Treatment with extracorporeal shockwave lithotripsy (ESWL), endourology and dissolution for staghorn calculi composed of cystine: report of two cases

Two cases of complete staghorn calculi composed of cystine that were treated with ESWL, endourology and dissolution are reported. After successful dissolution in vitro using tromethamine (pH 8-10), the same solution was used to irrigate the renal collecting system via nephrostomy tube for residual fragments after ESWL and/or endourology. One patient was treated with dissolution for 60 days, the other patient for 6 days. After this therapy, these patients became almost stone-free. Our experience demonstrates that the residual fragments after ESWL and/or endourology with staghorn calculi composed of cystine can be dissolved by tromethamine.     

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.     

Chemolysis of artificial cystine stones (BON(N)-STONES) in vitro using a new dissolution device: first results

BACKGROUND AND PURPOSE: The treatment of cystine stones is a clinical problem. This in vitro study was performed to establish an experimental system that enables standardized and reproducible investigations on chemolysis of cystine stones to look for an improvement of dissolution strategies. MATERIALS AND METHODS: Artificial spherical stones made of cystine (BON(N)-STONES) with a diameter of 0.9 cm were used. A new dissolution device was developed simulating the physiological conditions in the upper urinary tract with computer-assisted online measurement of data. For chemolysis of artificial cystine stones, different solvents (artificial urine, physiologic sodium chloride solution, 2 % acetylcysteine, 8.4 % sodium bicarbonate solution, THAM, and combinations) were used. RESULTS: Chemolysis is an effective tool in the management of cystine stone disease. Statistical analysis showed significant differences (p < or = 0.05) for all solutions compared with artificial urine alone. A combination of THAM at pH 10 with acetylcysteine (2%) showed a 48-fold stronger ability to dissolve cystine calculi than did artificial urine. CONCLUSION: By performing standardized in vitro investigations, new basics to improve the dissolution of cystine stones have been developed. It is recommended to use artificial stones made of cystine and a dissolution device simulating physiological conditions for investigations on chemolysis in the future.     

Dissolution kinetics of uric acid calculi

Dissolution of uric acid calculi was studied in vitro. Calculated rate constants were then applied to an in vivo situation. The time required for complete dissolution of a uric acid calculus in a patient on oral alkali therapy can be estimated. Sodium bicarbonate, acetylcysteine, [tris(hydroxymethyl)aminomethane] and [tris(hydroxymethyl)aminomethane]-E were tested for relative effectiveness in dissolving uric acid calculi in vitro. In patients who require irrigation for dissolution of uric acid calculi [tris(hydroxymethyl)-aminomethane] is the preferred agent.     

Kinetics of dissolution of calcium oxalate calculi with calcium-chelating irrigating solutions

Dissolution of calcium oxalate urinary calculi was studied in vitro. Rate constants were calculated by measuring the concentration of calcium in solution during dissolution. Various irrigating agents, including ethylenediaminetetraacetic acid (EDTA) and other calcium-chelating substances, were tested at different concentrations and pH values. EDTA was the most effective agent in dissolving calcium oxalate calculi. When EDTA was used, the rate of dissolution depended on both concentration and pH. At a pH of 7.5 or 10.0, the rate of dissolution increased progressively with the EDTA concentration. At each concentration tested, dissolution was faster at a pH of 10.0 than at a pH of 7.5. Calculated rate constants were extrapolated to determine whether in vivo irrigation with EDTA solutions is clinically practical. Even at an EDTA concentration of 0.03 M at a pH of 7.5, a two mm. calculus could be dissolved within 48 hr. Although dissolution of calcium oxalate calculi is not a practical first-line treatment, it might be a useful adjunct to percutaneous stone removal or extracorporeal shock wave lithotripsy.     

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.     

Urothelial injury to the rabbit bladder from various alkaline and acidic solutions used to dissolve kidney stones

Different irrigating solutions are used clinically to dissolve uric acid, cystine and struvite stones. These studies were undertaken to assess the toxicity to the rabbit bladder epithelium of several commonly used formulations. Test solutions were infused antegrade through a left ureterotomy overnight. Bladders were removed and routine histological sections made. A pH 7.6 solution of NaHCO3 appeared harmless. The same solution with two per cent acetylcysteine produced slight injury. All pH 4 solutions caused significant damage to the urothelium. Hemiacidrin, which contains magnesium, produced less damage than did other pH 4 solutions without that cation. Our data tend to support Suby's conclusions that addition of magnesium reduces urothelial injury even though the presence of magnesium will slow dissolution of struvite.     

