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Year : 2002  |  Volume : 19  |  Issue : 1  |  Page : 20-28

Current approaches in the medical management of urolithiasis: A review article

Department of Urology, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
N P Gupta
Department of Urology, AIIMS, Ansari Nagar, New Delhi - 110 029
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The medical management of urolithiasis has undergone a great change. In the present time the management of urolithiasis is not only stone removal but also to prevent its recurrence. With the recent advances in the knowledge of pathogenesis of urolithiasis, the medical management is not only restricted to increased fluid intake, but to de­termine the cause of urolithiasis by a battery of investiga­tion, the use of a particular drug to prevent urolithiasis if required and then to check the effectiveness of the drug by the application of investigations. This article has taken into consideration the various aspects of the etiopathogenesis of urolithiasis and its application towards the prevention of urolithiasis.

Keywords: Urolithiasis; Medical Management; Renal Calculus; Pathophysiology

How to cite this article:
Gupta N P, Kesarwani P. Current approaches in the medical management of urolithiasis: A review article. Indian J Urol 2002;19:20-8

How to cite this URL:
Gupta N P, Kesarwani P. Current approaches in the medical management of urolithiasis: A review article. Indian J Urol [serial online] 2002 [cited 2023 May 28];19:20-8. Available from:

   Introduction Top

The prevalence of urinary tract stone disease is esti­mated to be around 2-3% with the likelihood of a man developing stone disease by the age of 70 being 1 in 80. [1] The recurrence rate without treatment for calcium oxalate stone is about 10% at one year, 35% at five years and 50% at ten years. [2] The objective of medical approach in stone managmenent differs fundamentally from that of the surgical approach. [3]

In the last two decades there have been great advances in the field of removal of stones which includes extracor­poreal shock wave lithotripsy, percutaneous nephro­lithotomy and ureteroscopy. Taking into consideration the incidence of recurrence, surgical treatment of the urinary tract stone is an incomplete procedure. The goal of the surgical treatment is the removal of existing stones while that of the medical treatment is prevention of recurrent stone formation. Equally important progress has been made in the medical arena, continued medical diagnosis and treatment. The combined application of surgical and medical approaches is mandatory for the full control of the dis­ease.

The importance of a medical prophylactic program is emphasized by the findings that urolithiasis is a disease with a high probability of recurrence [4] and the removal of stones is not likely to prevent new stone formation. While the medical approach potentially offers effective preven­tion of stone recurrence, [5],[6],[7] its application requires patho­physiological elucidation and diagnostic assessment. This article reviews and updates the progress made in the areas of pathophysiology and medical management of urolithi­asis.


   Hypercalciuria Top

The association between increased urinary calcium ex­cretion and calcium oxalate renal stones has been re­ported [8],[9],[10] and about 30-60% of patients with calcium oxalate stones have increased urinary calcium excretion in the absence of raised serum calcium levels. Urinary calcium excretion depends on dietary calcium intake, which varies between 400-2000 mg/day. Thus, the diag­nosis of hypercalciuria requires a strict definition:

- Excretion of greater than 200 mg of calcium/24 hrs after one week adherence to a 400 mg of calcium and 100 mg of sodium diet. [11]

- Excretion of greater than 4 mg of calcium/kg body weight or greater than 7 mmol in men and 6 mmol in women. [12]

- Excretion of urinary calcium of greater than 0.11 mg/100 ml of glomerular filtrate. [13]

For the purpose of diagnosis and management hyper­calciuria is divided into three types:

1. Absorptive hypercalciuria - Where the primary ab­normality involves the increased intestinal absorption of calcium. This is further divided into three types:

Type 1 - the intestinal hyperabsorption of calcium ex­ists irrespective of calcium restricted diet.

Type 2 - a variant where the patients exhibit increased urinary calcium excretion while on their normal diet but normal calcium excretion on a low calcium, low sodium diet.

Type 3 - a variant with renal phosphate leak causing hypophosphatemia which leads to increased renal synthe­sis of 1, 25 (OH)2 D resulting in hyperabsorption of cal­cium and the syndrome of hypercalciuria.

2. Renal hypercalciuria characterized by primary re­nal leak of calcium.

This involves primary renal wasting of calcium with consequent reduction in serum calcium stimulating par­athyroid production. The increased parathyroid results in hydroxylation of 25 hydroxy Vit D to 1,25 dihydroxy Vit D3 increasing intestinal calcium absorption. These effects restore the serum calcium to normal at the expense of in­creased parathormone and 1,25 dihydroxy Vit D3.

Two factors which differentiate renal hypercalciuria from absorptive type hypercalciuria are elevated fasting urinary calcium and stimulated parathyroid function.

There is a more generalized disturbance is renal tubular function with renal hypercalciuria as shown by an exag­gerated natriuretic response to thiazide [16] and exaggerated calciuric response to carbohydrate load. [17]

3. Resorptive hypercalciuria characterized by increased bone demineralization. [15]

Hypercalciuria results from excess PTH dependent bone resorption as well as enhanced intestinal absorption of calcium caused by PTH itself or by a PTH dependent syn­thesis of 1,25 OH2 Vit D3. Although PTH causes increased tubular absorption of calcium, the increase in the filtered load of calcium overwhelms this and results in excessive urinary calcium excretion.

   Hyperoxaluria Top

Hyperoxaluria is related to calcium oxalate nephrolithiasis and is usually of three types.

  1. Increased oxalate production

    - primary hyperoxaluria

    - increased hepatic conversion

  2. Increased oxalate absorption

  3. Hyperoxaluria in idiopathic calcium oxalate stone disease.

Primary hyperoxaluria

It is of two types.

