What is the cause of nephrocalcinosis in Sjogren's (Systemic autoimmune disorder) disease?

Causes of Nephrocalcinosis in Sjögren's Syndrome

Distal renal tubular acidosis (dRTA) is the primary cause of nephrocalcinosis in Sjögren's syndrome, leading to chronic metabolic acidosis, hypercalciuria, and hypocitraturia which promote calcium phosphate precipitation in the renal tubules.

Pathophysiological Mechanism

• Sjögren's syndrome is characterized by lymphocytic infiltration of exocrine glands, particularly the lacrimal and salivary glands, with potential for systemic involvement including the kidneys 1
• Renal involvement occurs in up to 30% of patients with Sjögren's syndrome, with tubulopathies ranging from 2.6% to 33% of cases 2
• The predominant renal manifestation is distal renal tubular acidosis (dRTA), which is classified as a potential life-threatening systemic manifestation in the renal domain according to EULAR guidelines 3

Primary Mechanism: Distal Renal Tubular Acidosis

• Lymphocytic infiltration of the kidneys leads to tubulointerstitial nephritis affecting the distal tubules 4
• This results in impaired hydrogen ion secretion in the distal tubules, causing type I (distal) renal tubular acidosis with the following consequences:
  • Hyperchloremic metabolic acidosis with normal anion gap 4
  • Persistently alkaline urine pH (inability to acidify urine) 4
  • Hypercalciuria due to bone buffering of excess acid 4
  • Hypocitraturia (low urinary citrate) which normally inhibits stone formation 5

Secondary Contributing Factors

• Chronic metabolic acidosis leads to bone mineral dissolution as the body attempts to buffer excess acid, releasing calcium into circulation 6
• Hypercalciuria (increased urinary calcium excretion) results from this process 4
• Hypocitraturia occurs because metabolic acidosis increases proximal tubular reabsorption of citrate, reducing its excretion 5
• Hypokalemia is frequently present and may be the first presenting symptom 6
• Decreased renal concentrating capacity (hyposthenuria) is common and contributes to stone formation 4

Clinical Manifestations

• Nephrocalcinosis (calcium deposition in renal parenchyma) 2
• Nephrolithiasis (kidney stones), typically composed of calcium phosphate and calcium oxalate 5
• Recurrent renal colic due to stone passage 2
• Hypokalemic periodic paralysis may be the first presenting symptom in some patients 6
• Progressive decline in renal function if left untreated 4

Diagnostic Approach

• Laboratory evaluation should include:
  • Serum electrolytes showing hyperchloremic metabolic acidosis with normal anion gap 4
  • Urine pH persistently >5.5 despite acidemia 4
  • Serum potassium levels (often low) 6
  • Urinary calcium and citrate levels 5
• Imaging studies to detect nephrocalcinosis and nephrolithiasis 2
• Serological testing for Sjögren's syndrome markers (anti-SSA/Ro, anti-SSB/La antibodies) 7

Treatment Implications

• Correction of metabolic acidosis with alkali therapy (potassium citrate) is the cornerstone of treatment 5
• Thiazide diuretics may be added to reduce hypercalciuria 5
• Treatment of the underlying Sjögren's syndrome with immunomodulatory therapy may improve renal manifestations 6
• Regular monitoring of renal function, electrolytes, and imaging is essential 2

Clinical Pearls

• Consider underlying Sjögren's syndrome in any patient presenting with distal renal tubular acidosis or recurrent hypokalemic periodic paralysis 6
• Early diagnosis and treatment of both the metabolic derangements and underlying autoimmune disease is crucial to prevent progression to chronic kidney disease 2
• Multiple renal manifestations may coexist in the same patient, including diabetes insipidus, renal tubular acidosis, and nephrolithiasis 8