EAU Guidelines

European Urology

Eur Urol 2001;40:362371

Guidelines on Urolithiasis 1
H.G. Tiselius, D. Ackermann, P Alken, C. Buck, P Conort, M. Gallucci . .
Working Party on Lithiasis, Health Care Office, European Association of Urology 2

Key Words Acute stone colic Ureteral stones Kidney stones Risk factors Reccurrence prevention

Abstract Objectives: A project was initiated by the Health Care Office of the European Association of Urology in order to formulate common recommendations and guidelines for the treatment of patients with urolithiasis. The basic task for the working group therefore was to extract and evaluate evidence from the literature in order to reach a consensus on how these patients could best be managed. Methods: Extensive reviews of the literature together with a thorough and detailed discussion of the various topics, by a working group including of experts from several European countries, provided the basis for a consensus overview of urolithiasis and its management. Results and Conclusions: Recommendations are given for the management of patients with acute stone colic and for active removal of stones from the ureter and kidney. Moreover, the principles for risk evaluation of patients with recurrent stone formation and appropriate recurrence preventive treatment are given.
Copyright 2001 S. Karger AG, Basel

Urinary stone disease continues to occupy an important place in everyday urological practice. These guidelines and recommendations for the diagnosis, medical and interventional treatment of stone disease as well as for recurrence prevention have been formulated following a comprehensive and detailed evaluation of the current knowledge of various aspects of urolithiasis.
1 For more extensive information consult the EAU Guidelines presented at the 16th EAU Annual Congress, Geneva, Switzerland (ISBN 9080617939). 2

Classification

Based on the chemical composition of the stone and the severity of the disease different categories of stone formers can be identified (table 1). This classification enables useful sub-grouping of patients for decisions on the metabolic evaluation and medical treatment of the disease [1]. Irrespective of the previous course of the disease some patients need particular attention because of specific risk factors, summarized in table 2.

For the section on stone-preventive measures contributions also were made by the following members of the Advisory Board of European Urolithiasis Research: W. Achilles, J.M. Baumann, B. Dussol, K.-H. Bichler, R. Caudarella, M. Daudon, B. Hess, A. Hesse, P. Jaeger, D.J. Kok, B.D. Leusmann, P.N. Rao, K. Sarica, P.-O. Schwille, and W.L. Strohmaier.

2001 S.Karger AG, Basel 03022838/01/04040362 $17.50/0 Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Accessible online at: www.karger.com/journals/eur

Prof. Hans-Gran Tiselius Department of Urology Huddinge University Hospital SE-141 86 Stockholm (Sweden) Tel. +46 8 58 58 77 62, Fax +46 8 58 58 77 60, E-Mail hans-goran.tiselius@urol.hs.sll.se

Table 1. Categories of stone formers

Description Non-calcium stones Infection stone Uric acid/sodium urate/ammonium urate Cystine stone First time stone former without residual stone or stone fragments First time stone former with residual stone or stone fragments Recurrent stone former with mild disease without residual stone(s) or stone fragments Recurrent stone former with mild disease with residual stone(s) or stone fragments Recurrent stone former with severe disease with or without residual stone(s) or fragments Stone forming patient with specific risk factor irrespective of otherwise defined category

Abbreviation INF UR CY So Sres Rm-o Rm-res Rs Risk

Calcium stones

Table 2. Specific risk factors for stone formation

Start of disease early in life: d25 years Stones containing brushite Only one functioning kidney Disease associated with stone formation Hyperparathyroidism Renal tubular acidosis (complete/partial) Jejunoileal bypass Crohns disease Intestinal resection Malabsorptive conditions Sarcoidosis Hyperthyroidism Medication associated with stone formation Calcium supplements Vitamin D supplements Ascorbic acid in megadoses (c4 g/day) Sulfonamides a Triamterene a Indinavir a Anatomical abnormalities associated with stone formation Tubular ectasia (MSK) PUJ-obstruction Calix diverticulum/calcix cyst Ureteral stricture Vesicoureteral reflux Horseshoe kidney Ureterocele PUJ = Pelvoureteral junction. Noncalcium stones

