Dietary calcium and serum 1,25-(OH)2-vitamin D concentrations as determinants of calcium balance in healthy men

We previously reported that experimental elevations of serum 1,25-(OH)2-vitamin D [1,25-(OH)2-D] concentrations produced by the chronic oral administration of calcitriol, 0.75 micrograms every 6 hr, to healthy human males eating diets providing only 4 mmoles Ca/day stimulate net bone resorption as evidenced by more negative Ca balances and higher rates of urinary hydroxyproline excretion. To determine whether increased dietary Ca intake modifies this response we have compared serum 1,25-(OH)2-D and iPTH concentrations, Ca and PO4 balances, and urinary hydroxyproline excretion in three healthy human males adapted to diets providing 22.3 +/- 1.3 mmoles Ca/day and three healthy human males adapted to diets providing 9.3 +/- 0.7 mmoles Ca/day before and during the continuous oral administration of calcitriol 0.5 micrograms every 6 hr. For all six subjects, serum 1,25-(OH)2-D levels averaged 89 +/- 25 pM during control and 143 +/- 26 pM during calcitriol. Net intestinal Ca absorption and urinary Ca excretion rose during calcitriol but Ca balances did not change, averaging +2.2 +/- 2.2 mmoles/day during control and +4.3 +/- 2.2 mmoles/day during calcitriol for the subjects fed 22 mmoles Ca/day and -1.6 +/- 1.5 mmoles Ca/day during control and -1.7 +/- 2.0 mmoles Ca/day during calcitriol for the subjects fed 9 mmoles Ca/day. Urinary hydroxyproline excretion also did not change. Thus, when serum 1,25-(OH)2-D levels are elevated, the availability of dietary Ca appears to prevent more negative Ca balances and increased urinary hydroxyproline excretion suggesting that net bone resorption is not stimulated.     

Role of urinary zinc and copper on calcium oxalate stone formation

INTRODUCTION: It is considered that many factors may play a role in urolithiasis. Experimental and clinical studies have shown that zinc has an inhibitory effect on urolithiasis. MATERIALS AND METHODS: In this study, urinary zinc and copper were measured in 27 healthy controls and 30 calcium oxalate stone formers. RESULTS: Urinary zinc excretion was significantly higher (p < 0.001) in stone formers than healthy controls (2,575 +/- 274 and 960 +/- 80 mg/day, respectively). There was no significant difference in urinary copper excretion between healthy controls and stone formers (32.3 +/- 3.5 and 33.3 +/- 3.2 microg/day, respectively). CONCLUSIONS: According to our results, the potent inhibitory effect of urinary zinc excretion on urolithiasis could be reviewed.     

Hydroxyproline ingestion and urinary oxalate and glycolate excretion

Endogenous synthesis of oxalate is an important contributor to calcium oxalate stone formation and renal impairment associated with primary hyperoxaluria. Although the principal precursor of oxalate is believed to be glyoxylate, pathways in humans resulting in glyoxylate synthesis are not well defined. Hydroxyproline, a component amino acid of collagen, is a potential glyoxylate precursor. We have investigated the contribution of dietary hydroxyproline derived from gelatin to urinary oxalate and glycolate excretion. Responses to the ingestion of 30 g of gelatin or whey protein were compared on controlled oxalate diets. The time course of metabolism of a 10 g gelatin load was determined as well as the response to varying gelatin loads. Urinary glycolate excretion was 5.3-fold higher on the gelatin diet compared to the whey diet and urinary oxalate excretion was 43% higher. Significant changes in plasma hydroxyproline and urinary oxalate and glycolate were observed with 5 and 10 g gelatin loads, but not 1 and 2 g loads. Extrapolation of these results to daily anticipated collagen turnover and hydroxyproline intake suggests that hydroxyproline metabolism contributes 20-50% of glycolate excreted in urine and 5-20% of urinary oxalate derived from endogenous synthesis. Our results also revealed that the kidney absorbs significant quantities of hydroxyproline and glycolate, and their metabolism to oxalate in this tissue warrants further consideration.     

