NEPHROCALCINOSIS

Nephrocalcinosis means kidneys contain many calcium deposits. You can see them on CT scans or during surgery to remove stones. This article tells about where in kidneys the deposits reside, what they mean, and what significance we need to attach to the word.

Fuller Albright Made Up the Word Nephrocalcinosis

The boyish face of perhaps the greatest 20th century scientist concerned with kidney stones, Fuller Albright, fills the featured picture. In 1934, Albright, then an Assistant Physician at the MGH and an instructor in medicine at Harvard Medical School, used his newly coined word, nephrocalcinosis in a remarkable paper.  That paper described calcium deposits in kidneys of patients with hyperparathyroidism – a mineral disorder caused by enlargement of one or more parathyroid glands.

Who Were His Patients?

He described three types of kidney involvement in primary hyperparathyroidism. Whereas type 1 patients simply formed kidney stones, type 3 patients suffered from acute ‘parathyroid poisoning’, with kidney failure and death. Midway between these two, type 2 patients had stones and kidney tissue calcium deposits but adequate kidney function.

About these Type 2 patients he wrote this passage in which the word first appears (In text box below).

First use of nephrocalcinosisWhat Limitations Did His Patients Impose on His Understanding?    

All of his patients suffered from primary hyperparathyroidism, a disease found in only 5% or so of calcium stone formers we see today in our clinics.

Moreover, the tissues he observed came from autopsies, meaning from only his type 2 and 3 patients. His Type 1 patients, who simply formed kidney stones, rarely came to autopsy, so he did not have tissues from them.

As a result Albright coined the word nephrocalcinosis to describe the scarred, contracted kidneys of patients whose primary hyperparathyroidism had caused kidney disease. Their kidney calcifications were a mixture of those from stone formation and those that occur with kidney failure.

Who Are Our Patients?

Like Albright, some have primary hyperparathyroidism. But none have significant kidney failure. They resemble his Type l patients.

Unlike the patients for whom Albright coined nephrocalcinosis, we mainly study patients whose stones arise from no systemic disease at all. They just form stones we ascribe to excessive amounts of daily calcium or oxalate excretion, or low urine volume or citrate, or to combinations of these – so called idiopathic calcium stone formers.

So physicians today use the word nephrocalcinosis to describe very different patients than those Albright studied when he made the word up.

Who Uses the Word Nephrocalcinosis?

Radiologists

They mean many calcified – radio dense – regions overlay the outlines of the kidneys on various kinds of imaging studies: Simple flat plates, ultrasound studies, and CT scans.

But, as in the Cave of Shadows, radiographs are to the reality of tissue as shadows to real objects.

Many Others

When I looked up nephrocalcinosis in PubMed, I found 2686 entries.

Of these, most concerned diseases that calcify kidney tissues: Medullary sponge kidney, kidney transplant, distal renal tubular acidosis, primary hyperparathyroidism, inherited disorders of the kidney, hyperoxaluria, loop diuretics in neonates, vitamin D and A toxicity, FAM20A mutations – enamel renal syndrome -, claudins, hypomagnesemic states, and hypophosphatasia.

As well, I found an excellent review from which this this article takes its starting point: ‘What is Nephrocalcinosis?’ by professors Shavit, Jaeger, and Unwin.

That review begins with a definition: ‘Strictly, the term ‘nephrocalcinosis’ refers to the generalized deposition of calcium oxalate (CaOx) or calcium phosphate (CaPi) in the kidney.’

But where do they form in kidneys, and what do they signify?

Where Kidney Crystals Form

Cortex, Medulla, and Papilla

nephron-somso2

This stock web drawing depicts a slice through a kidney. The outer capsule runs along the top.

The cortex occupies the upper 1/3 of the kidney slice, above the crescent of red and blue vessels. In it are the filtering units that begin the nephron, the glomerulae, shown as round balls.

Below that crescent of vessels lies the medulla.

At the very bottom of the medulla lies the rounded papillum where urine drains into the renal pelvis and thence down the ureter. Urine exits through the terminal collecting ducts of Bellini – the opening of the thick long tube that runs vertically from cortex to the bottom.

Glomerulae

Each contains a tuft of capillary held within a complex web of cells. The force of the heart filters water and salts out of the capillaries into the tubule of the nephrons. Normal human kidneys contain about one million nephron units. Common measurements of ‘kidney function’ such as serum creatinine reflect the sum total of filtration through all  two million glomerulae. Obstruction from stones can reduce filtration.

