Role of the diurnal variation of urinary pH and urinary calcium in urolithiasis: A study in outpatients

BACKGROUND: We previously reported that the urinary excretion of calcium and the diurnal variation of urinary pH were important for stone formation in hospitalized inpatients with hospital standard diet. Because almost all urinary stones are formed in outpatients with ambulatory free diet, it is essential to investigate these factors in outpatients. METHODS: We examined the urinary excretion of calcium, oxalate, uric acid, phosphate and magnesium in 96 male outpatients and 142 male inpatients. We also studied the relationship between the stone composition and the diurnal variation of urinary pH in 32 male outpatients (five uric acid stones (UA), 13 pure calcium oxalate stones (CaOX) and 14 mixed calcium oxalate and calcium phosphate stones (CaOX-CaP)) and 53 male inpatients (nine UA, 15 CaOX and 29 CaOX-CaP). RESULTS: There was a significant difference in the urinary excretion of calcium among outpatients with UA, CaOX and CaOX-CaP (133 +/- 96 vs 219 +/- 97 vs 268 +/- 102 mg per day, P < 0.05). In outpatients with UA, urinary pH was constantly low throughout the entire day. In contrast, outpatients with CaOX and those with CaOX-CaP had diurnal variation of urinary pH that was low in the early morning, followed by elevation in the daytime and was lowered in the night. The pHs in the early morning, afternoon and night were significantly higher in outpatients with CaOX-CaP than in those with CaOX. CONCLUSION: The diurnal variation of urinary pH and the urinary calcium are important for stone formation.     

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.     

Biochemical profile of idiopathic uric acid nephrolithiasis

BACKGROUND: The objective of this study was to elucidate a biochemical profile of patients with idiopathic uric acid nephrolithiasis, without secondary causes (such as dehydration or diarrhea). Study subjects comprised 56 patients with idiopathic uric acid nephrolithiasis (UA stone group) who underwent a full outpatient evaluation. The control group was composed of 54 with absorptive hypercalciuria and 2 normal subjects, matched with the UA stone group according to age, body mass index, and gender. METHODS: Urinary pH and ammonium and serum and urinary uric acid were measured. The fractional excretion of urate was calculated. RESULTS: Compared with the control group, the UA stone group had a significantly higher serum uric acid and significantly lower urinary uric acid, pH (5.34 +/- 0.23 vs. 6.17 +/- 0.36, P < 0.001), and fractional excretion of urate (0.052 +/- 0.028 vs. 0.080 +/- 0.029, P < 0.001), but individual values overlapped considerably between the two groups. Discriminant analysis of the relationship between urinary pH and fractional excretion of urate yielded a "discriminant score," which provided a much better separation between the two groups, with a correct classification in 95.5% of subjects. In contrast, urinary ammonium, citrate, sulfate, and potassium did not differ between two groups. CONCLUSIONS: In idiopathic uric acid nephrolithiasis, urinary pH and fractional excretion of urate are significantly lower than in control subjects, suggestive of defects in urinary acidification and urate excretion. Since these impairments are believed to be associated with primary gout, the underlying disturbance in idiopathic uric acid nephrolithiasis may be primary gout.     

Clinical and Biochemical Presentation of Gouty Diathesis: Comparison of Uric Acid Versus Pure Calcium Stone Formation

PurposeWe compared gouty diathesis with uric acid versus calcium stones.Materials and MethodsWe retrospectively reviewed clinical and laboratory data from 95 gouty diathesis patients (28 with uric acid and 67 with calcium stones) and 99 normal subjects.ResultsOf the gouty diathesis patients gouty arthritis was present in 21 percent of those with uric acid and 12 percent of those with calcium stones. Hyperuricemia developed in 43 percent of those with uric acid and 27 percent of those with calcium stones, and 2 percent of controls. Urinary pH was independent of the net gastrointestinal absorption of alkali in the gouty diathesis groups. Urinary pH and citrate increased after potassium citrate treatment.ConclusionsThe characteristic features of primary gout were present in both gouty diathesis groups and both are responsive to treatment.     

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.     

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.     

