Friday, October 31, 2014

Hypercalciuria, Calcium in the Urine: Cause or Effect of Stone Disease?

Hypercalciuria, or excessive calcium in the urine, is the most common identifiable cause of kidney stone disease – about 50% of patients who form kidney stones will have hypercalciuria. Calcium is a chemical element used by all living organisms for many cellular processes including transport of molecules across cell membranes, transmission of messages through neurons, and electrical conduction through cardiac cells. In addition, calcium is used by a wide variety of organ-systems including the gastrointestinal, hormonal and skeletal systems – 99% of the body's calcium is stored in bones and teeth.


CALCIUM BALANCE OR HOMEOSTASIS

A careful balance of calcium is required to maintain normal function in the body. In the human, about 30-40% of dietary calcium is absorbed through the intestinal tract and much of the calcium that is not used is excreted through the urine. Other molecules like phosphate, citrate, oxalate, sulfate, and fatty acids bind to (complex) calcium and reduce its availability to be absorbed. Calcitriol (1,25(OH)2D3) is the hormonally active metabolite of Vitamin D and the most potent stimulating signal for calcium absorption by the intestine. Not only does calcitriol promote calcium absorption in the intestine, but it mobilizes osteoclasts – cells that mobilize calcium from the bones of the body – to promote increased calcium availability throughout the body. Parathyroid hormone (PTH) is a hormone released by the parathyroid glands that is turned on in low calcium levels in the body. PTH works with calcitriol to increase calcium levels through a variety of mechanisms, most importantly for this topic, reabsorption by the kidney.


From http://hmsphysiology.pbworks.com


HYPERCALCIURIA

As stated above, hypercalciuria is the most common abnormality found in calcium stone formers. In its normal state, the kidney filters and resorbs about 270mmol of calcium on a daily basis – only 4mmol is is excreted in the urine on average. Definitions of hypercalciuria include:
  • Greater than 200mg urinary calcium/day after adherence to 400mg Ca and 100mg Na diet for one week
  • Greater than 4mg/kg/day or greater than 7mmol/day in men and 6mmol/day in women
In general there are three subtypes of hypercalciuria. These will be discussed below and include:
  • Absorptive hypercalciuria
  • Renal hypercalciuria
  • Resorptive hypercalciuria

 

Absorptive Hypercalciuria

Absorptive hypercalciuria is defined by increased intestinal absorption of calcium. Patients with absorptive hypercalciuria often have normal fasting urinary calcium (<0.11mg/dL glomerular filtration) as increased absorption matched by increased renal excretion. These patients have normal kidney excretory function, but have increased calcium in the urine because their intestines absorb more calcium. Therefore if given an increased calcium load, they will respond appropriately and have increased calcium excretion.
Technically, absorptive hypercalciuria can be classified into two categories:
  • Type I: urinary calcium remains high despite low calcium diet
  • Type II: urinary calcium normalizes with restricted calcium intake
This classification has no implication for patients and is used for research purposes.

 

Renal Hypercalciuria

Sometimes called "renal calcium leak," these patients have an increased excretion of calcium without an inciting etiology. It is believed due to impaired renal tubular absorption of calcium, however the actual cause of renal hypercalciuria is unknown. These patients also demonstrate normal serum calcium levels as increased renal excretion is matched by increased intestinal absorption and bone resorption due to normal, compensatory increases in PTH and calcitriol.

 

Resorptive Hypercalciuria

Resorptive hypercalciuria is caused by primary hyperparathyroidism. In this state, excessive PTH causes elevated serum and urine calcium levels through excessive bone resorption and increased renal synthesis of calcitriol leading to enhanced intestinal absorption of calcium. Less than 5% of patients with resorptive hypercalciuria will develop stone disease. The diagnosis should be suspected in patient with nephrolithiasis and serum calcium levels >10.1mg/dL. Some patients may have normal serum calcium level, therefore repeated measurements of serum calcium may be necessary or measurement of serum ionized calcium may be helpful. It is important to note that thiazide diuretics enhance renal calcium reabsorption and exacerbates hypercalcemia in these patients.

 

DIAGNOSIS

The gold standard test for hypercalciuria is a 24-hour urine study that demonstrates >200mg/day of calcium. Fasting and calium load tests are no longer preferred by most physicians. Instead, the evaluation typically includes:
  • 24-hour urinalysis
  • Stone analysis (most patients present after a stone has been removed or passed)
  • Serum calcium
  • Serum intact parathyroid hormone (iPTH)

Fast and calcium load test:
·         Ca, Na, and oxalate restricted diet for at least 7 days
·         Distilled water (300mL each) taken 12 hours and 9 hours before calcium loading (otherwise fasting)
·         Empty bladder 2 hours before calcium loading and drink 600mL distilled water
·         All urine produced over next 2 hours pooled sample before oral calcium load (fasting urine)
·         1gm oral calcium given using 250mL of liquid synthetic diet (Calcitest) as carrier solution
·         4 hours urine collected as pooled sample (postload urine)
·         Both samples assayed for Ca and Cr – mg Ca /dL glomerular filtrate
·         Normal fasting urinary Ca <0.11mg/dL GF

Patients with absorptive hypercalciuria will have normal serum calcium and low to normal level of iPTH. Renal hypercalciuria will demonstrate normal serum calcium and may have mildly elevated iPTH. Resorptive hypercalciuria will have hypercalcemia (although can have normal serum calcium) and an elevated iPTH. In these patients, two weeks of thiazide diuretic can differentiate from renal hypercalciuria. If a patient does not meet any of these characteristics thay may have idiopathic hypercalciuria.