Nephron Segments

Proximal Convoluted tubules

Each glomerulus drains its filtrate into a squiggly – convoluted – ‘proximal’ tubule which gives way into the remaining nephron. These tubules reabsorb much of the filtered water and salt back into the blood. They leave behind materials destined for export into the final urine.

Proximal Straight Tubules

Mislabeled thick descending limbs on the drawing, a part of the proximal tubule extends below the arc of vessels into the medulla and is called the S3 segment. I mention it only because crystals form there sometimes.

Loops of Henle

As they travels downward below the proximal convoluted tubule each nephron thins into a hairpin shaped loop. Those hairpin loops of glomerulae that lie near the outside of the kidney (look at the nephron to the left) reach down only part ways into the medulla – the portion of the kidney below the red crescent of vessels. By contrast, loops from glomerulae near the medulla – just above the crescent of vessels – reach down into the deepest parts of the medulla.

These hairpin loops permit kidneys to concentrate the urine, which means extracting water from the filtrate and putting that water back into the blood. Unlike the proximal convoluted tubules that reabsorb water and salts back into the blood the loops permit reabsorption of water without the salts, so the salts destined for export are concentrated.

Names for the Segments of the Loops

As already mentioned, the ‘Thick Descending Limb‘ is actually the S3 segment of the proximal tubule.

It gives way to the descending and ascending thin limbs of the hairpin. The top of the thin ascending limb widens into the ascending thick limb. This segment reabsorbs sodium chloride back into the blood without water, leaving the ‘extra’ water – without its sodium – as a diluted fluid in its lumen. The sodium chloride collects in the medulla around these thick limbs which becomes saltier than blood.

So called Randall’s plaque, over which calcium oxalate stones may form, originates in the outer parts of the thin limbs,

Distal Convoluted Tubule

The dilute fluid drains into the ‘Distal’ convoluted tubule’. Here, the ‘extra’ water leaves, back into the blood. This segment can make the fluid more acidic, and remove calcium back into the blood.

Collecting Ducts

From there, fluid drains through the unmarked straight connecting segment and thence into the collecting ducts. Like any plumbing drains, these run from the cortex down the medulla all the way to the papilla where the final urine flows out. Along the collecting duct the ‘salty’ interstitium around the thick ascending limbs draws water – but not calcium or phosphate or oxalate back into the blood, supersaturating the fluid that remains in the tubule. Collecting duct cells make the fluid more acid, a protection against calcium phosphate crystals.

We name the portion of the collecting ducts that run alongside the medullary thick ascending limbs the outer, and the remainder the inner medullary collecting ducts.

Ducts of Bellini 

These terminate the nephron and empty the final urine into the urinary collecting system through tiny holes in the lining of the papillary tip. Because they hold the final, most supersaturated urine, crystals often form in them, creating plugs over which stones form.

Where is the Interstitium?

Envision a tall building. Pipes run from the basement to the roof – water, steam, drains, electrical conduits, elevator shafts, stairwells. Now, think about the space between the elevator shafts, stairwells, and all the pipes and conduits: That is the interstitium, what stands between.

In the kidney the long structures are the tubules and vessels; the interstitium is the space between them. That is where plaque is. There are cells in the interstitium – it is as though, as an example, insulation blocks were stuffed into the spaces between pipes.

Mice can live in the spaces between things, but not in the pipes. Rust can plug pipes but not the spaces between them.

The Reward for Brave Hearts

To those who have read the foregoing: My regards and admiration. Like tourists who climb the ancient, winding, broken stairs up into the towers of medieval cathedrals or the battlements of long abandoned castles, panting and worried about getting back down, you now come into the reward of so much virtue and endurance. Before you lies the architecture of the nephron.

Where the Crystals Form

From what I have told you, where would you surmise crystals might form?

Surely not, you might say, in the glomerulae or proximal tubules, or in the thick ascending limbs with their excess of water. The distal tubules, perhaps, as they extract water, but – you might think – it is only the extra water.

Ah! That vast long drain, where water extraction supersaturates urine – there would crystals form.

And, those uncanny thin limbs, so deep into the medulla.

You are right.

Who Sees Them?

