RTA: Calcium and Renal Stones

Risk factor for renal stones

•  Distal renal tubular acidosis (nephrocalcinosis, nephrolithiasis) 
•  Lower dietary calcium. Get calcium resorption from bones which enhances calcium excretion
•  Higher urinary pH (CaP stones)
•  Higher urinary calcium
•  Lower urinary citrate

Mechanism 

• by which distal (type 1) RTA promotes renal stones (calcium phosphate) formation
• Increase calcium and  phosphate release from bone buffering of retained acid and direct reduction in tubular reabsorption of these ion hence increase urinary calcium excretion (nephrocalcinosis) 
• Persistently high urine pH (alkaline) promotes calcium phosphate precipitation 
• Acidemia enhance proximal citrate reabsorption hence reduces citric acid excretion (hypocitruria). Urinary citrate normally binds calcium and helps to prevent stones from forming. The absence of citrate increases calcium stone risk (nephrolithiasis)

 Comments:

• Stone disease is also seen with carbonic anhydrase inhibitors but typically not with proximal (type 2) RTA
• In some families, hypercalciuria appears to be the primary abnormality, with calcium-induced interstitial and tubular damage possibly responsible for the RTA

 Dietary calcium & urinary calcium excretion                                            

• Increased intestinal absorption ("absorptive hypercalciuria") in which there is an increase in intestinal calcium absorption. 
• Ingested calcium is absorbed in the intestines and later excreted in the urine. Although this suggests that a diet high in calcium might promote stone disease, the opposite effect is seen as the risk of stone formation appears to be reduced in both men and women. 
• In contrast, calcium supplements may slightly increase the propensity to form stones, at least in older women. However, dietary calcium intake should not be restricted unless it is excessive (> 2000 mg/day).
• If hypercalciuria is present, calcium supplements are contraindicated in these patients.

 Recommendations:

• Patients with untreated distal (type 1) renal tubular acidosis may be at increased risk for nephrolithiasis due to higher urinary calcium excretion, higher urine pH, and lower urinary citrate excretion
• Both higher and lower dietary calcium might lead to an increase in urinary calcium excretion by "absorptive hypercalciuria” and “resorptive hypercalciuria” mechanism respectively. Hence, dietary calcium intake should not be restricted unless it is excessive (> 2000 mg/day). 
• The risk of stone formation is slightly increased with calcium supplementation, at least in older women.
• Calcium supplementation is generally not given in patient with distal RTA because there may be calcium deposits in the kidneys, even after bicarbonate therapy nevertheless in cases of osteoporosis in distal RTA patient, whereby its use is indicated calcium supplementation has been given.

References:

1. Up-to-date. Risk factors for calcium stones in adults. Updated on Sep 23, 2014. 
2. Up-to-date. Nephrolithiasis in renal tubular acidosis. Updated on Jan 13, 2016.
3. BMJ Best Practice Renal Acidosis BMJ Publishing Group Ltd 2015. Aug 5, 2015
4. Times Health Guide. Distal Renal Tubular Acidosis. Reviewed on Dec 19 2011
5. Ramen. C et al. Distal Renal Tubular Acidosis, Hypokalemic Paralysis, Nephrocalcinosis, Primary Hypothyroidism, Growth Retardation, Osteomalacia and Osteoporosis Leading to Pathological Fracture: A Case Report. Oman Med J. 2011 Jul; 26(4): 271–274.
6. KKM formulary (Bluebook)