Congenital Unilateral Hydronephrosis Research Articles

Hidronefrose e hidroureter congênito em cão – relato de caso

This paper reports a case of congenital hydronephrosis and hydroureter in a dog. One canine was seen presenting difficulty in walking and abdominal enlargement. After treatment, there was no improvement. On reassessment, x-ray and ultrasound examinations revealed an unidentified increase in volume in the abdomen, and exploratory laparotomy was indicated. Unilateral congenital hydronephrosis was diagnosed in the left kidney and hydroureter with stenosis in the distal third and adherence to the left uterine horn, and an ovariosalpingohysterectomy was performed during the ureteronephrectomy. One month later, the patient presented decreased abdominal volume and locomotion without difficulties. Hydronephrosis and hydroureter are chronic changes that can cause irreversible organ damage.

Selected Metal Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases as Potential Biomarkers for Tubulointerstitial Fibrosis in Children with Unilateral Hydronephrosis.

Renal tubulointerstitial fibrosis caused by congenital ureteropelvic junction obstruction (UPJO) may lead to the development of obstructive nephropathy (ON) and the impairment of kidney function. Hence, the identification of early biomarkers of this condition might be of assistance in therapeutic decisions. This study evaluates serum and urinary metalloproteinases MMP-1, MMP-2, and MMP-9 and tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 as potential biomarkers of ON in children with congenital unilateral hydronephrosis (HN) caused by UPJO. Forty-five (45) children with congenital HN of different grades of severity and twenty-one (21) healthy controls were enrolled in the study. Urinary and serum concentrations of MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured using specific ELISA kits. The urinary excretions were expressed as biomarker/creatinine (Cr) ratios. To evaluate the extracellular matrix remodelling process activity, the serum and urinary MMP-1, -2, -9/TIMP-1, -2 ratios were also calculated. In comparison with the controls, patients with HN, independent of the grade, showed significantly increased median serum MMP-9, TIMP-1, and TIMP-2, median urinary MMP-9/Cr, and TIMP-2/Cr ratios. Lower median values of serum MMP-2/TIMP-1, MMP-9/TIMP-1 in patients with HN were also revealed. Additionally, higher urinary MMP-2/Cr, lower urinary MMP-2/TIMP-2, and lower serum MMP-9/TIMP-2 ratios were observed in patients with HN grades 3 and 4. Patients with ON diagnosed by renal scintigraphy had a significantly higher median serum MMP-9 concentration and lower median serum MMP-9/TIMP-1, -2 ratios in comparison with those without this condition. Patients with nonglomerular proteinuria had a significantly higher median serum TIMP-1 concentration, a higher median urinary TIMP-2/Cr ratio, and a lower serum MMP-9/TIMP-1 ratio compared to those without this symptom. The relationship between the measured biomarkers and the relative function of the obstructed kidney showed no correlations. The ROC curve analysis showed a promising diagnostic profile for the detection of ON for serum MMP-9 and the serum MMP-9/TIMP-1 and MMP-9/TIMP-2 ratios. In conclusion, the results of this study suggest that patients with HN, particularly with grades 3 and 4, are at higher risk of renal tubulointerstitial fibrosis. The noninvasive markers of this condition considered are urinary MMP-2/Cr and MMP-9/Cr, serum MMP-9, serum and urinary MMP-2, MMP-9/TIMP-1, -2. Additionally, serum MMP-9 and MMP-9/TIMP-1, -2 may become promising markers of ON.

The clinical significance of detecting renal urinary proteins through nephrostomy tube in children with extremely severe hydronephrosis

