I. Pathologenesis of Stones:
Three states of urine saturation: 1) Undersaturated, 2) metastable, 3) unstable
When supersaturation (SS) >1, urine is metastable --> salts are able to form crystals on existing nidus.
Heterogeneous nucleation = primary stone components and nidus are different substrates (occurs in metstable urinary state)
Homogeneous nucleation = de novo crystal formation (occurs in unstable urinary state)
Randall's plaques = renal medullary crystallization within the subepithelium that erodes through the papilla to act as a nidus for nephrolithiasis.
Promoters and Inhibitors of Stone Formation:
| Promoters | Inhibitors |
| Calcium | Citrate |
| Sodium | Magnesium |
| Oxalate | Pyrophosphate |
| Urate | Phospate |
| Cystine | Glycosaminoglycans |
| Low urine pH | Osteopontin |
| Low urine volume | |
| Protein matrix |
II. Metabolic Workup:
1. Urinalysis: pH <5 is likely uric acid stone, pH >7 is likely infection stone
2. Serum electrolytes, Cr, Calcium, Uric acid, PTH, phosphorus
3. 24 hour urine collection: confirm adequate sample size with urine Cr (15-25mg/kg/day)
Indications for 24-hour Urine evaluation:
| Recurrent calcium stone former |
| Family history of stones |
|
Intestinal or malabsorptive disease |
| Osteoporosis and stone disease |
| Gout and stone disease |
| Young age of onset of stone disease |
| Uric acid stone |
| Cystine stone |
Normal Range for 24 hour Urine Analyses:
| Calcium | <200 mg / day |
| Citrate |
>450 mg / day (male) >550 mg / day (female) |
| Oxalate | <40 mg / day |
| pH | 5.8 - 6.2 |
| Uric Acid |
<800 mg / day (male) <750 mg / day (female) |
| Sodium | <150 mg / day |
| Potassium | 20 - 100 mg / day |
| Magnesium | 30 - 120 mg /day |
III. Medical Treatments for Stones:
A. Hypercalciuria
Tx: Thiazides, K citrate, increase water intake, decrease red meat intake, decrease Na intake, normal Ca intake
Thiazides work by inhibiting distal tubule Na secretion and Ca secretion
B. Hyperoxaluria
Tx: if dietary: avoid high oxalate foods (rhubarb, spinach, okra, leeks, nuts, seeds, etc.), Vitamin B6 supplementation, limit excessive Vitamin C
Tx: if GI related (Crohns, UC, short gut) - loss of terminal ileum --> decreased bile salt reabsorption --> increased bile + Ca chelation --> increased absorption of oxalate: treat with low oxalate and low fat diet, Vitamin B6 supplementation, K citrate
C. Hypocitraturia:
Tx: K citrate, increased water intake
K citrate works by: 1) urine alkalization, 2) increasing citrate which binds urinary calcium (so less Ca is able to bind oxalate)
D. Hyperuricosuria: (if pH <5.5 then likely Uric acid stone)
Tx: K citrate, Allopurinol
Allopurinol works by inhibiting xanthine oxidase and reducing uric acid production
E. Infection stones:
- Caused by UTI by Proteus, Klebsiella or Pseudomonas (urease producing), increased ammonium results in alkaline urine (pH >7)
- Stone compositions: Struvite (mag-NH4-phos) or carbonate apatite (calcium phosphate)
-Tx: Complete surgical removal of stone, treatment of infection
F. Cystinuria:
- Autosomal recessive defect of renal proximal tubule, no reabsorption of cystine
Tx: low methionine diet, K citrate, increase water, chelation with Thiola
IV: Additional Studies (Optional):
1. Pearle MS, Goldfarb DS, Assimos DG, et al. Medical management of kidney stones: AUA guidline. J Urol. 2014 Aug;192(2):316-24.
2. Bagga HS, Chi T, Miller J, Stoller ML. New insights into the pathogenesis of renal calculi. Urol Clin North Am. 2013 Feb;40(1):1-12.