Experience with more than 1,000 holmium laser prostate enucleations for benign prostatic hyperplasia.

PURPOSE: Holmium laser prostate enucleation is a contemporary treatment for benign prostatic hyperplasia. We report our experience with more than 1,000 procedures. MATERIALS AND METHODS: From June 1998 to March 2009 we performed 1,065 holmium laser prostate enucleations. After receiving institutional review board approval we retrospectively reviewed the database. Reported short-term, intermediate term and long-term results are 0 to 6, 6 to 12 and greater than 12 months, respectively. RESULTS: Bladder stones were present in 50 patients (4.7%) and 87 of the 717 (12.1%) with laboratory studies available had renal insufficiency. Preoperative urinary retention was present in 411 cases (38.7%). Significant preoperative stress and urge incontinence was noted in 8 and 16 patients, respectively. Mean transrectal ultrasound prostate volume was 99.3 gm (range 9 to 391). Mean preoperative American Urological Association symptom score was 20.3 (range 1 to 35) and maximum urinary flow was 8.4 cc per second (range 1.1 to 39.3). Intraoperative or postoperative complications occurred in 24 cases (2.3%). Mean followup was 287 days (range 6 to 3,571). At short-term, intermediate term and long-term followup the mean symptom score was 8.7, 5.9 and 5.3, and maximum urinary flow was 17.9, 19.5 and 22.7 cc per second, respectively. At the most recent followup 3 patients (0.3%) were in urinary retention. One patient with maximum urinary flow 20 cc per second required a second procedure for bleeding prostatic regrowth. Urethral stricture was noted in 9 (0.9%), 11 (1.3%), 4 (1.3%) and 0 patients, and bladder neck contracture was found in 0, 7 (0.8%), 4 (1.3%) and 5 (6.0%) at short-term, intermediate term, long-term and greater than 5-year followup, respectively. At the most recent followup significant stress and urge incontinence was noted in 9 and 6 patients, respectively. CONCLUSIONS: Holmium laser prostate enucleation is safe and effective for benign prostatic hyperplasia. The complication rate is low, and incontinence and the need for ancillary procedures are rare for holmium laser prostate enucleation with durable long-term results.

The utility of noncontrast computed tomography in the prompt diagnosis of postoperative complications after percutaneous nephrolithotomy.

INTRODUCTION: Noncontrast computed tomography (CT) is commonly utilized after percutaneous nephrolithotomy (PNL) to assess stone-free (SF) status. In addition to assessing SF status, CT is useful in the recognition of complications after PNL. We characterized complications demonstrated by postoperative CT scan and compared hospital re-admission rates based on whether or not CT was performed. METHODS: We retrospectively reviewed records of 1032 consecutive patients from April 1999 to June 2010. Patients were divided into two cohorts based on whether they had a CT within 24 hours of PNL. Demographic data, CT findings, and need for re-admission for complication management were assessed. RESULTS: Nine hundred fifty-seven patients (92.7%) underwent post-PNL CT. CT-diagnosed complications were perinephric hematoma in 41 (4.3%; 2 requiring embolization and 9 necessitating transfusion), pleural effusion in 25 (2.6%; 10 requiring intervention), colon perforation in 2 (0.2%), and splenic injury in 2 (0.2%). Of patients with postoperative complications, 33% required intervention. Among patients with a CT, 6 (0.6%) were readmitted despite negative postoperative CT (four perinephric hematomas, one calyceal-pleural fistula, and one pseudoaneurysm). The sensitivity of CT for diagnosing complications was 92.7%. Seventy-five patients (7.3%) did not undergo CT post-PNL. Of these, four (5.33%) were readmitted: three for perinephric hematomas and one for ureteral clot obstruction. Patients undergoing post-PNL CT were less likely to be readmitted because of missed complications (p=0.02). CONCLUSIONS: Serious post-PNL complications are uncommon, but their prompt diagnosis and treatment is imperative. In addition to identifying residual stones, CT is useful in diagnosing postoperative complications. Postoperative CT could potentially be considered for all patients undergoing PNL, particularly in complex cases such as patients with anatomical abnormalities (renal anatomic abnormality or retrorenal colon), patients requiring upper pole access (risk of thoracic, hepatic, and splenic complications), and patients requiring multisite access (higher risk of perinephric hematoma or need for transfusion).

