Genetic causes of hypercalciuric nephrolithiasis

Renal stone disease (nephrolithiasis) affects 3–5% of the population and is often associated with hypercalciuria. Hypercalciuric nephrolithiasis is a familial disorder in over 35% of patients and may occur as a monogenic disorder that is more likely to manifest itself in childhood. Studies of these monogenic forms of hypercalciuric nephrolithiasis in humans, e.g. Bartter syndrome, Dent’s disease, autosomal dominant hypocalcemic hypercalciuria (ADHH), hypercalciuric nephrolithiasis with hypophosphatemia, and familial hypomagnesemia with hypercalciuria have helped to identify a number of transporters, channels and receptors that are involved in regulating the renal tubular reabsorption of calcium. Thus, Bartter syndrome, an autosomal disease, is caused by mutations of the bumetanide-sensitive Na–K–Cl (NKCC2) co-transporter, the renal outer-medullary potassium (ROMK) channel, the voltage-gated chloride channel, CLC-Kb, the CLC-Kb beta subunit, barttin, or the calcium-sensing receptor (CaSR). Dent’s disease, an X-linked disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrolithiasis, is due to mutations of the chloride/proton antiporter 5, CLC-5; ADHH is associated with activating mutations of the CaSR, which is a G-protein-coupled receptor; hypophosphatemic hypercalciuric nephrolithiasis associated with rickets is due to mutations in the type 2c sodium–phosphate co-transporter (NPT2c); and familial hypomagnesemia with hypercalciuria is due to mutations of paracellin-1, which is a member of the claudin family of membrane proteins that form the intercellular tight junction barrier in a variety of epithelia. These studies have provided valuable insights into the renal tubular pathways that regulate calcium reabsorption and predispose to hypercalciuria and nephrolithiasis

Relationship between magnesium, potassium and sodium concentrations in lymphocytes and erythrocytes from normal subjects

Mg, K and Na were measured in erythrocytes, lymphocytes and serum obtained from 20 normal subjects. The cells of 20 ml of blood were separated in Ficoll gradient, washed with a choline buffer and digested with H2SO4. The cations were measured by atomic absorption photometry, protein was determined by the Lowry method and the results were expressed as nmol/mg of protein. Intracellular lymphocyte concentrations (mean +/- SD, n = 20) were: Mg: 57.6 +/- 5.1, Na: 30.0 +/- 7.9, K: 614.3 +/- 69. In the red cells, ion concentrations were: Mg: 7.97 +/- 0.8, Na: 20.9 +/- 4.8, K: 343.0 +/- 42.0. There was a highly significant correlation between Mg and K concentration in erythrocytes (p less than 0.001) and lymphocytes (p less than 0.001). A negative correlation (p less than 0.05) was also found between lymphocyte and erythrocyte K concentration and K serum concentration

Familial Bartter's syndrome: report of a case with early manifestations and persistent hypercalciuria

A case of familial Bartter's syndrome is reported. The child had early and severe clinical and biochemical manifestations. Indomethacin treatment effectively controlled the increased prostaglandin excretion but corrected only partially the potassium and the calcium losses. The child developed during treatment high serum calcium levels which were associated with high parathyroid hormone and calcitriol serum levels

Primary hyperparathyroidism and rickets. A case report and review of the literature

A case of primary hyperparathyroidism with clinical signs of rickets in a 15-year-old boy of South Morocco is presented. X-ray findings include a diffusely osteoporotic skeleton with areas of subperiostal resorption, cysts and metaphyseal rachitic changes. Hypercalcaemia, hypophosphataemia, increased alkaline phosphatase are found together with low calcidiol and high calcitriol plasma levels. The surgical removal of a chief-cell adenoma of a parathyroid gland leads to very rapid bone healing as well as normalization of blood chemistry. Reviewing the literature shows that 10 similar cases have been described. However, no correlation can be established between the occurrence of rachitic lesions and the Ca X P product. When limited calcium is available from the gut, elevated calcitriol then contributes to mobilize more mineral from bone, in conjunction with parathormone. In addition, the interaction of these 2 hormones on the renal tubule maintains a phosphate leak, creating proper conditions for the development of rachitic lesions

Serum and intracellular magnesium during normal pregnancy and in patients with pre-eclampsia

OBJECTIVE: To determine the serum and lymphocyte magnesium concentrations during normal pregnancy and to compare the magnesium status in the third trimester of pregnancy between women with normal pregnancy and those with gestational hypertension (GH) or pre-eclampsia (PE). DESIGN: A prospective cross-sectional study followed by a prospective comparative study. SETTING: Department of Obstetrics and Gynecology, Department of Pediatrics and Genetics, Hopital Cantonal Universitaire Geneve, Switzerland. SUBJECTS: Seventy-one healthy pregnant women, with normal pregnancies between 6 and 38 weeks gestation. The second part included 43 women in the third trimester of pregnancy, 11 had GH, 11 had PE and 21 formed the comparison group of healthy normotensive women. MAIN OUTCOME MEASURES: Total serum and intralymphocytic Mg concentrations and urinary Mg excretion. RESULTS: There was a progressive reduction in total serum magnesium concentrations during normal pregnancy, thought to be partly due to haemodilution, because the decline in concentration of serum proteins paralleled that of Mg (P less than 0.001). In the three groups studied in the third trimester the serum Mg concentration was very similar in the GH and the comparison groups, but it was significantly higher in the PE group (P less than 0.01). The intralymphocytic Mg concentrations and the urinary Mg excretion were similar in all three groups. In five patients treated with MgSO4 there was a large increase in the serum Mg concentration and in the urinary Mg excretion. The intralymphocytic Mg concentration remained remarkably stable. CONCLUSIONS: Our data does not support the conclusion that Mg deficiency is the primary cause of pre-eclampsia

Early hemodynamic and renal effects of tumor necrosis factor alpha: role of thromboxane

TNF alpha is an early mediator of endotoxemic shock. Its acute effect on renal hemodynamics is not known. In this study, the early hemodynamic and renal effects of TNF alpha were investigated in a rabbit model of shock, in which the measurement of the aortic blood flow before the bifurcation of the renal arteries allows one to differentiate between prerenal factors and hemodynamic renal response. Six groups of rabbits were studied, receiving either: (1) endotoxin, (2) endotoxin + thromboxane inhibitor Dazmegrel, (3) TNF alpha, (4) TNF alpha + Dazmegrel, (5) TNF alpha+indomethacin, or (6) placebo. Between 60 min and 3 hr after the injection, endotoxin induced a mean fall in arterial pressure of 32% (P < 0.01) and TNF alpha of 16% (P < 0.01). After endotoxin, the aortic blood flow decreased by 27% (P < 0.01) and after TNF alpha by 18% (P < 0.001). Both specific thromboxane inhibition and indomethacin abolished the TNF alpha central hemodynamic effect. The renal blood flow (-53%), the renal fraction of the aortic blood flow (-38%), and the glomerular filtration rate (-47%, P < 0.05) decreased 1 hr after endotoxin injection. In contrast, TNF alpha induced only a slight fall of the renal fraction of the aortic blood flow (-19%) after 2.5 hr. Glomerular filtration was not modified after TNF alpha injection most likely because of a 17% mean increase of filtration fraction in this group (P < 0.001). These data indicate that TNF alpha is implicated in the early hemodynamic changes of endotoxemic shock.(ABSTRACT TRUNCATED AT 250 WORDS