Studies on the mechanism of protein-induced hypercalciuria in older men and women

A human metabolic study was conducted to observe the effect of level of protein intake on urinary calcium, calcium absorption and calcium balance in older adults and to further study the mechanisms of protein-induced hypercalciuria. An increase in protein intake from about 47 to 112 g while maintaining calcium, magnesium and phosphorus intakes constant caused an increase in urinary calcium and a decrease in calcium retention. Glomerular filtration rate was increased and fractional renal tubular reabsorption was decreased by the increase in protein intake; total renal acid, ammonium and sulfate excretions more than doubled, whereas urinary sodium decreased by 38%. The changes in urinary calcium were positively correlated with the increase in total renal acid and sulfate excretion as well as with the decrease in fractional renal tubular reabsorption of calcium. Thus, the data indicate that protein-induced hypercalciuria is due to an increase in glomerular filtration rate and a decrease in fractional renal tubular reabsorption of calcium, the latter of which may be caused by the increased acid load on the renal tubular cells.     

Low calcium diet in hypercalciuric calcium nephrolithiasis: first do no harm

Many studies indicate that up-regulated production of 1,25(OH)2-vitamin D3 (calcitriol) with increased intestinal absorption of calcium is the primary event causing idiopathic hypercalciuria. Thus, a low calcium diet appears to be a straightforward strategy in calcium stone formers with hypercalciuria (HCSF). However, the efficacy of such a regimen has never been established, and lowering calcium intake from 1000 to 400 mg/day further enhances calcitriol production. On a diet chronically restricted in calcium, many stone formers increase their intake of animal flesh protein. The latter is known to increase renal mass, and calcitriol levels indeed are positively correlated with renal mass in animals as well as in HCSF. Thus, low calcium and high animal flesh protein consumption are independent stimuli for further up-regulation of calcitriol production. The rise in calcitriol suppresses parathyroid hormone synthesis thereby diminishing renal tubular calcium reabsorption, and increasing urinary calcium losses. Since calcitriol up-regulation also increases bone resorption, the combination of low calcium and high protein intake is particularly likely to induce negative calcium balance and thus osteopenia. Finally, low calcium intake carries the risk of insufficient intestinal binding of oxalate with subsequent increases in intestinal absorption and urinary excretion of oxalate. Indeed, most recent studies suggest that high amounts of calcium, when ingested simultaneously with oxalate-containing meals, are able to prevent hyperoxaluria during severe oral oxalate loading.     

Sex- and strain-specific expression of cytochrome P450s in ochratoxin A-induced genotoxicity and carcinogenicity in rats

There is an urgent need for drugs capable of inhibiting renal calcifications, nephrocalcinosis and stones included, in humans. Current anticalcification medication is based mainly on alkalinization of the metabolism using potassium-containing citrate alone, despite the fact that calcium stone patients suffer marginally from both magnesium and potassium deficiency. We investigated the anticalcification efficacy of oral potassium citrate versus the combined administration of this drug and magnesium citrate in the magnesium-deficient rat developing corticomedullary nephrocalcinosis and luminal microliths in the long term. Among other things we employed specific stains for calcium and oxalate, light microscopy and element analysis for renal tissue and calcifications, respectively. In addition, minerals in renal tissue, urine and plasma were determined, as well as the state of extracellular calcium homeostasis. Magnesium deficiency caused pure calcium phosphate tissue deposits, containing no magnesium, but no deposition of calcium oxalate in the tubular lumen; tissue magnesium, calcium and phosphorus were increased, and there was marked potassium wastage via urine; despite mild hypercalcemia other signs of hyperparathyroidism were not found. Alkalinization with the two kinds of medication evoked an increase in urinary pH, citrate, and potassium; however, potassium citrate alone tended to aggravate renal concretions, whereas the combination of this drug with magnesium citrate completely prevented concretions. It was concluded that: (1) magnesium deficiency-induced calcifications are oxalate-free and are not sensitive to mobilization by alkalinization with potassium citrate, which might explain the failure of the drug to prevent stone recurrence in clinical stone patients, and (2) the combination of potassium citrate and magnesium citrate, which shows enormous anticalcification efficacy, deserves high priority in clinical trials aimed at evaluating strategies for the prevention of stones.     

