Urolithiasis
CAUSES AND TREATMENT OF COMBINED DISTURBANCES
The majority of patients with stones present with more than one abnormal stone risk factor, involving a mixture of metabolic and environmental factors. This multiple presentation has posed a major confusion for many practicing urologists in medically managing patients with stones. In the following discussion, key examples of multiple presentation, selected from actual patient referrals, are discussed in detail (Table 2) .
|
Findings |
Condition |
Treatment |
|
1. Hypercalciuria |
Absorptive hypercalciuria with dietary abuse |
Thiazide |
|
Hyperuricosuria |
Potassium citrate |
|
|
Hypocitraturia |
Sodium restriction |
|
|
High urinary sodium |
||
|
2. Low urinary pH |
Gouty diathesis with dietary abuse |
Potassium citrate |
|
Hyperuricosuria |
Allopurinol if serum uric acid is high |
|
|
Hypocitraturia |
||
|
Sodium restriction |
||
|
3. Hypocitraturia |
Crohn’s disease |
Potassium-sodium citrate |
|
Hyperoxaluria |
||
|
Low urinary pH |
||
|
Low urine volume |
||
|
4. Hyperuricosuria |
Exaggerated animal-protein excess |
Potassium citrate |
|
Hyperphosphaturia |
||
|
Hypercalciuria |
||
|
Low urinary pH |
||
|
Hypocitraturia |
||
|
5. Hypocitraturia |
Incomplete renal tubular acidosis |
Potassium citrate |
|
High urinary pH |
||
|
Hypercalciuria |
||
|
6. High urinary pH |
Vegetarian diet with supplements |
Dietary modification |
|
Hyperoxaluria |
||
|
Normal urinary citrate |
||
Hypercalciuria, Hyperuricosuria, and Hypocitraturia
A 40-year-old man with calcium oxalate stones had a urinary calcium level of 350 to 400 mg/d, uric acid level of 790 mg/d, and citrate level of 300 mg/d. Urinary sodium and sulfate levels also were high, 300 mEq/d and 35 mmol/d, respectively. This presentation is perhaps the commonest picture describing a patient with absorptive hypercalciuria with dietary abuse.
Excessive intake of sodium is indicated by high urinary sodium levels. Assuming that the urinary sodium level is nearly equal to the intake at steady state, the patient’s daily sodium intake was 200 mEq above the recommended amount of 100 mEq. This dietary sodium excess could increase urinary calcium by about 100 mg/d. Even after this correction, the urinary calcium level still would be high at about 300 mg/d. The patient, therefore, had a metabolic background for hypercalciuria.
The high urinary uric acid and sulfate levels indicated that the patient had “purine gluttony.” The resulting acid load could explain a modest decline in urinary citrate.
The recommended treatment for this patient is trichlormethiazide (4 mg/d) and potassium citrate (20 mEq twice daily), with sodium restriction. Thiazide can lower urinary calcium levels by enhancing renal tubular reabsorption of calcium, even though this action may become attenuated after 2 years of treatment in some patients. [17] Sodium restriction is critical, because high sodium intake blunts the ability of thiazide to lower urinary calcium. Potassium citrate can not only prevent thiazide-induced hypokalemia but also neutralize the acid load from a diet high in animal protein and increase the urinary citrate level.
Low Urinary pH, Hyperuricosuria, and Hypocitraturia
A 45-year old man had a urinary pH (in a 24-hour specimen) of 5.0, urinary uric-acid level of 650 mg/d, and urinary citrate level of 310 mg/d. His urinary sulfate level was 32 mmol/d. The serum uric acid level was 7.0 mg/dL, and the serum triglyceride level was 350 mg/dL. He denied having had gouty arthritis, bowel disease, or chronic diarrheal condition. Analysis of one stone disclosed calcium oxalate but another contained uric acid. This patient probably suffered from gouty diathesis with dietary abuse.[7]
The key abnormality is low urinary pH, which cannot be explained by intestinal loss of bicarbonate or a high-acid diet. The patient did not suffer from diarrhea. He probably was ingesting a diet high in animal protein, indicated by high urinary uric acid, citrate, and sulfate levels. The amount of acid load from such a diet, however, is probably insufficient to produce a urinary pH of 5.0. By a process of exclusion, the diagnosis is gouty diathesis. Low urinary pH is the hallmark of primary gout, the underlying disturbance for stone formation in gouty diathesis.
