Electrical propagation in the renal pelvis, ureter and bladder.

Under normal conditions, following the passage of urine from the collecting duct, the urine is stored briefly in the renal pelvis before being transported through the ureter to the bladder where the urine is stored for a longer time (hours) before being voided through the urethra. The transport of urine from the renal pelvis to the bladder occurs spontaneously due to contractions of the muscles in the wall of the pelvis and ureter. Spontaneous contractions also occur in the detrusor muscle and are responsible for maintaining the bladder shape during the filling phase. These muscle contractions occur as result of electrical impulses, which are generated and propagated through different parts of the urinary tract. The renal pelvis and the ureter differ from the bladder in relation to the origin, characteristics and propagation of these electrical impulses. In the ureter, the electrical impulses originate mainly at the proximal region of the renal pelvis and are transmitted antegradely down the length of the ureter. The electrical impulses in the bladder, on the other hand, originate at any location in the bladder wall and can be transmitted in different directions with the axial direction being the prominent one. In this manuscript, an overview of the current state of research on the origin and propagation characteristics of these electrical impulses in the normal and pathological conditions is provided.

Bosentan normalizes the GFR response to renal nerve stimulation following reversible unilateral ureteric obstruction in the rat.

We investigated the renal response to direct renal nerve stimulation, 2 weeks following reversal of 24-h unilateral (left) ureteric obstruction. Renal nerve stimulation caused a 13-15 % fall in renal blood flow, in 4 groups of anesthetized rats following ureteric obstruction (n=9) or a sham operation (n=7) both with (n=9) and without (n=7) treatment with the mixed ET(A/B) receptor antagonist, bosentan. In the sham-operated rats, renal nerve stimulation did not change glomerular filtration rate but reduced urine flow rate (37+/-3 %, P<0.001), and absolute (38+/-4 %, P<0.001) and fractional (35+/-5 %, P<0.01) sodium excretion. Following unilateral ureteric obstruction, renal nerve stimulation increased glomerular filtration rate by 22+/-3 % (P<0.01), but reduced urine flow rate (14+/-2 %, P<0.001) and fractional sodium excretion (23+/-5 %, P<0.01). Bosentan treatment had no effect on baseline or renal responses to renal nerve stimulation in the sham group but normalized the renal response to renal nerve stimulation in the unilateral ureteric obstruction group. We conclude that 14 days after a 24-h period of unilateral ureteric obstruction there is an increase in GFR in response to direct renal nerve stimulation, which is due, in part, to the actions of endothelin at the time of obstruction.

Macroscopic electrical propagation in the guinea pig urinary bladder.

There is little knowledge about macroscopic electrical propagation in the wall of the urinary bladder. Recording simultaneously from a large number of extracellular electrodes is one technology that could be used to study the patterns of macroscopic electrical propagations. The urinary bladders from 14 guinea pigs were isolated and placed in an organ bath. A 16 × 4-electrode array was positioned at various sites on the serosal bladder surface, and recordings were performed at different intravesical volumes. In four experiments, carbachol (CCH; 10(-6) M), nifedipine (10 mM), or tetrodotoxin (TTX; 10(-6) M) was added to the superfusing fluid. After the experiments, the extracellular signals were analyzed and propagation maps were constructed. Electrical waves were detected at all sites on the bladder surface and propagated for a limited distance before terminating spontaneously. The majority of waves (>90%) propagated in the axial direction (i.e., from dome to base or vice versa). An increase in vesicle volume significantly decreased the conduction velocity (from 4.9 ± 1.5 to 2.7 ± 0.7 cm/s; P < 0.05). CCH increased, nifedipine decreased, while TTX had little effect on electrical activities. In addition, a new electrical phenomenon, termed a "patch," was discovered whereby a simultaneous electrical deflection was detected across an area of the bladder surface. Two types of electrical activities were detected on the bladder surface: 1) electrical waves propagating preferentially in the axial direction and 2) electrical patches. The propagating electrical waves could form the basis for local spontaneous contractions in the bladder during the filling phase.

Does aliskiren protect the kidney following ischemia reperfusion injury?

