC (P<0.05). Hypercalciuria was found in 6 of 10 patients with iRTA compared with 3 of 10 with NUA, and O of 10 NC. The citrate/calcium ratio in urine was significantly reduced in iRTA compared with the value in NUA (P<0.01), and in NUA compared with NC (P<0.05). Biochemical markers of bone formation (serum osteocalcin) and bone resorption (urinary hydroxyproline) were significantly increased in iRTA compared with NUA and NC (P<0.01), indicating increased bone turnover in stone formers with iRTA. Stone formers with iRTA thus presented with disturbed calcium, bone and citrate metabolism-the same metabolic abnormalities which characterize classic type 1 RTA. Mild non-carbonic acidosis during fasting may be a pathophysilogical factor of both nephrolithiasis and disturbed bone metabolism in stone formers with iRTA     

Serum,urinary and stone zinc,iron, magnesium and copper levels in idiopathic calcium oxalate stone patients

Many theories have been put forward to explain the mechanism of stone formation and growth. The aim of this study was to investigate the urinary, serum and stone levels of zinc, iron, magnesium, and copper in patients with calcium oxalate stones and to investigate urinary and serum element levels in healthy controls and to find a possible connection between the elements and calcium oxalate stone formation. A total of 104 patients with calcium oxalate stones ranging in age from 3 to 79 years (mean 44.0 ± 18.1) and 77 healthy controls ranging in age from 18 to 77 (mean 44.2 ± 17.9) were included in this study. The mean urinary iron and copper levels in stone patients were significantly higher than healthy controls (P = 0.000). The mean urinary zinc and magnesium levels in healthy controls were significantly higher than stone patients (P = 0.000). There was no significant difference in the serum levels of magnesium and copper in stone patients and healthy controls. Serum zinc and iron level were significantly high in healthy controls as compared to stone patients. Each stone had all 4 elements. Zn and Mg have inhibitory effect on calcium oxalate stone formation. Fe and Cu could be promotor of the calcium oxalate stone formation.     

In vivo effects of urease-producing bacteria involved with the pathogenesis of infection-induced urolithiasis on renal urokinase and sialidase activity

Many hypothese have been proposed for renal stone formation. It has been argued that with infection-induced renal stones the hydrolysis of urea by bacterial urease increases urinary pH, with consequent stone formation. Unfortunately, this theory is not applicable to the micro-organisms that do not produce urease (e.g. Escherichia coli). It has been recently reported that E. coli reduces the urinary urokinase activity of male rats, but does not influence the urinary sialidase activity. This study has now been expanded to the urease-producing bacteria Proteus mirabilis, Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa and Micrococcus luteus. Subcutaneous injections with these bacteria were found to significantly (P<0.003) reduce the UK activity of extrarenally obstructed kidneys. The urease-producing mammalian skin bacterium, M. luteus, was, however, the exception (P=0.1079). In contrast to S. epidermidis, P. aeruginosa and M. luteus (P<0.0213), P. mirabilis and S. aureus had no effect on renal sialidase activity (P<0.4047). These results may explain why Proteus species are predominant in infection-induced renal stones. According to the urokinase-sialidase hypothesis, a decrease in urinary urokinase activity should increase the uromucoid levels, whilst no effect on the urinary sialidase activity should favour conversion of urinary uromucoid to mineralizable matrix. These conditions may lead to renal stone formation. An increase in urinary pH resulting from urease-producing micro-organisms will increase salt precipitation on the uromucoid. It is thus concluded that urease-producing bacteria may play a double role in renal stone formation.     