Objective To explore the change of urine proteins from nephrostomy tube and renal function in patients with very severe hydronephrosis after nephrostomy in order to determine the treatment strategy of either renal preservation or resection. Methods Retrospective analysis of clinical data from March 2015 to March 2017 of 28 cases with congenital unilateral severe hydronephrosis in children's hospital affiliated to Zhejiang University, including 19 boys and 9 girls, with 20 cases on the left and 8 on the right, an average age of 26.6 (0.3 to 122.0) months at the first consultation and 2 cases of urinary biochemical abnormalities. Front to rear diameter for puncture were between 5.7 and 7.6 cm, with an average of 6.7 cm, and the differential renal function (DRF) for the affected kidneys were 6.98 %-9.89 % (average 8.65 %) before puncture. The children underwent percutaneous renal perforation fistula. According to the recovery of renal function after perforation fistula, those who underwent nephrectomy were recruited as a nephrectomy group and the children whose kidney were preserved as kidney preservation group. Comparison 24 hours before and 3 months after puncture was made beteween groups regarding the proportion of urine, pH of the renal pelvis urine, α1 microglobulin (α1-MG), albumin (Alb), β2 microglobulin (β2-MG), immunoglobulin G (IgG), transferrin (TRF), and the recovery of the damaged renal function (direnal function DRF). Results Twenty-eight cases of percutaneous nephrolithotomy were successful without puncture complications, with 10 cases in the nephrectomy group and 18 cases in the renal preservation group. The difference of renal pelvis urine from the affected kidney of the nephrectomy group showed no statistical significance 24 hours before and 3 months after the procedure when comparing the following parameters, including urinary specific gravity (1.006±0.007 vs. 1.009±0.005), pH value (7.74±0.41 vs. 7.70±0.32), urine creatinine value [(462.20 ±158.01)μmol/L and (449.20±143.41) μmol/L], α1 microglobulin [(14.03±4.360) mg/L vs. (13.84±2.55) mg/L], β2 microglobulin [(0.76±0.28) mg/L vs. (0.65±0.14) mg/L], immunoglobulin G [(1 292.20±303.50) mg/L vs. (1 175.33±376.67) mg/L], and kidney function (DRF) [(8.86±0.67) % vs. (9.90±1.26)%]. While microalbumin [(8 644.40±829.54) mg/L vs. (3 145.10±1 445.02) mg/L] and transferrin [(445.70±46.71) mg/L vs. (214.30±40.13) mg/L, P 0.05). The creatinine value of 3 months after the procedure was significantly increased than that 24 hours within the procedure [(654.50±154.52μmol/L) vs. (423.94±172.74)μmol/L], and the urine pH (7.28±0.32 vs. 7.91±0.56), α1 microglobulin [(5.85±0.38)mg/L vs. (12.58±3.40)mg/L], microalbumin [(571.50±167.14)mg/L vs. (2 343.28±576.22)mg/L], β2 microglobulin [(0.14±0.05)mg/L vs. (0.53±0.13) mg/L], immunoglobulin G [(247.38±75.29)mg/L vs. (1 026.44±245.42)mg/L], and transferrin [(67.64±16.34)mg/L vs. (249.17±78.62) mg/L] were significantly decreased 3 months after than 24 hours before the procedure. The renal function was higher 3 months after than 24 hours within the procedure [(8.53±0.80)% vs. (20.50±7.87)%, P<0.05]. Conclusions The increase of creatinine value and the decrease of urine pH, α1 microglobulin, microalbumin, β2 microglobulin, immunoglobulin G and transferrin in renal pelvis urine suggested that renal function recovered after renal puncture, which is important for next-step plan of treatment strategy. Key words: Hydronephrosis, severe; Urine protein; Children; Percutaneous nephrostomy

Potential Novel Biomarkers of Obstructive Nephropathy in Children with Hydronephrosis

Obstructive nephropathy (ON) secondary to the congenital hydronephrosis (HN) is one of the most common causes of chronic kidney disease in children. Neither currently used imaging techniques nor conventional laboratory parameters are sufficient to assess the onset and outcome of this condition; hence, there is a need to prove the usefulness of newly discovered biomarkers of kidney injury in this respect. The purpose of the study was to assess the urinary excretion of alpha-GST, pi-GST, NGAL, and KIM-1 and the serum level of NGAL in children with congenital unilateral hydronephrosis secondary to ureteropelvic junction obstruction. The results were evaluated in relation to severity of HN, the presence of ON, relative function of an obstructed kidney, and the presence of proteinuria. The study comprised 45 children with HN of different grades and 21 healthy controls. Urinary and serum concentrations of biomarkers were measured using specific ELISA kits. Urinary biomarker excretions were expressed as a biomarker/creatinine (Cr) ratio. Patients with the highest grades of HN showed significantly increased values of all measured biomarkers, whereas those with the lowest grades of HN displayed only significant elevation of urinary alpha-GST and the serum NGAL. Urinary NGAL positively correlated with percentage loss of relative function of an obstructed kidney in renal scintigraphy. In patients with proteinuria, significantly higher urinary alpha-GST excretion was revealed as compared to those without this symptom. The ROC curve analysis showed the best diagnostic profile for urinary alpha-GST/Cr and NGAL/Cr ratios in the detection of ON. In conclusion, the results of the study showed that urinary alpha-GST and NGAL are promising biomarkers of ON. Ambiguous results of the remaining biomarkers, i.e., urinary pi-GST and KIM-1, and serum NGAL level may be related to a relatively small study group. Their utility in an early diagnosis of ON should be reevaluated.