procedure. This makes it possible to decide if a conservative approach is justified or if another form of treatment has to be considered. Imaging is imperative for patients with fever (c38 C), solitary kidney and when the stone diagnosis is in doubt. Routine examination involves a plain film of kidneys, ureters and bladder plus an ultrasound examination or an excretory pyelography (urography). The latter examination must not be carried out in patients with: an allergy to contrast media, serum creatinine c200 mol/l, treatment with metformine and myelomatosis. Other special examinations that can be useful in diagnosis are spiral (helical) unenhanced computed tomography (CT), retrograde and antegrade pyelography and scintigraphy. Because of the risk of impaired renal function due to lactic acidosis, the anti-diabetic drug metformine should be stopped 23 days prior to administration of iodine containing contrast medium [2]. Spiral (helical) CT is a new noninvasive technique [3, 4], which might be considered in case iodine containing contrast medium cannot be administered.
Laboratory Investigations Routine Analyses. The routine laboratory investigation should include examination of the urinary sediment and/or a dip stick test for red cells, white cells, nitrate and pH, and a measurement of serum creatinine. In patients with fever, analysis of C-reactive protein, blood white cell count and a urine culture should be carried out. In cases of vomiting serum sodium and serum potassium should be measured. To exclude metabolic risk factors, it is important to measure the serum calcium and serum urate. Extended Urinalysis. In order to further identify abnormalities that might be of importance for stone-formation the following alternative urinanalyses are recommended [5, 6]: Option 1: Two 24-hour urine collections sample 1 collected in a bottle containing 1530 ml of 6 mol/l hydrochloric acid (HCl)

Diagnosis

Diagnostic Imaging Patients with an episode of renal stone colic usually present with typical pain, vomiting and mild fever. The clinical diagnosis should be supported by an appropriate imaging

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Table 3. Analytical workup in patients with

uncomplicated stone disease

Stone analysis In every patient one stone should be analysed

Blood analysis Calcium Albumin a Creatinine Urate b

Urinalysis Fasting morning spot urine sample Dip-stick test: pH Leucocytes / Bacteria c Cystine test d

a b c d

Either calcium + albumin or free calcium ion concentration. Optional analysis. Urine culture in case of bacteriuria. Cystine test if cystinuria cannot be excluded by other means.

sample 2 collected in a bottle containing 2030 ml of 0.3 mol/l sodium azide Option 2: One 24-hour urine collection sample collected in a bottle containing 1530 ml of 6 mol/l HCl Option 3: One 16-hour urine and one 8-hour urine collection [7] sample 1 collected between 06.00 and 22.00 in an bottle containing 1020 ml of 6 mol/l HCl sample 2 collected between 22.00 and 06.00 in a bottle containing 10 ml of 0.3 mol/l sodium azide Option 4: Spot urine sample the excretion of each urine variable is related to creatinine [8] Hydrochloric acid is used to prevent precipitation of calcium oxalate and calcium phosphate, and to counteract oxidation of ascorbate to oxalate [9]. Analysis of urate can be carried out in collections with sodium azide but in samples with HCl only following alkalinization with sodium hydroxide. Analysis of urine should be postponed until at least 4 weeks have elapsed following an episode of obstruction and/or after stone removal and never in the presence of infection or hematuria. Stone Composition. Stones or stone fragments should be subjected to stone analysis to establish their composition [10]. The preferred analytical procedures are x-ray crystallography and infrared spectroscopy. Every patient, whenever possible, should have at least one stone analyzed. Where stone material has not been analyzed conclusions on stone composition might be based on other observations, i.e. a qualitative cystine test with sodium nitroprussideBrands test, test for bacteriuria or urine culture, demonstration of crystals of struvite or cystine in the urinary sediment, serum urate (when a uric acid or urate stone is suspected), urine pH (low in patients with uric acid stones, high in pa-