Changing composition of renal calculi in patients with musculoskeletal anomalies.

BACKGROUND AND PURPOSE: Calculi from patients with musculoskeletal (MS) anomalies who are largely immobile and prone to urinary infections have been traditionally composed primarily of struvite and carbonate apatite. Because of substantial improvements in the care of these patients in recent decades, stone etiology may have shifted from infectious to metabolic. We assessed the composition of renal calculi and metabolic characteristics in a contemporary cohort of patients with MS anomalies who underwent percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: Retrospective analysis of patients who underwent PCNL between April 1999 and June 2009 and had follow-up 24-hour urine studies was performed. Patients with MS anomalies included spinal cord injury, myelomeningocele, muscular dystrophy, multiple sclerosis, cerebral palsy, or other clinical syndromes causing kyphoscoliosis and contractures. RESULTS: Our cohort included 33 patients with MS anomalies and 334 consecutive patients as a control group who underwent PCNL and had metabolic workup. Stones were infectious in etiology in 18.4% and 6.2% in MS and control groups, respectively. Thus, most patients harbored stones of metabolic origin. Metabolic stones in the MS group were composed of 52.7% hydroxyapatite, 10.5% calcium oxalate, 7.9% brushite, 2.6% uric acid, 0% cystine, and 7.9% other. Metabolic stones in the control group were 50.5% calcium oxalate, 16.4% hydroxyapatite, 11.5% brushite, 10.8% uric acid, 4.3% cystine, and 0.3% other. Mean 24-hour urine values for patients with metabolic stones in MS/control groups were volume 2.18/1.87 L/d, pH 6.78/6.05, calcium to creatinine ratio 220/151 mg/g, and oxalate 44.8/39.5 mg/d. CONCLUSIONS: Although patients with MS anomalies are traditionally thought to harbor infection-related calculi, most will be found to have calculi of metabolic etiology. The incidence of calcium phosphate stones is high in this group of patients, perhaps reflecting their high urinary pH.

Randomized controlled, multicentre clinical trial comparing a dual-probe ultrasonic lithotrite with a single-probe lithotrite for percutaneous nephrolithotomy.

OBJECTIVES: • To compare the Cyberwand (Gyrus/ACMI, Southborough, MA, USA), a dual-probe ultrasonic lithotrite, with a single-probe ultrasonic lithotrite. • The Cyberwand incorporates coaxial high- and low-frequency ultrasonic probes that work synergistically. PATIENTS AND METHODS: • An institutional review board-approved, multicentre, randomized controlled trial to compare the Cyberwand to the Olympus LUS-II (Olympus America, Inc., Melville, NY, USA) single-probe lithotrite was performed. • Patients undergoing a percutaneous nephrolithotomy (PCNL) with a target stone > 2 cm in diameter were eligible for the study. • The primary outcome was the time to removal of the targeted stone. RESULTS: • A total of 57 PCNLs were performed after randomization: 25 Cyberwand and 32 LUS-II. • There was no difference (P > 0.05) observed between the two devices for target stone surface area (Cyberwand 526.6 cm³ vs LUS-II 540.1 cm³), time to clearance of target stone (Cyberwand 15.8 min vs LUS-II 14.2 min) and target stone clearance rate (Cyberwand 61.9 mm²/min vs LUS-II 75.8 mm²/min). • Of the patients with stone analysis, hard stones (calcium oxalate monohydrate, brushite and cystine) were noted in 14 (56.0%) of the 25 Cyberwand and 18 (62.1%) of the 29 LUS-II patients. • Fifteen of the 25 (60.0%) Cyberwand and 20 of the 32 (62.5%) LUS-II patients were stone-free after the initial PCNL. • Those patients not rendered stone-free went on to receive a secondary PCNL. • Device malfunction occurred in eight of 25(32.0%) Cyberwand and five of 32 (15.6%) LUS II patients. • Complications were similar in both treatment groups. CONCLUSION: • No appreciable difference between the dual-probe Cyberwand and the standard ultrasonic Olympus LUS-II lithotrites can be identified.

Nephrocalcinosis: re-defined in the era of endourology.