Two cases of uric acid stones unsuccessfully dissociated by oral chemolysis

We report two patients with renal uric acid (UA) stones in whom chemolysis by oral administration of alkaline citrate and allopurinol was unsuccessful. The stone in a 58-year old female did not dissolve because her urinary pH remained low throughout the day after alkaline citrate administration. The stone in a 50-year old man did not dissolve because his urinary pH was 5.5-6.0 after alkaline citrate administration. Alkalization of the urine helps reduce the stone size and the calcification of the stone. Extracorporeal shockwave lithotripsy was performed and the stone composition showed mixed calcium oxalate and calcium phosphate. The indication of oral chemolysis of uric acid stones is discussed.     

Successful management of uric acid nephrolithiasis with potassium citrate

Eighteen patients with uric acid nephrolithiasis (six with uric acid stones alone and 12 with both uric acid and calcium stones) underwent long-term treatment (1 to 5.33 years, mean of 2.78 years) with potassium citrate (30 to 80 mEq/day, usually 60 mEq/day). Urinary pH increased from low (5.30 +/- 0.31 SD) to normal (6.19 to 6.46) during treatment. Urinary content of undissociated uric acid, which was high to begin with at 204 +/- 82 mg/day, decreased to the normal range (64 to 108 mg/day) following treatment. Urinary citrate rose from 503 +/- 225 mg/day to 852 to 998 mg/day. Urinary saturation of calcium oxalate significantly declined with potassium citrate treatment. New stone formation rate declined from 1.20 +/- 1.68 stones/year to 0.01 +/- 0.04 stones/year (P less than 0.001 by chi square). Remission was experienced in 94.4% of patients, and the group stone formation rate declined by 99.2%. Detailed case reports were obtained in five patients showing different responses between sodium alkali and potassium alkali treatment. All five patients had persistently low urinary pH (typically less than 5.5) and normouricosuria, and four had hyperuricemia. Before treatment, they had stones surgically removed or spontaneously passed, which were pure uric acid in composition. When sodium alkali was give (as bicarbonate or citrate, 60 to 118 mEq/day), new stone formation continued in four patients, and a radiolucent (uric acid) calculus become "calcified" in the remaining patient. The stone analysis disclosed calcium oxalate in five patients and calcium phosphate in three patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stone forming risk of calcium citrate supplementation in healthy postmenopausal women

PURPOSE: We evaluated the effect of calcium citrate supplementation alone or in combination with potassium citrate on the stone forming propensity in healthy postmenopausal women. MATERIALS AND METHODS: A total of 18 postmenopausal women without stones underwent a randomized trial of 4 phases comprised of 2 weeks of treatment with placebo, calcium citrate (400 mg calcium twice daily), potassium citrate (20 mEq twice daily), and calcium citrate and potassium citrate (at same doses). During the last 2 days of each phase urine was collected in 24-hour pools for complete stone risk analysis. RESULTS: Compared to placebo, calcium citrate increased urinary calcium and citrate but decreased urinary oxalate and phosphate. Urinary saturation of calcium oxalate, brushite and undissociated uric acid did not change. Potassium citrate decreased urinary calcium, and increased urinary citrate and pH. It decreased urinary saturation of calcium oxalate and undissociated uric acid, and did not change the saturation of brushite. When calcium citrate was combined with potassium citrate, urinary calcium remained high, urinary citrate increased even further and urinary oxalate remained reduced from the calcium citrate alone, thereby marginally decreasing the urinary saturation of calcium oxalate. Urinary pH increased, decreasing urinary undissociated uric acid. The increase in pH increased the saturation of brushite despite the decrease in urinary phosphorus. CONCLUSIONS: Calcium citrate supplementation does not increase the risk of stone formation in healthy postmenopausal women. The co-administered potassium citrate may provide additional protection against formation of uric acid and calcium oxalate stones.     

Hypocitraturia as a pathogenic risk factor in the mixed (calcium oxalate/uric acid) renal stones.

