Medical evaluation and treatment of urolithiasis.

Nephrolithiasis is responsible for 1 in 1000 to 1 in 7600 pediatric hospital admissions annually throughout the United States. Seventy-five percent of children with nephrolithiasis have an identifiable predisposition to stone formation. This article reviews the different causes and disease states associated with nephrolithiasis in the pediatric population. The initial evaluation and the metabolic evaluation of children with nephrolithiasis are reviewed. Treatment modalities for the different stone types are also described.

Changes in renal hemodynamics and tubular function of surgically cured primary hyperparathyroid patients are probably due to chronic hypercalcemic nephropathy.

To understand the mechanisms responsible for the persistent hypercalciuria and reduced glomerular filtration rate (GFR) previously found in 6 of 10 patients surgically cured of primary hyperparathyroidism (PHPx), the tubular handling of lithium, sodium, calcium, and phosphate as well as the renal hemodynamics were evaluated in these 10 PHPx patients, in 10 control subjects, and in 5 patients with renal hypercalciuria (RH), during fasting and after an oral calcium load. A positive correlation between the fractional excretions of calcium and sodium was found in all groups, but the PHPx patients excreted more calcium for the same amount of sodium than control subjects. The fractional proximal sodium reabsorption (FPRNa), distal delivery, and fractional phosphate reabsorption were similar in all groups; a significant positive correlation was found between the fractional calcium reabsorption and the FPRNa, indicating that proximal tubular function was preserved and that the urinary calcium losses in RH and in the hypercalciuric PHPx patients (h-PHPx) occurred in the distal nephron. However, only h-PHPx patients had reduced renal plasma flow, renal blood flow, and GFR, as well as a high renal vascular resistance, which was even more evident after the calcium challenge. These findings lead us to conclude that RH and h-PHPx patients are very different, as far as kidney dysfunction is concerned, and that a hypercalcemic nephropathy is the most probable cause of the alterations in distal calcium reabsorption and renal hemodynamics found in the h-PHPx patients.

[Studies of calcium metabolism in patients with hypercalciuria]. / Kalziumstoffwechseluntersuchungen bei Patienten mit Hyperkalziurie.

The different subgroups of hypercalciuria cannot be separated clearly by the Pak calcium-load test. To improve the diagnosis and therapy we examined all relevant parameters of calcium metabolism in 32 patients with calcium urolithiasis and hypercalciuria (> 6.25 mmol/day). We also conducted bone mineral density measurements as well as the Pak calcium-load test. In most cases the pathophysiological constellations which Pak takes as the basis for his classification of hypercalciuria could not be shown. To date, diagnostics only insufficiently explains the genesis of hypercalciuria (except pHPT). As a consequence, a therapeutic problem arises: a low-calcium diet should not be generally recommended, since some patients may develop osteopenia. From our investigation the following diagnostic and therapeutic conclusions can be drawn: (1) Hypercalciuria in primary hyperparathyroidism should be treated by surgical removal of the adenoma. (2) The parathormone-independent osteogenic form should be treated with thiazides. (3) Hypercalciuria with increased 1.25-dihydroxyvitamin D should be treated by low-calcium diet.

The cause of maintained hypercalciuria after the surgical cure of primary hyperparathyroidism is a defect in renal calcium reabsorption.

The hypercalciuria that eventually remains after the successful removal of a solitary parathyroid adenoma may originate from excessive intestinal calcium absorption, bone resorption or deficient renal reabsorption. In order to clarify this question, ten patients surgically cured from primary hyperparathyroidism (PHPx), ten age-matched normal subjects and five nephrolithiasic patients with renal hypercalciuria (RH) were studied after five days on a low calcium diet, either during fasting or after oral calcium load. Fasting serum calcium, amino-terminal and intact PTH levels and also urinary cAMP excretion were normal in every individual patient. Serum ionized calcium and inulin clearance (GFR) were used for calculations of the filtered load (FL Ca) and the fractional excretion of calcium (FE Ca). Six PHPx patients displayed fasting calciuria above the upper limit calculated for control subjects, despite having the lowest GFR and FL Ca (p < 0.05 vs control). These patients (h-PHPx) had a small calciuric response to oral calcium load. Serum 1,25-(OH)2D3 and 25OHD3 did not correlate with calciuria. Our findings exclude intestinal hyperabsorption and excessive bone resorption in h-PHPx patients, and strongly suggest a renal tubular defect in calcium reabsorption as the cause of their hypercalciuria. This defect could be primary, as in RH, but only three hPHPx patients had recurrent kidney stones before surgery. On the other hand, as a negative correlation between GFR and FE Ca was only found in PHPx patients, it seems probable that the disturbances in glomerular and tubular functions were secondary to the long standing hypercalcemic hyperparathyroidism.

