eMedicine Specialties > Nephrology > Tubulointerstitial Diseases of the Kidney

Nephrocalcinosis: Differential Diagnoses & Workup

Author: Tibor Fulop, MD, Assistant Professor, Department of Internal Medicine, Division of Nephrology, University of Mississippi Medical Center
Coauthor(s): Mahendra Agraharkar, MD, MBBS, FACP, FASN, Clinical Associate Professor of Medicine, Baylor College of Medicine, President & CEO, Space City Associates of Nephrology; Rupert Patel, MD, Physician, Division of Nephrology, Houston, Texas; Rajiv Gupta, MD, Assistant Professor, Department of Medicine, Texas A & M University Health Science Center; Consulting Staff, Veterans Affairs Medical Center
Contributor Information and Disclosures

Updated: Apr 21, 2009

Differential Diagnoses

Other Problems to Be Considered

Hypercalcemic nephropathy
Renal tubular acidosis

Workup

Laboratory Studies

  • Serum calcium, phosphate, albumin
    • These are needed to establish whether nephrocalcinosis in a patient is associated with hypercalcemia. Determining the albumin level is important when 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. However, ionized calcium levels remain unchanged. 
    • The serum phosphate is low in primary hyperparathyroidism with normal renal function and in hypophosphatemic rickets due to urinary wasting; however, it is typically elevated in nephrocalcinosis associated with renal insufficiency.
  • Serum electrolytes, BUN, creatinine - BUN and serum creatinine are elevated if the nephrocalcinosis is associated with renal insufficiency. Many laboratories in the United States now routinely report, along with serum creatinine, an estimated glomerular filtration rate (eGFR), if predicted renal function falls between 1 and 60 cc/min/1.72 m2. The serum potassium may be low when nephrocalcinosis is caused by certain conditions, such as distal RTA, Bartter syndrome, primary hyperaldosteronism and Liddle syndrome.
  • Urinalysis with microscopic examination -  Urine analysis and urine culture should always be performed to look for evidence of chronic infection. An elevated urinary pH can be suggestive of distal RTA, can be found when overzealous alkali supplementation for nephrolithiasis prophylaxis has occurred, or can exist in the presence urea-splitting pathogens in the urine. Crystals observed on microscopy may provide valuable diagnostic clues about abnormal urine composition.
  • Twenty four – hour urinary excretion of calcium, oxalate, citrate, and uric acid, with simultaneous determination of BUN, creatinine, and protein excretion - Such analyses can be very helpful. BUN and creatinine excretions will help to determine the completeness of timed urine collection and aid in calculating measured renal function. Excess urinary calcium excretion may be observed in patients with idiopathic hypercalciuria. Increased urinary oxalate excretion indicates a primary or secondary cause of hyperoxaluria. Patients with nephrocalcinosis generally have low-grade proteinuria of a nonglomerular etiology. Nephrotic-range proteinuria is not expected in this context and is an indication for further evaluation of underlying renal disease.
  • Parathyroid hormone levels - In the presence of hypercalcemia or renal failure, parathyroid hormone levels should be obtained to rule out primary or secondary hyperparathyroidism.
  • Thyroid-stimulating hormone (TSH) levels - These should be obtained to rule out a thyroid disorder.
  • Urinary magnesium levels - Assessing these may be useful in detecting magnesium-losing nephropathy.

Imaging Studies

Despite advances in renal imaging technologies,30 the correlation between the extent of radiographically demonstrable nephrocalcinosis and the degree of renal impairment remains limited. Plain kidney-ureter-bladder (KUB) radiographs visualize only advanced cases. 

Furthermore, the diagnostic correlation between currently used techniques is imperfect, and there is interobserver variability when test results are interpreted.31

Ultrasonography is more sensitive than conventional radiography, but papillary cysts or hilar fat deposition can lead to false-positive results. (See image below and Image 7.)

Ultrasonogram of the right kidney in a woman with...