Type 1 - an autosomal recessive inborn error of me­tabolism characterized by nephrolithiasis, tissue deposi­tion of oxalate and death from renal failure before the age of 20 in untreated patients. [18] There is increased excretion of oxalic, glycolic and glyoxalic acids due to the defect of enzyme alanine glyoxalic acid aminotransferase (AGT) in the liver. [19]

Type 2 - a rare variant occurs due to the deficiency of hepatic enzyme D-glycerate dehydrogenase and glyoxylate reductase, which leads to increase in urinary oxalate and glycerate excretion. [20]

Increased hepatic conversion occurs due to the pyridox­ine deficiency, ethylene glycol ingestion and methoxy­flurane anesthesia.

Increased Oxalate Absorption

Conditions causing increased oxalate absorption lead­ing to hyperoxaluria are malabsorption occurring from bowel resection, intrinsic disease or jejunoileal bypass, which leads to increased colonic permeability of oxalate as a result of exposure of the colonic epithelium to bile salts; further the unabsorbed fats bind with the calcium making the dietary oxalate free for absorption.

Mild Metabolic Hyperoxaluria

Increased urinary oxalate excretion is seen in 0.3-0.5% of patients with calcium stones. [21] Increased dietary pro­tein intake and altered renal excretion of oxalate have been predicted as an important cause for increased oxalate excretion. [22]

   Hyperuricosuria Top

Patients with gout or hyperuricosuria form calcium oxalate stones apart from the uric acid stones. The most important cause for hyperuricosuria is excessive purine intake. Apart from this some patients have tendency to excrete more uric acid in the urine than do the normal subjects even on purine-free diet due to the increased uric acid production from endogenous purine metabolism.[23]

Factors leading to uric acid lithiasis in these patients are

(i) Excessive excretion of acid urine at relatively fixed low urinary pH;

(ii) Absorb, produce and excrete more uric acid than patients without gout to uric acid stones;

(iii) Diminished urine volumes.

All these factors serve as an ideal mechanism for the crystallization of uric acid in the urine. Uric acid further promotes calcium oxalate crystallization by facilitating the formation of nuclei. Addition of crystal:; of uric acid to the supersaturated calcium oxalate solution induces the deposition of well-oriented crystals of calcium oxalate over the uric acid. Sodium acid urate also nullifies the effectiveness of naturally occurring inhibitors of calcium oxa­late crystal growth.

Hyperuricosuria may be seen in patients with specific enzyme defects such as increased activity of 5 phosphori­bosyl 1-pyrophosphate synthetase, the enzyme that initi­ates purine metabolism and Lesh-Nyhan syndrome, with deficiency or complete lack of hypoxanthine guanine phosphoribosyl transferase resulting in shunting of hypox­anthine to xanthine/uric acid pathway leading to hyperuri­cosuria and hyperuricimea. Myeloproliferative disorders such as acute leukemia are important causes in childhood.

   Hypomagnesuria Top

Decreased magnesium excretion is also a known fact for increased stone formation. [24] The most common cause of overt hypomagnesuria is inflammatory bowel disease associated with malabsorption. Patients with hypomagne­suria also have hypocitraturia.[25] The loss of inhibitory or complexing activity of magnesium or citrate is responsi­ble for calcium oxalate crystallization.

   Ammonium Acid Urate Stones Top

The stones are commonly found in children of devel­oping countries and females with a history of laxative abuse. Conditions giving rise to these stones are [26],[27]

  • low fluid intake;
  • urealytic infection in the presence of excessive uric acid excretion;
  • urinary phosphate deficiency.

   Cystinuria Top

It is an autosomal recessive disorder of transmembrane cystine transport manifested as disease in absorption in the intestine and reabsorption in the proximal tubule. [28] The cystine excreted in the urine is poorly soluble within the range of normal pH and thus crystallizes to form the stone.

   Hypocitraturia Top

Hypocitraturia has been reported in 19-63% of patients with nephrolithiasis. [29] There is wide range of variation for the normal level of citrate in urine. According to Dallas the low normal limit of citrate in urine is 320 mg/day for both men and women, irrespective of age and this limit provides a good empirical definition of hypocitraturia, since patients with urinary citrate below this level often show a clinical response to potassium citrate therapy su­perior to those whose citrate exceeds 320 mg/day. [30]

Hypocitraturia results from acidosis owing to a variety of disturbances, including distal renal tubular acidosis (complete and incomplete), [31] acidosis of chronic diarrhoea) state [32],[33] and potassium loss occurring from thiazide therapy.

In some patients, the exact cause of hypocitraturia is not known. [34],[35] In these patients, it is usually related to the consumption of a diet rich in animal proteins consisting of sulphur-containing amino acids (producing acid load),[36] strenuous physical exercise [30] and high sodium intake in the setting of low potassium intake (resulting in intracel­lular acidosis). Hypocitraturia is also encountered in pa­tients with active urinary tract infection, presumably from the degradation of citrate by bacterial enzymes.

Pathogenic Role of Citrate in Calcium Nephrolithiasis

Citrate retards the crystallization of stone forming calcium salts by two mechanisms:

  1. The principal action is the complexation of calcium causing a reduction in ionic calcium concentration and in the urinary saturation of stone-forming calcium salts. [37],[38]
  2. Citrate directly inhibits the crystallization of calcium oxalate and calcium phosphate by agglomeration of calcium oxalate. It has a modest inhibitory role on the growth of calcium oxalate crystal. [39] Citrate acts as a potent inhibitor of crystal growth of calcium phos­phate. In addition citrate has the ability to impair urate­ induced crystallization of calcium oxalate. [40]

When expressed relative to molecular weight, the in­hibitory activity is much less than that of other inhibitors such as pyrophosphate, glycosaminoglycans, glycopro­teins or Tamm-Horsfall protein but the amount of citrate normally present in the urine is many times that of other inhibitors.

