Postprandial mineral metabolism and secondary hyperparathyroidism in early CKD

Normophosphatemia and normocalcemia are maintained in chronic kidney disease (CKD) by increased levels of fibroblast growth factor-23 (FGF-23) and parathyroid hormone (PTH), but the stimuli for secretion of these hormones in early CKD are incompletely understood. Most human physiologic studies have focused on random or fasting measurements of phosphorus, calcium, FGF-23, and PTH, but in this study, the hypothesis was that measurements in the postprandial state may reveal intermittent stimuli that lead to increased FGF-23 and PTH levels. The 4-h postprandial response in 13 patients with CKD and fasting normophosphatemia and normocalcemia (mean GFR 41 +/- 8 ml/min per m(2)) was compared with 21 healthy volunteers. Compared with healthy subjects, fasting patients with CKD had significantly higher levels of FGF-23 and fractional excretion of phosphorus; lower fractional excretion of calcium; and no difference in serum calcium, phosphorus, and PTH levels. After standardized meals, urinary phosphorus excretion in both groups increased despite unchanged serum phosphorus and FGF-23 levels. Postprandial urinary calcium excretion also increased in both groups, and this was accompanied by significantly reduced serum calcium and increased PTH levels in patients with CKD only; therefore, FGF-23 does not seem to be an acute postprandial regulator of phosphaturia in CKD or in health, but inappropriate postprandial calciuria with episodic, relative hypocalcemia may represent a previously unreported mechanism of secondary hyperparathyroidism in CKD.     

Postprandial hyperinsulinaemia, insulin resistance and inappropriately high phosphaturia are features of younger males with idiopathic calcium urolithiasis: Attenuation by ascorbic acid supplementation of a test meal

In idiopathic recurrent calcium urolithiasis (RCU) the state of insulin and carbohydrate metabolism, and relationships to minerals such as phosphate, are insufficiently understood. Therefore, in two groups of males with RCU (n = 30) and healthy controls (n = 8) the response to an oral carbohydrate- and calcium-rich test meal was studied with respect to glucose, insulin, and C-peptide in peripheral venous blood (taken before and up to 180 min post-load), and phosphate and glucose in fasting and post-load urine. In one RCU group (n = 16) the meal was supplemented with ascorbic acid (ASC; 5 mg/kg body weight). The mean age (RCU 29, RCU + ASC 30, controls 27 years) and mean body mass index [RCU 24.4, RCU + ASC 25.0, controls 24.0 kg/m²] were similar. Insulin resistance (synonymous sensitivity of peripheral organs to insulin) was calculated from insulin serum concentration, as was also integrated insulin, C-peptide, and glucose. Untreated stone patients (RCU) developed hyperinsulinaemia between 60 and 120 min post-load, increased integrated insulin, and insulin resistance (P 0.05 vs controls)., whereas the rise of C-peptide and glycaemia (absolute and integrated values) was only of borderline significance. Fasting phosphaturia was low in both RCU subgroups vs controls; however, phosphaturia in untreated RCU rose in response to the meal, contrasting sharply with a decrease in controls. ASC supplementation of the meal (in the RCU + ASC subgroup) normalized insulin, failed to normalize postload phosphaturia, but reduced post-load glucosuria and urinary pH significantly (mean pH values 5.55 vs 5.93 in untreated RCU, controls 5.50). Postprandial urinary oxalate, calcium, protein, and supersaturation products were not changed. The postprandial changes in phosphaturia and insulin sensitivity were inversely correlated (n = 38,r = -0.44,P = 0.007). It was concluded that in younger RCU males: (1) postprandial hyperinsulinaemia, the failure to reduce phosphaturia and —within limits — glucosuria, appropriately, as well as poor urine acidification are important features of the metabolism; (2) these phenomena are probably caused by insulin resistance of organs, the kidney included; and (3) the addition of a supraphysiological dose of ASC to a meal, the subsequent abolition of hyperinsulinaemia, and the restoration of normal urine acidification suggest that this antioxidant is capable of counteracting some preexisting basic abnormality of cell metabolism in RCU.     

