Biomedical subjects

Charles Y C Pak

Publications and source records attributed to Charles Y C Pak.

At least 19 recordsLinked to original sources

PubMed2006

Effect of high and low calcium diets on stone forming risk during liberal oxalate intake.

PURPOSE: Recent studies suggest that a high calcium diet protects against calcium oxalate stone formation. We compared the effect of high and low calcium diets on urinary saturation of calcium oxalate during liberal oxalate intake. MATERIALS AND METHODS: A total of 10 healthy subjects (5 male, 5 female) participated in a 2-phase, randomized, crossover study comparing high (1,000 mg daily) and low (400 mg daily) calcium intake on a liberal oxalate diet (200 mg daily). During each phase subjects adhered to an instructed diet for 3 days followed by a controlled, metabolic diet for 4 days. Blood and 24-hour urine specimens collected on the last 2 days of each phase were analyzed for serum biochemistry studies and stone risk factors, respectively. RESULTS: Urinary calcium was higher (mean +/- SD 171 +/- 64 vs 124 +/- 49 mg daily, p = 0.002) and oxalate was lower (25 +/- 4.8 vs 27 +/- 4 mg daily, p = 0.02) on the high vs low calcium diet. Overall, the urinary relative saturation ratio of calcium oxalate was higher on the high compared with the low calcium diet (3.3 vs 2.5, p <0.0001) even after adjusting for confounding variables. CONCLUSIONS: In normal subjects urinary saturation of calcium oxalate was higher on a high calcium diet than a low calcium diet during liberal oxalate intake because the decrease in urinary oxalate did not overcome the effect of increased calcium. A high calcium diet during liberal oxalate intake may pose an increased risk of calcium oxalate stone formation.

Adult↗

PubMed2005

Effects of potassium alkali and calcium supplementation on bone turnover in postmenopausal women.

Potassium citrate may improve calcium balance by conferring an alkali load. Calcium supplementation slows postmenopausal bone loss by inhibiting PTH secretion. This study explores whether combined treatment with potassium citrate and calcium citrate is more effective than either agent alone in inhibiting bone loss. In a crossover study involving 18 postmenopausal women, the following treatments were compared: potassium citrate (4.3 g or 40 mmol/d), calcium citrate (800 mg or 20 mmol/d), combined treatment, and placebo. During the last 2 d of each 2-wk phase, serum and 24-h urine were collected for assessment of calcium metabolism, alkali load, and bone turnover markers. Compared with placebo, potassium citrate provided an alkali load and significantly decreased urinary calcium without changing serum PTH (sPTH) or bone turnover markers. Calcium citrate significantly increased absorbed calcium, marginally decreased sPTH, and significantly reduced bone resorption markers. Combined treatment retained key features of potassium citrate and calcium citrate. However, more alkali was delivered than with potassium citrate alone, and absorbed calcium did not differ from calcium citrate alone. Compared with placebo, combined treatment increased urinary calcium, marginally reduced sPTH, provided a clear alkali load, and reduced the bone resorption markers serum type I collagen C-telopeptide and urinary N-telopeptide by 20.4% (P < 0.0001) and 18.2% (P = 0.005), respectively. A significant trend was noted for the decrease in bone resorption markers as treatment changed from placebo to potassium citrate to calcium citrate to combined treatment. In postmenopausal women, combined treatment with potassium citrate and calcium citrate inhibits bone resorption by providing an alkali load and increasing absorbed calcium.

Bone Resorption↗

PubMed2005

Reduction in normalized bone elasticity following long-term bisphosphonate treatment as measured by ultrasound critical angle reflectometry.