The effect of blocking the first and rate-limiting step in renin-angiotensin cascade on the renal function in ischemia reperfusion injury has not been previously investigated. We investigated the effect of aliskiren, the first approved direct oral renin inhibitor, on the alterations in renal functional parameters in this condition. Wistar rats underwent left renal ischemia for 40 min. Group-1 received normal saline whereas Group-2 received aliskiren (30 mg/kg/day) by gavage for 6 days commencing one day before IRI. The hemodynamic and tubular functions and gene expression of neutrophil gelatinase-associated lipocalin (NGAL) and plasminogen activating inhibitor (PAI-1) in the right and left kidneys were measured five days following the IRI. Comparing Group-1 and Group-2, the left renal blood flow was significantly higher in Group-2 (1.28+/-0.36 vs. 0.39+/-0.05, P=0.007). Left kidney glomerular filtration rate was also higher in Group-2 but did not reach statistical significance (0.18+/-0.05 vs. 0.10+/-0.02, P=0.07). The left renal FE(Na) was significantly lower in Group-2 (29.9+/-6.4 vs. 49.7+/-7.8, P=0.03). Aliskiren also caused a significant decrease in the gene expression of both NGAL and PAI-1 in the left ischemic kidney. In conclusions, the administration of aliskiren before and after IRI appears to have ameliorated the IRI effect on the total renal artery blood flow, fractional excretion of sodium and gene expression of both NGAL and PAI-1 indicating a renoprotective effects in IRI.

Curcumin provides incomplete protection of the kidney in ischemia reperfusion injury.

Curcumin, a component of the spice turmeric, was shown to have a protective effect on acute kidney injury markers following ischemia-reperfusion injury (IRI). However, its effect on glomerular and tubular renal functions following IRI is not known and this data is probably of more clinical relevance. In this study, curcumin was tested for its effect on renal functional parameters following two different periods of warm IRI in the rat. Groups V-30 (n=10) and C-30 (n=10) underwent ischemia for 30 minutes whereas groups V-45 (n=8) and C-45 (n=8) underwent ischemia for 45 minutes. C-30 and C-45 received oral curcumin (200 mg/kg/day) whereas V-30 and V-45 received a vehicle. The left renal artery blood flow was measured by a flowmeter before and 15 minutes after reperfusion. Serum TNF-alpha was measured before and 2 days after ischemia. The function of both kidneys was measured 2 days following ischemia using clearance technique. IRI caused significant increase in TNF-alpha in all groups. Curcumin significantly ameliorated the ischemia-induced alterations in serum TNF-alpha and associated histological changes but did not affect the alterations in renal artery blood flow, glomerular (glomerular filtration rate, renal blood flow) or tubular (urinary volume, urinary sodium and fractional excretion of sodium) functions following 30 or 45 min of IRI.

Does curcumin protect against renal dysfunction following reversible unilateral ureteric obstruction in the rat?

AIMS: To investigate the effect of curcumin on the alterations in renal functional parameters following reversible unilateral ureteric obstruction in the rat. METHODS: Wistar rats underwent reversible left ureteric obstruction for 72 h. The group Cm (n = 7) received oral curcumin (200 mg/kg/day), whereas the Vx group (n = 8) had only a vehicle. RESULTS: Ureteric obstruction caused a significant increase in the serum tumour necrosis factor α in both groups. However, the post-obstruction level in the Cm group was significantly lower than in the Vx group. In the Vx group, the glomerular filtration rate, renal blood flow, urine volume and urinary sodium excretion in the left obstructed kidney were significantly lower than those in the right kidney, but the fractional excretion of sodium was comparable in the 2 groups. The left kidney in the Cm group behaved similar to that in the Vx group. Moreover, there was no difference in any variable when comparing the right and left kidneys among the groups. CONCLUSION: Curcumin appears to have no significant protective effect on the haemodynamic or tubular glomerular functions when measured as early as 3 days following reversible ureteric obstruction despite the amelioration in some of the indicators of renal injury.

The effect of diclofenac sodium on renal function in reversible unilateral ureteric obstruction.