Due to these inhibitors of citrate, the urinary environ­ment of patients with hypocitraturic nephrolithiasis is char­acterised by an increased propensity for the crystallization of calcium salts.

Physiologic Basis For Hypocitraturia: Normal Physiology

Citrate is a key component of the citric acid cycle con­stituting an important source of energy. Only a small frac­tion of the large amount of citrate metabolized by the whole organism appears in the urine. Dietary citrate is a poor source of citrate since only 0.7% of it appears in the urine. [41]

In the circulation, citrate is present as a trivalent anion at a concentration of about 0.14 mM. Of the 9 micromoles of the citrate filtered by the kidney each minute 75% of it is reabsorbed in the proximal tubule and the rest 25% ap­pears in the urine. [42] The proximal tubule also extracts citrate from the post glomerular blood at a rate of 1.5 mi­cro mol./mt. making it to a total of 8.25 micro mol./mt.

The subsequent citrate oxidation to carbon dioxide and water via the citric acid cycle in the mitochondria of the tubular cell provides an important source of energy for the kidney. The tubular uptake of citrate alone accounts for the fact that citrate concentration in the renal cortex often exceeds that of peripheral blood.

Alternation in RenalCitrate Handling by Change in Acid Base Status

An alteration in acid base status profoundly influences the renal handling of citrate making it a major determi­nant of urinary citrate excretion. Metabolic acidosis fa­cilitates the influx of citrate to the renal mitochondria, promoting citrate oxidation. A subsequent fall in the cytosolic citrate concentration leads to enhanced citrate uptake by the tubular cells, involving the sodium citrate cotransporter in the brush border basement membrane and the peritubular uptake. The increased tubular reabsorp­tion of citrate reduces urinary citrate excretion, while stimulated mitochondrial citrate oxidation lowers the tis­sue content of citrate. Thus reduced citrate clearance par­allels the fall in citrate concentration in the renal cortex.

These changes often occur without a substantial altera­tion in serum citrate concentration, moreover negligible citrate is secreted or synthesized during metabolic acido­sis. The citrate finally appearing in the urine is that small fraction of citrate that escapes reabsorption. Metabolic aci­dosis reduces citrate excretion by augmenting citrate re­absorption.

Exactly the opposite sequence prevails in metabolic al­kalosis; mitochondria) uptake of citrate is reduced retard­ing citrate oxidation while cytosolic concentration rises leading to reduced tubular reabsorption and peritubular uptake of citrate. Urinary citrate increases since a smaller fraction of filtered citrate is reabsorbed.

Other Determinants Of Citrate Excretion

Hypokalemia causes an intracellular metabolic acido­sis in the renal cortex[43] leading to reduced citrate excre­tion by the same mechanism as in metabolic acidosis.

Organic acids (malate, succinate and furnerate) stimu­late intrarenal citrate synthesis by providing substrate. [44] In addition, they provide an alkali load. These compounds enhance citrate excretion mostly through the effect of al­kali on renal citrate handling and partly from the escape into the urine of synthesized citrate.

The ingestion of tamarind, a food item rich in tartaric acid, is believed to be useful in preventing stone forma­tion. [45] The ability of tartaric acid to stimulate citrate ex­cretion may explain this action.

Certain hormones may affect renal citrate excretion by a mechanism still poorly defined. Urinary citrate excretion is higher during the latter half of the normal menstrual cy­cle than the first half (by 100-200m-/day). [46] During preg­nancy, urinary citrate excretion increases by 500 - 1000mg/ day. These results have been attributed to the action of oestrogen or progesterone or both. Parathyroid hormone also augments citrate excretion [47] as seen in patients suffer­ing from primary hyperathyroidism. Vitamin D and calci­tonin augment while androgen reduces citrate excretion.


With time, there have been notable advances in the man­agement of urolithiasis. The aim of the medical manage­ment is prevention of recurrent stones and if possible dissolution of the stone. The medical management of uro­lithiasis is a multistep approach that involves a detailed history and complete investigation. The institution of the medical therapy depends on the conclusion derived from the detailed workup.

The workup involves a detailed history to predict any causative factor for urolithiasis followed by the investiga­tion which includes urine examination, serum investiga­tions, stone analysis and if required twenty-four hours urine analysis on customary and controlled diet to detect any pathological factor (environmental, metabolic, physio­chemical) which may lead to further stone formation.

The medical therapy consist of two parts:

  • dietary modification;
  • treatment of individual abnormal stone risk factors.

   Dietary Modification Top

All patients of stone disease are advised to follow the dietary modification irrespective of their normal investi­gations.

High fluid intake

Patient is informed to measure urine output once a week and then adjust the fluid intake to maintain urine output more than two litres per day. They are also advised to take maximum intake of fluid within three hours after tak­ing the meals, during periods of physical exercises, bed­time and once at midnight. Plain water is good enough but potassium rich citrus fruit juices such as orange, grape fruit and cranberry are preferable to low potassium citrus fruits such as lime and lemon. Orange juice, for example, represents a natural form of potassium citrate and pos­sesses alkalinizing and citraturic action. [48] Lime juice, on the other hand, is composed largely of citric acid, and does not affect acid base balance appreciably, so it does not alter urinary pH and only modestly increases urinary citrate. [49] Increasing fluid intake actually has been demon­strated to have positive effect on two urinary inhibitors, citrate and Tamm-Horsfall protein. Hydration augments urinary citrate excretion, which is thought to result from an increased fluid flux in the proximal tubule resulting in the delivery of more bicarbonate to the cells of this por­tion of the nephron. [50],[51],[52] Urinary dilution has been found to increase the inhibitory activity of Tamm-Horsfall pro­tein on the calcium oxalate monohydrate crystal aggrega­tion in the urine of the stone formers. [53]

