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*Corresponding author email: [email protected] Symbiosis Group Symbiosis www.symbiosisonline.org www.symbiosisonlinepublishing.com Alkaline Citrate Medication to Prevent Stent Encrustation in Urolithiasis Therapy Yasin Idweini* Department of Urology, Al-Bashir Hospital, Amman, Jordan Journal of Urology and Nephrology Open Access Open Access Research Article Introduction Zimskind, in 1967, was the first who prescribed endoscopic stent placement to relieve ureteral obstruction [1]. This early era was plagued with frequent stent migration and device expulsion. It was not until the year 1976; when the revolutionary development of the Double J and pigtail stents independently by Finney and Hepperten and colleagues (1978) [2], that the use of ureteral stents witnessed widespread status [3]. Since then Ureteral stents became a fundamental tool in today’s urologic armamentarium and are prescribed for number of indications including obstruction relief, prophylaxis against obstruction or ureteral injury and is used as a ureteral splint. Stents are often inserted to relieve either extrinsic (tumor, retroperitoneal fibrosis) or intrinsic ureteral obstruction (stones, tumors, strictures), as a temporary measure while definitive treatment is instituted, or as permanent tool when no corrective treatment is possible. Indications for pre- ESWL stenting are stone burden greater than 2 cm, when bilateral ESWL is recommended to be undertaken (at least one renal unit) and in solitary kidney’s treatment [4,5]. All stents may cause morbidity such as flank pain, dysuria, hematuria, infection, migration and encrustation. We reviewed the literature on the subject of the encrusted stents; discussed the risk factors for encrustation, and methods of preventing thereof. We could identify variety of factors that contribute in determining the occurrence rate of this process, the material of the stent, urine composition and duration of using thereof. We noticed that risk of stent encrustation is increased in patient with a history of urolithiasis and at progressively longer indwelling time [6]. Selective medical therapy for nephrolithiasis is highly effective in preventing new stone formation. Citrate efficacy for the management of hyper uricosuric calcium nephrolithiasis may stem from inhibitory activity of citrate with respect to calcium and oxalate crystallization. We evaluated the clinical efficacy of long- term preventive treatment of stent encrustation with alkaline citrate medication. The annual and cumulative rates of stents encrustation were compared before and during the treatment. Material and Methods We compared two groups of patients in a retrospective study First group from June 2003 to June 2004, 82 patients were Abstract Objectives: We evaluated the clinical efficacy of long –term preventive treatment of stent encrustation by using alkaline citrate medication. The annual and cumulative rates of stents encrustation were compared before and during the treatment Material and Methods: We compared two groups of patients in a retrospective study. First group from June2003 to June 2004, 82 patients were selected among 923 patients with urolithiasis who underwent extracorporeal shock waves lithotripsy (ESWL) and needed previously double J (J-J) insertion because of what are the burden of stone >2cm or treating obstructive anuria due to urolithiasis or after open surgery on the kidney and ureter for lithiasis when needed. The second group from June 2010 to June 2011 who have taken preventive alkaline K and Na citrate therapy to prevent stent encrustation in addition to ESWL, this second group consisted of 130 patients were chosen from 1182 patients who underwent ESWL therapy and they needed (J-J) insertion because of similar reasons of the first group. Patient age ranged from 6 years to 73 years (mean age 42years) in the first group. But in the second group patient age ranged from 2 years to 80 years (mean age 37 years). Ratio male to female was identical in both groups and was 59%: 41%. Results: Stent encrustation was quantified by visual analog score 0 (none) to 4 (heavy). Group 1: The mean stenting time was 6.2 months. a) Score (0 and 1) none encrusted: 55 patients (67%). b) Score (2, 3 and4) encrusted: 27 patients (33%). Group 2: The mean stenting time was 8.6 months. a) Score (0-1) none encrusted: 121 patients (93%). b) Score (2, 3 and 4) encrusted: 9 patients (7%). Conclusion: Alkaline medication, potassium and sodium citrate is effective in preventing and reducing stent encrustation. Keywords: Stent; Encrustation; Urolithiasis; Citrate Received: July 09, 2016; Accepted: July 26, 2016; Published: August 05, 2016 *Corresponding author: Yasin Idweini, Department of Urology Al-Bashir Hospital Amman Jordan, Email: [email protected] Abbreviations ESWL: Extracorporeal Shock Wave Lithotripsy; J-J Double J Stent U/S: Ultrasound; CT: Computerized Tomography IVU: Intravenous Urography; PCNL: percutaneous nephrolithotripsy