Crystalluria determined by polarization microscopy

Summary A retrospective study was done on the nature and degree of crystalluria in spontaneously voided fasting and postprandial urine of patients with recurrent idiopathic calcium urolithiasis (RCU) divided into normocalciuria (20 males, 20 females) and hypercalciuria patients (20 males, 20 females), and controls (20 males, 20 females). The crystals were obtained using a filter technique and identified by microscopy. In addition, individual data, clinical chemistry variables and indices reflecting the risk of calcium phosphate and calcium oxalate crystallization were evaluated. In contrast to findings of other investigators of crystalluria we observed only a few crystals on the filters. The most frequently occurring phases were (in this order) a urate-containing phase (tentatively termed uric), an amorphous calcium phosphate phase (tentatively termed isotropic) and a phase of spheroid-like particles, not yet definitely characterized (tentatively termed spheroid). Calcium oxalate crystals were found only exceptionally. There was no relationship between the degree of calciuria (normo-versus hypercalciuric RCU) and crystalluria. Among RCU, males generally had a predominance of the isotropic, females of the spheroid phase, as compared with controls. Also, RCU females were generally obese, and their spheroid score and lean body mass correlated negatively and significantly. The calcium phosphate and calcium oxalate risk indices were always low in normal individuals, higher in RCU. Patients of both sexes with urinary stones had normal parathyroid gland function, but higher total calcium in fasting serum and higher urinary pH as compared with controls. From these data we concluded that (1) crystalluria is a regular finding in human urine, but is more pronounced in RCU; (2) in males, the isotropic phase, in terms of frequency and its score, may be causally related to the development of urolithiasis; (3) the spheroid phase, more frequently observed in RCU females, may reflect an as yet unknown metobolic disorder; (4) the rareness of calcium oxalate crystals despite a high calcium oxalate risk index suggests that such crystals may be adherent to upstream tissue.Part of this work was published as an abstract in Urol Res (1988) 16:235     

Urinary pyrophosphate in patients with recurrent calcium urolithiasis and in healthy controls: a re-evaluation

The excretion of inorganic pyrophosphate was studied in daily, fasting and postprandial urine specimens of normocalciuric and hypercalciuric patients with recurrent renal calcium stone disease (40 men and 40 women), and healthy controls (20 men and 20 women). Both populations were subdivided into younger (20 to 40 years old) and older (more than 40 years old) individuals. In general, there was a tendency towards higher urinary pyrophosphate excretion with increasing age (both sexes and all groups studied), and lower excretion in women than in men. The urinary pyrophosphate excretion rate was unchanged in daily and fasting urine specimens of the younger male normocalciuric and idiopathic hypercalciuric stone patients, whereas in the daily and postprandial urine of younger women the median excretion rate was reduced (controls versus normocalciuric plus idiopathic hypercalciuric subjects, 3 versus 1 mumol., p less than 0.05). In contrast, in older men urinary pyrophosphate was reduced in daily specimens (controls versus normocalciuric plus idiopathic hypercalciuric subjects, 55 versus 33 mumol., p less than 0.05) but it was unchanged in fasting urine specimens. In older women no change was detectable in any of the 3 urine portions. Factorization of urinary pyrophosphate for the associated urinary creatinine did not alter these results substantially, and the presence of renal stones did not modify pyrophosphate excretion significantly. Urinary pyrophosphate was correlated significantly with urinary volume, citrate and phosphorus. We conclude that only subclassification of stone patients with respect to sex, age and type of calciuria, and consideration of additional urine portions besides the daily urine may help to uncover states of urinary pyrophosphate deficit. On the basis of the data, we recommend that clinically relevant studies on inhibitory effects of urinary pyrophosphate on the nucleation and growth of crystals and stones should be done preferentially in urine portions with a proved pyrophosphate deficit.     

