scholarly journals Sex differences in proximal and distal nephron function contribute to the mechanism of idiopathic hypercalcuria in calcium stone formers

2015 ◽  
Vol 309 (1) ◽  
pp. R85-R92 ◽  
Author(s):  
Benjamin Ko ◽  
Kristin Bergsland ◽  
Daniel L. Gillen ◽  
Andrew P. Evan ◽  
Daniel L. Clark ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Distal Tubule ◽  
Normal Subjects ◽  
Idiopathic Hypercalciuria ◽  
Distal Nephron ◽  
Stone Formers ◽  
Calcium Reabsorption ◽  
Normal Women ◽  
Normal Males ◽  
Normal Men

Idiopathic hypercalciuria (IH) is a common familial trait among patients with calcium nephrolithiasis. Previously, we have demonstrated that hypercalciuria is primarily due to reduced renal proximal and distal tubule calcium reabsorption. Here, using measurements of the clearances of sodium, calcium, and endogenous lithium taken from the General Clinical Research Center, we test the hypothesis that patterns of segmental nephron tubule calcium reabsorption differ between the sexes in IH and normal subjects. When the sexes are compared, we reconfirm the reduced proximal and distal calcium reabsorption. In IH women, distal nephron calcium reabsorption is decreased compared to normal women. In IH men, proximal tubule calcium reabsorption falls significantly, with a more modest reduction in distal calcium reabsorption compared to normal men. Additionally, we demonstrate that male IH patients have lower systolic blood pressures than normal males. We conclude that women and men differ in the way they produce the hypercalciuria of IH, with females reducing distal reabsorption and males primarily reducing proximal tubule function.

scholarly journals Evidence for increased postprandial distal nephron calcium delivery in hypercalciuric stone-forming patients

2008 ◽  
Vol 295 (5) ◽  
pp. F1286-F1294 ◽  
Author(s):  
Elaine M. Worcester ◽  
Fredric L. Coe ◽  
Andrew P. Evan ◽  
Kristin J. Bergsland ◽  
Joan H. Parks ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Stone Formation ◽  
Selective Reduction ◽  
Normal Subjects ◽  
Idiopathic Hypercalciuria ◽  
Calcium Excretion ◽  
Distal Nephron ◽  
Clinical Research Center ◽  
Calcium Reabsorption ◽  
New Finding

A main mechanism of idiopathic hypercalciuria (IH) in calcium stone-forming patients (IHSF) is postprandial reduction of renal tubule calcium reabsorption that cannot be explained by selective reduction of serum parathyroid hormone levels; the nephron site(s) responsible are not as yet defined. Using fourteen 1-h measurements of the clearances of sodium, calcium, and endogenous lithium during a three-meal day in the University of Chicago General Clinical Research Center, we found reduced postprandial proximal tubule reabsorption of sodium and calcium in IHSF vs. normal subjects. The increased distal sodium delivery is matched by increased distal reabsorption so that urine sodium excretions do not differ, but distal calcium reabsorption does not increase enough to match increased calcium delivery, so hypercalciuria results. In fact, urine calcium excretion and overall renal fractional calcium reabsorption both are high in IHSF vs. normal when adjusted for distal calcium delivery, strongly suggesting a distal as well as proximal reduction of calcium reabsorption. The combination of reduced proximal tubule and distal nephron calcium reabsorption in IHSF is a new finding and indicates that IH involves a complex, presumably genetic, variation of nephron function. The increased calcium delivery into the later nephron may play a role in stone formation via deposition of papillary interstitial apatite plaque.

Evidence that postprandial reduction of renal calcium reabsorption mediates hypercalciuria of patients with calcium nephrolithiasis

2007 ◽  
Vol 292 (1) ◽  
pp. F66-F75 ◽  
Author(s):  
Elaine M. Worcester ◽  
Daniel L. Gillen ◽  
Andrew P. Evan ◽  
Joan H. Parks ◽  
Katrina Wright ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Serum Magnesium ◽  
Normal Subjects ◽  
Urinary Calcium ◽  
Idiopathic Hypercalciuria ◽  
Calcium Excretion ◽  
Stone Formers ◽  
Calcium Reabsorption ◽  
Renal Tubular ◽  
Filtered Load

