Metabolism of fructose to oxalate and glycolate.

Much attention has been recently directed at fructose consumption because of its association with obesity and subsequent development of chronic diseases. It was recently reported that an increased fructose intake increases the risk of forming kidney stones. It was postulated that fructose consumption may increase urinary oxalate, a risk factor for calcium oxalate kidney stone disease. However, conflicting results have been obtained in human studies examining the relationship between fructose metabolism and oxalate synthesis. To test whether fructose intake influences urinary excretions impacting kidney stone risk, healthy subjects consumed diets controlled in their contents of fructose, oxalate, calcium, and other nutrients. Subjects consumed diets containing 4, 13, and 21% of calories as fructose in a randomized order. No changes in the excretions of oxalate, calcium, and uric acid were observed. In vitro investigations with cultured liver cells incubated with (13)C-labeled sugars indicated that neither fructose nor glucose was converted to oxalate by these cells. Fructose metabolism accounted for 12.4 ± 1.6% of the glycolate detected in the culture medium and glucose 6.4 ± 0.9%. Our results suggest that mechanisms for stone risk associated with fructose intake may lie in factors other than those affecting the major stone risk parameters in urine.

Hydroxyproline ingestion and urinary oxalate and glycolate excretion.

Endogenous synthesis of oxalate is an important contributor to calcium oxalate stone formation and renal impairment associated with primary hyperoxaluria. Although the principal precursor of oxalate is believed to be glyoxylate, pathways in humans resulting in glyoxylate synthesis are not well defined. Hydroxyproline, a component amino acid of collagen, is a potential glyoxylate precursor. We have investigated the contribution of dietary hydroxyproline derived from gelatin to urinary oxalate and glycolate excretion. Responses to the ingestion of 30 g of gelatin or whey protein were compared on controlled oxalate diets. The time course of metabolism of a 10 g gelatin load was determined as well as the response to varying gelatin loads. Urinary glycolate excretion was 5.3-fold higher on the gelatin diet compared to the whey diet and urinary oxalate excretion was 43% higher. Significant changes in plasma hydroxyproline and urinary oxalate and glycolate were observed with 5 and 10 g gelatin loads, but not 1 and 2 g loads. Extrapolation of these results to daily anticipated collagen turnover and hydroxyproline intake suggests that hydroxyproline metabolism contributes 20-50% of glycolate excreted in urine and 5-20% of urinary oxalate derived from endogenous synthesis. Our results also revealed that the kidney absorbs significant quantities of hydroxyproline and glycolate, and their metabolism to oxalate in this tissue warrants further consideration.

Lower pole I: a prospective randomized trial of extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy for lower pole nephrolithiasis-initial results.

PURPOSE: The efficacy of shock wave lithotripsy and percutaneous stone removal for the treatment of symptomatic lower pole renal calculi was determined. MATERIALS AND METHODS: A prospective randomized, multicenter clinical trial was performed comparing shock wave lithotripsy and percutaneous stone removal for symptomatic lower pole only renal calculi 30 mm. or less. RESULTS: Of 128 patients enrolled in the study 60 with a mean stone size of 14.43 mm. were randomized to percutaneous stone removal (58 treated, 2 awaiting treatment) and 68 with a mean stone size of 14.03 mm. were randomized to shock wave lithotripsy (64 treated, 4 awaiting treatment). Followup at 3 months was available for 88% of treated patients. The 3-month postoperative stone-free rates overall were 95% for percutaneous removal versus 37% lithotripsy (p <0.001). Shock wave lithotripsy results varied inversely with stone burden while percutaneous stone-free rates were independent of stone burden. Stone clearance from the lower pole following shock wave lithotripsy was particularly problematic for calculi greater than 10 mm. in diameter with only 7 of 33 (21%) patients becoming stone-free. Re-treatment was necessary in 10 (16%) lithotripsy and 5 (9%) percutaneous cases. There were 9 treatment failures in the lithotripsy group and none in the percutaneous group. Ancillary treatment was necessary in 13% of lithotripsy and 2% percutaneous cases. Morbidity was low overall and did not differ significantly between the groups (percutaneous stone removal 22%, shock wave lithotripsy 11%, p =0.087). In the shock wave lithotripsy group there was no difference in lower pole anatomical measurements between kidneys in which complete stone clearance did or did not occur. CONCLUSIONS: Stone clearance from the lower pole following shock wave lithotripsy is poor, especially for stones greater than 10 mm. in diameter. Calculi greater than 10 mm. in diameter are better managed initially with percutaneous removal due to its high degree of efficacy and acceptably low morbidity.