Using an improved version of ultrasound critical angle reflectometry, the bone quality of cortical and trabecular bone was assessed in vivo by measuring elastic moduli (normalized for bone density) at both principal axes, referred to as the minimum and maximum normalized elasticities. The measurements were made in 30 normal premenopausal women, 30 normal postmenopausal women, 22 untreated postmenopausal women with osteoporosis, 74 postmenopausal women with osteoporosis or osteopenia on bisphosphonate treatment, and 32 patients with renal transplantation (16 women and 16 men) taking steroids. Cortical elasticity was higher than trabecular elasticity; both declined slightly and non-significantly with age in normal women. Among untreated postmenopausal women with osteoporosis, cortical maximum normalized elasticity (E(cmax)) remained within 95% prediction intervals of normal women. Among patients on bisphosphonate, E(cmax) was low in the majority of patients. E(cmax) was significantly more depressed among those taking the drug > or =3 years than <3 years (22.1% below normal premenopausal women versus 17.2%, P =0.001), and among those with incident non-spinal fractures than without (75.9 vs. 81.5%, P =0.008). E(cmax) was independent of bone mineral density at the calcaneus. Most patients with renal transplantation had low E(cmax), with a mean 20.8% below the normal premenopausal mean. Qualitatively similar findings were found with cortical minimum elasticity and with trabecular minimum and maximum elasticities. Thus, the material bone quality of cortical and trabecular bone may be impaired following bisphosphonate treatment, as in renal transplantation on steroids.

Adult↗

PubMed2005

Cloning and characterization of the human soluble adenylyl cyclase.

We identified the human ortholog of soluble adenylyl cyclase (hsAC) in a locus linked to familial absorptive hypercalciuria and cloned it from a human cDNA library. hsAC transcripts were expressed in multiple tissues using RT-PCR and RNA blotting. RNA blot analysis revealed a predominant 5.1-kb band in a multiple human tissue blot, but three splice transcript variants were detected using RT-PCR and confirmed by performing sequence analysis. Immunoblot analysis showed 190- and 80-kDa bands in multiple human cell lines from gut, renal, and bone origins in both cytosol and membrane fractions, including Caco-2 colorectal adenocarcinomas, HEK-293 cells, HOS cells, and primary human osteoblasts, as well as in vitro induced osteoclast-like cells. The specificity of the antiserum was verified by peptide blocking and reduction using sequence-specific small interfering RNA. Confocal immunofluorescence cytochemistry localized hsAC primarily in cytoplasm, but some labeling was observed in the nucleus and the plasma membrane. Cytoplasmic hsAC colocalized with microtubules but not with microfilaments. To test the function of hsAC, four constructs containing catalytic domains I and II (aa 1-802), catalytic domain II (aa 231-802), noncatalytic domain (aa 648-1,610), and full-length protein (aa 1-1,610) were expressed in Sf9 insect cells. Only catalytic domains I and II or full-length proteins showed adenylyl cyclase activity. Mg(2+), Mn(2+), and Ca(2+) all increased adenylyl cyclase activity in a dose-dependent manner. While hsAC had a minimal response to HCO(3)(-) in the absence of divalent cations, HCO(3)(-) robustly stimulated Mg(2+)-bound hsAC but inhibited Mn(2+)-bound hsAC in a dose-dependent manner. In summary, hsAC is a divalent cation and HCO(3)(-) sensor, and its HCO(3)(-) sensitivity is modulated by divalent cations.

Adenylyl Cyclases↗

PubMed2005

Physicochemical metabolic characteristics for calcium oxalate stone formation in patients with gouty diathesis.

PURPOSE: We determined why calcium oxalate stones instead of uric acid stones form in some patients with gouty diathesis. MATERIALS AND METHODS: Gouty diathesis was diagnosed from absence of secondary causes of uric acid stones or low urinary pH, and reduced fractional excretion of urate with discriminant score of the relationship between urinary pH and fractional excretion of urate less than 80. From the stone registry 163 patients with gouty diathesis were identified, including 62 with uric acid stones (GD + UA) and 101 patients with calcium oxalate stones (GD + Ca). Metabolic data and 24-hour urinary chemistry study were compared between the 2 groups. RESULTS: Compared with GD + UA, GD + Ca had significantly greater urinary calcium (196 +/- 96 mg per day vs 162 +/- 82 mg per day, p <0.05) and significantly lower urinary citrate (430 +/- 228 vs 519 +/- 288 mg per day, p <0.05), resulting in higher urinary saturation of calcium oxalate. Both groups had low urinary pH (less than 5.5) and high urinary undissociated uric acid (greater than 100 mg/dl). Urinary calcium post-oral calcium load was significantly higher in GD + Ca than in GD + UA (0.227 vs 0.168 mg/dl glomerular filtrate, p <0.001). CONCLUSIONS: Calcium oxalate stones may form in some patients with gouty diathesis due to increased urinary excretion of calcium and reduced excretion of citrate. Relative hypercalciuria in GD + Ca may be due to intestinal hyperabsorption of calcium.

