Chemolysis of cystine calculi

Historically, cystine stone chemolysis has been approached with 2 different categories of compounds--alkalizing agents (sodium bicarbonate and tromethamine) and, more recently, protonated thiols and disulfide compounds (alpha-mercaptopropionylglycine, N-acetylcysteine and penicillamine). To establish the relative efficacy of these agents an in vitro model was devised that simulates the clinical setting. The optimal molar concentrations for sodium bicarbonate, N-acetylcysteine and tromethamine were determined initially and then compared at these strengths. Lastly, a variety of solution combinations were made to determine if a synergistic effect could be demonstrated. Results of this study demonstrate that the combination of acetylcysteine, a protonated thiol, with the strong alkalizing agent sodium hydroxide yields the most effective solution for chemolysis of cystine stones. The mechanism of action is believed to occur by a synergistic combination of the pH dependent increase in cystine solubility, with a simultaneously occurring thiol disulfide interchange.     

Percutaneous catheter dissolution of cystine calculi

In 11 kidneys with presumed cystine stones that were symptomatic and obstructing, percutaneous nephrostomy and stone lavage with either acetylcysteine-bicarbonate solution or tromethamine-E were performed. There were 7 complete stone dissolutions: 2 of 6 attempts with acetylcysteine-bicarbonate alone, 3 of 5 with tromethamine-E, 1 partial with acetylcysteine-bicarbonate, which was completed with tromethamine-E, and 1 proved mixed stone (cystine and calcium phosphate) that required acetylcysteine-bicarbonate and hemiacidrin. In 1 case tromethamine-E irrigation was 97 per cent complete but a few tiny caliceal fragments remained. There were 3 failures of chemolysis: 2 pure cystine stones (1 each acetylcysteine-bicarbonate and tromethamine-E) and 1 mixed calculus with a surface shell of calcium oxalate. Irrigation time was 6 to 42 days for the 7 unoperated kidneys. Tromethamine-E appears to be a more effective agent for cystine stone dissolution. Percutaneous nephrostomy and dissolution are an alternative to an operation in patients with cystine calculous disease.     

In vitro dissolution of cystine urinary calculi

Dissolution of cystine urinary calculi was studied in vitro. Sodium hydroxide, acetylcysteine and tris(hydroxymethyl)aminomethane (tromethamine) were tested for effectiveness in dissolving cystine calculi. Calculi were mounted in a dissolution apparatus. Dissolution rates were calculated from the amount of cystine released into solution per unit time and were compared with linear regression techniques. Calculated dissolution rates of all the irrigating agents tested were similar at a pH of 7.5 and were significantly different at pH 10.0. The most effective agent in the promotion of cystine dissolution was 2 per cent acetylcysteine. Sprague-Dawley rats were used to test the effect of 2 per cent acetylcysteine, 0.3 molar tromethamine and 2 per cent acetylcysteine mixed with 0.3 molar tromethamine on the urothelium. A nephrostomy tube was placed in the left kidney of each rat. The kidneys were irrigated for 3 days with either 2 per cent acetylcysteine, 0.3 molar tromethamine or 2 per cent acetylcysteine mixed with 0.3 molar tromethamine. The rats then were sacrificed at various intervals after infusion. Irrigation with 2 per cent acetylcysteine at a pH of 10 caused an acute inflammatory response at 3 days that was healed almost completely in 4 weeks. The addition of tromethamine to the acetylcysteine did not prevent the inflammatory response.     

Therapeutic dilemmas in management of cystine calculi

The appropriate management of patients with cystine calculi necessitates a fundamental understanding of the pathophysiology of cystinuria and a working knowledge of the available therapeutic modalities. The following case reports and review of the literature serve to illustrate that successful treatment involves a multidimensional approach to eradication of calculi with long-term follow-up aimed at prevention.     