A small group of patients with nephrolithiasis who forms mixed (calcium oxalate and uric acid) calculi presents particular problems in their clinical management. In 3,158 stones analyzed in our laboratory, we found 158 mixed calculi in 86 of the patients. In this work, the clinical and biochemical results obtained from 27 patients with mixed stones were compared with those from 27 control patients with calcium oxalate renal lithiasis. A significant difference was found in oxalate and citrate urinary elimination (mean +/- SD) in mixed stone formers versus pure calcium oxalate stone formers: oxaluria (mg/24 h: 38 +/- 15 vs. 28 +/- 12; p less than 0.01) and citraturia (mg/24 h: 214 +/- 139 vs. 437 +/- 303; p less than 0.01). Citraturia was decreased in a high proportion (77%) in mixed stone formers, and only a reduced percentage of them (23%) presented normal values, although in the low limit of normality. As treatment and prophylactic measure, we proposed oral administration of citrates in mixed stone patients because citrate inhibits spontaneous nucleation of calcium salts and crystal growth, and it also increases the urinary pH with a consequent increase in uric acid solubility.     

Reduction of renal stone risk by potassium-magnesium citrate during 5 weeks of bed rest

PURPOSE: Exposure to the microgravity environment of space increases the risk of kidney stone formation, particularly for calcium oxalate and uric acid stones. This study was performed to evaluate the efficacy of potassium alkali as potassium-magnesium citrate in reducing renal stone risk and bone turnover. MATERIALS AND METHODS: This study was performed as a double-blind, placebo controlled trial. We studied 20 normocalciuric subjects randomized to either placebo or potassium-magnesium citrate (42 mEq potassium, 21 mEq magnesium, 63 mEq citrate per day) before and during 5 weeks of strict bed rest. The study was performed in the General Clinical Research Center and under a controlled dietary regimen composed of 100 mEq of sodium, 800 mg of calcium, 0.8 gm/kg animal protein and 2,200 kcal per day. Two 24-hour urine collections were obtained under oil each week for assessment of stone risk parameters and relative saturation of calcium oxalate, brushite and undissociated uric acid. Blood was also collected for determination of serum immunoreactive parathyroid hormone and vitamin D metabolites. RESULTS: Bed rest promoted a rapid increase in urinary calcium excretion of approximately 50 mg per day in both groups. Despite this increase subjects treated with potassium-magnesium citrate demonstrated significant decreases in the relative saturation of calcium oxalate and in the concentration of undissociated uric acid compared to placebo. Immunoreactive parathyroid hormone, serum 1,25-dihydroxyvitamin D and intestinal calcium absorption all decreased in both groups with no difference in response between the 2 treatment arms. CONCLUSIONS: Provision of alkali as potassium-magnesium citrate is an effective countermeasure for the increased risk of renal stone disease associated with immobilization. Despite an increase in urine calcium concentration, the relative saturation of calcium oxalate decreased due to citrate chelation of calcium and the concentration of undissociated uric acid decreased due to the significant increase in urine pH.     

Urolithiasis in Okinawa, Japan: A relatively high prevalence of uric acid stones

AIM: The aim of the present study was to investigate the composition of urinary tract stones in patients from Okinawa, the most southern island group of Japan. METHODS: The study was conducted by 12 hospitals in Okinawa. A total of 1816 urinary tract calculi were obtained from 1816 patients (1323 males; 493 females). The patients had a mean age of 53 +/- 15.3 years (mean +/- SD). The calculi were examined to determine their chemical composition. Stone samples were analyzed by computed infrared spectrophotometer. RESULTS: Pure stones comprised 58.4% of the total, with calcium oxalate stones accounting for 40% (21% monohydrate [whewellite]; 6.6% dihydrate [weddellite]; and 12.4% combined monohydrate and dihydrate stones), uric acid/urate stones for 9.6%, calcium phosphate stones for 5.1%, and struvite stones for 3.7%. The other 41.6% of the stones consisted of calcium oxalate mixed with other components. The male-to-female ratio was 2.7:1. CONCLUSION: In our series, calcium oxalate stones accounted for 81.6% of the urinary tract calculi, while uric acid/urate stones accounted for 15.8%. Uric acid stones, predominantly the anhydrous and/or dihydrate forms, showed a relatively high prevalence. Calcium oxalate stones, predominantly in the form of whewellite, showed a high prevalence among pure calculi; while the predominant combinations among mixed calculi were weddellite + calcium phosphate and whewellite + uric acid/urate.     