Hypercalciuria and ultrasound abnormalities in children with cystinosis.

We noted microscopic haematuria in children with cystinosis. To investigate this we studied urinary calcium excretion and undertook renal ultrasound scans. Most patients had elevated urinary calcium excretion and all had abnormal appearances on ultrasound scan, ranging from increased cortical echogenicity only to those with increased cortical and medullary echogenicity. The ultrasound scan appearance was graded and correlated with laboratory parameters. It remains unclear as to the aetiology of the ultrasound findings and whether they are a consequence of treatment or a hitherto unrecognised feature of the disease.

Calciuria y relación calcio creatitina en orina de niños sanos / Calciuria and relation calcium creatinine in urine of healthy children

La hipercalciuria representa un factor de riesgo por ser causa importante de nefrourolitiasis y hematuria en niños. La excreción de calcio en orina de 24 horas y la relación calcio-cretinina se determinaron en una muestra de niños sanos de la ciudad de Mérida, entre 5 y 15 años de edad, de ambos sexos. La media de la excreción de calcio fue de 1,39 ñ 0,74 mg/Kg/24hr (DE). La media del índice de relación Ca/Cre fue 0,10 ñ 0,06. Hubo correlación estadísticamente significativa entre calciuria de 24 hrs y la relación Ca/Cre. Se considera que el índice Ca/Cre es una prueba muy útil para detectar hipercalciuria y es de fácil aplicación en niños. La espectrofotometría de absorción atómica debe ser el método a usar para cuantificar el calcio en la orina; la muestra debe ser procesada con los agentes liberadores de calcio para evitar su precipitación con otros elementos.

Hipocalciuria en preeclampsia / Hypocalciuria in preeclampsia

Estudios recientes han asociado a la preeclampsia con hipocalciuria, otros estudios no muestran esta asociación. Con el propósito de determinar si existe tal asociación se estudiaron 25 pacientes con embarazo de término; 13 normotensas, 7 hipertensas transitorias y 5 preeclámpticas. No se encontró diferencias significativas en el hematocrito, calcemia, creatininemia, recuento de plaquetas y diuresis de 24 horas entre los 3 grupos estudiados. La uricemia en las normotensas 3,5 ñ 0,8 mg/dl fue significativamente menor que las preeclámpticas 4,9 ñ 0,8 mg/dl, mediana ñ DS, p<0,05. La calciuria de 24 horas en el grupo de preeclámpticas 121 ñ 78 mg/24 horas fue significativamente menor que en el grupo de normotensas 256 ñ 71 mg/24 horas e hipertensas transitorias 229 ñ 93 mg/24 horas, p<0,05. Determinamos el clearance de creatinina y fracción de excreción del calcio en las hipertensas transitorias y preeclámpticas, encontrándose diferencias significativas sólo en la fracción de excreción del calcio 2,5 ñ 0,8 por ciento y 1,1 ñ 0,8 por ciento , p<0,05 respectivamente. La evolución clínica de las pacientes fue favorable, con un período medio de normalización de presiones arteriales postparto menor de 1 semana. Fueron catalogados como pequeños para la edad gestacional 3 recién nacidos, 1 en el grupo de hipertensas transitorias y 2 en el grupo de preeclámpticas. Las diferencias encontradas en la calciuria de 24 horas y fracción de excreción del calcio se correlacionan con los hallazgos de otros autores y sugieren la necesidad de nuevos estudios que permitan dilucidar el metabolismo del calcio en pacientes con embarazo normal, hipertensión transitoria y preeclampsia

Screening for hypercalciuria.

Reference values for the urinary calcium/creatinine ratio (Ca/Cr ratio) in the first morning urine were established in 361 healthy children aged 5 to 15 years, on unrestricted diets. The urinary Ca/Cr ratio in the urine upon arising was independent of sex but dependent upon age. The measurement of the urinary Ca/Cr ratio in the urine upon arising while on unrestricted diets may be a reasonable screening test for elevated calcium excretion. On the basis of the urinary Ca/Cr ratios in the urine upon arising during unrestricted diets and the calciuric response to calcium restricted diets and the oral calcium loading test, idiopathic hypercalciuria (IH) was subclassified into three groups: (1) absorptive hypercalciuria; (2) renal hypercalciuria; (3) dietary hypercalciuria. The pathogenesis of IH is controversial. Our data suggest that disordered 1,25 (OH)2 vitamin D metabolism with excessive urinary phosphate excretion occurs in absorptive hypercalciuria.

Effect of parathyroid extract on renal cyclic AMP excretion in patients with normocalciuric nephrolithiasis.