Idiopathic hypercalciuria (IH) is common among calcium stone formers (IHSF). The increased urinary calcium arises from increased intestinal absorption of calcium, but it is unclear whether increased filtered load or decreased renal tubular reabsorption of calcium is the main mechanism for the increased renal excretion. To explore this question, 10 IHSF and 7 normal subjects (N) were studied for 1 day. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, and calories. Fasting and fed, ultrafiltrable calcium levels, and filtered load of calcium did not differ between N and IHSF. Urine calcium rose with meals, and fractional reabsorption fell in all subjects, but the change was significantly higher in IHSF. The changes in calcium excretion were independent of sodium excretion. Serum parathyroid hormone levels did not differ between N and IHSF, and they could not account for the greater fall in calcium reabsorption in IHSF. Serum magnesium and phosphorus levels in IHSF were below N throughout the day, and tubule phosphate reabsorption was lower in IHSF than N after meals. The primary mechanism by which kidneys ferry absorbed calcium into the urine after meals is via reduced tubule calcium reabsorption, and IHSF differ from N in the magnitude of the response. Parathyroid hormone is not likely to be a sufficient explanation for this difference.

scholarly journals Evidence for disordered acid-base handling in calcium stone-forming patients

2020 ◽  
Vol 318 (2) ◽  
pp. F363-F374
Author(s):  
Elaine M. Worcester ◽  
Kristin J. Bergsland ◽  
Daniel L. Gillen ◽  
Fredric L. Coe
Keyword(s):  
Idiopathic Hypercalciuria ◽  
Same Sex ◽  
Mineral Phase ◽  
Acid Base ◽  
Urine Ph ◽  
Stone Formers ◽  
Normal Individuals ◽  
Normal Women ◽  
Alkali Absorption ◽  
Normal Men

In stone formers (SFs) with idiopathic hypercalciuria, urine pH governs the mineral phase of stones. Calcium phosphate (CaP) SFs have higher urine pH than calcium oxalate (CaOx) SFs. Normal women have higher urine pH than men on fixed diets, accompanied by greater absorption of food alkali. Female CaP and male CaOx SFs have similar urine pH as same sex normal individuals, but male CaP and female CaOx SFs may have abnormal acid-base handling. We studied 25 normal individuals (13 men and 12 women), 17 CaOx SFs (11 men and 6 women), and 15 CaP SFs (8 men and 7 women) on fixed diets. Urine and blood samples were collected under fasting and fed conditions. Female CaOx SFs had lower urine pH and lower alkali absorption, fed, compared with normal women; their urine NH4 was higher and urine citrate excretion lower than in normal women, consistent with their higher net acid excretion. Male CaOx SFs had higher urine citrate excretion and higher serum ultrafilterable citrate levels than normal men. Both male and female CaP SFs had higher urine pH fasting than same sex normal individuals, but only men were higher in the fed period, and there were no differences from normal in gut alkali absorption. CaP SFs of both sexes had higher urine NH4 and lower urine citrate than same sex normal individuals. The lower urine pH of female CaOx SFs seems related to decreased gut alkali absorption, while the higher pH of CaP SFs, accompanied by higher urine NH4 and lower urine citrate, suggests a proximal tubule disorder.

scholarly journals Role of proximal tubule in the hypocalciuric response to thiazide of patients with idiopathic hypercalciuria

2013 ◽  
Vol 305 (4) ◽  
pp. F592-F599 ◽  
Author(s):  
Kristin J. Bergsland ◽  
Elaine M. Worcester ◽  
Fredric L. Coe
Keyword(s):  
Proximal Tubule ◽  
Stone Formation ◽  
Idiopathic Hypercalciuria ◽  
Sodium Absorption ◽  
Distal Nephron ◽  
Urine Ph ◽  
Stone Formers ◽  
Vasa Recta ◽  
Clinical Research Center ◽  
Stone Growth

