The Diagnostic Dilemma of Medullary Sponge Kidney

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Diagnosis of MSK is Increasing

Urologists and nephrologists specializing in the treatment of kidney stones seem to encounter patients with medullary sponge kidney (MSK) far more often than one would predict given the fact that this disease affects less than 0.5-1% of the general population.

One potential explanation is the high frequency of stones in such patients, nearly 70%. Stones call attention to themselves. Even so, referrals for MSK seem to be occurring at ever increasing rates, out of proportion to the prevalence of the disease.

Another explanation is that we can see more because of dramatic improvements in CT scanners and endoscopic equipment we use for stone removal.

Latest generation, thin slice CT scans can isolate tiny stones as small as a millimeter in size.  Meanwhile, modern flexible endoscopes not only visualize every crevice of the renal collecting system but are able to do so in high definition. Consequently we can identify previously unrecognized variations in the appearance of stone forming kidneys, of particular interest here nephrocalcinosis on CT and tubular plugging on endoscopy.

But diagnostic capabilities may be progressing faster than our ability to comprehend the significance of what we see. As a result, one can misclassify patients as having MSK when the correct diagnosis is another more common finding such as nephrocalcinosis or tubule plugging.

For example, a urological surgeon performing ureteroscopy with a modern high resolution digital instrument notices “hundreds of tiny stones,”, “abnormal papillary architecture” or “stones located under the urothelium” and proceeds to label the patient with MSK. Or, a patient with urologic symptoms such as renal colic, recurrent urinary tract infections, or microhematuria has a CT scan showing ‘nephrocalcinosis’ and is labeled as having MSK.

In both instances, the true likelihood of actually having MSK is, by a recent small study, only 4/15 (25%), but physicians are not generally aware of the differences between MSK, nephrocalcinosis, and tubule plugging because these are new areas of knowledge which have not been proliferated widely.

This article is one way we hope to make the diagnosis of MSK, a unique and complex disorder of renal development, clearer for physicians and their patients.

What Is MSK?

Our collective understanding regarding the development and pathophysiology of MSK is rather sparse even though G. Lenarduzzi first described it in 1939.

The Cause of MSK

The exact mechanisms that produce MSK are unknown. It is believed to be a result of abnormal renal development in utero. More specifically, scientists believe the ureteric bud – which will give rise to the ureters – interacts abnormally with the metanephric blastema tissue in the embryo which will produce much of the kidney substance.

There appears to be a genetic component to the disease. Recent evidence is that about half of patients diagnosed with MSK will have at least one relative with some degree of similar affliction. This kind of familial clustering can suggest an autosomal dominant gene expression or the actions of multiple genes giving that impression. The review of the above link is an excellent recent treatment of the matter of development and genetics which we highly recommend.

The Anatomy of MSK

MSK, as its name implies, is characterized by sponge like, cavitary regions within one or both kidneys (Figure 1).

 

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Figure 1 – A normal appearing kidney (left) compared to MSK kidney (right).

More specifically, the dilations occur in the inner medullary (precalyceal) collecting ducts. These collecting ducts are the terminal region of the nephrons, the individual functional units of the kidney.The inner medullary collecting ducts (IMCD) have the job of delivering urine to progressively larger ducts (ducts of Bellini) that deliver the final urine out of the renal papilla into the minor calyces (Figure 2) which connect into the renal pelvis and thence into the ureter to the bladder.

Renal Anatomy copy

One way to think of the IMCD is as a collection of streams merging and forming a river (duct of Bellini) which leads to a delta (minor calyx) and then a lake (major calyx) and ultimately an ocean (renal pelvis) (Figure 2).

Figure 2 – Anatomic depiction of kidney and collecting system

The IMCDs are not visualized in Figure 2 but if you scan down to Figure 3 just below several human nephrons which were microdissected from an MSK kidney show what is really wrong with them.

In MSK, some IMCD are dilated markedly and have outpouchings (cysts): blind sacs which begin at the IMCD lumen but go nowhere – like a hallway someone walled off at one end. It is at the ends of these hallways one finds the stones, free floating and probably trouble. Other IMCD are not dilated and do not have cystic outpouchings.

