Metabolic abnormalities and the medical management of calcium oxalate nephrolithiasis.

The lifetime prevalence of urolithiasis is approximately 12% for men and 7% for women in the United States and seems to be increasing; the cost of managing kidney stones continues to escalate. The most common kidney stones continue to be composed primarily of calcium and are an admixture of phosphate and oxalate. Of these, calcium oxalate stones are the most predominant. This review will focus only on the pathogenesis and medical management of calcium oxalate stones.

Economics of urolithiasis: cost-effectiveness of therapies.

The cost of treating urolithiasis with extracorporeal shockwave lithotripsy and endoscopic surgery continues to be a significant burden on a nation's healthcare economy. Cost-effectiveness evaluations of various medical and surgical treatment options for urolithiasis is a practical method of developing rational allocation strategies for limited economic resources. In this review, the cost-effectiveness of shockwave lithotripsy and that of endoscopic surgery in the management of kidney and ureteral stones are compared. This is followed by a discussion of the cost of the medical management of urolithiasis in comparison with repeated surgical treatment.

10-year experience with extracorporeal shockwave lithotripsy in the state of Colorado.

PURPOSE: To evaluate trends in the utilization of extracorporeal shockwave lithotripsy (SWL) and the potential need for medical prophylaxis of urolithaisis in the state of Colorado. MATERIALS AND METHODS: We examined patient and stone characteristics of individuals undergoing SWL for renal or upper-ureteral stones over a 10-year period (1987-1996) at the Kidney Stone Center of the Rocky Mountains. There were no significant changes in the in-state physician referral patterns nor SWL treatment criteria over this time interval. All patients were treated on the Dornier HM3 lithotripter. From September 1999 to December 1999, 198 consecutive patients undergoing SWL filled out a 10-point questionnaire regarding their interest in medical prophylaxis of urolithiasis. RESULTS: The number of patients from Colorado rose 32.5%: from 15.7 per 100,000 population in 1987 to 20.8 per 100,000 in 1996. Patient demographics such as sex, race, age, and history of nephrolithiasis did not change. Furthermore, there were no significant changes in the treated stone size or stone location. The overall increase in treatment numbers was attributable equally to increases in the number of upper ureteral and renal stones. Of the 198 patients questioned, 114 (58%) were recurrent stone formers, but only 52 (45%) of these had been offered a metabolic evaluation. CONCLUSIONS: Over the 10 years since the introduction of WSL in Colorado, there has been a gradual increase in its utilization. This higher utilization is probably multifactorial. Patients undergoing SWL have a strong desire to prevent future stone episodes and are very interested in medical prophylaxis of their stone disease.

Transport of oxalate across the rabbit papillary surface epithelium.

PURPOSE: The renal papilla and pelvic recesses of the mammalian kidney are thought to be the anatomical sites of initial kidney stone formation. We studied oxalate transport across the renal papillary surface epithelium. MATERIALS AND METHODS: In vitro oxalate transport across the papillary surface epithelium was studied by dissecting it off of the papilla and mounting it in a modified Ussing chamber. Experiments were conducted using physiological Ringer's solution at 37C. Removal or appearance of radioactive oxalate from the solution bathing the apical papillary surface epithelium surface was used as a measure of transepithelial transport. RESULTS: When only the papillary surface epithelium apical surface was exposed to oxalate (17 micromol./l.), the apical to basolateral flux of oxalate was 7.1 +/- 1.5 nmol./cm.2 per hour. When only the basolateral side was perfused with oxalate, the basolateral to apical oxalate flux was 1.6 +/- 0.7 nmol./cm.2 per hour. When the apical and basolateral surfaces were exposed to oxalate, a net apical to basolateral flux of oxalate was 3.0 +/- 0.7 nmol./cm.2 per hour. There was almost complete inhibition of apical to basolateral oxalate transport when the experiments were conducted at 20C. Absorption of oxalate across the papillary surface epithelium was decreased by the addition of 1 mM. 4, 4'-diisothiocyanatsostilbene-2,2'-disulphonic acid (DIDS), independent of sodium, but reduced by the presence of chloride in the apical solution. Increasing the pH of the apical solution from 7. 4 to 7.8 also resulted in a significant decrease in papillary surface epithelium oxalate uptake. CONCLUSIONS: Rabbit papillary surface epithelium demonstrates oxalate absorption by mechanisms that may be similar to those described previously for renal and colonic epithelia. Absorption of oxalate across the papillary surface epithelium may have a role in the prevention of initial calcium oxalate stone formation within the pelvic recesses.

Anatomic and metabolic risk factors for nephrolithiasis in patients with autosomal dominant polycystic kidney disease.