The most common metabolic abnormality found in calcium (Ca) kidney stone formers is idiopathic hypercalciuria (IH). Using endogenous lithium (Li) clearance, we previously showed that in IH, there is decreased proximal tubule sodium absorption, and increased delivery of Ca into the distal nephron. Distal Ca reabsorption may facilitate the formation of Randall's plaque (RP) by washdown of excess Ca through the vasa recta toward the papillary tip. Elevated Ca excretion leads to increased urinary supersaturation (SS) with respect to calcium oxalate (CaOx) and calcium phosphate (CaP), providing the driving force for stone growth on RP. Thiazide (TZ) diuretics reduce Ca excretion and prevent stone recurrence, but the mechanism in humans is unknown. We studied the effect of chronic TZ administration on renal mineral handling in four male IH patients using a fixed three meal day in the General Clinical Research Center. Each subject was studied twice: once before treatment and once after 4–7 mo of daily chlorthalidone treatment. As expected, urine Ca fell with TZ, along with fraction of filtered Ca excreted. Fraction of filtered Li excreted also fell sharply with TZ, as did distal delivery of Ca. Unexpectedly, TZ lowered urine pH. Together with reduced urine Ca, this led to a marked fall in CaP SS, but not CaOx SS. Since CaOx stone formation begins with an initial CaP overlay on RP, by lowering urine pH and decreasing distal nephron Ca delivery, TZ might diminish stone risk both by reducing CaP SS, as well as slowing progression of RP.

Relations between Oxalic Acid, Calcium, Magnesium and Creatinine Excretion in Normal Men and Male Patients with Calcium Oxalate Kidney Stones

1974 ◽  
Vol 46 (3) ◽  
pp. 357-367 ◽  
Author(s):  
A. Hodgkinson
Keyword(s):  
Calcium Oxalate ◽  
Normal Subjects ◽  
Calcium Excretion ◽  
Oxalate Excretion ◽  
Stone Formers ◽  
Calcium Magnesium ◽  
Male Patients ◽  
Calcium And Magnesium ◽  
Magnesium Excretion ◽  
Normal Men

1. The daily excretion of oxalate, calcium, magnesium and creatinine was determined in fifty-two normal men and sixty-five male patients with calcium oxalate-containing renal stones. 2. Direct relationships were found between calcium and oxalate excretion, magnesium and oxalate excretion and calcium and magnesium excretion in both normal subjects and stone-formers. The significance of these relationships is discussed. 3. The mean excretion of calcium and oxalate was significantly higher in the stone-formers, compared with the controls, both calcium and oxalate excretion being raised by about 20%. 4. The effect of oral ingestion of glucose and casein on the rate of excretion of calcium, magnesium, oxalate and phosphate was examined. Glucose increased the rate of calcium and magnesium excretion but had no effect on oxalate excretion and suppressed phosphate excretion. Casein also increased calcium excretion but had little or no effect on magnesium or oxalate excretion, and it increased phosphate excretion. 5. The association of high calcium excretion with high oxalate excretion, in both normal subjects and stone-formers, results in a high degree of supersaturation of the urine with respect to calcium oxalate. The implication of these findings with respect to the cause and treatment of calcium oxalate stones is discussed.

High affinity Ca2+–Mg2+ ATPase in the distal tubule of the mouse kidney

1987 ◽  
Vol 65 (10) ◽  
pp. 2093-2098 ◽  
Author(s):  
Michèle G. Brunette ◽  
Sylvie Blouin ◽  
Meathan Chan
Keyword(s):  
Proximal Tubule ◽  
Kinetic Parameters ◽  
Atp Hydrolysis ◽  
Limit Of Detection ◽  
Distal Tubule ◽  
Mouse Kidney ◽  
Distal Nephron ◽  
Low Concentrations ◽  
Distal Tubules ◽  
Shed Light