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Page 1: Alkaline Citrate Medication to Prevent Stent Encrustation ... · urolithiasis or after open surgery on the kidney and ureter for lithiasis when needed. The second group from June

*Corresponding author email: [email protected] Group

Symbiosis www.symbiosisonline.org www.symbiosisonlinepublishing.com

Alkaline Citrate Medication to Prevent Stent Encrustation in Urolithiasis Therapy

Yasin Idweini*Department of Urology, Al-Bashir Hospital, Amman, Jordan

Journal of Urology and Nephrology Open Access Open AccessResearch Article

Introduction

Zimskind, in 1967, was the first who prescribed endoscopic stent placement to relieve ureteral obstruction [1]. This early era was plagued with frequent stent migration and device expulsion. It was not until the year 1976; when the revolutionary development of the Double J and pigtail stents independently by Finney and Hepperten and colleagues (1978) [2], that the use of ureteral stents witnessed widespread status [3]. Since then Ureteral stents became a fundamental tool in today’s urologic armamentarium and are prescribed for number of indications including obstruction relief, prophylaxis against obstruction or ureteral injury and is used as a ureteral splint. Stents are often inserted to relieve either extrinsic (tumor, retroperitoneal fibrosis) or intrinsic ureteral obstruction (stones, tumors, strictures), as a temporary measure while definitive treatment is instituted, or as permanent tool when no corrective treatment is possible. Indications for pre- ESWL stenting are stone burden greater than 2 cm, when bilateral ESWL is recommended to be undertaken (at least one renal unit) and in solitary kidney’s treatment [4,5]. All stents may cause morbidity such as flank pain, dysuria, hematuria, infection, migration and encrustation. We reviewed the literature on the subject of the encrusted stents; discussed the risk factors for encrustation, and methods of preventing thereof. We could identify variety of factors that contribute in determining the occurrence rate of this process, the material of the stent, urine composition and duration of using thereof. We noticed that risk of stent encrustation is increased in patient with a history of urolithiasis and at progressively longer indwelling time [6]. Selective medical therapy for nephrolithiasis is highly effective in preventing new stone formation. Citrate efficacy for the management of hyper uricosuric calcium nephrolithiasis may stem from inhibitory activity of citrate with respect to calcium and oxalate crystallization. We evaluated the clinical efficacy of long-term preventive treatment of stent encrustation with alkaline citrate medication. The annual and cumulative rates of stents encrustation were compared before and during the treatment.

Material and MethodsWe compared two groups of patients in a retrospective

study First group from June 2003 to June 2004, 82 patients were

AbstractObjectives: We evaluated the clinical efficacy of long –term

preventive treatment of stent encrustation by using alkaline citrate medication. The annual and cumulative rates of stents encrustation were compared before and during the treatment

Material and Methods: We compared two groups of patients in a retrospective study. First group from June2003 to June 2004, 82 patients were selected among 923 patients with urolithiasis who underwent extracorporeal shock waves lithotripsy (ESWL) and needed previously double J (J-J) insertion because of what are the burden of stone >2cm or treating obstructive anuria due to urolithiasis or after open surgery on the kidney and ureter for lithiasis when needed. The second group from June 2010 to June 2011 who have taken preventive alkaline K and Na citrate therapy to prevent stent encrustation in addition to ESWL, this second group consisted of 130 patients were chosen from 1182 patients who underwent ESWL therapy and they needed (J-J) insertion because of similar reasons of the first group. Patient age ranged from 6 years to 73 years (mean age 42years) in the first group. But in the second group patient age ranged from 2 years to 80 years (mean age 37 years). Ratio male to female was identical in both groups and was 59%: 41%.

Results: Stent encrustation was quantified by visual analog score 0 (none) to 4 (heavy).

Group 1: The mean stenting time was 6.2 months.

a) Score (0 and 1) none encrusted: 55 patients (67%).

b) Score (2, 3 and4) encrusted: 27 patients (33%).

Group 2: The mean stenting time was 8.6 months.

a) Score (0-1) none encrusted: 121 patients (93%).

b) Score (2, 3 and 4) encrusted: 9 patients (7%).

Conclusion: Alkaline medication, potassium and sodium citrate is effective in preventing and reducing stent encrustation.

