Calcitriol And Absorptive Hypercalciuria
The main component of kidney stones is calcium oxalate, and, to a lesser extent, calcium phosphate. Increased urinary calcium excretion or hypercalciuria is one of the main risk factors promoting calcium kidney stone formation. Early studies have demonstrated increased intestinal absorption of calcium in most cases of idiopathic hypercalciuria, defining absorptive hypercalciuria . Intestinal calcium absorption depends on the calcium intraluminal concentration , but the main factor responsible for transcellular calcium absorption is 1,25-dihydroxyvitamin D or calcitriol, the active form of vitamin D . Vitamin D, whether produced in the skin from 7-dehydrocholesterol or absorbed from the diet or supplements must actually be activated as 25-hydroxyvitamin D in the liver and then as calcitriol in the kidneys to exert its biological effects.
Calcitriol binds the vitamin D receptor in enterocytes and increases calcium transport across digestive epithelia through the gatekeeper transient receptor potential vanilloid 6 transporter .
Calcitriol also binds VDR in parathyroid cells, decreasing parathyroid hormone synthesis. PTH increases calcium influx through the gatekeeper TRPV5 in distal tubular kidney cells. Thus, PTH decrease by calcitriol may be associated with increased urine calcium excretion .
A Picture Of This Elaborate Web
I cannot leave this mass of hormones and their mutual regulations without some try at synthesis. So many names, so many loops. Here, I placed the main names but left our RANKL RANK osteoprotegerin, and osteopontin no more room. As I have already referenced each regulation step I omit them here. Blue lines show upregulation, red the opposite. Most receptors are left out to avoid clutter FGFR and VDR are included.
What Do The Results Mean
If your results show higher than normal calcium levels in your urine, it may indicate:
- Risk for or the presence of a kidney stone
- Hyperparathyroidism, a condition in which your parathyroid gland produces too much parathyroid hormone
- Sarcoidosis, a disease that causes inflammation in the lungs, lymph nodes, or other organs
- Too much calcium in your diet from vitamin D supplements or milk
If your results show lower than normal calcium levels in your urine, it may indicate:
- Hypoparathyroidism, a condition in which your parathyroid gland produces too little parathyroid hormone
- Vitamin D deficiency
- A kidney disorder
If your calcium levels are not normal, it doesn’t necessarily mean you have a medical condition needing treatment. Other factors, such as diet, supplements, and certain medicines, including antacids, can affect your urine calcium levels. If you have questions about your results, talk to your health care provider.
Learn more about laboratory tests, reference ranges, and understanding results.
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Multiple Endocrine Neoplasia Type 1
This well known genetic disease accounts for about 20% of familial PHPT. The affected people inherit one defective gene copy but if the parathyroid cells lose the other as a somatic mutation they develop parathyroid tumors that overproduce PTH. Carriers with one normal copy seem normal. The MEN1 gene codes for menin, a nuclear protein that suppresses cell proliferation. MEN 1 gene deletions cause not only four gland enlargement PHPT but also a mixture of islet cell and pituitary endocrine tumors and endocrine tumors of the duodenum that produce the hormone gastrin that stimulates gastric acid production and fosters peptic ulcer. Other tumors include adrenal glands, thyroid glands and benign lipomas fatty deposits beneath the skin. PHPT is usually the first manifestation of MEN 1 gene abnormalities.
What Is Casr And What Is Its Relationship To The Parathyroid And Kidneys
CaSR is a protein made from the CASR gene CASR provides instructions that enable the body to produce CaSR.The CaSR protein is found on the surface of all parathyroid cells in the parathyroid glands, which produce and release PTH to regulate calcium in the blood. Calcium molecules can attach themselves to CaSR, which enables the protein to monitor and regulate calcium in the blood.
To activate CaSR, the blood calcium level must reach a higher level then what is appropriate for your body . Once activated the CaSR blocks PTH production and release into the blood stream. When CaSR is not activated because calcium levels are lower then expected then more PTH is produced and released into the blood.
In instances where the parathyroid glands are not working correctly, the CaSR becomes less sensitive to calcium , and so it takes a higher level of calcium in the blood to activate CaSR and stop PTH production. .
Additionally in one study, researchers found a direct correlation between kidney stones and two modifications of CaSR. They also discovered that patients coping with primary hyperparathyroidism were prone to kidney stones and CaSR modifications.