The role of serum and urinary carbohydrate antigen 19-9 in predicting renal injury associated with ureteral stone

This study was designed to evaluate the role of urinary and serum carbohydrate antigen 19-9 (CA19-9) as a biomarker in the assessment of patients with ureteral stone. A total of 38 patients with ureteral stone and hydronephrosis who underwent transurethral lithotripsy (TUL) (Group A) and 24 age-matched healthy controls (Group B) were evaluated in this study. Urinary and serum CA19-9 concentrations were measured in group A patients before TUL as well as 4 and 8 weeks following the operation. Urinary and serum CA19-9 concentrations were also measured in group B participants. Median concentration of urinary and serum CA19-9 was 34.0 and 15.0 kU/L in group A patients and 16.1 and 5.3 kU/L in group B, respectively (p?<?0.001). Medians of CA19-9 concentration in urine and serum reduced to 12.5 and 4.5 kU/L 8 weeks after TUL (p?<?0.001). Following successful TUL and hydronephrosis resolution, a significant decline was detected in serum and urinary CA19-9. We also noted that duration of ureteral obstruction was associated with serum and urinary CA19-9 concentrations, suggesting the potential role of this marker in predicting renal damage associated with urinary tract obstruction and determining the appropriate timing of interventions.     

Quantification of osteopontin in the urine of healthy and stone-forming men

Osteopontin (OPN) is one of the most important components in calcium stone matrix, but its role in stone formation is not clear. Since quantitative data regarding the excretion of OPN are necessary to assess its role, we have developed a quantitative enzyme-linked immunosorbent assay (ELISA) for OPN, and measured the urinary OPN concentrations in urolithiasis patients. Forty-seven men with urinary stones composed chiefly of calcium oxalate participated in the study. The controls were 13 normal healthy male volunteers. Urine samples were collected early in the morning and analyzed by a quantitative ELISA employing purified polyclonal antibodies to synthesized OPN aminopolypeptides. The urinary ratio of the concentrations of OPN and creatinine (OPN/Cre) in the urolithiasis patients (0.039 ± 0.029) was significantly lower than that in the control subjects (0.062 ± 0.030) (P<0.05). Single stone formers (n = 26; 0.050 ± 0.020) had significantly higher OPN/Cre ratios compared with recurrent stone formers (n = 21; 0.031 ± 0.021) (P<0.05). The results show that OPN excretion in urolithiasis patients was lowered, presumably because of the incorporation of OPN by kidney stones. Received: 4 September 1998 / Accepted: 1 March 1999     

Effect of potential renal acid load of foods on urinary citrate excretion in calcium renal stone formers

The aim of this study was to investigate the influence of the potential renal acid load (PRAL) of the diet on the urinary risk factors for renal stone formation. The present series comprises 187 consecutive renal calcium stone patients (114 males, 73 females) who were studied in our stone clinic. Each patient was subjected to an investigation including a 24-h dietary record and 24-h urine sample taken over the same period. Nutrients and calories were calculated by means of food composition tables using a computerized procedure. Daily PRAL was calculated considering the mineral and protein composition of foods, the mean intestinal absorption rate for each nutrient and the metabolism of sulfur-containing amino acids. Sodium, potassium, calcium, magnesium, phosphate, oxalate, urate, citrate, and creatinine levels were measured in the urine. The mean daily PRAL was higher in male than in female patients (24.1±24.0 vs 16.1±20.1 mEq/day, P=0.000). A significantly (P=0.01) negative correlation (R=−0.18) was found between daily PRAL and daily urinary citrate, but no correlation between PRAL and urinary calcium, oxalate, and urate was shown. Daily urinary calcium (R=0.186, P=0.011) and uric acid (R=0.157, P=0.033) were significantly related to the dietary intake of protein. Daily urinary citrate was significantly related to the intakes of copper (R=0.178, P=0.015), riboflavin (R=0.20, P=0.006), piridoxine (R=0.169, P=0.021) and biotin (R=0.196, P=0.007). The regression analysis by stepwise selection confirmed the significant negative correlation between PRAL and urinary citrate (P=0.002) and the significant positive correlation between riboflavin and urinary citrate (P=0.000). Urinary citrate excretion of renal stone formers (RSFs) is highly dependant from dietary acid load. The computation of the renal acid load is advisable to investigate the role of diet in the pathogenesis of calcium stone disease and it is also a useful tool to evaluate the lithogenic potential of the diet of the individual patient.     