It is uncertain whether normocalcemic, normocalciuric patients with calcium nephrolithiasis have a disorder of calcium metabolism. We studied the effect of a parathyroid extract (PTE) INFUSION (1.4 U/kg body weight) on the urinary cyclic AMP excretion in 16 such patients. For comparison, we investigated groups of normal individuals and patients with primary hyperparathyroidism, renal insufficiency and different gastrointestinal diseases. The increase of cyclic AMP above basal excretion in patients with nephrolithiasis was only 1.2 +/- 0.3 mumol/h (mean +/- SEM), versus 2.5 +/- 0.5 mumol/h in normal subjects (p less than 0.05) although the basal excretion was similar. Patients with renal insufficiency had low basal excretion of cyclic AMP and little stimulation of excretion by PTH (increase, 0.3 +/- 0.06 mumol). Patients with primary hyperparathyroidism had high baseline cyclic AMP excretion but sub-normal stimulation by PTE (increase, 0.46 +/- 0.13); in contrast, patients with different gastrointestinal disease had high baseline excretion and supranormal stimulation of cyclic AMP excretion (increase, 5.2 +/- 0.6). We speculate that an impaired response to PTH might be involved in the slightly increased urinary calcium excretion in normocalcemic stone formers suggested by others.

[Determination of urinary cyclic AMP in phosphorus and calcium pathology]. / Dosage de l'AMP cyclique urinaire en pathologie phosphocalcique

Quantitative analysis of urinary cyclic AMP in phospho-calcic pathology. The authors describe a method measuring amounts of cyclic AMP. Normal daily elimination in urine was measured in a group of normal subjects. Elimination was found to be raised in two-thirds of the patients with primary hyperparathryroidism, normal in those with idiopathic hypercalcaemia and neoplastic hypercalcaemia, and subnormal in patients with hypoparathyroidism. The urinary excretion of cyclic AMP after perfusion of parathyroid hormone was very low in cases of pseudo-hypoparathyroidism compared with that in surgical hypoparathroid controls. The results are compared with data from the literature. The theoretical and diagnostic value of these quantitative analyses is discussed.

The hypercalciurias. Causes, parathyroid functions, and diagnostic criteria.

The causes for the hypercalciuria and diagnostic criteria for the various forms of hypercalciuria were sought in 56 patients with hypercalcemia or nephrolithiasis (Ca stones), by a careful assessment of parathyroid function and calcium metabolism. A study protocol for the evaluation of hypercalciuria, based on a constant liquid synthetic diet, was developed. In 26 cases of primary hyperparathyroidism, characteristic features were: hypercalcemia, high urinary cyclic AMP (cAMP, 8.58+/-3.63 SD mumol/g creatinine; normal, 4.02+/-0.70 mumol/g creatinine), high immunoreactive serum parathyroid hormone (PTH), hypercalciuria, the urinary Ca exceeding absorbed Ca from intestinal tract (Ca(A)), high fasting urinary Ca (0.2 mg/mg creatinine or greater), and low bone density by (125)I photon absorption. The results suggest that hypercalciuria is partly secondary to an excessive skeletal resorption (resorptive hypercalciuria). The 22 cases with renal stones had normocalcemia, hypercalciuria, intestinal hyperabsorption of calcium, normal or low serum PTH and urinary cAMP, normal fasting urinary Ca, and normal bone density. Since their Ca(A) exceeded urinary Ca, the hypercalciuria probably resulted from an intestinal hyperabsorption of Ca (absorptive hypercalciuria). The primacy of intestinal Ca hyperabsorption was confirmed by responses to Ca load and deprivation under a metabolic dietary regimen. During a Ca load of 1,700 mg/day, there was an exaggerated increase in the renal excretion of Ca and a suppression of cAMP excretion. The urinary Ca of 453+/-154 SD mg/day was significantly higher than the control group's 211+/-42 mg/day. The urinary cAMP of 2.26+/-0.56 mumol/g creatinine was significantly lower than in the control group. In contrast, when the intestinal absorption of calcium was limited by cellulose phosphate, the hypercalciuria was corrected and the suppressed renal excretion of cAMP returned towards normal. Two cases with renal stones had normocalcemia, hypercalciuria, and high urinary cAMP or serum PTH. Since Ca(A) was less than urinary Ca, the hypercalciuria may have been secondary to an impaired renal tubular reabsorption of Ca (renal hypercalciuria). Six cases with renal stones had normal values of serum Ca, urinary Ca, urinary cAMP, and serum PTH (normocalciuric nephrolithiasis). Their Ca(A) exceeded urinary Ca, and fasting urinary Ca and bone density were normal. The results support the proposed mechanisms for the hypercalciuria and provide reliable diagnostic criteria for the various forms of hypercalciuria.