Crystalluria in idiopathic recurrent calcium urolithiasis

Summary A retrospective study was done on the nature and degree of crystalluria in fasting and postprandial urine in patients with recurrent idiopathic calcium urolithiasis (RCU) for whom stone analysis was available. RCU was stratified into subgroups in accordance with stone analysis. The crystals were obtained and identified using a filter technique and polarization microscopy, respectively. Crystalluria score, relative saturation products (RSPs), and low-molecular-weight inhibitors were assessed. Calcium oxalate crystals were never observed in either male or female patients with stones composed exclusively of calcium oxalate, and only sporadically in patients with mixed stones (the additional component was calcium phosphate in most cases). Other crystalluria phases, such as amorphous calcium phosphate, a urate-containing phase, and a phase presenting as spherolytic particles, were slightly more frequent in patients with mixed stones. In contrast to crystalluria, RSPs and inhibitors differed in male and female patients, suggesting that crystalluria may not be under the exclusive control of these factors. The following conclusions were reached. (1) Calcium oxalate crystalluria is absent from RCU with pure calcium oxalate stones; hence, calcium oxalate crystalluria does not qualify as a diagnostic aid. (2) The co-existence of the isotropic phase and mixed stones may indicate that the formation of these concretions is characteristic for a major RCU subgroup. (3) On the basis of clinical chemistry and physicochemical data in urine and of crystalluria, it appears that the pathogenesis of RCU differs in male and female subjects.     

Fasting gastrinemia and elevated supersaturation with hydroxyapatite of fasting urine — Observations in renal calcium stone patients and controls

Summary We evaluated serum gastrin, acid-base status, variables of mineral metabolism in fasting blood, as well as pH, relative supersaturation of stone forming constituents, and crystalluria in the associated fasting urine, of control subjects (n=12), and in age-and weight-matched male normocalciuric (n=12) and hypercalciuric (n=12) patients with idiopathic recurrent calcium urolithiasis (RCU). In RCU, mineral metabolism and acid-base data are unchanged, whereas mean serum gastrin is only insignificantly higher as compared to controls. Subclassification of all participants into categories with either high-normal or low-normal gastrin reveals that in RCU with low-normal gastrin there is a higher-than-normal urinary pH and significantly elevated supersaturation of urine with hydroxyapatite. Crystalluria and stone analysis support the assumption that the physicochemical environment accompanied by low gastrin levels predisposes to urinary precipitation of calcium phosphate with subsequent formation of a stone nidus. pH in fasting urine and integrated fasting serum gastrin correlate significantly, suggesting that low fasting serum gastrin in RCU patients may be considered a rick factor for calcium phosphate stone formation.Abbreviations used in this paper RCU Recurrent calcium urolithiasis - NC Normocalciuria - I-HC Idiopathic hypercalciuria - HAP Hydroxyapatite - cAMP cyclic AMP     

Diet, vitamin D and vertebral mineral density in hypercalciuric calcium stone formers

To elucidate the pathophysiology of dietary calcium independent hypercalciuria, 42 calcium stone formers (Ca SF) were selected because they had on free diet a calciuria greater than 0.1 mmol/kg/day. For four days they were put on a diet restricted in calcium (Ca RD) by exclusion of the dairy products. They collected 24 hour urines on free diet and on day 4 of Ca RD as well as the two-hour fasting urines on the morning of the day 5 and the four-hour urines passed after an oral calcium load of 1 g, for measurement of creatinine, Ca, PO4, urea and total hydroxyprolinuria (THP). On day 5 fasting plasma concentrations of Ca, PO4, intact PTH, Gla protein, calcidiol and calcitriol were measured. The patients were firstly classified into dietary hypercalciuria (DH, 18 patients) and dietary calcium-independent hypercalciuria (IH, 24 patients) on the basis of the disappearance or not of hypercalciuria on Ca RD. Then the patients with IH were subclassified into absorptive hypercalciuria (AH) because of normal fasting calciuria (8 patients) and into fasting hypercalciuria (16 patients). Fasting hypercalciuric patients were subsequently divided according to the PTH levels into renal hypercalciuria (RH, 1 patient) with elevated fasting PTH becoming normal after the Ca load and undetermined hypercalciuria (UH, 15 patients) with normal PTH levels. Furthermore, their vertebral mineral density (VMD) was measured by quantitative computerized tomography which was normal in DH (91 +/- 6% of the normal mean for age and sex) but was decreased in IH to 69 +/- 4%. No difference in VMD was observed between AH and UH. Urinary excretions of urea, phosphate and THP was higher in IH than in DH and comparable in AH and UH. Sodium excretion Ca RD was the same in all groups and subgroups as well as the plasma parameters. Plasma calcitriol was increased in IH and DH comparatively to normal in spite of normal plasma calcidiol. Calciuria increase after oral calcium load, an index of Ca absorption, was higher in IH than in controls and comparable in IH and DH as well as in the three subgroups of IH. From these data and correlation studies in IH it is concluded: (1.) VMD is decreased in Ca stone formers with IH but not in those with DH, making the distinction of these two groups of hypercalciuria patients clinically relevant.(ABSTRACT TRUNCATED AT 400 WORDS)     

