Jian Guo Wen

Obstructive nephropathy: an update of the experimental research

Abstract Ureteral obstruction (UO) is one of the most common problems confronting the urologist. Although large amounts of animal and clinical research have been done, the pathophysiologic mechanisms accompanying UO are not fully elucidated. Most of our knowledge on UO has been derived from experimental studies in a variety of animal models. Both antenatal and postnatal UO models have been developed mainly by ligation of the ureter or by burying the ureter into the psoas muscle. Most experimental studies have focused on short-term complete ureteral obstruction. The long-term effects of partial ureteral obstruction have been less intensively studied. It is now clear that obstructive nephropathy is not a simple result of mechanical impairment to urine flow but a complex syndrome resulting in alterations of both glomerular hemodynamics and tubular function caused by the interaction of a variety of vasoactive factors and cytokines that are activated in response to UO. Leukocyte infiltration appears to play an important role in obstructive nephropathy suggesting that UO also has an immunological component. Growth factors such as platelet-derived growth factor, transforming growth factor-beta, epidermal growth factor and insulin-like growth factor I may all play a role in the development and progression of fibrotic and sclerotic changes in the obstructed kidney. At present, the selection of patients with congenital hydronephrosis for operative treatment is controversial. Studies in animals and patients have shown that partial unilateral UO does not always cause a loss of renal function or progression in urinary tract dilation during long-term follow-up. The implications of UO continue to raise many questions and further work is necessary to achieve a better understanding of the pathogenesis in obstructive nephropathy.

EXPERIMENTAL PARTIAL UNILATERAL URETER OBSTRUCTION. I. PRESSURE FLOW RELATIONSHIP IN A RAT MODEL WITH MILD AND SEVERE ACUTE URETER OBSTRUCTION

PURPOSE To create an animal model with mild and severe partial unilateral ureter obstruction in young rats using a modified Ulm and Miller technique and to characterize the model by acute renal pelvic pressure measurements. MATERIAL AND METHODS During anesthesia the upper fourth (n = 15) or the upper two-thirds of the left ureter (n = 15) was embedded into the psoas muscle causing either a mild or severe partial obstruction. Sham-operated control rats were prepared in parallel (n = 20). The baseline pelvic pressure, the perfusion pelvic pressure (perfusion rates: 0.2 to 1.0 ml. per minute) and peristaltic waves were recorded after a resting period. RESULTS Mean baseline pelvic pressure and perfusion pelvic pressure were significantly higher in obstructed kidneys than in non-obstructed kidneys, and significantly higher in severely obstructed kidneys than in mildly obstructed kidneys (p < 0.05). A fair linear relationship existed between the increase in pelvic pressure and the increase in perfusion rates in all groups. In the severely obstructed kidneys, baseline pelvic pressure was 16.9 +/- 2.3 cm. H2O and the perfusion pelvic pressure increased significantly from 41.7 +/- 3.3 cm. H2O to 68.6 +/- 6.3 cm. H2O. The pelvic peristaltic amplitude increased significantly following the increase in perfusion rate and there was a significant difference in the amplitude between severely obstructed and non-obstructed kidneys when the perfusion rate exceeded 0.4 ml. per minute (p < 0.05). CONCLUSION Embedding either the upper fourth or the upper two-thirds of the ureter into the psoas muscle produced a mild or a severe partial obstruction. In the latter model a significant increase in pelvic pressure and amplitude was observed, indicating the existence of severe obstruction.

EVALUATION OF RENAL FUNCTION IN NORMAL AND HYDRONEPHROTIC KIDNEYS IN RATS USING GADOLINIUM DIETHYLENETETRAMINE-PENTAACETIC ACID ENHANCED DYNAMIC MAGNETIC RESONANCE IMAGING

PURPOSE Magnetic resonance imaging (MRI) is becoming established as a modality complementary to computerized tomography and ultrasound for evaluating kidney function. The evaluation of renal function during ureteral obstruction may be improved by contrast enhanced MRI. We evaluated dynamic changes in relative signal intensity in normal and hydronephrotic rat kidneys after intravenous injection of gadolinium (Gd) diethylenetetramine-pentaacetic acid (DTPA). MATERIALS AND METHODS Using Gd-DTPA enhanced dynamic MRI we evaluated 35, 1-year-old rats, including 10 with partial and complete unilateral ureteral obstruction, respectively, and 15 with sham operated nonobstructed kidneys. Partial obstruction was created in 2-day-old rats by embedding the left ureter into the psoas muscle. Complete obstruction was created 10 days before MRI by placing a ligature around the upper third of the left ureter. MRI was performed before and 0.1 to 60 minutes after and intravenous injection of Gd-DTPA. We calculated relative signal intensity per time interval in the renal cortex, medulla and pelvis. RESULTS Dynamic relative signal intensity patterns differed significantly among normal, and partially and completely obstructed kidneys. In normal kidneys signal intensity changes were divided into 3 phases after Gd-DTPA administration. During phase 1 rapid parenchymal uptake of Gd-DTPA within the initial minute after injection produced a rapid signal intensity decrease in the cortex, which achieved a minimum of 28% of pre-injection intensity. During phase 2 signal intensity decreased in the medulla and pelvis to a minimum of 18% and 22%, respectively, of pre-injection intensity within 5 minutes. During phase 3 significant relative signal intensity recovery began in the cortex at 7 minutes, and in the medulla and pelvis at 10 to 15 minutes, and lasted 30 to 60 minutes. In partially obstructed kidneys the 3 phases were significantly slower than in controls. In completely obstructed kidneys only phase 1 occurred within 60 minutes. CONCLUSIONS Gd-DTPA enhanced dynamic MRI provides useful information for distinguishing obstructed from nonobstructed and partially from completely obstructed kidneys.