Adult↗

PubMed2005

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.

Acid-Base Equilibrium↗

PubMed2005

Effect of dietary modification on urinary stone risk factors.

BACKGROUND: This study was undertaken to ascertain the effect of dietary modification on urinary stone risks, and to determine whether the response depends on the prevailing urinary calcium. METHODS: A retrospective data analysis was conducted from our stone registry involving 951 patients with calcareous stones undergoing ambulatory evaluation, whereby 24-hour urine samples were collected during random diet and after dietary modification composed of restriction of calcium, oxalate, sodium, and meat products. Samples were analyzed for stone risk factors. Urinary calcium was also obtained after overnight fast and following a 1 g-calcium load. Changes produced by dietary modification from the random diet were evaluated in 356 patients with moderate-severe hypercalciuria (>6.88 mmol/day, group I), 243 patients with mild hypercalciuria (5.00-6.88 mmol/day, group II), and 352 with normocalciuria (<5.00 mmol/day, group III). RESULTS: Urinary calcium postcalcium load and the percentage of patients with absorptive hypercalciuria type I were highest in group I, intermediate in group II, and lowest in group III. During dietary modification, urinary calcium declined by 29% in group I, 19% in group II, and 10% in group III. Urinary oxalate did not change. Urinary saturation of calcium oxalate declined by only 12% in group I, 6% in group II, and nonsignificantly in group III, owing to various physicochemical changes in urinary biochemistry, which attenuated the effect of the decline in urinary calcium. Urinary saturation of brushite declined in all 3 groups due to the fall in urinary calcium, phosphorus, and pH. This reduction was more marked in the hypercalciuric groups than in the normocalciuric group. Urinary saturation of monosodium urate also decreased from a decline in urinary sodium and uric acid. CONCLUSION: Secondary rise in urinary oxalate occurring from calcium restriction can be avoided by concurrent dietary oxalate restriction. Dietary modification (restriction of dietary calcium, oxalate, sodium, and meat products) is more useful in reducing urinary saturation of calcium oxalate among patients with hypercalciuria than among those with normocalciuria.

Adult↗

PubMed2004

Severely suppressed bone turnover: a potential complication of alendronate therapy.

Alendronate, an inhibitor of bone resorption, is widely used in osteoporosis treatment. However, concerns have been raised about potential oversuppression of bone turnover during long-term use. We report on nine patients who sustained spontaneous nonspinal fractures while on alendronate therapy, six of whom displayed either delayed or absent fracture healing for 3 months to 2 yr during therapy. Histomorphometric analysis of the cancellous bone showed markedly suppressed bone formation, with reduced or absent osteoblastic surface in most patients. Osteoclastic surface was low or low-normal in eight patients, and eroded surface was decreased in four. Matrix synthesis was markedly diminished, with absence of double-tetracycline label and absent or reduced single-tetracycline label in all patients. The same trend was seen in the intracortical and endocortical surfaces. Our findings raise the possibility that severe suppression of bone turnover may develop during long-term alendronate therapy, resulting in increased susceptibility to, and delayed healing of, nonspinal fractures. Although coadministration of estrogen or glucocorticoids appears to be a predisposing factor, this apparent complication can also occur with monotherapy. Our observations emphasize the need for increased awareness and monitoring for the potential development of excessive suppression of bone turnover during long-term alendronate therapy.

Aged↗

PubMed2004

Biochemical and physicochemical presentations of patients with brushite stones.