Keywords: Stent; Encrustation; Urolithiasis; Citrate

Received: July 09, 2016; Accepted: July 26, 2016; Published: August 05, 2016

*Corresponding author: Yasin Idweini, Department of Urology Al-Bashir Hospital Amman Jordan, Email: [email protected]

AbbreviationsESWL: Extracorporeal Shock Wave Lithotripsy; J-J Double

J Stent U/S: Ultrasound; CT: Computerized Tomography IVU: Intravenous Urography; PCNL: percutaneous nephrolithotripsy

Page 2: Alkaline Citrate Medication to Prevent Stent Encrustation ... · urolithiasis or after open surgery on the kidney and ureter for lithiasis when needed. The second group from June

Page 2 of 4Citation: Idweini Y (2016) Alkaline Citrate Medication to Prevent Stent Encrustation in Urolithiasis Therapy. J Urol Nephrol Open Access 2(3): 1-4. DOI: 10.15226/2473-6430/2/3/00117

Alkaline Citrate Medication to Prevent Stent Encrustation in Urolithiasis Therapy Copyright: © 2016 Idweini

selected among 923 patients with urolithiasis who underwent ESWL therapy and needed previously J-J insertion because of whatever the burden of stone > 2cm or treating obstructive anuria because of stone formation or after open surgery on the kidney and ureter due to stones when needed. The second group from June 2010 to June 2011 who has taken preventive alkaline K and Na citrate therapy to prevent stent encrustation in addition to ESWL this second group consisted of 130 patients who were chosen from 1182 patients who underwent ESWL therapy and they needed J-J insertion because of similar reasons of the first group. Material of Stents in both groups was polyurethane which shares characteristics common to both silicone and polyethylene the first plastic polymer used in stents and the two companies of stents we used to use were B. Brown from USA and Coloplast from France. Patient age ranged from 6 years to73 years (mean age 42 years) in the first group. But in the second group patient age ranged from 2 years to 80 years (mean age37 years). Ratio male to female was identical in both groups and was 59%: 41%. Patients were evaluated monthly by KUB film; U/S, blood urea and serum creatinine, urine analysis for each patient. Urine culture, IVU, and coronal CT scan were done when indicated. The administration of Uralyt-U granules (potassium sodium hydrogen citrate) started at the first week of insertion of J-J. Patients were instructed to take 1-4 spoons of granules (2.5 - 10gr) daily according to the pH of their fresh urine examined by test strip of indicator paper daily in the early morning.

Results Stent encrustation was quantified by visual analog score 0 (none) to 4 (heavy)

Group I: The mean stenting time was 6.2 months

a) Score (0 and 1) none encrusted: 55 patients (67%). (Figure 1)

b) Score (2, 3 and 4) encrusted: 27 patients (33%). (Figure 2-5)

Group ΙΙ: The mean stenting time was 8.6 months.

a) Score (0-1) none encrusted: 121 patients (93%). (Figure 1)

b) Score (2, 3 and 4) encrusted: 9 patients (7%) (Among them those patients who did not comply the treatment or had forgotten the stent).

No complications were recorded in our patients.

Alkaline medication, potassium and sodium citrate( group two) about 3-fold (Odd- 2.8) significantly effective in prevention and reducing stent encrustation compared with group one (Considered significant when P- value < 0.05). DiscussionThe ideal stent material should be biocompatible and radiopaque, relieve intraluminal and extra luminal obstruction, resist encrustation and infection, cause little discomfort to the patient, and should be widely available at reasonable cost.

Figure 1

Figure 2

Figure 3

Figure 4

Page 3: Alkaline Citrate Medication to Prevent Stent Encrustation ... · urolithiasis or after open surgery on the kidney and ureter for lithiasis when needed. The second group from June

Page 3 of 4Citation: Idweini Y (2016) Alkaline Citrate Medication to Prevent Stent Encrustation in Urolithiasis Therapy. J Urol Nephrol Open Access 2(3): 1-4. DOI: 10.15226/2473-6430/2/3/00117

Alkaline Citrate Medication to Prevent Stent Encrustation in Urolithiasis Therapy Copyright: © 2016 Idweini