Sodium excretion in children with lithogenic disorders

INTRODUCTION: The causes of nephrolithisis are multifactorial and have not yet been enough investigated [1]. Hypercalciuria is the most common cause of metabolic nephrolithiasis [2-4]. Close relationship between urinary calcium and urinary sodium has been a subject of reported observations in the past, showing that high urinary sodium is associated with high urinary calcium [5-7]. Hyperoxaluria, hyperuricosuria and cystinuria are also metabolic disorders that can lead to nephrolithiasis. Recent studies have indicated that urinary elimination of cystine is influenced by urinary sodium excretion. Based on these observations it has been hypothesised that patients with high urinary sodium excretion are at high risk of urinary stone disease. The purpose of the study was to investigate sodium excretion in a 24-hour urine and first morning urine collected from children with lithogenic metabolic abnormalities (hypercalciuria, hyperoxaluria, hyperuricosuria, cystinuria), both with nephrolithiasis and without it, in order to determine its significance in urinary calculi formation. PATIENTS AND METHODS: Urinary sodium excretion was investigated in 2 groups of children: patients with lithogenic metabolic abnormalities, but without urinary stone disease (L group) and patients with nephrolithiasis (C group). Both groups were divided into 2 subgroups: patients with hypercalciuria and without it. There were 22 patients in group L (mean age 11.97 +/- 4.13 years), of whom 17 formed a hypercalciuric subgroup and 5 formed a non-hypercalciuric subgroup (3 patients with hyperuricosuria and 2 patients with hyperoxaluria). Group C consisted of 21 patients with nephrolithiasis (mean age 12.67 +/- 3.44 years), of whom 6 formed a hypercalciuric subgroup and 15 formed a non-hypercalciuric group (2 patients with cystinuria and 13 patients without lithogenic metabolic abnormalities). Control group consisted of 42 healthy age-matched children. All subjects had a normal renal function. A detailed history and clinical examination were done, and ultrasonography was performed in all patients. A 24-hour urine, first morning urine and serum specimen were analysed for sodium, potassium, calcium, uric acid, urea and creatinine. Fractional excretion of sodium, as well as urinary sodium to creatinin ratio and urinary sodium to potassium ratio, were calculated from the findings. Sodium and potassium levels were determined by flame photometry, calcium was measured by atomic absorption technique (Beckman Atomic Spectrophotometer, Synchron CX-5 model, USA), uric acid by carbonate method and creatinine by Jaffe technique. Cystine and dibasic amino acids were quantified by ion chromatography. Urinary oxalate excretion was determined by enzyme spectrophotometry. Hypercalciuria was defined by 24-hour calcium excretion greater than 3.5 mg/kg per day and/or calcium to creatinine ratio greater than 0.20 [8]. Uric acid excretion was expressed as uric acid excretion factored for glomerular filtration, according to Stapleton's and Nash's formula [9]. Normal values were lower than 0.57 mg/dl of glomerular filtration rate in 24-hour samples. Mean values were statistically analyzed by Pearson's linear correlation and analysis of variance (ANOVA). RESULTS: Urinary sodium concentration values including urinary sodium to potassium ratios, are shown in Table 1. We found that urinary sodium excretion was significantly increased in patients of both L and C groups when compared with controls (p < 0.05). Further analysis of the subgroups showed that urinary sodium excretion was significantly higher only in patients with hypercalciuria of both L and C groups in comparison to controls (p < 0.05) (Table 2). A significant positive correlation was found between 24-hour urinary sodium to creatinine ratio and urinary calcium to creatinine ratio (r = 0.31; p < 0.001) (Graph 1), as well as between urinary sodium to potassium ratio in 24-hour and first morning urine (r = 0.69; p < 0.001) (Graph 2). (A     

