Newer therapies and surgical management of ketamine-induced uropathy: A review.

BACKGROUND AND AIMS: Ketamine use as a recreational drug is becoming more popular nowadays. Ketamine-induced uropathy (KIU) is a late finding observed with long-term use of ketamine. A systematic review of Ketamine-Induced Uropathy was performed to emphasise its key clinical manifestations, mechanism of action and establish an effective treatment pathway. METHODS AND RESULTS: A literature search was conducted in MEDLINE via Pubmed and Cochrane using the keywords ketamine and bladder, ketamine and uropathy, and ketamine and epidemiology. The search strategy was limited to articles published from 2000 to 2023. Both animal and human studies were included. A total of 101 papers were reviewed based on topic relevance from the title and abstracts available. While ketamine is a controlled drug in the United Kingdom (UK) and other countries, 283 ketamine-related deaths have been reported in the UK. There is no definite pathogenesis but multiple potential mechanisms that cause KIU and its related symptoms. KIU involves chronic inflammation of the bladder, ureteral wall thickening, hydronephrosis and finally, chronic renal failure. A multidisciplinary approach is paramount when managing these patients to break the vicious cycle. The mainstay of medical and surgical treatment pathways is continued abstinence to prevent symptom relapse. This review included the pathophysiology, novel medical treatments and surgical management of KIU. CONCLUSION: KIU is a rare but significantly disabling condition often seen among ketamine abusers. With the rising trend in drug addiction, KIU is expected to be more common. Unfortunately, it is a late complication in chronic ketamine abusers and is only partially reversible even with abstinence. This review discusses this rare entity's newer medical treatments and surgical options.

Consistent alteration of chain length-specific ceramides in human and mouse fibrotic kidneys.

BACKGROUND: Several studies revealed alterations of single sphingolipid species, such as chain length-specific ceramides, in plasma and serum of patients with kidney diseases. Here, we investigated whether such alterations occur in kidney tissue from patients and mice suffering from renal fibrosis, the common endpoint of chronic kidney diseases. METHODS: Human fibrotic kidney samples were collected from nephrectomy specimens with hydronephrosis and/or pyelonephritis. Healthy parts from tumor nephrectomies served as nonfibrotic controls. Mouse fibrotic kidney samples were collected from male C57BL/6J mice treated with an adenine-rich diet for 14 days or were subjected to 7 days of unilateral ureteral obstruction (UUO). Kidneys of untreated mice and contralateral kidneys (UUO) served as respective controls. Sphingolipid levels were detected by LC-MS/MS. Fibrotic markers were analyzed by TaqMan® analysis and immunohistology. RESULTS: Very long-chain ceramides Cer d18:1/24:0 and Cer d18:1/24:1 were significantly downregulated in both fibrotic human kidney cortex and fibrotic murine kidney compared to respective control samples. These effects correlate with upregulation of COL1α1, COL3α1 and αSMA expression in fibrotic human kidney cortex and fibrotic mouse kidney. CONCLUSION: We have shown that very long-chain ceramides Cer d18:1/24:0 and Cer d18:1/24:1 are consistently downregulated in fibrotic kidney samples from human and mouse. Our findings support the use of in vivo murine models as appropriate translational means to understand the involvement of ceramides in human kidney diseases. In addition, our study raises interesting questions about the possible manipulation of ceramide metabolism to prevent progression of fibrosis and the use of ceramides as potential biomarkers of chronic kidney disease.

Risk of Renal Function Decline in Patients with Ketamine-Associated Uropathy.

