Editing Stones: Epidemiology and Pathogenesis (section)

=== Renal tubular acidosis (RTA) ===
* '''RTA is a clinical syndrome characterized by metabolic acidosis'''
* '''Classified: acquired vs. inherited'''
** '''Causes of acquired RTA: A CASH POT'''
*# '''Analgesic nephropathy'''
*# '''Idiopathic hyperCalciuria'''
*# '''Acute tubular necrosis (ATN)'''
*# '''Sarcoidosis'''
*# '''Hyperparathyroidism (primary)'''
*# '''Pyelonephritis, recurrent'''
*# '''Obstructive uropathy'''
*# '''Transplant (renal)'''
* '''<span style="color:#ff0000">3 types: type 1 (distal), type 2 (proximal), and type 4 (distal)</span>'''
*# '''<span style="color:#ff0000">Type 1 (distal) RTA</span>'''
*#* '''<span style="color:#ff0000">Most common form of RTA and most commonly associated with kidney stones</span>''' (up to 70% of adults with type 1 RTA have kidney stones)
*#* '''<span style="color:#ff0000">Characterized by (5):</span>'''
*#*# '''<span style="color:#ff0000">Increased urinary pH''' (>6.0)
*#*#'''Hyperchloremic, non-anion gap metabolic acidosis'''
*#*# </span>'''Hypercalcuria'''
*#*# '''Hypocitraturia'''
*#*# '''Hypokalemia'''
*#** '''<span style="color:#ff0000">Due to impaired acid (H+, hydrogen is first element in periodic table so type 1 ) excretion into the urine in the presence of systemic acidosis, from dysfunction of the alpha-type intercalated cells</span>''', which secrete protons into the urine via an apical H+-ATPase
*#*** Metabolic acidosis may cause a negative calcium balance as a result of impaired renal tubular reabsorption of calcium in the proximal tubule, leading to excessive renal loss of calcium. In addition, intestinal calcium absorption is diminished in patients with persistent acidosis. Slow dissolution of bone mineral can also be identified as calcium and phosphate act as buffering mechanisms to correct the acidosis. Chronic acidosis has been cited as a major factor in the genesis of bone disease.
*#** Patients with the incomplete form of distal RTA are not persistently acidemic despite their inability to lower urinary pH with an acid load. '''The diagnosis of incomplete distal RTA can be confirmed by inadequate urinary acidification''' after an ammonium chloride loading test.
*#* '''Potassium citrate therapy is able to correct the metabolic acidosis and hypokalemia'''
*#* '''<span style="color:#ff0000">Most common stone composition associated with Type 1/distal RTA is calcium phosphate</span>''' as a result of increased urinary pH, hypercalciuria, and hypocitraturia
*#*'''<span style="color:#ff0000">Associated with nephrocalcinosis on imaging</span>'''
*# '''<span style="color:#ff0000">Type 2 (proximal) RTA</span>'''
*#* '''<span style="color:#ff0000">Due to impaired bicarbonate (bi=2, type 2) reabsorption</span>'''
*#* Proximal RTA is characterized by a defect in HCO3− reabsorption associated with initial high urine pH that normalizes as plasma HCO3– decreases and the amount of filtered HCO3– falls.  With reduced capacity of the proximal tubule to reclaim filtered HCO3−, more HCO3− is delivered to the distal tubule, which has a limited capacity for bicarbonate reabsorption. Consequently, bicarbonaturia ensues, resulting in reduced net acid excretion and metabolic acidosis. As the filtered HCO3- load declines with progressive metabolic acidosis, less bicarbonate reaches the distal tubule until eventually the capacity of the distal tubule is sufficient to handle the load and no further bicarbonate is lost. '''At steady state, serum HCO3− is low (15 to 18 mEq/L) and urine pH is acidic (<5.5).'''
*#* '''Nephrolithiasis is uncommon in this disorder as urinary citrate levels are not decreased, in contrast to type 1 RTA'''
*# '''Type 4 (distal) RTA'''
*#* '''Usually seen in patients with chronic renal damage''' (obstructive uropathy, interstitial renal disease, diabetic nephropathy, multicystic dysplasia)
*#* '''Pathophysiology results from impaired response to mineralocorticoid''' caused by damage to the cortical collecting duct
*#* Associated with hyperkalemia
*#* '''Nephrolithiasis is uncommon in this disorder'''