Restriction of animal proteins

Patient is informed to avoid nonvegetarian diet and the recommendation is of 8 oz or less of dry meat per day. Animal proteins are rich in sulphur-containing amino ac­ids such as cystine and methionine, which on oxidation produces sulphate which forms a soluble complex with calcium in the nephron and limits the reabsorption of this cation. Bone serves as a buffer and the resultant osseous dissolution provides more calcium to be excreted. [54],[55],[56] Chronic metabolic acidosis decreases calcium reabsorp­tion within the nephron, which further augments excre­tion of this mineral. Increased protein consumption also augments glomerular filtration, thus delivering more cal­cium to the nephron, which promotes its excretion. [57] Ani­mal protein has a high purine content, which leads to increase in uric acid excretion. The associated acidosis results in a decrease in urinary pH that could potentiate uric acid urolithiasis. Acidosis also enhances citrate reasbsorption in the proximal tubule, thus decreasing the excretion of citrate in the urine.

Sodium restriction

Patient is asked to avoid high sodium-containing food with restriction of salt in the diet and salty shakers. In­creased sodium intake may promote a variety of meta­bolic changes that may be detrimental to stone formers, including increase in the urinary pH, calcium and cystine excretion and a decrease in citrate excretion.

Oxalate restriction

Avoidance of nuts, spinachs, dark roughage, chocolate, tea, and vitamin C coupled with the advice to maintain recommended daily intake of calcium and to ensure that calcium consumption accompanies the ingestion of oxalate rich foods to prevent the absorption of oxalate.

Restriction of calcium

Moderate restriction of calcium is recommended and about 250m1 of milk or milk products can be taken daily. In patients who are advised for long-term restriction of calcium intake, measurement of bone density, particularly in the spine is recommended.

   Treatment of Individual Abnormal Stone Risk Factors Top


The management of hypercalciuria depends on its type.

Absorptive hypercalciuria

Type I - Cellulose phosphate in the dose of 10-15g orally in three divided dosages is to be taken with meals. It is an effective nonabsorbable exchange resin, which binds the calcium in the gut and prevents bowel absorption. It has no impact on the calcium transport mechanism and the urinary calcium excretion returns to normal values with therapy. This therapy is contraindicated in postmenopau­sal women and in children during the period of active growth. Hydrochlorothiazide is an alternative treatment but the effect on calcium excretion is temporary. It causes a decrease in the renal excretion of calcium. The increased absorbed calcium is deposited in the bone. Gradually the bone reservoir reaches its capacity and the drug becomes ineffective. Hydrochlorothiazide may be alternated with cellulose phosphate for an effective treatment regimen.

Type II - Since this is dietary dependent reduction of the calcium intake to 400-600 mg/day reduces calcium excretion to normal.

Type III - Orthophosphate is administered in the dos­age of 250 - 2000 mg 3-4 times/day preferably after meals and before bedtime. It inhibits vitamin D synthesis, which finally decreases absorption of the calcium.

Renal Hypercalciuria

Thiazide diuretics like trichlorthiazide are recom­mended. They have effect on the proximal and the distal tubules. Acting as a diuretic, it decreases the circulating blood volume and subsequently stimulates proximal tu­bular absorption of calcium.


Patients suffering from mild hyperoxaluria (<60 mg/ day) are easily managed on the dietary restriction of oxalate rich foods such as spinach, dark roughage, tea, chocolate and nuts. Vitamin C supplementation should not increase more than 500 mg/day in such patients. Patients suffering from absorptive hypercalciuria maintained on calcium re­striction could have mild hyperoxaluria due to insufficient amount of calcium left in the bowel to bind oxalate.

In patients with moderate to severe hyperoxaluria com­monly seen in patients suffering from intestinal malab­sorption of fat, inflammatory disease or resection of the small bowel, patients with aborptive hypercalciuria tak­ing cellulouse phosphate, a rigid restriction of dietary oxalate is critical. Solublized calcium may further help to lower urinary oxalate by binding oxalate.

In the absence of bowel disease or absorptive hypercal­ciuria in the patients suffering from moderate to severe hyperoxaluria, mild metabolic hyperoxaluria or primary hyperoxaluria must be suspected and pyridoxine in the dosage of 100 to 200 mg/day is required for suppression of oxalate synthesis in vivo.


In patients with normouricimea, hyperuricosuria is caused by dietary excess of animal proteins. The general recommendation in these patients is a balanced diet with a reduced intake of animal proteins and increased intake of vegetables and fruits, although the long-term compliance in patients with dietary modification is very poor. Allopurinol (300 mg/day) is indicated in such patients if hyperuricosuria is more than 800 mg/day.

In patients with hyperuricimea e.g., gouty diathesis, al­lopurinol (300 mg/day) is indicated to reduce serum uric acid. Potassium citrate is also added to alkalinize the urine.


The main goal of therapy is to lower cystine concentra­tion in the urine below 200 mg/L. Dietary restriction is the primary therapy with the avoidance of diet containing essential amino acid methionine such as meat, poultry, fish, and dairy products. Increasing urine output on 3 L/day allows dissolution of existing stones and prevents new stone formation. The pH of the urine is kept high (>7.5) to allow dissolution of the stone. Sodabicarbonate (15-25 gm/ day) and potassium citrate (15-20 mmol two to three times per day) are commonly used to alkalinize the urine. Aceta­zolamide 250 mg three times a day augments the alkalini­zation achieved by the citrate and bicarbonate. Glutamine 2 g/day can further reduce the excretion of the cystine especially if the intake of sodium is very high.