The objective of the study was to investigate the effect of diclofenac sodium, when administered similar to its use in clinical practice, 2 weeks following different periods of complete reversible unilateral ureteric obstruction in the rat using accurate indicators of renal function. Male Wistar rats underwent reversible left ureteric obstruction for 2 days [D2-untreated (n = 8) and D2-DS (n = 8) groups] and 5 days [D5-untreated (n = 7) and D5-DS (n = 7) groups]. D2-DS and D5-DS received intramuscular diclofenac sodium (3 mg/kg per day) during the time of obstruction, whereas D2-untreated and D5-untreated groups did not receive any treatment. The renal functions of both kidneys were studied 2 weeks following the reversal. The basal heart rate and mean arterial blood pressure were similar in D2-untreated and D2-DS and in D5-untreated and D5-DS groups. In the D2-untreated group, the GFR and RBF of the left obstructed kidney were 76 and 72% that of the right non-obstructed kidney [0.99 ± 0.06 vs. 1.30 ± 0.08 (P < 0.05) and 4.25 ± 0.33 vs. 5.92 ± 0.61 (P < 0.05), respectively]. The urine volume and urinary and fractional sodium excretion were not significantly different from the right kidney. Similar response was obtained in the D2-DS group. In the D5-untreated group, the GFR and RBF of the left kidney was 66 and 62% that of the right kidney (0.80 ± 0.12 vs. 1.21 ± 0.6, P < 0.05 and 3.79 ± 0.32 vs. 6.16 ± 0.59, P < 0.05; respectively). The tubular functions of both kidneys were similar. In the D5-DS group, there was no difference in GFR or RBF between both kidneys (1.02 ± 0.08 vs. 1.12 ± 0.3, P = 0.24 and 5.10 ± 1.25 vs. 6.46 ± 1.11, P = 0.44, respectively). Similarly, there was no difference in the tubular functions. Treatment with diclofenac sodium during a relatively long period of reversible unilateral ureteric obstruction, similar to its use in the management of ureteric colic, appears to ameliorate the alterations in the hemodynamic glomerular functions at least 2 weeks following the reversal of obstruction.

TVT can also cause urethral diverticulum.

Since the introduction of tension-free vaginal tape (TVT) procedure by Ulmsten, the majority of reports have concentrated on TVT procedure's success to correct urinary stress incontinence with fewer reports on its complications. In this study, we describe the first case in the English literature, of urethral diverticulum, which occurred after the use of polypropylene synthetic sling in a woman with previous vaginal surgery.

Bladder calculi: did the clinical picture change?

OBJECTIVES: Recent improvements in socioeconomic conditions have changed the clinical picture of urinary stones, including bladder calculi. With the ongoing changes in these predisposing factors, it is possible that the clinical picture of bladder calculi will show additional changes. Nevertheless, few contemporary series of bladder calculi in published English reports have addressed these issues. METHODS: We retrospectively reviewed the records of 328 patients who underwent surgical therapy for bladder calculi at our institution from January 1995 to June 2005. RESULTS: Acute urinary retention was the most common presenting symptom (n = 221, 67%). Patients who presented with urinary retention were younger (37 versus 48 years, P <0.001), had a greater incidence of recent renal colic (40% versus 19%, P <0.01), and had a lower incidence of bladder outlet obstruction (14% versus 37%, P <0.001) compared with the nonretention group. However, previous stone passage did not influence the probability of presenting with urinary retention. Small bladder stones were associated with a greater likelihood of presenting with urinary retention. The retention group had greater incidence of stones less than 1 cm in diameter compared with the nonretention group (72% versus 39%, P <0.001). Finally, calcium oxalate was found in 78% of patients with bladder calculi. CONCLUSIONS: Acute urinary retention was the main mode of presentation in patients with bladder calculi. Younger age, a history of recent renal colic, and smaller stones appeared to increase the likelihood for patients to present with urinary retention.

Indications for nephrectomy in children: what has changed?

OBJECTIVE: To review the indications for nephrectomy in children between 1990 and 2001, at the Starship Children's Hospital, Auckland, New Zealand. PATIENTS AND METHODS: There were 206 nephrectomies. A retrospective review of the patients' notes was performed. The 12-year period was divided into two halves (1990-1996 and 1996-2001) which were then compared. RESULTS: The total number of nephrectomies per year significantly increased over the period of the study (11.5 and 22.2 per year for 1990-1995 and 1996-2001, respectively; P<0.05), as did the number of partial nephrectomies (one and 23 for 1990-1995 and 1996-2001, respectively; P<0.01). Multicystic dysplastic kidney (MCDK), Wilms' tumour and vesico-ureteric reflux (VUR) accounted for more than half of the nephrectomies (60% and 68% for 1990-1995 and 1996-2001, respectively). The proportion of nephrectomies performed for these indications did not change (MCDK 25% and 34%, Wilms' 25% and 18%, VUR 16% and 18%, for 1990-1995 and 1996-2001, respectively), but fewer nephrectomies were performed for pelvi-ureteric junction (PUJ) obstruction in the second half of the study period (13% and 4% for 1990-1995 and 1996-2001, respectively; P<0.05). CONCLUSION: The total number of nephrectomies, including partial nephrectomies, has increased significantly. The decrease in nephrectomies for PUJ obstruction could be accounted for by a more aggressive approach in the management and follow up of prenatally diagnosed hydronephrosis. Of note is that there was no significant change in the proportion of nephrectomies performed for Wilms' tumour, MCDK and VUR.