Nephrocalcinosis generally refers to the presence of calcium salts within renal tissue, but this term is also used radiologically in diagnostic imaging in disease states that also produce renal stones, so that it is not always clear whether it is tissue calcifications or urinary calculi that give rise to the characteristic appearance of the kidney on x-ray or computed tomography (CT). Recent advances in endoscopic imaging now allow the visual distinction between stones and papillary nephrocalcinosis, and intrarenal endoscopy can also verify the complete removal of urinary stones, so that subsequent radiographic appearance can be confidently attributed to nephrocalcinosis. This report shows exemplary cases of primary hyperparathyroidism, type I distal renal tubular acidosis, medullary sponge kidney, and common calcium oxalate stone formation. In the first three cases--all being conditions commonly associated with nephrocalcinosis--it is shown that the majority of calcifications seen by radiograph may actually be stones. In common calcium oxalate stones formers, it is shown that Randall's plaque can appear as a small calculus on CT scan, even when calyces are known to be completely clear of stones. In the current era with the use of non-contrast CT for the diagnosis of nephrolithiasis, the finding of calcifications in close association with the renal papillae is common. Distinguishing nephrolithiasis from nephrocalcinosis requires direct visual inspection of the papillae and so the diagnosis of nephrocalcinosis is essentially an endoscopic, not radiologic, diagnosis.

Contralateral ureteroscopy performed at percutaneous nephrolithotomy: a unique evaluation of stone-free rates.

PURPOSE: Immediate stone-free rates of ureteroscopy are rarely reported. To establish accurate stone-free rates after ureteroscopy we assessed the safety and success of ureteroscopy for patients undergoing the procedure at contralateral percutaneous nephrolithotomy. MATERIALS AND METHODS: From our prospectively collected, institutional review board approved, percutaneous nephrolithotomy database we identified patients who underwent contralateral ureteroscopy for urolithiasis at percutaneous nephrolithotomy from December 2001 to December 2008. Stone-free status was assessed with noncontrast computerized tomography on postoperative day 1. RESULTS: A total of 65 patients underwent ureteroscopy for urolithiasis at contralateral percutaneous nephrolithotomy. There were 63 patients available for review who had noncontrast computerized tomography on postoperative day 1. Immediate stone-free status was achieved after ureteroscopy in 37 of 63 patients (58.7%). The remaining 26 patients (41.3%) demonstrated a residual stone burden. Of these patients with residual stones after ureteroscopy 65.4% (17 of 26) had residual fragments of 1 to 3 mm and 34.6% (9 of 26) had residual stones larger than 3 mm. Three patients (4.8%) underwent repeat ureteroscopy at secondary percutaneous nephrolithotomy. There was no association of stone composition, patient age, stone location, gender or surgical complications with residual fragments (p>0.05). CONCLUSIONS: Based on noncontrast computerized tomography 58.7% of patients who underwent ureteroscopy were rendered immediately stone-free. When residual passable stone fragments less than 3 mm were included the success rate increased to 85.7%. We found no association between characteristics of patients, stones or procedures and residual fragments.

Profile of the brushite stone former.

PURPOSE: The incidence of brushite stones has increased during the last 3 decades and we report our experience with brushite stone formers. MATERIALS AND METHODS: From 1996 to 2008 we identified 82 patients with brushite urinary calculi. After institutional review board approval a review of our prospectively collected database was performed. RESULTS: There were 54 (65.9%) male and 28 (34.1%) female stone formers. Mean age was 44 years (range 4 to 84). Prior stone events were reported by 69 (84.1%) patients with 54 (78.3%) having received shock wave lithotripsy. Bilateral calculi were present in 28 (34.1%) patients. Mean stone area was 29.2 mm(2) (range 2 to 130). Surgery was performed in 80 patients including 63 (76.8%) percutaneous nephrolithotomy, 8 (9.8%) ureteroscopy, 3 (3.7%) shock wave lithotripsy, and 6 (7.3%) ureteroscopy and percutaneous nephrolithotomy. After primary and secondary procedures 76 (92.7%) patients were rendered stone-free. Metabolic urine studies were available in 45 patients. All patients demonstrated 1 or more abnormalities, with hypercalciuria (greater than 250 mg daily for women and greater than 275 mg daily for men) in 38 (80.9%), urine pH greater than 6.2 in 29 (61.7%), urine volume less than 2 l in 27 (57.4%), hypocitraturia (less than 320 mg daily) in 22 (46.8%), hyperuricosuria (greater than 750 mg daily in women, greater than 800 mg daily in men) in 8 (17%) and hyperoxaluria (greater than 32 mg daily in women and greater than 43 mg daily in men) in 5 (10.6%). Recurrent stone events occurred in 31 (37.8%) patients at a mean of 33 (range 2 to 118) months from treatment. CONCLUSIONS: Brushite stone formers are a treatment challenge. Almost a third will present with bilateral stones and the stone burden is sizeable. Nearly 80% of patients report having prior shock wave lithotripsy and recurrent stone events occurred approximately 3 years after treatment. All patients with brushite stones in this cohort had an underlying metabolic abnormality and specifically brushite stones should be heralded as a marker for hypercalciuria. Based on these data we recommend all brushite stone formers undergo 24-hour urine studies and have close long-term followup.