If hydration and alkalinisation is ineffective in reduc­ing the excretion of cystine or cystine formation then complexing agents such as penicillamine or alfa mercap­topurine can be used. These agents bind cystine, forming a complex solution that is soluble in the urine. Captopril has also been used to lower cystine excretion by forming a captopril-cystine disulfide complex.


Citrate is an important inhibitor of crystallization of stone-forming salts and hypocitraturia being common among patients with calcium nephrolithiasis. It is appar­ent that maneuvers that maintain urinary pH between 6&7 and that raise urinary citrate levels to the normal would be desirable in preventing the formation of calcium oxalate stones.

Potassium citrate taken orally is absorbed mostly under normal circumstances. The citrate after absorption is me­tabolized to bicarbonate. In absence of a deficit of bicar­bonate in plasma, the bicarbonate ions are excreted in urine that is rendered alkaline.

The small amount of absorbed citrate that escapes oxi­dation in the urine contributes in a minor way to the citraturic action of potassium citrate.[58]In the presence of hypokalemia, the potassium ion augments citrate excre­tion by correcting intracellular acidosis.

During long-term treatment, potassium citrate has been shown to cause a sustained rise in urinary citrate and pH.[29] In patients with mild to moderate hypocitraturia (100-320 mg/day), potassium citrate (60 meq/day) increases urinary citrate by about 400 mg/day. The urinary pH rises by about 0.5 units and can be maintained at about 6.5. The citraturic action is less prominent in those cases with severe hypocitraturia (e.g., complete renal tubular acidosis and severe chronic diarrhoeal syndrome). The total rise in uri­nary pH is less marked in renal tubular acidosis in which urinary pH is usually high.

Potassium citrate has a hypocalciuric effect because of enhanced renal calcium absorption and is usually tran­sient. [59] In patients with renal tubular acidosis the hypocal­ciuric effect is sustained. [31] This is in contrast to sodium citrate where calcium excretion is unaffected since alkali mediated hypocalciuric effect is offset by sodium linked calciuresis. [60],[61]

Physiochemical effects of potassium citrate are associated to its citraturic and alkalinizing action resulting in [29]

  • Inhibition of the crystallization of calcium salts in the urine. [5]
  • Rise in pH contributes to the retardation of the crystallization of calcium salts and inhibits uric acid crystallization.
  • At a high pH more phosphate and citrate ions become dissociated further augmenting the complexation of calcium.
  • Dissociation of citrate, pyrophosphate and other macromolecules may accentuate their inhibitor activity against crystallization of calcium salts.
  • The rise in urinary pH increases the dissociation of uric acid, reducing the concentration of undissociated uric acid and the propensity for the uric acid lithiasis. [34]

Distal Renal Tubular Acidosis Type 1

Potassium citrate therapy is capable of correcting both metabolic acidosis and hypokalemia. In severe acidosis, large doses (up to 120 mEq/day) may be required to re­store normal urinary citrate level. [62] Urinary calcium de­clines with the correction of acidosis. The overall rise in urinary pH is generally below 7.5 during treatment unless there is a complication by a urinary tract infection.

If there is a substantial renal sodium leak, alkali must be provided as a mixed sodium potassium salt, although renal sodium wasting is not prominent in most patients with renal tubular acidosis who present with stones.

Potassium citrate is contraindicated in patients with moderate to severe renal disease (endogenous creatinine clearance of <40 ml/mt). If it were to be used in those with moderate renal disease, it should be begun at a lower dosage and the serum potassium levels should be care­fully monitored.

Chronic Diarrhoeal Syndrome [29],[32]­

In patients with mild to moderate severity of intestinal fluid loss and in whom hypocitraturia is not severe (100-320 mg/day), potassium citrate (40-60 mEq/day in 3-4 divided doses, is effective in restoring normal urinary citrate.

A liquid preparation is usually preferred in such cases rather than a slow release tablet because some of these patients have intestinal adhesion and may be prone to ob­struction from a tablet preparation. Furthermore, a slow release medication may be poorly absorbed due to rapid intestinal transit. A frequent dose schedule (3-4 times/day) is advisable for the liquid preparation because of relatively short duration of biological action. Other drugs may be necessary for the treatment of additional disturbances.

If hypomagnesuria is present, magnesium citrate (10 mEq two to four times/day) may raise urinary magnesium and increase urinary citrate and pH.

When hyperoxaluria coexists, dietary oxalate restriction is a must. In patients of hyperoxaluria with hypocalciuria, calcium citrate is useful which lowers renal excretion of oxalate by binding it in the intestinal tract, raises urinary citrate, corrects malabsorption of calcium and averts po­tential developments of bone disease.

Thiazide Induced Hypocitraturia [63],[64]

Hypokalemia resulting from thiazide leads to hypo­citraturia, which may attenuate the beneficial hypocalciuric effects of therapy in urolithiasis. Use of potassium citrate with thiazide raises urinary pH and citrate. It is recom­mended that potassium citrate (15-20 mEq twice a day) be given to all patients being treated with thiazide for hypercalciuric nephrolithiasis. [65]

Idiopathic Hypocitraturic Calcium Nephrolithiasis [63],[66]

This includes hypocitraturia occurring alone with cal­cium stones and hypocitraturia occurring in conjunction with absorptive and renal hypercalciuria and hyperurico­suric calcium oxalate nephrolithiasis. [40] In these patients the stones are predominantly calcium oxalate.

Potassium citrate (15-30 mEq twice a day) produces a sustained increase in urinary citrate excretion, maintains pH between 6.5-7.0 and decreases the urinary saturation of calcium oxalate to normal limits.