MSK NephronFigure 3 Microdissection of complete nephrons from MSK. Irregular dilation of the IMCD is present. Cystic outpouchings are present, of varying sizes. The blind ends are obvious. It is in these cysts that tiny stones are found.

Quite apart from the IMCD dilatation and cysts, the kidneys of MSK have two other abnormalities which mark it as a specific disease. Those IMCD which are not dilated nor cystic have a multilayered epithelial lining, whereas a normal undilated IMCD lining is one cell layer thick. The interstitial cells of the renal papillum – the cells between the tubules and vessels – are more numerous than in normal kidneys, and have an immature appearance much like is seen in fetal kidneys.

Why Stones Form in MSK

Elsewhere on this site we have pointed out that supersaturation is a force, a source of energy directed at forming solid phases such as stone crystals. The kinetic retardants in urine, which include citrate, stave off crystallization but can never prevent it: A supersaturated solution will eventually collapse into two phases, crystals and a residual solution precisely at the solubility point, devoid of extra free energy.

The stagnant flow as a result of the dilated MSK IMCD, and particularly the static conditions in the fluid filled blind ended cysts, are the probable reason those innumerable tiny stones form which end up packing the ‘sponges’ with masses of crystals. How MSK patients produce larger stones, big enough to block the ureter is unknown. It is not true that MSK patients have remarkably high urine supersaturations or other physiologic abnormalities such as hypercalciuria and hypocitraturia. Possibly the tiny stones somehow leave their cysts and enter the urine where they act as nucleation centers. 

Other Associations

Other common associations with MSK include urinary tract infection, microscopic and gross hematuria, and impaired renal function. Perhaps the stagnant flow in dilated IMCD and particularly in cysts, predisposes to infection. But since the papillae are abnormal in other ways it seems likely that these intrinsic abnormalities themselves must be clinically important, and more work needs to be done on the problem. 

Making the Diagnosis of MSK

Of course, when we speak of what is wrong in the MSK kidneys, and how it affects people, we base everything on knowing that a given patient has MSK. If you have a kidney from such a patient and can show the dilated IMCD, the cysts, the tri-layered IMCD epithelium, and abnormal interstitial cells, diagnosis is certain. But what can we do when we are dealing with a patient?

Radiological Studies

Intravenous Urography

Historically, the diagnosis of MSK has been made on intravenous urography (IVU). Radiographic contrast is administered and x-rays of the kidneys, ureter, and bladder are taken periodically as the contrast is absorbed and later excreted by the kidneys through the urinary tract.

The delayed phase image is essential for diagnosis. This is when contrast material fills the masses of dilated IMCD and cysts which make up the sponge.

The masses of dilated IMCD filled with contrast material produce a characteristic ‘papillary blush’ which appears like flames on the outer edges of the papillae. When particularly large it can mimic a bouquet of flowers peripheral to the collecting system.

IVP Medullary Sponge

Figure  4 – IVU image of medullary sponge kidney. The arrow designates the papillary blush in the mass of dilated IMCD space.

CT Scans and Other Imaging

Over the past 10-15 years, noncontrast CT scans have replaced IVU as the imaging method of choice for stone formers. While these scans are more sensitive in detecting small stones, the lack of contrast limits the ability to accurately diagnose MSK and has raised concerns regarding the potential for under-diagnosis of this disease.

CT does have the capability of making this diagnosis when contrast is given and CT urography is performed; though this is not used as a first line choice for stone imaging and is generally reserved for specific indications such as hematuria and concern for urinary tract injuries.

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Figure 5 – Demonstration of papillary blush (small arrows) on CT urography for patient with medullary sponge kidney.

Use of other imaging modalities have been investigated as well though they have proven suboptimal in their diagnostic capabilities. Ultrasound has poor sensitivity to detect dilation of the collecting ducts and MRI has the potential to delineate detailed renal anatomy but can not detect stones or calcification.

High Definition Endoscopy

State of the art high definition endoscopes have allowed investigators to make observations at the time of renal endoscopy correlating the appearance of the renal papillae and collecting system to specific types of diseases and metabolic derangements associated with stone formation. Because endoscopy is now being performed as a common and often preferred way to manage stones, this kind of detailed imaging of kidneys will be available more and more in the course of regular patient care and permit physicians to diagnose the exact kinds of disorders in the kidneys of stone formers. 