Melamine Related Bilateral Renal Calculi in 50 Children: Single Center Experience in Clinical Diagnosis and Treatment

PURPOSE We investigated the clinical diagnosis and treatment features of bilateral renal calculi in young children who ingested melamine tainted infant milk formula. MATERIALS AND METHODS We retrospectively analyzed clinical data on 50 children (mean +/- SE age 23.4 +/- 3.1 months) with a history of ingesting melamine tainted infant milk formula and suffering from bilateral renal calculi. All patients underwent ultrasound and renal function evaluation. Treatment included cessation of melamine tainted formula consumption, hydration, urine basification and hemodialysis if necessary. RESULTS Bilateral renal calculi peaked in 6 to 18-month-olds (58% of cases). The male-to-female ratio was 3.1:1.0. Calculi ranged in diameter from 4 to 10 mm in 33 patients (66%) and 2.5 to 4 mm in 17 (34%). Of the 11 patients with renal failure 8 underwent 1 to 4 sessions of hemodialysis. Of the 9 bilateral obstruction cases with renal failure 8 did not require surgical intervention but 1 required ureteral catheterization to drain the renal pelvis. All children experienced a good outcome and were discharged home after a mean +/- SE hospitalization of 8.1 +/- 0.7 days. CONCLUSIONS Melamine related urinary calculi were most often seen in patients 6 to 18 months old. Conservative management has been sufficient in most cases. However, these children need to be monitored for long-term effects of melamine tainted milk formula consumption.

Contralateral compensatory kidney growth in rats with partial unilateral ureteral obstruction monitored by magnetic resonance imaging.

PURPOSE We studied dynamic changes in total volume and renal vein blood flow in the kidneys contralateral to partial ureteral obstruction induced in newborn rats. MATERIALS AND METHODS Using magnetic resonance imaging we investigated changes in total kidney volume and renal vein blood flow in 20 rats with mild and 18 with severe partial ureteral obstruction that was induced on the left side 2 days after birth. A total of 15 sham operated control rats were also studied. Total kidney volume and renal vein blood flow were monitored sequentially every 2 to 6 weeks for a total of 24 weeks. Renal parenchymal volume measured in vivo by magnetic resonance imaging was compared with that measured in vitro at week 24. RESULTS Total volume and renal vein blood flow increased significantly in contralateral nonobstructed kidneys from week 14 and thereafter in rats with severe partial unilateral ureteral obstruction. At week 24 volume had increased by 22% and blood flow had increased by 25%. Volume and flow did not increase significantly in contralateral nonobstructed kidneys in rats with mild partial unilateral ureteral obstruction (p = 0.09). Before changes occurred in volume and blood flow in the contralateral nonobstructed kidneys, renal vein blood flow had decreased significantly from week 8 and thereafter in severely obstructed kidneys. In rats with mild partial unilateral ureteral obstruction renal vein blood flow decreased significantly in obstructed kidneys from week 18 and thereafter. Good correlation was noted between MRI in vivo and in vitro kidney volume measurements (r = 0.972, p <0.001). CONCLUSIONS A significant increase in total volume and renal vein blood flow in contralateral nonobstructed kidneys did not develop immediately after the onset of detectable functional deterioration in partially obstructed kidneys. Therefore, caution should be used when incorporating compensatory growth into surgical decision making.

Bed-wetting in Chinese children: epidemiology and predictive factors.

AIMS To estimate the prevalence and severity of bed-wetting in 1-18-year-old Chinese children. MATERIALS AND METHODS A cross-sectional study of bed-wetting was performed by using 13,515 self-administered questionnaires distributed to the parents of 1-18-year-old Chinese children in Henan province. The prevalence of bed-wetting was determined. The relationship of wetting to age, gender, community characteristics (rural or urban), arousal dysfunction, associated day-time symptoms (frequency, urgency, and incontinence), and family history were analyzed. RESULTS There was a response rate of 87% (5,978 boys and 5,786 girls). The overall prevalence of bed-wetting was 23.03% in those aged 1-4, 5.66% in those 5-12, and 1.37% in those 13-18. When a logistic regression analysis was applied to determine risk factors for the bed-wetting, a positive relationship was seen with male gender and living in rural areas. Further, living in rural areas, arousal dysfunction, and associated day symptoms were significantly related to more severe bed-wetting. Only 3.64% of the children had undergone professional evaluation. CONCLUSION The prevalence of bed-wetting is significant in Chinese children, but lower than in most western countries, which is likely due to cultural differences. Living in rural areas, having arousal dysfunction, and having associated day-time symptoms may be predicative factors for marked bed-wetting.