Brushite stone disease as a consequence of lithotripsy?

The incidence of calcium phosphate (CaP) stone disease has increased over the last three decades; specifically, brushite stones have been diagnosed and treated more frequently than in previous years. Brushite is a unique form of CaP, which in certain patients can form into large symptomatic stones. Treatment of brushite stones can be difficult since the stones are resistant to shock wave and ultrasonic lithotripsy, and often require ballistic fragmentation. Patients suffering from brushite stone disease are less likely to be rendered stone free after surgical intervention and often experience stone recurrence despite maximal medical intervention. Studies have demonstrated an association between brushite stone disease and shock wave lithotripsy (SWL) treatment. Some have theorized that many brushite stone formers started as routine calcium oxalate (CaOx) stone formers who sustained an injury to the nephron (such as SWL). The injury to the nephron leads to failure of urine acidification and eventual brushite stone formation. We explore the association between brushite stone disease and iatrogenic transformation of CaOx stone disease to brushite by reviewing the current literature.

Experience with more than 1,000 holmium laser prostate enucleations for benign prostatic hyperplasia.

PURPOSE: Holmium laser prostate enucleation is a contemporary treatment for benign prostatic hyperplasia. We report our experience with more than 1,000 procedures. MATERIALS AND METHODS: From June 1998 to March 2009 we performed 1,065 holmium laser prostate enucleations. After receiving institutional review board approval we retrospectively reviewed the database. Reported short-term, intermediate term and long-term results are 0 to 6, 6 to 12 and greater than 12 months, respectively. RESULTS: Bladder stones were present in 50 patients (4.7%) and 87 of the 717 (12.1%) with laboratory studies available had renal insufficiency. Preoperative urinary retention was present in 411 cases (38.7%). Significant preoperative stress and urge incontinence was noted in 8 and 16 patients, respectively. Mean transrectal ultrasound prostate volume was 99.3 gm (range 9 to 391). Mean preoperative American Urological Association symptom score was 20.3 (range 1 to 35) and maximum urinary flow was 8.4 cc per second (range 1.1 to 39.3). Intraoperative or postoperative complications occurred in 24 cases (2.3%). Mean followup was 287 days (range 6 to 3,571). At short-term, intermediate term and long-term followup the mean symptom score was 8.7, 5.9 and 5.3, and maximum urinary flow was 17.9, 19.5 and 22.7 cc per second, respectively. At the most recent followup 3 patients (0.3%) were in urinary retention. One patient with maximum urinary flow 20 cc per second required a second procedure for bleeding prostatic regrowth. Urethral stricture was noted in 9 (0.9%), 11 (1.3%), 4 (1.3%) and 0 patients, and bladder neck contracture was found in 0, 7 (0.8%), 4 (1.3%) and 5 (6.0%) at short-term, intermediate term, long-term and greater than 5-year followup, respectively. At the most recent followup significant stress and urge incontinence was noted in 9 and 6 patients, respectively. CONCLUSIONS: Holmium laser prostate enucleation is safe and effective for benign prostatic hyperplasia. The complication rate is low, and incontinence and the need for ancillary procedures are rare for holmium laser prostate enucleation with durable long-term results.

Holmium laser enucleation of the prostate for prostates larger than 175 grams.