Relationship between lower urinary tract symptoms and serum levels of sex hormones in men with symptomatic benign prostatic hyperplasia

Study Type – Aetiology (case series)
Level of Evidence 4

OBJECTIVES

To investigate a possible association between the severity of lower urinary tract symptoms (LUTS) and the serum levels of sex hormones in men with symptomatic benign prostatic hyperplasia (BPH) that underwent surgery for severe benign prostatic obstruction.

PATIENTS AND METHODS

In all, 127 selected men with symptomatic BPH attending our urology clinic were recruited. The clinical conditions of BPH were assessed by digital rectal examination, serum prostate‐specific antigen (PSA) determination, International Prostate Symptom Score (IPSS), transrectal ultrasonography and maximum urinary flow rate (Q_max) value at uroflussimetry. Before surgery, we measured the serum concentrations of total testosterone (TT) and free testosterone (FT), oestradiol, prolactin, luteinizing hormone and follicle‐stimulating hormone. We excluded men with endocrine diseases, those with prostate disease who were receiving antiandrogen therapy and those with psychological diseases. The relationships between the IPSS score and serum sex hormone levels were determined.

RESULTS

The final study population consisted of 122 men (mean age of 70.66 years), as five were excluded (three due to incomplete evaluation and two who were diagnosed with prostate cancer). On statistical analysis, the total IPSS was significantly associated with age (r= 0.405, P < 0.001) and TT (r= 0.298, P= 0.020) but not with FT or the serum levels of the other sex hormones. The serum levels of testosterone and IPSS did not correlate with prostate volume and Q_max. PSA level and age correlated with prostate volume (r= 0.394, P < 0.001; r = 0.374, P < 0.001, respectively). We distinguished two subgroups of patients: the first group of 40 men with an IPSS of <19 and the second group of 82 with an IPSS of >19, and we evaluated the median levels of TT in each group. There was an increased risk of LUTS in men with a greater serum concentration of TT (P= 0.042), although the mean TT level was in the normal range.

CONCLUSIONS

In the present study, the severity of LUTS was associated with age and serum levels of TT but only age correlated with the measures of BPH, especially prostate volume. The potential effects of testosterone on LUTS may well be indirect. Additional large studies are needed to confirm these preliminary results.     

Comparison of biochemistry and diet in patients with enterocystoplasty who do and do not form stones

OBJECTIVE

To evaluate patients with a history of urinary stones in intestinal reservoirs and compare them with similar patients who have never formed stones.

PATIENTS AND METHODS

One consequence of storing urine in an intestinal reservoir is urolithiasis, and there are several theories on its cause, all based on limited evidence. There are many factors predisposing to stone formation, and dietary and biochemical factors might be useful to distinguish those who form stones from those who do not. In a prospective study (with ethical committee approval) we identified 15 patients (six male and six female, mean age 29 years) who had formed stones after an enterocystoplasty (group 1), and another 10 (three male and seven female, mean age 44 years) with no history of urolithiasis after enterocystoplasty (group 2). The respective mean (range) follow‐up was 14.6 (8–24) and 15.2 (6–23) years. They were investigated using our stone‐screening protocol described previously and the results compared between the groups using an unpaired Student’s t‐test, with statistically significance indicated at P < 0.05.

RESULTS

There was a statistically significant difference in almost all the variables assessed. The mean 24‐h urine output was 41% higher (P = 0.009) and the mean citrate excretion 173% higher (P = 0.002) in group 2. The mean (range) urinary pH was 6.46 (6.0–7.0) and 6.93 (6.3–7.8) in groups 2 and 1, respectively (P = 0.005). Of the stone‐forming elements, only the excretion of calcium was significant (2.78 vs 5.2 mmol/day, P < 0.001). The biochemical risk of stone formation was significantly higher for both calcium oxalate and calcium phosphate stones in group 1 than group 2 (P < 0.001 in both). From the dietary diaries there was a 24% higher fluid intake in group 2 (P = 0.04). The difference between group 2 and group 1 for the intake of magnesium (18.2 vs 12.38 mmol/day) and phosphate (49 vs 37.8 mmol/day) was statistically significant (P = 0.04 and 0.02, respectively).

