Use of methotrexate in older patients - A risk-benefit assessment

Methotrexate is eliminated almost entirely by the kidneys. The risk of methotrexate toxicity is therefore increased in patients with poor renal function, most likely as a result of drug accumulation. Declining renal function with age may thus be an important predictor of toxicity to methotrexate. Up to 60% of all patients who receive methotrexate for rheumatoid arthritis (RA) discontinue taking it because of adverse effects, most of which occur during the first year of therapy. Gastrointestinal complications are the most common adverse effects of methotrexate, but hepatotoxicity, haematological toxicity, pulmonary toxicity, lymphoproliferative disorders and exacerbation of rheumatic nodules have all been reported, Decreased renal function as a result of disease and/or aging appears to be an important determinant of hepatic, lymphoproli ferative and haematological toxicity, Concomitant use of low doses of folic acid has been recommended as an approach to limiting toxicity. Interactions between methotrexate and several nonsteroidal anti-inflammatory drugs have been reported, but they may not be clinically significant. However, caution is advised in the use of such combinations in patients with reduced renal function. More serious toxicities (e.g. pancytopenia) may result when other inhibitors of folate utilisation [e.g. cotrimoxazole (trimethoprim-sulfamethoxazole)] or inhibitors of renal tubular secretion (e.g. probenecid) are combined with methotrexate. Before starting low dose methotrexate therapy in patients with RA, a full blood count, liver function tests, renal function tests and chest radiography should be performed. Blood counts and liver function tests should be repeated at regular intervals. Therapeutic drug monitoring of methotrexate has also been suggested as a means of limiting toxicity. Patients with RA usually respond very favourably to low dose methotrexate therapy, and the probability of patients continuing their treatment beyond 5 years is greater than for other slow-acting antirheumatic drugs. Thus, given its sustained clinical utility and relatively predictable toxicity profile, low dose methotrexate is a useful addition to the therapy of RA.

Distribution of C-14 Cylindrospermopsin in vivo in the mouse

Radiolabelled C-14 cylindrospermopsin (CYN) has been prepared and used to investigate the distribution and excretion of CYN in vivo in male Quackenbush mice. At a dose of 0.2 mg/kg (i.e., approx. median lethal dose) the following mean (SID) urinary and faecal recoveries (cumulative) were obtained, respectively: (0-6 hours, n = 4) 48.2 (29.3)%, 11.9 (21.4)%; (0-12 hours, n = 12) 66.0 (27.1)%, 5.7 (5.6)%; (0-24 hours, n = 12) 68.4 (26.7)%, 8.5 (8.1)%. Mean (SD) recoveries from livers at 6 hours were 20.6 (6.4)% (n = 4), at 48 hours 13.1 (7.7)% (n = 8), and 5-7 days were 2.1 (2.1)% (n = 8). A substantial amount (up to 23%) can be retained in the liver for up to 48 hours with a lesser amount retained in the kidneys. The excretion patterns show substantial interindividual variability between predominantly faecal or urinary excretion, but these patterns are not related in any simple manner to the outcome in terms of toxicity. There is at least one methanol-extractable metabolite as well as a nonmethanol-extractable metabolite in the liver. The methanol-extractable metabolite was not found in the kidney and is more hydrophilic than CYN itself on reverse phase. (C) 2001 by John Wiley & Sons, Inc.

Reversal of cardiac and renal fibrosis by pirfenidone and spironolactone in streptozotocin-diabetic rats

1 Fibrosis leads to chronic impairment of cardiac and renal function and thus reversal of existing fibrosis may improve function and survival. This project has determined whether pirfenidone, a new antifibrotic compound, and spironolactone, an aldosterone antagonist, reverse both deposition of the major extracellular matrix proteins, collagen and fibronectin, and functional changes in the streptozotocin(STZ)-diabetic rat. 2 Streptozotocin (65 mg kg(-1) i.v.)-treated rats given pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone; approximately-200 mg kg(-1) day(-1) as 0.2-2g l(-1) drinking water) or spironolactone (50 mg kg(-1) day(-1) s.c.) for 4 weeks starting 4 weeks after STZ showed no attenuation of the increased blood glucose concentrations and increased food and water intakes which characterize diabetes in this model. 3 STZ-treatment increased perivascular and interstitial collagen deposition in the left ventricle and kidney, and surrounding the aorta. Cardiac, renal and plasma fibronectin concentrations increased in STZ-diabetic rats. Passive diastolic stiffness increased in isolated hearts from STZ-diabetic rats. Both pirfenidone and spironolactone treatment attenuated these increases without normalizing the decreased + dP/dt(max) of STZ-diabetic hearts. 4 Left ventricular papillary muscles from STZ-treated rats showed decreased maximal positive inotropic responses to noradrenaline, EMD 57033 (calcium sensitizer) and calcium chloride; this was not reversed by pirfenidone or spironolactone treatment. STZ-treatment transiently decreased GFR and urine flow rates in isolated perfused kidneys; pirfenidone but not spironolactone prevented the return to control values. 5 Thus, short-term pirfenidone and spironolactone treatment reversed cardiac and renal fibrosis and attenuated the increased diastolic stiffness without normalizing cardiac contractility or renal function in STZ-diabetic rats.