Urinary glycosaminoglycans in normal subjects and patients with stones

Urinary glycosaminoglycans are thought to be macromolecular inhibitors of calcium stone formation. The 24-hour excretion of urinary glycosaminoglycans was measured quantitatively in 24 normal subjects and 206 patients with different etiologies of stone disease. In both groups a positive correlation was found between urinary glycosaminoglycans and total urinary volume and urinary sulfate. In normal subjects total urinary volume was r equals 0.716, p less than 0.001 and urinary sulfate was r equals 0.813, p less than 0.001, while in patients with stones these values were r equals 0.338, p less than 0.001 and r equals 0.326, p less than 0.001, respectively. The only significant difference in excretion of urinary glycosaminoglycans between the groups was found in the subgroup of patients with type I absorptive hypercalciuria. The type I absorptive hypercalciuria value of 33.4 +/- 14.9 mg. per day in patients with stones was significantly higher than the 25.8 +/- 8.3 mg. per day detected in normal subjects (p less than 0.05). Urinary glycosaminoglycan excretion in all other subgroups of nephrolithiasis as well as in a combined group of all patients with stones showed no significant difference when compared to that of normal subjects. Thus, no major quantitative relationship could be demonstrated between urinary glycosaminoglycan excretion and calcium stone formation in this study.     

An evaluation of the physicochemical risk for renal stone disease during pregnancy

Seventeen subjects were studied during the third trimester of pregnancy (PG) and post partum (NPG) to evaluate the effect of pregnancy on the physicochemical risk of renal stone disease. Levels of urinary saturation for calcium oxalate (CaOx), brushite (Br), uric acid (UA), and monosodium urate (NaU) were determined as well as urinary excretions of stone-forming elements. In addition to urinary calcium excretion, assessment of calcium metabolism included serum calcium and parathyroid hormone. Urinary calcium excretion was 251 +/- 127 mg/day during pregnancy and 121 +/- 67 mg/day post partum (p < 0.001). This was associated with a higher intake of dietary calcium and altered renal handling of calcium with an increase in the filtered load and a decrease in renal tubular reabsorption. The increase in urinary calcium resulted in a higher level of saturation of the urine for calcium oxalate (NPG 2.1 +/- 1.0 vs PG 3.0 +/- 1.1, p < 0.02) and brushite (NPG 1.2 +/- 0.9 vs PG 1.9 +/- 1.1, p < 0.05) compatible with an increased risk of stone formation.     

Studies of urinary risk factors in urolithiasis

Urinary excretions of calcium, oxalate and uric acid were estimated in 160 stone-formers (male 118, female 42) and 257 healthy controls (male 207, female 50). Stone-formers were divided into two groups according to their stone analysis: calcium containing stone-formers and non-calcium stone-formers. Calcium stone-formers were divided again into those who had a single stone episode and multiple or recurrent stone episodes. Urinary calcium and oxalate showed significant increases in calcium stone-formers, while urinary uric acid increased only in male calcium stone-formers. Recurrent calcium stone-formers demonstrated significant high levels of urinary calcium excretion especially in males, whereas no difference of urinary oxalate excretion between recurrent and single stone-formers. The frequency distributions on the excretion of three subjects were estimated respectively in patients with calcium stone and in controls. Relative risks, risk curves and stone probabilities were proposed and compared. The higher excretion values of urinary calcium and oxalate closely related to higher risks of forming calcium stones. On the other hand, urinary uric acid did not have such a relation to calcium stone formation. We defined the states which urinary excretions exceeded 95% upper confidence limits of normal controls as hyperexcretions. Hypercalciuria was more than 200 mg/day in male and female, hyperoxaluria was 50 mg/day in male and 45 mg/day in female and hyperuricosuria was 850 mg/day in male and 650 mg/day in female according to our definition. Among male calcium stone-formers, hypercalciuria was found in 45.3%, hyperoxaluria in 26.4% and hyperuricosuria in 15.1%. While in female calcium stone-formers, hypercalciuria in 23.7%, hyperoxaluria in 26.3% and hyperuricosuria in 13.2%. Of the male calcium stone-formers 57.5% showed either or both hypercalciuria and hyperoxaluria, and recurrent stone-formers also demonstrated a higher incidence among them. Excretion products of urinary calcium and oxalate were calculated and compared in each group. Calcium stone-formers showed significant high values especially in male recurrent stone-formers. The estimation by combining some risk factors will provide more useful means of assessing severity of urinary calculous diseases and therapeutic effects of their various treatments.     