Medullary sponge kidney in particular has an entirely unique appearance unlike any other type of stone related disease, making endoscopy a particularly exacting diagnostic procedure. Detailed anatomic descriptions from twelve such patients each with evidence of MSK on biopsy were recently described by Evan et al.

The Papillary Malformations Seen Via Endoscopy

In stone formers the papillae often appear abnormal, a concept that merits its own post and which we can only briefly summarize here.

Plaque

The renal Screen Shot 2015-06-11 at 9.37.45 PMpapilla is the anatomic subunit of the kidney where the IMCD merge together into the terminal Bellini ducts which empty into the minor calyx. Normally, it should have the appearance of a smooth walled mound or mountain without much if any calcification (plaque) along its surface. The link is to a detailed post about plaque by Dr Andrew Evan.

Figure 6 – Healthy appearing renal papilla with a minimal amount of Randall’s plaque (arrowhead).

Ductal Plugging

Another common abnormality identified in many papillae at the time of endoscopy are plugged ducts. The physiologic mechanisms for this process are currently unclear; Screen Shot 2015-06-07 at 9.48.55 PMhowever, we believe it is a reflection of injury that begins a potentially disastrous chain of events for stone formers.

Figure 7 – Abnormal papilla in a patient with severe ductal plugging. Yellow mineral deposits (arrows) can be seen protruding from dilated ducts of Bellini.

Our present assumptions are that once crystals begin to form within a duct, they damage the lining cells and the duct loses its ability to make acidic urine. This in turn raises the local pH level and leads to the growth of more calcium phosphate mineral deposits which are favored by high pH.

Unclear is what begins this process. Since these ducts contain fluid which is very close in composition to the final urine, we suspect it is high supersaturation with respect to calcium phosphate. This occurs in those patients with both high urine calcium excretions (hypercalciuria) and higher urine pH levels – above 6.2. Such patients often form stones high in calcium phosphate composition and plugging is strongly associated with formation of such stones.

The mineral deposits subsequently grow and we believe can even act as a nidus for stone formation. The corresponding papillae can look markedly abnormal and the dilated ducts are easily evident. Remnant dilated ducts left behind after the mineral is spit out or surgically removed (Figure 8) show dilation without the mineral plug.

Screen Shot 2015-06-07 at 9.48.20 PMFigure 8 – Evidence of abnormally dilated ducts (arrowheads) at the surface of a papilla.

MSK

The findings in MSK are comparable in some ways to ductal plugging; however, rather than the papillae having one or several abnormally dilated ducts, the entirety of the papillum is markedly abnormal.

Therefore MSK and plugging type papillae look remarkably different.

The MSK papillae are excessively round, enlarged, and billowy (Figure 9). 

MSK two plot from our MSSFigure 9 – A papillum in a patient with medullary sponge kidney. The papillae are rounded and enlarged with a billowy appearance. The papillary tips are blunted. No other kind of papillary disease is known to present this appearance which is therefore pathognomonic of MSK. Panel a shows dilated Bellini duct openings at asterisk; the arrows show yellow plaque – plugging of IMCD completely separate from the stones which fill dilated IMCD, the arrowheads show traces of white plaque. Panel b shows the billowy papillum with a blunted tip surrounded by calyceal stones.

In the majority of such cases, these changes are seen diffusely throughout each kidney, though segmental sponge findings are present in a minority of patients.

The differences in appearance are well demonstrated in the post by Dr. Evan and the following video.  With ductal plugging the bulk architecture of the papilla is intact though many ductal plugs are seen.  Note the way the ductal plugs are adherent to the lumen.

In MSK on the other hand, the papillary architecture has and unique, billowy appearance with massively dilated ducts and freely mobile stones within them.  The following video is from a patient with MSK.  A duct of Bellini is massively dilated and numerous tiny stones which are free floating pass out of it during the visualization as the opening is enlarged with a laser. You can see stones bouncing within the duct because of movement of the irrigation fluid.

Clearly neither papillum is “normal” and one can imagine the tendency to misdiagnose a plugging patient as a MSK patient unless the two patterns are clearly in one’s mind.