Ketamine-associated diseases have been increasing with the rise in ketamine abuse. Ketamine-associated uropathy is one of the most common complications. We investigated the effects of ketamine-associated uropathy on renal health and determined predictors of renal function decline in chronic ketamine abusers. This retrospective cohort study analyzed 51 patients (22 with ketamine-associated hydronephrosis and 29 with ketamine cystitis) from Kaohsiung Veterans General Hospital in Taiwan. Primary renal outcome was end-stage renal disease or estimated glomerular filtration rate decline >30% from baseline. Compared with the ketamine cystitis group, the hydronephrosis group had lower initial and final estimated glomerular filtration rates and higher alkaline phosphatase and gamma-glutamyl transferase levels (p < 0.05). Elevated cholestatic liver enzyme levels correlated with renal dysfunction in ketamine-associated uropathy. The hydronephrosis group had a higher proportion of patients reaching endpoints than the ketamine cystitis group (50% and 7%, respectively, p < 0.001). After adjusting for age, sex, and initial serum creatinine level, hydronephrosis remained an independent risk factor for renal function deterioration. Ketamine-associated hydronephrosis was a poor renal outcome and strong predictor of renal function decline in chronic ketamine abusers. Elevated cholestatic liver enzyme levels correlated with the severity of ketamine-associated uropathy. Ultrasonography screening of these high-risk groups and regular renal function follow-ups are necessary.

Mechanisms of Developmental Toxicity of Dioxins and Related Compounds.

Dioxins and related compounds induce morphological abnormalities in developing animals in an aryl hydrocarbon receptor (AhR)-dependent manner. Here we review the studies in which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is used as a prototypical compound to elucidate the pathogenesis of morphological abnormalities. TCDD-induced cleft palate in fetal mice involves a delay in palatogenesis and dissociation of fused palate shelves. TCDD-induced hydronephrosis, once considered to be caused by the anatomical obstruction of the ureter, is now separated into TCDD-induced obstructive and non-obstructive hydronephrosis, which develops during fetal and neonatal periods, respectively. In the latter, a prostaglandin E2 synthesis pathway and urine concentration system are involved. TCDD-induced abnormal development of prostate involves agenesis of the ventral lobe. A suggested mechanism is that AhR activation in the urogenital sinus mesenchyme by TCDD modulates the wingless-type MMTV integration site family (WNT)/ß-catenin signaling cascade to interfere with budding from urogenital sinus epithelium. TCDD exposure to zebrafish embryos induces loss of epicardium progenitor cells and heart malformation. AHR2-dependent downregulation of Sox9b expression in cardiomyocytes is a suggested underlying mechanism. TCDD-induced craniofacial malformation in zebrafish is considered to result from the AHR2-dependent reduction in SRY-box 9b (SOX9b), probably partly via the noncoding RNA slincR, resulting in the underdevelopment of chondrocytes and cartilage.

Significance of AHR nuclear translocation sequence in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cPLA2α activation and hydronephrosis.

The aryl hydrocarbon receptor (AHR) plays a major role in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced toxicity phenotypes. TCDD bound to AHR elicits both genomic action in which target genes are transcriptionally upregulated and nongenomic action in which cytosolic phospholipase A2α (cPLA2α) is rapidly activated. However, how either of these actions, separately or in combination, induces toxicity phenotypes is largely unknown. In this study, we used AHRnls/nls mice as a model in which AHR was mutated to lack nuclear translocation sequence (NLS), and AHRd/- mice as the corresponding control. Using this model, we studied TCDD-induced alterations in cPLA2α activation and related factors because of the pivotal roles of cPLA2α both in AHR's nongenomic action and in regulation of causative genes of TCDD-induced hydronephrosis. Dams were orally administered TCDD at a dose of 300 µg/kg body weight on postnatal day 1, and pups subsequently exposed to TCDD via milk were examined for gene expression on PND 7 and for histological changes on PND 14. The activation of the AHR genomic action and hydronephrosis onset were observed in the control group but not in the AHRnls/nls group. An ex vivo experiment using peritoneal macrophages exposed to 100 nM TCDD resulted in rapid activation of cPLA2α, an indicator of the nongenomic action, only in the control group but not in the AHRnls/nls group. These results indicated that an NLS is required for the AHR's genomic and nongenomic actions.