When radiologists spy calcium deposits in kidneys so numerous they name them nephrocalcinosis, the deposits lie – with rare exceptions – in the medulla, the papillum. Surgeons can see them in the collecting ducts and interstitium. For pathologists they lie in the thin limbs, the collecting ducts, and the interstitium – the space between the ducts.

Crystal Deposits in the Cortex

These occur in rare stone diseases. I list them for completeness only.

Glomeruli

In humans, high blood calcium can produce glomerular crystals. Hyperparathyroidism for example, when severe.

Shall I mention  intravenous dibasic phosphate in rats, Vitamin D intoxication in suckling ratscalcifications of large immune deposits? No; I demur. Not relevant to humans.

Proximal tubules

We have found calcium oxalate crystals in the proximal tubule S3 segment in primary hyperoxaluria. 2,8 dihydroxyadanine crystals due to APRT deficiency can plug proximal tubules. In transplanted kidneys we have seen scattered birefringent crystals presumably calcium oxalate.

In other words, common stone formers have no proximal tubule calcifications, only patients with rare diseases.

Distal Convoluted Tubules and Cortical Collecting ducts.

Acute phosphate nephropathy from bowel preparation is well known. Distal convoluted tubules contain calcium phosphate deposits in cystine and primary hyperparathyroid patients,and calcium oxalate in primary hyperoxaluria stone formers. In transplanted kidneys tubule and interstitial deposits are found not rarely and are said to be calcium phosphate. In primary hyperparathyroidism with stones, and ileostomy patients, deposits were found in the cortical collecting ducts.

This means, here and there, uncommonly, scattered deposits can lie in the cortex.

Cortical Interstitium

When kidneys fail and blood accumulates excesses of salts and molecules kidneys normally eliminate, crystals form in the space between tubules, the interstitium because blood itself supersaturates. The same for primary hyperoxaluria: so much oxalate is produced it can accumulate in blood and crystallize in the interstitium.

Cortical Blood Vessels?

We believe it is potentially confusing to lump vascular disease and its associated calcifications together with calcifications within the renal tubules and interstitium.

Crystal Deposits in the Medulla and Papilla – Work by Us

Our reports comprises the bulk of human kidney tissue work to date.

Thick ascending limbs

No deposits have been found in any stone formers to date.

Thin Loops of Henle

We have found rare hydroxyapatite deposits plugging thin limbs in ileostomy, cystinuria and primary hyperoxaluria patients with reduced renal function. These are best illustrated in Figure 4 of the ileostomy reference. As I have mentioned, plaque begins in the outer shells of the thin limbs.

Outer Medullary Collecting Ducts

Patients with primary hyperparathyroidism are the only stone formers who show deposits (calcium phosphate) plugging this tubular segment.

Inner Medullary Collecting Ducts

Here is the main place for crystal formation. Are you surprised? The tubule contains supersaturated fluid progressively approximating urine itself. No wonder of it: crystals from where supersaturation is.

Hydroxyapatite crystal plugs

Crystal intraluminal plugs have been found in all eleven stone forming phenotypes examined. The majority of these plugs are composed of hydroxyapatite. Note the link goes to an article on this site which lists 10 phenotypes; ICSF, the 11th phenotype, did not reveal collecting duct deposits in our work but deposits of HA were found in cases of ICSF reported by Wang et al

Calcium oxalate crystal plugs

Obesity bypass surgery, distal renal tubular acidosis, small bowel resection, and medullary sponge kidney stone patients form calcium oxalate deposits.

Mixture of sodium acid urate and ammonium acid urate was admixed with biological apatite in ileostomy stone formers.

The Odd Microliths of MSK

Microliths, myriads of extremely small, round, non-adherent stones have been found only in the dilated IMCD of MSK patients. These differ from plugs in virtually all respects. Plugs adhere to IMCD lining cells and cause cell damage, and death, MSK microliths do not adhere nor cause any perceptible damage. Microliths are round, not cylindrical, and made up of concentric layers of crystal; plugs also have layers but much less regular.

Cystine Plugs

Cystine plugs also differ from all other plugs in not adhering to tubule cells. They move freely and do not appear to damage the cells.

Ducts of Bellini

We have found Bellini duct crystal plugs in all stone forming phenotypes.

This is expected as these ducts contain the final urine.

Bellini duct plugs may attract overgrowths at their distal ends that protrude through a dilated opening of the duct into the flowing final urine. These proto stones may well grow to clinically significant size. Growth on plugs is one pathway for stone production.

