Examination of hypercalciuria in anterior pituitary-implanted rats

1987 ◽  
Vol 252 (5) ◽  
pp. F916-F921
Author(s):  
L. S. Costanzo ◽  
B. Smith ◽  
R. A. Adler

The anterior pituitary (AP) grafted, adrenalectomized, steroid hormone-replaced male rat is characterized by hyperprolactinemia and hypercalciuria. To determine the origin of the hypercalciuria, clearance experiments were performed under Inactin anesthesia in adrenalectomized Fischer rats 8-10 wk after implantation of extra AP glands under the kidney capsule. Glomerular filtration rate, ultrafilterable calcium, and fractional sodium excretion were comparable in the AP and control groups. However, fractional calcium excretion was significantly higher in the AP-implanted rats, P less than 0.05, resulting in a marked dissociation of the calcium/sodium clearance ratio. Because filtered calcium load did not change, these results clearly demonstrate that AP-implanted animals have a defect in tubular calcium reabsorption. The dissociation of calcium transport from sodium transport suggests the distal tubule as a likely site of action. Parathyroidectomy did not alter the calciuric response to AP implantation. To test whether hyperprolactinemia was responsible for decreased calcium reabsorption in AP-implanted rats, purified rat prolactin was infused into normal rats to achieve high blood prolactin levels, or was injected into normal rats daily for 8 days. Changes in fractional calcium excretion and the ratio of calcium to sodium clearance were identical in animals receiving prolactin or control infusions. Thus, hypercalciuria in the AP-implanted rat may be attributed to an unidentified factor, perhaps secreted from the implanted anterior pituitaries, rather than to prolactin excess.

1989 ◽  
Vol 67 (10) ◽  
pp. 1278-1282 ◽  
Author(s):  
M. Derrick McPhee ◽  
Susan J. Whiting

The chronic effects of dietary caffeine, theophylline, and theobromine on urinary calcium excretion were investigated in the adult male rat. The effect of acutely administered adenosine and adenosine analogues on methylxanthine-induced hypercalciuria was concurrently investigated. When rats were fed equimolar amounts of theobromine, caffeine, and theophylline, it was found that urinary calcium excretion increased; on day 7 values were increased over controls (p < 0.05) by 54, 146, and 208%, respectively. On day 20, an injection of adenosine reduced calcium excretion in methylxanthine-treated rats to levels not different from control values. In another series of experiments, theophylline was fed to a group of rats to establish hypercalciuria. Three adenosine analogues N6-(L-2-phenylisopropyl)adenosine (R-PIA), N6-(D-2-phenylisopropyl)adenosine (S-PIA), and 5′-(N-ethylcarboxamido)adenosine (NECA) with different adenosine receptor specificities (A2, A1, and weakly A2, respectively) were administered to different groups of theophylline-fed and control rats, and their calcium excretions were measured. It was found that the order of efficacy of the analogues in reducing calcium excretion was NECA > R-PIA > S-PIA, which is consistent with the receptor being A2. A proportion of the methylxanthine-induced hypercalciuria may be due to adenosine antagonism.Key words: caffeine, theobromine, theophylline, calcium, adenosine.


1986 ◽  
Vol 112 (4) ◽  
pp. 541-546 ◽  
Author(s):  
J. H. Kristiansen ◽  
J. Brøchner-Mortensen ◽  
K. O. Pedersen

Abstract. To investigate the nephron site of the enhanced tubular calcium reabsorption in familial hypocalciuric hypercalcaemia (FHH), the renal plasma clearance of lithium and calcium and the glomerular filtration rate were determined simultanously after an overnight fast in nine FHH patients and ten healthy controls. As the renal plasma clearance of lithium equals the rate of the proximal tubular fluid delivered into the thin descending loop of Henle's loop, the reabsorption of calcium in the proximal and distal tubule, respectively, could be calculated. We found that the FHH patients had a significantly higher fractional calcium reabsorption in the proximal tubule (77.6 ± 4.7 (%) vs 73.3 ± 3.1, P < 0.05). The same held true for the absolute proximal calcium reabsorption (1.49 ± 0.12 (mmol/l) vs 1.07 ± 0.05, P < 0.001). There was a significant linear correlation between the increased tubular capacity for calcium reabsorption and the absolute proximal calcium reabsorption (r = 0.70, P < 0.05). The distal tubular calcium reabsorption did not differ in the two groups. Our results therefore suggest that the enhanced tubular calcium reabsorption in FHH takes place exclusively in the proximal renal tubule.