The role of prostaglandin E2 receptor EP1 in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced neonatal hydronephrosis in mice.

Prostaglandin E2 (PGE2) is a critical factor in the pathogenesis of dioxin-induced neonatal hydronephrosis. Since the PGE2 receptor has four subtypes, EP1 - EP4, this study was aimed to challenge the hypothesis that at least one of the four subtypes is responsible for the pathogenesis of dioxin-induced hydronephrosis. To this end, we used mouse pups, with a C57BL/6 J background, genetically lacking EP1, EP2, or EP3, and wild-type pups in whom EP4 was suppressed by administering ONO-AE3-208 (ONO), an EP4 antagonist, from postnatal day 1 (PND 1) to PND 13. To expose the pups to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) via lactation, the dams were administered TCDD at an oral dose of 20 µg/kg on PND 1. The pups' urine and kidneys were collected on PND 14 for urinalysis and histological examination, respectively. We found that the incidence of hydronephrosis was 80% in the EP1+/+ group, but was markedly reduced to 28.6% in the EP1-/- group despite the fact that PGE2 concentration in the urine was similarly increased in the both groups. In contrast, the incidence of hydronephrosis was 80% and 100% in the EP2+/+ and EP2-/-groups, respectively, and 88.9% and 100% in the EP3+/+ and EP3-/- groups, respectively. With regard to EP4, the incidence of hydronephrosis in vehicle (saline)-treated groups and ONO-treated was 88.9% and 100%, respectively. Therefore, we concluded that among PGE2 receptor subtypes, EP1 plays a predominant role in the onset of TCDD-induced neonatal hydronephrosis in mouse pups.

Roles of cytosolic phospholipase A2α in reproductive and systemic toxicities in 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed mice.

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces a variety of toxicities upon binding of TCDD to aryl hydrocarbon receptor. Although this binding upregulates the synthesis of prostaglandins and their related lipid mediators via cytosolic phospholipase A2α (cPLA2α), toxicological significance of this signaling pathway remains elusive. Herein, we investigated the roles of cPLA2α in TCDD toxicities using cPLA2α-null mice. In a first set of experiments, pregnant mice were orally administered TCDD at a dose of 40 µg/kg on gestation day (GD) 12.5, and fetuses were collected on GD 18 for subsequent analyses. The number of live male fetuses of cPLA2α-null type was significantly less than that of wild-type in TCDD-exposed litters. TCDD-induced hydronephrosis was more severe in wild-type fetuses than in cPLA2α-null fetuses regardless of sex, and kidney expression levels of the inflammatory cytokines interleukin-1ß and tumor necrosis factor-α were increased in a cPLA2α-dependent manner in TCDD-exposed fetuses. In a second set of experiments, following intraperitoneal administration of TCDD at 50 µg/kg, body weight of the male adult mice was decreased within 2 days in wild-type mice but was not changed in cPLA2α-null mice. In addition, TCDD-induced lipid accumulation in the livers of cPLA2α-null mice was at an intermediate level compared with TCDD-exposed wild-type and vehicle-control mice. In conclusion, the present results show that cPLA2α is involved in TCDD-induced body weight loss, lipid accumulation in the liver, fetal hydronephrosis, and cytokine gene expression, and that the molecular basis of TCDD toxicity differs considerably between target tissues and life stages.

Clinical Assessment of Urinary Tract Damage during Sustained-Release Estrogen Supplementation in Mice.