Erosions and urinary retention following polypropylene synthetic sling: Australasian survey.

INTRODUCTION: There are few published reports on the incidence and management of urethral and vaginal erosions following the use of polypropylene synthetic slings. Moreover, there is very little Australasian data on their use for management of female urinary incontinence or on their associated complications. METHODS: A 1-page survey was mailed to the Australian and New Zealand members of the Urological Society of Australasia (N=326). The survey included questions on the use of polypropylene synthetic sling and the incidence and management of post-operative vaginal and urethral erosions and urinary retention. RESULTS: 198 surveys were returned (response rate: 61%). Polypropylene synthetic sling procedure is practiced by 39% of the respondents with a total of 1459 cases (TVT: 993, SPARC: 466). The incidence of vaginal erosions, urethral erosions and urinary retention was 1.2%, 0.6% and 6.5%, respectively. Thirty five percent of vaginal erosions were asymptomatic and only identified on routine post-operative vaginal examination. One third of urethral erosions presented more than 1 year after surgery and 89% of these were symptomatic. Thirty four percent of patients with urinary retention required surgical intervention to correct the retention. CONCLUSIONS: The incidence of urethral and vaginal erosions following polypropylene synthetic sling procedures is lower than that with other synthetic slings. However, a high index of suspicion and long-term follow-up are required to identify and manage these complications of this relatively new procedure.

Role of endothelin ET(A) receptor antagonism in the post-transplant renal response to angiotensin II in the rat.

The role of endothelins in the renal damage associated with ischaemic-reperfusion (I-R) injury during organ transplantation was determined by selective blockade of the ET(A) receptors with the receptor antagonist ABT-627. The integrity of kidney function was determined 2 and 8 weeks after transplantation by investigation of the renal response to angiotensin II. Under pentobarbitone anaesthesia (70 mg x kg(-1), I.P.), rats underwent a right nephrectomy. Transplantation of the left kidney was performed after 2 h cold ischaemia without or with ABT-627 treatment. Control animals underwent left renal denervation. The renal response to angiotensin II was measured 2 weeks later following blockade of endogenous production of angiotensin II with captopril. A further transplant group was allowed to recover for 8 weeks before the terminal study. In the control group, angiotensin II reduced renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (UV), and fractional sodium excretion (FE(Na)) by 29 +/- 5 %, 19 +/- 4 %, 25 +/- 4 % and 32 +/- 7 %, respectively. Conversely, in the transplant group, angiotensin II left RBF unchanged and increased GFR (59 +/- 12 %) and UV (93 +/- 8 %). FE(Na) decreased by 24 +/- 9 %. In both the transplant group treated with ABT-627 and the long-term recovery group, the renal response to angiotensin II was normalised. In conclusion, renal transplantation following 2 h cold I-R injury resulted in a temporary abnormal renal response to angiotensin II, which was reversed by ET(A) receptor antagonism at the time of transplantation.

Endotelin ETA and ETB receptor antagonism during cold preservation in renal transplantation.

BACKGROUND: In this study, we investigated the effects of selective endothelin (ET) receptor antagonism during different periods of cold ischemia on glomerular and tubular function and long-term survival in renal transplantation. METHODS: Left renal transplantation was performed in Lewis rats after 2 hr of cold ischemia without (n=8) and with (n=6) ETA receptor antagonism and after 16 hr of cold ischemia without treatment (n=6), with ETA receptor antagonism (n=8) and with ETB receptor antagonism (n=6). A control group (n=8) underwent right nephrectomy and left renal denervation. The ETA and ETB receptor antagonists (BQ-610 and A-192621, respectively) were added to the preservation solution (EuroCollins). After transplantation, renal glomerular and tubular functions were monitored for up to 60 days or death. RESULTS: All animals in the control and 2-hr groups survived the follow-up protocol, with early postoperative recovery of glomerular and tubular function while the entire untreated 16-hr group died between day 3-6 postoperatively. BQ-610 treatment had no measurable effect on the renal function in the 2-hr group, however, it improved glomerular and tubular functions and led to 50% long-term survival (60 days) in the 16-hr group. A-192621 treatment had no effect on long-term survival or renal parameters. CONCLUSION: ETA receptor antagonism had protective renal effects after prolonged ischemic preservation in renal transplantation while ETB receptor antagonism had not.