Currently, there is no stent material that meets all these criteria. Minor degrees of encrustation, particularly on the bladder curl, are not uncommon in many stented patients. More extensive encrustation often relating to the forgotten/ retained stent can be one of the most challenging tasks for the urologist requiring various endourology interventions and sometimes open surgery, and if are untreated, extreme degrees of encrustation may lead to compromise of the renal unit and even patient mortality [7, 8] .The duration of indwelling time seems to affect the rate of stent encrustation with polyurethane stents. El-Faqih et al reported an incidence of stent encrustation of (9.2%before 6 weeks, 47.5% in 6-12 weeks, and 76.3% after 12 weeks) [9]. Infection and encrustation rise due to biofilm formation on the surface of the stent, which occurs within hours after insertion [10, 11] after a conditioning film coat, the surface of any foreign object in the urinary system, glycoprotein, exopolymer and matrix form a biofilm in which bacteria may become embedded. In our department, while we use citrate; as medical alkaline therapy in association to ESWL, in treating staghorn stones of uric acid and insertion of J-J stent previously to prevent steine-strasse obstruction, we noted that removal of stent was easier compared to those patients without alkaline therapy, because of lack heavy encrustation on it, in spite of long period of stenting. From that time we started to use alkaline therapy in association to ESWL to urolithiasis in general, when J-J stent insertion needed, providing that alkaline citrate is indicated as pharmacological treatment of calcium oxalate stones according to the aetiology, as well as hypercalciuria, hypocitraturia, enteric hyperoxaluria and distal renal tubular acidosis as EAU guidelines mentioned in addition to treating uric acid and ammonium urates stones, as well as support treatment in cistinuria, we also noted the lack of encrustation on stent in the majority of cases on removal . These results lead us to conduct retrospective comparative study between two groups of stented patients: one with ESWL therapy only and the other with ESWL and alkaline therapy taking in consideration the base evidence as we know from the literature that, potassium citrate therapy may produce a sustained increase in urinary citrate and a decline in the urine saturation of calcium oxalate. Citrate is an important inhibitor that can reduce calcium stone formation through several mechanisms: Citrate reduces urinary saturation of calcium salts by complexing with calcium [12]. Citrate directly prevents spontaneous nucleation of calcium oxalate [13, 14].

Citrate inhibits agglomeration and sedimentation of calcium oxalate crystals [15, 16] as well as growth of calcium oxalate and calcium/ phosphate crystals. Ultimately, normal urinary citrate levels can enhance the inhibitors effect of Tamm- Horsfall glycoproteine [17]. And as we know hypocitraturia is an important and correctable abnormality associated with nephrolithiasis that exists as an isolated abnormality in up to 10% of calcium stone formers and is associated with other abnormalities in 20% to 60% [18, 19] and we may correct this underlying cause of lithiasis by using alkaline therapy to prevent encrustation as stated hereinabove. An interesting observation deserves mentioning herein, is that not all stents become encrusted, even after long indwell times. In a series of patients who had an indwelling stent for more than 1 year (mean 36 months), Park and colleagues (2004) found this occurred in only 33% of the stents [20]. In our series, in the first stented group treated by ESWL only, the rate of encrusted stent was 33% (27 patients) is identical to the reported series ratio. Regarding to the second group treated by ESWL and citrate medication, the rate of encrusted stent was 7% (9 patients), among them those patients who did not comply the alkaline treatment or had forgotten the stent with calcification all over the stent, which also were treated by ESWL and citrate medication, and in this group the removal of stent was easier because of mild encrustation seen on it. Management of the retained encrusted ureteral stent may require multiple procedures; many options include chemolisis, ESWL, endoscopic lithotripsy, PCNL, open lithotomy and nephrectomy. In our series we did not need in the second group any further treatment than ESWL and citrate. We have taken a policy in our hospital to add a new indication for alkaline citrate medication which is reducing of ureteral stent encrustation in addition to lithotripsy. Conclusion

Stent encrustation and management challenges even experienced urologist. The key to prevent this problem is to

Figure 5

Table 1: Demographic baseline and treated patients characteristics:

Demographic data First group Second group

Gender:-Male N. (%) 48, (59%) 77, (59%)

Female N. (%) 33, (41%) 53, (41%)

Total N. 82 patients 130 patientsAge, years, median,(range) 42 years,(6-73y) 37years,(2 - 80y)

Rt. Side N. (%) -48% -45%

Lt. Side N. (%) -38% -37%

Bil. N. (%) -14% -18%Stenting time,mean,(range)

6.2months,(2-9months)

8.9months,(2-48months)

Non-encrusted stent N (%) 55 (67%) 121(93%)

Encrusted- stent N. (%) 27(33%) 9 (7%)Statistical Analysis: First Group; 55(67%), 27(33%) Second Group: 121(93%), 9 (7%) Chi Square (χ2 )=24.12 P-value < 0.0001 Relative Risk=2.8

Page 4: Alkaline Citrate Medication to Prevent Stent Encrustation ... · urolithiasis or after open surgery on the kidney and ureter for lithiasis when needed. The second group from June