Surgical treatment reduces blood pressure in children with unilateral congenital hydronephrosis

Renal disorders can cause hypertension, but less is known about the influence of hydronephrosis on blood pressure. Hydronephrosis due to pelvo-ureteric junction obstruction (PUJO) is a fairly common condition (incidence in newborns of 0.5-1%). Although hypertensive effects of hydronephrosis have been suggested, this has not been substantiated by prospective studies in humans [1-3]. Experimental studies with PUJO have shown that animals with induced hydronephrosis develop salt-sensitive hypertension, which strongly correlate to the degree of obstruction [4-7]. Moreover, relief of the obstruction normalized blood pressure [8]. In this first prospective study our aim was to study the blood pressure pattern in pediatric patients with hydronephrosis before and after surgical correction of the ureteral obstruction. Specifically, we investigated if preoperative blood pressure is reduced after surgery and if split renal function and renographic excretion curves provide any prognostic information. Twelve patients with unilateral congenital hydronephrosis were included in this prospective study. Ambulatory blood pressure (24 h) was measured preoperatively and six months after surgery. Preoperative evaluations of bilateral renal function by Tc99m-MAG3 scintigraphy, and renography curves, classified according to O'Reilly, were also performed. As shown in the summary figure, postoperative systolic (103 ± 2 mmHg) and diastolic (62 ± 2 mmHg) blood pressure were significantly lower than those obtained preoperatively (110 ± 4 and 69 ± 2 mmHg, respectively), whereas no changes in circadian variation or pulse pressure were observed. Renal functional share of the hydronephrotic kidney ranged from 11 to 55%. There was no correlation between the degree of renal function impairment and the preoperative excretory pattern, or between the preoperative excretory pattern and the blood pressure reduction postoperatively. However, preoperative MAG3 function of the affected kidney correlated with the magnitude of blood pressure change after surgery. Correction of the obstruction lowered blood pressure, and the reduction in blood pressure appeared to correlate with the degree of renal functional impairment, but not with the excretory pattern. Thus, in the setting of hypertension, it appears that the functional share of the hydronephrotic kidney should be considered an indicator of the need for surgery, whereas the renography curve is less reliable. The strength of the present study is the prospective nature and that ambulatory blood pressure monitoring was used. Future longitudinal prolonged follow-up studies are warranted to confirm the present findings, and to understand if a real nephrogenic hypertension with potential necessity of treatment will develop. This novel prospective study in patients with congenital hydronephrosis demonstrates a reduction in blood pressure following relief of the obstruction. Based on the present results, we propose that the blood pressure level should also be taken into account when deciding whether to correct hydronephrosis surgically or not.

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

Background/PurposeDown-regulation of aquaporin 1 (AQP1) and up-regulation of transforming growth factor β1 (TGF-β1) 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-β1 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-β1 on the first and the second day after surgery in children who underwent pyeloplasty. MethodsTwenty-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, β2-microglobulin (β2-MG), and creatinine, as well as urinary exosomal AQP1 and TGF-β1 excretion, were tested in each sample. ResultsAfter 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-β1 and β2-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. ConclusionsThe down-regulation of urinary exosomal AQP1 in the postobstructed kidney may account for the polyuria, hypotonic urine, and elevated urinary β2-MG. The urinary TGF-β1 level locally increased in the postobstructed kidney may be involved in renal AQP1 down-regulation.