tients with infection stones), and radiographic appearance of the stone or conclusions from the ultrasound examination. Based on the main chemical constituents the stones can be grouped as follows: Radio-opaque calcium containing stones, when not associated with infection, include calcium oxalate monohydrate, calcium oxalate dihydrate, hydroxyapatite, carbonate apatite (in the absence of infection), octacalcium phosphate and brushite. Uric acid/urate stones (UR) include uric acid, sodium urate and ammonium urate. Infection stones (INF) include magnesium ammonium phosphate and carbonate apatite. Cystine stones (CY) are composed of cystine. Calcium stones, uric acid/urate stones, and cystine stones associated with infection are referred to as stones with infection. There are also less commonly encountered stone constituents such as 2,8-dihydroxyadenine, xanthine and various drug metabolites (sulfonamide, triamterene and indinavir). Analytical Workup of Patients with Calcium Stones. Patients with uncomplicated disease are stone-free either after the first stone episode or have a mild recurrent disease (categories So and Rm-o). For these patients the limited set of analyses in table 3 is recommended. Patients with a complicated disease have a history of frequent recurrences with or without residual fragments or stones in the kidney, or specific risk factors (categories Rs and Risk). Also, first time stone formers and those with a mild disease who have residual fragments (categories Sres and Rm-res) might be included in this group. The analytical program recommended for these patients is shown in table 4. The recommended principles for metabolic evaluation and further medical management are given in table 5. In selected patients some additional special analyses such as acid [11, 12] and calcium loading [13] might be useful.

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Table 4. Analyses in patients with complicated stone disease

Table 5. Analytical program for metabolic evaluation of patients

with stone disease related to category Stones analysis In every patient on stone should be analyzed Blood analysis Calcium Albumin a Creatinine Urate b Potassium Urinalysis Fasting morning spot urine sample Dip-stick test pH Leukocytes/bacteria Cystine test 24-hour urine collection c Calcium, oxalate, citrate, urate d, creatinine, volume, magnesium b, e, phosphate b, e, f, urea b, f, sodium b, f, chloride b, f, potassium b, f Either calcium + albumin or free calcium ion concentration. Optional analysis. c 24-hour urine can be replaced by collections during other periods of the day. d In samples that have not been acidified. e Magnesium and phosphate are necessary for calculations of estimates of the ion activity products of CaOx and CaP, respectively. f Urea, phosphate, sodium and potassium reflect dietary habits.
b a

Category

Blood analysis

Urinalysis

Prevention follow-up Yes Yes Yes No Yes No Yes Yes Yes

INF UR CY So Sres Rm-o Rm-res Rs Risk

S creatinine S urate S creatinine S creatinine Yes (see table 3) Yes (see table 4) Yes (see table 3) Yes (see table 4) Yes (see table 4) Yes (see table 4)

Culture pH Urate pH Cystine pH Limited urinalysis (see table 3) Yes (see table 4) Limited urinalysis (see table 3) Yes (see table 4) Yes (see table 4) Yes (see table 4)

S = Serum.

Treatment

In patients with a high serum calcium (c2.60 mmol/l), hyperparathyroidism should be excluded by assessing the parathyroid hormone level [14]. Incomplete or complete renal tubular acidosis should be suspected in patients with a pH above 5.8 in fasting morning urine [15]. From the analysis of urine composition as shown in table 4 valuable information can be derived. Based on the urine urea concentration (mmol/l) and the urine volume (V, liters) the protein intake can be calculated [16]. The net alkali absorption in mEq/24 h is derived from information on the excretion of sodium, potassium, calcium, magnesium, chloride and phosphate [17]. Estimates of the ion-activity products of calcium oxalate [AP(CaOx) index] and calcium phosphate [AP(CaP) index] can be calculated if the urine volume and the excretion of calcium, oxalate, citrate, magnesium, phosphate and pH are known [18]. In these expressions the AP(CaOx) index approximately corresponds to the 108 E APCaOx, where APCaOx is the ion-activity product of calcium oxalate. The AP(CaP) index approximately corresponds to 1015 E APCaP, where APCaP is the ion-activity product of calcium phosphate.