PURPOSE: We determined whether the biochemical and physicochemical backgrounds of patients with brushite stones differ from those with hydroxyapatite and calcium oxalate stones. MATERIALS AND METHODS: From a computer data base of patients completing ambulatory evaluation 19 with brushite stones, 24 with hydroxyapatite stones and 762 with calcium oxalate stones were identified with the specified composition in greater than 70% of stones. RESULTS: Absorptive hypercalciuria type I was present in 63% of patients with brushite, 17% with hydroxyapatite and 30% with calcium oxalate stones. Distal renal tubular acidosis was noted in 32% of patients with brushite, 42% with hydroxyapatite and 3% with calcium oxalate stones. Mean urinary calcium in the brushite group was significantly higher than in the hydroxyapatite and calcium oxalate groups (265 +/- 125 vs 186 +/- 103 and 187 +/- 95 mg daily, respectively). Urinary pH in the brushite group was slightly but significantly higher than in the calcium oxalate group (6.15 +/- 0.30 vs 5.91 +/- 0.42). The brushite relative saturation ratio in the brushite group was marginally higher than in the hydroxyapatite group and significantly higher than in the calcium oxalate group (3.25 +/- 2.03 vs 2.34 +/- 1.51 and 1.83 +/- 1.66, respectively). CONCLUSION: Patients with predominantly brushite stones could be distinguished from those with predominantly hydroxyapatite and calcium oxalate stones by higher urinary saturation with respect to brushite due mainly to hypercalciuria from absorptive hypercalciuria.

Adult↗

PubMed2004

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.

Aged↗

PubMed2004

Elucidation of factors determining formation of calcium phosphate stones.

PURPOSE: In this study we compared the effect of the urinary concentration of calcium with that of oxalate on the urinary relative saturation ratio (RSR) of calcium oxalate and brushite in patients with pure or mixed calcium phosphate stones. MATERIALS AND METHODS: A retrospective data analysis was performed of urinary stone risk analysis in 133 patients with pure or mixed calcium phosphate stones (30% or greater). Correlation was sought between stone events and urinary stone risk factors, and between brushite and urinary constituent RSRs before and after adjustment for variables. RESULTS: The formation rates of total events and stone surgeries weakly but significantly correlated with RSR urinary brushite (total events r = 0.22, p = 0.01) but not with RSR calcium oxalate. Urinary RSR brushite significantly correlated positively with urinary calcium (r = 0.67, p <0.0001), phosphorus and pH. After adjustment RSR brushite inversely correlated with citrate (r = -0.3, p = 0.0006). However, it did not correlate with oxalate. CONCLUSIONS: In stone formers with calcium phosphate or mixed calcium oxalate-calcium phosphate stones the stone formation rate depends on the urinary saturation of brushite but not of calcium oxalate. RSR brushite is determined by the urinary concentration of calcium, phosphate, citrate and pH but not by oxalate. Hypercalciuria should be controlled in patients with idiopathic calcareous renal calculi who form stones of pure or mixed calcium phosphate.

Adult↗

PubMed2004

Cost-effectiveness of medical management strategies for nephrolithiasis.

PURPOSE: We evaluated the cost-effectiveness and stone recurrence rates of common management strategies in stone formers. MATERIALS AND METHODS: A decision tree model was created to compare the costs of 6 medical treatment strategies, namely dietary measures alone (conservative), empiric drug treatment (empiric), or directed drug therapy based on simple or comprehensive metabolic evaluation. The model assumed cost accrual for evaluation, medications, emergency treatment and surgery for stone recurrence. We determined recurrence rates, medical evaluation sensitivity and the risk reduction of medical treatments from the literature and the costs of surgery, emergency room and medical evaluation at our county hospital. Drug costs were obtained from 2 national pharmacy chains. RESULTS: In first time stone formers conservative treatment was the least costly strategy and it yielded a stone formation rate of 0.07 stones per patient yearly. In recurrent stone formers conservative treatment was less costly than drug treatments but it was associated with a higher stone recurrence rate (0.3 stones per patient yearly). The remaining drug treatments were more costly than conservative treatment ($885 to 1,187 vs $258 yearly) but they further decreased recurrence rates by 60% to 86%. Modified simple medical evaluation and management (SMEM), that is drug treatment in all patients after simple evaluation) was slightly more costly than empiric treatment and minimally more effective. Comprehensive evaluation and treatment offered no advantage in cost or efficacy over empiric treatment or modified SMEM. CONCLUSIONS: In first time stone formers conservative therapy is cost-effective and efficacious. In recurrent stone formers conservative therapy is unsatisfactory despite low cost because of a high recurrence rate. Modified SMEM and empiric therapy yield the same cost and efficacy as treatments that follow comprehensive evaluation. However, modified SMEM may be advantageous because it offers useful additional medical information.

