Re-evaluation of kidney histopathology from 13-week toxicity and two-year carcinogenicity studies of melamine in the F344 rat: morphologic evidence of retrograde nephropathy.

The histopathologic changes induced in F344 rat kidney by oral administration of melamine for 13-week and 2-year periods in studies conducted by the National Toxicology Program, NIH,(25) from 1976 to 1983 have been re-evaluated and described in detail. A constellation of tubule changes extending from papilla to cortex consistently included tubule dilatation and tubule basophilia as salient features at the subchronic time point. By 2 years, these lesions had usually resolved into fibrotic scars, in which tubule loss and collagen deposition were prominent, running from superficial cortex into the medulla. These fibrotic lesions required discrimination from chronic scars resulting from infarcts and foci of chronic progressive nephropathy (CPN). A case is presented here for interpreting the constellation of histologic changes induced in rats by melamine as representing an ascending form of nephropathy. The term retrograde nephropathy is considered to be the appropriate nomenclature for both the acute and chronic lesions. The cause for the reflux, emanating from the lower urinary tract, appeared not to be infection as an inflammatory response was not prominent. It can be speculated that melamine precipitation in the lower urinary tract created pressure effects through transient obstruction leading to the renal changes. These changes were different from those involved in a major US outbreak of renal disease and death in cats and dogs associated with triazine-contaminated pet food, in which crystalluria from insoluble melamine/cyanuric acid complexes occurred in the kidney. However, the rat findings may be relevant to melamine-associated kidney disease recently reported in infants in China.

Trigonal injection of botulinum toxin-A does not cause vesicoureteral reflux in neurogenic patients.

AIMS: We evaluated the effect of botulinum toxin type A (BTX-A) injections in the trigone on the antireflux mechanism and evaluated its short-term efficacy. MATERIALS AND METHODS: Between April and December 2006, 21 patients (10 men and 11 women) were prospectively evaluated. All were incontinent due to refractory NDO and underwent detrusor injection of 300 units of BTX-A, including 50 units into the trigone. Baseline and postoperative evaluation after eight weeks included cystogram, urinary tract ultrasound and urodynamics. RESULTS: At baseline, 20 patients had no vesicoureteral (VUR) and one had grade II unilateral VUR. Postoperative evaluation revealed no cases of de novo VUR and the patient with preinjection VUR had complete resolution of the reflux. Ultrasound showed 5 (23.8%) patients with hydronephrosis before BTX-A injection and only one (4.8%) at the followup evaluation (p=0.066). After treatment, 9 (42.8%) patients became dry, 11 (52.4%) were improved and one (4.8%) had no improvement. Improved patients received antimuscarinic treatment and 8 (38.1%) became dry, with a final total continence rate of 80.1%. Cystometric capacity increased from 271+/-92 to 390+/-189 ml (p=0.002), reflex volume varied from 241+/-96 to 323+/-201 ml (p=0.020) and maximum detrusor pressure reduced from 66+/-39 to 38+/-37 cm H(2)O (p<0.001). CONCLUSIONS: Our results confirm the safety of trigone injections of BTX-A in terms of development of VUR and upper urinary tract damage. Whether they are beneficial for patients with NDO or other causes of voiding dysfunction will need further studies.

Treatment of complications of cyclophosphamide cystitis.

Since 1976, 23 patients with cyclophosphamide-induced cystitis were treated. These patients presented with a variety of urinary problems, including incontinence, hematuria and vesicoureteral reflux. Vesicoureteral reflux was found in 9 patients, hydronephrosis in 4 and a contracted fibrotic bladder in 3. Of the 23 patients 18 had undergone a combination of radiation and cyclophosphamide therapy. Based on this experience a general outline is developed for evaluation and treatment of patients with cyclophosphamide-induced cystitis and its potentially severe complications.

Management of severe reflux in the patient with cyclophosphamide cystitis.

Cyclophosphamide cystitis with a high grade of vesicoureteral reflux can lead to rapid renal deterioration. Conventional ureteral reimplantation is inadvisable and urinary diversion, although providing a temporary solution, could lead to long-term complications, particularly in children. We present a case of cyclophosphamide cystitis with vesicoureteral reflux and upper tract deterioration managed successfully with ileocecocystoplasty. This method of management should be considered early in such a patient.