Experimental observations on dissolution of uric acid calculi

An in vitro model was devised to evaluate the efficacy of the different irrigating solutions utilized for local dissolution of uric acid stones. Tris (hydroxymethyl) aminomethane proved to be several times faster than sodium bicarbonate in dissolving uric acid calculi. The maximal dissolution rate was obtained when the highest pH (10.5) of Tris buffer was used in concentrations at or above 0.2 M. This makes the commercially available THAM-E an optimal choice. Stones averaging 1 cm. in diameter were dissolved in less than 48 hours when this compound was used. Sodium bicarbonate should only be used in solutions with concentrations lower than 0.2 M and pH below 9, if some dissolution is to be attempted. Concentrations and pH's above these levels will coat the stones with hard shells of sodium urate, making it impossible to dissolve them. The in vitro findings were confirmed in vivo in a limited study in pigs with human uric acid calculi surgically placed in their kidneys. Our results indicate how to make the best use of the solutions clinically available in order to obtain total dissolution of uric acid stones in short periods of time. We recommend the use of a 0.3 molar concentration of this buffer (THAM-E) at flow rates of about 50 cc per hour.     

Dissolution of uric acid calculi with intravenous 1/6 molar lactate

The use of intravenous 1/6 molar sodium lactate for dissolution of uric acid calculi is reported in 4 patients. All presented with a urine pH of 5. The calculi were located in the proximal ureter in 2 patients and in the renal pelvis in the other 2 patients. After infusion of 1/6 molar lactate, rapid alkalinization of the urine to pH 8 was achieved and maintained. The mean time required for dissolution of the calculi was 6.2 days precluding the need for surgical intervention. The mechanism of action of lactate is oxidative conversion to bicarbonate, providing a sustained alkaline urine. While our patients experienced no metabolic complications, one should monitor serum electrolytes, blood pressure, and fluid balance, particularly in cardiac-compromised patients.     

The spectrum of metabolic abnormalities in patients with cystine nephrolithiasis

To elucidate the pathophysiology of mixed stone formation in cystinuria, 27 patients with documented cystine nephrolithiasis underwent an inpatient evaluation under a constant dietary regimen. All patients had homozygous cystinuria, since the daily urinary cystine excretion exceeded 250 mg. per gm. creatinine. Hypercalciuria was noted in 5 patients (18.5 per cent), 4 of whom had fasting hypercalciuria. Hyperuricosuria was found in 6 patients (22.2 per cent) and it was not caused by a consumption of a diet rich in animal proteins, since urinary pH was higher and urinary sulfate lower than in control subjects. Serum uric acid was slightly lower and uric acid clearance was higher in hyperuricosuric patients than in control subjects. Hypocitraturia was found in 12 patients (44.4 per cent) and it was associated with defective renal acidification in 4 of 5 patients in whom it was tested. Thus, hypercalciuria, hyperuricosuria and hypocitraturia frequently accompany cystinuria in patients with cystine nephrolithiasis. These conditions might be renal in origin, rather than a result of dietary or environmental aberrations. They may contribute to the formation of calcium and uric acid stones, which sometimes complicate cystine nephrolithiasis.     

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.     

Comparison of results and morbidity of percutaneous nephrostolithotomy and extracorporeal shock wave lithotripsy

Two new therapies, percutaneous nephrostolithotomy and extracorporeal shock wave lithotripsy, are revolutionizing the treatment of upper urinary tract calculi. We report the success and morbidity rates in 110 patients undergoing percutaneous nephrostolithotomy and 982 patients treated with extracorporeal shock wave lithotripsy. Staghorn calculi were excluded from this series. The over-all success rate (free of stones plus small asymptomatic residual fragments) was comparable with both modalities (percutaneous nephrostolithotomy 98 per cent and extracorporeal shock wave lithotripsy 95 per cent), although the presence of residual fragments was more common in kidneys treated with extracorporeal shock wave lithotripsy (24 versus 7 per cent). Patient morbidity as measured by temperature elevation, length of postoperative stay, pain and blood loss was significantly less (p less than 0.05) with extracorporeal shock wave lithotripsy than with percutaneous nephrostolithotomy. Re-treatment rates were similar with both procedures, and tended to increase in relation to increasing stone size and stone number. Post-treatment ancillary procedures (cystoscopy and stone manipulation, and percutaneous nephrostomy) were used more frequently with extracorporeal shock wave lithotripsy. Because of its efficacy and low morbidity, we conclude that extracorporeal shock wave lithotripsy is the treatment of choice for upper urinary tract calculi less than 2 cm. in diameter. However, percutaneous nephrostolithotomy will continue to have a primary role in the management of larger stones and cystine stones, and it will be used as a secondary procedure after unsuccessful extracorporeal shock wave lithotripsy treatments. In addition, because of the complimentary nature of these 2 new technologies certain complex stones, such as staghorn calculi, may be handled best by a combination of the 2 techniques.     