Estrogen supplementation is a key component of numerous mouse research models but can adversely affect the urinary system. The goal of this study was to develop a clinical scoring system and identify biomarkers of occult urinary tract lesions prior to the development of systemic illness in mice. Ovariectomized or sham-surgery SCID mice were implanted subcutaneously with a placebo pellet or one containing sustained-release estradiol (0.18 mg 60-d release 17ß-estradiol). Mice were assessed twice weekly for 4 to 6 wk by using a clinical scoring system that included body condition, general activity, posture, hair coat, hydration, abdominal distension, urine staining of coat and skin, and ability to urinate. Samples were collected weekly for urinalysis, BUN, creatinine, and serum estradiol levels. Terminal samples were analyzed for histopathologic lesions. Compared with placebo controls, estradiolsupplemented mice had higher serum estradiol levels at weeks 2 and 3; significant differences in total clinical scores by the 3-wk time point; and in body condition, general activity, posture, hair coat, and urine staining scores by the 6-wk terminal time point. Urinary tract lesions included hydronephrosis, pyelonephritis, cystitis, and urolithiasis. All mice with urolithiasis had crystalluria, and 5 of the 6 mice with pyelonephritis or hydroureter had dilute urine (that is, specific gravity less than 1.030). However, these findings were not specific to mice with lesions. A total clinical score of 3.5 (maximum, 24) identified estradiol-supplemented mice with 83% specificity and 50% sensitivity, but no single clinical parameter, biomarker, or the total clinical score accurately predicted occult urinary tract lesions. Considering the lesions we observed, prudence is warranted when using pelleted sustained-release estradiol in mice, and important parameters to monitor for animal health include urine staining, body condition score, urine sediment, and urine specific gravity.

Polyuria-associated hydronephrosis induced by xenobiotic chemical exposure in mice.

Hydronephrosis is a commonly found disease state characterized by the dilation of renal calices and pelvis, resulting in the loss of kidney function in the severest cases. A generally accepted etiology of hydronephrosis involves the obstruction of urine flow along the urinary tract. In the recent years, we have developed a mouse model of hydronephrosis induced by lactational exposure to dioxin and demonstrated a lack of anatomical obstruction in this model. We also showed that prostaglandin E2 synthesis system plays a critical role in the onset of hydronephrosis. In the present study, we found that neonatal hydronephrosis was not likely to be associated with functional obstruction (impaired peristalsis) but was found to be associated with polyuria and low urine osmolality with the downregulation of proteins involved in the urine concentrating process. The administration of an antidiuretic hormone analog to the dioxin-exposed pups not only suppressed the increased urine output but also decreased the incidence and severity of hydronephrosis. In contrast to the case in pups, administration of dioxin to adult mice failed to induce polyuria and upregulation of prostaglandin E2 synthesis system, and the adult mice were resistant to develop hydronephrosis. These findings suggest the possibility that polyuria could induce hydronephrosis in the absence of anatomical or functional obstruction of the ureter. It is concluded that the present animal model provides a unique example of polyuria-associated type of hydronephrosis, suggesting a need to redefine this disease state.

[Bilateral hydronephrosis as a result of opioid-induced bowel spasm in a patient with an ileal conduit]. / Harnstauungsnieren beidseits infolge opiatinduzierter Darmspastik bei einer Patientin mit Ileumconduit.

A 47-year-old woman with spina bifida and an ileal conduit since childhood presented with left-sided flank pain, bilateral hydronephrosis and oliguria suspicious for a recurrent stenosis at the ureteral implantation site. Her history revealed a recent increase in her pain medication with opioids for treatment of neuropathic pain. After insertion of percutaneous nephrostomy on the left side and confirmation of the stenosis, open reimplantation of the ureter was already discussed with the patient. However after dose reduction of the opioid therapy hydronephrosis resolved. Thus opioid-induced bowel spasm was probably the cause for the obstruction.

Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study.

BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that has been shown to improve survival in two placebo-controlled phase 3 trials, and is approved for patients with metastatic castration-resistant prostate cancer. The objective of the TERRAIN study was to compare the efficacy and safety of enzalutamide with bicalutamide in patients with metastatic castration-resistant prostate cancer. METHODS: TERRAIN was a double-blind, randomised phase 2 study, that recruited asymptomatic or minimally symptomatic men with prostate cancer progression on androgen-deprivation therapy (ADT) from academic, community, and private health-care provision sites across North America and Europe. Eligible patients were randomly assigned (1:1) via an interactive voice response system to receive enzalutamide 160 mg/day or bicalutamide 50 mg/day, both taken orally, in addition to ADT, until disease progression. Patients were stratified by a permutated block method (block size of four), by whether bilateral orchiectomy or receipt of luteinising hormone-releasing hormone agonist or antagonist therapy started before or after the diagnosis of metastases, and by study site. Participants, investigators, and those assessing outcomes were masked to group assignment. The primary endpoint was progression-free survival, analysed in all randomised patients. Safety outcomes were analysed in all patients who received at least one dose of study drug. The open-label period of the trial is in progress, wherein patients still on treatment at the end of the double-blind treatment period were offered open-label enzalutamide at the discretion of the patient and study investigator. This trial is registered with ClinicalTrials.gov, number NCT01288911. FINDINGS: Between March 22, 2011, and July 11, 2013, 375 patients were randomly assigned, 184 to enzalutamide and 191 to bicalutamide. 126 (68%) and 168 (88%) patients, respectively, discontinued their assigned treatment before study end, mainly due to progressive disease. Median follow-up time was 20·0 months (IQR 15·0-25·6) in the enzalutamide group and 16·7 months (10·2-21·9) in the bicalutamide group. Patients in the enzalutamide group had significantly improved median progression-free survival (15·7 months [95% CI 11·5-19·4]) compared with patients in the bicalutamide group (5·8 months [4·8-8·1]; hazard ratio 0·44 [95% CI 0·34-0·57]; p<0·0001). Of the most common adverse events, those occurring more frequently with enzalutamide than with bicalutamide were fatigue (51 [28%] of 183 patients in the enzalutamide group vs 38 [20%] of 189 in the bicalutamide group), back pain (35 [19%] vs 34 [18%]), and hot flush (27 [15%] vs 21 [11%]); those occurring more frequently with bicalutamide were nausea (26 [14%] vs 33 [17%]), constipation (23 [13%] vs 25 [13%]), and arthralgia (18 [10%] vs 30 [16%]). The most common grade 3 or worse adverse events in the enzalutamide or bicalutamide treatment groups, respectively, were hypertension (13 [7%] vs eight [4%]), hydronephrosis (three [2%] vs seven [4%]), back pain (five [3%] vs three [2%]), pathological fracture (five [3%] vs two [1%]), dyspnoea (four [2%] vs one [1%]), bone pain (one [1%] vs four [2%]), congestive cardiac failure (four [2%] vs two [1%]), myocardial infarction (five [3%] vs none), and anaemia (four [2%] vs none]). Serious adverse events were reported by 57 (31%) of 183 patients and 44 (23%) of 189 patients in the enzalutamide and bicalutamide groups, respectively. One of the nine deaths in the enzalutamide group was thought to be possibly related to treatment (due to systemic inflammatory response syndrome) compared with none of the three deaths in the bicalutamide group. INTERPRETATION: The data from the TERRAIN trial support the use of enzalutamide rather than bicalutamide in patients with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer. FUNDING: Astellas Pharma, Inc and Medivation, Inc.

Bilateral hydronephrosis and cystitis resulting from chronic ketamine abuse.

Ketamine associated urinary dysfunction has become increasingly more common worldwide. Point-of-care ultrasound (POCUS) is an established modality for diagnosing hydronephrosis in the emergency department. We describe a case of a young male ketamine abuser with severe urinary urgency and frequency in which POCUS performed by the emergency physician demonstrated bilateral hydronephrosis and a focally thickened irregular shaped bladder. Emergency physicians should consider using POCUS evaluate for hydronephrosis and bladder changes in ketamine abusers with lower urinary tract symptoms. The mainstay of treatment is discontinuing ketamine abuse.

A mouse strain less responsive to dioxin-induced prostaglandin E2 synthesis is resistant to the onset of neonatal hydronephrosis.