Ureteroscopic management of recurrent renal cystine calculi

BACKGROUND AND PURPOSE: Patients with recurrent cystine nephrolithiasis oftentimes require multiple procedures for stone removal. As the majority of cystine stones are resistant to the effects of shockwave lithotripsy, repeat percutaneous surgery is often required and may cause renal damage. Moreover, repeat percutaneous access may become more difficult as perinephric fibrosis develops. Small-caliber ureteroscopes along with the holmium laser now enable routine intrarenal ureteroscopic access to symptomatic renal stones. Herein, we present our experience in managing recurrent renal cystine calculi using flexible ureterorenoscopy and assess whether such an approach may be used as an alternative to percutaneous surgery in selected patients. PATIENTS AND METHODS: Three patients with large-volume (mean diameter 22 mm) renal cystine stones were managed with a 7.5F flexible ureterorenoscope combined with holmium laser lithotripsy to fragment the stones completely. RESULTS: The mean treatment time was 97 minutes, with successful fragmentation in all cases. Two of the three patients were completely stone free on follow-up intravenous urography, with the third patient having only small-volume residual fragments in a lower pole calix. All patients are currently asymptomatic and are being maintained on high oral fluid intake, urinary alkalization with potassium citrate, and alpha-mercaptopropionylglycine to reduce urinary cystine excretion. CONCLUSION: Flexible ureterorenoscopy with holmium laser lithotripsy provides a reasonable alternative for the management for recurrent cystine calculi in patients who are not candidates for repeat percutaneous procedures. Although it is time consuming, complete stone fragmentation, along with clearance of fragments, can be achieved in the majority of patients.     

Endourological experience with cystine calculi and a treatment algorithm

Between May 1984 and January 1988, 18 patients (31 pyeloureteral units) with documented symptomatic cystine stones were treated. Stone size ranged from 5 to 56 mm. in largest diameter, with an average of 21 mm. All pyeloureteral units were treated initially by endourological methods, including ureteroscopy in 10, percutaneous ultrasonic lithotripsy in 9, extracorporeal shock wave lithotripsy (ESWL) in 10 and chemolysis in 2. Of the patients 10 required a combination of these technologies and 2 required an open operation. Of the 31 units 23 were free of stones when the patient was discharged from the hospital. Of 8 patients with retained stones only 3 had fragments greater than 3 mm. in diameter. Based on this experience an algorithm was developed for the urological management of cystine stones. Ureteral calculi may be removed by ureteroscopic techniques or manipulated into the renal pelvis and managed as renal stones. Cystine renal calculi of less than 1.5 cm. may be treated with ESWL monotherapy. Stones of 1.5 to 3 cm. may be treated with ESWL and dissolution, or percutaneous ultrasonic lithotripsy plus dissolution. Staghorn calculi may be treated by percutaneous ultrasonic lithotripsy plus ESWL and/or dissolution for retained fragments.     

Treatment of cystine calculi using intra-urologic methods and extracorporeal lithotripsy

The hardness and frequent recurrence of cystine stones represent a special challenge for the urologist. Fifteen cystinuric patients were treated in our department and followed over a mean period of 30 months. Most patients had a previous history of open surgery (1.5 pyelolithotomy/patient). Diagnosis of cystinuria was confirmed by metabolic studies and stone analysis. Over the follow-up period recurrence was observed in 23 instances in 11 patients thus leading to 38 stone treatments on 74 cystine stones. Stone size was less than 10 mm: 35 (47%); 10-20 mm: 21 (28%); 20-30 mm: 14 (19%); 30 mm: 4 (staghorn stones). A percutaneous approach was used in 9 cases as monotherapy (55% success) and in association with ESWL in 10 cases (50% success). ESWL was employed 18 times as monotherapy (39% success). Medical treatment included high fluid intake, alkalinisation and thiola in 6 patients. In conclusion, results obtained are poor in terms of stone clearance when compared to non-cystine stones. Recurrence rate is very high. Instrumental treatment should not be used excessively and is only indicated in symptomatic stones or refractory to intensive medical therapy.     