Uric Acid Nephrolithiasis [34],[67]

Potassium Citrate is recommended in patients with hyperuricosuric (gouty diasthesis) for prevention of both calcium oxalate and uric acid stone formation.

Potassium citrate creates an environment less condu­cive to the crystallization of uric acid by increasing uri­nary pH and reducing the amount of undissociated uric acid. It inhibits urinary crystallization of calcium oxalate by reducing urinary saturation and augmenting the inhibi­tor activity owing to the rise in urinary citrate and pH.

Post Extra Corporeal Shock Wave Lithotripsy Fragments [68],[69]

The natural history of residual stone fragments after ESWL shows growth and persistence of the calculus. In patients with residual fragments <5 mm or clinically in­significant residual fragments (CISF) with calcium oxalate and/or infection stones use of potassium citrate (6-8 gm in 2-3 divided doses) has significantly ameliorated the outcome of these residual fragments by decreasing growth or agglomeration, allowing spontaneous passage and fi­nally improving the clearance rate.

Advantages of Potassium Citrate Compared with other Alkali

Potassium citrate is a better substitute than potassium bicarbonate because of more prolonged rise in urinary citrate and pH. The increment in urinary citrate is more pronounced with potassium citrate due to the renal excre­tion of small amount of absorbed citrate that has excaped oxidation. [62]­

When compared with sodium citrate, potassium citrate reduces calcium excretion by augmenting the renal tubu­lar absorption of calcium. [60] Urinary sodium remains unal­tered with potassium citrate but increases during sodium citrate therapy. [62] In patients with hypokalemia, potassium citrate causes a more pronounced rise in citrate excretion than sodium citrate.

   Conclusions Top

The medical management of urolithiasis is a rational approach based on the abnormal parameters detected on full investigation. However, in clinical practice it is very difficult as the patients may have all normal urinary pa­rameters or multiple deranged parameters. In patients with all normal urinary parameters (idiopathic) the patient is advised dietary restriction and kept on periodic surveil­lance. In patients with multiple deranged parameters the drug approach in a permutation combination rationale is applied with periodic surveillance of the parameters at repeated intervals for dose modification or temporary dis­continuation of the drug therapy. Both surgical and medi­cal treatment is necessary for the complete management of patients of urolithiasis.