This diagnosis is supported by the findings of uric acid on stone analysis and hypertriglyceridemia. Gouty diathesis is still a likely diagnosis even if uric acid is not found on stone analysis. Calcium oxalate stones frequently are found among patients with primary gout. Some patients with gouty diathesis present with calcium oxalate stones. [7] Hypertriglyceridemia commonly is encountered in primary gout. The patient probably had latent gout, in which the disease is manifested mainly with defective ammoniagenesis and low urinary pH. This explanation could account for the absence of marked hyperuricemia and gouty arthritis.
The treatment is potassium citrate at a dose sufficient to increase and maintain urinary pH between 6.0 and 6.5 (initial dose of 20 mEq twice daily). There is no need to add allopurinol in the absence of hyperuricemia. Urinary alkalinization (by potassium citrate) is much more effective than reduction in urinary uric acid (by allopurinol) in decreasing the amount of sparingly soluble undissociated uric acid. Dietary sodium restriction is recommended to avoid complication of calcium-stone formation. [13]
Hypocitraturia, Hyperoxaluria, Low Urinary pH, and Low Urine Volume
A 30-year-old woman had severe hypocitraturia of 60 mg/d, severe hyperoxaluria of 100 mg/d, low urinary pH of 5.3, and low urine volume of 800 mL/d. She also had low urinary sodium (40 mEq/d), potassium (30 mEq/d), calcium (80 mg/d) and magnesium (30 mg/d) levels. She had fat malabsorption and frequent watery bowel movements secondary to Crohn’s disease. Her stones were composed of uric acid and calcium oxalate. This patient had enteric hyperoxaluria.[4]
Patients with inflammatory disease or resection of ileum are at increased risk of developing stones of uric acid and calcium oxalate from multiple disturbances. Urinary citrate and pH are low because metabolic acidosis from intestinal bicarbonate loss. Hyperoxaluria develops from enhanced intestinal absorption of oxalate. Urinary volume is low because of intestinal fluid loss, increasing the urinary concentration of stone-forming substances. Calcium oxalate saturation is increased by hyperoxaluria and low urine volume. The saturation of undissociated uric acid is high because of low urinary pH and volume.
Some stone-forming patients with ileal disease may not show all of these urinary stone risk factors. For example, hyperoxaluria may not be present in all patients, and urine volume may be relatively normal. Most patients, however, display hypocitraturia and low urinary pH. The treatment has been discussed previously.
Hyperuricosuria, Hyperphosphaturia, Hypercalciuria, Low Urinary pH, and Hypocitraturia
A 36-year-old woman had a urinary uric acid level of 750 mg/d, a phosphorus level of 1400 mg/d, a calcium level of 270 mg/d, pH of 5.4, and a citrate level of 250 mg/d. Her urinary sulfate level was high at 36 mmol/d, but urinary oxalate level was low normal at 20 mg/d. She had been on a weight-reducing diet for 1 month, emphasizing animal proteins with severely limited intake of fruits and vegetables. She formed a stone composed of uric acid.
This picture represents the characteristic presentation of markedly exaggerated animal protein excess. Hyperuricosuria results from purine load, and hyperphosphaturia from high phosphate content of meat products. Low urinary pH, hypocitraturia, and hypercalciuria are produced by acid load. Urinary oxalate sometimes is reduced because of low content of oxalate in meat products. These derangements theoretically could be prevented by potassium citrate therapy.
Hypocitraturia, High Urinary pH, and Hypercalciuria
A 50-year-old woman had severe hypocitraturia of 50 mg/d, pH of 7.0, and hypercalciuria of 250 mg/d. She had formed stones composed of hydroxyapatite. An abdominal radiograph disclosed nephrocalcinosis. Although serum electrolyte levels were normal, her urinary pH did not decline below 5.4 on ammonium chloride challenge. She had incomplete distal RTA. The treatment is potassium citrate.
High Urinary pH, Hyperoxaluria with Normal Urinary Citrate
A 40-year-old man had urinary pH of 7.0, urinary oxalate level of 70 mg/d, and urinary calcium level of 260 mg/d. His urinary citrate level was high normal at 750 mg/d, as was his uric acid level at 480 mg/d. His urinary ammonium level was low normal at 20 mmol/d. His wife had imposed a “healthy diet” composed of limited intake of meat products (one serving per day) with plentiful intake of vegetables and fruits and many multivitamins and minerals. Diet history disclosed a high intake of oxalate. He also was found to be taking 1.5 g/d vitamin C and 1.5 g/d calcium. He formed a calcium oxalate stone.