Risk factors in the development of early technetium-99m dimercaptosuccinic acid renal scintigraphy lesions during first urinary tract infection in children.

AIM: To establish the variables that correlate with uptake defects in dimercaptosuccinic acid (DMSA) scintigraphy performed in the acute phase of a first episode of urinary tract infection (UTI). METHODS: A prospective observational study was conducted in a cohort of 158 consecutive children with a first episode of symptomatic UTI. The therapeutic delay time (TDT) was recorded. DMSA scintigraphy was performed in all children and voiding cystourethrography in 150 of them. RESULTS: 85% of the patients were younger than 2 y. Mean TDT was 33.5 h. The aetiological agent was Escherichia coli in 140 children. DMSA scintigraphy was normal in 81. Vesicoureteric reflux was detected in 33. After a multivariate logistic regression analysis the following variables were retained in the final model: TDT > or = 48 h, growth of bacteria other than E. coli, percentage of polymorphonuclear cells > or = 60% and C-reactive protein > or = 30 mg l(-1). CONCLUSION: TDT > or = 48 h, bacteria other than E. coli, percentage of polymorphonuclear cells > or = 60% and CRP > or = 30 mg l(-1) influence the findings detected in the DMSA scintigraphy performed in the acute phase of a first episode of UTI.

Unanticipated vesicoureteral reflux: a possible sequela of long-term thio-tepa instillations to the bladder.

Vesicoureteral reflux was studied by retrograde cystograms in 75 patients with recurrent transitional cell carcinoma of the bladder. Unilateral reflux was detected in 6 of the 14 patients (42.8 per cent) treated by transurethral resection of the bladder tumors. Five of these cases of reflux were anticipated and 1 was unanticipated. Among 61 patients treated by tumor resection and adjuvant instillations of thio-tepa reflux was found in 33 ureters of 25 patients (41.0 per cent). Of the 33 cases of reflux 15 were anticipated, while 18 were unanticipated. All the anticipated cases of reflux resulted from the direct effect of tumor resection on the ureteral orifice. The effect of thio-tepa on bladder mucosa and the ureteral orifices is suggested as a possible cause of the unanticipated cases of reflux.

Effects of formalin on bladder urothelium.

Formalin instillation into canine bladders was followed by serial radiographic and histologic evaluation. A generalized slough of epithelial tissue was seen with the deposition of an amorphous substance. Telangiectasia resulted in moderate bleeding. No ureterovesical junction obstruction was seen and reflux occurring in 60 per cent of the animals reverted to normal. Correlation with clinical experience is made.

An unusual complication of silver nitrate treatment of hemorrhagic cystitis: case report.

A patient with severe cyclophosphamide cystitis was treated with intravesical silver nitrate instillation to control bleeding. This resulted in apparent reflux and extravasation of the silver nitrate solution with secondary retroperitoneal inflammation. Subsequently, the patient required treatment for a small, fibrotic bladder with persistent reflux. The precautions and recommendations for treatment of such difficult patients are discussed.

Effect of prenatal ethanol administration on the urogenital system of mice.

The purpose of the present series of studies was to determine whether an obstruction in the urogenital system or vesicoureteral reflux (reflux, the retrograde passage of urine from the bladder into the kidney) existed in mice prenatally exposed to ethanol which might account for the high incidence of hydronephrosis and hydroureter observed. In order to examine these possibilities, indigo carmine was injected into the bladder of 19-day fetuses previously exposed to ethanol on Day 10 of gestation and the presence of hydronephrosis and/or reflux determined. As expected, we found a greatly increased incidence of hydronephrosis and hydroureter. In addition, there was a significant increase in reflux in the ethanol-treated mice. The incidence of reflux appeared to be related to the severity of the hydronephrosis observed, though cases of hydronephrosis without reflux and reflux without hydronephrosis were found. These data suggest both hypotheses may be salient and that a multiplicity of urogenital abnormalities are found following prenatal ethanol exposure.