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Patient Evaluation And Management
Patients who present for the first time with renal colic are often evaluated with an unenhanced helical CT scan. This is generally the most sensitive method for establishing the presence of a renal stone. The CT provides valuable information regarding the size and location of the stone, and any anatomical abnormalities can be defined. Ureteral stones smaller than 5 mm will generally pass spontaneously with adequate hydration. In the absence of fever, infection, or renal failure, these stones are generally followed conservatively. Pain may be managed with opioid analgesics and nonsteroidal anti-inflammatory drugs . Intravenous hydration is usually administered until the patient is able to consume adequate amounts of fluid by mouth. Most of these patients can be stabilized in the emergency room and then followed as an outpatient. Alpha1-adrenergic receptor blockers or calcium channel blockers are sometimes prescribed to assist with stone passage. Stones greater than 10 mm will generally not pass spontaneously and will require urologic intervention. Stones ranging from 5 mm to 10 mm will have variable outcomes. More distal stones will generally pass more readily than stones in the proximal ureter. Again, if the patient is afebrile, pain is controlled, and there is no evidence of infection or renal failure, the patient can be followed initially conservatively. Stones in this size range that do not pass will require intervention.3
Upper End Of The Normal Range
A valid and alternative definition of hypercalciuria is that it consists in very high urine calcium excretion, and a way to gauge the meaning of very high would be values at the upper end of the normal range. This idea of the upper end is usually taken as above the upper 95% of values encountered in surveys of people without known diseases.
The Curhan data actually give a reasonable measure of this upper end from the means and 95% limits of the non stone formers in the three cohorts. The lower dot marks the position of the lower 95th percentile of urine calcium for the two nurse cohorts and the physician cohort. The upper dot gives the upper 95th percentile . The intervening bars are for visual effect.
For those who want to study hypercalciuria, as an example, and want a reliable gauge of who is really high the three figures are 374 372 and 351 mg/day for the three groups.
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Do Kidney Stones Cause High Liver Enzymes
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ACE inhibitors, or angiotensin converting enzyme inhibitors, is a class of drugs that interact with blood enzymes to enlarge or dilate blood vessels and reduce blood pressure. These drugs are used to control high blood pressure , treat heart problems, kidney disease in people with diabetes high blood pressure.
Since ARCUS can be delivered via AAV or LNP, it has potential utility in treating diseases in the liver as well as many.
toxic metabolite called oxalate that causes extremely severe and potentially.
High Sugar Diet And Kidney Stones Jan 10, 2018 · Can A High Sugar Diet Cause Kidney Stones? Summary: When you eat a lot of sugar your body secretes insulin. Insulin, aside from handling the sugar load, also forces more calcium to be excreted through your kidneys. This increases your risk of forming kidney stones as a good amount of kidney
Typically, kidney stones do not cause elevated liver enzymes. However, a sever urinary tract infection within the kidneys can cause elevated liver enzymes. A kidney stone. and made in your liver. Less than 3 in 100 stones are made of the amino acid cystine.
In one of the studies it also reduced alcohol craving, and in additional analyses it improved patients quality of life as well as their blood pressure, liver-enzyme, and cholesterol levels.
May 18, 2016.
Randalls Plaque And Calcium Stone Formation: A Link With Vitamin D Prescription
We still ignore whether vitamin D prescription or vitamin D metabolite serum levels could influence Randalls plaque formation. We compared serum and urine biochemistry from calcium oxalate stone formers, with and without Randalls plaque at the origin of the stones. We did not find evidence for any difference in vitamin D metabolites between the two groups, but patients affected by plaques had higher serum calcium levels, higher osteocalcin serum levels, lower phosphate excretion levels and a trend toward decreased parathyroid hormone levelsall features compatible with an increased sensitivity to vitamin D . Nevertheless, VDR polymorphisms could not explain the phenotype observed. Whether individual sensitivity to vitamin D could promote Randalls plaque formation needs to be confirmed by additional studies. Patients who form stones from Randalls plaques are younger, raising concerns about a potential role of vitamin D prescribed during infancy in Randalls plaque development, whereby stones are formed years or decades later .
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Serum Calcium Rises Phosphate Falls
All factors raise serum calcium. Bone loses calcium and phosphate into the blood. Calcitriol increases because of high PTH. The higher serum calcium suppresses calcitriol, but lowered phosphate does the opposite. So high serum calcium opposes high serum PTH and low serum phosphate. The two outweigh the one. Calcitriol exceeds normal, and increases GI calcium and phosphate absorption into the blood. Kidneys release the phosphate but retain the calcium. Calcitriol would suppress PTH secretion but the glands no longer listen as attentively.
Sex Vs Percent Cap In Stones
The same study furnished this nice graph showing the sexes as the percent of stone CaP increases. The bulk of patients have very little CaP in stones . These are the common CaOx stone formers, mainly men . But when CaP percent is 20 50% in stones, women and men are nearly equal.
This graph blurs the sex distinction because we used stone CaP% from both brushite and hydroxyapatite. Today, I would have left the brushite to one side, which would have made the female preponderance among those with high stone CaP% more marked because the sex ratio for brushite stone formers is closer to 1.
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It’s All About Duration How Long Has The Calcium Been High
This next graph shows the same patients but this time we graphed them according to how long their calcium was above 10.0 mg/dl . So this time the bottom X axis is the number of years their calcium has been above 10.0 instead of how high the blood calcium was in the previous graph. You can see that the longer a person has high calcium the higher the chance of getting kidney stones. Even very mild elevations of calcium for a few years dramatically increases the incidence of kidney stones.
