Endoscopic treatment of children with vesico-ureteric reflux.

Endoscopic subureteric injection of tissue-augmenting substances has become an alternative to long-term antibiotic prophylaxis and open surgery in the treatment of children with vesico-ureteric reflux. Successful elimination of reflux in about 80% of patients after a single injection (and in 90% after a repeat) has been achieved using the foreign-body non-degradable substances Teflon and silicone. Few patients have required open surgery and recurrence of reflux after initial successful treatment has occurred in only 5-10%. Concern has arisen, however, about possible distant migration and granuloma formation after injection of particulate plastic materials. Cross-linked bovine collagen is a biodegradable alternative substance, but with a lower response rate of 60% after the first treatment and a recurrence rate of 10-20%. Dextranomer in sodium hyaluronan is a new biological substance with microparticles with a response rate of 69% after the first injection. Biological substances have caused few complications. Present literature on injection treatment unfortunately focuses on elimination of reflux, with little attention to subsequent frequency of pyelonephritis or to the long-term development of the kidneys. Furthermore, there are no controlled, randomized studies with subureteric injection as one of the treatment alternatives. Thus, although having the advantage of being a minimally invasive procedure that can be performed on an outpatient basis, this technique needs to be tested in a large prospective study with the long-term renal outcome as the main end-point.

Relief of chronic partial ureteral obstruction attenuates salt-sensitive hypertension in rats.

AIM: The incidence of hydronephrosis due to ureteropelvic junction obstruction is approx. 0.5%. During the last decade, the management of non-symptomatic hydronephrosis has become much more conservative, but the long-term physiological consequences of this policy are not clear. Previously, we have shown that animals with chronic partial unilateral ureteral obstruction develop salt-sensitive hypertension. In this study, the effects of ipsilateral and contralateral nephrectomy and ureterovesicostomy on blood pressure were studied in hydronephrotic animals. METHODS: Partial unilateral ureteral obstruction was created in 3-week-old male Sprague-Dawley rats and blood pressure was measured telemetrically 4-6 weeks later during a normal and high salt diet before and after uninephrectomy or ureterovesicostomy. Plasma samples for renin assay were collected during both diets before and after ipsilateral nephrectomy. RESULTS: All hydronephrotic animals developed salt-sensitive hypertension, of different degrees. Before nephrectomy the plasma renin concentration was significantly higher in the hydronephrotic animals than in controls (160 +/- 15 microGU mL(-1) vs. 96 +/- 12 microGU mL(-1), respectively), but after the ipsilateral nephrectomy no differences were found between the groups. In the hydronephrotic animals both ipsilateral nephrectomy and ureterovesicostomy reduced the blood pressure and salt-sensitivity but the former still differed significantly from the controls. In contralaterally, nephrectomized hydronephrotic animals the salt-sensitive hypertension became more pronounced. CONCLUSION: Hydronephrosis in rats causes salt-sensitive hypertension that can be markedly reduced by removing the hydronephrotic kidney or relieving the obstruction by ureterovesicostomy. The mechanisms appear to be intrarenal and primarily located in the diseased kidney, but a secondary mechanism is also present.

Hydronephrosis causes salt-sensitive hypertension and impaired renal concentrating ability in mice.

AIM: Hypertension is a common disease in the industrialized world and approximately 5% of all cases are secondary to kidney malfunction. We have recently shown that hydronephrosis due to partial unilateral ureteral obstruction (PUUO) causes salt-sensitive hypertension in rats. The mechanisms are still unclear, but appear to be intrarenal and primarily located to the diseased kidney. In the present study, we have developed a model for PUUO to study if hydronephrotic mice develop salt-sensitive hypertension. METHODS: PUUO was created in 3-week-old mice (C57bl/6J). Blood pressure and heart rate were measured telemetrically in adult animals on normal and high salt diets. Metabolism cages were used to study the renal excretion of electrolytes and water. Plasma samples for renin analysis were collected and renal histological changes were evaluated. RESULTS: All hydronephrotic animals developed salt-sensitive hypertension that correlated to the degree of hydronephrosis. In hydronephrotic animals, blood pressure increased from 114 +/- 1 mmHg on normal salt diet to 120 +/- 2 mmHg on high salt diet, compared with 103 +/- 1 to 104 +/- 1 in controls. Hydronephrotic animals showed increased diuresis and reduced ability to regulate electrolyte concentration. No differences in plasma renin concentration were found between the groups. The parenchymal weight and glomerular area of contralateral kidneys were significantly increased in the hydronephrotic animals. Histopathology of the hydronephrotic kidneys displayed areas with fibrosis, inflammation and glomerular changes. CONCLUSION: This study provides a model for PUUO in mice and demonstrates the presence of salt-sensitive hypertension and an impaired renal concentrating ability in mice which has not been described before.