   References Top

1.Menon M, Parulkar B, Druch G. Urinary lithiasis : Etiology, diag­nosis and medical management. In Walsh P, Retik A, Darracott E et al (eds.). Campbells Urology (ed. 7). Philadelphia, WB Saunders, 1998; 2659-2733.  Back to cited text no. 1    
2.Uribari J, Man S, Carroll JH. The first kidney. Ann. Intern. Med. 1989; 111: 1006-1009.  Back to cited text no. 2    
3.Resnick MI, Pak CYC. Are metabolic studies of urolithiasis neces­sary ? J Urol 1987; 137: 960.  Back to cited text no. 3    
4.Coe FL, Keck J, Norton ER. The natural history of calcium uro­lithiasis. JAMA 1977; 238: 1519.  Back to cited text no. 4    
5.Pak CYC. Medical management of nephrolithiasis. J Urol 1982; 128: 1157.  Back to cited text no. 5    
6.Coe FL, Kavalach AG. Hypercalciuria and hyperuricosuria in patients with calcium nephrolithasis. New Engl J Med 1974; 291: 1344.   Back to cited text no. 6    
7.Yendt ER. Cohanim M. Prevention of calcium stones with thiazides. Kidney Int 1978; 13: 397.  Back to cited text no. 7    
8.Flocks RH. Calcium and phosphorus excretion in the urine of pa­tients with renal and ureteric calculi. JAMA 1939; 113: 1466.  Back to cited text no. 8    
9.Albright F, Refienstein EC. The parathyroid glands and metabolic bone diseases. Baltimore, Williams and Wilkins, 1948.  Back to cited text no. 9    
10.Albright F, Suby H, Sulcowitch HE. In Albright F, Refienstein EC, (eds). The parathyroid glands and metabolic bone diseases. Balti­more, Williams and Wilkins 1948.  Back to cited text no. 10    
11.Pak CYC. Renal stone disease. Boston, Martirus, Nijhoff Publish­ing 1987.  Back to cited text no. 11    
12.Parks JH, Coe FL. A urinary calcium citrate index for the evalua­tion of nephrolithiasis. Kidney Int 1986; (3) 85-90.  Back to cited text no. 12    
13.Broadus AE, Domoingres M, Bartter FC. Pathophysiological stud­ies in idiopathic Hypercalciuria : Use of an oral calcium tolerance test to characterize distinctive Hypercalciuria subgroups. J Clinic Endocrinol Metab 1978; 47: 751-760.  Back to cited text no. 13    
14.Pak CYC. Ohata M, Lawrence EC, Synder W. The hypercalciurias: causes, parathyroid functions and diagnostic criteria. J Clin Invest 1974;54:387.  Back to cited text no. 14    
15.Pak CYC, Petus P, Hurt G, Kadesky M. Fine M, Reisman D, Splan F, Caramela C, Freena A, Britton F, Sakahee K, Breslar NA. Is selective therapy of recurrent nephrolithiasis possible ? Amer J Med 1981;71:615.  Back to cited text no. 15    
16.Sakahee K, Nicar MJ, Brater DC, Pak CYC. Exaggerated natriu­retic and calciuric response to hydrochlorothiazide in renal hypercalciuria but not in absorptive hypercalciuria : J Clin Endo Metab 1985: 61: 825.  Back to cited text no. 16    
17.Barilla DE, Townsend J, Pak CYC. An exaggerated augmentation of renal calcium excretion after oral glucose ingestion in patients with renal Hypercalciuria : Invert, Urol 1978; 15: 486.  Back to cited text no. 17    
18.Williams HE. Smith LH. L-glyceric aciduria : A new genetic vari­ant of primary hyperoxaluria. N Engl J Med 1978; 278: 233-328.  Back to cited text no. 18    
19.Menon M, Mahle CJ. Oxalate metabolism and renal calculi. J Urol 1982; 127: 148-151.  Back to cited text no. 19    
20.Williams HE, Smith LH. Disorders of oxalate metabolism. Am J Med 1968; 45: 715-735.  Back to cited text no. 20    
21.Menon M, Mahle CJ. Prevalence of hyperoxaluria in idiopathic cal­cium oxalate urolithiasis : Relationship to other metabolic abnor­malities (abstract 458). Presented at AUA, Las Vegas 1983.  Back to cited text no. 21    
22.Pinto B. Crespi G, Sole BF, Barcelo P. Patterns of oxalate metabo­lism in recurrent oxalate stone formers. Kidney Int 1974: 5: 285-­329.  Back to cited text no. 22    
23.Coe FL, Kavalach AG. Hypercalciuria and hyperuricosuria in pa­tients with calcium nephrolithiasis. New En-1 J Med 1974; 291: 1344.  Back to cited text no. 23    
24.King JS, O'Connor FJ, Smith MJV. The urinary calcium magne­sium ratio in calcigerous stone formers. Invest Urol 1968; 6: 60-65.  Back to cited text no. 24    
25.Preminger GM, Baker S, Peterson R. Hypomagnesuric hypocitra­turia: An apparent new entity for calcium nephrolithiasis. J Lith­stone Dis 1989; 1: 22-25.  Back to cited text no. 25    
26.Hsu TG. Ammonium acid urate lithiasis, experimental observations. J Urol 1966; 96: 88-94.  Back to cited text no. 26    
27.Klohn M, Bolle JF, Reverdin NP et al. Ammonium urate urinary stones. Urol Res 1986; 14: 315-318.  Back to cited text no. 27    
28.Their SO, Segal S. Cystinuria. In Stanbury JB, Wyngaarden JB, Fredrickson DS. (eds). The Metabolic Basis of Inherited Diseases, New York, McGraw Hill 1972; 504-519.  Back to cited text no. 28    
29.Pak CYC. Citrate and renal calculi. Miner. Electrolyte Metab 1987; 13: 257-266.  Back to cited text no. 29    
30.Sakahee K, Nigam S, Snell P et al. Assessment of the pathogenic role of exercise in renal stone formation. J Clinic Endocrin Metab 1987; 65: 974-979.  Back to cited text no. 30    
31.Preminger GM. Sakahee K, Skurla C, Pak CYC. Prevention of re­current calcium stone formation with potassium citrate therapy in patients with distal renal tubular acidosis. J Urol 1985; 134: 20-23.  Back to cited text no. 31    
32.Pak CYC. Fuller C, Sakahee K. Preminger GM, Britton F. Long term treatment of calcium nephrolithiasis with potassium citrate. J Urol 1985; 134: 11-19.  Back to cited text no. 32    
33.Rudman D, Deodnis JL, Fountain MT. Chandler JB, Garren GG, Fleminf GA. Kutner MH. Hypocitraturia in patients with GI mal­absorption. New Eng J Med 1980; 303: 657.  Back to cited text no. 33    
34.Pak CYC, Sakahee K, Fuller C. Successful management of uric acid nephrolithiasis with potassium citrate. Kidney Int 1986; 30: 422-428.  Back to cited text no. 34    
35.Pak CYC, Fuller C. Idiopathic hypocitraturic calcium oxalate ne­phrolithiasis successfully treated with potassium citrate. Ann In­tern Med 1986; 104: 33-37.  Back to cited text no. 35    
36.Breslau NA. Brinkley L, Hill KA, Pak CYC. Relationship role of animal protein rich diet to kidney stone formation and calcium metabolism. J Clin Endocrin Metab 1988; 66: 140-146.  Back to cited text no. 36    
37.Meyer JL, Smith LH. Growth of calcium oxalate crystals. Invest Urol 1975: 13: 36-39.  Back to cited text no. 37    