Hypertension in kidney stone patients

The prevalence of arterial hypertension (HT) was investigated in 258 patients (171 m, 87 f, 22-68 years) with a history of primary stone disease. HT was detected in 64 patients (24.8%), with no difference between males (25.7%) and females (23.0%). The prevalence of HT by age was very similar to that of a general population, especially in the calcium stone group. The discriminant analysis demonstrated that the composition of stones, other than the age and body weight of the patients, were the main factors associated with HT. As far as the different kind of stone is concerned, the prevalence of HT was higher in patients with uric acid (17/37, 45.9%) and struvite stones (11/27, 40.7%) than in calcium stone formers (35/188, 18.6%) (chi 2 16.31, p < 0.001). The prevalence of hypercalciuria was higher in the calcium stone group than in uric acid or struvite stone patients (36.4 vs. 9.7 vs. 13.7%; chi 2 10.35, p < 0.01). Furthermore, the hypercalciuria showed a trend to be more prevalent in the untreated (47.0%) than in the treated (31.2%) hypertensives, or normotensives (35.1%). Uric acid stone formers were older, heavier and with higher triglycerides and uric acid plasma levels than calcium or struvite patients. Also the struvite stone formers were older than the calcium stone ones. Our data suggest that the prevalence of HT in kidney stone patients and particularly in calcium stone formers is similar to that of a general population. The role of hypercalciuria as the link for HT-urolithiasis association seems quite uncertain. Struvite and uric acid stone formers have higher risk for HT than calcium stone formers, probably due to the old age or to the associated metabolic abnormalities.     

Urinary calcium oxalate saturation in healthy infants and children

PURPOSE: A number of factors influence the development of renal calculi, the most essential of which is the supersaturation of urine with lithogenic substances. Calcium oxalate stones occur most frequently in adult and pediatric patients with urolithiasis. Therefore, we established normal age and sex related data for urinary calcium oxalate saturation in infancy and childhood to allow a more specific prediction of the risk of (recurrent) stone disease. MATERIALS AND METHODS: We collected 24-hour urine samples from 473 healthy infants and children without a history of renal stones. Urinary lithogenic and stone inhibitory substances were measured, and the urinary calcium oxalate saturation was calculated using a computer program. RESULTS: Mean urinary calcium oxalate saturation was always higher in boys than in girls, which was significant in infancy (5.22 versus 2.03, p < 0.05) and at ages 7 to 9 years (8.84 versus 5.47, p < 0.05). The saturation first increased (p < 0.05) until age 7 to 9 years in boys and girls, and remained at high levels at ages 10 to 12 years (7.03 versus 5.49, p < 0.05 compared to infancy). Calcium oxalate saturation then decreased until adolescence when values were comparable to those of infancy (5.29 versus 3.35). CONCLUSIONS: We recommend calculating urinary calcium oxalate saturation for diagnostic purposes as well as for therapy control. Normal age and sex related values must be considered.     

Idiopathic hypercalciuria in childhood

This review describes the supposed mechanisms leading to idiopathic hypercalciuria (IHU) in childhood, further the diagnostic criteria and the proposed treatment modalities are discussed. IHU is not only one of the main causes of renal stone disease in children but it's also at the origin of the postglomerular haematuria and the frequency-dysuria syndrome. Its role in the development of osteoporosis in adults is also documented. The diagnosis of raised calcium excretion is based on age specific values during early infancy. In older children and adults a urinary calcium/creatinine ratio exceeding 0.6 mmol/mmol is regarded as elevated. Dietary calcium restriction can no longer be recommended for the treatment of IHU because it results in secondary hyperoxaluria and on the long-term causes decreased bone mineral density. Patients should be kept on dietary sodium restriction and high fluid intake. In cases IHU associated with recurrent episodes of macroscopic haematuria or recurrent stone disease a therapeutic trial with hydrochlorothiazide in the dose of 0.5-1 mg/kg/day with potassium-citrate supplementation and possibly magnesium citrate should be started. In some special forms of hypercalciuria such as the X-linked recessive nephrolithiasis syndrome or Bartter syndrome the localization and in some cases even the molecular mechanism of the events leading to increased calcium excretion are elucidated. In IHU enhanced Ca(++)-ATPase, and Na-Li countertransport activity and decreased Na+/K+ ATPase activity were described in the erythrocyte membrane model. It is expected that with the molecular genetic development the clinical classification of the hypercalciuric syndromes will become a rational genome-based one.     