Author(s):  
Jinho Lee ◽  
Kyung Don Ju ◽  
Hyo Jin Kim ◽  
Bodokhsuren Tsogbadrakh ◽  
Hyunjin Ryu ◽  
...  

Hypercalciuria is one of early manifestations of diabetic nephropathy (DN). This is partially due to a decrease in the expression of renal transient receptor potential vanilloid type 5 (TRPV5), which is responsible for renal calcium reabsorption. Soluble klotho was previously determined to increase TRPV5 by cleaving sialic acid, causing TRPV5 to bind to membrane protein galectin-1. However, a recent study showed that soluble klotho binds to α2-3-sialyllactose - where sialic acid is located - on TRPV5, rather than cleave it. Here, we report that soluble klotho tethers TRPV5 on the membrane by binding both TRPV5 and galectin-1, thereby protecting membrane TRPV5 from diabetes-induced endocytosis. We injected recombinant soluble α-klotho protein (rKL) into db/db and db/m mice for 8 weeks and collected urine and the kidney. We administered rKL, AZD4547 (FGFR1 inhibitor), and OTX008 (Galectin 1 inhibitor) to cultured mouse distal tubular cells, with or without 30 mM high glucose (HG) exposure. db/db mice showed increased renal calcium excretion and decreased renal TRPV5 expression. rKL treatment reversed this change. In vitro, TRPV5 expression in distal tubular cells decreased under HG conditions, and rKL successfully upregulated TRPV5 with or without FGF23. Also, immunofluorescence showed co-localization of klotho, TRPV5, and galectin-1 in distal tubule cells, suggesting that klotho binds to both TRPV5 and galectin 1. Moreover, when both FGFR1 and galectin-1 were inhibited, rKL failed to increase TRPV5 under HG conditions. Our results indicate that soluble klotho prevents TRPV5 from degradation and subsequent diabetes-induced endocytosis by anchoring TRPV5 through binding with both TRPV5 and galectin-1.


1984 ◽  
Vol 66 (2) ◽  
pp. 187-191 ◽  
Author(s):  
S. H. Ralston ◽  
I. Fogelman ◽  
M. D. Gardner ◽  
F. J. Dryburgh ◽  
R. A. Cowan ◽  
...  

1. The renal handling of calcium was examined in 31 patients with hypercalcaemia of malignancy. Results were compared with those from patients with primary hyperparathyroidism, and normal controls rendered hypercalcaemic by calcium infusion. 2. On relating the urinary calcium excretion indices to serum calcium values, inappropriately low rates of urinary calcium excretion were generally found in patients with malignancy associated hypercalcaemia. Further, the pattern of urinary calcium excretion in these subjects was similar to that found in patients with primary hyperparathyroidism. 3. These observations suggest that, in many solid tumours, the development of hypercalcaemia may be attributable to a humoral mediator with a parathyroid hormone-like effect on renal tubular calcium reabsorption. 4. The relatively frequent occurrence of hypercalcaemia in malignant disease thus may be partially explained by the presence of this humoral agent, which may impair the renal excretion of an increase in filtered calcium load, whether due to bone metastases, or humorally mediated osteolysis.


1983 ◽  
Vol 245 (4) ◽  
pp. F515-F520
Author(s):  
R. A. Sutton ◽  
N. L. Wong ◽  
G. A. Quamme ◽  
J. H. Dirks

Micropuncture experiments were performed in thyroparathyroidectomized dogs to examine the influence of changes in filtered calcium load on segmental tubular calcium reabsorption. Filtered calcium load was changed either by reducing glomerular filtration rate (GFR) by aortic clamping (group I) or by progressive calcium infusion (group II) to increase plasma ultrafilterable calcium concentration (UFCa). The results suggest that fractional proximal calcium reabsorption responds similarly to altered filtered load, whether produced by changes in GFR or UFCa. In contrast, fractional reabsorption by the loop segment is progressively reduced as UFCa is increased but is relatively unchanged by alterations in filtered load secondary to altered GFR. These data indicate a specific parathyroid hormone-independent reciprocal effect of UFCa on calcium reabsorption in the loop segment, which may be an important determinant of urinary calcium excretion.