Intra- and post-operative assessment of renal cortical perfusion by laser Doppler flowmetry in renal transplantation in the rat.

Renal blood flow (RBF) in the period immediately following transplantation has an important prognostic value. Here we report for the first time on the use of laser Doppler flowmetry (LDF) for the measurement of renal cortical perfusion (RCP) during all the important steps in renal transplantation. Left orthotopic kidney transplantation was performed in Lewis rats (n = 14) after 2 h of cold ischaemia and preservation in EuroCollins solution. Under baseline conditions, RCP in the donor and recipient kidneys were similar with a coefficient of variability of 11 and 12%, respectively. There was a progressive increase in RCP during the first 60 min after transplantation with a return to normal values 2 weeks later. In conclusion, LDF provides a rapid and continuous measure of RCP without interference to the operative site and may prove a useful tool for the measurement of RBF during kidney transplantation.

Long-term renal effects of unilateral ureteral obstruction and the role of endothelin.

BACKGROUND: Angiotensin II (Ang II) and endothelin (ET) are involved in the alteration of renal function in unilateral ureteral obstruction (UUO). The renal response to Ang II following the reversal of a 24-hour UUO and the effect of ET blockade by bosentan during the time of obstruction were investigated. METHODS: Following blockade of the endogenous production of Ang II by captopril, the renal response to Ang II was studied in rats 15 to 18 days after a 24-hour UUO (N = 10) or a sham operation (N = 9) both with (N = 10) and without (N = 8) bosentan treatment in the periobstruction period. Similar studies were performed in another group (N = 9) two months following the reversal of obstruction. RESULTS: In the sham-operated group, Ang II reduced renal blood flow (RBF) by 42 +/- 9% (P < 0.01), glomerular filtration rate (GFR) by 30 +/- 8% (P < 0.01), urine volume (UV) by 44 +/- 9% (P < 0.001), and absolute (UNaV) and fractional sodium excretion (FENa) by 52 +/- 9% (P < 0.001) and 33 +/- 9% (P = 0.054), respectively. In the previously obstructed kidney, Ang II did not change RBF but increased GFR by 106 +/- 40% (P < 0.01), UV by 75 +/- 21% (P < 0.001), UNaV by 190 +/- 60% (P < 0.001), and FENa by 40 +/- 13% (P < 0.05). Bosentan treatment in the obstructed group prevented these Ang II-induced effects and did not have any effect on the sham-operated kidney. Two months following reversal of the obstruction, the response of the kidney was similar to that of the control kidney. CONCLUSION: Twenty-four-hour UUO results in a temporary abnormality in the renal response to Ang II, which is due, in part, to the actions of ET at the time of obstruction.

The role of endothelin in early renal cortical reperfusionin renal transplantation.

The role of specific endothelin receptors in the early renal reperfusion and long-term survival in renal transplantation was investigated in Lewis rats. Left renal transplantation was performed following 2 h cold ischaemia without and with ET(A) receptor antagonism and following 16 h cold ischaemia with no treatment, with ET(A) receptor antagonism and with ET(B) receptor antagonism. The ET(A) and ET(B) receptor antagonists, BQ-610 and A-192621 respectively, were added to the preservation solution. Renal cortical perfusion (RCP) was measured postoperatively using laser Doppler flowmetry. All rats in the 2-hour groups survived for 15 days. Animals in the untreated 16-hour group or in the A-192621-treated group died between days 3 and 6 after surgery. Fifty percent of the rats in the 16-hour and BQ-610-treated group died between days 4 and 7 after surgery while the other 50% survived for 15 days. Survival rates correlated well with both the postoperative serum creatinine and the recovery of RCP. We conclude that addition of an ET(A) receptor antagonist to the preservation solution improves renal reperfusion and long-term survival following prolonged ischaemia, whereas ET(B) receptor antagonism does neither.