Urinary calculi in children: contribution of anamnesis, biological exploration and physical analysis of calculi to the etiological diagnosis

BACKGROUND: It is always of importance to define the cause of urinary calculi disease in children to prevent recurrence and possible impairing of renal function. Nevertheless, etiology is not always easy to prove and must be deduced from both clinical and biological arguments. PATIENTS AND METHODS: The aim of this prospective study including 39 Tunisian children with urinary stones was to identify etiology and stone risk factors and detail the part of clinical and biological data and results of physical analysis of stones in determining the cause of the stone. RESULTS: In 31 cases among 39, clinical and biological data were not sufficient to identify clearly the stone etiology. When considering the structure and stone composition, the cause of the stone could be determined in 97.4% of the cases. An inherited disease was found responsible for the stone in 11 children, urinary tract infection in 13 cases, idiopathic hypercalciuria in nine cases and a nutritional deficiency disease in seven cases. In one case, polycystic kidney disease with metabolic risk factors could explain the stone process. No precise etiology was found in one case. Among infection stones, struvite stones could be related to urea-splitting bacteria while other calculi, containing whitlockite and protein matrix could be related to other micro-organisms. Earlier severe chronic diarrhoea episodes were noted in six among seven children presenting stones with a nucleus mainly composed of ammonium urate. CONCLUSION: Clinical data, biological data from both urine and blood of the patients and also the structure and composition of the stones are needed to identify the cause of urinary calculi. Such a procedure could provide the stone etiology in most cases.     

Renal stones and primary hyperparathyroidism: natural history of renal stone disease after successful parathyroidectomy

The aim of the study was to evaluate the risk of renal stone recurrence after successful surgical treatment of primary hyperparathyroidism (pHPT). Of 297 consecutive patients with surgically verified pHPT, 151 patients had had renal stone disease; a total of 113 patients were eligible for follow-up; and of these, 107 patients remained normocalcemic during follow-up and formed the study group. The number of new stones were calculated by subtracting the stones present on preoperative urograms from the number of stones on urograms after 1, 3, and 5 years and the number of stones passed or eliminated by intervention. Among 107 patients, 32 (30%) formed one to four new stones within 5 years. This recurrence rate is comparable to the expected recurrence rate in idiopathic stone formers. Primary hyperparathyroidism and renal stone disease are common. As all renal stone formers are screened for pHPT by serum calcium analysis, the two diseases might by coincidence be found in the same patients. A considerable number of patients with pHPT and renal stone disease therefore experience recurrence of their stone disease irrespective of the presence of normocalcemia after successful parathyroidectomy.     

Sustained reduction in urinary calcium during long-term treatment with slow release neutral potassium phosphate in absorptive hypercalciuria

PURPOSE: We tested whether UroPhos-K, a new slow release neutral form of potassium phosphate (155 mg. phosphate, 8 mEq. potassium per tablet) in a dose of 4 tablets twice daily would produce a sustained hypocalciuric response and maintain bone mass in patients with absorptive hypercalciuria, a major cause of nephrolithiasis characterized by excessive intestinal calcium absorption accompanied in some patients by excessive bone loss. MATERIALS AND METHODS: A total of 25 patients with absorptive hypercalciuria were studied in a 4-year, prospective, open trial with UroPhos-K at yearly intervals during a 4-day inpatient physiological study with a constant metabolic diet containing 400 mg. calcium, 100 mEq. sodium and 800 mg. phosphate daily. RESULTS: Treatment with UroPhos-K caused a sustained, marked reduction in urinary calcium (264 to 181 mg. daily). Fractional 47calcium absorption decreased modestly (74.0 to 64.6%) commensurate with a reduction in serum 1,25-dihydroxyvitamin D (42 to 34 pg./ml.). Intact parathyroid hormone increased within the normal range (30 to 42 pg./ml.). Bone mineral density was stable at the lumbar spine, femoral neck and distal third of the radius. CONCLUSIONS: UroPhos-K may provide a long-term alternative for hypercalciuric patients in whom thiazide therapy fails.     