Virtual endoscopy.

Virtual endoscopy is a technique in which three-dimensional viewing of hollow structures is conducted through the utilization of high-resolution imaging and unique computer processing methods. The basic components of this technique and its applications for urology and other clinical disciplines are reviewed.

Anatrophic nephrolithotomy.

INTRODUCTION: Anatrophic nephrolithotomy is a procedure in which a parenchymal incision is made in an intersegmental plane, allowing removal of large renal calculi. TECHNICAL CONSIDERATIONS: A flank incision is made and the kidney carefully mobilized. The main renal artery is isolated and the posterior segmental artery identified. The anatrophic plane is defined by occluding the posterior segmental artery and administering methylene blue intravenously. Renal hypothermic ischemia is established, and a nephrotomy is made through the previously identified plane. The calculi are extracted, which may require incising stenotic infundibula to facilitate removal. Intraoperative radiography is performed to confirm complete stone removal. The collecting system is reconstructed with absorbable suture, and special techniques are used to correct the infundibular stenosis. The renal capsule is closed with absorbable suture after which the renal circulation is re-established. CONCLUSIONS: This procedure is currently used to treat patients with large-volume staghorn calculi and complex collecting system anatomy.

Contribution of dietary oxalate to urinary oxalate excretion.

BACKGROUND: The amount of oxalate excreted in urine has a significant impact on calcium oxalate supersaturation and stone formation. Dietary oxalate is believed to make only a minor (10 to 20%) contribution to the amount of oxalate excreted in urine, but the validity of the experimental observations that support this conclusion can be questioned. An understanding of the actual contribution of dietary oxalate to urinary oxalate excretion is important, as it is potentially modifiable. METHODS: We varied the amount of dietary oxalate consumed by a group of adult individuals using formula diets and controlled, solid-food diets with a known oxalate content, determined by a recently developed analytical procedure. Controlled solid-food diets were consumed containing 10, 50, and 250 mg of oxalate/2500 kcal, as well as formula diets containing 0 and 180 mg oxalate/2500 kcal. Changes in the content of oxalate and other ions were assessed in 24-hour urine collections. RESULTS: Urinary oxalate excretion increased as dietary oxalate intake increased. With oxalate-containing diets, the mean contribution of dietary oxalate to urinary oxalate excretion ranged from 24.4 +/- 15.5% on the 10 mg/2500 kcal/day diet to 41.5 +/- 9.1% on the 250 mg/2500 kcal/day diet, much higher than previously estimated. When the calcium content of a diet containing 250 mg of oxalate was reduced from 1002 mg to 391 mg, urinary oxalate excretion increased by a mean of 28.2 +/- 4.8%, and the mean dietary contribution increased to 52.6 +/- 8.6%. CONCLUSIONS: These results suggest that dietary oxalate makes a much greater contribution to urinary oxalate excretion than previously recognized, that dietary calcium influences the bioavailability of ingested oxalate, and that the absorption of dietary oxalate may be an important factor in calcium oxalate stone formation.

(L)-2-oxothiazolidine-4-carboxylate in the treatment of primary hyperoxaluria type 1.

OBJECTIVE: To evaluate the short-term efficacy of (l)-2-oxothiaolidine-4-carboxylate (OTZ, which reduces urinary oxalate excretion in normal subjects) in the treatment of primary hyperoxaluria type 1 (PH1) in a phase II study. PATIENTS AND METHODS: Two patients with PH1 received intravenous infusions of OTZ (100 mg/kg body weight for 2 h) given every 8 h for four doses. One patient also received a placebo treatment. Urine samples (24-h collections) were obtained before and during OTZ treatment and assayed for oxalate, citrate, creatinine, sulphate and pH. Daily blood samples were assayed for plasma oxalate and serum creatinine. RESULTS: Urinary oxalate excretion was unaffected by OTZ treatment. Plasma oxalate declined in both individuals with OTZ treatment, but the effect was small. Plasma cysteine was normal in one patient, rising from a mean (sd) of 36 (3.7) micromol/L before treatment to a peak of 141 micromol/L after OTZ, but was not detected in samples from the other patient. The ratio of oxalate to creatinine clearances was high in both patients, with mean values of 3.1 and 3.8. CONCLUSIONS: Treatment with OTZ did not lead to clinically significant changes in urinary oxalate excretion. The high clearance of oxalate in these patients suggests a substantial renal secretion of oxalate.