Dioxin is a ubiquitous environmental pollutant that induces toxicity when bound to the aryl hydrocarbon receptor (AhR). Significant differences in susceptibility of mouse strains to dioxin toxicity are largely accounted for by the dissociation constant of binding to dioxins of AhR subtypes encoded by different alleles. We showed that cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1), components of a prostanoid synthesis pathway, play essential roles in the onset of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced hydronephrosis of neonatal mice. Although C57BL/6J and BALB/cA mice harbor AhR receptors highly responsive to TCDD, they were found by chance to differ significantly in the incidence of TCDD-induced hydronephrosis. Therefore, the goal of the present study was to determine the molecular basis of this difference in susceptibility to TCDD toxicity. For this purpose, we administered C57BL/6J and BALB/cA dams' TCDD at an oral dose of 15 or 80 µg/kg on postnatal day (PND) 1 to expose pups to TCDD via lactation, and the pups' kidneys were collected on PND 7. The incidence of hydronephrosis in C57BL/6J pups (64%) was greater than in BALB/cA pups (0%, p < 0.05), despite similarly increased levels of COX-2 mRNA. The incidence of hydronephrosis in these mouse strains paralleled the levels of renal mPGES-1 mRNA and early growth response 1 (Egr-1) that modulates mPGES-1 gene expression, as well as PGE2 concentrations in urine. Although these mouse strains possess AhR alleles tightly bound to TCDD, their difference in incidence and severity of hydronephrosis can be explained, in part, by differences in the expression of mPGES-1 and Egr-1.

Predominant role of cytosolic phospholipase A2α in dioxin-induced neonatal hydronephrosis in mice.

Hydronephrosis is a common disease characterized by dilation of the renal pelvis and calices, resulting in loss of kidney function in the most severe cases. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces nonobstructive hydronephrosis in mouse neonates through upregulation of prostaglandin E2 (PGE2) synthesis pathway consisting of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) by a yet unknown mechanism. We here studied possible involvement of cytosolic phospholipase A2α (cPLA2α) in this mechanism. To this end, we used a cPLA2α-null mouse model and found that cPLA2α has a significant role in the upregulation of the PGE2 synthesis pathway through a noncanonical pathway of aryl hydrocarbon receptor. This study is the first to demonstrate the predominant role of cPLA2α in hydronephrosis. Elucidation of the pathway leading to the onset of hydronephrosis using the TCDD-exposed mouse model will deepen our understanding of the molecular basis of nonobstructive hydronephrosis in humans.

Peroxiredoxin I protein, a potential biomarker of hydronephrosis in fetal mice exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

OBJECTIVE: In previous studies, we established an animal model of human congenital hydronephrosis with exposure of developing mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), but the etiopathogenesis is not entirely clear. The present study was to identify the changes that may be involved in the etiology at the protein level. METHODS: C57BL/6J mice fetuses were treated with TCDD. Comparative proteomic analysis was adopted to identify the proteins associated with hydronephrosis induced by TCDD. RESULTS: Two-dimensional electrophoresis display revealed that 19 protein spots were differentially expressed in the upper urinary tract tissues in fetal mice after exposure to TCDD. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) identified 12 up-regulated proteins: peroxiredoxin I (Prx I), cadherin 6, gamma-actin, radixin, desmin, type II transforming growth factor-beta receptor, chromogranin B, serum albumin precursor, transferrin, hypothetical protein LOC70984, lipk protein, and zinc finger protein 336. Histochemical staining indicated that Prx I protein was positively expressed in the ureteric epithelium in the treated group, and not in the control group, which is consistent with MALDI-TOF-MS. CONCLUSION: Prx I protein may be a potential biomarker or responsive protein of hydronephrosis in fetal mice induced by TCDD.

The ameliorative effect of various antioxidants on Adriamycin-induced fetal renal abnormalities.