Effect of oral calcium loading on intact PTH and calcitriol in idiopathic renal calcium stone formers and healthy controls

The calciuric response after an oral calcium load (1000 mg elemental calcium together with a standard breakfast) was studied in 13 healthy male controls and 21 recurrent idiopathic renal calcium stone formers, 12 with hypercalciuria (UCa x V > 7.50 mmol/24 h) and nine with normocalciuria. In controls, serum 1,25(OH)2 vitamin D3 (calcitriol) remained unchanged 6 h after oral calcium load (50.6 +/- 5.1 versus 50.9 +/- 5.0 pg/ml), whereas it tended to increase in hypercalciuric (from 53.6 +/- 3.2 to 60.6 +/- 5.4 pg/ml, P = 0.182) and fell in normocalciuric stone formers (from 45.9 +/- 2.6 to 38.1 +/- 3.3 pg/ml, P = 0.011). The total amount of urinary calcium excreted after OCL was 2.50 +/- 0.20 mmol in controls, 2.27 +/- 0.27 mmol in normocalciuric and 3.62 +/- 0.32 mmol in hypercalciuric stone formers (P = 0.005 versus controls and normocalciuric stone formers respectively); it positively correlated with serum calcitriol 6 h after calcium load (r = 0.392, P = 0.024). Maximum increase in urinary calcium excretion rate, delta Ca-Emax, was inversely related to intact PTH levels in the first 4 h after calcium load, i.e. more pronounced PTH suppression predicted a steeper increase in urinary calcium excretion rate. Twenty-four-hour urine calcium excretion rate was inversely related to the ratio of delta calcitriol/deltaPTHmax after calcium load (r = -0.653, P = 0.0001), indicating that an abnormally up-regulated synthesis of calcitriol and consecutive relative PTH suppression induce hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence of absorptive hypercalciuria in tuberculosis patients

In patients with granulomatous diseases, disturbances in calcium metabolism have been described. The aim of the study was to evaluate alterations in calcium metabolism in patients with tuberculosis. Forty patients with tuberculosis (TB) were studied in a baseline state (calcium intake 1000 mg/day). Fourteen of these patients were also studied after restrictive calcium diet (400 mg/calcium/day) and after a load of oral calcium of 1000 mg. In all the studies, calcium and phosphorus were measured in serum and urine, and parathyroid hormone (PTH) in plasma. In addition, serum 25OHD and 1,25(OH)2D (calcitriol) levels were measured in the baseline state and after the restrictive diet. In the baseline state, 25OHD levels were lower and urinary calcium higher in TB patients than in the control group. No patients had hypercalcemia, but hypercalciuria was present in 10 patients (25%). The patients with tuberculosis were divided according to the presence or absence of hypercalciuria. In both groups, the 25OHD levels were lower than in controls. Hypercalciuric patients had lower plasma parathyroid hormone levels and higher serum calcitriol levels than the control group and the TB patients without hypercalciuria. Urinary calcium excretion after a calcium load was higher in TB patients with hypercalciuria than in controls. A positive correlation was found between the calcitriol levels and postcalcium load urinary calcium excretion in patients with calcium hyperabsorption. These data indicate that absorptive hypercalciuria is frequently observed in patients with TB and is possible due to inappropriately high serum calcitriol levels.     

MRI of pseudoaneurysm of a brachial venous coronary bypass graft

We studied the following responses to restriction of dietary calcium and phosphorus in the growing hamster: (i) serum concentrations of calcium, inorganic phosphorus, magnesium, and vitamin D metabolites; and (ii) calcium transport by ileum. Diets fed were normal calcium with normal or low phosphorus or low calcium with normal or low phosphorus. We found serum 1 alpha,25-dihydroxycalciferol (1,25-[OH]2D) concentration did not differ significantly among the diet groups. Calcium absorption, measured as serosal/mucosal calcium concentration ratio produced by everted ileal sac, was greater in the low calcium, normal phosphorous group than in all other groups. The other groups did not differ from one another in calcium absorption. Feeding the low calcium, normal phosphorus diet increased inorganic phosphorus and magnesium but decreased calcium concentration in serum in comparison with the three other diets. Both low phosphorus diets were without effect on serum calcium, but the low calcium, low phosphorus diet increased serum inorganic phosphorus and magnesium above that of the normal calcium, low phosphorus diet. Ileal calcium absorption in hamster (i) was independent of serum 1,25-(OH)2D concentration; (ii) increased in response to low dietary calcium if dietary phosphorus was normal; and (iii) was independent of dietary calcium, if dietary phosphorus was low. Despite increased calcium absorption, serum calcium was decreased in the low calcium-normal phosphorus group as compared with all other groups. Feeding low calcium diets increased serum inorganic phosphorus and magnesium as compared with feeding the corresponding normal calcium diets (i.e., independently of whether dietary phosphorus content was normal or low). These studies demonstrate that the interrelationships between calcium absorption and vitamin D and mineral metabolism in hamster differ from other mammals.     