Clinical experience of extracorporeal shock wave lithotripsy for cystine calculi

Thirty patients (16 men and 14 women) with cystine urinary stones were treated by extracorporeal shock wave lithotripsy (Dormer HM-3) from December 1984 through October 1989. The average patient age was 35.2 years with a range of 14 to 59 years. Seventy per cent of these subjects had had previous open surgical operations for stones. The cases consisted of 7 ureteral stones and 37 renal stones, including 15 staghorn calculi. An average of 1.3 session of ESWL was carried out to treat ureteral stones. Thirty-seven renal units with renal stone required 96 sessions of lithotripsy (average 2.6 sessions per unit). Seven patients with ureteral stones required auxiliary procedures, i.e., one transurethral lithotripsy (TUL), two percutaneous nephrostomies (PNS) and one open surgery. Thirty-seven renal stones, including staghorn calculi was treated by ESWL and auxiliary treatment of 21 TUL procedures, one PNS, 16 PNL procedures and one chemical chemolysis. Successful fragmentation (residual debris less than or equal to 4 mm) was achieved in 85.7% of ureteral stones, 90.9% of renal stones and 73.3% of staghorn calculi. The stone free rates of patients with ureteral stones, renal stones and staghorn calculi were 71.4%, 50.0% and 53.5%, respectively, at 3 months after ESWL. No serious complications were seen in this series. Fever above 38.5 degrees C was the most common complications (13.5%). Ureteral perforation was encountered once in TUL procedures. Transfusion and selective arterial embolization were needed for one case treated by PNL procedures. Although cystine stone is harder to be fragmented by ESWL than other stone composition, ESWL and endourology may be effective and safe procedures for cystine stone patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preliminary experiences with the use of the Holmium-YAG laser in the treatment of soft tissues and of cystine calculi in children]

INTRODUCTION: Experience of the use of the Holmium: Yttrium-Aluminium-Garnet (Ho:YAG) laser in children has been limited. However, the Ho:YAG laser has been in clinical use in urology for several years but has mainly been used for the treatment of renal stones and benign prostatic hyperplasia. Due to its unique combination of vaporization and coagulation, the Ho:YAG laser allows a precise cutting action. The depth of penetration in water and tissue is limited to < 0.5 mm and therefore provides a safety margin. The Ho:YAG laser can be used in children, as the energy can be delivered via fibers that range from 200 to 1000 mu in diameter. MATERIALS AND METHODS: We used the Ho:YAG laser in 5 children (2-15 years): one child (2 years) with bladder exstrophy had a urethral stricture after bladder neck reconstruction, two children (6 years and 14 years) had ureteropelvic junction (UPJ) stenosis and refused open surgery and two children (5 years and 15 years) suffered from cystine stones (ESWL failed). The urethral stricture was incised in a retrograde fashion. We performed an antegrade incision of the UPJ with the Ho:YAG laser in the 6-year-old child and a retrograde incision in the 14-year-old child. We removed the stones in antegrade fashion in the 5-year-old child and in retrograde fashion in the 15-year-old child. RESULTS: All children now have more than 12 month's follow-up. There were no immediate or late complications. The boy with urethral stricture remained free of recurrence, the boy with UPJ stenosis obtained improved drainage on the excretory renogram and the two children with cystine stones remained stonefree. CONCLUSION: We have shown that the safety and efficacy of the Ho:YAG laser is also reproducible in urologic pathology in children. In addition, due to its vaporizing quality, the Ho:YAG laser is more effective in the treatment of cystine stones and allows minimaly invasive treatment in children.     

Chemolysis of cystine calculi incarcerated in the ureter by the alkaline organic amine, tromethamine-E