CONCLUSIONS

Apparently the use of bowel in the urinary tract does not alone increase the risk of urolithiasis. Patients in group 1 were more prone due to the constituents of urine and possibly their dietary habits. This implies that with adequate fluid intake and eating a healthy balanced diet, the risk of urolithiasis can be reduced in patients with enterocystoplasty, as with idiopathic stone formers.     

Effect of menopause and aging on serum total and ionized calcium and protein concentrations

Summary The effects of menopause and aging on serum total and ionized calcium concentrations were evaluated in 402 healthy women (aged 18–71 years), of whom 83 were premenopausal and 319 postmenopausal. Serum albumin and globulin concentrations and serum pH were also measured in most of these women. Serum total but not ionized calcium concentration increased significantly at menopause. This increase in the protein-bound component of total calcium in postmenopausal women was associated with increases in mean serum globulin concentration (P=0.03) and in serum pH (P=0.03). Serum total calcium declined with age within the pre- and postmenopausal groups (r=−0.225,P=0.04 and r=−0.121,P=0.03, respectively). This was associated with an age-related decrease in serum albumin concentration in all women (r=−0.47,P<0.0001). Neither serum globulin concentration or pH varied with age. Thus, menopause and aging affect serum total, but not ionized calcium concentration.     

Cystinuria: the South Indian experience

Gout is well known to be produced by increased uric acid level in blood. The objective of this paper is to assess the relationship between gout and calcium oxalate stone formation in the humans. 48 patients with combination of gout and calcium oxalate stone problem were included. The biochemical values of this group were compared with 38 randomly selected uric acid stone patients with gout, 43 stone patients with gout alone, 100 calcium oxalate stone patients without gout and 30 controls, making a total of 259 patients. Various biochemical parameters, namely serum calcium, phosphorus and uric acid and 24-h urine calcium, phosphorus, uric acid, oxalate, citrate and magnesium were analysed. ANOVA and Duncan’s multiple-range tests were performed to assess statistical significance of the variations. The promoters of stone formation, namely serum calcium (P < 0.05), phosphorus (P < 0.05) and uric acid (P < 0.05) and urine calcium (P < 0.05), uric acid (P < 0.05) and oxalate (P < 0.05) were significantly variable in the different groups. The inhibitor citrate (P < 0.05) was also significantly variable. Multiple-range test showed that the promoters, namely serum calcium (P < 0.05) and urine uric acid (P < 0.05) were in a significantly higher range in the gouty patients, gouty uric acid stone patients and gouty calcium oxalate stone patients compared to the non-gouty patients and controls. Urine oxalate (P < 0.0001) was in the highest range in the gouty calcium oxalate or gouty uric acid stones patients. The inhibitor urine citrate (P < 0.001) was significantly lower in the gouty, gouty uric acid and gouty calcium oxalate patients. Serum uric acid was highest in the non-stone gouty patients, followed by the gouty uric acid stone formers and gouty calcium oxalate stone patients. The high values of promoters, namely uric acid and calcium in the gouty stone patients indicate the tendency for urinary stone formation in the gouty stone patients. There is probably a correlation between gout and calcium oxalate urinary stone. We presume this mechanism is achieved through the uric acid metabolism. The findings point to the summation effect of metabolic changes in development of stone disease.     