The purpose of this study was to investigate whether Ca2+–Mg2+ ATPase in the distal tubule (where calcium transport is active, against a gradient, and hormone dependent) presents some characteristics different from those observed in the proximal tubule, and whether these characteristics are likely to shed light on the respective roles of this enzyme at the two sites of the nephron. The Ca2+- and Mg2+-dependent ATP hydrolysis was measured in microdissected segments of the distal nephron, the kinetic parameters were determined, and the influence of magnesium upon the sensitivity to calcium was examined. Results were compared with those obtained in the proximal tubule, and in purified membranes as reported by others. In the distal tubule, low concentrations of Mg2+ (< 10−7 M) did not influence ATP hydrolysis. At concentrations above 10−7 M, Mg2+ increased ATP hydrolysis according to Michaelis kinetics (apparent Km = 11.3 ± 2.4 μM, Vmax = 219 ± 26 pmol∙mm−1∙20 min−1). The addition of 1 μM Ca2+ decreased the apparent Km for Mg2+ and the Vmax for Mg2+. Similar results were obtained in the proximal tubule. At low Mg2+ concentrations, Ca2+ also stimulated ATP hydrolysis according to Michaelis kinetics with an apparent Km value for Ca2+ of 0.18 ± 0.06 and 0.10 ± 0.03 μM Ca2+ (ns) and a Vmax of 101 ± 12 and 89 ± 9 pmol∙mm−1∙20 min−1 (ns) in the distal and proximal tubules, respectively. In the two segments, the addition of Mg2+ strongly decreased the sensitivity to 1 μM Ca2+ so that at 1 mM Mg2+, the Ca2+-dependent ATPase activity was at the limit of detection. In conclusion, the kinetic parameters of the Ca2+- and Mg2+-dependent ATP hydrolysis were similar at the two sites of the nephron, and were also similar to those reported for the enzyme present in purified basolateral membranes. The nonadditive effect of the two cations Ca2+ and Mg2+ suggests that the two ATPase activities belong to the same enzyme, and this enzyme is the same in the proximal and distal tubules. Differences in Ca2+ transport characteristics should be attributed to factors other than variations in the nature of the Ca2+–Mg2+ ATPase.

scholarly journals Endopeptidases (kininases) are able to hydrolyze kinins in tubular fluid along the rat nephron

1999 ◽  
Vol 277 (1) ◽  
pp. F66-F74 ◽  
Author(s):  
D. E. Casarini ◽  
M. A. Boim ◽  
R. C. R. Stella ◽  
N. Schor
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Proximal Tubule ◽  
Physiological Role ◽  
Distal Tubule ◽  
Neutral Endopeptidase ◽  
Prolyl Endopeptidase ◽  
Proximal Tubules ◽  
Converting Enzyme ◽  
Distal Nephron ◽  
Distal Tubules

The activities of serine endopeptidase, prolyl endopeptidase and neutral endopeptidase were determined in tubular fluid collected from several portions of the rat nephron as well as in urine. The enzyme activities were measured by HPLC using bradykinin (BK) as substrate. Free residual peptides of BK obtained by the action of these enzymes on the locally produced BK were also determined. The endopeptidase activities were found to be present throughout the nephron. Equimolar fragments of BK were detected in the early proximal tubule (Arg1-Pro7, Phe8-Arg9, Arg1-Gly4, Phe5-Arg9, and BK), late proximal tubule (Arg1-Phe5, Arg1-Pro7, Gly4-Pro7, Gly4-Arg9, and BK), late distal tubule (Arg1-Gly4, Phe5-Arg9, Arg1-Phe5, Ser6-Arg9, Gly4-Arg9, BK, and [des-Arg9]BK) and urine (Phe8-Arg9, Phe5-Arg9, Arg1-Phe5, Ser6-Arg9, Arg1-Pro7, Gly4-Pro7, Gly4-Arg9, BK, and [des-Arg9]BK). Our data suggest that the endopeptidases and exopeptidases are secreted by the nephron. Early proximal tubules secrete angiotensin converting enzyme and neutral endopeptidase, differing from late distal tubules that produce prolyl endopeptidase, serine endopeptidase, carboxypeptidase, and also neutral endopeptidase. All enzymes detected along the rat nephron were found in the urine. The existence of endopeptidases and carboxypeptidase in the distal nephron may have a potential physiological role in the inactivation of the kinins formed by kallikrein in the kidney and also in the inactivation of additional peptides other than BK.