The metabolic syndrome and uric acid nephrolithiasis: novel features of renal manifestation of insulin resistance

BACKGROUND: Uric acid nephrolithiasis primarily results from low urinary pH, which increases the concentration of the insoluble undissociated uric acid, causing formation of both uric acid and mixed uric acid/calcium oxalate stones. These patients have recently been described as exhibiting features of insulin resistance. This study was designed to evaluate if insulin resistance is associated with excessively low urinary pH in overtly healthy volunteers (non-stone formers) and if insulin resistance may explain the excessively low urinary pH in patients with uric acid nephrolithiasis. METHODS: Fifty-five healthy volunteers (non stone-formers) with a large range of body mass index and 13 patients with recurrent uric acid nephrolithiasis underwent hyperinsulinemic euglycemic clamp, 24-hour urinary studies, and anthropometric measurements of adiposity. A subgroup of 35 non-stone formers had 2-hour timed urinary collection before and during the hyperinsulinemic phase of the clamp studies. RESULTS: For the non-stone former population, low insulin sensitivity measured as glucose disposal rate significantly correlated with low 24-hour urinary pH (r= 0. 35; P= 0.01). In addition to the previously described acidic urine pH and hypouricosuria, patients with recurrent uric acid nephrolithiasis were found to be severely insulin resistant (glucose disposal rate: uric acid stone-formers vs. normals; 4.1 +/- 1.3 vs. 6.9 +/- 2.1 mg/min/kg of lean body mass, P= 0.008). Acute hyperinsulinemia was associated with higher urinary pH (6.1 +/- 0.7 at baseline to 6.8 +/- 0.7 during hyperinsulinemia; P < 0.0001), urinary ammonia excretion (2.7 +/- 1.6 mEq/2 hr at baseline and 4.0 +/- 2.6 mEq/2 hr P= 0.002) and urinary citrate excretion (48 +/- 33 mg/2 hr at baseline and 113 +/- 68 mg/2 hr P < 0.0001). CONCLUSION: We conclude that one renal manifestation of insulin resistance may be low urinary ammonium and pH. This defect can result in increased risk of uric acid precipitation despite normouricosuria.     

Nephrolithiasis and urine ion changes in ulcerative colitis patients undergoing colectomy and endorectal ileal pullthrough

Nephrolithiasis occurs in 5 to 13% of patients with ulcerative colitis (UC) who undergo colectomy and abdominal ileostomy, presumably from chronic dehydration and urinary concentration. Whether endorectal ileal pullthrough with ileal reservoir (PTR) changes the incidence of stones (primarily calcium oxalate) after colectomy is not known. Urinary excretion of Na2+, K+, Ca2+, Mg2+, phosphate, urate, oxalate, and citrate was measured in a prospective study of 12 UC patients undergoing PTR with temporary end ileostomy. Twenty-four-hour urine samples were obtained before colectomy (t1), after colectomy but before ileostomy closure (t2), and 5 months after ileostomy closure (t3). Urine volumes decreased from 831 +/- 101 cc (mean +/- SE) at t1 to 715 +/- 101 cc at t2 and then increased to 1278 +/- 421 cc at t3 (significant, with P less than 0.01 by t test). Urinary excretions of Mg2+, oxalate, and citrate were low in UC patients compared to those in controls (15 healthy adult volunteers). Excretion of Ca2+ increased significantly following temporary ileostomy while excretion of Mg2+ fell. Excretion of Ca2+ fell and excretion of Mg2+ and citrate increased following PTR. We conclude that PTR patients have increased urine volumes and urinary ion changes known to decrease the risk of developing renal stones.     

Shmakovka narzan mineral water in the treatment of chronic pyelonephritis in children

The impact of "Pasechny?" spa of the Shmakovka health resort on the circadian urinary output, renal excretion of magnesium, calcium, nonorganic phosphorus, oxalates, uric acid, phospholipids, acido- and ammoniogenases, daily fluctuations of urinary pH was studied for the first time in 65 children with chronic pyelonephritis. In the presence of spa treatment the authors revealed a 75-100 per cent increase in the circadian urinary output, urinary excretion of magnesium, uric acid, ammonia, titrated acids, a decrease in the levels of calcium, oxalates, nonorganic phosphorus and acidification of the urine at 9 o'clock in the morning mainly in children with primary pyelonephritis and at 9 and 6 o'clock in the morning in patients with concurrent uricosuria. Other parameters were not significantly different from those in the controls. Acidification of the urine in the presence of high uricosuria resulted in crystalluria of urates and oxalates in 26.31 per cent of patients with the concurrent urate diathesis. The water of Shmakovka mineral springs is recommended for patients with primary pyelonephritis, phosphaturia and calcium oxalate crystalluria with alkaline reaction of the urine and unjustified for those who suffered from urate diathesis.     