Interstitium

To date, all interstitial deposits found in human kidneys have been hydroxyapatite ‘Randall’s’ plaque. Growth of stones over plaque is another pathway for stone production.

What About Blood Vessels?

No evidence exists showing calcium deposits within the vasa recta within the medulla or papilla. Deposits of hydroxyapatite can be found within and involving capillaries, but this is not evidence of a primary calcification. Theoretical papers proposing vascular injury and calcification as causes of plaque have failed to advance direct evidence in support of the theory.

Crystal Deposits in the Medulla and Papilla – Work by Others

Idiopathic calcium oxalate stone formers

Idiopathic calcium oxalate stone formers display variable amounts of interstitial plaque. Those with hypercalciuria had the heavier plaque deposits, much as we have found. Unlike our work, many patients had crystal plugs in Bellini ducts. Wang et al described much the same.

In biopsy tissue from 15 patients with ‘idiopathic calcium stones’ not otherwise characterized, Khan et al found Large areas of interstitial plaque. Crystals were HA. No plugging was found. Stones were calcium oxalate. The main finding was intimate association of plaque with collagen, as we have also described.

Mixtures of stone formers

Linnes et al studied ICSF, ICSF with malabsorption, phosphate stone formers which included struvite stones, and, also, uric acid stone formers. In 99% of patients they found interstitial plaque with an average low abundance. It was only when they separated out hypercalciuric ICSF that they found high plaque abundances as we have. They found plugging in all stone phenotypes. The patients were mostly female, and hypercalciuria was not impressive. They did not analyse the crystals in the plugs.

Single case report

Report of a single case describes interstitial plaque deposits identical to those we have described. The patient had large calcium oxalate staghorn stones. By EDX analysis the interstitial deposits were calcium phosphate. Tubule plugs were found in the medullary collecting ducts and these were calcium oxalate. We suspect this patient had primary hyperoxaluria.

Putting it All Together

Overall, these and our papers more or less agree. Stone former kidneys contain interstitial calcium phosphate deposits and plugs in Bellini duct and inner medullary collecting ducts. Only we and Khan have described the crystals in plugs to date. So, when we speak of multiple crystal deposits in the kidneys of stone formers, or nephrocalcinosis, we all seem to mean plaque and plugs. MSK differs altogether, because dilated ducts contain myriads of calcium oxalate microliths.

Virtually all Stone Formers Manifest Nephrocalcinosis

Virtually all Stone Formers Form Kidney Crystal Deposits

Shavit, Jaeger, and Unwin concur with Albright: ‘Strictly, the term ‘nephrocalcinosis’ refers to the generalized deposition of calcium oxalate (CaOx) or calcium phosphate (CaPi) in the kidney.’ Since virtually all stone formers deposit crystals in their kidney tissues, virtually all have nephrocalcinosis.

The Kinds of Deposits Number Three

One kind is plaque – calcium phosphate as hydroxyapatite – in the interstitium.

The second kind is plugging of the lumens of the various tubule segments, mainly the medullary and papillary collecting ducts. These plugs are usually calcium phosphate but can be calcium oxalate, cystine, or uric acid salts.

Of the three, the microliths of MSK, unique to this one disease, make up the third.

The Word Means Plaque and Plugs, or MSK

In any one patient nephrocalcinosis means interstitial calcium phosphate crystals, tubule crystal plugs of diverse kinds, or both, and microliths in the dilated tubules of MSK.

Because of this specificity, I propose we restrict the word to this exact meaning: Calcifications within kidney tissues as demonstrated directly in the tissues themselves.

Radiographic Nephrocalcinosis

Because tissue calcifications and stones both brighten the confining shadows of the radiologist with similar points of light but stones do, also. Therefore, we propose the term ‘radiographic nephrocalcinosis’ define what radiologists report. I say this because radiological means cannot always distinguish masses of tissue plugs or of microliths in MSK from stones.

Surgery

Because they visualize stones, plaque, and plugging, and also the odd contours of MSK, surgeons can not only specify nephrocalcinosis but the type of calcium deposit. Therefore, they mean by nephrocalcinosis what pathologists mean. The only difference between them is in resolution. One has a microscope, the other simply an external view of the kidneys at modest magnification.