Cost-Benefit Analysis↗

PubMed2004

Association of urinary pH with body weight in nephrolithiasis.

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

Adult↗

PubMed2004

Rapid Communication: relative effect of urinary calcium and oxalate on saturation of calcium oxalate.

BACKGROUND: The study compared the effect of urinary calcium with that of oxalate on urinary saturation [relative saturation ratio (RSR)] of calcium oxalate. METHODS: A retrospective data analysis was conducted on urinary stone risk analysis from 667 patients with predominantly calcium oxalate stones. Urinary RSR of calcium oxalate was individually calculated using Equil 2. A "theoretical" curve of the relationship between urinary RSR of calcium oxalate and concentration of calcium or oxalate was obtained at two stability constants for calcium oxalate complex, while varying calcium or oxalate and using group mean values for urinary constituents. RESULTS: At the stability constant of 7.07 x 10(3), the increase in RSR of calcium oxalate was less marked with calcium than with oxalate. However, at the stability constant of 2.746 x 10(3) from the Equil 2 that is considered the "gold standard," calcium and oxalate were equally effective in increasing RSR of calcium oxalate. The above theoretical curves (relating RSR with calcium or oxalate) were closely approximated by the actual curves constructed with data from individual urine samples. Urinary saturation of calcium oxalate was equally dependent on urinary concentrations of calcium and oxalate (r= 0.75 unadjusted and 0.57 adjusted for variables, and P < 0.0001 for calcium; r= 0.73 unadjusted and 0.60 adjusted, P <0.0001 for oxalate). CONCLUSION: Among calcium oxalate stone-formers, urinary calcium is equally effective as urinary oxalate in increasing RSR of calcium oxalate.

Adult↗

PubMed2004

Medical management of urinary stone disease.

A variety of dietary and metabolic factors may contribute or cause stone formation in idiopathic calcium oxalate nephrolithiasis. Dietary factors include a high intake of animal proteins, oxalate and sodium, and a low intake of fluids and potassium-containing citrus products. Some of the metabolic causes of stones are hypercalciuria, hypocitraturia, gouty diathesis, hyperoxaluria, and hyperuricosuria. Dietary modification, to be applied in all patients with stones includes a high fluid intake, restriction of oxalate and sodium, and balanced diet with animal proteins complemented by adequate intake of fruits and vegetables. When dietary modification is ineffective in controlling stone formation or in the presence of severe metabolic derangements, a pharmacologic intervention may be necessary. In a simple approach, thiazide or indapamide with potassium citrate is recommended for patients with hypercalciuria, and potassium citrate alone for the remaining normocalciuric subjects.

Diet↗

PubMed2003

Predictive value of kidney stone composition in the detection of metabolic abnormalities.

PURPOSE: To determine if kidney stone composition can predict the underlying medical diagnosis, and vice versa. METHODS: We studied 1392 patients with kidney stones who underwent a complete ambulatory evaluation and who submitted one or more stones for analysis. We ascertained the associations between medical diagnosis and stone composition. RESULTS: The most common kidney stones were composed of calcium oxalate (n = 1041 patients [74.8%]), mixed calcium oxalate-calcium apatite (n = 485 [34.8%]), and calcium apatite alone (n = 146 [10.5%]). The most common medical diagnoses were hypocitraturia (n = 616 patients [44.3%]), absorptive hypercalciuria (n = 511 [36.7%]), and hyperuricosuria (n = 395 [28.4%]). Calcium apatite and mixed calcium oxalate-calcium apatite stones were associated with the diagnoses of renal tubular acidosis and primary hyperparathyroidism (odds ratios >/=2), but not with chronic diarrheal syndromes. As the phosphate content of the stone increased from calcium oxalate to mixed calcium oxalate-calcium apatite, and finally to calcium apatite, the percentage of patients with renal tubular acidosis increased from 5% (57/1041) to 39% (57/146), and those with primary hyperparathyroidism increased from 2% (26/1041) to 10% (14/146). Calcium oxalate stones were associated with chronic diarrheal syndromes, but not with renal tubular acidosis. Pure and mixed uric acid stones were strongly associated with a gouty diathesis, and vice versa. Chronic diarrheal syndromes and uric acid stones were associated with one another, and brushite stones were associated with renal tubular acidosis. As expected, there was a very strong association between infection stones and infection, and between cystine stones and cystinuria. CONCLUSION: Stone composition has some predictive value in diagnosing medical conditions, and vice versa, especially for noncalcareous stones.