The ductal deposits themselves are an important clue. In all plugging diseases but cystinuria ductal mineral plugs are fixed within the ducts because the crystals adhere to the lining cells and often destroy them. As the lining cells are destroyed crystals fix themselves to the basement membranes, the collagen shell on which the lining cells once grew. Inflammation follows such injury with scarring and loss of the tubule segments. Deposits therefore never float free from a dilated duct except in cystinuria and in MSK. Cystinuria is usually diagnosed directly from stone analysis and urine cystine screening.

Perhaps because the tiny stones in MSK do not attach to the epithelium of IMCD there is no evidence of cell injury or inflammation, in marked contrast to all of the plugging diseases. Even in cystinuria injury occurs, not from the free floating distal cystine plugs but from calcium phosphate plugs which form in the IMCD.

Stones may cause pain in MSK despite the lack of ureteral obstruction and inflammation and cell injury. Possibly distention of the dilated ducts by masses of tiny stones could be a factor. Consequently, laser unroofing has been postulated as a potential treatment option in both disease states: those with plugging and MSK.

The video may not make it easy for everyone to visualize the stones and cavities of MSK. The 4 still pictures below show much the same thing for clarity.

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Figure 10 (a-d) – Example of laser unroofing of sponge cavity full of freely floating stones. The massively dilated MSK bellini ducts are seen in Panel a; the white speckles at 9 o’clock are tiny stones in dilated IMCD or cysts. Panel b shows a holmium laser fiber being used to open dilated IMCD or cysts.  Panel c shows masses of tiny stones free in dilated IMCD or cysts which float out as the surface is incised with the laser. In panel d, the remnant sponge cavity can be seen now free of stones.

Nephrocalcinosis and MSK

Strictly speaking, nephrocalcinosis refers to the presence of calcium deposits in the kidney tissue. Of course, this includes ductal plugging and the masses of tiny micro – stones inside cavities produced by numerous dilated IMCD in MSK. However, the word ‘nephrocalcinosis’ is also used as a radiological diagnosis which is far less specific.

Limitations of Radiology

When radiologists speak of nephrocalcinosis they can mean large numbers of calcifications within the collecting system or kidney tissue, because they cannot differentiate reliably between tissue calcifications and stones. When urologists speak of nephrocalcinosis seen during high resolution endoscopy they can specify if it refers to tissue calcifications, stones, or both, and will reserve the term for that component arising from tissue calcifications.

MSK is one of several disease states that is commonly associated with extensive nephrocalcinosis observed by radiologists. Other common conditions are stones caused by renal tubular acidosis and primary hyperparathyroidism. Calcium phosphate stone formers without any systemic disease can also produce sufficient combinations of ductal plugging and stones that nephrocalcinosis is diagnosed radiologically.

In a recent study of 67 idiopathic calcium stone forming patients undergoing percutaneous nephrolithotomy, rates of nephrocalcinosis ranged from 18-71% depending on the type of associated stone.

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Figure 11– X-ray example of patient with MSK affecting the left kidney. Extensive nephrocalcinosis is seen.

Because radiographs cannot reliably distinguish tissue calcifications from stones adjacent to tissues, the very word ‘nephrocalcinosis’ needs to be re-defined. 

In particular, the situation with respect to diagnosis of MSK has worsened as radiological techniques have changes. When IVU was the first line imaging modality for stones, contrast enhanced urographic phase imaging gave additional clues to MSK – the papillary blush illustrated in a prior section.

Nowadays since a single non-contrast CT series is all that is typically performed, the papillary blush effect cannot be seen, and diagnosis of MSK must rely more on the presence and pattern of nephrocalcinosis itself, which is not very specific to MSK. This means that the diagnosis of MSK by radiology has become unreliable.

The Power of Endoscopy

Differentiation of Nephrocalcinosis from Stones

During endoscopic procedures, stones and tissue calcifications can be directly identified and told apart. For example, in the images below, some of the calcifications were identified as stones. Others were tissue calcium deposits such as plugging or extensive plaque.

This has led to the notion that kidneys should only be labeled as having nephrocalcinosis once confirmed visually on endoscopy.

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Figure 12 (A-C) – Evidence of increasing degrees of nephrocalcinosis confirmed visually at the time of percutaneous nephrolithotomy. In each image a nephrostomy tube (not calcification) is depicted by an arrow. The remainder of the images have increasing degrees of calcification (bright white) within the kidney. Ignoring the nephrostomy tube, one can clearly appreciate a minimal but very present degree of accessory brightness (calcification) in panel A, a moderate amount in panel B and a severe amount in panel C.