Meaning of Nephrocalcinosis

Since all stone forming patients deposit calcium in their kidney tissues, it signifies a quantitative vs. a qualitative distinction. Unlike other patients, those with nephrocalcinosis have more tissue calcium deposits and therefore, perhaps, what one might call more disease burden.

By disease burden I mean the tissues carry more crystals in them, and therefore a greater hazard from whatever evil it is that crystals might do.

One such evil: lodgment for new stones to form on. Because stones form on plaque and the ends of plugs, more plaque and more plugs implies a greater stone production potential. Although evidence for such potential must come, eventually, from prospective observations greater tissue mineral burden seems a proper spur to greater treatment effort even now. Such greater treatment efforts mean perhaps more emphasis to patients about diet and fluid change, and earlier use of medications.

Another is tissue damage. For example, crystal plugs cause obvious tubule cell loss and inflammation in the surrounding interstitium. Although papillary, plugging may affect the cortex. Compared to patients without plugging, those with plugging have more cortical interstitial scarring that treatment might benefit. Such treatment, as opposed to stone prevention alone, would specially emphasize reduction of calcium phosphate supersaturation.

Like many stones, nephrocalcinosis quantifies stone diseases. But in a new dimension, one that complements those already in use. Because complementary, the word adds specific value, provided we use it carefully.

130 Responses to “NEPHROCALCINOSIS”

  1. Jonie C Vogt

    I have had no less than 26 stones and all unpassable. I’ve had lithotripsy half a dozen times and my urethra is wore out from stents. I recently started urinating blood and went to the ER and they told me my kidneys are turning to stone. That’s all. I have a cup of stones I’ve passed and most look like elbow macaroni. I just want to know if im going to die.

    Reply
  2. Christine Dammen

    Four years ago I had an eGFR of 12 and a biopsy showing calcium oxalate nephrocalcinosis with focal acute tubular injury (consistent with an oxalate cast nephropathy); arterioschlerosis, focal & moderate. My diagnosis was hyperoxaluria. Since then, I have progressed to Stage III. I avoid all high oxalate foods and most moderate ones as well. I eat about 4 oz. of fish or fowl per day, have a diary product with every meal, drink 2.5L of water daily, avoid processed foods, sugar, caffeine, and salt (other than what naturally occurs in the meat and dairy that I eat). I take 10 meq of potassium citrate, 100 mg B6, and 2000 IU D3 (for osteopenia). I’ve been tested for the hereditary forms of hyperoxaluria, and do not have these. I would love to know more about why I became ill and how to prevent its recurrence. I continue to have small stones and periodic flank pain, but I’ve never knowingly passed a stone. My 24 hr. citrate is 223 mg/24 hour for a volume of 3650 ML. Potassium is 95 mmol (17-77). PH is 6.4 (4.5-8.0). Creatinine is very good at 1095 mg/24 h. I am undersaturated for all crystals except hydroxyapatite, and I’m below the mean for that. So, I think I should feel really good about this. Right? Do I need to be concerned with the hypocitraturia? What about low blood sodium, 127 meq/L, and chloride, 95 meq/L? Low RBC, 3.62 million/uL; hematocrit, 32.8%; and hemoglobin, 11.2 G/DL (even though I take an iron daily); a recent unexplained loss of consciousness accompanied by dehydration (despite drinking 2.5L daily); pre diabetes; elevated PTH 81 PG/ML, and hypothyroidism. I am willing to do the work of leading a healthy life. I’m just confused as to what I should do next, or if I need to do anything. I don’t have loose bowels leading to the hypocitraturia. I don’t have a high protein diet (unless I need to further reduce my protein to account for the milk products I consume). My serum CO2 is normal and my doctor says I have secondary, not primary, hyperparathyroidism, and he has not suggested I do anything about that. I’m not taking any of the listed medications that can cause hypocitraturia. Finally, thank you for the incredible gift of your mind on these pages. I cannot imagine all the people–patients and professionalx–you have helped. What a wonderful gift to the world!