Ultrasonogram of the right kidney in a woman with nephrocalcinosis. This image shows hyperechoic foci in the pyramids.

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Ultrasonogram of the right kidney in a woman with...

Ultrasonogram of the right kidney in a woman with nephrocalcinosis. This image shows hyperechoic foci in the pyramids.


CT scanning is more effective in detecting calcification and can be used to locate medullary versus cortical deposition.32 It may also be used to detect defects that are too small to be diagnosed with conventional radiography. (See images below and Images 5, 6.)

Nonenhanced coronal computed tomography scans thr...

Nonenhanced coronal computed tomography scans through the kidneys. These images show cortical and medullary nephrocalcinosis (left kidney). Both kidneys appear scarred. Note the thinning of the renal cortex at the upper pole of the left kidney. This patient gave a long history of chronic pyelonephritis, which is an unusual cause of nephrocalcinosis.

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Nonenhanced coronal computed tomography scans thr...

Nonenhanced coronal computed tomography scans through the kidneys. These images show cortical and medullary nephrocalcinosis (left kidney). Both kidneys appear scarred. Note the thinning of the renal cortex at the upper pole of the left kidney. This patient gave a long history of chronic pyelonephritis, which is an unusual cause of nephrocalcinosis.


Axial computed tomography scans obtained from a p...

Axial computed tomography scans obtained from a patient with a long history of renal tubular acidosis. These images show bilateral medullary nephrocalcinosis (early arterial phase).

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Axial computed tomography scans obtained from a p...

Axial computed tomography scans obtained from a patient with a long history of renal tubular acidosis. These images show bilateral medullary nephrocalcinosis (early arterial phase).


Magnetic resonance imaging (MRI) offers no advantages over these alternatives, and in the absence of other compelling indications, it should not be utilized. 

Histologic Findings

Histologic findings 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, such as von Kossa and Pizzolato, may be required for better visualization.

More on Nephrocalcinosis

Overview: Nephrocalcinosis
Differential Diagnoses & Workup: Nephrocalcinosis
Treatment & Medication: Nephrocalcinosis
Follow-up: Nephrocalcinosis
Multimedia: Nephrocalcinosis
References
Further Reading
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References

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Keywords

nephrocalcinosis, kidney, kidneys, kidney stones, kidney stone, hypercalcemia, hypercalciuria, hyperparathyroidism, nephrolithiasis, urinary stones, urinary stone, medullary nephrocalcinosis, crystal-induced nephropathy, increase in renal calcium content, microscopic nephrocalcinosis, macroscopic nephrocalcinosis, hypercalcemic nephropathy

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Contributor Information and Disclosures

Author

Tibor Fulop, MD, Assistant Professor, Department of Internal Medicine, Division of Nephrology, University of Mississippi Medical Center
Tibor Fulop, MD is a member of the following medical societies: American College of Physicians and American Society of Diagnostic and Interventional Nephrology
Disclosure: Nothing to disclose.

Coauthor(s)

Mahendra Agraharkar, MD, MBBS, FACP, FASN, Clinical Associate Professor of Medicine, Baylor College of Medicine, President & CEO, Space City Associates of Nephrology
Mahendra Agraharkar, MD, MBBS, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Nephrology, and National Kidney Foundation
Disclosure: South Shore DaVita Dialysis Center  Ownership interest Other

Rupert Patel, MD, Physician, Division of Nephrology, Houston, Texas
Disclosure: Nothing to disclose.

Rajiv Gupta, MD, Assistant Professor, Department of Medicine, Texas A & M University Health Science Center; Consulting Staff, Veterans Affairs Medical Center
Rajiv Gupta, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, and Society of Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

Medical Editor

James W Lohr, MD, Fellowship Program Director, Professor, Department of Internal Medicine, Division of Nephrology, State University of New York at Buffalo
James W Lohr, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, and Central Society for Clinical Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology
Disclosure: Nothing to disclose.

 
 
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