Urinary cytokine profiles in unilateral congenital hydronephrosis

BackgroundWe aimed to evaluate possible clinical application of urinary monocyte chemotactic protein-1 (MCP-1), osteopontin (OPN), and regulated upon activation, normal T-cell expressed and secreted (RANTES) chemokine as useful noninvasive markers in children with congenital hydronephrosis (HN) caused by ureteropelvic junction obstruction (UPJO).MethodsThe study cohort consisted of surgical cases (study group 1), comprising 15 children with severe HN who required surgery (median age 1.03 years), conservative cases (study group 2), comprising 21 patients with mild, nonobstructive HN, and control group, comprising 19 healthy children. All children had normal renal function. Urinary (u) concentrations of MCP-1, OPN, and RANTES were measured using immunoenzymatic enzyme-linked immunosorbent assay (ELISA) commercial kits and were expressed in nanograms per milligram creatinine. Increased levels of MCP-1 and OPN were found in children with HN in comparison with study group 2 and controls (p < 0.05). UMCP-1/Cr correlated with half-time (T1/2) of the elimination phase of tracer excretion of technetium-99m-mercaptoacetyltriglycine (99mTc-MAG-3) (p < 0.05).ResultsReceiver operator characteristic (ROC) analyses revealed good diagnostic profile for uMCP-1 only in identifying children (<40 %) with abnormal differential renal function (DRF) [area under the curve (AUC) 0.862], and in detecting kidney injury in all examined children (AUC 0.704).ConclusionsAdditional studies with larger number of patients are required to confirm a potential application of uMCP-1 as a promising parameter for early identification of kidney obstruction.

When is it necessary to perform nuclear renogram in patients with a unilateral neonatal hydronephrosis?

To examine whether anteroposterior(AP) pelvic diameter on postnatal renal ultrasound scan (US) can predict both initial differential renal function (DRF) and deterioration in DRF in patients with prenatally diagnosed hydronephrosis. One hundred and thirty-three patients diagnosed with a unilateral prenatal hydronephrosis, confirmed postnatally, were evaluated. We tried to find the cutoff values for initial AP diameter and change in AP diameter based on initial DRF and renal outcome. Reduction of 5% or more was considered as deterioration in function. All patients had an initial US scan at a mean age of 1.62weeks (1-4) and nuclear renogram at 13.24weeks (7-21). All patients had a second US at a mean age of 10.58weeks (6-19). 119 patients had a second renogram. Initial mean pelvic diameter was 20.86 (11-49)mm. When AP pelvic diameter was less than 20mm, 98.6% of all renal units had a function of ≥40%. The cutoff point for AP pelvic diameter was 19.05 when DRF was ≥45% (P<0.001). When the reduction in hydronephrosis in pelvic diameter was analyzed to predict the initial renal function, a cutoff point of 1.3mm decrease was found when initial renal function was ≥40% (P<0.001). The reduction in AP pelvic diameter was 2.1mm when initial DRF was ≥45% (P=0.009). For all patients except 3 individuals, if there was a reduction in AP diameter or the AP diameter was stable, then no reduction in function was observed. When the AP pelvic diameter is less than 20mm at presentation, DRF is normal. If the AP diameter is stable or decreases, there is unlikely to be a significant deterioration in renal function. Consequently, in selected patients, congenital unilateral hydronephrosis can be followed with serial ultrasounds.

Pregnancy after renal transplantation: A single‐center experience

To examine women with renal transplants who became pregnant, and delivered at our hospital. Twenty-six women who had undergone renal transplantation between 1977 and 2002 became pregnant, and delivered at Osaka University Hospital. Complete medical records of twenty of them were retrieved and retrospectively analyzed. Overall, twenty-nine pregnancies occurred in these twenty women after renal transplantation. There were spontaneous abortions in three cases, whereas pregnancy was artificially terminated five times. Thus, neonates were delivered in 21 of 29 pregnancies. One woman delivered twice and two women delivered twins. As a result, a total of 23 neonates were delivered. Mean gestational period was 35.4 weeks (range, 27-41 weeks), and mean birth weight was 2229 g (range, 724-3544 g). Regarding fetal complications, intrauterine growth retardation was observed in three cases. One child with intrauterine growth retardation died at 3 months old due to respiratory distress syndrome. One child displayed double-outlet right ventricle and another child had congenital unilateral hydronephrosis. Regarding maternal complications, prevalence of toxemia of pregnancy was 38.1%. In four of the 21 deliveries (19.0%), renal function exacerbated after delivery. Rates of graft survival for the 20 women at 1, 5 and 10 years after delivery were 100%, 85.1% and 74.4%, respectively. Prognosis for renal transplant resulted to be significantly poorer for recipients with hypertension before pregnancy than for recipients without hypertension before pregnancy (log-rank test, P = 0.043). Rates of graft survival after delivery were mostly favorable. However, prognosis for renal function was poorer for recipients who displayed hypertension prior to pregnancy.

