Progressive increase of lithotripter output produces better in-vivo stone comminution.

BACKGROUND AND PURPOSE: Shockwave lithotripsy (SWL) has become a first-line intervention for treatment of nephrolithiasis. However, few studies have examined the effects of modifications in the method of shockwave energy administration on comminution efficiency. We propose that a gradual increase in output voltage will produce superior stone fragmentation in comparison with a constant or a decreasing output voltage by optimizing the stress wave and cavitation erosion forces on renal calculi. MATERIALS AND METHODS: BegoStone phantoms were implanted in the renal pelvis of 11 pigs that underwent SWL at a pulse repetition rate of 1 Hz. Animals in the increasing strategy group (N = 4) were subjected to 18, 20, and 22 kV for 600, 600, and 800 shocks, respectively. The second group (N = 4) received a decreasing strategy of 22, 20, and 18 kV for 800, 600, and 600 shocks, respectively. The third group (N = 3) received all 2000 shocks at 20 kV, mimicking the clinical protocol. RESULTS: A progressively decreasing strategy and constant output voltage produced a mean comminution efficiency, or percentage of stone fragments <2 mm, of 89.0% +/- 3.3% and 87.6% +/- 1.7%, respectively. The mean comminution efficiency was improved to 96.5% +/- 1.4% by using the increasing strategy (P = 0.01). CONCLUSIONS: A progressive increase in lithotripter output voltage during SWL can produce greater stone fragmentation than protocols employing constant or decreasing output voltage.

Controlled survival study of the effects of Tisseel or a combination of FloSeal and Tisseel on major vascular injury and major collecting-system injury during partial nephrectomy in a porcine model.

PURPOSE: We report the results of a controlled survival study in a porcine model investigating Tisseel or a combination of FloSeal and Tisseel in dealing with vascular and collecting-system injury during partial nephrectomy. MATERIALS AND METHODS: We performed an open right lower-pole partial nephrectomy on 15 large female pigs. The defect was repaired using standard open techniques (N = 5; controls), Tisseel only (N = 6; group I), or FloSeal followed by Tisseel (N = 4; group II). A Jackson-Pratt drain was placed. Nephrectomy and retrograde pyelography were performed at 1 week. RESULTS: Operative times were shorter in both study groups, achieving statistical significance in group I (P = 0.008). Warm-ischemia times were significantly improved in both study groups (P = 0.029 and P = 0.00005 in groups I and II, respectively). Time to hemostasis was significantly shorter in group II only (P = 0.002) but approached significance in Group I as well (P = 0.09). Estimated blood loss was not significantly different from the controls in either group. When Tisseel was placed alone after hilar control, hematoma formation under the Tisseel was noted on release of the hilar clamp. After 1 week, there was one urinoma and three urine leaks in the control group. In group I, there was one urinoma and four urine leaks, and there was only one urine leak and no urinomas in group II. There were no hematomas in any of the groups. CONCLUSIONS: Tisseel alone is not adequate for either hemostasis or management of major collecting-system injury. FloSeal capped with Tisseel appears sufficient to control major vascular and collecting-system injuries without adjunctive surgical measures. A proposed technique for laparoscopic partial nephrectomy without reconstructive techniques is presented that warrants clinical study.

Induction of tolerance to heart transplants by simultaneous cotransplantation of donor kidneys may depend on a radiation-sensitive renal-cell population.

BACKGROUND: To determine the mechanism by which cotransplantation of a donor kidney and heart allograft induces tolerance to both organs in miniature swine, we examined the renal elements responsible for tolerance induction. METHODS: Recipients received 12 days of cyclosporine, and transplants were performed across a major histocompatibility complex (MHC) class I mismatch. Group 1 animals received heart transplants (n=5); group 2 animals received heart and kidney allografts with no other manipulation (n=4); group 3 animals received heart transplants and donor-specific renal parenchymal cells (n=4); group 4 animals received heart and kidney allografts from lethally irradiated donors (n=7); group 5 animals received irradiated hearts and nonirradiated kidneys (n=2); group 6 animals received nonirradiated hearts and peripheral blood leukocytes from swine MHC matched to recipients and becoming tolerant to donor antigen (n=2); group 7 animals received nonirradiated hearts and donor-specific peripheral blood monocyte cells (PBMC) (n=2). RESULTS: Animals in group 1 developed vasculopathy and fulminant rejection by day 55. Animals in group 2 never developed vascular lesions. Parenchymal kidney cell infusion (group 3) did not prolong cardiac survival. Animals in group 4 developed arteriopathy by postoperative day (POD) 28. Group 5 recipients accepted allografts without vascular lesions. Adoptive transfer of leukocytes from tolerant swine (group 6) prolonged cardiac graft survival as much as 123 days, whereas donor PBMC infusion (group 7) did not affect cardiac survival or development of arteriopathy. CONCLUSIONS: Radiosensitive elements in kidney allograft may be responsible for tolerance induction and prevention of chronic vascular lesions in recipients of simultaneous heart and kidney allografts.