BACKGROUND AND PURPOSE: Open simple prostatectomy has been considered the treatment of choice for symptomatic benign prostatic hyperplasia (BPH) of large prostates because traditional endoscopic techniques have not proven either effective or feasible. We present our experience with holmium laser enucleation of the prostate (HoLEP) for glands >175 cc. METHODS: An Institutional Review Board approved prospective database has been maintained since January 1999 for all HoLEP procedures. The database was reviewed retrospectively for patients who underwent HoLEP for BPH with a preoperative transrectal ultrasonography (TRUS) volume of >175 cc. RESULTS: From January 1999 to November 2008, we identified 57 patients with a mean pretreatment TRUS volume of 217.8 cc (range 175-391 cc). Preoperative retention was present in 30 patients. Preoperative mean prostate-specific antigen level was 14.6 ng/mL, mean American Urological Association (AUA) symptom index was 19.0, and mean peak flow (Qmax) was 8.2 mL/sec. Mean hospital stay was 26 hours, and postoperative catheterization was 18.5 hours (range 6-96 hrs). All patients were able to void after catheter removal. Mean enucleated tissue weight was 176.4 g (range 48-532.2 g). At 6-month follow-up, AUA symptom index was 6.5, mean PSA level was 0.78 ng/mL, and Qmax was 18.5. During the follow-up period, no patient needed catheterization or had persistent incontinence. CONCLUSIONS: Even in the large prostate gland, HoLEP provides a satisfactory outcome with low morbidity. HoLEP is the only endoscopic technique that allows for tissue removal comparable to that of open prostatectomy for such patients.

In idiopathic calcium oxalate stone-formers, unattached stones show evidence of having originated as attached stones on Randall's plaque.

OBJECTIVE: To analyse the structure and composition of unattached stones in idiopathic calcium oxalate (CaOx) stone-formers (ICSF) and compare them to attached stones from the same cohort, to investigate whether there is more than one pathogenic mechanism for stone formation in ICSF. PATIENTS AND METHODS: ICSF undergoing percutaneous nephrolithotomy or ureteroscopy for the treatment of nephrolithiasis gave consent to participate in this study. All accessible renal papillae were endoscopically imaged using a digital endoscope. All stones were removed and determined by the operating surgeon to be attached or unattached to the underlying papilla. Micro-computed tomography (micro-CT), which provides three-dimensional analysis of entire stones, was used to compare the structure and composition of attached and unattached stones. RESULTS: Of 115 stones collected from nine patients (12 renal units), only 25 stones were found not to be attached to renal papillae. Of these 25 stones, four were lost and 12 showed definite morphological evidence of having been attached to tissue, probably having been displaced from papillae during access. For the remaining nine stones, micro-CT analysis showed at least one internal region of calcium phosphate within each of these unattached CaOx stones, i.e. the internal structure of the unattached stones is consistent with their having originated attached to Randall's plaque, and then having become detached but retained in the kidney, with new layers of CaOx eventually covering the original attachment site. CONCLUSIONS; Micro-CT analysis supports the hypothesis that in ICSF, both attached and unattached stones occur as a result of a common pathogenic mechanism, i.e. in this type of stone former, CaOx stones, even those not showing morphology that betrays attachment, all originate attached to interstitial plaque on the renal papilla.

Renal functional effects of multiple-tract percutaneous access.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) can involve establishing more than one access into the urinary collecting system. The present study examined whether multiple percutaneous accesses results in a more severe reduction in renal function than that after single-percutaneous access. METHODS: Adult female pigs were anesthetized, and percutaneous access to the left urinary collecting system was achieved by puncturing the lower pole calyx (single-tract access, n = 16) or serially puncturing the lower pole, interpolar region, and upper pole calyces [multiple (three)-tract access, n = 11]. Renal function measurements included glomerular filtration rate and effective renal plasma flow, and were taken immediately before and 1.5 and 4.5 hours after percutaneous access. We also examined glomerular function in a group of adult patients with normal preoperative serum creatinine (Cr) levels (

Holmium laser enucleation of the prostate--outcomes independent of prostate size?