Prediction of spinal cord ischemia with a retrievable stent graft on endovascular treatment for a case of thoracic aortic aneurysm

OBJECTIVE: To determine the pharmacokinetics and absolute bioavailability of ciprofloxacin in 12 critically ill patients receiving continuous enteral feeding. Design: a prospective, cross-over study. SETTING: 12-bed surgical intensive care unit in a University Hospital. PATIENTS: 12 stable critically ill patients on mechanical ventilation and receiving continuous enteral feeding (Normoreal fibres) without diarrhea or excessive residual gastric contents ( < 200 ml/4 h). None had gastro-intestinal disease, renal insufficiency (estimated creatinine clearance > or = 50 ml/min) or was receiving medications that could interfere with ciprofloxacin absorption or metabolism. MEASUREMENTS AND MAIN RESULTS: The study was carried out after the fourth (steady state) b. i. d. intravenous (i. v.) 1-h infusion of 400 mg and the second b. i. d. nasogastric (NG) dose of 750 mg (crushed tablet in suspension). Plasma concentrations were measured by high-performance liquid chromatography. The median (range) peak concentration after i. v. infusion was 4.1 (1.5-7.4) mg/l, and that after NG administration was 2.3 (0.7-5.8) mg/l, occurring 1.25 (0.75-3.33) h after dosing. The median [range] areas under plasma concentration-time curves were similar for the two administration routes (10.3 [3.3-34.6] and 8.4 [3.6-53.4] for i.v. infusion and NG administration, respectively). Ciprofloxacin bioavailability ranges from 31 to 82 % (median, 44%). CONCLUSIONS: In tube-fed critically ill patients, a switch to the NG ciprofloxacin after initial i. v. therapy to simplify the treatment of severe infections is restricted to those for whom serial assessments of ciprofloxacin levels are routinely available.     

Gallbladder motility and cholecystokinin release during long-term enteral nutrition in patients with Crohn's disease

BACKGROUND: Gallbladder bile stasis during long-term continuous enteral feeding may contribute to the high prevalence of gallstones in patients with Crohn's disease. We therefore examined the effects of continuous enteral nutrition on gallbladder motility and cholecystokinin (CCK) release in six patients. METHODS: Gallbladder volume was measured ultrasonographically for 12 h on days 1 (start), 8, 22 (6-h interruption of enteral feeding), 36, and 43 (end) of enteral feeding. Plasma CCK was assessed at several time points. RESULTS: Initial fasting gallbladder volume was 19.3 +/- 4.5 (mean +/- SEM) ml, which decreased to 4.9 +/- 3.6 ml after start of feeding. CCK increased from 1.5 +/- 0.3 to 3.9 +/- 1.1 pmol/l. On days 8 and 36 the gallbladder was almost completely contracted, and CCK increased to 7.5 +/- 2.7 and 8.3 +/- 2.6 pmol/l, respectively. On days 22 and 43 gallbladder volume increased, and CCK decreased rapidly to fasting concentrations after interruption of feeding. CONCLUSIONS: During continuous enteral nutrition the gallbladder is completely contracted, and CCK concentrations remain elevated. It is therefore unlikely that long-term enteral nutrition contributes to the increased prevalence of gallstones in patients with Crohn's disease.     