Urinary calcium excretion in healthy children and adolescents

Urinary calcium (Ca) excretion was determined in 1,578 24-h urine samples from 507 healthy children and adolescents (252 boys, 255 girls; 2.8–18.4 years) participating in the DONALD Study and is presented for 32 different age and sex groups. Calciuria values related to body weight (mg/kg per day) were relatively constant except for a transient decrease during puberty in all centiles, with a later onset in boys than girls. Distribution of calciuria (mg/kg per day) was best normalized by log transformation, with an almost constant standard deviation of the log-transformed values. Ca excretion was ≥4 mg/kg per day in 8.6% and ≥6 mg/kg per day in 1.5% of the urine samples. Based on Ca excretion rates of 1,080 pairs of 24-h urine samples from 364 children and adolescents, sensitivity, specificity, and the predictive value for hypercalciuria (≥4 mg/kg per day) in the next urine sample were calculated at three test levels classifying calciuria of the initial urine sample. In summary, this study presents normal values of urinary Ca excretion related to age and sex in a population of healthy German children and adolescents consuming a typical western-style diet. A high level of calciuria in a random urine sample is important in the diagnosis of hypercalciuria. Received: 25 February 1997 / Revised: 28 April 1999 / Accepted: 3 May 1999     

Human lactation: forearm trabecular bone loss, increased bone turnover, and renal conservation of calcium and inorganic phosphate with recovery of bone mass following weaning

The calcium (Ca) metabolism of established human lactation was studied in 40 adult women (mean age 32.4 years) who had been breast-feeding for 6 months (Lac) and in 40 age-matched controls (Con) using fasting urine and blood biochemistry and forearm single-photon bone mineral densitometry (BMD). Serial studies were performed up to 6 months after weaning in Lac women and repeated once in Con women. During lactation the significant findings were (1) a selective reduction (7.1%, P less than 0.03) in BMD at the ultradistal site containing 60% trabecular bone, but not at two more proximal, chiefly cortical bone sites; (2) increased bone turnover affecting bone resorption [fasting hydroxyproline excretion, Lac 2.22 +/- 0.12 mumol/liter GF (mean +/- SEM), Con 1.19 +/- 0.04, P less than 0.001] and affecting bone formation (plasma alkaline phosphatase, Lac 81.9 +/- 2.5 IU/liter, Con 53.5 +/- 2.7, P less than 0.001, and serum osteocalcin, Lac 14.0 +/- 0.7 microgram/liter, Con 7.3 +/- 0.4, P less than 0.001); and (3) renal conservation in the fasting state of both Ca and inorganic phosphate (Pi) with a resultant moderate increase in plasma Pi but not in plasma Ca (total or ionized). There were no differences between the groups in serum parathyroid hormone (PTH, intact and midmolecule assays), 25-hydroxy- and 1,25-dihydroxyvitamin D, nephrogenous cyclic AMP production, or plasma creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of ethyl icosapentate on urinary calcium and oxalate excretion