PURPOSE: Generally treatment decisions for benign prostatic hyperplasia are based on prostate size and surgeon experience. Prostates greater than 100 gm often require open surgery. However, less invasive options are available. Randomized, controlled trials have demonstrated that holmium laser enucleation of the prostate is a viable and effective treatment for benign prostatic hyperplasia. We examined the outcome of holmium laser enucleation of the prostate based on prostate size. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients in our institutional review board approved database who underwent holmium laser enucleation of the prostate from January 1999 to October 2006. Patients were divided into 3 cohorts based on preoperative transrectal ultrasound prostate measurements, including less than 75, 75 to 125 and more than 125 gm. Patients with prostate cancer were excluded from study. Demographic, laboratory, operative, preoperative and postoperative data were obtained. RESULTS: As prostate size increased, so did prostate specific antigen, and the urinary retention and enucleation rates. Hospitalization, catheterization, preoperative and postoperative outcomes were similar among the groups. On linear regression the decrease in prostate specific antigen highly correlated with the amount of tissue removed (p <0.0001). The complication rate was similar among the treatment groups. All patients did equally well in terms of postoperative urinary function independent of prostate size. CONCLUSIONS: Holmium laser enucleation of the prostate is a safe and effective minimally invasive treatment for benign prostatic hyperplasia. It improved patient prostate specific antigen, American Urological Association symptom score and maximum urinary flow rate independent of the amount of benign prostatic hyperplasia present. Our results demonstrate the advantage of holmium laser enucleation of the prostate to treat all prostates regardless of size with favorable and equivalent outcomes.

Transsplenic percutaneous nephrolithotomy.

BACKGROUND AND PURPOSE: Percutaneous nephrolithotomy (PNL) is the treatment of choice for patients with large or complex renal calculi. Although injuries to intra-abdominal organs are rare during PNL, splenic injuries have been reported. The management of a splenic injury after PNL is not well defined; therefore, we performed a study to define a management strategy for such an event. PATIENTS AND METHODS: A retrospective, multi-institutional study was performed to identify all cases of splenic injury that occurred during PNL. All procedures were performed as a single-stage operation, with percutaneous access obtained in the operating room by the urologist. A review of patient records and imaging was conducted to identify treatment strategies and outcomes. RESULTS: Three patients were identified as having undergone a transsplenic PNL. All puncture sites were upper pole, supracostal access of the left kidney. All cases of injury were identified after the procedure, with two stable patients' injuries identified on postoperative CT scan, and a third patient presenting with significant bleeding at removal of the nephrostomy tube. The spleen-preserving, conservative management strategy was successful, because no patients needed exploratory surgery. CONCLUSION: Splenic injury is a rare complication sustained most commonly during supracostal, upper-pole access to the left renal unit. When patients are hemodynamically stable, this complication can be conservatively managed, with prolonged nephrostomy drainage and observation in a monitored setting before and after nephrostomy tube removal.

The presence of horseshoe kidney does not affect the outcome of percutaneous nephrolithotomy.

BACKGROUND AND PURPOSE: Large or complex calculi within a horseshoe kidney can present a challenge because many cases are associated with other aberrant anatomy. We performed a study to define the outcome of patients with a horseshoe kidney who were treated with percutaneous nephrolithotomy (PNL). PATIENTS AND METHODS: From August 1999 to February 2007, 44 PNLs were performed in 35 patients for calculi within a horseshoe kidney. Mean age was 55.4 years. Parameters evaluated to assess the outcomes of PNL included presenting symptoms, stone burden, location of access, stone-free rate, need for secondary intervention, length of stay (LOS), complication rate, stone analysis, and metabolic data. RESULTS: The average stone burden per kidney was 2.59 cm (range 1-6.2 cm). Single percutaneous access was used in 97.7%. Location of the access tract was upper pole (82.2%), interpolar (13.4%), and lower pole (4.4 %). Flexible nephroscopy was performed in all patients. The stone-free rate after primary PNL was 84.1%. Second-look nephroscopy was performed in five kidneys. Overall stone-free rate was 93.2%. Average LOS was 1.92 days (range 1-4 d). Overall complication rate was 14.3%. Stone analysis revealed predominantly calcium stones, and metabolic abnormalities were demonstrated in all patients with 24-hour urine studies. CONCLUSIONS: PNL is the treatment of choice for large and/or complex stones. The presence of a horseshoe kidney does not affect the outcome of PNL. Upper pole access is usually preferred, and flexible nephroscopy is essential to maximize stone-free rates. SA and metabolic data support the premise that calculus formation is a metabolic event.

Role of Nitric oxide in the renal and systemic vasodilatory responses to platelet-activating factor in the rat, in vivo.