The influence of hemodialysis on serum sialic acid levels in chronic renal failure

Background. It has been observed that there is an increase in serum sialic acid level in chronic renal diseases and endstage renal failure requiring hemodialysis, and the hemodialysis procedure causes increased cytokine production. Thus, it is expected that hemodialysis causes increases in the serum levels of acute phase reactants and sialic acid. Nevertheless, the changes in serum sialic acid level in hemodialysis have not been examined sufficiently. In our study, we examined the effect of hemodialysis on serum sialic acid level. Methods. A total of 54 patients on hemodialysis therapy for chronic renal failure (32 men; 22 women) were examined. The patients were evaluated in four groups according to their age, sex, duration of hemodialysis, and whether they were diabetic. Serum sialic acid levels before and after hemodialysis, done with a hemophane membrane, were measured by the thiobarbituric acid method described by Warren. Results. The serum sialic acid levels of chronic renal failure patients requiring hemodialysis were increased with respect to the healthy control group, independent of age, duration of therapy, and whether there was accompanying diabetes. Hemodialysis did not provide clearance of sialic acid; to the contrary, it caused an insignificant increase in serum sialic acid levels. Conclusions. In chronic renal failure, the improved serum sialic acid level probably reaches a definite value, and this value is not affected by factors such as diabetes, age, or sex. Serum sialic acid level is minimally influenced by hemodialysis performed with a hemophane membrane. Received: August 20, 2001 / Accepted: May 10, 2002     

Tamm-Horsfall protein: are serum levels a marker for urinary tract obstruction?

Tamm-Horsfall protein (THP) has been found in the renal interstitium in patients with obstructive uropathy. The aim of this study was to investigate whether serum concentrations of THP could serve as a screening test for urinary tract obstruction. The presence of THP in normal human serum was confirmed by sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blotting. A specific enzyme immunoassay was then used to measure the serum concentration of THP. Serum THP concentrations were estimated in a cross-sectional study of a group of 23 patients who had technetium-99m-diethylenetriaminepenta-acetic acid (DTPA) nuclear urinary excretion studies to define urinary tract obstruction, and in longitudinal studies in 2 patients who developed acute bilateral ureteric obstruction following operations for ureteric reimplantation. The subjects with DTPA-proven urinary tract obstruction had higher concentrations of serum THP (n=10, median = 43.9 ng/ml, range 10.4–152.1 ng/ml) than those who did not have obstruction (n=13, median = 9.6 ng/ml, range 1.26–61.9 ng/ml). While this difference was significant (P<0.01, Mann-Whitney U test), 6 of the 10 patients with obstruction had serum THP concentrations within the range of those patients without obstruction. The patients who developed acute bilateral ureteric obstruction both had increases in serum THP concentrations with obstruction and decreases in serum THP concentrations following relief of obstruction. These changes paralleled those in serum creatinine. The studies indicate that urinary tract obstruction results in increases in serum THP concentrations but these changes are not sufficient in magnitude to allow screening of children for urinary tract obstruction.     

Association between serum folic acid level and erectile dysfunction

This study measured the serum folic acid (FA) level in patients with erectile dysfunction (ED) and evaluated the possible association between the serum FA level and erectile function. The study divided 120 patients with ED into 3 groups of 40 patients each: those with severe, moderate and mild ED. Forty healthy men served as controls. Fasting serum samples were obtained, and the total testosterone, cholesterol and FA levels were measured using chemiluminescent immunoassays. There were no significant differences in the mean age, mean body mass index or mean serum total testosterone and cholesterol levels among the three ED groups and controls (P > 0.05). The mean serum FA concentrations were 7.2 ± 3.7, 7.1 ± 3.2, 10.2 ± 4.6 and 10.7 ± 4.6 ng ml^?1 in the severe, moderate and mild ED and control groups respectively. The mean serum FA concentration was significantly higher in the control group than in the severe and moderate ED groups (both P < 0.001), but not the mild ED group (P = 0.95). Considering the significant differences in the serum FA levels between the control and ED groups, serum FA deficiency might reflect the severity of ED.     