BACKGROUND: The effect of ethyl icosapentate (EPA-E) on urinary calcium and oxalic acid excretion was examined to evaluate whether EPA-E is useful in the prevention of calcium-containing urinary stones. METHODS: For 6 months, urine was measured daily from 40 calcium-containing urinary stone producers at an outpatient clinic, before and after the administration of 1800 mg/day EPA-E. The urine was measured for volume, urea nitrogen, creatinine, calcium, magnesium, phosphorus, uric acid, oxalic acid and citric acid. Serum total cholesterol and triglyceride were also measured. RESULTS: Urinary calcium excretion was not reduced in any of the patients or particular hypercalciuric groups, nor did the level of calcium change. However, nine of the 25 hypercalciuric patients experienced a significant urinary calcium reduction to the normal calciuric level (a reduction of approximately 44%). It is not known why these particular patients experienced a reduction. Urinary oxalic acid did not change, whether hypercalciuria was present or not. CONCLUSIONS: These findings suggest that EPA-E is not particularly effective in reducing urinary calcium excretion in the hypercalciuric patients, but it needs future investigation because some patients experienced significant urinary calcium reduction.     

The comprehensive examination of patients with recurrent calcium nephrolithiasis]

Hypercalciuria is one of the main causes of recurrent generation of urinary calcium-containing calculi. 107 patients with recurrent calcium nephrolithiasis were examined and results presented. Concentrations of potassium, sodium, chlorides, calcium, phosphorus, uric acid and creatinine were investigated in serum and urine, as well as indices of acid-base balance in arterial blood. pH-metry, "preliminary" and oral calcium tolerance test were also carried out. The microcomputer data analysis established that the diagnosis of primary hyperparathyroidism may be identified in case of increased serum calcium level before and after calcium load test, the same of parathyroid, and increased urinary cAMP excretion. Renal hypercalciuria is characterized by low blood calcium level in both periods of the oral test, high basal calciuria, increased urinary cAMP excretion and its slight decrease after the oral calcium load test, by a tendency to lower serum magnesium levels in high magnesuria. The patients with absorptive hypercalciuria had an upper normal or increased blood calcium level, a significant calcemic and calciuric "response" to the calcium load, reduction in urinary cAMP elimination and more severe decrease (close to 0) of these indices after oral calcium load and normal magnesium levels in blood and urine. On a base of the "preliminary" test data the patients with relapsing calcium nephrolithiasis and metabolic disorders may be differed from those without calcium and phosphorus metabolic deteriorations. The "preliminary" test defines indications for the oral calcium tolerance test, automatic diagnosis and computer data storage facilitate physician to work and to solve problems of the patients' survey.     

The effects of the calcium-restricted diet of urolithiasis patients with absorptive hypercalciuria type II on risk factors for kidney stones and osteopenia

The calcium (Ca)-restricted diet of urolithiasis patients with absorptive hypercalciuria type II may decrease Ca excretion but increase biochemical markers of risk for osteopenia. We randomly allocated 25 patients from six hospitals into an experimental group (Ca restriction to 500 mg/day, oxalate-rich products discouraged and normalization of animal protein and sodium) and a control group (no restrictions) for one month. The urinary Ca excretion did not decrease significantly, but the oxalate excretion decreased, although not significantly. The hydroxyproline:creatinine ratio in fasting urine seemed to increase and the calcium:creatinine ratio to decrease. The deoxypyridinoline:creatinine ratio in fasting urine did not change. We conclude that our Ca-restricted diet, which is lower in Ca, animal protein and table salt due to the omission of dairy products, may be of benefit for absorptive hypercalciuria type II patients without enhancing the risk for osteopenia. However, a long-term clinical trial is required. Received: 12 September 1996 / Accepted: 31 July 1997     

Frequency of renal phosphate leak among patients with calcium nephrolithiasis.