Bone resorption stimulated by elevated serum 1,25-(OH)2-vitamin D concentrations in healthy men

We evaluated whether calcitriol administration to healthy men stimulates bone resorption. We compared serum 1,25-(OH)2-D concentrations, Ca and PO4 balances, and urinary hydroxyproline excretion rates in four healthy men adapted to a low Ca diet providing only 4.0 +/- 0.2 SD mmoles Ca/day to those in four healthy men eating a comparable diet (4.2 +/- 0.9 mmoles Ca/day) during the chronic oral administration of calcitriol, 0.75 micrograms every 6 hr. Serum 1,25-(OH)2-D levels averaged 94 +/- 16 pM during the control studies and 209 +/- 35 pM during calcitriol administration. Net intestinal Ca absorption averaged 0.5 +/- 0.3 mmoles/day during control and 1.8 +/- 0.5 mmoles/day during calcitriol (P less than 0.005), but urinary Ca excretion averaged 8.7 +/- 2.0 mmoles/day during calcitriol as compared to 2.9 +/- 1.4 mmoles/day during control (P less than 0.005). Thus, mean Ca balance, which averaged -2.4 +/- 1.2 mmoles/day during control, was more negative during calcitriol at -6.3 +/- 2.4 mmoles/day (P less than 0.05). Average daily PO4 balances averaged +7.7 +/- 1.5 mmoles/day during control but only tended to be negative during calcitriol at -1.1 +/- 5.4 mmoles/day, (NS). Urinary hydroxyproline excretion averaged 0.26 +/- 0.03 mmoles/day during control and 0.49 +/- 0.06 during calcitriol (P less than 0.001). We conclude that elevated serum 1,25-(OH)2-D concentrations in healthy men eating low Ca diets stimulate bone resorption.     

Urinary excretion of inorganic pyrophosphate by normal subjects and patients with renal calculi in north-western India and the effect of diclofenac sodium upon urinary excretion of pyrophosphate in stone formers.

24 h urinary pyrophosphate excretion was studied in 20 normal healthy subjects and 75 idiopathic stone formers from north-western regions of India. The mean 24-hour urinary excretion of pyrophosphate was significantly low in stone formers (50.67 +/- 2.16 mumol/24 h) as compared to that of normal subjects (71.46 +/- 5.46 mumol/24 h) (p less than 0.01). Diclofenac sodium, a non-steroidal anti-inflammatory agent, was administered 50 mg thrice daily for 1 week to 18 stone formers and 24-hour urinary pyrophosphate excretion was studied before and after drug therapy. The 24-hour urinary excretion of pyrophosphate increased from 54.32 +/- 21.40 to 78.31 +/- 28.03 mumol subsequent to diclofenac sodium therapy (p less than 0.01).     

Effect of dietary control of urinary uric acid excretion in calcium oxalate stone formers and non-stone-forming controls

BACKGROUND AND PURPOSE: Hyperuricosuria is a well-recognized risk factor for calcium oxalate urolithiasis. Some studies have demonstrated elevated urinary uric acid excretion in stone formers compared with non-stone-forming controls; nevertheless, these studies were limited by patient consumption of self-selected diets. With the recognition that dietary differences may induce variations in urinary uric acid excretion, we evaluated excretion of this compound in stone formers and controls consuming a standardized diet. SUBJECTS AND METHODS: A standardized formula diet was administered to 65 calcium oxalate stone formers and 61 age-matched non-stone-forming controls. During the 3 days of dietary intervention, 24-hour urine collections were obtained. Mean urinary uric acid excretion indexed to urinary creatinine was calculated for each subject, and the results in the two groups were compared. RESULTS: Stone-forming subjects did not have an elevation in urinary uric excretion compared with control subjects, with mean indexed urinary uric acid excretions of 337 +/- 64 mg/g of creatinine and 379 +/- 76 mg/g of creatinine, respectively. CONCLUSIONS: With dietary standardization, there was no observed increase in urinary uric acid excretion in our sampled populations. These findings emphasize the role of dietary factors in urinary uric acid excretion and highlight the potential value of dietary interventions.     