A comparison of the lateral and posterior retroperitoneoscopic approach for complete and partial nephroureterectomy in children

Objective To report the comparative results of a selective posterior or lateral retroperitoneoscopic approach (RPA) for nephroureterectomy in children. Patients and methods Following an established experience with RPA, 36 complete and 19 partial nephrouretectomies were prospectively randomized to a posterior and lateral retroperitoneoscopic approach. The patients were aged 4 months to 14 years, with a body weight at operation of 5.7-82 kg. For posterior RPA the child is positioned prone, with three access ports. The operating space was created with balloon dissection and maintained with CO2 insufflation. The child was then rotated 30 degrees with the kidney in the dependent position, and the operator and assistant standing on the affected side. In the lateral approach the child is in the lateral decubitus position with the operator and assistant facing the dorsal aspect of the patient. Results There was no significant difference in operative duration between the lateral and posterior approaches for nephrectomy (65 and 47 min) or partial nephrectomy (85 and 75 min). Two lateral nephrectomies required open conversion (one upper pole and one lower pole). Conclusion The posterior approach gives easy and quick access to the renal pedicle. It is preferable for complete nephrectomy alone and partial or polar excision. In children under 5 years old a near complete ureterectomy can be achieved. The lateral approach creates more inferomedial space, gives better access to ectopic kidneys and allows complete ureterectomy in all cases, Access to the pedicle in the normal position requires more frequent positioning of the kidney. Care must be taken as peritoneal tears are more common.

Renal cell carcinoma may adapt to and overcome anti-angiogenic intervention with thalidomide

Objective To report on the failure of thalidomide to inhibit tumour growth in an animal model of human renal cell carcinoma (RCC). Materials and methods An orthotopic xenograft model of human RCC was used in which tumour cells were implanted in the left kidney of male 'severe combined immunodeficient' mice. Thalidomide was administered by intraperitoneal injection and after 34 days the mice were killed. The extent of tumour growth was compared in treated and untreated mice. Total RNA was extracted from both tumour-affected and contralateral kidneys, and analysed by reverse transcription-polymerase chain reaction for various genes implicated in angiogenesis and metastasis in RCC. Results Thalidomide failed to inhibit the growth of xenograft tumours. The expression of angiogenic genes, e.g. vascular endothelial growth factor and fibroblast growth factor type 2 (FGF-2) within normal and tumour-affected kidney tissue was not reduced by thalidomide. Intratumoral transcription Of beta(3)-integrin, a critical component of angiogenesis, was significantly increased in response to thalidomide treatment (P

Role of complement C5 and T lymphocytes in pathogenesis of disseminated and mucosal candidiasis in susceptible DBA/2 mice

The aims of the study were to compare the pathogenesis of Candida albicans infection in various organs and anatomical regions of C5-deficient (DBA/2) and C5-sufficient (BALB/c) mice, and to evaluate the importance of complement C5 and T lymphocytes as factors that determine host susceptibility or resistance. The kidneys of DBA/2 mice showed higher colonisation and more severe tissue damage than those of BALB/c, but infection at other sites, including oral and vaginal mucosa, was generally similar in the two strains. Passive transfer of C5-sufficient serum into DBA/2 mice decreased the fungal burden in the kidney, and prolonged survival of the reconstituted animals. Depletion of CD4(+) and/or CD8(+) cells did not exacerbate either systemic or mucosal infection when compared to controls, and passive transfer of splenocytes from infected donors caused only a small and transient reduction in numbers of yeasts recovered from the kidney of sub-lethally infected recipients. It is concluded that the acute susceptibility of the kidneys in this mouse strain is due to C5 deficiency expressed on a susceptible genetic background. T lymphocytes, however, appear to have minimal influence on recovery from systemic infection with this isolate of C. albicans. (C) 2003 Elsevier Science Ltd. All rights reserved.