BACKGROUND: Nephrolithiasis is a frequent disorder affecting 10 to 15% of the population in Europe and the United States. More than 80% of renal stones are made of calcium oxalate and calcium phosphate. The main identified risks for calcium renal stone formation are hypercalciuria and urinary saturation. A urine phosphate (Pi) loss is often associated with hypercalciuria; furthermore, hyperphosphaturia increases urinary saturation. METHODS: To determine whether urinary phosphate loss is associated with calcium urolithiasis, we measured renal Pi threshold (TmPi) in 207 stone formers with normal parathyroid hormone (PTH) serum concentration and in 105 control subjects. RESULTS: The TmPi followed a normal distribution in both groups. The mean TmPi was significantly lower in stone formers versus controls (0.72 +/- 0.13 vs. 0.87 +/- 0.18 mmol/L, P < 0.0001) because of a shift to the left of the TmPi distribution curve in the stone former population, with no evidence for bimodal distribution. Five percent of the controls had a TmPi <0.63 versus 19% of the stone formers. Daily urinary calcium excretion was significantly higher in stone formers than in controls. Calcium excretion was also significantly higher in stone formers with TmPi <0.63 mmol/L compared with those with TmPi > or =0.63. Serum PTH and ionized calcium concentrations were not different in stone formers and in control subjects, whatever the TmPi value. CONCLUSIONS:: A low TmPi is more frequently encountered in stone formers with a normal PTH concentration than in control subjects and is associated with a high urinary Ca excretion. The hypophosphatemia induced by a renal phosphate leak may predispose the subject to calcium stone formation by increasing the serum calcitriol level, calcium excretion, and urinary saturation.     

Parathyroid hormone is normal in renal stone patients with idiopathic hypercalciuria and high fasting urinary calcium

Summary In a group of patients with idiopathic hypercalciuria and an increased fasting urinary calcium excretion we re-examined the question: does secondary hyperparathyroididsm exist? Eight out of 51 patients with calcium renal stones had a high calcium excretion in both fasting and in 24 h urines. The carboxyl-terminal immunoreactive PTH (iPTH) values in these patients were 16±5 ngeq/ml (M±SD), no higher than the iPTH values in the other groups, e.g. normocalciuric patients had an iPTH of 23±8 ngeq/ml. The existence of secondary hyperparathyroidism in a subgroup of stone patients with increased fasting urinary calcium excretion is questionable.Supported by the DFG (Li 253/3, 5)     

The use of a test for the differential diagnosis of hypercalciuria.

28 renal stone formers (18 men and 10 women) with idiopathic hypercalciuria (IH) and 27 controls have been subjected to a test proposed for the diagnosis of absorptive, resorptive and renal hypercalciurias. Fasting serum calcium concentration, urinary calcium and cyclic AMP excretion were measured after overnight fasting and an oral load of calcium. Absorptive hypercalciuria was demonstrated in 14 patients. High fasting urinary calcium first suggested resorptive or renal hypercalciurias in 5 other patients, but since fasting urinary calcium was normalized following cellulose phosphate therapy, absorptive hypercalciuria was more likely. Renal hypercalciuria was a possibility in 1 single case. Both fasting and post-load urinary calcium were normal in 7 men and 1 woman. The test did not appear as useful as expected since it was of no diagnostic value in about 30% of the cases and erroneously suggested resorptive or renal hypercalciuria in about 15% of the cases. On the other hand it indicated that absorptive IH is common and renal IH exceptional.     

Accentuated hyperparathyroidism in type II Bartter syndrome

Background

Bartter syndrome (BS) may be associated with different degrees of hypercalciuria, but marked parathyroid hormone (PTH) abnormalities have not been described.

Methods

We compared clinical and laboratory data of patients with either ROMK-deficient type II BS (n?=?14) or Barttin-deficient type IV BS (n?=?20).

Results

Only BS-IV patients remained mildly hypokalemic in spite of a higher need for potassium supplementation. Estimated glomerular filtration rate (eGFR) was mildly decreased in only four BS-IV patients. Average PTH values were significantly higher in BS-II (160.6?±?85.8 vs. 92.5?±?48 pg/ml in BS-IV, p?=?0.006). In both groups, there was a positive correlation between age and log(PTH). Levels of 25(OH) vitamin D were not different. Total serum calcium was lower (within normal limits) and age-related serum phosphate (Pi)-SDS was increased in BS-II (1.19?±?0.71 vs. 0.01?±?1.04 in BS-IV, p?<?0.001). The GFR threshold for Pi reabsorption was higher in BS-II (5.63?±?1.25 vs. 4.36?±?0.98, p?=?0.002). Spot urine calcium/creatinine ratio and nephrocalcinosis rate (100 vs. 16 %) were higher in the BS-II group.

Conclusions

PTH, serum Pi levels, and urinary threshold for Pi reabsorption are significantly elevated in type II vs. type IV BS, suggesting a PTH resistance state. This may be a response to more severe long-standing hypercalciuria, leading to a higher rate of nephrocalcinosis in BS-II.