Serum and urine zinc response in head-injured patients

A prospective longitudinal evaluation of serum zinc concentrations was performed in 26 head-trauma patients, and 24-hour urine zinc excretion was determined in 15 of these subjects. Patients had markedly depressed admission serum zinc concentrations (mean +/- standard error of the mean: 40.2 +/- 3.2 micrograms/dl; normal values: 70 to 120 micrograms/dl), which gradually increased during the 16-day study period. All subjects demonstrated increased urinary zinc losses throughout the study period. Urinary zinc excretion was greater in patients with more severe head injuries. Indeed, patients with more severe head trauma had mean peak urinary zinc losses of greater than 7000 micrograms/day (normal less than 500 (micrograms/day). The implications of this altered zinc metabolism for protein metabolism, wound healing, and immune function, and the specific role of zinc in brain function and recovery from injury are discussed.     

Hypercalciuria and stones

Hypercalciuria, defined as the urinary excretion of more than 0.1 mmol Ca/kg/d (4 mg/kg/24 h), is observed in approximately 50% of patients with calcium oxalate/apatite nephrolithiasis and is one of the risk factors for stone formation. Urinary Ca excretion rates among such patients are higher than normal, despite comparable ranges of glomerular filtration rate (GFR) and serum ultrafiltrable Ca concentrations, and thus glomerular filtration of Ca, suggesting that hypercalciuria is the result of inhibition of net tubular Ca reabsorption. Although increased dietary NaCl or protein intake and reduced K intake increase urinary Ca excretion rates, urinary Ca excretion rates are higher among hypercalciuric stone formers than among normal subjects in relation to comparable ranges of urinary Na, SO4 (as a reflection of protein intake), or K excretion rates, indicating that these dietary factors are not primarily responsible for hypercalciuria. Hypophosphatemia is observed among a subset of hypercalciuric patients and consequent activation of 1,25-(OH)2-D synthesis increases intestinal Ca absorption and urinary calcium excretion. Other hypercalciuric patients exhibit augmented intestinal Ca absorption without elevated plasma 1,25-(OH)-2-D levels, suggesting that either the capacity of 1,25-(OH)2-D to upregulate its own receptor in the intestine or 1,25-(OH)2-D-independent intestinal Ca transport are responsible for increased Ca absorption and hypercalciuria. Hypercalciuric patients also exhibit accelerated radiocalcium turnover, negative Ca balances, reduced bone density, delayed bone mineralization, fasting hypercalciuria, and increased hydroxyproline excretion, all of which reflect participation of the skeleton and presumably a more generalized acceleration of Ca transport. Hypercalciuria may be familial.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determinants of urinary excretion of Tamm-Horsfall protein in non-selected kidney stone formers and healthy subjects.

BACKGROUND: The aim of the study was to measure urinary excretion of Tamm-Horsfall protein (THP), an important inhibitor of crystallization, and to identify possible determinants of urinary THP excretion in non-selected kidney stone formers (SF) and healthy subjects (C). METHODS: By means of a commercially available ELISA (Pharmacia and Upjohn/Elias, Germany), we measured THP in 24-h urines of 104 SF (74 males/30 females, age 16-74 years) who had formed 8.7+/-2.4 stones (range 1-240), and of 71 C (41 males/30 females, age 22-62 years). Types of stones formed by SF were 88 calcium, eight uric acid, six infection, and two cystine. All values are means+/-SE. RESULTS: The normal range (5th to 95th percentile) of U(THP)xV was 9.3-35.0 mg/day in males and 9.0-36.3 mg/day in females respectively. Mean U(THP)xV was 21.3+/-1.2 mg/day (range 3. 4-51.6) in male and 15.2+/-1.6 mg/day (range 1.8-32.3) in female SF (P=0.008 vs male SF). Since U(THP)xV was positively correlated with C(Crea) (r=0.312, P=0.001) in SF as well as with U(Crea)xV (r=0.346, P=0.0001) and with body surface (r=0.271, P=0.0003) in all study subjects, mean THP/Crea (mg/mmol) was used for all further calculations. Overall, THP/Crea was lower in SF (1.42+/-0.07 vs 1. 68+/-0.08, P:=0.015), mainly due to increased THP/Crea in female C (2.08+/-0.11, P=0.0036 vs female SF, P=0.0001 vs male C and vs male calcium SF), which also explains decreased THP/Crea values in calcium SF (1.46+/-0.08, P=0.041 vs C). In addition, THP/Crea was reduced in uric acid SF (1.11+/-0.21, P=0.049 vs C). Whereas THP/Crea was not related to age, urine volume, intake of dairy calcium, or urinary markers of protein intake, either in C or in SF, it correlated significantly with urinary Citrate/Crea, both in C (r=0.523, P=0.0001) and in SF (r=0.221, P=0.025). In C only, but not in SF, THP/Crea was correlated with urinary Calcium/Crea (r=0. 572, P=0.0001) and with Oxalate/Crea (r=0.274, P=0.022). CONCLUSIONS: Both in C and SF, urinary THP excretion is related to body size, renal function and urinary citrate excretion, whereas dietary habits apparently do not affect THP excretion. Uric acid and calcium stone formation predict reduced THP excretion in comparison with C, whereas female gender goes along with increased urinary THP excretion in C. Possibly most relevant to kidney stone formation is the fact that THP excretion rises only in C in response to increasing urinary calcium and oxalate concentrations, whereas this self-protective mechanism appears to be missing in SF.     