Limitations of pulse oral calcitriol therapy in continuous ambulatory peritoneal dialysis patients

Calcitriol is increasingly used for therapy of secondary hyperparathyroidism in patients with end-stage renal disease. Its therapeutic efficacy, however, often has been limited by the associated increase in intestinal calcium and phosphorus absorption. Previous studies reported that these side effects could be avoided by intermittent administration of calcitriol in high doses, subsequently referred to as pulse therapy. The present study was designed to investigate pulse oral calcitriol therapy in a patient subgroup especially susceptible to the development of hypercalcemia and hyperphosphatemia under standard continuous calcitriol treatment. We examined 15 peritoneal dialysis patients with moderate degrees of hyperparathyroidism (intact parathyroid hormone [iPTH] levels, 150 to 903 pg/mL) ingesting between 1.5 and 6 g of calcium salts as the sole phosphate binders. Treatment consisted of 0.5 microgram calcitriol twice weekly. Eight of these patients had been previously converted to low calcium dialysate to tolerate the necessary doses of phosphate-binding calcium salts. During the study period, comprising 8 pretreatment weeks and 8 weeks of therapy, dialysates and doses of calcium salts were not changed, so that only calcitriol influenced the determined parameters. As expected, iPTH levels decreased rapidly in all patients (P < 0.0001). However, within 4 weeks of treatment a marked increase in calcium phosphorus products was observed (P < 0.0001). Overt hypercalcemia developed in five patients. We concluded that pulse oral calcitriol has to be carefully monitored in peritoneal dialysis patients receiving high doses of calcium salts because of the increased risk for hypercalcemia and hyperphosphatemia.     

Effect of renal perfusion pressure on excretion of calcium, magnesium, and phosphate in the rat

Abnormalities in renal handling of calcium, magnesium, or phosphate have been implicated in the development and/or maintenance of human hypertension. We have shown recently that renal excretion of these ions is correlated to blood pressure in Dahl salt-sensitive as well as salt-resistant rats. The present study was designed to determine whether renal perfusion pressure per se could affect excretion of these ions. Urinary excretion of calcium, magnesium, and phosphate was studied in anaesthetized Sprague-Dawley rats under basal conditions and during an intravenous infusion of angiotensin II (ANG II), vasopressin (AVP) or phenylephrine (PE). A cuff, placed around the aorta between the two renal arteries, allowed maintenance of normal perfusion pressure in the left kidney, while that in the right kidney was allowed to rise. Infusion of pressor agents raised mean arterial blood pressure to comparable levels (means +/- SE): ANG II (n = 7), before = 102 +/- 4, during = 133 +/- 3 mmHg, AVP (n = 8), before = 110 +/- 7, during = 136 +/- 5 mmHg, PE (n = 6), before = 111 +/- 6, during = 141 +/- 6 mmHg. Although there was no difference in excretion of calcium, magnesium and phosphate between the two kidneys under basal conditions, infusion of ANG II or PE induced hypercalciuria, hypermagnesiuria and hyperphosphaturia in the right kidney which was exposed to the increased arterial pressure. Such effects did not appear in the pressure-controlled left kidney. Infusion of AVP was associated with reduced excretion of calcium and magnesium, and increased excretion of phosphate, in the normotensive kidney. The response to the similarly increased renal perfusion pressure in this group was also reduced for calcium and magnesium, and enhanced for phosphate. The results indicate (1) renal excretion of calcium, magnesium and phosphate is renal perfusion pressure-dependent; the higher the renal perfusion pressure, the greater the excretion of these ions. (2) Independently of perfusion pressure, AVP can inhibit phosphate reabsorption and stimulate divalent cation reabsorption.     

Association of thin basement membrane nephropathy with hypercalciuria, hyperuricosuria and nephrolithiasis

