Nephrocalcinosis Clinical Presentation

Updated: Aug 09, 2021
  • Author: Tibor Fulop, MD, PhD, FACP, FASN; Chief Editor: Vecihi Batuman, MD, FASN  more...
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The underlying etiology primarily determines the presentation of nephrocalcinosis, though in many cases the condition remains asymptomatic and is identified only as a radiologic abnormality. The physical findings are nonspecific and reflect the underlying disorders responsible for nephrocalcinosis. Potential clinical features of the 3 types of nephrocalcinosis are described below.

Hypercalcemic nephropathy (chemical nephrocalcinosis)

Hypercalcemic nephropathy is commonly characterized by relative vasopressin resistance with decreased renal concentrating ability and increased free water diuresis (nephrogenic diabetes insipidus), manifesting as polyuria and polydipsia. Other defects, such as renal glycosuria, reduced glucose tubular maximum, aminoaciduria, and nonglomerular proteinuria, have occasionally been reported. Reversible hypertension occurs in approximately 50% of patients as a consequence of increased peripheral vasoconstriction.

Hypercalcemia is also a well-established cause of kidney failure, through direct renal vasoconstriction and volume depletion induced by excessive diuresis. This process usually is reversible, with normal kidney function returning as the hypercalcemia is corrected with volume replacement. However, irreversible failure can occur with long-standing hypercalcemia and is always associated with calcium crystal deposition.

Microscopic nephrocalcinosis

A few studies describe the effects of nephrocalcinosis on kidney function in rats. [51]  Various investigators have observed reduced concentration capacity, increased blood urea nitrogen (BUN), and prolongation of a single nephron transit time in a distal tubule, [52]  though no detailed studies of glomerular filtration or renal tubular function exist in these models. Occasionally, rats with the pelvic type of nephrocalcinosis may develop acute pyelonephritis or calculous ureteral obstruction with kidney failure.

It should be kept in mind, however, that nephrocalcinosis in rats is a poor model for humans because of the high incidence of spontaneous glomerulosclerosis in laboratory rats, the different distribution of calcium in the kidney, and the absence of a rat model for many of the diseases that cause human nephrocalcinosis.

Macroscopic nephrocalcinosis

A wide range of abnormalities can occur with medullary nephrocalcinosis. Calcium nodules may rupture through the papillary epithelium into the calyceal system to become urinary stones and elicit the clinical presentations of renal colic, hematuria, passage of urinary stones, or urinary tract infection. However, macroscopic nephrocalcinosis should not be considered synonymous with urinary stones, because nephrocalcinosis usually implies a more profound metabolic derangement.

The following may be noted:

  • Polyuria and polydipsia may be prominent because of the excess of free water diuresis with reduced renal concentrating ability
  • Hypertension is relatively less common, probably reflecting a reduced ability to conserve sodium
  • Proteinuria may be observed, though it is in the nonnephrotic range and usually below 500 mg/day
  • In Dent disease, loss of low-molecular-weight proteins may exceed 2 g/day; hypercalciuria, nephrolithiasis, and nephrocalcinosis are additional presenting features
  • Microscopic pyuria is common and represents a chronic inflammatory response to medullary calcification
  • Distal tubular dysfunction is common with a mild salt-losing defect; it may become obvious only with profound decrease of oral intake (anorexia) or when another source of salt-water loss (eg, diarrhea or vomiting) emerges
  • Proximal tubular dysfunction is unusual, except for tubular proteinuria and the aminoaciduria of Dent disease
  • Medullary nephrocalcinosis of any etiology can cause secondary distal tubular acidosis related to distal tubular calcium deposition and chronic inflammation in the medulla
  • Patients may present with kidney failure or with features of their underlying disease

Physical Examination

While nephrocalcinosis is a radiologic finding, some features on physical exam may provide hints of underlying genetic abnormality in some cases. Enamel-renal syndrome is characterized by nephrocalcinosis and dental manifestations including enamel defects, gingival hyperplasia, and eruption failures. [53]  Amelogenesis imperfecta (AI) repesents a goup of diseases with tooth enamel defects. It is now recognized that some patients with familial hypercalciuria and hypomagnesemia with nephrocalcinosis caused by claudin-16 mutation will have findings of AI on exam. [35]

Gross bone deformity with rickets can be observed with X-linked hypophosphatemia without proper phosphorus supplementation, although the contribution of phosphate supplementation is debated. [54]  Older individuals (over age 40) often require joint replacement and decompressive laminectomy. [55]



Persistent hypercalcemia can cause dehydration and acute kidney injury. Nephrocalcinosis can lead to progressive chronic kidney disease and eventually end-stage renal disease requiring dialysis.