Kidney Disease and Primary Hyperparathyroidism (PHPT)

• Approximately 80% of patients with PHPT:
  • Have some degree of renal dysfunction or symptoms / signs
• Kidney stones were previously reported in up to 80% of patients with PHPT:
  • But now occur in roughly 15% to 20% of the cases PHPT:
    • The calculi are typically composed of:
      • Calcium oxalate or
      • Calcium phosphate
    • In contrast, PHPT is found to be the underlying disorder:
      • In only 3% to less than  5% of patients presenting with nephrolithiasis
• Nephrocalcinosis:
  • Which refers to renal parenchymal calcification:
    • Is found in less than 5% of patients with PHPT and is more likely to lead to renal dysfunction
• Chronic hypercalcemia also can impair the concentrating ability of the kidney:
  • Thereby resulting in:
    • Polyuria
    • Polydipsia
    • Nocturia
• The incidence of hypertension is variable but has been reported to occur:
  • In up to 50% of patients with PHPT:
    • Hypertension appears to be more common in:
      • Older patients and correlates with the magnitude of renal dysfunction:
        • In contrast to other symptoms:
          • It is least likely to improve after parathyroidectomy
• Among normocalcemic patients with nephrolithiasis:
  • PHPT should be suspected if:
    • The serum calcium concentration is in the:
      • High-normal range:
        • Because the hypercalcemia may be intermittent and detected only by multiple measurements:
          • In one series of 48 patients with nephrolithiasis and PHPT:
            • 30 patients (63%) had:
              • Serum calcium concentrations between 10.2 and 11 mg/dL (2.55 and 2.75 mmol/L)
• Most stones in patients with PHPT are composed of:
  • Calcium oxalate:
    • Although a slightly alkaline urine:
      • May favor the precipitation of calcium phosphate leading to calcium phosphate stones
  • A possible contributing factor for stone formation in PHPT:
    • Is hypercalciuria:
      • Although PTH directly stimulates the distal tubular reabsorption of calcium:
        • This effect is overshadowed by the increase in filtered calcium due to the hypercalcemia:
          • Leading to increased urinary calcium excretion:
            • In 35% to 40% of patients with PHPT
      • However, urinary calcium excretion per gram of creatinine:
        • Does not necessarily differentiate patients with or without stones:
          • This is likely due to the limited precision of a 24-hour urine calcium collection and to the complexity of factors that determine stone formation
      • Urinary calcium concentration:
        • Is only one of at least six urinary risk factors that determine the urine saturation of the calcium salts that lead to calcium stone formation:
          • It is for this reason that elevated levels of urinary calcium excretion are no longer, in and of itself, considered an indication for surgery in PHPT
  • A high serum calcitriol concentration:
    • Caused by PTH stimulation of renal hydroxylation of 25-hydroxyvitamin D:
      • May contribute to both hypercalciuria and stone formation:
        • This was illustrated in a report of 50 patients with PHPT:
          • In which 19 of the 30 patients who had:
            • High serum calcitriol concentrations, hypercalciuria, and increased dietary calcium absorption:
              • Had kidney stones
          • As compared with only 3 of 20 patients who had:
            • Normal to high-normal serum calcitriol concentrations and normal urinary calcium excretion and dietary calcium absorption
        • However, this distinction was not apparent in another series of 70 patients with mild PHPT, 18% of whom had kidney stones;
          • There was no difference in serum PTH, calcium, or calcitriol concentrations between patients with and without kidney stones, but more of the kidney stone group had hypercalciuria
  • In several studies, clinically silent kidney stones were reported in:
    • 7% to 21% of patients with PHPT:
      • Patients with undiagnosed (subclinical) nephrocalcinosis or calcium kidney stones are regarded as having symptomatic disease:
        • Regardless of the absence of symptoms:
          • Thus, these patients meet criteria for surgical intervention
• For patients who do not have other overt indications for surgery:
  • Some UpToDate authors and editors obtain renal imaging (ultrasound, computed tomography [CT], or abdominal radiograph) to look for nephrocalcinosis or asymptomatic nephrolithiasis at the time of the original evaluation for PHPT:
    • Ultrasound is typically the imaging modality used

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