Metabolic abnormalities associated with calyceal diverticular stones.

OBJECTIVE: To review the metabolic analyses of patients with calyceal diverticular stones who had surgical treatment of their calculi and to examine the effect of selective medical therapy on stone recurrence, as recent reports suggest that metabolic abnormalities contribute to stone development. PATIENTS AND METHODS: In all, 37 patients who had endoscopic treatment of symptomatic calyceal diverticular calculi were retrospectively reviewed. Stone composition and initial 24-h urine collections (24-h urinary volumes, pH, calcium, sodium, uric acid, oxalate, citrate, and the number of abnormalities/patient per collection) were compared with 20 randomly selected stone-forming patients (controls) with no known anatomical abnormalities. Stone formation rates before and after the start of medical therapy were calculated in the patients available for follow-up. RESULTS: Twelve of the diverticulum patients (five men and seven women) had complete 24-h urine collections, all of whom had at least one metabolic abnormality. Seven patients had hypercalciuria, four had hyperuricosuria and three had mild hyperoxaluria. The most common abnormality was a low urine volume; 11 of the 12 patients had urine volumes of <2000 mL/day (range 350-1950). Ten patients had hypocitraturia in at least one of the two 24-h urine samples; seven had low urinary citrate levels (172-553 mg/day) on both samples. The findings were similar in the control group. The diverticulum patients had 3.1 abnormalities/patient, and the controls had 2.9 abnormalities/patient (P > 0.05). No patients had gouty diathesis and none developed cystine stones. Stone analyses were similar in the two groups; both developed either calcium oxalate or mixed calcium oxalate/calcium phosphate stones. Six patients were followed for a mean of 23.1 months while on selective medical therapy; only one passed any additional stones, thought to be existing calculi, for a remission rate of five of six (83%). CONCLUSIONS: All patients with symptomatic calyceal diverticular stones who had comprehensive metabolic evaluation had metabolic abnormalities. There were similar abnormalities in the control random stone-formers. The abnormalities were corrected with selective medical therapy, as shown by the high remission rate. We recommend that, for patients with symptomatic calyceal diverticular calculi, a metabolic evaluation should be considered to determine stone forming risk factors.

Ethnic background has minimal impact on the etiology of nephrolithiasis.

PURPOSE: Nephrolithiasis disproportionately affects white patients. However, recent studies propose an increase in the incidence of stone disease in nonwhite populations. We compared the metabolic risk factors of ethnically disparate stone formers from the same geographic region. MATERIALS AND METHODS: A retrospective review of 1,141 patients identified 98 (9%) nonwhite stone formers. Of these individuals 60 underwent a comprehensive metabolic evaluation, comprising 44 black, 8 Asian and 8 Hispanic patients. A similar sex and age matched group of 66 white stone forming patients were also identified for comparative analysis. Stone analyses were recorded when available. Urinary metabolic abnormalities were defined as low urine volume-urine volume less than 2,000 cc, gouty diathesis-pH 5.5 or less (normal level 5.5 to 6.5), hypercalciuria-calcium greater than 200 mg, hyperoxaluria-oxalate greater than 45 mg, hyperuricosuria-uric acid greater than 600 mg, hypocitraturia-citrate less than 600 mg and purine gluttony-sulfate greater than 20 mg. RESULTS: The incidence of metabolic abnormalities was surprisingly similar between the white and nonwhite stone formers. Whites have a higher prevalence of hypercalciuria compared with nonwhites (67% vs 25%, respectively, p <0.01). This comparison persisted when the white group was compared with individual ethnic groups (25% in each group). Whites also displayed a higher mean urinary calcium level (233 mg) than their nonwhite counterparts overall (146 mg), specifically with respect to blacks (146 mg, p <0.01). Asians had higher urine volumes with respect to whites and blacks (p <0.01) and, therefore, a decreased prevalence of low urine volumes (37.5% vs 74.2% and 79.5%, respectively). Hypocitraturia, hyperuricosuria, hyperoxaluria, gouty diathesis and high sulfate levels were equally represented among all ethnic groups. CONCLUSIONS: Although there appears to be a predominance of stone disease among whites, all racial groups demonstrated a remarkable similarity in the incidence of underlying metabolic abnormalities. These results suggest that dietary and environmental factors may be as important as ethnicity in the etiology of stone disease.

Effect of ureteral access sheath on stone-free rates in patients undergoing ureteroscopic management of renal calculi.