     

Uric acid disorders in patients with calcium stones.

Plasma and uric acid levels were measured in 132 men with calcium-containing renal stones and in 24 healthy men of similar ages. Fasting resulted in a significant fall in the mean plasma uric acid level of normal subjects. Intermittent hyperuricaemia was observed in 7% of fasting patients. Intermittent hyperuricosuria was found in 17% of non-fasting patients but in only 2 to 6% of fasting subjects. Most of the uric acid abnormalities in patients with calcium stones therefore appear to be due to diet and may be prevented by reducing the consumption of purine-rich foods. A direct relationship was observed between uric acid excretion and urine flow at normal flow rates. It is suggested that the apparent increase in stone incidence, which occurs with rising living standards, may be due partly to increased consumption of purine-rich foods.     

Effects of acute oral sodium potassium citrate load in healthy males--outlook for treatment of patients with calcium-containing renal stones

The acute effects of a single (5 g) oral load of sodium potassium citrate (SPC), given together with a liquid test meal, were studied in 6 healthy male volunteers with respect to changes in serum citrate, blood acid base status, urine pH, citrate, calcium and minerals, and oxalate, as well as the calculated relative supersaturation of urine with several stone-forming phases, and the associated crystalluria. It was found that, apart from making the urine more alkaline, SPC induces mild compensated metabolic alkalosis, increases serum and urinary citrate, and reduces fractional urinary calcium excretion, but leaves urinary oxalate and the accompanying crystalluria unchanged. Except for the increase in urinary supersaturation with hydroxyapatite, the supersaturation of other important stone-forming constituents is statistically unchanged. In addition, there are indications that SPC reduces postprandial intestinal calcium absorption without affecting serum parathyroid hormone and 1,25-dihydroxyvitamin D. It is concluded that there is a spectrum of acute effects of oral SPC that may warrant long-term trials on this medication in the metaphylaxis of calcium-containing urinary stones.     

Hypercalcaemia is associated with poor mental health in haemodialysis patients: results from Japan DOPPS.

BACKGROUND: The Dialysis Outcomes and Practice Patterns Study (DOPPS) reported high incidence of depression in haemodialysis patients. Hypercalcaemia and high parathyroid hormone (PTH) levels are aetiological factors of psychological disorders. We examined the association between mineral metabolism abnormalities and mental health in Japanese-DOPPS patients. METHODS: We used baseline data of Japan-DOPPS, Phase 1 (2755 patients, 1999-2001) and Phase 2 (2286 patients, 2002-03). The outcome variable was mental health using the mental health domain of SF-36. We examined the association between serum corrected calcium, phosphorus, calcium x phosphorus product and intact PTH concentrations, and mental health using analysis of covariance and also the associations between corrected calcium levels and current use of vitamin D and calcium-containing phosphate binder. RESULTS: There was a significant association between mental health and corrected calcium levels. A significantly lower mental health score was noted in patients with corrected calcium > or = 11 mg/dl than in <8.4 (P = 0.04), > or =8.4 to <10.2 (P = 0.009) and > or =10.2 to <11 mg/dl (P = 0.003). The association was significant even after adjustment for age, sex and other confounders. However, there was no relationship between intact PTH and mental health. High-corrected calcium levels were significantly associated with the use of intravenous active vitamin D and calcium-containing phosphate binder. CONCLUSIONS: Hypercalcaemia, but not high intact PTH, is associated with poor mental health in dialysis patients. While a cause-effect relationship between hypercalcaemia and deterioration of mental health needs further confirmation by longitudinal and prospective studies, our observational findings suggest the importance of control of serum calcium concentration in dialysis patients.     

Seasonal variations in urinary excretion of calcium and magnesium in healthy subjects and patients with renal calculus and chronic renal failure

Renal excretion of calcium in healthy subjects and in patients with renal stones increases in the summer, as compared to the winter values. In patients with chronic renal failure calciuria shows no seasonal variations. No essential difference in the monthly excretion of magnesium in 24-hour urine has been found between healthy persons and patients with renal stones.