Diagnosis of MSK

Of course, all of the problems of nephrocalcinosis are compounded when it comes to MSK. Stones and tissue mineral are easily mistaken for one another in CT scans, and ‘MSK’ affixed as a label to patients who do not have it. Endoscopy will easily identify the remarkably abnormal papillary shapes and dilated sponges, so MSK patients are properly diagnosed.

Tips for diagnosing MSK

1) Confirmation with flexible renal endoscopy can make a definitive diagnosis in patients suspected to have MSK and can be diagnostic as well as potentially therapeutic in terms of stone removal.

2) Consider urographic phase imaging either with IVU or CTU to confirm MSK suspicion in cases where renal endoscopy is not clinically indicated.

3) MSK should not be confused with ductal plugging as these are distinct clinical entities.

4) Nephrocalcinosis is more common than previously appreciated and does not necessarily indicate systemic disease or the specific developmental disorder of MSK.

A Final Word on Treatment

MSK is a true disease and deserves more attention and research efforts to help clarify its etiology and optimize treatment strategies. Because diagnosis by CT scanning is unreliable, the condition is easily overdiagnosed, a problem which leads to many kinds of confusion, clinical and research.

Alternative diagnoses to MSK, such as severe ductal plugging, are not benign and require their own treatment in order to prevent progression. Very often patients with plugging have multiple and severe abnormalities of urine chemistry which can be treated with diet and medications. Proper classification of patients is therefore especially important as different disease states may require unique treatment strategies.

In the event that an accurate MSK diagnosis is made, the tendency to give up on treatment and surrender to the inherent challenges of the disease should be avoided. In fact, these are the patients where metabolic evaluations and attempts at stone prevention are most critical.

Moreover, just because many of these patients tend to have extensive nephrocalcinosis on imaging does not mean they can’t form symptomatic stones in the collecting system as well. In fact, for such patients the clinical history is especially important as visualizing new stones in the setting of extensive nephrocalcinosis can be quite challenging.

Oftentimes when there is a high index of suspicion based on clinical factors, the optimal approach is ureteroscopy as this can be both diagnostic and therapeutic.

That being said, realistic surgical goals should be established. Clearing all stones from such kidneys is rarely feasible, though unroofing those pockets closest to the collecting system or largest on CT imaging offers a good place to start.

MSK is a complex and poorly understood disease that can manifest uniquely from patient to patient. In that respect what works for one person may not be appropriate for another and treatment strategies should thus be organized on a patient to patient basis.

243 Responses to “The Diagnostic Dilemma of Medullary Sponge Kidney”

  1. Amanda G

    Hi ,

    Im a 29 year old female, ive had 64 lithrotripsys in 14 years. I currently have had a 27 mm stone in my left and a 9 and 12 mm in my right. Ive constantly had kidney infections and UTI. I have medullary sponge kidney disease. ive been battling this disease since i was 15, Ive had respectfully over 300 Cat Scans done. Im a traveler so ive had scans in many states, The radiologist in california and Iowa said no more cat scans unless its life threatening but doctors keep pushing it, to the point they refuse treatment unless i have one.

    My question is, Should I be worried about the stone in my left kidney? Im in a ton of pain always, which they say if its in my kidney it shouldnt cause pain, but every time i bend or walk fast it feels like its grinding away the meat in my kidney. And I fall to the ground. Its been 4 months since i was diagnosed and no doctor will accept me, they keep sayin go back to my specialist in Iowa City. the pain management is terrible, my blood pressure is always 170/130 or higher, their solution is more blood pressure meds and anti biotics, well they recently stopped the anti biotics due to them not working anymore.
    Im lost…

    Reply
    • Fredric Coe, MD

      Dear Amanda, I cannot believe 64 SWL! Stop having them. If you have MSK they are useless. In general no one needs so many. You do not mention stone type, nor prevention efforts. Start here, because your case is a total confusion and not of your own making. As for CT scans, 300 sounds out of all bounds. My only hope is that your doctors in Iowa – I guess at the university – prevail. You need more consistent physicians, and likewise some repository of all of your records to stop repetitions. Most of all you need prevention. I advise home blood pressures as hospital readings may reflect pain and stress. Regards, Fred Coe