He probably had an alkali load from his vegetarian diet, indicated by high urinary pH, high normal urinary citrate level, and low normal urinary ammonium and uric acid levels. This presentation alone probably did not cause stone formation. He also had taken calcium supplements and vitamin C, which led to hypercalciuria and hyperoxaluria.
SUMMARY
A simple, step-by-step approach to diagnosis and medical treatment of stone disease is described. It uses urinary stone risk profile obtained before and after dietary modification, history, and minimum diagnostic tests. For each abnormal stone risk factor, potential causes are discussed and treatment options are presented. The article concludes with diagnosis and treatment of combined disturbances.
Urologic Clinics of North America
Volume 27 • Number 2 • May 2000
Copyright © 2000 W. B. Saunders Company
Charles Y. C. Pak 1 MD
Martin I. Resnick 2 MD
1 Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical School, Dallas, Texas (CYCP)
2 Department of Urology, Case Western Reserve University, School of Medicine, Cleveland, Ohio (MIR)
Supported by USPHS grants P01-DK20543 and M01-RR00633
Address reprint requests to
Charles Y. C. Pak, MD
Center for Mineral Metabolism and Clinical Research
University of Texas Southwestern Medical School
5323 Harry Hines Boulevard
Dallas, TX 75390-8885
References
1. Chaussey C, Schridt E, Brendel W: Extracorporeally induced destruction of kidney stones by shock waves. Lancet ii:1265-1268, 1980
2. Coe FL: Hyperuricosuric calcium oxalate nephrolithiasis. Kidney Int 13:418-426, 1978
3. Coe FL, Keck J, Norton R: The natural history of calcium nephrolithiasis. JAMA 238:1519-1523, 1977
4. Earnest DL, Williams HE, Admirand WH: A physicochemical basis for treatment of enteric hyperoxaluria. Trans Assoc Am Phys 88:224-234, 1975
5. Fine JK, Pak CYC, Preminger GM: Effect of medical management and residual fragments on recurrent stone formation following shock wave lithotripsy. J Urol 153:27-33, 1995
6. Hayashi Y, Kaplan RA, Pak CYC: Effect of sodium cellulose phosphate therapy on crystallization of calcium oxalate in urine. Metabolism 24:1273-1278, 1975
7. Khatchadurian J, Preminger GM, Whitson PA, et al: Clinical and biochemical presentation of gouty diathesis: Comparison of uric acid versus pure calcium stone formation. J Urol 154:1665-1669, 1995
8. Nicar MJ, Peterson R, Pak CYC: Use of potassium citrate as potassium supplement during thiazide therapy of calcium nephrolithiasis. J Urol 131:430-433, 1984
9. Pak CYC: Medical prevention of renal stone disease. Nephron, in press
10. Pak CYC: Physiological basis for absorptive and renal hypercalciurias. Am J Physiol 237:F415-F423, 1979
11. Pak CYC: Southwestern Internal Medicine Conference: Medical management of nephrolithiasis: A new, simplified approach for general practice. Am J Med Sci 313:215-219, 1997
12. Pak CYC, Peterson R: Successful treatment of hyperuricosuric calcium oxalate nephrolithiasis with potassium citrate. Arch Intern Med 146:863-868, 1986
13. Pak CYC, Sakhaee K, Fuller C: Successful treatment of uric acid nephrolithiasis with potassium citrate. Kidney Int 30:422-428, 1986
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16. Pak CYC, Oh MS, Baker S, et al: Effect of meal on the physiological and physicochemical actions of potassium citrate. J Urol 146:803-805, 1991
17. Preminger GM, Pak CYC: Eventual attenuation of hypocalciuric response to hydrochlorothiazide in absorptive hypercalciuria. J Urol 137:1104-1109, 1987
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19. Rudman D, Dedonis JL, Fountain MT, et al: Hypocitraturia in patients with gastrointestinal malabsorption. N Engl J Med 303:657-661, 1980
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22. Sakhaee K, Nigam S, Snell P, et al: Assessment of the pathogenetic role of physical exercise in renal stone formation. J Clin Endocrinol Metab 65:974-979, 1987
23. Sakhaee K, Williams RH, Oh MS, et al: Alkali absorption and citrate excretion in calcium nephrolithiasis. J Bone Miner Res 8:787-792, 1993
24. Wabner CL, Pak CYC: Effect of orange juice consumption on urinary stone risk factors. J Urol 149:1405-1408, 1993
25. Yendt ER, Guay GF, Garcia DA: Use of thiazides in the prevention of renal calculi. Can Med Assoc J 102:614-620, 1970
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