Ureteroscopic management of patients with upper tract transitional cell carcinoma.

Endoscopic therapy for the management of upper urinary tract TCC is mainly indicated for patients with an anatomically or functionally solitary kidney, renal insufficiency, bilateral tumors, or severe medical comorbidity. It may be a reasonable alternative to distal ureterectomy with bladder-cuff resection in individuals with low-grade superficial distal ureteral tumors. Although use of this approach has been suggested for treating standard patients with low-grade, low-stage collecting system tumors, this recommendation should not be embraced until more supporting evidence is generated. The efficacy of adjuvant therapy for the prevention of recurrent or progressive disease needs to be defined. If current adjuvant strategies prove ineffective, alternative ones will need to be developed. It is anticipated that advancements in endoscopic technology will facilitate the performance of this type of surgery in the future.

Are coagulation studies necessary before percutaneous nephrostomy?

PURPOSE: Performance of coagulation studies for patients undergoing percutaneous nephrostomy (PCN) has been advocated by some investigators. We performed a retrospective study to assess this practice. MATERIALS AND METHODS: The medical records of 180 patients subjected to PCN for various reasons between October 1991 and July 1998 were reviewed. This represents a subset of patients in whom PCN was performed by an experienced interventional radiologist at our institution. Patients were excluded if they had a history of active liver disease, hematologic or bleeding disorder, current use of heparin or warfarin, or platelet count <100,000. The remaining 160 patients were separated into two groups. Group 1 consisted of 153 patients with a normal prothrombin time (PT) and partial thromboplastin time (PTT). Group 2 comprised 7 patients with an abnormal PT or PTT. Demographic and laboratory data including PT, PTT, complete blood, and platelet counts were analyzed to determine if a hemorrhagic complication could be predicted by an abnormal PT or PTT. RESULTS: In group 1 the mean PT was 12.2 seconds and the mean PTT was 25.0 seconds; in group 2 the mean PT was 13.9 seconds and the mean PTT was 30.3 seconds. The hemorrhagic complication rates were not statistically different between the two patient cohorts (p = .203). Demographic and standard laboratory data were not predictive of abnormal coagulation parameters. CONCLUSIONS: Screening coagulation studies are unnecessary in the standard patient subjected to PCN.

Is there a learning curve in diagnosing urolithiasis with noncontrast helical computed tomography?

OBJECTIVE: To report one department's experience with helical computed tomographic (HCT) evaluation of patients with suspected renal colic to diagnose ureteral calculi; to determine whether there is a learning curve in performing HCT in this context; and to determine whether HCT for the evaluation of renal colic exposes patients to more radiation than the standard intravenous pyelography (IVP) combined with nephrotomography. METHODS: All patients presenting to the emergency department with flank or abdominal pain were evaluated with nonreformatted noncontrast HCT. To determine changes in diagnostic accuracy, patients were divided into 2 groups: those evaluated between September 1996 and January 1997 (group 1, 67 patients), and those seen from February to June 1997 (group 2, 53 patients). A radiation exposure study was performed using phantoms, and radiation exposure for HCT, IVP and nephrotomography was measured. RESULTS: Review of HCT scans to diagnose ureteral calculi had a sensitivity of 91.7%, specificity of 82.6%, and accuracy of 87.2% in group 1, and a sensitivity of 95.5%, specificity of 86.7%, and accuracy of 91.9% in group 2. Patients undergoing IVP with nephrotomography were exposed to an effective dose equivalent of 343 mrem (dSv) (for men) and 664 mrem (for women). The effective dose equivalent for an HCT scan was 180 mrem. CONCLUSION: HCT offers excellent, rapid diagnostic accuracy without the need for intravenous contrast medium and with a lower radiation exposure level than IVP in evaluating patients with acute flank pain. There is a small but real learning curve in evaluating patients with acute flank pain with HCT.