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.     

Endoscopic management of upper urinary tract stones

Since 1981, 525 renal and ureteric calculi have been removed with percutaneous nephrolithotomy (PCN) or transurethral ureteroscopy as the primary modalities of therapy. Successful extraction of the stone at the first attempt was achieved in 92 per cent of cases by PCN and 70 per cent of cases by ureteroscopy, whilst further endoscopic surgery improved the overall success rates to 98 per cent and to 80 per cent respectively. Complication rates from these procedures have both been low as has the morbidity, with most patients leaving hospital within 4 days and returning to work within 2 weeks. The successful development of endoscopic lithotomy and the use of in situ destruction techniques has meant that we now reserve open surgery for difficult multibranched staghorn calculi and ureteric stones embedded in the urothelium. With the advent of extracorporeally generated shockwave lithotripsy it is likely that even these types of stone will be amenable to minimally invasive procedures.     

Extracorporeal shock wave lithotripsy for cystine urolithiasis in children: Outcome and complications

The Siemens Lithostar Litotriptor was used to treat 6 children withcystine nephrolithiasis, previously treated by open surgery. Fivechildren had renal calculi (3 multiple caliceal, 2 pelvis) and one hadureteral calculus. Stone size ranged from 0.2–2.5 cm in diameter,and stone burden was from 0.24 to 10.81 cm³ per kidney. Fromone to 4 ESWL sessions per unit were applied, with a total of 1,800 to12,000 shock waves. The stone free rate at 3 months was 50%. Acomplete elimination was obtained with cystine stones in renal pelvisand ureter, however, up to 4 ESWL treatments failed in caliceal stones.Rather location of cystine calculi than previous surgery was associatedwith ESWL success rate. Two patients with positive urine cultures weresuccessfully treated with appropriate antibiotics before ESWL wasattempted. Perirenal hematoma was major complication demonstrated byradionuclide scintigraphy in one patient, and resolved spontaneously by3 months. In the combined treatment of cystine urolithiasis in childrenESWL, as auxillary procedure, was safe and effective in pelvis stone butfailed in caliceal stones. Medical dissolution for retained fragmentswas found effective.     

Extracorporeal shock wave lithotripsy: the Methodist Hospital of Indiana experience

A total of 982 patients underwent 1,416 treatments with extracorporeal shock wave lithotripsy for upper urinary tract calculi between February 23 and December 17, 1984. A single treatment was performed in 90 per cent of the patients. Morbidity was extremely low and hospital stay was short (3.0 days). Adjunctive procedures were required in 13 per cent of the patients. Of the kidneys 72 per cent were free of stones at the 3-month followup, while 23 per cent contained small (less than 5 mm.), asymptomatic fragments believed to be passable spontaneously. Only 1 per cent of the patients required surgical removal of the calculi. Morbidity was related directly to stone burden, while results were inversely related to stone burden. Extracorporeal shock wave lithotripsy is the preferred form of management for symptomatic upper ureteral and renal calculi less than 2 cm. in diameter.     

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)     

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.     

Ultrasound diagnosis of ureteral stones: its usefulness with subsequent excretory urography

The diagnostic accuracy of ultrasound scanning and excretory urography was compared in 157 patients with ureteral stones. Over-all, the diagnostic accuracy rates were 78.3 per cent for ultrasound scanning and 81.5 per cent for excretory urography. These rates were 83.2 and 85.0 per cent, respectively, in 107 cases of upper ureteral calculi, and 68.0 and 74.0 per cent, respectively, in 50 cases of lower ureteral stones. When the studies were combined the diagnostic accuracy rates increased to 98.1, 94.0 and 96.8 per cent for upper, lower and all stones, respectively. Ultrasound scanning is useful in the diagnosis of ureteral stones, especially in patients with ureteral colic. However, ultrasound combined with subsequent excretory urography is the most reliable method for the diagnosis of ureteral calculi. Bladder filling is a useful diagnostic aid for ultrasound scanning of lower ureteral calculi.     

Primary dissolution therapy of struvite calculi

Percutaneous nephrostomy and hemiacidrin were used as primary treatment of magnesium ammonium phosphate calculi in 32 surgical candidates. Of 28 patients who actually received hemiacidrin 24 (85 per cent) had successful treatment (no surgery necessary), including 19 (68 per cent) who had total stone dissolution. There were no significant complications. Patients have been followed for 3 months to 7 years. Percutaneous nephrostomy with hemiacidrin infusion is another possible treatment in the growing alternatives available for patients with urinary struvite calculi.