"Triple incision plasty". A convenient procedure for preputial relief.

Circumcision is the accepted operation to treat phimosis. However, when the purpose is to achieve retractility of a narrow foreskin to avoid further scarring and phimotic development after recurrent balanitis, a preputial plasty might be sufficient. Several methods with single or multiple incisions have been introduced throughout the years. None of them seems to have gained general acceptance. Single plasties tend to give cosmetically unsatisfactory results with an apparent cleft or deformity, while the multiple ones, where the deformity is more or less spread around the circumference, are not always easily done, at least not in children. Still, circumcision seems to remain the standard procedure for preputial relief. A simple technique, where three longitudinal incisions are transversely sutured, is described. It has been used in a series of 63 consecutive patients with good results, and seems to offer a good compromise between simplicity and cosmetical demands.

Renal blood flow increase during volume expansion in hydronephrotic rats.

PURPOSE: We assessed the renal blood flow pattern in experimental hydronephrosis during normal hydration and extracellular volume expansion. MATERIALS AND METHODS: Partial obstruction of the left ureter was created in 3-week-old Sprague-Dawley rats by embedding the ureter in a psoas muscle groove. Moderate hydronephrosis without kidney weight reduction developed in all cases. The effects on renal hemodynamics were studied with real-time ultrasound flowmetry 3 weeks later during normal hydration and then during volume expansion. The degree of hydronephrosis was classified as mild, moderate or severe. RESULTS: Under baseline conditions renal blood flow was normal in mild and moderate hydronephrosis but low in severe hydronephrosis. During volume expansion renal blood flow increased significantly in all experimental animals (mean 14%) compared to that in controls, which remained unaffected or decreased (mean -3%). The flow increase was related to the degree of dilatation, which was 2% in mild, 13% in moderate and 44% in severe hydronephrosis when the groups were considered separately. CONCLUSIONS: A significant increase in renal blood flow proportional to the degree of hydronephrosis occurred as a result of volume expansion. This finding may be explained by a state of vasodilatation combined with a reduction in the filtration coefficient.

Tubuloglomerular feedback in rats with chronic partial bilateral ureteral obstruction.

UNLABELLED: Rats with chronic partial unilateral ureteral obstruction (UUO) have a paradoxical resetting of the tubuloglomerular feedback (TGF) mechanism. During extracellular fluid volume expansion (VE) in control animals, a decrease in TGF sensitivity is normally noted. In rats with partial UUO, however, TGF sensitivity in the obstructed kidney was increased, associated with a relative reduction in single nephron glomerular filtration rate. In the present study, we examined the tubular and interstitial pressures, whole kidney function and the TGF system in rats with chronic partial bilateral ureteral obstruction. The rats were divided into preferentially ipsilaterally and preferentially contralaterally obstructed, as judged by pelvic volume. Measurements were performed both during hydropenia and during VE. During hydropenia TGF characteristics were the same in the 2 groups. During VE, however, TGF sensitivity was unchanged in the most obstructed kidneys (ipsilateral), while if the obstruction was preferentially contralateral, TGF-sensitivity decreased. This opposite change in TGF sensitivity resulted in higher electrolyte and water excretion from the least obstructed kidney. The change in TGF sensitivity was not correlated to renal interstitial pressure. IN CONCLUSION: rats with moderate chronic partial bilateral ureteral obstruction have an almost preserved function with regard to renal hemodynamics and excretion during hydropenia. During volume expansion, however, different responses were found in the least and most obstructed kidneys, with a decreased sensitivity of TGF in the least obstructed kidney, while TGF sensitivity was unchanged in the most obstructed kidney.

Effect of thromboxane and nitric oxide blockade on renal blood flow increase during volume expansion in hydronephrotic rats.