Contribution of dietary oxalate to urinary oxalate excretion

BACKGROUND: The amount of oxalate excreted in urine has a significant impact on calcium oxalate supersaturation and stone formation. Dietary oxalate is believed to make only a minor (10 to 20%) contribution to the amount of oxalate excreted in urine, but the validity of the experimental observations that support this conclusion can be questioned. An understanding of the actual contribution of dietary oxalate to urinary oxalate excretion is important, as it is potentially modifiable. METHODS: We varied the amount of dietary oxalate consumed by a group of adult individuals using formula diets and controlled, solid-food diets with a known oxalate content, determined by a recently developed analytical procedure. Controlled solid-food diets were consumed containing 10, 50, and 250 mg of oxalate/2500 kcal, as well as formula diets containing 0 and 180 mg oxalate/2500 kcal. Changes in the content of oxalate and other ions were assessed in 24-hour urine collections. RESULTS: Urinary oxalate excretion increased as dietary oxalate intake increased. With oxalate-containing diets, the mean contribution of dietary oxalate to urinary oxalate excretion ranged from 24.4 +/- 15.5% on the 10 mg/2500 kcal/day diet to 41.5 +/- 9.1% on the 250 mg/2500 kcal/day diet, much higher than previously estimated. When the calcium content of a diet containing 250 mg of oxalate was reduced from 1002 mg to 391 mg, urinary oxalate excretion increased by a mean of 28.2 +/- 4.8%, and the mean dietary contribution increased to 52.6 +/- 8.6%. CONCLUSIONS: These results suggest that dietary oxalate makes a much greater contribution to urinary oxalate excretion than previously recognized, that dietary calcium influences the bioavailability of ingested oxalate, and that the absorption of dietary oxalate may be an important factor in calcium oxalate stone formation.     

Plasma oxalate concentration in calcium oxalate stone formers

A sensitive, simplified method for plasma oxalate determination by gas chromatography is described. After deproteinizing the plasma with 3N HC1 and 20% sulfosalicylic acid, the oxalate was methylated, extracted and analysed by gas chromatography. This method has three advantages i.e., smaller sample size (plasma 5.0 ml), rapidity (takes less than 3 hours) and accuracy. The recovery rate of oxalate added to plasma was 91.42 +/- 11.31% (SD) and the coefficient of variation of replicate determinations was 4.18%. The minimum detectable concentration of oxalate was 0.3 micrograms/ml (oxalate peak was higher than 5 mm). The mean oxalate concentration under fasting conditions from 16 healthy subjects was 1.37 +/- 0.39 micrograms/ml (SD), while that from 31 calcium oxalate stone formers was 1.45 +/- 0.39 micrograms/ml (SD). There was no significant difference in plasma oxalate concentration between the two groups. The dietary influence of oxalate on plasma and urinary oxalate was investigated in 5 healthy subjects and 5 calcium oxalate stone formers. When 100 g spinach (total oxalate 545.5 mg, soluble oxalate 381.5 mg) was given, the increase of plasma oxalate concentration was more prominent in stone formers; in stone formers it increased to 142% of control value at 2 hours (p less than 0.05) after spinach loading, to 163% at 4 hour (p less than 0.01) and to 232% at 6 hours (p less than 0.01); while in healthy subjects increased to 119% at 2 hours (ns) after loading, to 144% at 4 hours (p less than 0.05) and only to 167% at 6 hours (p less than 0.01). Urinary oxalate excretion increased promptly between 1 and 2 hours after loading in both groups, reaching peak levels between 2 and 4 hours after loading in healthy subjects and between 4 and 6 hours or later in stone formers. The mean renal clearance of oxalate was 18.0 ml/min in 6 healthy subjects and 19.0 ml/min in 4 calcium oxalate stone formers. There was no significant difference in oxalate clearance between the two groups. The mean ratio of oxalate/creatinine clearance was 0.22 for stone formers, which was equal to that for healthy subjects.     