Ultrasonographic monitoring of hydronephrosis and ureteropelvic junction obstruction in children

Objective: To appreciate the role of ultrasonography in monitoring of pelvic dilatation and renal parenchyma thickness in infants and children with unilateral congenital hydronephrosis.

Imaging Kidney in Conscious Rats with High-Frequency Ultrasound and Detection of Two Cases of Unilateral Congenital Hydronephrosis

A quick noninvasive screen of laboratory animal organ phenotype by high-resolution ultrasound is useful in biomedical research and new drug discovery. During new drug testing, imaging animal at the conscious state avoiding anaesthesia does not only speed up the screening process, but also avoids the potential compounding interaction of anaesthetic agents with the new drugs. The feasibility of imaging kidney in conscious rats with high-frequency ultrasound was explored in this study. Two operators were involved with the procedure, with one operator holding the rat and the other operator doing the imaging process. A VisualSonics ultrasound system was used, with a 30 MHz central frequency probe at the resolution of 115 × 55 μm. It was feasible to hold the conscious rats still, allowing ultrasound imaging of kidneys, without causing stress to the animals. In a group of 12 male Han Wistar rats (Charles River, UK), two cases of unilateral congenital hydronephrosis of the right kidney were identified. The right kidneys with hydronephrosis showed an echolucent dilated pelvis and overall parenchymal hypotrophy. (E-mail: yixiang_wangmd@yahoo.co.uk)

Hidronefrosis congénita primaria unilateral grave en lactantes asintomáticos. Revisión de 98 casos

Currently, consensus is lacking on the indications for surgery in primary congenital unilateral hydronephrosis. To analyze the clinical characteristics, treatment and outcome of severe asymptomatic primary congenital unilateral hydronephrosis (grades 3 and 4). We performed a retrospective study of 98 neonates with severe primary congenital unilateral hydronephrosis. Diagnostic techniques consisted of ultrasound, renogram, and DMSA scan. The mean age at diagnosis was 24 days. The mean length of follow-up was 4 years. Forty-eight percent of cases were grade 3 and the remaining cases were grade 4. Fifty-six percent of the patients received conservative treatment. Forty-four percent underwent surgery. Surgical indications consisted of prolonged T1/2, reduced differential renal function and/or very severe hydronephrosis. The mean age at surgery was 5.5 months. In 94 % of the patients who received conservative treatment, hydronephrosis resolved spontaneously. In this group, renal parenchyma and renal function were normal in all patients except two. In 97 % of the patients who received surgical treatment, hydronephrosis was corrected or improved after pyeloplasty. At diagnosis, 19 kidneys had reduced function. In the postsurgical renogram, although T1/2 had markedly improved, 8 kidneys showed reduced function. DMSA performed in 63 patients belonging to both groups, outside the active phase of hydronephrosis, revealed 8 atrophic kidneys, 4 with moderately reduced renal size and function and 4 with scarring and normal renal size and function. During the study period, overall function was maintained in all patients and none developed hypertension. Severe congenital unilateral hydronephrosis resolves spontaneously in most patients. Consequently, clinicians increasingly adopt a conservative approach. The available diagnostic techniques cannot identify patients who will benefit from pyeloplasty. In general, accepted surgical indications are an increase in hydronephrosis and/or worsening of renal function. In our series, 15 % of the patients with hydronephrosis had an irreversible lesion of variable severity, which in some patients seemed to have developed during embryogenesis. Kidneys at risk of presenting a lesion were those that had grade 4 hydronephrosis.