Immobility as a Major Cause of Bone Remodeling in Residents of a Long-Stay Geriatric Ward

Residents of a long-stay geriatric ward at the University Hospital Basel were included in a study to investigate the effects of hypovitaminosis D and immobility. All 91 women (mean age 82.5 years) and 92 men (mean age 78.7 years) were enrolled in the study. Measurements included bone resorption, as measured by urinary deoxypyridinoline (dpd), serum 25-hydroxyvitamin D (25OHD), serum intact parathyroid hormone (iPTH), and their correlations with a four grade mobility score. Mobility score reflected the degree of weight bearing, ranging from walking independently to primarily bed bound. In 86% of all residents, serum 25OHD levels were below the normal limit of 12 ng/ml. Secondary hyperparathyroidism (HPT) was detected in 24% of all patients, using 55 pg/ml as the upper limit for serum iPTH. No significant correlation was found between urinary dpd and serum 25OHD or serum iPTH. Mobility index and both urinary dpd (f: P= 0.001, r = 0.37; m: P < 0.0001, r= 0.47) and serum calcium (female: P= 0.007, r = 0.28; male: P= 0.02, r= 0.24) were positively related. In institutionalized elderly people with a high prevalence of vitamin D deficiency serum intact PTH levels did not correlate with bone resorption as measured by urinary deoxypyridinolin. However, more immobile subjects had significantly higher excretion rates for urinary dpd and higher serum calcium levels. Our results suggest that in elderly people immobility may contribute to bone loss that might preempt the development of secondary HPT through elevation of serum calcium. Received: 12 February 1998 / Accepted: 1 November 1998     

Urinary calcium and uric acid excretion in children with vesicoureteral reflux

Urolithiasis is relatively common in children, and identifiable predisposing factors for stone formation, including metabolic and structural derangements, can be established in most cases. Vesicoureteral reflux (VUR) is a common cause of kidney stone formation. The pathophysiological mechanism of urolithiasis in reflux is related to urinary tract infection and urinary stasis, both of which promote urinary crystal formation, but metabolic causes, such as crystallurias (mostly hypercalciuria), may also be involved in this process. However, few studies on urinary calcium and uric acid excretion in children with VUR have been conducted. We have studied the frequency of hypercalciuria and hyperuricosuria in children with VUR and compared the results with those from a control group. The VUR group comprised 108 children with VUR (19 boys, 89 girls; age range 3 months to 12 years), and the control group comprised 110 healthy children without any history of reflux or urinary tract infection (30 boys, 80 girls; age range 2 months to 12 years). Fasting urine was analyzed for the calcium/creatinine (Ca/Cr) and uric acid/creatinine (UA/Cr) ratios. Hypercalciuria was more frequently diagnosed in the VUR patients than in the control group (21.3 vs. 3.6%; P = 0.0001). Significant differences between the two groups were also found for the mean Ca/Cr and UA/Cr ratios (P = 0.0001 and P = 0.0001, respectively). No differences were found in the urinary Ca/Cr or UA/Cr ratios related to VUR grading or unilateral/bilateral VUR in the patient group, with the exception of those for hypercalciuria and mild VUR (P = 0.03). The association of urinary stones and microlithiasis in the VUR group was 29.6%. Our results demonstrate that the frequency of hypercalciuria and hyperuricosuria was higher in pediatric patients with VUR than in healthy children. Knowing this relationship, preventive and therapeutic interventions for stone formation in VUR could be greatly expanded.     

Increased acid excretion in kidney stone formers with essential hypertension

Background. Although several studies have reported that kidneystone disease and hypertension are associated, the link betweenthe two conditions has not been identified. This study investigatedurinary excretion of different solutes, particularly citrateand acids, in kidney stone formers and examined their associationwith high blood pressure. Methods. The retrospective study included 234 consecutive subjects,aged 47.0 ± 15.6, attending our metabolic clinic afterepisodes of kidney stones. Essential hypertension was presentin 82 patients (35.0%). A difference in the urinary excretionof some of the investigated components was found between subjectswith normal blood pressure and those with hypertension. Results. The results showed that hypertensive subjects wereolder and had a higher body mass index (BMI) and serum uricacid. They had a significantly lower urinary pH (5.6 ±0.4 versus 6.0 ± 0.5) and citrate (2.55 ± 1.36versus 2.83 ± 1.65 mmol/24 h), higher titratable acid(38.8 ± 19.0 versus 26.8 ± 15.0 mEq/24 h) andammonium (41.6 ± 17.6 versus 34.2 ±12.4 mmol/24h). Logistic regression analysis with the presence of hypertensionas the dependent variable produced a model with the followingpredictors: age (P < 0.0001), BMI (P = 0.026), titratableacid (P = 0.025) and low urinary citrate level (P = 0.033).Urinary acid excretion increased with the stage of hypertension.No difference was found in the urinary excretion of other solutes. Conclusions. These findings suggest that essential hypertensionand acid excretion are linked in stone formers.     