38.Pak CYC. Nicar MJ, Northcutt C. The definition of the mechanism of hypercalciuria is necessary for the treatment of recurrent renal stone for men. Contrib Nephrol 1982; 33: 136-151.  Back to cited text no. 38    
39.Meyer JL, Smith LH. Growth of calcium oxalate crystals : Inhibi­tion by natural urinary crystal growth inhibitors. Invest Urol 1975: 13: 36.  Back to cited text no. 39    
40.Pak CYC, Paterson R. Successful treatment of hyperuricosuric cal­cium oxalate nephrolithiasis with potassium citrate. Arch Intern Med 1986:146:863.  Back to cited text no. 40    
41.Sherman CC. Mendel LB, Smith AH. The metabolism of orally administered citric acid. J Biol Chem 1936; 113: 265-271.  Back to cited text no. 41    
42.Simpson DP. Citrate excretion : A window on renal metabolism. Am J Physiol 244; Renal Fluid Electrolyte Physiol 1983; 13: F223-­F234.  Back to cited text no. 42    
43.Fourman P, Robinson JR. Diminished urinary excretion of citrate during deficiencies of potassium in man. Lancet 1953; 2: 656-657.  Back to cited text no. 43    
44.Baruch SB. Burch RL, Eun CK, King VF. Renal metabolism of citrate. Med Clinic North Am 1975; 59: 569-582.  Back to cited text no. 44    
45.Down WH. Sachrin RN, Shasseud LF et al. Renal and bone uptake of tartaric acid in rats : Comparison of L(+) and DL-forms. Toxi­cology 1977: 8: 333-346.  Back to cited text no. 45    
46.Shorn E, Bernhiem AR, Tassuky H. The relation of urinary citric acid excretion to the menstrual cycle and the steroidal reproductive hormones. Science 1942; 95: 607.  Back to cited text no. 46    
47.Costello LC, Stacey R. Franklin R. Parathyroid hormone effects on soft tissue citrate levels. Horm Metab Res 1976; 2: 242-245.  Back to cited text no. 47    
48.Wabner CL, Pak CYC. Effect of orange juice consumption on uri­nary stone risk factors. J Urol 1993; 149: 1405-1408.  Back to cited text no. 48    
49.Sakahee K, Alprem R, Poindexter J et al. Citraturic response to oral citric acid load. J Urol 1992; 147: 975-976.  Back to cited text no. 49    
50.Hess B, Michel R, Takkinen R et al. Risk factors for low urinary citrate in calcium nephrolithiasis : Low vegetable fiber intake and low urinary volume to be added to the list. Nephrol Dial Transplant 1994;9:642.  Back to cited text no. 50    
51.Simpson DP. Citrate excretion : A window on renal metabolism. Am J Physiol 1983; 244: f223.  Back to cited text no. 51    
52.Simpson DP. Regulation of renal citrate metabolism by bicarbo­nate ion and pH observations in tissue slices and mitochondria. Biochem Biophys Acta 1973: 298: 115.  Back to cited text no. 52    
53.Jaeger P, Hess B, Takkinen R et al. Nutritional determinants of ne­phrolithiasis. Adv Nephrol 1995; 24: 217.  Back to cited text no. 53    
54.Lemann J. Urinary calcium excretion and net acid excretion : Ef­fects of dietary protein, carbohydrate and calories. In Schwille PO, Smith LH, Robertson WG et al (eds.). Urolithiasis and Related Clini­cal Research. New York, Plenum 1985; 53.  Back to cited text no. 54    
55.Lemann J, Adams ND, Gray RW. Urinary calcium excretion in hu­man beings. N Engl J Med 1979; 301: 535.  Back to cited text no. 55    
56.Lemann J, Litzow JR Jr, Lennon EJ. The effects of chronic acid loads in normal man : Further evidence for the participation of bone mineral in the defence against chronic metabolic acidosis. J Clin Invest 1766; 45: 1608.  Back to cited text no. 56    
57.Schuette SA. Zemel MB, Linkswiler HM. Studies on the mecha­nism of protein induced hypercalciuria in older men and women. J Nutr 1980; 110; 305.  Back to cited text no. 57    
58.Sakahee K, Pak CYC. Contrasting effects of various potassium salts on acid-base status, urinary citrate excretion and renal citrate clear­ance. Abstracts from Urologic Research : VI International Sympo­sium on Urolithiasis and Related Clinical Research. Vancouver, British Columbia; 197.  Back to cited text no. 58    
59.Pak CYC. Physichemical action and extrarenal manifestations of alkali therapy. Presented at Urologic Research : VI International Symposium on Urolithiasis and Related Clinical Research. Van­couver, British Columbia 1988; July 24-29.  Back to cited text no. 59    
60.Sakahee K, Nicar M. Hill K, Pak CYC. Contrasting effects of potas­sium citrate and sodium citrate therapies on urinary chemistries and crystallization of stone forming salts. Kidney Int 1983; 24: 348-352.  Back to cited text no. 60    
61.Preminger GM. Sakahee K. Pak CYC. Alkali action on the urinary crystallization of calcium salts: Contrasting response to sodium citrate and potassium citrate, J Urol 1988; 139: 240-242.  Back to cited text no. 61    
62.Resnick MI, Pak CYC. Urolithiasis - A medical and Surgical Reference. WB Saunders 1990; 91.  Back to cited text no. 62    
63.Pak CYC, Fuller C. Idiopathic hypocitraturic calcium nephrolithi­asis successfully treated with potassium citrate. An Int Med 1986; 104: 33-37.  Back to cited text no. 63    
64.Pak CYC, Peterson R, Sakahee K et al. Correction of hypercitraturia and prevention of stone formation by combined thiazide and potas­sium citrate therapy in thiazide-unresponsive hypercalciuric neph­rolithiasis. Am J Med 1985; 79: 284-288.  Back to cited text no. 64    
65.Nicar MJ, Peterson R, Pak CYC. Use of potassium citrate as potas­sium supplement during thiazide therapy of calcium nephrolithi­asis : J Urol 1984; 131: 430-433.  Back to cited text no. 65    
66.Barcello P, Wahl O, Servitage E, Rousad A, Pak CYC. Randomized double blind study of potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis. J Urol 1993: 150: 1761-1764.  Back to cited text no. 66    
67.Pak CYC. Medical management of nephrolithiasis in Dallas : Up­date 1987. J Urol 1988; 140: 461-467.  Back to cited text no. 67    
68.Cicerello E, Merlo F, Gambaro G, Maccatrozzo L, Fandella A. Baggio B, Anselmo G. Effects of alkaline citrate therapy on clear­ance of residual renal stone fragments after ESWL in sterile cal­cium and infection nephrolithiasis patients. J Urol 1994; 151: 5-9.  Back to cited text no. 68    
69.Fine JK, Pak CYC, Preminger GM. Effect of medical management and residual fragments on recurrent stone formation following shock wave lithotripsy. J Urol 1995; 153: 27-33.  Back to cited text no. 69    

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