Nephrocalcinosis Workup

Updated: Aug 09, 2021
  • Author: Tibor Fulop, MD, PhD, FACP, FASN; Chief Editor: Vecihi Batuman, MD, FASN  more...
  • Print

Laboratory Studies

The workup for nephrocalcinosis should include the following studies:

  • Serum calcium
  • Serum phosphate
  • Serum albumin
  • Blood urea nitrogen (BUN) and serum creatinine 
  • Serum potassium
  • Urinalysis and urine culture

Also consider measuring the following:

  • 24-hour urinary excretion of calcium, oxalate, citrate, and uric acid
  • Urinary magnesium
  • Parathyroid hormone
  • Thyroid-stimulating hormone 

Measurement of serum calcium and albumin levels is necessary to establish whether nephrocalcinosis is associated with hypercalcemia. Determining the albumin level is important for interpreting the serum calcium level in the face of hypoalbuminemia: for every 1 g/dL decrease in serum albumin, measured serum calcium decreases by approximately 0.8 mg/dL. The reliability of calcium corrected for albumin has been questioned; ionized calcium should be used to confirm when in doubt.

The serum phosphate level is low in primary hyperparathyroidism with normal kidney function and in hypophosphatemic rickets due to urinary wasting; however, it is typically elevated in nephrocalcinosis associated with kidney insufficiency.

BUN and creatinine levels are elevated when nephrocalcinosis is associated with kidney insufficiency. Many laboratories in the United States now routinely report, along with serum creatinine, an estimated glomerular filtration rate (eGFR), if predicted kidney function falls to less than 60 mL/min/1.73 m2.

The serum potassium concentration may be low when nephrocalcinosis is caused by certain conditions, such as the following:

Urinalysis and urine culture should always be performed to look for evidence of chronic infection. An elevated urinary pH may suggest distal RTA, which may be found when overzealous alkali supplementation for nephrolithiasis prophylaxis has occurred, or may exist in the presence of urea-splitting pathogens in the urine. The type of crystals observed on urine sediment microscopy may provide valuable diagnostic clues about abnormal urine composition.

Assessment of 24-hour urinary excretion of calcium, oxalate, citrate, and uric acid, with simultaneous determination of BUN, creatinine, and protein excretion, can be very helpful. [56]  BUN and creatinine excretions will help to determine the completeness of timed urine collection and aid in calculating measured kidney function.

Excess urinary calcium excretion may be observed in patients with idiopathic hypercalciuria. [56]  Increased urinary oxalate excretion indicates a primary or secondary cause of hyperoxaluria. Patients with nephrocalcinosis generally have low-grade proteinuria of nonglomerular origin. Nephrotic-range proteinuria is not expected in this context and is an indication for further evaluation of underlying kidney disease.

Assessment of urinary magnesium levels may be useful in detecting magnesium-losing nephropathy.

In the presence of hypercalcemia or kidney failure, parathyroid hormone levels should be obtained to rule out primary or secondary hyperparathyroidism. [56] Both primary and secondary hyperparathyroidism may coexist with chronic kidney disease. Thyroid-stimulating hormone levels should be obtained to rule out a thyroid disorder.


Radiography, CT, and Ultrasonography

Despite advances in renal imaging technologies, [57, 58] the correlation between the extent of radiographically demonstrable nephrocalcinosis and the degree of kidney impairment remains limited (see the images below). Plain kidney-ureter-bladder (KUB) radiographs visualize only advanced cases. Furthermore, the diagnostic correlation between currently used techniques is imperfect, and there is considerable interobserver variability with respect to the interpretation of test results. [59]

Excretory urogram obtained at 15 minutes in man wi Excretory urogram obtained at 15 minutes in man with renal papillary necrosis (most likely, patient with diabetes mellitus and repeated urinary tract infections). Image shows bilateral hydronephrosis and hydroureter due to obstruction by sloughed papillae at lower end of ureter.
Plain kidney-ureter-bladder (KUB) radiograph in ma Plain kidney-ureter-bladder (KUB) radiograph in man with renal papillary necrosis (most likely, patient with diabetes mellitus and repeated urinary tract infections). Image shows bilateral renal calcification. Large, sloughed, and calcified renal papilla is present in region of left vesicoureteric junction. Note 2 pelvic phleboliths opposite ischial spine on right.

Ultrasonography (see the image below) is more sensitive than conventional radiography in this setting, but papillary cysts or hilar fat deposition can lead to false-positive results. Ultrasonography is better than x-ray, but has interoperator variability and is not better than computed tomography (CT).

Ultrasonogram of right kidney in woman with nephro Ultrasonogram of right kidney in woman with nephrocalcinosis. Image shows hyperechoic foci in pyramids.

CT is more effective in detecting calcification and can be used to differentiate between medullary and cortical deposition (see the images below). [60] It may also be used to detect defects that are too small to be diagnosed with conventional radiography and can identify deposits even up to 1 mm.

Nonenhanced coronal CT scans through kidneys, show Nonenhanced coronal CT scans through kidneys, showing cortical and medullary nephrocalcinosis (left kidney). Both kidneys appear scarred. Note thinning of renal cortex at upper pole of left kidney. Patient gave long history of chronic pyelonephritis, which is unusual cause of nephrocalcinosis.
Axial CT scans from patient with long history of r Axial CT scans from patient with long history of renal tubular acidosis. Images show bilateral medullary nephrocalcinosis (early arterial phase).

Magnetic resonance imaging (MRI; see the image below) offers no advantages over the aforementioned imaging modalities except for avoidance of radiation exposure. In the absence of other compelling indications, it should not be utilized.

Nephrocalcinosis. Nephrocalcinosis.

For more information, see Nephrocalcinosis Imaging.


Histologic Findings

Histologic findings (see the images below) include crystal deposition, which occurs mainly in the interstitium. The deposits may be observed within or between the tubules. The deposits consist of calcium phosphate or calcium oxalate. Special stains (eg, von Kossa and Pizzolato) may be required for better visualization.

Nephrocalcinosis. Nephrocalcinosis.
Nephrocalcinosis. Nephrocalcinosis.