OBJECTIVES: To evaluate the effect of ureteral access sheaths (UASs) on stone-free rates (SFRs) during ureteroscopic treatment of renal calculi. Several advantages of UASs during flexible ureteroscopy have been documented. However, no study has evaluated their impact on SFRs. METHODS: We retrospectively reviewed all ureteroscopic cases for the management of renal stones performed at our Stone Center. Data were stratified according to the use or lack of use of the UAS. The groups were stratified by stone location within the kidney. Stone-free status was determined at 2 months postoperatively by either intravenous urography with tomograms or noncontrast renal computed tomography in patients with contrast allergies. RESULTS: A total of 256 ureteroscopic procedures for the removal of renal calculi were performed between 1997 and 2003 (173 with UAS and 83 without). The groups were similar in age, sex, and stone burden. Stents were placed in nearly 80% of patients. The lower renal pole represented the most common presenting location. Stone displacement with a ureteroscopic basket for efficient fragmentation was necessary in 34%. The overall SFR in the UAS group and non-UAS group was 79% and 67%, respectively (P = 0.042). The SFRs were improved for calculi in all portions of the kidney. CONCLUSIONS: In addition to facilitating ureteroscopic access, reducing costs, and lowering intrarenal pressures, the results of the current study suggest that UASs improve SFRs during the management of renal calculi. It is now our current practice to use the UAS routinely during ureteroscopic treatment of renal and upper ureteral calculi.

Effects of mycophenolate mofetil on cardiac allograft survival and cardiac allograft vasculopathy in miniature swine.

BACKGROUND: Chronic rejection, as manifested by cardiac allograft vasculopathy, remains the leading cause of late graft failure in heart transplant recipients. Despite recent clinical trials, the efficacy of mycophenolate mofetil in preventing human cardiac allograft vasculopathy remains controversial. We investigated whether mycophenolate mofetil would prevent cardiac allograft vasculopathy and prolong cardiac allograft survival in our well-established miniature swine model of heart transplantation. METHODS: Hearts disparate at the major histocompatibility complex class I locus were heterotopically transplanted into miniature swine recipients treated with a 12-day course of mycophenolate mofetil (n = 3) or cyclosporine A (n = 3). Allograft survival, acute rejection, and chronic rejection were monitored in the two groups. RESULTS: Hearts transplanted with 12 days of cyclosporine were rejected between 46 and 61 days, whereas two of the three hearts transplanted with mycophenolate mofetil remained beating beyond 120 days (p = 0.02). At necropsy, there was a 4.9% mean prevalence of cardiac allograft vasculopathy in the mycophenolate mofetil group as compared with 16.6% in the cyclosporine group (p = 0.03). Cardiac allograft rejection and vasculopathy in the cyclosporine-treated group was associated with prominent myocardial interferon-gamma gene expression, a finding absent in two thirds of the mycophenolate mofetil-treated swine. Moreover, the mycophenolate mofetil-treated swine failed to develop IgM or IgG alloantibodies. CONCLUSIONS: A short course of mycophenolate mofetil resulted in a longer allograft survival than a similar course of cyclosporine. Moreover, mycophenolate mofetil reduced the prevalence of cardiac allograft vasculopathy as compared with cyclosporine-treated controls. The salutary effect of mycophenolate mofetil may be related to its ability to decrease interferon-gamma expression in the myocardium and prevent the generation of alloantibodies.

Metabolic risk factors and the impact of medical therapy on the management of nephrolithiasis in obese patients.

PURPOSE: Previous studies have demonstrated that obesity can increase the risk of stone formation as well as recurrence rates of stone disease. Yet appropriate medical management can significantly decrease the risk of recurrent stone disease. Therefore, we analyzed our obese patient population, assessing the risk factors for stone formation and the impact of selective medical therapy on recurrent stone formation. MATERIALS AND METHODS: A retrospective chart review was performed to identify obese patients with stone disease from our Stone Center. Metabolic risk factors for stones were identified as well as patient response to medical therapy. A similar analysis was performed on a group of age and sex matched nonobese stone formers. RESULTS: Of 1,021 patients 140 (14%) were identified as obese (body mass index greater than 30). Of these patients complete metabolic evaluations were available in 83 with an average followup of 2.3 years. The most common presenting metabolic abnormalities among these obese patients included gouty diathesis (54%), hypocitraturia (54%) and hyperuricosuria (43%), which presented at levels that were significantly higher than those of the nonobese stone formers (p <0.05). Stone analysis was available in 32 obese patients with 63% having uric acid calculi. After initiating treatment with selective medical therapy obese and nonobese patients demonstrated normalization of metabolic abnormalities, resulting in an average decrease in new stone formation from 1.75 to 0.15 new stones formed per patient per year in both groups. CONCLUSIONS: Obesity, as a result of dietary indiscretion, probable purine gluttony and possible type II diabetes, appears to have a significant role in recurrent stone formation. Appropriate metabolic evaluation, institution of medical therapy and dietary recommendations to decrease animal protein intake can significantly improve the risk of recurrent stone formation in these often difficult to treat patients.