Comparison of Laboratory Test Results for Assessing Thyroid Function in Normal Subjects and Treated and Untreated Hyper- and Hypothyroid Patients

1971 ◽  
Vol 17 (3) ◽  
pp. 174-182 ◽  
Author(s):  
Norman D Lee ◽  
Boris Catz ◽  
M S Margolese ◽  
Vincent J Pileggi
Keyword(s):  
Binding Capacity ◽  
Normal Subjects ◽  
Free Thyroxine ◽  
Significant Finding ◽  
Normal Limits ◽  
Laboratory Test Results ◽  
Free Thyroxine Index ◽  
Normal Women ◽  
Normal Men ◽  
Hypothyroid Patients

Abstract Various indexes of thyroid status were measured in sera from normal men and women, normal women who were using oral contraceptives, hyper- and hypothyroid patients, and hypothyroid patients being successfully managed with various forms of replacement therapy. Total circulating thyroxine concentrations were measured by three methods as well as the thyroxine-binding capacity of the serum inter-alpha globulin, "free" thyroxine, and "free" thyroxine index. Our purpose was to compare the various measurements, and to assess their diagnostic usefulness. The most significant finding was that, of 197 hypothyroid patients, all of whom possessed total circulating thyroxine concentrations within normal limits, 28% showed subnormal "free" thyroxine concentrations.

Stress Reactions Resulting from the Relocation of an aged Population

1968 ◽  
Vol 13 (3) ◽  
pp. 201-209 ◽  
Author(s):  
V. A. Kral ◽  
B. Grad ◽  
J. Berenson
Keyword(s):  
Respiratory Infections ◽  
Normal Subjects ◽  
Lower Number ◽  
The Body ◽  
Stress Reactions ◽  
Men And Women ◽  
Relative Percentage ◽  
Significant Difference ◽  
Normal Women ◽  
Normal Men

Fifty-four subjects from 64 to 94 years of age were investigated for their stress reactions following their relocation from one site to another. Forty of them, 16 men and 24 women, were psychiatrically normal, while the remainder (eight men and six women) were suffering from a psychosis, which in all cases, except one, was of organic type. There was no statistically significant difference between the ages of the men and women, and of the normals and psychotics. The same was true in the case of the body weight, except that the men weighed more than the women. Plasma corticoid (PC) levels were determined two to nine days before relocation and eight to 17 days afterwards. One-third of the subjects made no complaints in regard to their health within four months of relocation (NC 33%), while the rest either reported symptoms for which there did not appear to be any apparent organic cause (WS 43%) or presented organic signs (OS 24%). Most of the complaints in the WS category were related to the abdomen, while most of those in the OS group were either due to respiratory infections or cardiovascular conditions. The relative percentage of persons falling into these three categories was essentially similar in normal men and in normal women and in psychotic men and psychotic women. However, the psychotics had a significantly higher incidence of OS persons and a significantly lower number of NC subjects than did the normals, while the incidence of WS was essentially the same in these two groups. Following relocation the PC levels increased in normal men, but decreased in normal women. Furthermore, a greater PC increase was observed in men of the OS group than in those of the WS category, who in turn showed a greater increase than the NC males. This was not observed in the women. Men in each of the NC, WS and OS categories had higher PC levels than women of the same category, and psychotics higher than normals. Twenty-five per cent of the normal men died within the first six months of relocation but none of the normal women, a statistically significant difference. Within 23 months of relocation reliably more psychotics died than normals. In conclusion, normal aged men appeared to suffer more from the relocation than normal aged women, and psychotic aged persons more than psychiatrically normal subjects of the same age.

Regulation of Breathing during Exercise in Normal Subjects and in Chronic Lung Disease

1976 ◽  
Vol 51 (6) ◽  
pp. 575-582 ◽  
Author(s):  
G. W. Bradley ◽  
R. Crawford
Keyword(s):  
Lung Disease ◽  
Chronic Lung Disease ◽  
Obstructive Lung Disease ◽  
Breathing Pattern ◽  
Normal Subjects ◽  
Men And Women ◽  
Restrictive Lung Disease ◽  
Regulation Of Breathing ◽  
Normal Women ◽  
Normal Men

1. The breathing pattern in normal subjects during exercise was compared with that in patients with obstructive and restrictive lung defects. 2. In most normal women and patients with obstructive or restrictive lung disease, as the frequency of breathing increased both inspiratory and expiratory duration fell. However, in most normal men (74%) inspiratory duration did not fall as ventilation increased. 3. Women breathed faster than men, and both obstructed and restricted patients breathed faster than normal subjects. 4. The airflow patterns in normal men and women were similar, but most patients with restrictive or obstructive lung disease showed an approximately exponential fall in flow during expiration.

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