Pain Relief Pain relief can be achieved with the administration by various routes of the following agents: diclophenac sodium (Voltaren), indomethacin, hydromorphone hydrochloride + atropin sulfate (Dilaudid-Atropin), methamizol, pentazocin and tramadol. Treatment should be started with an NSAID and changed to an alternative drug if the pain persists. Hydromorphone and other opiates without simultaneous administration of atropine should be avoided. Diclophenac sodium affects glomerular filtration rate in patients with reduced renal function, but not in patients with normal renal function [19]. When spontaneous stone passage is anticipated 50-mg suppositories or tablets of diclophenac sodium administered twice daily during 310 days might be useful in reducing ureteral edema and the risk of recurrent pain. Passage of stone and evaluation of renal function should be confirmed with appropriate methods. Retrieved stone(s) should be analyzed. When pain relief cannot be achieved by medical means, drainage by stenting or percutaneous nephrostomy, or by stone removal should be carried out. Stone Removal General Recommendations for Stone Removal. For all patients in whom stone removal is planned screening for bacteriuria must be carried out. Dip-stick tests are sufficient in the uncomplicated cases. In others a urine culture is necessary. When the test is positive for bacteriuria, or the urine

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Table 6. Principles for active removal of stones in the ureter

Proximal ureter Radioopaque stones (1) ESWL in situ (2) ESWL after push-up (3) Perc. antegrade URS (4) URS + disintegration (1) AB + ESWL in situ (2) AB + ESWL after push-up (3) AB + Perc. antegrade URS (4) AB + URS + disintegration (1) Stent + oral chemolysis (2) ESWL in situ + oral chemolysis (3) Perc. antegrade URS (4) URS + disintegration

Mid ureter (1) ESWL in situ, prone position (1) URS + disintegration (2) UC /i.v. contrast + ESWL (2) Push-up + ESWL (3) Perc. antegrade URS (1) AB + ESWL in situ, prone position (1) AB + URS + disintegration (2) AB + UC /i.v. contrast + ESWL (2) AB + push-up + ESWL (3) AB + Perc. antegrade URS (1) ESWL in situ, prone position (1) URS + disintegration (2) UC /i.v. contrast + ESWL (2) Push-up + ESWL (2) Stent + oral chemolysis (3) Perc. antegrade URS (1) ESWL in situ, prone position (1) URS + disintegration (2) UC /i.v. contrast + ESWL (2) Push-up + ESWL (3) Perc. antegrade URS

Distal ureter (1) ESWL in situ (1) URS + disintegration (2) UC + ESWL

Infection stones, stones with infection

(1) AB + ESWL in situ (1) AB + URS + disintegration (2) AB + PN + ESWL in situ (2) AB + UC + ESWL (1) ESWL in situ, i.v contrast (1) URS + disintegration (2) UC + contrast + ESWL (3) PN + contrast + ESWL

Uric acid stones

Cystine stones

(1) ESWL in situ (2) ESWL after push-up (3) Perc. antegrade URS (4) URS + disintegration

(1) ESWL in situ (2) URS + disintegration (2) UC + ESWL

ESWL = Includes piezolithotripsy; Perc. = percutaneous; UC = ureteral catheter; AB = antibiotics; PN = percutaneous nephrostomy catheter.

culture shows bacterial growth, or when there is suspicion of an infection, treatment with antibiotics should be started before the stone-removing procedure. Bleeding disorders and anticoagulation treatment should be considered. These patients should be referred to an internist for appropriate therapeutic measures in association with the stone removal. Treatment with salicylic acid preparations should be stopped 10 days before the stone-removing procedure. Extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PNL), ureteroscopy (URS) and open surgery are all contraindicated in patients with coagulation disorders. ESWL, PNL and URS are contraindicated in pregnant women. In expert hands, URS has been performed successfully to remove ureteral stones during pregnancy, but it needs to be emphasized that complications following such a procedure might be difficult to manage. The preferred treatment during pregnancy, therefore is drainage either with a double-J stent or a percutaneous nephrostomy catheter [20]. For patients with a pacemaker it is wise to consult a cardiologist before an ESWL treatment.

Indications for Active Stone Removal. The size, site and shape of the stone influence the decision on how to deal with it. Spontaneous stone passage can be expected in up to 80% of patients with stones not larger than 4 mm. For stones with a diameter exceeding 7 mm the chance of spontaneous passage is low [21, 22]. The overall passage rate is 25% for proximal, 45% for mid, and 70% for distal ureteral stones. Stone removal usually is indicated for stones with a diameter exceeding 67 mm, and is strongly recommended in patients with the following: persistent pain despite adequate medication, persistent obstruction with impaired renal function, urinary tract infection, risk of pyonephrosis or urosepsis, bilateral obstruction and obstructing calculus in a solitary functioning kidney. Principles for Active Removal of Ureteral Stones. For stones in different parts of the ureter and with different composition the most appropriate methods for stone removal are given in table 6. Numbers 1, 2, 3 and 4 are designated to the procedures according to the consensus reached. The preferred alternative is always given the number 1, and when two procedures are considered equally useful they have been given the same number.