Effect of cranberry juice consumption on urinary stone risk factors

PURPOSE: We evaluated the effect of cranberry juice on urinary stone risk factors. MATERIALS AND METHODS: A total of 12 normal subjects and 12 calcium oxalate stone formers underwent 2, 7-day phases of study in random order while on a controlled metabolic diet. Subjects ingested 1 l of cranberry juice (CBJ) daily in 1 phase and 1 l of deionized water in the other phase. On the last 2 days of each phase 2, 24-hour urine collections and blood samples were obtained for stone risk factors and serum chemistries. RESULTS: No significant differences were found between normal subjects and stone formers in response to CBJ and, therefore, the groups were combined. CBJ significantly increased urinary calcium (from 154 to 177 mg per day, p =0.0008) and urinary oxalate (from 26.4 to 29.2 mg per day, p =0.04), thereby increasing urinary saturation of calcium oxalate by 18%. Urinary citrate was unchanged and urinary magnesium increased slightly. Urinary pH decreased (from 5.97 to 5.67, p =0.0005), and urinary ammonium, titratable acidity and net acid excretion increased during CBJ ingestion. Urinary uric acid decreased (from 544 to 442 mg per day, p <0.0001) as did serum uric acid. Thus, the urinary saturation of brushite and monosodium urate was reduced by CBJ but the amount of undissociated uric acid increased. CONCLUSIONS: CBJ exerts a mixed effect on urinary stone forming propensity. It reduces urinary pH likely by providing an acid load and decreases urinary uric acid perhaps by retarding urate synthesis. Overall CBJ increases the risk of calcium oxalate and uric acid stone formation but decreases the risk of brushite stones.     

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     

Blood sugar control reverses the increase in urinary excretion of prostaglandin D synthase in diabetic patients

BACKGROUND/AIMS: We investigated basal levels of serum and urinary lipocalin-type prostaglandin D synthase/beta-trace (L-PGDS) in type-2 diabetic patients and explored whether glycemic control affects L-PGDS status in another 55 diabetic inpatients with normoalbuminuria. METHODS: Fifty-five type-2 diabetic outpatients (HbA1c, 9.14 +/- 0.20%; creatinine (Cr), 85.1 +/- 2.4 micromol/l), and 55 age-matched healthy control subjects were recruited. Serum and urinary levels of L-PGDS were determined with respect to the stage of diabetic nephropathy. The L-PGDS was localized by immunohistochemistry. RESULTS: The urinary L-PGDS index increased in diabetic patients, compared with the controls (234.8 +/- 27.4 vs. 73.8 +/- 7.8 microg/mmol Cr, p < 0.001). Even in normoalbuminuric patients as well as in microalbuminuric patients, urinary L-PGDS indexes were higher than the controls (166.0 +/- 21.1, p < 0.0001 and 338.6 +/- 62.5 microg/mmol Cr, p < 0.0001, respectively), although the serum L-PGDS level was equal to that in the control subjects. Multiple regression analysis revealed that the urinary L-PGDS index was predicted solely by glucose levels and type-IV collagen index, whereas the serum L-PGDS was determined mainly by age and serum Cr. Glycemic control reduced the urinary L-PGDS index towards the normal range in diabetic patients with normoalbuminuria (172.3 +/- 6.6 vs. 118.1 +/- 2.6 (SE) microg/mmol Cr, p < 0.0001). Immunohistochemistry showed that L-PGDS was uniquely present in the renal tubules in diabetes while in nondiabetics, L-PGDS occurred solely in the peritubular interstitium, not in the tubular cells. CONCLUSION: Inadequate glycemic control is responsible for urinary L-PGDS excretion in the diabetic patients. Urinary L-PGDS is useful to predict subclinical renal injury associated with type-2 diabetes.     