Acidosis, Renal Tubular↗

PubMed2003

Biochemical profile of stone-forming patients with diabetes mellitus.

OBJECTIVES: To test the hypothesis that stone-forming patients with type II diabetes (DM-II) have a high prevalence of uric acid (UA) stones and present with some of the biochemical features of gouty diathesis (GD). METHODS: The demographic and initial biochemical data from 59 stone-forming patients with DM-II (serum glucose greater than 126 mg/dL, no insulin therapy, older than 35 years of age) from Dallas, Texas and Durham, North Carolina were retrieved and compared with data from 58 patients with GD and 116 with hyperuricosuric calcium oxalate urolithiasis (HUCU) without DM. RESULTS: UA stones were detected in 33.9% of patients with DM-II compared with 6.2% of stone-forming patients without DM (P <0.001). Despite similar ingestion of alkali, the urinary pH in patients with DM-II and UA stones (n = 20) was low (pH = 5.5), as it is in patients with GD, and was significantly lower than in patients with HUCU. The urinary pH in patients with DM-II and calcium stones (n = 39) was intermediate between that in those with DM-II and UA stones and those with HUCU. However, both DM groups had fractional excretion of urate that was not depressed, as it is in those with GD, and was comparable to the value obtained in those with HUCU. The urinary content of undissociated UA was significantly higher, and the saturation of calcium phosphate (brushite) and sodium urate was significantly lower in those with DM-II and UA stones than in those with HUCU. CONCLUSIONS: Stone-forming patients with DM-II have a high prevalence of UA stones. Diabetic patients with UA stones share a key feature of those with GD, namely the passage of unusually acid urine, but not the low fractional excretion of urate.

Adolescent↗

PubMed2003

Effect of high protein diet on stone-forming propensity and bone loss in rats.

BACKGROUND: High protein diets are believed to cause kidney stone formation and bone loss, but the mechanisms mediating these changes are unknown. The purpose of this study was to create an animal model of animal protein excess and to evaluate the response of kidney and bone to the dietary protein load. METHODS: Rats (12 per group) were pair-fed with a high (48%) and low (12%) casein diets that were otherwise identical in their content of sodium, potassium, calcium, phosphorus, and magnesium. RESULTS: Compared with the low casein group, the high casein group delivered a substantial acid load during 59 days of study, since it significantly decreased urinary pH, and increased urinary ammonium, titratable acidity, and net acid excretion. Animals on high casein diet also had higher urinary volumes. On the high casein diet, urinary calcium excretion was significantly higher and urinary citrate excretion and concentration was significantly lower. On the high casein diet, urinary saturation of calcium phosphate was higher. Serum calcitriol concentration did not significantly differ between the two groups. Histomorphometric analysis of femur procured after 59 days on the diet showed marked increase in bone resorption in the high casein group. Hypocitraturia was associated with increased activity of sodium-citrate cotransporter in renal cortical brush-border membranes (BBM) in the high casein group. CONCLUSION: Both the kidney and bone contribute to the pathogenesis of hypercalciuria during high casein diet in rats. Hypocitraturia is probably renal in origin. This rat model will be useful in elucidating the mechanisms by which high protein intake increases the risk of nephrolithiasis and bone loss in human beings.

Acid-Base Equilibrium↗