The prevalence of nephrolithiasis is considerably greater in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the general population. We evaluated anatomic and metabolic factors that may be associated with an increased prevalence of nephrolithiasis in patients with ADPKD. We compared anatomic parameters among ADPKD patients with or without nephrolithiasis as diagnosed by ultrasonography, whereas metabolic factors were determined by 24-hour urinary chemical analysis. Patients with ADPKD and nephrolithiasis had more renal cysts (P < 0.05) and a larger predominant renal cyst size (P < 0.005) than patients without nephrolithiasis. Concurrently, individual stone-forming kidneys had a greater cyst number (P < 0.05) and a significantly larger predominant cyst size (P < 0.01) compared with kidneys without stones. Patients with ADPKD and nephrolithiasis had a significantly lower creatinine clearance than those without nephrolithiasis (68.7 +/- 8.6 versus 94.8 +/- 5.4 mL/min, respectively; P < 0.05). Twenty-four-hour urinary analysis showed that patients with ADPKD and nephrolithiasis had significantly lower urinary volumes (P < 0. 05), and levels of urinary phosphate (P < 0.05), magnesium (P < 0. 005), and potassium (P < 0.05). Although not statistically significant, patients with ADPKD with stones tended to have lower levels of urinary citrate, and both groups showed a high percentage (range, 49% to 60%) of patients with hypocitraturia. Our data are consistent with the hypothesis that patients with ADPKD who develop nephrolithiasis do so because of increased intrarenal anatomic obstruction, as well as lower levels of such urinary inhibitors of stones as magnesium and citrate.

Role of the renal collecting system in initial kidney stone formation.

BACKGROUND: The anatomic site where the initial kidney stone grows to a clinically significant size is unknown. METHODS AND MATERIALS: We studied human forniceal anatomy by microdissection and correlated the anatomic findings with the clinical presentation of kidney stones. In addition, we examined crystal attachment sites within the collecting system by direct infusion of calcium oxalate crystals into the renal pelvis of rabbits. RESULTS: Secondary urinary dead spaces were found in the fornices of compound papillae only, which were located at the poles of the kidneys. This feature correlated with a higher incidence of stones in these areas at the time of lithotripsy. Calcium oxalate crystals tended not to attach to either the renal papilla nor the pelvic sidewall unless these epithelia were previously injured with hydrochloric acid. CONCLUSION: The renal collecting system may serve as an anatomic site for crystal retention and growth but is unlikely to be the principal site for crystal attachment, unless prior cellular injury occurs.

Role of sex hormones in experimental calcium oxalate nephrolithiasis.

It is unclear why men have a higher incidence of calcium oxalate nephrolithiasis than women. This study examined the role of sex hormones on urinary oxalate excretion and kidney stone formation in an experimental model of urolithiasis. Adult male and female Sprague Dawley rats with different sex hormone modulations were given 0.75% ethylene glycol for 2 wk to induce hyperoxaluria and kidney calcium oxalate crystal deposition. The study groups were: intact male and female rats; castrated male and female rats; intact male or female rats with opposite sex hormone implants; and castrated male and female rats with either testosterone or estradiol implants. Overall, a significant negative correlation between urinary oxalate and plasma estradiol/testosterone ratio was found. None of the estradiol-implanted rats, whether male or female, intact or castrated, developed kidney crystal deposits. The three groups of testosterone-implanted rats had a 43 to 88% rate of kidney calcium oxalate crystal deposition. These results indicate that androgens increase and estrogens decrease urinary oxalate excretion, plasma oxalate concentration, and kidney calcium oxalate crystal deposition. These findings may partly explain why nephrolithiasis is a predominantly male disease.

Comparison of comprehensive and limited metabolic evaluations in the treatment of patients with recurrent calcium urolithiasis.

PURPOSE: We compared diagnostic information from limited and comprehensive metabolic evaluations of recurrent calcium stone formers. MATERIALS AND METHODS: A total of 74 men and 45 women with recurrent calcium stones underwent comprehensive metabolic evaluation. The number of specific and total metabolic abnormalities diagnosed on 1 or 2 random 24-hour urinalyses were compared to those obtained on a comprehensive metabolic evaluation. We also examined the ability of the comprehensive evaluation to detect dietary calcium sensitive oxaluria. RESULTS: The comprehensive metabolic evaluation yielded a specific metabolic diagnosis in 90% of the patients compared to 68% for 1 and 75% for 2 urinalyses. Average total number of specific metabolic abnormalities for each patient was approximately 50% higher on a comprehensive metabolic evaluation compared to 1 urinalysis (1.59 +/- 0.08 versus 0.94 +/- 0.07, p <0.05). Hypercalciuria, hyperoxaluria and hypocitruria were diagnosed significantly more often by the comprehensive than by the limited evaluation. Type II absorptive hypercalciuria was the most common pattern of hypercalciuria, and dietary calcium sensitive oxaluria was present in 22% of the patients. CONCLUSIONS: Comprehensive metabolic evaluation yields significantly more useful diagnostic information and allows implementation of a more specific therapeutic plan than limited metabolic evaluation for the recurrent calcium stone former.