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Table 7. Principles for active removal of stones in the kidney

Kidney stones b20 mm Radioopaque stones (1) ESWL (2) PNL

Kidney stones a20 mm (1) PNL (2) ESWL (3) PNL + ESWL

Complete or partial staghorn stones (1) PNL (2) PNL + ESWL (3) ESWL + PNL (4) Open surgery (1) PNL (2) PNL + ESWL (3) PN:/ESWL + oral chemolysis (4) ESWL + PNL (5) AB + ESWL + chemolysis (1) PNL (2) PNL + ESWL (2) PNL/ESWL + oral chemolysis (3) ESWL + PNL (4) Open surgery (1) PNL (2) PNL + ESWL (3) ESWL + PNL (4) Open surgery

Infection stones, stones with infection

(1) AB + ESWL (2) AB + PNL

(1) AB + PNL (2) AB + ESWL with or without stent (3) AB + PNL + ESWL

Uric acid stones

(1) Oral chemolysis (2) Stent + ESWL + oral chemolysis

(1) Oral chemolysis (2) Stent + ESWL + oral chemolysis

Cystine stones

(1) ESWL (2) PNL (3) Open or videoendoscopic surgery

(1) PNL (2) PNL + ESWL (3) PNL + flexible nephroscopy

ESWL = Includes piezolithotripsy; UC = ureteral catheter; AB = antibiotics.

Repeated sessions are frequently necessary for in situ ESWL treatment. Large and impacted stones have the highest retreatment rate. The success rate in difficult cases can be improved by bypassing the stone with a catheter or by pushing it up into the kidney. UR stones can be localized with ultrasound, intravenous and retrograde contrast medium. Stones composed of uric acid, but not of sodium urate or ammonium urate, can be dissolved by oral chemolytic treatment. Percutaneous chemolytic treatment can be useful in selected cases of infection, uric acid, cystine and pure calcium phosphate stones [2325]. Blind basketing without endoscopic or fluoroscopic control is not recommended. In case of failure with minimally invasive techniques, an open surgical procedure might be required. Videoendoscopic retroperitoneal surgery is a minimally invasive alternative to open surgery. There is controversy as to whether ESWL or URS is the best method for removal of ureteral stones, particularly for those situated in the lower ureter [26]. Principles for Active Removal of Stones in the Kidney. The success rate of ESWL is related to the concrement volume. Larger stones need more treatment sessions [27, 28], but there is an ongoing debate as to whether large renal stones are best treated with ESWL or PNL. The recommended treatments according to stone size and composition are summarized in table 7.

Residual fragments, so-called clinically insignificant fragments, are common after ESWL treatment of stones in the kidney. Lower calix fragments are more commonly seen when there is an acute (d90 ) infundibulopelvic angle [29]. A lower pole resection is an alternative that should be considered in case of residual fragments and no functioning parenchyma [30]. Percutaneous chemolysis is an alternative treatment for stone fragments composed of magnesium ammonium phosphate, carbonate apatite, uric acid, cystine and brushite. In case of chemolysis it is important to give appropriate antibiotics and to avoid a high intrarenal pressure and leakage by using two percutaneous nephrostomy catheters. Fragments in the upper and middle calices can be removed with URS and contact disintegration. For stones with a diameter exceeding 20 mm double-J stenting before ESWL is recommended to avoid an accumulation of stones obstructing the ureter (steinstrasse) [31, 32]. Stones composed of brushite and calcium oxalate monohydrate are characterized by particular hardness [36]. This might militate in favor of percutaneous removal if the stones are large. There are two types of cystine stones, those responding well to ESWL and those responding poorly [33]. For large ESWL-resistant stones, PNL with or without lithotripsy will be the best alternative for efficient removal. It should be observed that also small stones residing in a cal-