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.     

瘦猪肉餐对草酸钙结石患者尿生化的影响

目的研究瘦猪肉餐对一水草酸钙（calciumoxalate monohydrate,COM）与二水草酸钙（calciumoxalate dehydrate,COD）结石患者尿生化的影响,探讨草酸钙结石形成的机制。方法正常人、COM与COD结石患者各6例,共18例同予以煮瘦猪肉350g食用,收集实验日晨5-7时2h尿为样本,餐后各留3次2h尿标本,测定尿pH值和尿晶体成分浓度;采用SPSS软件对检测结果进行方差分析。结果三组受试者瘦猪肉餐后尿钙、尿酸和尿草酸排泄逐渐增加,而尿量、尿pH值和尿枸橼酸降低;瘦肉餐前后比较,COM与COD结石患者尿pH值、尿枸橼酸、尿钙和尿草酸有显著性差异（P〈0.05）,尿酸排泄有极显著性差异（P〈0.01）;对照组,尿钙、尿酸排泄均有显著性差异（P〈0.05,P〈0.01）。结论大量饮食猪瘦肉可导致尿pH值和尿晶体成分变化,可能是尿结石形成的重要原因之一。     

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.     

Long-term treatment of calcium nephrolithiasis with potassium citrate

The long-term effects of potassium citrate therapy (usually 20 mEq. 3 times daily during 1 to 4.33 years) were examined in 89 patients with hypocitraturic calcium nephrolithiasis or uric acid lithiasis, with or without calcium nephrolithiasis. Hypocitraturia caused by renal tubular acidosis or chronic diarrheal syndrome was associated with other metabolic abnormalities, such as hypercalciuria or hyperuricosuria, or occurred alone. Potassium citrate therapy caused a sustained increase in urinary pH and potassium, and restored urinary citrate to normal levels. No substantial or significant changes occurred in urinary uric acid, oxalate, sodium or phosphorus levels, or total volume. Owing to these physiological changes, uric acid solubility increased, urinary saturation of calcium oxalate decreased and the propensity for spontaneous nucleation of calcium oxalate was reduced to normal. Therefore, the physicochemical environment of urine following treatment became less conducive to the crystallization of calcium oxalate or uric acid, since it stimulated that of normal subjects without stones. Commensurate with the aforementioned physiological and physicochemical changes the treatment produced clinical improvement, since individual stone formation decreased in 97.8 per cent of the patients, remission was obtained in 79.8 per cent and the need for surgical treatment of newly formed stones was eliminated. In patients with relapse after other treatment, such as thiazide, the addition of potassium citrate induced clinical improvement. Thus, our study provides physiological, physicochemical and clinical validation for the use of potassium citrate in the treatment of hypocitraturic calcium nephrolithiasis and uric acid lithiasis with or without calcium nephrolithiasis.     

A study on the cause of urolithiasis of the upper urinary tract--clinical study of risk factors in the formation of stones in the upper urinary tract

Various risk factors and inhibitors of the stone formation of the upper urinary tract have been pointed out in urine. We examined the amount of daily excretion of several important risk factors (calcium, phosphorus, urate and oxalate) and inhibitors (magnesium and citrate) in the urine of 21 healthy males, 13 male single stone formeks and recurrent and/or multiple stone formers before and after taking the regular diet which contains 500 mg of calcium and 1,000 mg of phosphorus a day. The daily excretion of calcium, phosphorus and magnesium indicated no significant differences among the 3 groups. The excretion of oxalate in urine for 24 hours was significantly decreased in the stone formers after taking the regular diet. The urinary excretion of the urate per body surface area in the stone formers was significantly higher than that in the healthy control. The amount of the excretion of the citrate in urine in the recurrent and/or multiple stone formers was significantly lower than that in the other 2 groups. Many patients of the recurrent and/or multiple urinary stones had more than two abnormal values of above-mentioned risk factors and inhibitors. These results suggest that the causes of the formation of the upper urinary stone were not single but multiple and that the dietary advice to these patients was important against the recurrence of the urolithiasis.