Examination of crystalluria in freshly voided urines of recurrent calcium stone formers and normal individuals using a new filter technique.

PURPOSE: We evaluated calcium oxalate (CaOx) and calcium phosphate (CaP) crystalluria in freshly voided urines of normal individuals (controls) and recurrent calcium stone formers (RSF) using a new filter technique. MATERIALS AND METHODS: Chemical analysis of urinary sediment retained by a 0.45 microm. Millipore filter was used to quantitate crystalluria. A CaOx and CaP crystal suspension initially confirmed the reliability of the filter technique. Freshly voided urine samples from 11 controls and 15 RSF were then evaluated. Sediment calcium (S-Ca), oxalate (S-Ox) and phosphate (S-PO4) were compared with routine light microscopy for crystal detection. RESULTS: The recoveries of calcium (Ca) and oxalate (Ox) from the CaOx crystal suspension were 83.8% and 87.5%, respectively. The recoveries of Ca and phosphate (PO4) from the CaP crystal suspension were 97.7% and 89.7%, respectively. The CaOx and CaP crystal volumes (S-Ox and S-PO4) were similar between controls and RSF. However, the sediment to urinary ionic ratios, a parameter indicative of crystal formation under similar levels of supersaturation, was significantly higher in RSF. S-PO4 was 3 to 4 times higher than S-Ox, both in controls and RSF. There was a strong positive correlation between urinary Ox (U-Ox) concentration, and S-Ox and S-Ca concentrations in RSF, but not in controls. There was also a positive correlation between urinary phosphate (U-PO4) and S-PO4 in both groups. A good correlation was also found between the filter technique and standard microscopy for the detection of crystalluria. CONCLUSIONS: We conclude that the filter technique is a simple and sensitive quantitative method to study crystalluria. The predominant crystal type in fresh urines of both controls and RSF appears to be calcium phosphate. The principal difference between crystalluria of RSF and normals is its tendency to form at a lower urinary ionic concentration in RSF, suggesting a higher crystallization inhibitor activity in normal individuals.

Metabolic risk factors in patients with first-time and recurrent stone formations as determined by comprehensive metabolic evaluation.

OBJECTIVES: To determine whether patients with recurrent calcium stone formation have more significant metabolic abnormalities compared with patients with first-time stone formation as determined by a comprehensive metabolic evaluation. METHODS: We investigated metabolic abnormalities in 37 patients (14 men, 23 women) with first-time and 136 patients (83 men, 53 women) with recurrent calcium stones, stratified according to sex. Calcium oxalate supersaturation indexes of Tiselius (1991) and Ogawa (1996) were also compared between the groups. In addition to the specific metabolic abnormalities, we analyzed the total number of such defects for each group. RESULTS: In men, the average number of metabolic abnormalities in each patient was greater in patients with recurrent stones (2.20+/-0.86) than in those with first-time stones (1.46+/-1.27). Such a difference could only be demonstrated for women if low urine volume was excluded as a specific abnormality. Although the frequency of each abnormality was higher in patients with recurrent stones, a statistically significant difference was only noted in the frequency of hypocitraturia between women with first-time and recurrent stone formation (11.1% versus 37.8%, P < 0.05). There were no significant differences in the calcium oxalate supersaturation indexes between first-time and recurrent stone formation in either men or women. CONCLUSIONS: Women with recurrent stones have a higher prevalence of hypocitraturia than women with first-time stones. Potassium citrate therapy for prevention of urolithiasis may be especially useful for this patient population.

Lower-pole caliceal stone clearance after shockwave lithotripsy, percutaneous nephrolithotomy, and flexible ureteroscopy: impact of radiographic spatial anatomy.

Spatial anatomy of the lower renal pole, as defined by the infundibulopelvic angle (LIP angle), infundibular length (IL), and infundibular width (IW), plays a significant role in the stone-free rate after shockwave lithotripsy. A wide LIP angle, a short IL, and a broad IW, individually or in combination, favor stone clearance, whereas a LIP <70 degrees, an IL >3 cm, or an IW < or =5 mm are individually unfavorable. When all three unfavorable factors or an unfavorable LIP and IL coexist, the post-SWL stone-free rate falls to 50% or less. Using these criteria, more than one fourth of our patients with a lower-pole calculus might have been better served by an initial percutaneous or perhaps ureteroscopic procedure, neither of which is significantly affected by the lower-pole spatial anatomy.