    Reply
    • Fredric Coe, MD

      Hi Christine, You do not mention your urine oxalate. Was it ever high?? Oxalate crystals in a renal biopsy arise in hyperoxaluric people, so you must have had a high urine oxalate excretion. What was the level, what is it now. The other findings are of no interest by comparison. The low serum sodium may be from high water intake with advanced kidney disease, the other findings seem commonplace for kidney disease as well. Please let me know. Regards, Fred Coe

      Reply
  3. Betsy

    Hi Dr. Coe,
    I am 42 years old and have recently been diagnosed with nephrocalcinosis on both kidneys using a CT scan with contrast. I had a surgery for a kidney stone when I was 22 but never had any stone attacks since until recently. A 24 hour urine test by Lithiolink showed the following:
    Low urine volume, Hypercalciuria, borderline hypocytraturia, moderate CaOx stone risk, moderate CaP stone risk.
    In addition, my blood pressure has increased slightly and I am having a pain on my left side. I recently had a hysterectomy and my physician did not “see” anything unusual causing the pain on my left side . I have since had two more scans without contrast, finding nothing but diverticulosis. I am assuming the pain might be the kidney condition??? Also, my vision was changed since my surgery, but no doctor seems to think it was related to the surgery. Could it be kidney related? My doctor wants me to start hydrochlorothiazide but I have no idea what to eat and how to manage so many different things. I am also sensitive to dairy and gluten and try to avoid it. What should I eat and should I take this medication?

    Reply
    • Fredric Coe, MD

      Hi Betsy, Prevention of more stones and kidney calcifications is a complete program. Take a look at my favorite article on how to proceed. The kidney stone diet is critical. Meds are uses when the diet proves inadequate. Dairy products are various and you will not be sensitive to them all – supplements are a last resort, I rarely need to use them. As for your blood pressure, here is what I have to say about it. The kidney stone diet is ideal for lowering blood pressure. Regards, Fred Coe

      Reply
  4. Joyce

    Hi again, Dr. Coe!

    I have written before regarding my nephrocalcinosis, after a high protein diet. They had me on Potassium Citrate for a year (and I also had a pregnancy during that time), but recently the doctor I saw at U of Michigan, Dr Adil Jadoon, took me off of the Potassium Citrate, as based on my urine results (very high pH, but extremely low supersaturations across the board), he didn’t think I needed it.

    I recently had my first blood work since stopping it 3 months ago. A few things are concerning to me. First of all, my blood Potassium is 4.9, which is higher than it’s ever been. Secondly, my BUN , while still within the reference range, is 19, also the highest it has ever been (previous numbers from 2010 until now are 7, 11, 8, 14, 12, 7, 12, 19). My creatinine is normal at 0.74. The only other thing of concern is maybe Alkaline Phosphatase, at 102, mildly high.

    Things to note: I am breastfeeding. I typically take in about a gallon of water a day, but the blood work was done when I had not yet drank water for the day and it was done around 11 am. I am on a low salt diet.

    Also to note- after my most recent urine test showed very low supersaturations if anything stone-forming, and a high pH, my original urologist suggested increasing potassium citrate because the oxalate was slightly high at 49. For a second opinion, I went back to u of M neprhology, where Dr. Jadoon completely disagreed and thought I should not be on it at all, as my supersaturations were low and urine pH was 7.3.

    My concerns are as follows:

    I am only 31 years old, and in good health. I’ve always exercised, eaten quite healthy, and maintained a normal weight, etc. I am worried that the doctors are not putting much effort into my care, as my situation doesn’t seem “that bad”. I want to be confident in my health care plan and know that I am preventing further kidney damage from developing.

    As a recap, my history is that of a few isolated kidney stones during pregnancies. I drank very little water. Then an extreme high protein diet for 9 months or so led to rapid nephrocalcinosis bilaterally, which they assume was a result of the protein. I have no fam history of stones.

    Let me know if you need any more info. I highly respect you and your knowledge on this disease, and appreciate your help so much!

    Reply
    • Fredric Coe, MD

      Hi Joyce, while breast feeding, 24 your testing can be misleading and therefore futile. Urine calcium falls because of the demands for milk calcium, so there is no sense in doing the test. High fluids are a good thing, and right now you seem to have little risk. Just high protein to convert a few scattered stones into nephrocalcinosis – how unusual! Perhaps. I would finish breast feeding, and then do another 24 hour urine; obviously with a high urine pH and lots of fluid the potassium citrate cannot do much for you and could be stopped – of course I am saying this based only a few fragments of your total situation. Regards, Fred Coe

      Reply
      • Joyce

        Thank you so much. No one mentioned to me the effect of breastfeeding on 24 h tribe calcium. That is good to know. I will see my doctor after I finish breastfeeding. Thanks so much for your input and knowledge.

        Reply

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