Prognostic significance of captopril renography for managing congenital unilateral hydronephrosis.

In this prospective study we evaluated the results of captopril enhanced diuretic renography in patients with congenital unilateral ureteropelvic junction type hydronephrosis. Captopril renography helps to distinguish patients who have renin-angiotensin system activation from those in whom it is not yet activated. Renin-angiotensin system activation heralds the beginning of compensatory vasoactive response in the kidney. Identifying grades of such activation may help in determine the end points of nonoperative management. We prospectively studied 25 patients with suspected unilateral ureteropelvic junction obstruction treated at our department. A prenatal diagnosis was made in 60% of cases. Patient age was 1 to 144 months (mean 40) and the male-to-female ratio was 4:1. Followup was 6 to 72 months (mean 30). Patient evaluation and analysis included sonography, standard diuretic and captopril renography, glomerular filtration rate, serum creatinine and blood pressure. The indications for surgery were symptoms, differential function below 35%, or a documented decrease of 10% or more during followup. Activation of the renin-angiotensin system was considered positive when split renal function decreased significantly by 5% or more in an obstructed system on a post-captopril study. The results of captopril renography were examined retrospectively in patients who required surgery according to preexisting criteria. Society for Fetal Urology hydronephrosis grade was II to IV in 8, 10 and 7 renal units, respectively. The renin-angiotensin system was activated in 8 of the 25 cases (32%) of unilateral ureteropelvic junction obstruction. In 15 patients there was no change on pre-captopril and post-captopril studies and in 2 split renal function on the obstructed side marginally increased on the post-captopril study. Surgical correction was required in only 6 of the 8 patients with renin-angiotensin system activation. Of those who required surgery hydronephrosis was grades II to IV in 3, 1 and in 2 patients, respectively. In the current study renin-angiotensin system activation correlated with the need for surgery in 75% of the cases of congenital unilateral ureteropelvic type hydronephrosis. Since captopril serves to identify patients who have renin-angiotensin system activation, it may also be possible to grade this activation. Our preliminary results show that there may be a role for captopril renography for identifying the risk group for surgical intervention.

CONGENITAL UNILATERAL HYDRONEPHROSIS: A REVIEW OF THE IMPACT OF DIURETIC RENOGRAPHY ON CLINICAL TREATMENT

The natural history of and optimal treatment for asymptomatic congenital hydronephrosis is unknown, mainly because most published series are nonrandomized or retrospective with nonstandardized followup regimens. In this survey we provide an overview of the different strategies used for the treatment of congenital unilateral hydronephrosis. A comprehensive literature review of clinical studies of asymptomatic congenital unilateral hydronephrosis is presented. Different criteria for surgical intervention and different followup regimens have been used. Identification of the population at risk has been attempted but results are ambiguous. Surgery is done in approximately 25% of cases when using deteriorating differential function, symptoms and/or increasing hydronephrosis as criteria for operation. A nonstandardized renographic assessment does not compromise evaluation of the ideal followup but it may compromise the functional outcome. More studies of kidneys with decreased function, severe hydronephrosis or poor drainage investigated with a standardized protocol are needed to clarify the natural history and establish optimal guidelines for treatment and followup.

INCREASED NEPHRON VOLUME IS NOT A CAUSE OF SUPRANORMAL RENOGRAPHIC DIFFERENTIAL RENAL FUNCTION IN PATIENTS WITH URETEROPELVIC JUNCTION OBSTRUCTION

Increasing clinical importance is being placed on the role of differential renal function (DRF) in the management of congenital ureteropelvic junction obstruction. Supranormal DRF of the hydronephrotic kidney on renal scan is a puzzling phenomenon and is hypothesized to be due to an increase in single nephron filtration or nephron volume without sound evidence. We studied the histopathological changes of hydronephrotic kidneys to determine whether glomerular hypertrophy underlies supranormal DRF. We retrospectively evaluated the records of 3 females and 32 males with unilateral congenital hydronephrosis who underwent pyeloplasty. Mean patient age at operation was 12.6 months (range 0.1 to 144). Needle biopsies from 3 different sites at the lower pole of the kidney were performed during surgery. To evaluate the presence of glomerular hypertrophy, the maximal planar area of glomeruli was measured under light microscopy using an image analyzer. Tissue samples obtained from kidneys without a history of urinary tract disease at autopsy were used as controls. The mean glomerular areas of the patient and control groups were evaluated according to DRF and age. The mean glomerular area values of the patient group were smaller than those of the control group, except for 4 patients. The glomerular areas of the hydronephrotic kidneys with supranormal DRF were not significantly different from those of the control group. Instead, the probability of larger renal glomeruli increased with decreasing DRF (p = 0.1155). Increased nephron volume can be discounted as a cause of supranormal DRF.