OBJECTIVE: To examine the efficacy of nine antiapoptotic compounds in preventing the development of Adriamycin-induced fetal renal abnormalities or ameliorating the resultant renal damage in a rat model. METHODS: Thirty-three Sprague-Dawley rats were randomly divided into sham-control, Adriamycin and prevention groups. The prevention group was divided into 9 subgroups. The rats were time mated and experimental rats were injected with Adriamycin on gestational day 7-9. Sham-control rats were injected with saline on the same days. The preventive medications were administered to the prevention group from 7 days prior to mating to the end of pregnancy. Samples were prepared from fetuses for histological and biochemical analyses. RESULTS: A total of 331 fetuses were recovered. There were no resorptions in the Deferoxamine, Amifostine and sham-control groups. Significant decrease of antioxidant activities was noted in the Adriamycin group compared to the sham-control group. In all prevention groups, antioxidant activities were significantly increased compared to the Adriamycin group. The highest rate of hydronephrosis was observed in the Adriamycin group (82%). The lowest rates of renal abnormalities were noted with Deferoxamine and Amifostine: 8% and 11%. CONCLUSION: Oxidant injury plays a critical role in the development and progression of Adriamycin-induced fetal renal abnormalities. Some antiapoptotic medications, notably Deferoxamine and Amifostine, may have preventive and therapeutic potential in the management of fetal renal abnormalities.

Critical role of microsomal prostaglandin E synthase-1 in the hydronephrosis caused by lactational exposure to dioxin in mice.

Hydronephrosis induced in the kidney of neonatal mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) via lactation is a sensitive and characteristic hallmark of TCDD teratogenicity. We previously found that cyclooxygenase-2 (COX-2) activity induced in mouse neonate kidneys by lactational TCDD exposure is required for this toxicity. COX-2 is an inducible form of cyclooxygenase and is responsible for producing prostaglandins (PGs) and thromboxane. PGE(2), a prostaglandin, is elevated in TCDD-exposed mouse pups. In this study, we investigated the role of microsomal prostaglandin E synthase-1 (mPGES-1), an inducible form of PGE(2) synthase, in TCDD-induced hydronephrosis. A dose of 10 µg TCDD/kg to dams increased mPGES-1 messenger RNA abundance, urinary PGE(2) levels, and the incidence of hydronephrosis in mPGES-1 wild-type pups. In homozygous mPGES-1 knockout (KO) mice, in contrast, TCDD-induced hydronephrosis was suppressed, demonstrating an essential role of mPGES-1 in the response. Lack of the mPGES-1 gene also suppressed urinary PGE(2) level to near the basal level in TCDD-exposed pups. In conclusion, mPGES-1 upregulation upon lactational TCDD exposure is a causal factor for TCDD-induced hydronephrosis in mouse neonates.

Hydronephrosis after embolization of internal iliac artery aneurysms.

The treatment of internal iliac artery aneurysms is aimed at the prevention of rupture. Traditionally, this is undertaken surgically; however, endovascular techniques are an acceptable alternative and these techniques are also not without complication. Herein, the authors describe the endovascular treatment of two patients with internal iliac aneurysms. Although the treatments were initially successful, both patients presented with ureteric obstruction and hydronephrosis 2 months later.

[Comparative analysis of the role of individual peculiarities of kidney structure in predisposition to the nephrotoxicity of gentamicin in intact and hydronephrotic rabbits].

Comparative analysis of relationships between individual peculiarities of the structure of nephrons in intact and hydronephrotic right rabbit kidneys, on one hand, and the degree of expression of nephrotoxicity of gentamicin with respect to the only intact and as well hydronephrotic left kidney, on the other hand, was undertaken. Damage of the kidney by this antibiotic is more expressed in rabbits with smaller diameter of distal convoluted tubules of nephrons and smaller size of the cells lining their lumen. These peculiarities of the structure of nephrons lead to predisposition to the gentamicin-induced nephropathy in intact rabbits to a higher degree than in animals with hydronephrosis. The method of predicting individual predisposition to gentamicin-induced nephropathy has been patented (No. 7722 of 13.10.2005).