Renal osteopontin expression in experimental urolithiasis.

Although osteopontin (Opn) is a strong inhibitor of calcium oxalate crystallization in vitro, its role in stone formation in vivo is unknown. We investigated the renal expression of Opn in normal, ethylene glycol (EG), and EG + ammonium chloride-treated rats. Male Sprague-Dawley rats were divided into three groups. Group 1 (N = 5) was the control. Animals in Group 2 (N = 6) received 4 weeks of treatment with 0.75% EG, and Group 3 animals (N = 6) were given 1 week of treatment with 0.75% EG and 1.0% NH4Cl. The kidneys were then examined for crystal deposition and Opn localization. In normal rats, staining for Opn was evident in the proximal tubules (PT; S3 > S2 > S1), distal tubules (DT), and the thick ascending limbs of Henle (TAL) and a few collecting ducts (CD). All rats in Group 3 had significant crystal deposition throughout their kidneys. In Group 2 rats, Opn staining increased in all segments of the PT, DT, and TAL. Staining in these tubular segments was even greater in Group 3 rats, including the CD and the papillary surface epithelium. In addition, Opn was present within all crystal deposits. Renal Opn expression in experimental urolithiasis becomes stronger and more diffuse as the severity of the lithiasis-inducing treatment increases. These results are consistent with the hypothesis that renal epithelial cells produce larger amounts of osteopontin to combat the development of kidney stones.

Laparoscopic nephrectomy in children.

Using the techniques for laparoscopic nephrectomy developed in adults, pediatric nephrectomy results in equivalent surgical outcomes compared with open surgery. To date, both transperitoneal and retroperitoneal laparoscopic approaches to nephrectomy for benign renal disease have been described. Controversy exists among pediatric urologists, however, regarding the advantages of laparoscopic nephrectomy in children because convalescence from an open nephrectomy is also rapid. This article reviews the current indications and techniques for laparoscopic nephrectomy in children as well as other surgical applications of laparoscopy with respect to the pediatric patient.

Effect of castration and finasteride on urinary oxalate excretion in male rats.

We investigated the effects of castration and finasteride administration on urinary oxalate (Ox) excretion in a rat ethylene glycol (EG) model of urolithiasis. Male adult SD rats were divided into six groups. Group 1 were normal, untreated rats. The other five groups, all treated with 0.75% EG for 4 weeks; were as follows: group 2, non-castrated (intact) rats; group 3, castrated rats; group 4, castrated rats with a 4-cm testosterone implant; group 5, intact rats treated with high-dose finasteride (7.5 mg%); and group 6, intact rats treated with low-dose finasteride (0.75 mg%). Urinary Ox excretion increased 12.8-fold after 4 weeks of EG treatment (group 2 vs group 1). Both castration (group 3) and finasteride administration (groups 5 and 6) significantly decreased urinary Ox excretion compared with intact rats (group 2). We conclude that dihydrotestosterone is partially responsible for the exaggerated hyperoxaluria observed in the rat EG model of urolithiasis.

Cost-effectiveness analysis: application to endourology.

A literature review was conducted on the application of economic analysis to clinical medicine, particularly urology. The surgical management of urolithiasis and the treatment of ureteropelvic junction obstruction were used as specific disease examples to evaluate how cost-effectiveness analysis has been used to address the clinical concerns of practicing urologists. As the costs and outcomes of the treatment of kidney stone disease and ureteropelvic junction obstruction can be specifically defined, the application of cost-effectiveness analysis in these two areas meets most standards of economic analysis. Economic models that incorporate poor assumptions, incomplete data, or both are unlikely to have significant clinical utility. The most useful models are those that are structurally simple and evaluate healthcare program alternatives from the patient's, provider's, or society's perspective.

Efficacy and cost-effectiveness of extracorporeal shock wave lithotripsy for solitary lower pole renal calculi.