1986 ◽  
Vol 7 (10) ◽  
pp. 295-318

Hypercalciuria in children is diagnosed when the urinary calcium excretion is greater than 4.0 mg/kg in 24 hours, the ratio of urinary concentration of calcium to creatinine (UCa/UCr) is greater than 0.20, and there is normal serum calcium. Hypercalciuria may be the result of increased intestinal absorption of calcium (absorptive hypercalciuria) or an impaired proximal tubular defect in calcium reabsorption (renal hypercalciuria). Oral calcium load tests will differentiate the two types of hypercalciuria. Elevated fasting UCa/UCr with normal levels of parathormone (PTH) or urinary cyclic-AMP indicates renal hypercalciuria. After an oral calcium load, the UCa/UCr ratio will be greater than normal in absorptive hypercalciuria. However, Hymes and Warshaw suggest that both subtypes may coexist in some patients.


Author(s):  
Robert R. Cardell

Hypophysectomy of the rat renders this animal deficient in the hormones of the anterior pituitary gland, thus causing many primary and secondary hormonal effects on basic liver functions. Biochemical studies of these alterations in the rat liver cell are quite extensive; however, relatively few morphological observations on such cells have been recorded. Because the available biochemical information was derived mostly from disrupted and fractionated liver cells, it seemed desirable to examine the problem with the techniques of electron microscopy in order to see what changes are apparent in the intact liver cell after hypophysectomy. Accordingly, liver cells from rats which had been hypophysectomized 5-120 days before sacrifice were studied. Sham-operated rats served as controls and both hypophysectomized and control rats were fasted 15 hours before sacrifice.


1988 ◽  
Vol 152 (3) ◽  
pp. 1213-1220 ◽  
Author(s):  
Jerome M. Goldman ◽  
Ralph L. Cooper ◽  
Georgia L. Rehnberg ◽  
W. Keith McElroy ◽  
Joy F. Heln ◽  
...  

2018 ◽  
Vol 06 (10) ◽  
pp. E1206-E1213 ◽  
Author(s):  
Bruno Moulin ◽  
Thierry Ponchon

Abstract Background and study aims Colonoscopy is a widely used diagnostic procedure which requires prior cleansing of the bowel. Many different bowel cleansing preparations have been developed, all of which have specific advantages and disadvantages. This review compares two low-volume high-osmolarity bowel cleansing preparations, oral phosphate salts and oral sulphate salts, with a particular focus on risk of nephrotoxicity. Patients and methods An electronic search of the Medline database was performed using the search terms “(phosphates OR sulfates) AND cathartics [MeSH Term] AND kidney” restricted to humans with a cut-off date of December 31, 2016. Results Introduction of oral phosphate salts offered the advantage of low intake volume and low risk of bowel irritation compared to previous options. However, phosphate salts have been associated with renal toxicity (acute phosphate nephropathy [APN]), thought to arise due to perturbations of calcium and phosphate homeostasis as a consequence of increases in serum phosphate. This results in high concentrations of calcium phosphate in the distal tubule and collecting ducts of the kidney, where it may precipitate. Although APN is rare, it may lead to permanent kidney damage. For this reason, phosphate salts are contraindicated in vulnerable patient groups. As an alternative to phosphate salts, oral sulphate salts have recently been introduced. Because sulphate absorption from the intestinal tract is saturable, serum sulphate concentrations increase only minimally after ingestion. Furthermore, excretion of sulphate in the kidney is not accompanied by calcium excretion and urine calcium levels are unchanged. For these theoretical reasons, use of sulphate salts as bowel cleansing solutions is not expected to lead to calcium precipitation in the nephron. Conclusions Oral phosphate salts are no longer recommended for routine use as bowel cleansing preparations as they carry significant risk of kidney damage and a safer alternative is available in the form of oral sulphate solutions. To date, use of sulphate salts has not been associated with elevations in serum creatinine or other markers of renal impairment, nor with clinical manifestations of kidney injury. Nonetheless, experience with sulphate salts in everyday practice is limited and physicians should be vigilant in detecting potential safety issues.


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