Role of diet in the therapy of urolithiasis.

The data reviewed in this paper indicate that there is compelling direct and indirect evidence that certain dietary modifications can limit the risk for stone formation. Fluid therapy should be a front-line approach for all stone formers, because it is safe, cheap, and effective. Restricting sodium and animal-protein consumption produces changes in the urinary environment that should benefit the majority of stone formers, including a decrease in calcium and increase in citrate excretion. Minimizing the intake of processed goods limits sodium gluttony. These dietary modifications also reduce cardiovascular risks. Indiscriminant calcium restriction should be avoided, because it could accelerate stone formation and violate skeletal integrity. Oxalate restriction should be considered for calcium oxalate stone formers, especially those with hyperoxaluria. Specific recommendations for modifying the consumption of other nutrients cannot be made at this time because of the limited available information about the resultant effects. The aforementioned goals can be achieved within the context of a nutritionally balanced diet providing adequate sources of fruits and vegetables. There is a definite need for better designed studies of the nutritional effects on stone disease. This would promote a better understanding of the interplay between the genetic and environmental components of this disorder.

Guaifenesin- and ephedrine-induced stones.

PURPOSE: We report a new type of drug-induced stone that is caused by overconsumption of preparations containing guaifenesin and ephedrine. MATERIALS AND METHODS: Clinical and stone analysis data from the Molecular Structure Laboratory at the Veterans Affairs Medical Center in Milwaukee, Wisconsin, were reviewed. Stone analysis was performed by Fourier transform infrared spectroscopy, high-resolution X-ray crystallographic powder diffraction, or both. The urine and stone material from one of the subjects were analyzed with high-performance liquid chromatography. RESULTS: Stone analysis from seven patients demonstrated metabolites of guaifenesin. High-performance liquid chromatography revealed that the stone and urine from one subject had a high content of guaifenesin metabolites and a small amount of ephedrine. Demographic data were available on five patients. Three had a history of alcohol or drug dependency. All were consuming over-the-counter preparations containing ephedrine and guaifenesin. Four admitted to taking excessive quantities of these agents, mainly as a stimulant. Hypocitraturia was identified in two individuals subjected to urinary metabolic testing. These stones are radiolucent on standard X-ray imaging but can be demonstrated on unenhanced CT. Shockwave lithotripsy was performed in two patients, and the calculi fragmented easily. CONCLUSIONS: Individuals consuming large quantities of preparations containing ephedrine and guaifenesin may be at risk to develop stones derived mainly from metabolites of guaifenesin and small quantities of ephedrine. These patients may be prone to drug or alcohol dependency.

Glycolate metabolism by Hep G2 cells.

The pathways of oxalate synthesis in humans are not well defined despite their clinical significance in primary hyperoxaluria and idiopathic calcium oxalate nephrolithiasis. Furthermore, the functional roles, if any, of this synthesis have not been elucidated. This study examines pathways of oxalate synthesis from glycolate in Hep G2 cells, a human hepatoma cell line. Incubation of these cells with glycolate has revealed that a pathway may function to synthesize oxalate from glycolate that does not depend on the oxidation of glycolate to glyoxylate by glycolate oxidase. Labeling cells with 14C-glycolate and chromatographic analyses indicated that detectable amounts of 14C-glyoxylate were not formed. A radioactive peak that coeluted with oxalate on ion exclusion chromatography was the only peak yet identified. A detailed examination of glycolate metabolism in these cells should help clarify the terminal steps associated with oxalate synthesis and aid in our understanding of two-carbon metabolism.

Recurrent suture urolithiasis 29 years after open pyelolithotomy.

A case of a foreign body-induced renal stone in which the patient was treated successfully with a ureterorenoscopic approach is presented.

Diagnostic and therapeutic laparoscopy for the adult cryptorchid testicle.