PURPOSE: We determined the efficacy of extracorporeal shock wave lithotripsy monotherapy and compared its cost-effectiveness with percutaneous nephrolithotomy for the management of lower pole renal calculi. MATERIALS AND METHODS: The efficacy (stone-free rates at 3-months posttreatment) of shock wave lithotripsy with the modified Dornier HM3* machine was determined retrospectively in 114 patients with solitary lower pole renal calculi. Using cost data available from patient billing charges and efficacy data from the literature, the cost-effectiveness for percutaneous nephrolithotomy and shock wave lithotripsy as primary therapy was evaluated. To make this cost-effectiveness comparison, we developed a decision analysis model in which a patient in whom primary therapy failed was rendered stone-free with a secondary percutaneous nephrolithotomy procedure. RESULTS: The stone-free rates of solitary lower pole stones with a size range of less than 10, 11 to 20 and greater than 20 mm. were 76, 74 and 33%, respectively, with a single shock wave lithotripsy treatment. Based on average treatment costs for shock wave lithotripsy and percutaneous nephrolithotomy, the model results show that for stone sizes less than 2 cm. primary lithotripsy therapy followed by nephrolithotomy for failed cases is the least costly approach. For stone sizes greater than 2 cm. primary percutaneous nephrolithotomy may be more cost-effective. CONCLUSIONS: Whereas shock wave lithotripsy with the Dornier HM3 should be considered the initial treatment choice for most lower pole stones less than 2 cm., primary percutaneous nephrolithotomy should be considered for stones larger than 2 cm.

Cost-effectiveness of different treatment options for staghorn calculi.

PURPOSE: The cost-effectiveness of shock wave lithotripsy monotherapy, percutaneous nephrolithotomy and combined sandwich therapy in the treatment of staghorn calculi was examined. MATERIALS AND METHODS: The cost-effective index, which estimates the average cost of making 1 patient stone-free, was computed for the various treatment options. Data for effectiveness of each therapy were used as available from the literature. Billing charges were used as cost data from University Hospital and the Kidney Stone Center. RESULTS: Average charges for a single percutaneous nephrolithotomy were $26,622, of which 81% were facility charges and 7.9% urologist fees. Average charges for a single shock wave lithotripsy were $8,213, 60.3% of which were facility fees and 33.3% of which were urologist charges. Overall, percutaneous nephrolithotomy and combined sandwich therapy were more cost-effective than shock wave lithotripsy monotherapy. When the stone surface area was less than 500 mm2 combined sandwich therapy and shock wave lithotripsy monotherapy were equally cost-effective. However, when the stone burden was greater than 500 mm2 combined sandwich therapy clearly became more cost-effective than shock wave lithotripsy monotherapy. CONCLUSIONS: Percutaneous nephrolithotomy followed by shock wave lithotripsy, if necessary, and second look nephroscopy are the most cost-effective methods of treating staghorn calculi.

Laparoscopic repair of vesicoureteral reflux utilizing the Lich-Gregoir technique in the pig model.

To date, laparoscopic urological surgery has largely been limited to diagnostic or ablative procedures. Herein we report our experience with laparoscopic reconstructive surgery to perform an extravesical ureteral reimplantation. Seven anesthetized pigs with iatrogenic ureteral reflux underwent a laparoscopic extravesical ureteral reimplantation. The newly created ureteral tunnel varied from 2 to 4 cm. In 3 pigs, the tunnel was created with tacking staples, while in the other 4 pigs, the tunnel was created with intracorporeal suturing techniques using a 3-zero polyglyconate running suture. The procedure required an average of 132 minutes. There was one anesthetic death. There were no urinary tract infections. At 3 to 8 weeks after reimplantation, the cystograms were repeated on 5 pigs. One of 2 stapled reimplant pigs still had reflux; 1 of 3 sewn reimplant pigs had reflux. At 6 months following the reimplantation, only 1 pig had residual grade I reflux and this was a sutured reimplantation. None of the stapled reimplantations exhibited any residual reflux on the surgical side; however, in 1 animal a submucosal staple was noted at the time of harvest.

Outcome of extracorporeal shockwave lithotripsy monotherapy for large renal calculi: effect of stone and collecting system surface areas and cost-effectiveness of treatment.

The treatment options for large renal calculi are controversial. We report on our experience with 65 treatments of renal calculi > 3 cm using extracorporeal shockwave lithotripsy (SWL) monotherapy. We stratified our results according to stone and collecting system surface areas (measured by computer image analyses), stone location, and stone type. The overall success rate of SWL monotherapy was 27% at 3 months. The best stone-free rate (60%) was obtained for stones < 500 mm2 and located primarily within the renal pelvis. The stone-free rate for stones with surface areas > 1000 mm2 was only 8%. None of the cystine stones was treated successfully, whereas 80% of patients with uric acid stones became stone free. We estimated an average cost of $67,048 to render a patient with a large renal calculus stone free using SWL monotherapy. We recommend that other treatment options, such as percutaneous nephrolithotomy, be considered as first-line therapy for large renal calculi.