Effect of urinary tract infection on ureteropelvic junction obstruction in a rat model

Objectives When a partially obstructed kidney becomes infected, more rapid and extreme renal parenchymal damage appears to occur than might result from either infection or obstruction alone. Previously, we showed that either bacteriuria or partial obstruction in congenital unilateral hydronephrosis causes elevated renal pelvic pressures in a rat model. In this same model, we examined the combined effects of partial upper tract obstruction and bacteriuria on renal pelvic and bladder pressures. Methods Female rats from an inbred colony in which more than one half are born with unilateral obstructive hydronephrosis were studied. Type 1 piliated Escherichia coli was instilled into the bladder. Two to 6 days later, the bladder and renal pelvic pressures were measured during varying urinary flows (less than 2 to more than 30 mL/kg/hr). All animals were killed and the kidneys and bladder grossly and histologically assessed. Hydronephrosis was determined at pathologic examination. Results Eight rats had congenital unilateral hydronephrosis; five were normal. Acute inflammation was found in all bladder and renal specimens. In hydronephrotic, infected kidneys, the renal pelvic pressures exceeded those in nonhydronephrotic, infected kidneys at all urinary flow rates. Bladder capacity and pressures did not differ between the two groups. Conclusions This model demonstrates that the combination of infection and obstructive hydronephrosis in this model causes renal pelvic pressure elevation that is higher than that associated with either infection or obstructive hydronephrosis alone. These data demonstrate the compound effect that infection and obstruction may have on the kidney and offers an explanation for why this clinical situation is more likely to be associated with greater renal parenchymal injury than either alone.

Prognostic Significance of Captopril Renography for Managing Congenital Unilateral Hydronephrosis

In this prospective study we evaluated the results of captopril enhanced diuretic renography in patients with congenital unilateral ureteropelvic junction type hydronephrosis. Captopril renography helps to distinguish patients who have renin-angiotensin system activation from those in whom it is not yet activated. Renin-angiotensin system activation heralds the beginning of compensatory vasoactive response in the kidney. Identifying grades of such activation may help in determine the end points of nonoperative management. We prospectively studied 25 patients with suspected unilateral ureteropelvic junction obstruction treated at our department. A prenatal diagnosis was made in 60% of cases. Patient age was 1 to 144 months (mean 40) and the male-to-female ratio was 4:1. Followup was 6 to 72 months (mean 30). Patient evaluation and analysis included sonography, standard diuretic and captopril renography, glomerular filtration rate, serum creatinine and blood pressure. The indications for surgery were symptoms, differential function below 35%, or a documented decrease of 10% or more during followup. Activation of the renin-angiotensin system was considered positive when split renal function decreased significantly by 5% or more in an obstructed system on a post-captopril study. The results of captopril renography were examined retrospectively in patients who required surgery according to preexisting criteria. Society for Fetal Urology hydronephrosis grade was II to IV in 8, 10 and 7 renal units, respectively. The renin-angiotensin system was activated in 8 of the 25 cases (32%) of unilateral ureteropelvic junction obstruction. In 15 patients there was no change on pre-captopril and post-captopril studies and in 2 split renal function on the obstructed side marginally increased on the post-captopril study. Surgical correction was required in only 6 of the 8 patients with renin-angiotensin system activation. Of those who required surgery hydronephrosis was grades II to IV in 3, 1 and in 2 patients, respectively. In the current study renin-angiotensin system activation correlated with the need for surgery in 75% of the cases of congenital unilateral ureteropelvic type hydronephrosis. Since captopril serves to identify patients who have renin-angiotensin system activation, it may also be possible to grade this activation. Our preliminary results show that there may be a role for captopril renography for identifying the risk group for surgical intervention.