Vitamin D Serum Levels And Vitamin D Prescription: A Link With Kidney Stones
Since calcitriol increases digestive calcium absorption and, at least temporarily, serum calcium levels, it should necessarily increase urine calcium excretion to maintain calcium homeostasis . The prescription of cholecalciferol or analogous treatments increases circulating levels of 25-hydroxyvitamin D, which may act with low affinity on VDR or be transformed into calcitriol, with a higher affinity to VDR . The production of calcitriol is fortunately limited by parathyroid hormone synthesis suppression, through calcium sensing receptors and calcitriol signalling in parathyroid cells. Since parathyroid hormone promotes renal calcium handling in the distal tubules, its suppression may also increase urinary calcium excretion.
Although there is a large consensus that high calcitriol levels increase urine calcium and kidney stone formation, whether serum 25-hydroxyvitamin D circulating levels or widespread vitamin D prescription could influence kidney stone formation is still debated.
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More Rare Genetic Mutations
These conditions are almost always evident in childhood, very rare, and not what a clinician in the practice of stone prevention expects to encounter. However every once in a while they do show up. The best reading source for all of the genetic hypercalciurias is OMIM, the wonderful online library that is free to everyone. In reading the tiny blurbs below keep in mind that almost no stone formers have these rare diseases, that those who have them present typically as ill children, even infants.
Bartter Syndromes 1-3
These are gene defects of transporters in the thick ascending limbs of the loops of Henle . There is hypercalciuria but also a picture that resembles lasix use because lasix acts on this segment. Urine losses are high for sodium, potassium, and chloride, and people with these diseases are prone to low blood pressure if they do not get enough sodium replacement. The blood bicarbonate is high, potassium is low.
Bartter Syndrome 5.
There is excessive signalling of the cell surface calcium receptor which produces a lasix like picture but because of the specific problem serum calcium is low and so is serum magnesium. The parathyroid glands are regulated by serum calcium via via the CaSR which is the reason for the low serum calcium level.
Autosomal dominant hypercalciuric hypocalcemia
Urine Calcium Not Low
One expects elevated urine calcium excretion as a common trait given stones and PHPT although in fact patients with just bone disease and no stones had urine calcium levels no different from those with stones. Our own data show very few patients with normal urine calcium levels, and these were older women with modest renal function impairment. Measurement of urine calcium will disclose the uncommon FHH patient as FE calcium will be very low usually below 1%.
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Learn More About Surgery For Phpt And Kidney Stones
Dr. Babak Larian of the CENTER for Advanced Parathyroid Surgery in Los Angeles is available to discuss surgery for PHPT and kidney stones. He is an expert parathyroid gland surgeon who can evaluate a patient and determine the best course of action to treat their PHPT and/or kidney stones. To learn more or to schedule a free phone or video consultation with Dr. Larian, please contact us online or call us today at 310-461-0300.
Hour Urine Test For Urine Calcium Levels
There is a test to measure the amount of calcium in your urine. This is almost always done by having you collect your pee in a jug for 24 hours and keeping that jug in your refrigerator the entire time . This test is supposed to tell your doctors if you have too much calcium in your urine, and from this they are supposed to tell you if you are at risk for more stones. The concept being that people with higher calcium in their kidneys are more likely to get kidney stones. Unfortunately, it isn’t that simple and this test is pretty worthless. Let’s take a look at the 24-Hour-Urine results for 10,000 of our patients who had hyperparathyroidism. This graph shows the amount of calcium along the bottom X axis from a low near zero up to 1000 mg/24 hours . The normal range is less than 350, but you can see that most patients with hyperparathyroidism have urine calcium that is in the normal range. We then made every patient with kidney stones have a red dot, and those that never had a kidney stone have a blue dot. And guess what, they are exactly the same. The amount of calcium in the urine is the same for those with kidney stones and those without kidney stones.
As a review from above, even mildly elevated calcium in the BLOOD will dramatically increase your risk of kidney stones , with the risk being related to the duration of high calcium , and not related at all to how HIGH the blood calcium is in the BLOOD or in the urine.
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A Coherent Clinical Entity
Reputable mineral research groups have reported cases, mainly older people with bone mineral reduction, whose PTH levels are high and whose serum calcium levels are always normal. In this review of the Columbia University experience of 37 patients who met these criteria, 95% were women, 84% of the women were menopausal, and 73% had low bone mass. None had reduced serum 25 vitamin D nor reduced kidney function.
Over 4 years 22% developed frank PHPT. Their upper limit for serum calcium of 10.4 mg/dl, however, seems high. Although ours is very low because of atomic absorption as our technique, many commercial laboratories consider values over 10.2 mg/dl as an upper limit. Of interest in this point, those who developed PHPT tended to have the highest serum calcium levels.
A review of this subject, that includes references to the 2014 International Workshop on asymptomatic PHPT dutifully reviews the many exclusions needed to fully define high PTH and normal serum calcium as a reliable clinical entity: low vitamin D, any intestinal cause of calcium malabsorption, reduced kidney function, absence of idiopathic hypercalciuria, and exclusion of drugs at the times of measurements. Neither review mentions the obvious low diet calcium intake that can produce exactly the picture described in these patients. Kidney stones are frequently present and bone mineral loss and fractures. Some patients have come to parathyroid surgery.