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ix might cause considerable pain or discomfort [34, 35]. In certain cases a narrow caliceal neck might require dilatation.
Complete or Partial Staghorn Stones For patients with small staghorn stones and a nondilated system, repeated ESWL sessions with a stent can be a reasonable treatment alternative. Nephrectomy should be considered in case of a nonfunctioning kidney. In selected cases of infection, cystine, uric acid and calcium phosphate stones, the combined use of ESWL and chemolysis might be useful. Managing Special Problems A stone in a caliceal diverticulum can be treated with ESWL, PNL (if possible) or retrograde ureteroscopy. An optional method for removal of diverticular stones is videoendoscopic retroperitoneal surgery [36]. In case of a narrow communication between the diverticulum and the renal collecting system, well-disintegrated stone material will remain in the original position. These patients might become asymptomatic as a result of the stone disintegration alone. Horseshoe kidneys may be treated according to the principles for stone treatment presented above. It needs to be emphasized, however, that according to the anterior position of the kidney, it is often necessary to deliver shock waves from the abdominal aspect. Recommendations for the removal of stones in transplanted kidneys are ESWL or PNL. For the pelvic kidney, ESWL or videoendoscopic laparoscopic surgery are recommended. ESWL, PNL or open surgery are the options for treating obese patients. The stones formed in a continent reservoir constitute a varied and often difficult problem [37]. General directives for the management of this problem cannot be given. Each stone problem has to be considered and treated on its individual merits. In patients with pelvoureteral junction obstruction, the stones can be removed at the same time as the outflow abnormality is corrected either by percutaneous endopyelotomy [38, 39] or by open reconstructive surgery. Transureteral endopyelotomy (Acucise) is another alternative that might be considered provided the stones are prevented from falling down in the pelvoureteral incision [40]. Residual Fragments The importance of so-called clinically insignificant fragments is a matter of debate [4143]. Although some residual fragments will represent a nidus for new stone formation, this is not the case for all. Patients with residual fragments or stones should be regularly followed to monitor the course of the disease. Identification of biochemical risk factors and

Table 8. Recommendations for treatment of

steinstrasse Unobstructed Proximal ureter (1) ESWL Obstructed (1) PNL (2) Stent (3) ESWL (1) PN (2) Stent (3) ESWL (1) PN (2) Stent (3) URS

Mid ureter

(1) ESWL

Distal ureter

(1) ESWL (2) URS

ESWL = Includes piezolithotripsy; PN = percutaneous nephrostomy catheter.

an appropriate stone prevention might be particularly indicated for patients with residual fragments or stones. In symptomatic patients, it is important to rule out obstruction and deal with this problem if present. In other cases appropriate therapeutic steps need to be taken to eliminate symptoms. In asymptomatic patients where the stone is unlikely to pass, treatment should be applied according to the corresponding stone situation.
Steinstrasse A steinstrasse or a fragment column in the ureter is an accumulation of gravel that does not pass within a reasonable period of time and that interferes with urine passage [44]. The frequency of this complication has decreased with the liberal insertion of double-J stents before ESWL of large renal stones. In all patients with signs of infection, it is necessary to give antibiotics and to provide adequate drainage as soon as possible. Insertion of a percutaneous nephrostomy catheter usually results in the passage of the fragments [45]. For distally located accumulations of fragments, URS might be useful to remove the leading stone fragment by contact disintegration. Recommendations for treatment are given in table 8. Preventive Treatment in Calcium Stone Disease The preventive treatment of patients with calcium stone disease should be started with conservative measures. Pharmacological treatment should be instituted only when the conservative regimen fails. Patients should be encouraged to have a high fluid intake [46]. This advice is valid irrespective of the stone composition. For a normal adult the 24-hour

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Table 9. Recommended pharmacological treatment of patients with calcium stone disease

Indication

Recommended

Sometimes useful Note

Hypercalciuria

Thiazide Orthophosphate Thiazide + magnesium Alkaline citrate Alkaline citrate Alkaline citrate Calcium supplement Pyridoxine Alkaline citrate Alkaline citrate Alkaline citrate Thiazide + magnesium Alkaline citrate Allopurinol Alkaline citrate Alkaline citrate Orthophosphate

Potassium supplements should be given with thiazides

Hyperoxaluria (moderate) Hyperoxaluria (enteric)

Hyperoxaluria (primary)