Is it possible to use urodynamic variables to predict upper urinary tract dilatation in children with neurogenic bladder‐sphincter dysfunction?

In this section, authors from China attempt to use urodynamic indices to predict upper urinary tract dilation in children with neurogenic bladder‐sphincter dysfunction.

Expression of renal aquaporins is down-regulated in children with congenital hydronephrosis

Abstract Objective. This study investigated mRNA and protein expression of four renal aquaporin isoforms [AQP1, 2, 3 and 4 (AQP1–4)] in congenital hydronephrotic kidneys (HK) due to pelviureteral junction obstruction and normal control kidneys. Material and methods. The expression of AQP1–4 was evaluated in 22 children (15 boys, seven girls, aged 58.9±54.3 months) using semi-quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) techniques, immunoblotting and immunohistochemistry. Hydronephrosis was graded by ultrasound according to the Society for Fetal Urology. Results. Both RT-PCR and immunoblotting showed significantly reduced mRNA and protein expression of AQP1–4 in grade IV compared with those in grade III HK and controls. Sequencing demonstrated 99% homology of AQP1–4 with those in GenBank. Positive immunoreactivity of AQP1 was found in plasma membranes of the proximal tubule, thin descending limb of Henle and descending vasa recta; AQP2 in the apical membrane of collecting duct principal cells; and AQP3 and 4 in the basolateral membrane of the same cells. In kidneys with grade IV hydronephrosis there was reduction in the protein abundance of all four AQP isoforms which was more pronounced compared with the protein abundance seen in kidneys with grade III hydronephrosis and control kidneys. Conclusion. The expression of AQP1–4 mRNA and protein abundance is reduced in proportion with the degree of hydronephrosis graded by ultrasound in human congenital HK.

The effect of familial aggregation on the children with primary nocturnal enuresis

To evaluate the effect of familial aggregation on the children with PNE by evaluating nocturnal urine output, bladder, and arouse function.

Early alteration of urinary exosomal aquaporin 1 and transforming growth factor β1 after release of unilateral pelviureteral junction obstruction

BACKGROUND/PURPOSE Down-regulation of aquaporin 1 (AQP1) and up-regulation of transforming growth factor β(1) (TGF-β(1)) in the renal parenchyma have been demonstrated in children who underwent pyeloplasty for pelviureteral junction obstruction. However, no information about urinary exosomal AQP1 and TGF-β(1) during postobstructive polyuria in children with congenital unilateral hydronephrosis is available. The aim of the present study is to evaluate the urine concentration of exosomal AQP1 and TGF-β(1) on the first and the second day after surgery in children who underwent pyeloplasty. METHODS Twenty-two patients (age, 36.2 ± 17.1 months) with unilateral pelviureteral junction obstruction were examined in the study. For the first 2 days after the operation, the urine was collected separately from pyelostomy draining only from the postobstructed kidney and from the bladder catheter draining mostly from the contralateral kidney, which was used as an internal control. Urinary output, urinary osmolality, sodium, β(2)-microglobulin (β(2)-MG), and creatinine, as well as urinary exosomal AQP1 and TGF-β(1) excretion, were tested in each sample. RESULTS After pyeloplasty, a significantly decreased urinary excretion of exosomal AQP1 (≈ 64%) was found in the postobstructed kidney. The patients developed polyuria (807 ± 216 mL/24 h vs 484 ± 144 mL/24 h at day 1, 1021 ± 348 mL/24 h vs 603 ± 228 mL/24 h at day 2; P < .01) and reduced urine osmolality (115 ± 44 mOsm/kg vs 282 ± 61 mOsm/kg at day 1, 139 ± 39 vs 303 ± 46 mOsm/kg at day 2; P < .01) that persisted for 48 hours. In parallel, urinary TGF-β(1) and β(2)-MG (normalized for creatinine) from the postobstructed kidney were significantly higher compared with the contralateral kidney. The urine output and urinary sodium concentration from the postobstructed kidney elevated significantly on the second day after the release of obstruction compared with those on the first day. The contralateral kidney also showed same trends. CONCLUSIONS The down-regulation of urinary exosomal AQP1 in the postobstructed kidney may account for the polyuria, hypotonic urine, and elevated urinary β(2)-MG. The urinary TGF-β(1) level locally increased in the postobstructed kidney may be involved in renal AQP1 down-regulation.