BACKGROUND/AIM: Chemical mediator(s) involved in the renal vasodilatory and systemic hypotensive effects of platelet-activating factor (PAF) remain unresolved. Because nitric oxide (NO) and PAF have many similar cardiovascular actions, we examined whether endogenous NO contributes to the renal and systemic actions of PAF. METHODS: PAF was administered into the renal arterial or systemic venous circulation of anesthetized rats. The change in renal blood flow (RBF) and/or mean arterial blood pressure (MAP) was recorded in the absence and presence of NO synthase inhibition. RESULTS: Transient exposure of the renal vacsular bed to intrarenal PAF boluses (1-10 ng kg(-1)) resulted in an immediate increase in RBF that was partially inhibited by the intrarenal administration of a NO synthase inhibitor, whereas the ensuing rapid fall in MAP was unaffected by NO synthase blockade. A sustained exposure to intrarenal PAF infusion (2.5 ng min(-1) kg(-1)) in intrarenal NO synthase inhibitor-treated rats (hypertensive with vasoconstricted kidneys) had no effect on RBF and MAP, which was in contrast to the increase in RBF and modest fall in MAP in control intrarenal vasopressin-treated rats (hypertensive with vasoconstricted kidneys). To dissociate the influence of systemic hypotension on the RBF response, rat kidneys were denervated and MAP elevated by a pressor agent whilst maintaining renal arterial blood pressure constant. Subsequent intrarenal PAF infusion at 2.5 and 10 ng min(-1) kg(-1) resulted in a substantial rise in RBF and modest fall in MAP, responses that were abolished by intrarenal NO synthase inhibition at the lower intrarenal PAF infusion or abolished/attenuated at the higher intrarenal PAF infusion. Additional experiments administered drugs intravenously to exclude the possibility that the modified MAP response by NO synthase inhibition was related to the drugs being administered into the kidney. Intravenous PAF boluses (0.1-1 microg kg(-1)) resulted in a transient fall in MAP that was independent of the NO pathway, whereas the systemic hypotension induced by intravenous PAF infusion (10 ng min(-1) kg(-1)) was greatly attenuated by NO synthase inhibition. CONCLUSION: NO has a major role in mediating the renal and peripheral vasodilatory responses induced by a sustained exposure to PAF in the rat, whereas NO's overall contribution was less or absent during transient PAF exposure.

Platelet-activating factor and solute transport processes in the kidney.

We examined the hemodynamic and tubular transport mechanisms by which platelet-activating factor (PAF) regulates salt and water excretion. In anesthetized, renally denervated male Wistar rats, with raised systemic blood pressure and renal arterial blood pressure maintained at normal levels, intrarenal PAF infusion at 2.5 ng. min(-1) x kg(-1) resulted in a small fall in systemic blood pressure (no change in renal arterial blood pressure) and an increase in renal blood flow and urinary water, sodium, and potassium excretion rates. The PAF-induced changes in cardiovascular and renal hemodynamic function were abolished and renal excretory function greatly attenuated by treating rats with a nitric oxide synthase inhibitor. To determine whether a tubular site of action was involved in the natriuretic effect of PAF, cortical proximal tubules were enzymatically dissociated from male Wistar rat kidneys, and oxygen consumption rates (Qo(2)) were used as an integrated index of transcellular sodium transport. PAF at 1 nM maximally inhibited Qo(2) in both untreated and nystatin-stimulated (sodium entry into renal cell is not rate limiting) proximal tubules by approximately 20%. Blockade of PAF receptors or Na(+)-K(+)-ATPase pump activity with BN-52021 or ouabain, respectively, abolished the effect of PAF on nystatin-stimulated proximal tubule Qo(2). Inhibition of nitric oxide synthase or guanylate cyclase systems did not alter PAF-mediated inhibition of nystatin-stimulated proximal tubule Qo(2), whereas phospholipase A(2) or cytochrome-P-450 monooxygenase inhibition resulted in a 40-60% reduction. These findings suggest that stimulation of PAF receptors on the proximal tubule decreases transcellular sodium transport by activating phospholipase A(2) and the cytochrome-P-450 monooxygenase pathways that lead to the inhibition of an ouabain-sensitive component of the basolateral Na(+)-K(+)-ATPase pump. Thus PAF can activate both an arachidonate pathway-mediated suppression of proximal tubule sodium transport and a nitric oxide pathway-mediated dilatory action on renal hemodynamics that likely contributes to the natriuresis and diuresis observed in vivo.