      Reply
  2. Marcella Torres

    can you explain my mri result please “increase in bilateral renal parenchyma abnormality consistent with worsening medullary sponge kidney

    thank you

    Reply
    • Fredric Coe, MD

      Hi Marcella, Off hand, and without the details, I am afraid I cannot be of much help. Generally we never use MRI for stone work as one cannot see the stones. Possibly the stones are creating an artefact. This is one for those who did the test. Sorry I cannot do better. Regards, Fred Coe

      Reply
  3. Mrs K

    Yes what I desribed has normalized soon after and has remained normal since. Calcium levels are nomal now both in urine and serum. Now I am just left with nephrocalcinosis in kidney. And trying to figure out if the calcification as a result from that episode can be reduced/dissolved with dietary changes (low calcium diet, eating food that make the urine perhaps?

    Reply
    • Fredric Coe, MD

      Hi, I doubt that can happen. But the presumed calcium phosphate crystals are still an issue; why do they form. Would you share your actual urine calcium and pH values, and urine calcium phosphate supersaturation? At best lowering supersaturations might put off more papillary calcifications. But vitamin D excess can cause medullary and even cortical calcifications that would be more or less indifferent to urine chemistry. Regards, Fred Coe

      Reply
      • Mrs K

        Thank you so much! I really appreciate you taking the time to read my questions and respond. I will get a copy of my results and post them for you at a later time, I would very much like to share them with you for your opinion. If this type of calcification is indifferent to urine composition does that mean it shouldn’t worsen over time? I really wish there was something more I can do to undo the damage, it might not be perfect but do you have specific recommendations for phosphate stones? Because if there’s a chance it will help, I’ll take it. I have read your insightful article on supersaturations and will act on that for now. Thank you once again!

        Reply
  4. Mrs K

    Thank you for such an insightful informative article. I have a question, I have what is being labeled as MSK via ultrasound, but I think nephrocalcinosis is more appropriate because the cause is either the period I had high serum calcium due to hypervitaminosis D, or due to kidney injury from iodine contrast administed for CT pulmonary embolism evaluation. Or both since both occurred same month. Is it possible to develop calcification in the areas injured/burned by contrast?
    What can I do to prevent further calcification? I got the advice to consume lemons and citrate but my understanding is if the calcifications are phosphate the opposite would be needed I would need to acidity my urine while lemons make the urine alkaline? I would be grateful for any advice in my case. Thank you.

    Reply
    • Fredric Coe, MD

      Hi Mrs K, I gather you have renal calcifications of unknown composition and have had a bout of vitamin D intoxication. The latter can indeed cause the former, whereas contrast may reduce kidney function but does not cause calcifications. I would be fully evaluated for any causes of stones or calcifications and reverse any remaining issues. This is my best guide article. Never assume the cause, test and find out. Regards, Fred Coe

      Reply
      • Mrs K

        Thank you for a quick reply! I have been tested for other possible causes but nothing else has been found. All points to the very symptomatic and blood test confirmed vitamin D intoxification, if it is indeed calcification from that bout what is your guess as to the composition of the calcifications and which approach (medicine, diet) should I take to reduce and preventing further buildup? Early on I found lemon water increased my renal colic, and the urine was milky when it was alkaline after a calcium rich meal (turned clear when vinegar was added to the turbulent urine). Does this sound like phosphate calcifications?
        I have a hard time finding any info on how to deal with this from Drs or tbe internet. If you have any insight i would greatly appreciate it. Thank you.

        Reply
        • Fredric Coe, MD

          Hi, Your whole story worries me. Vitamin D intoxication would produce calcium phosphate stones and tissue calcium deposits. On CT the two cannot always be told apart. As for your crystal story, it suggests high urine calcium excretion with calcium phosphate crystallization as urine pH goes up from the lemon. You have said your evaluation has been complete and normal but I am not so sure that is correct given the crystals. The vitamin D intoxication would have raised your urine calcium massively and your blood calcium also could have risen but if that is over both should have become normal. Ask your physicians to reconsider matters, perhaps. Regards, Fred Coe

          Reply

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