We dissolved the cystine calculi incarcerated in the ureter by irrigation with tromethamine-E via percutaneous nephrostomy. Case 1: A 25-year-old man with a past history of cystinuria and staghorn calculi in the right kidney, suffered from obstructive renal failure caused by the incarceration of a stone (18 x 15 mm) in the left middle ureter. After recovering promptly from renal failure by left percutaneous nephrostomy, he received continuous irrigation with tromethamine-E through an angiographic catheter percutaneously placed in the ureter. The ureteral calculus was reduced by 70% in size after the irrigation for 35 days, and then extracted percutaneously. Case 2: A 3-year-old child had multiple cystine calculi in the right renal pelvis and ureter. Although a calculus in the renal pelvis was extracted by the percutaneous ultrasound lithotripsy, two calculi incarcerated in the middle ureter were impossible to remove by a percutaneous approach. The irrigation with tromethamine-E was initiated through the catheter placed percutaneously in the right ureter. Both calculi completely dissolved 47 days later. The chemolysis by irrigation with tromethamine-E was greatly valuable in the treatment of cystine calculi. This dissolution could be an alternative to surgery especially in the treatment of ureteral cystine calculi, which might be difficult to be extracted by the percutaneous or transurethral approach.     

Dissolution of cystine calculi by irrigation with acetylcysteine through percutaneous nephrostomy.

Cystine calculi in the renal pelvis of a patient with cystinuria were dissolved by irrigation with a saline solution of acetylcysteine and bicarbonate through percutaneous nephrostomy.     

Place of extracorporeal shock-wave lithotripsy (ESWL) in management of cystine calculi

We treated 12 patients with sixteen renal and one ureteral cystine stones primarily with extracorporeal shock-wave lithotripsy (ESWL). Among the stones thirteen were greater than 25 mm. In four stones less than 25 mm, three stones completely disappeared and 1 was reduced to small fragments, following ESWL. In thirteen stones greater than 25 mm, twelve were treated by ESWL initially, and one by surgery. Of the 12 cases treated initially by ESWL, 4 became stone-free, 4 remained with small fragments, and 1 remained with large fragments. Two patients were operated on because of poor response to ESWL and 1 patient lost kidney function because of prolonged obstruction. Disintegration of cystine stones greater than 25 mm required an average of 8,522 shock-waves in 4.33 sessions. The problems associated with application of ESWL monotherapy to cystine stones are presented.     

Ureolytic Citrobacter freundii infection of the urine as a cause of dissolution of cystine renal calculi

We report a case of cystinuria with staghorn renal lithiasis in a solitary right kidney and chronic renal failure. Right nephropyelolithotomy was performed and although 29 renal calculi were extracted many stones remained in situ. A permanent nephrostomy was left in the kidney. Several months later the urine was infected chronically with a ureolytic Citrobacter freundii bacteria and urinary pH oscillated between 8.0 and 9.2. Spontaneous dissolution of the cystine calculi was observed and many tiny fragments of cystine were expulsed through the nephrostomy, following which renal function improved. Despite the conditions favoring struvite calculi, formation did not occur.     

Long-term followup in patients with cystine urinary calculi treated by percutaneous ultrasonic lithotripsy

From February 1983 through 1986, 15 patients (17 renal units) with cystine urinary lithiasis were treated by percutaneous ultrasonic lithotripsy. Three patients were lost to followup. Of the 13 renal units in the remaining 12 patients 7 (54 per cent) had retained stone fragments and 6 (46 per cent) were free of stones. While on medical management 7 of the 13 renal units (54 per cent) had new stones, 5 (38 per cent) remained unchanged and in 1 (8 per cent) the retained stones dissolved. The rate for reoperations was 43 per cent for the group with retained stones (3 of 7) and 17 per cent for the group that was free of calculi after percutaneous ultrasonic lithotripsy (1 of 6). Our study suggests that the optimal treatment with percutaneous ultrasonic lithotripsy should result in a patient who is free of stones.     

Treatment with percutaneous nephrolithotripsy and dissolution for bilateral renal cystine calculi in an infant

A 20-month-old child was admitted to our hospital due to obstructive renal failure caused by cystine calculi. After recovering from the renal failure by bilateral percutaneous nephrostomy, pelvic irrigation with N-acetylcysteine was performed using a 12Fr. flexible double lumen catheter. In 2 weeks the calculus was reduced by 39% in size, then residual calculi were successfully removed by percutaneous nephrolithotripsy using 11.5Fr. rigid ureteroscope and postoperative irrigation with N-acetylcysteine.