Page 4 of 4Citation: Idweini Y (2016) Alkaline Citrate Medication to Prevent Stent Encrustation in Urolithiasis Therapy. J Urol Nephrol Open Access 2(3): 1-4. DOI: 10.15226/2473-6430/2/3/00117

Alkaline Citrate Medication to Prevent Stent Encrustation in Urolithiasis Therapy Copyright: © 2016 Idweini

give preventive alkaline medication, potassium and sodium citrate, they are equally effective in preventing uric acid stone formation because of their ability to increase both urinary Ph and its inhibitor effect on spontaneous nucleation of Ca oxalate and growth of Ca phosphate crystals interrupting stone formation, stent encrustation and decrease stent blockage in the long run.References1. Zimskind P D, Fetter TR, Wilkerson J L. Clinical use of long-term

indwelling silicone rubber ureteral splints inserted cystoscopically. J. Urol. 1967;97:840.

2. Finny RP. Experience with new double J ureteral catheter stent. Jr. Urol 1978;120(6):678-81.

3. Chew B H, Duvdevani M, Denstedt J D. New developments in ureteral stent design material and coating . Expert Rev Med Devices. 2006;3(3):395-403.

4. Libby J M , Meacham R B, Griffith D P. The role of silicone ureteral stents in ESWL of large renal calculi. J Urol. 1988;139(1):15-7.

5. Sulieman M N, Buchholz N P, Clark P B. The role of ureteral stent placement in the prevention of steinstrasse. J of Endourology. 2009;13(3):151-155. doi:10.1089/end.1999.13.151.

6. Preminger G M, Assimos D G, Lingeman J E, Nakada S Y, Pearle M S, Wolf J S, et al. AUA guidelines on management of staghorn calculi diagnosis and treatment recommendations. J Urol. 2005;173(6):1991-2000.

7. Walther P J, Robertson C N, Paulson D F. Lethal complications of standard self-retaining ureteral stent in patients with ileal conduite urinary diversion. J Urol. 1985;133(5):851-3.

8. Singh V, Srinivastava A, Kapoor R, Kumar A. Can the complicated forgotten indwelling ureteric stents be lethal? Int Urol Nephrol. 2005;37(3):541-6.

9. El-Faqih S R, Shamsuddin A B, Chakrabarti A, Atassi R, Kardar A H, Osman M K, et al: Polyurethane internal ureteral stents in treatment

of stones patients: morbidity related to indwelling times. J Urol. 1991;146(6):1487-91.

10. Tieszer C, Reid G, Denstedt J. Conditioning film deposition on ureteral stents after implantation. J Urol. 1998;160(3 Pt 1):876-81.

11. Wollin T A, Tieszer C, Riddell J V, Denstedt J D, Reid G. Bacterial biofilm formation, encrustation, and antibiotic adsorption to ureteral stents indwelling in humans. J Endourol. 1998 ;12(2):101-11.

12. Pak CY. Citrate and renal calculi: An update. Miner Electrolyte Metab. 1994;20(6):371-7.

13. Preminger GM, Sakhaee K, Skurla C, Pak CY. Prevention of recurrent calcium stone formation with potassium citrate therapy in patients with distal renal tubular acidosis. J Urol. 1985 ;134(1):20-3.

14. Sakhaee. Recent advances in the pathophysiology of nephrolithiasis. Kidney Int. 2009; 75(6):585-95. doi: 10.1038/ki.2008.626.

15. Kok D J, Papapoulos S E, Bijvoet O L. Excessive crystal agglomeration with low citrate excretion in recurrent stones formers. Lancet. 1986;1(8489):1056-8.

16. Tiselius H G, Fornander A M, Nilsson M A. The effects of citrate and urine on calcium oxalate crystal aggregation Urol Res. 1993;21(5):363-6.

17. Hess B, Zipperle L, Jaeger P. Citrate and calcium effects on Tamm-Horsfall glycoprotein as modifier calcium oxalate crystal aggregation. Am J Physiol, 1993;265-f 784-f 791.

18. Menon M, Mahle C J. Urinary citrate excretion in patients with renal calculi . J Urol. 1983;129, 1158-1160.

19. Charles C, Pak, Candy Fullen B S, Idiopathic Hypocitraturic Calcium-Oxalate Nephrolithiasis Successfully Treated with Potassium Citrate. Ann Inter Med. 1986;104:33-37.

20. Park and Colleagues (2004): Stent Encrustation, risk factors are urinary tract infection from Campbell-Walsh Urology- chapter-7 Fundamentals of instrumentation and urinary tract drainage.