Acute caffeine effects on urine composition and calcium kidney stone risk in calcium stone formers

PURPOSE: Caffeine increases urinary calcium (ca) excretion in nonstone formers. We designed a study to determine the effect of caffeine consumption on urinary composition in stone formers. MATERIALS AND METHODS: A total of 39 normocalcemic patients with calcium stones consumed caffeine (6 mg/kg lean body mass) after 14 hours of fasting. Urinary composition was compared 2 hours before and 2 hours after caffeine consumption. Control subjects included 9 nonstone formers studied contemporaneously with patients plus data from 39 nonstone formers from previous studies matched to each patient by level of fasting calcium/creatinine (Cr), gender and age. RESULTS: Caffeine increased urinary Ca/Cr, magnesium/Cr, citrate/Cr and sodium/Cr but not oxalate/Cr in stone formers and controls. The Tiselius stone risk index for calcium oxalate precipitation increased from 2.4 to 3.1 in stone formers and from 1.7 to 2.5 in nonstone formers. Of the 39 stone formers 32 had an increased Tiselius risk index after caffeine. Post-caffeine increases in Ca/Cr and Na/Cr were highly correlated. CONCLUSIONS: Caffeine consumption may modestly increase risk of calcium oxalate stone formation.     

Glycosaminoglycans Excretion in Interstitial Cystitis

Glycosaminoglycans (GAGs) have been identified histochemically and biochemically in urothelium. They have been suggested to have an anti-adherence effect at the bladder surface important in the urothelial defence against bacterial and carcinogenic insult. The aim of this study was to investigate urinary GAGs excretion in patients with interstitial cystitis.Urinary GAG excretion was determined in patients with interstitial cystitis (n:34; 16 males, 18 females) and healthy subjects (n:34; 16 males, 18 females). Urinary GAG determinations were made by the dimethymethylene blue method. Student's t-test was used for statistical analysis of the results.Urinary GAG excretion was found to be elevated significantly in patients with interstitial cystitis (14.45±2.02 mg/g Cr) as compared to healthy subjects (10.11±2.3 mg/g Cr) (p<0.01). There was no significant difference in urinary GAG excretion between males and females in either the healthy subjects or in the patients.Determination of urinary GAG excretion may be an important non-invasive test in the investigation of patients with interstitial cystitis.     

The effect of oral phosphate administration on major indices of skeletal metabolism in normal subjects

The effect of brief periods of phosphate administration on indices of human skeletal metabolism was investigated. Thirteen subjects (8 women, 5 men; 19-36 years old) received 2 g of oral phosphate daily for 5 days. Serum phosphorus rose 26% (3.8 +/- 0.1 mg/dl to 4.8 +/- 0.1 mg/dl; p less than .01) while total calcium fell (9.3 +/- 0.1 mg/dl to 8.9 +/- 0.1 mg/dl; p less than .01). Parathyroid hormone levels increased by 50% (14.1 +/- 2.0 pg/ml to 21.5 +/- 1.7 pg/ml; p less than .05) although values remained within the normal range. A persistent phosphaturia (0.64 +/- 0.10 g/g Cr to 1.8 +/- 0.4 g/g Cr; p less than .05) and a 69% fall in urinary calcium (80.8 +/- 10.0 mg/g Cr to 24.6 +/- 6.0 mg/g Cr; p less than .001) were observed. 1,25-dihydroxyvitamin D3 and urinary hydroxyproline concentrations did not change significantly but the bone gamma-carboxyglutamic acid protein (BGP) concentration rose 41% by day 2 (9.6 +/- 1.3 mg/ml to 13.5 +/- 2.2 mg/ml; p less than .005) and remained elevated throughout the study period. These results support the possibility that brief periods of phosphate administration may be useful in the therapy of disorders associated with low bone turnover, such as osteoporosis.