Urinary nitric oxide levels are increased and correlated with plasma concentrations in patients with Behçet's disease: Is it a new urinary activity marker?

SUMMARY: Nitric oxide (NO) is a free radical and serves many functions within the kidney. Excess NO causes glomerular injury. Behçet's disease (BD) is a systemic immunoinflammatory vasculitis, affecting every organ in the body including the kidneys (subclinic glomerulonephritis). We investigated the role of urinary total nitrite levels (end product of NO) in BD and evaluated whether urinary concentrations were correlated with its plasma levels or disease activity. Thirty‐six consecutive Behçet's patients (19 men, 17 women; 35.9 years), and 20 age‐ and sex‐matched healthy control volunteers (12 men, eight women; 33.2 years) were divided into an active (n = 16) and inactive (n = 20) period. Urinary and serum NO levels (µmol/mg urinary creatinine) were higher in BD patients (4.1 ± 0.3) than control subjects (1.7 ± 0.2; P < 0.001). Serum NO levels in Behçet's patients and control subjects were 51.3 ± 9.8 and 21.7 ± 7.3 µmol/L, respectively (P < 0.001). Active patients had higher urinary NO excretion (4.9 ± 0.3) than inactive patients (3.3 ± 0.3; P < 0.01). Urinary NO levels were correlated with its serum levels (r² = 0.69, P < 0.001). Higher urinary NO levels found in BD may be produced by the kidney as a result of an inflammatory stimulation. As excess NO is toxic to the tissues, increased NO levels may play a role in mediating subclinic glomerular injury of such patients. However, we could not determine the exact site(s) of NO synthesis by the kidney, such as the glomeruli, blood vessels and/or the tubular cells. Whatever the source, urinary NO levels may be used as a new activity marker in the diagnosis and follow up of BD by serial measurements.     

Bone Turnover and Insulin-like Growth Factor I Levels Increase After Improved Glycemic Control in Noninsulin-dependent Diabetes Mellitus

It is unclear whether both bone resorption and formation are affected by glycemic control, and contribute to diabetic osteopenia. In this study, 20 patients with noninsulin-dependent diabetes mellitus (12 men and 8 postmenopausal women) and 20 healthy control subjects (10 men and 10 postmenopausal women) were examined at baseline and 2 months. The diabetic patients showed an improvement of glycemic control (decreased HbA_1c) at the second measurement. Analysis of variance showed that there was no effect of gender on the variables that increased with improved glycemic control, and therefore results are presented for both male and female subjects. Baseline values of serum osteocalcin, a marker of formation, were significantly lower in diabetic patients compared with healthy subjects (2.5 ± 1.3 versus 4.4 ± 1.4 ng/ml; P= 0.0006), but markers of bone resorption [urinary pyridinoline (PYD), deoxypyridinoline (DPD)] did not differ. Improved glycemic control in diabetic patients resulted in increased values of PYD (P= 0.012), DPD (P= 0.049), serum osteocalcin (P= 0.001), and serum insulin-like growth factor I (IGF-I, P= 0.003), but no change in serum parathyroid hormone or 25-hydroxyvitamin D. In diabetic patients there were inverse correlations for the percent change from baseline to improved glycemic control for osteocalcin and HbA_1c (r =−0.53; P= 0.016) and glucose (r =−0.46; P= 0.050). These data suggest that improved glycemic control is accompanied by an increase in bone turnover for male and female diabetic patients, possibly mediated by increased levels of circulating IGF-I. Received: 8 August 1997 / Accepted: 20 January 1998