Type of hypercalciuria
Calcium stones
Urine calcium
Serum PTH
Serum Calcium
Absorptive hypercalciuria
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Renal leak hypercalciuria
+
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Primary hyperparathyroidism
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TREATMENT

The treatment for hypercalciuria depends on the type of hypercalciuria and involves the use of medications and dietary management of calcium levels.


Medical Management

Thiazide diuretics are widely used to control blood pressure and have secondary effects on urinary metabolites. By inhibiting sodium and chloride transport, they increase calcium reabsorption in proximal tubule and distal tubule of the nephron. This causes extracellular volume depletion with resultant increase in proximal tubular reabsorption of calcium and directly stimulates calcium reabsorption in distal tubule. Patients on thiazide diuretics require potassium supplementation to prevent the side effects of hypokalemia (decreased potassium levels in the blood) and hypocitraturia (decreased citrate in the urine).


For patients with absorptive hypercalciuria, thiazides will reduce calcium excretion but does not directly affect GI calcium absorption. In these patients, their excess calcium is often stored in bone. As the thiazide helps to normalize calcium levels, calcium will leave the bones. When bone density is stabilized, the effect of thiazide becomes attenuated. Thiazide diuretics are the ideal treatment for renal hypercalciuria as they will often correct the "renal leak." In contrast, thiazides are inappropriate for patients with resorptive hypercalciuria as they may exacerbate hypercalcemia.
Sodium cellulose phosphate is a nonabsorbable exchange resin that binds calcium in GI tract and inhibits its absorption. While it appears an ideal medication for patients with absorptive hypercalciuria, Sodium cellulose phosphate is no longer available in U.S. due to significant hazards related to negative calcium balance, magnesium depletion and hyperoxaluria.
For patients with primary hyperparathyroidism (resorptive hypercalciuria), there is no established medical treatment and surgery (parathyroidectomy) is indicated for optimal treatment.


Dietary Management

The general dietary suggestions for patients with stone disease was described in a previous blog entry (http://bradyurology.blogspot.com/2014/03/classic-manuscripts-in-urology-borghi.html). For patients with hypercalciuria, the recommendations include:
  • High fluid intake (goal urine output > 2L/day)
  • Reduced sodium intake (50 mmol sodium chloride daily)
    • Dietary sodium can influence renal calcium excretion
    • Increase of 100mEq/day of sodium will increase urinary calcium by 50mg/day
    • Excess dietary sodium will overwhelm/attenuate hypocalciuric effect of thiazides
  • Reduced animal protein (52 grams per day) intake
  • Normal calcium (30 mmol per day) intake
A common concern is calcium supplementation in the many patients who take supplements, especially postmenopausal women with concern for bone disease.  In patients with hypercalciuria, calcium supplementation can promote worsening hypercalciuria.  If calcium supplementation is suggested, patients should use Calcium Citrate (Citrical).  Calcium Citrate does not significantly change the urinary saturation of CaOx (calcium oxalate) and CaP (calcium phosphate), the two biggest components of most kidney stones.  Therefore, for stone-formers, a 24-hour urine calcium can identify patients at risk for worsening hypercalciuria before starting Calcium Citrate.  If urinary calcium is elevated, they can begin thiazide treatment – which will help with calcium resorption

 


 


 

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    you can also contact me for more info about Dr Oso faceynancy1@gmail.com

    ReplyDelete
  25. HOW I GOT CURED OF HERPES DISEASE
    I'm here to testify about what DR. OSO did it for me. I have been suffering from (HERPES) disease for the past 5 years and had constant pain,especially inside my body. During the first year, I had faith in God that I would be healed someday. This disease started circulating all over my body and I have been taking treatment from my doctor, few weeks ago I came across a testimony of one lady on the internet testifying about a Man called DR. OSO on how he cured her from herpes disease. And she also gave the email address of this man and advised anybody to contact him for help for any kind of sickness that he would be of help. so I emailed him telling him about my (HERPES) he told me not to worry that i was going to be cured!! Well I never believed it, well after all the procedures and remedies given to me by this man a few weeks later i started experiencing changes all over me as DR. OSO assured me that I will be cured, after some time. I went to my doctor to confirm if I had finally healed Behold, it was TRUE, the test came out negative. So friends my advice is if you have such sickness or any other at all you can contact DR. OSO for help.

    Email} drosohaberhome@gmail.com

    WhatsApp /call +2348162084839

    https://www.facebook.com/drosoherbalhome/

    https://sites.google.com/view/drosohaberhome/

    His blog pagehttps://drosohaberhome.blogspot.com

    you can also email me for more information about DR oso via smithmorgan2777@gmail.com ALL THANK TO DR OSO

    ReplyDelete
  26. People actually believe there is no cure for herpes due to what our medical Doctor's do always say to us..but now i know that there is a cure for it Through herbal remedy' i and my boyfriend was once haven herpes type 1&2 i contacted DR.ODUDU for herbal treatment and he prepared us some herbs which we takes for some couples of days, and we take it as he says before i am to known' i and my boyfriend was perfectly cure for it and never experience the Outbreaks again. please friends if you have herpes virus and you really want to get rid of it permanently, Kindly contact this great DR.ODUDU for herbal treatment and you will get rid of it.. truly truly home remedies works perfectly. EMAIL dr.oduduherbalhome@gmail.com cell phone contact +2348101571054 his whatsapp contact is +2348101571054 https://www.facebook.com/DR.ODUDU

    ReplyDelete
  27. Finally I have been cured from cancer after suffering from the diseases for over 5years with several outbreaks.thank you dr ADAZAL I we to continue sharing your testimony , so others people can be cured too , He also has medicine , HIV , DIABETIC , LUPUS , INFER TILITY , Herpes , and many more which I can't say get cured Email dr.adazalherbalcure@gmail.com whatsapp/Call +2348073688335 Website https://dr-adazal-herbal-cure.jimdosite.com/

    ReplyDelete