Laparoscopy can be utilized in the management of male patients with impalpable gonads. However, there have been few reports of its application in the management of adult men with cryptorchidism. Fourteen adult men with 15 undescended testicles were referred to our urology department over 6 years. Eight testicles from seven men could not be localized clinically or radiographically to the inguinal canal. Laparoscopy was utilized to assess for the presence and location of the gonad and to perform orchiectomy when testicular tissue was encountered. The average age of the seven men undergoing laparoscopy was 40 years. Three testicles were found proximal to the internal ring and were removed using laparoscopic techniques. The ipsilateral testicular vessels and vas deferens were visualized entering the internal ring in three cases and dense ipsilateral adhesions from previous inguinal surgery prevented adequate visualization of the cord structures in one individual, leading to four inguinal explorations in the same setting. Two inguinal orchiectomies were performed and two vanishing testicles were identified. Gonadal vessels were absent in the remaining patient as demonstrated by extensive laparoscopic dissection. The average total operative time was 105 minutes, which included additional procedures in four patients. No patient experienced an intraoperative or postoperative complication. Six of seven patients were discharged on the day of surgery. An intratesticular germ cell neoplasm was found in one of seven specimens, which stresses the importance of diagnosing and managing this uncommon problem in the adult man.

Iatrogenic superior gluteal mononeuropathy.

Injuries to the superior gluteal nerve (SGN) have been reported as a result of trauma, pyriformis muscle entrapment, injections, and lumbar lordosis and inadequate back stabilization. We report 3 patients who developed isolated SGN injuries, 1 after a partial nephrectomy and 2 following revision of a total hip arthroplasty. SGN should be suspected in anyone developing an abnormal gait after hip or pelvic surgery or after prolonged lateral decubitus positioning.

Glyoxylate synthesis, and its modulation and influence on oxalate synthesis.

PURPOSE: We define the major pathways of hepatic oxalate synthesis in humans, examine the association with other metabolic pathways and identify ways that oxalate synthesis may be modified. In addition, we suggest what is required for further progress in this area. MATERIALS AND METHODS: We consolidated relevant data primarily from recently published literature, considered new pharmacological approaches to decrease oxalate synthesis, and formulated an overview of the regulation and modification of oxalate synthesis pathways. RESULTS: Experiments with animals, including humans, animal cells and in vitro preparations of cellular components, support the existence of a major metabolic pathway linking the amino acids serine, glycine and alanine. Oxalate synthesis is a minor, secondary reaction of a cascade of reactions termed the glyoxylate pathway, which has a prominent role in gluconeogenesis and ureagenesis. The enzymatic steps and effectors which regulate glyoxylate and oxalate synthesis are not well characterized. Pharmacological approaches can reduce oxalate synthesis by diminishing the glyoxylate pool and possibly modifying enzymatic reactions leading to glyoxylate synthesis. CONCLUSIONS: The individual steps associated with glyoxylate and oxalate synthesis can be identified. The glyoxylate pathway has a significant functional role in intermediary liver metabolism but the way it is regulated is uncertain. Oxalate synthesis can be modified by drugs, indicating that primary and idiopathic hyperoxaluria may respond to pharmacological intervention.

Genetic and dietary influences on urinary oxalate excretion.

Several genes contribute to the development of calcium oxalate nephrolithiasis as it is a polygenic disease. To explore the influence of genetic factors on oxalate excretion we have examined the distribution of oxalate excretions in 101 normal individuals who consumed self-selected diets. The distribution was apparently trimodal, consistent with the existence of three classes of oxalate excretors reflecting two allelic genes determining high and low oxalate excretion occurring with frequencies of 0.32 and 0.68 respectively. The pattern of inheritance in eight families was compatible with the expression of a pair of codominant alleles. A comparison of the distribution of excretory classes among the 101 normal individuals with that of 101 calcium oxalate stone formers suggests that high oxalate excretion may be associated with a 4-fold increased risk of stone disease and intermediate excretion with a 1.6-fold increase. Control of dietary factors influencing oxalate excretion apparently improved the discrimination between excretory classes in 17 individuals but the intra-individual variability in oxalate excretion was not reduced in four of nine individuals in whom this parameter was evaluated. More stringent dietary control than that applied in this study may be required before more extensive genotyping of individuals is attempted.