Prognostic Significance of Captopril Renography for Managing Congenital Unilateral Hydronephrosis

Prognostic Significance of Captopril Renography for Managing Congenital Unilateral Hydronephrosis

Increased transforming growth factor-beta1 and tubulointerstitial fibrosis in rats with congenital hydronephrosis.

Most of our knowledge concerning renal obstruction has been derived from experimental animal models, and it is not yet well defined in spontaneous hydronephrosis. The aim of our study is to evaluate the roles of transforming growth factor-beta1 (TGF-beta1) and apoptosis in congenital hydronephrotic kidneys in comparison with experimental models. We made histological studies on kidneys from 6-week-old Wistar-Imamichi rats with congenital unilateral hydronephrosis as well as surgical models of complete or partial unilateral ureteral obstruction. The severity of hydronephrotic kidneys was evaluated on routine hematoxylin and eosin (H&E) stained sections, and the tubulointerstitial fibrosis analyzed morphometrically on Masson's trichrome stained sections. Renal tubular atrophy was assessed on periodic acid Schiff (PAS) stained sections, and tubular cell apoptosis assessed with TUNEL technique. The renal TGF-beta1 level was determined by a sandwich enzyme-linked immunosorbent assay (ELISA). We observed a significant loss of kidney weight with profound compensatory growth of the contralateral kidney in rats with congenital hydronephrosis. Most of the hydronephrotic kidneys were markedly enlarged with dilatation of the collecting system, renal parenchymal thinning, tubular atrophy, interstitial infiltration and fibrosis. The renal TGF-beta1 level was markedly elevated in hydronephrotic kidneys as compared with normal controls (326.01 +/- 30.64 pg/mg protein vs 227.81 +/- 11.07 pg/mg protein, P < 0.01). The tubular apoptotic score in hydronephrotic kidneys was also significantly higher than normal controls (2.17 +/- 0.50/HPF [high power field]vs 0.14 +/- 0.04/HPF, P < 0.01). The increased TGF-beta1 and apoptotic status paralleled the histological changes of tubulointerstitial fibrosis and tubular atrophy. Similar findings were also obtained in experimental obstructive models. In comparison with surgical models of partial and complete ureteral obstruction, our data provide solid morphological and molecular evidences of renal obstruction in rats with congenital hydronephrosis.

SUPRANORMAL DIFFERENTIAL RENAL FUNCTION IS REAL BUT MAY BE PATHOLOGICAL: ASSESSMENT BY 99mTECHNETIUM MERCAPTOACETYLTRIGLYCINE RENAL SCAN OF CONGENITAL UNILATERAL HYDRONEPHROSIS

It is unclear whether supranormal differential renal function of the hydronephrotic kidney is real or artifactual. We investigated the effect of clinical and renographic parameters on differential renal function. The study included 34 males and 10 females from 1 to 9 months old (median age 2.6 months) with unilateral congenital hydronephrosis. A 99mtechnetium (Tc) mercaptoacetyltriglycine (MAG3) scan was performed, and regions of interest were drawn on the kidneys, and perirenal and lateral backgrounds. Differential renal function was calculated with and without background subtraction at 30-second intervals from 0.5 to 3 minutes after injection of 99mTc-MAG3. The effects of age, sex, obstruction, site and size of the hydronephrotic kidney were analyzed using the generalized estimating equations method. There were 11 right and 33 left hydronephrotic kidneys. An obstructive renographic pattern was present in 33 cases. The trends of differential renal function according to intervals were different between kidneys with and without background subtraction, and differential renal function increased significantly as size increased (p <0.05). Differential renal function of the hydronephrotic kidney with an obstructive renographic pattern increased with time when perirenal or no background subtraction was applied (p <0.05). The effects of age, sex or laterality on differential renal function were not significant. Supranormal function (differential renal function 55% or greater) was present regardless of background subtraction methods and measurement time. Differential renal function is higher in larger hydronephrotic kidney but function of the kidney with an obstructive pattern is overestimated on later phases of 99mTc-MAG3 renal scan. Supranormal differential renal function is real and may be pathologic since it is prone to occur in larger obstructive hydronephrotic kidneys.