OBJECTIVE: It has recently been found that hydronephrotic rats, despite low diuresis, show a significant increase in renal blood flow (RBF) during volume expansion. The present experiments were designed to evaluate the mechanisms underlying this phenomenon. MATERIAL AND METHODS: Three-week-old Sprague-Dawley rats underwent partial obstruction of the left ureter using the Ulm-Miller psoas groove technique. The effects on RBF were studied 3 weeks later under general anesthesia using real-time ultrasound flowmetry, first during normohydration and then during extracellular volume expansion, in both untreated animals, and after prior blockade of either thromboxane or nitric oxide. RESULTS: Significant hydronephrosis developed in all cases. RBF was normal under control conditions. During volume expansion RBF increased significantly in untreated experimental animals (mean 7.5%). In contrast to this finding, RBF remained unchanged during volume expansion in both the thromboxane and nitric oxide blockade groups. CONCLUSION: It is concluded that a thromboxane- and/or nitric oxide-dependent RBF redistribution takes place in hydronephrotic kidneys during volume expansion.

Long-term followup of children treated with dextranomer/hyaluronic acid copolymer for vesicoureteral reflux.

PURPOSE: Dextranomer/hyaluronic acid copolymer is a novel substance that has favorable properties for endoscopic treatment of vesicoureteral reflux. We assess the long-term efficacy and safety of this treatment of children. MATERIALS AND METHODS: Children 1 to 15 years old with grade III or greater vesicoureteral reflux were eligible for enrollment in our study. All patients received endoscopic treatment with dextranomer/hyaluronic acid copolymer and were scheduled to have a voiding cystourethrogram 3 and 12 months after implantation. Children with reflux grade III or greater after treatment received up to 2 more implantations, and those with persistent reflux were referred for open surgery. In some cases long-term clinical followup was accompanied by a late voiding cystourethrogram. RESULTS: A total of 228 patients received endoscopic treatment. The efficacy population was comprised of 221 children, including 67 who received 2 and 8 who received 3 implantations. Endoscopic treatment was performed without complications in all cases. Patients were followed clinically for 2 to 7.5 years (mean 5). On the last voiding cystourethrogram 68% of patients had a positive response (grade I or less) and 81% had no dilating reflux. The corresponding results for treated ureters were 75% and 85%, respectively. Only 27 (12%) patients were referred for open surgery. A late voiding cystourethrogram was performed in 49 patients 2 to 5 years after treatment. Of the ureters free of reflux (grade 0) 3 to 12 months after treatment 96% remained free of dilating reflux. Adverse events occurred in association with implantation in only 2% of patients, although urinary tract infection subsequently developed in 8%. CONCLUSIONS: Endoscopic treatment with dextranomer/hyaluronic acid copolymer was effective and well tolerated in children with vesicoureteral reflux. Long-term followup indicated that there was no deterioration in patients responding positively to treatment.

Pressure flow measurement of hydronephrosis in children: a new approach to definition and quantification of obstruction.

PURPOSE: Hydronephrosis due to obstruction of the ureteropelvic junction is not uncommon in children. The critical level of outflow resistance characterizing obstruction remains to be established. It was previously found in our laboratory that the outflow resistance could be calculated in an animal model by servoregulating the infused flow to preset pressure levels. We determine whether this procedure is also feasible in patients with hydronephrosis. MATERIALS AND METHODS: A total of 46 patients with 48 hydronephrotic kidneys were examined. There were 32 boys and 14 girls with a diagnosis of hydronephrosis and suspected ureteropelvic junction obstruction who underwent a pressure flow study under general anesthesia for evaluation before possible surgery. The kidney was punctured percutaneously under ultrasonic guidance, and the study was performed under fluoroscopy. Flow levels were measured when steady state flow was achieved at pressures 5, 10, 15, 20, 25 and 30 mm. Hg greater than the intra-abdominal pressure. A conventional Whitaker test at an infusion rate of 10 ml. per minute was performed for comparison. The patient then underwent pyeloplasty if the kidney was considered obstructed. RESULTS: There were 2 patients excluded from evaluation because of significant leakage of contrast medium. Stable and repeatable recordings were obtained in all pressure flow studies but only in 7 of 46 Whitaker tests. A total of 41 kidneys were considered obstructed at pressure flow studies and operated on. The resistance was pressure dependent. Thus, mean resistance in the previous range 5 to 15 mm. Hg was considered a good overall measure of outflow resistance. Mean resistance less than 0.75 was normal and greater than 1.25 obstruction. There were 7 patients who had crossing vessels and a high mean resistance (3 or greater). CONCLUSIONS: The Whitaker test proved to be of no value for calculating the outflow resistance in ureteropelvic junction obstruction. The pressure flow study is superior to the Whitaker test for determining the outflow resistance and also allowing categorization of ureteropelvic junction obstruction.