These patients should be referred to someone with experience of this disease

Hyperoxaluria RTA Brushite stone

Potassium supplements should be given with thiazides

Hyperuricosuric CaOx stone Low inhibitory activity No abnormality

RTA = Renal tubular acidosis.

urine volume, thereby, should exceed 2,000 ml, but the supersaturation level should be used as a guide to the necessary degree of urine dilution. The fluid intake should be evenly distributed over the 24-hour period and particular attention should be paid to situations with an unusual loss of fluid. Diet should be dictated by common sense, a mixed balanced diet with contributions from all nutrient groups, but avoiding any excesses [47]. The intake of fruits and vegetables should be encouraged because of the beneficial effects of fibers. Care must be taken, however, to avoid fruits and vegetables rich in oxalate. Wheat bran is rich in oxalate and should be avoided. In order to avoid an oxalate load, the excessive intake of products rich in oxalate should be limited or avoided. This is of particular importance in those patients in whom a high excretion of oxalate has been demonstrated. The following products have a high content of oxalate: rhubarb, spinach, cocoa, tea leaves and nuts. Vitamin C in doses up to 4 g per day can be taken without increasing the risk of stone formation [48]. Animal protein should not be ingested in excessive amounts [49, 50]. It

is recommended that the animal protein intake is limited to approximately 150 g/day. Calcium intake should not be restricted unless there are very strong reasons for such advice [51]. The minimum daily requirement of calcium is 800 mg and the general recommendation is 1,000 mg/day. Supplements of calcium are not recommended except in enteric hyperoxaluria, in which additional calcium should be ingested with meals. The intake of food stuffs particularly rich in urate should be restricted in patients with hyperuricosuric calcium oxalate stone disease [52, 53], as well as in patients with uric acid stone disease. The intake of urate should not be more than 500 mg/day. Here are some examples of food rich in urate: calf thymus, liver, kidneys, poultry skin, herring with skin, sardines, anchovies and sprats.
Pharmacological Treatment of Calcium Stone Disease The recommended forms of pharmacological treatment are summarized in table 9. The use of magnesium salts as monotherapy is discouraged. Neither cellulose phosphate nor sodium cellulose phosphate has a place in the preven-

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tion of recurrence of calcium stones. Neither is there a place for synthetic or semisynthetic glycosaminoglycans.
Pharmacological Treatment of Patients with Uric Acid Stones Prevention of uric acid stone formation can be accomplished with a high fluid intake producing a urine volume of at least 2,000 ml per 24 h. Alkalization is of fundamental importance whereby 37 mmol of potassium citrate or 9 mmol of sodium potassium citrate should be given 23 times daily. In case of high levels of serum urate or urineurate a daily dose of 300 mg of allopurinol should be given as well. To attain dissolution of uric acid stones, the high fluid regimen should be combined with 610 mmol of potassium citrate or 918 mmol of sodium potassium citrate three times daily and 300 mg of allopurinol also in case of normal levels of serum and urine urate. Pharmacological Treatment of Patients with Cystine Stones The fluid intake should give a 24-hour urine volume of more than 3,000 ml. To achieve this goal at least 150 ml has to be taken per hour. Alkalization should be undertaken so

that the pH exceeds 7.5. This might be accomplished with potassium citrate 310 mmol in two to three divided doses. In patients with a 24-hour cystine excretion below 3 3.5 mmol administration of 35 g of ascorbic acid may be useful. With a higher excretion of cystine it is necessary to give Thiola (tiopronin) 2502,000 mg/day or Captopril (75150 mg/day).
Pharmacological Ttreatment of Stone Disease with Infection In those patients who have formed a stone composed of magnesium ammonium phosphate and carbonate apatite caused by urease producing microorganisms, surgical stone clearance should be as complete as possible. Antibiotics should be given according to the resistance pattern and a long-term course is recommended to eradicate the infection. Acidification with ammonium chloride 1 gE23 or methionine 500 mgE23 might be of value. In very selected cases with severe infections, treatment with acetohydroxamic acid (Lithostat) might be a therapeutic option. The nonhydroxamate derivative, N-(diaminophosphinyl)-4-fluorobenzamide (flurofamide), is a potent urease inhibitor and may be used as a safer alternative to Lithostat.

References
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