BACKGROUND: Familial persistent microhematuria with normal renal function is the most common presentation of thin basement membrane nephropathy (TBMN). Gross hematuria episodes and loin pain attacks are other manifestations of the disease. On the other hand, it has been shown that hypercalciuria (HC) and hyperuricosuria (HU) can produce both gross or microscopic non-glomerular hematuria, in addition to their role in renal stone formation. METHODS: We studied the prevalence of HC, HU and nephrolithiasis in a group of 27 biopsy-proven TBMN as well as in 19 non-biopsied first-degree relatives with persistent microhematuria and 25 first-degree relatives without microhematuria. A group of 27 patients with IgA nephropathy (IgAN) and persistent microhematuria, and another group of 20 healthy subjects without known renal diseases were selected as control groups. RESULTS: Ten (37%) patients with TBMN and 8 (42%) relatives with microhematuria showed HC and/or HU at presentation; relatives without microhematuria, IgAN patients and normal controls showed a significantly lower prevalence of HC and HU. The prevalence of previous nephrolithiasis among TBMN patients (25%) was significantly higher than in IgAN patients (3%; P < 0.05). Family history of nephrolithiasis was recorded in 14 (51%) of the 27 TBMN families, in contrast with 2 of 27 (7%) with IgAN and 1 of 20 (5%) in normal controls (P < 0.05). The prevalence of nephrolithiasis, gross hematuria bouts and loin pain episodes among TBMN patients and microhematuric relatives showing HC and/or HU at presentation (44%, 44% and 27%, respectively) were significantly higher than those of TBMN patients and microhematuric relatives with normal calcium and uric acid urinary excretions (10%, 7% and 3%, respectively; P < 0.05). At the end of follow-up (8.8+/-4.1 years in TBMN patients and 9.1+/-4.2 years in relatives with microhematuria), all the cases maintained normal renal function. CONCLUSIONS: We found a high prevalence of HC, HU, and nephrolithiasis among TBMN patients and relatives with microhematuria. Our study also shows a significant relationship between the presence of HC and/or HU and the prevalence of nephrolithiasis, gross hematuria bouts and loin pain episodes.     

Efficacy of pancreatic transplantation on cardiovascular alterations in diabetic rats: an ultrastructural and immunohistochemical study

OBJECTIVES: To determine whether a neural network is superior to standard computational methods in predicting stone regrowth after shock wave lithotripsy (SWL) and to determine whether the presence of residual fragments, as an independent variable, increases risk. METHODS: We reviewed the records of 98 patients with renal or ureteral calculi treated by primary SWL at a single institution and followed up for at least 1 year; residual stone fragment growth or new stone occurrence was determined from abdominal radiographs. A neural network was programmed and trained to predict an increased stone volume over time utilizing input variables, including previous stone events, metabolic abnormality, directed medical therapy, infection, caliectasis, and residual fragments after SWL. Patient data were partitioned into a training set of 65 examples and a test set of 33. The neural network did not encounter the test set until training was complete. RESULTS: The average follow-up period was 3.5 years (range 1 to 10). Of 98 patients, 47 had residual stone fragments 3 months after SWL; of these 47, 8 had increased stone volume at last follow-up visit. Of 51 patients stone free after SWL, 4 had stone recurrence. Coexisting risk factors were incorporated into a neural computational model to determine which of the risk factors was individually predictive of stone growth. The classification accuracy of the neural model in the test set was 91%, with a sensitivity of 91%, a specificity of 92%, and a receiver operating characteristic curve area of 0.964, results significantly better than those yielded by linear and quadratic discriminant function analysis. CONCLUSIONS: A computational tool was developed to predict accurately the risk of future stone activity in patients treated by SWL. Use of the neural network demonstrates that none of the risk factors for stone growth, including the presence of residual fragments, is individually predictive of continuing stone formation.     

Metabolic abnormalities in patients with caliceal diverticular calculi

PURPOSE: We determined the incidence and spectrum of metabolic abnormalities in patients with caliceal diverticular calculi. MATERIALS AND METHODS: Five men and 9 women with caliceal diverticular calculi underwent metabolic evaluation, including determination of serum electrolytes, calcium, phosphate and uric acid, and 24-hour urinary volume, creatinine, calcium, oxalate, uric acid and citrate. RESULTS: Of the 14 patients 7 (50%) had urinary excretion abnormalities promoting stone formation, including hypercalciuria in 3, hyperoxaluria in 1, hypercalciuria combined with hyperuricosuria in 1 and hyperoxaluria combined with hyperuricosuria in 2. Two patients had a history of gout while another had radiographic evidence of medullary sponge kidney. Of the patients 9 (64.3%) had a history of synchronous or metachronous calculi distant from the involved caliceal diverticular stone and 5 (55.6%) of these 9 had definable metabolic disorders. However, there was no statistically significant difference in urinary excretion values between patients with or without a history of additional extra diverticular stones. CONCLUSIONS: Urinary stasis alone does not explain stone formation in a significant number of patients with caliceal diverticular calculi. Rather, the local physiological environment of the urine likely has a predisposing role and evaluation for metabolic abnormalities should be considered. In some patients cure may be effected by treating the stone and any associated metabolic disorders rather than the diverticulum.