Facilitation of renal autoregulation by angiotensin II is mediated through modulation of nitric oxide

Aims: This study was designed to investigate the influence of angiotensin II (Ang II) and nitric oxide (NO) on autoregulation of renal perfusion. Methods: Autoregulation was investigated in isolated perfused kidneys (IPRK) from Sprague-Dawley rats during stepped increases in perfusion pressure. Results: Ang II (75-200 pM) produced dose-dependent enhancement of autoregulation whereas phenylephrine produced no enhancement and impaired autoregulation of GFR. Enhancement by Ang II was inhibited by the AT(1) antagonist, Losartan, and the superoxide scavenger, Tempol. Under control conditions nitric oxide synthase (NOS) inhibition by 10 muM N-omega-nitro-L-arginine methyl ester (L-NAME) facilitated autoregulation in the presence of non-specific cyclooxygenase (COX) inhibition by 10 muM indomethacin. Both COX and combined NOS/COX inhibition reduced the autoregulatory threshold concentration of Ang II. Facilitation by 100 pM Ang II was inhibited by 100 muM frusemide. Methacholine (50 nM) antagonised Ang II-facilitated autoregulation in the presence and absence of NOS/COX inhibition. Infusion of the NO donor, 1 muM sodium nitroprusside, inhibited L-NAME enhancement of autoregulation under control conditions and during Ang II infusion. Conclusions: The results suggest than an excess of NO impairs autoregulation under control conditions in the IPRK and that endogenous and exogenous NO, vasodilatory prostaglandins and endothelium-derived hyperpolarizing factor (EDHF) activity antagonise Ang II-facilitated autoregulation. Ang II also produced a counterregulatory vasodilatory response that included prostaglandin and NO release. We suggest that Ang II facilitates autoregulation by a tubuloglomerular feedback-dependent mechanism through AT(1) receptor-mediated depletion of nitric oxide, probably by stimulating generation of superoxide.

In vivo and in vitro models demonstrate a role for caveolin-1 in the pathogenesis of ischaemic acute renal failure

Caveolae and their proteins, the caveolins, transport macromolecules; compartmentalize signalling molecules; and are involved in various repair processes. There is little information regarding their role in the pathogenesis of significant renal syndromes such as acute renal failure (ARF). In this study, an in vivo rat model of 30 min bilateral renal ischaemia followed by reperfusion times from 4 h to 1 week was used to map the temporal and spatial association between caveolin-1 and tubular epithelial damage (desquamation, apoptosis, necrosis). An in vitro model of ischaemic ARF was also studied, where cultured renal tubular epithelial cells or arterial endothelial cells were subjected to injury initiators modelled on ischaemia-reperfusion (hypoxia, serum deprivation, free radical damage or hypoxia-hyperoxia). Expression of caveolin proteins was investigated using immunohistochemistry, immunoelectron microscopy, and immunoblots of whole cell, membrane or cytosol protein extracts. In vivo, healthy kidney had abundant caveolin-1 in vascular endothelial cells and also some expression in membrane surfaces of distal tubular epithelium. In the kidneys of ARF animals, punctate cytoplasmic localization of caveolin-1 was identified, with high intensity expression in injured proximal tubules that were losing basement membrane adhesion or were apoptotic, 24 h to 4 days after ischaemia-reperfusion. Western immunoblots indicated a marked increase in caveolin-1 expression in the cortex where some proximal tubular injury was located. In vitro, the main treatment-induced change in both cell types was translocation of caveolin-1 from the original plasma membrane site into membrane-associated sites in the cytoplasm. Overall, expression levels did not alter for whole cell extracts and the protein remained membrane-bound, as indicated by cell fractionation analyses. Caveolin-1 was also found to localize intensely within apoptotic cells. The results are indicative of a role for caveolin-1 in ARF-induced renal injury. Whether it functions for cell repair or death remains to be elucidated. Copyright (C) 2003 John Wiley Sons, Ltd.

ATP-dependent K+ channels in renal ischemia reperfusion injury

ATP-dependent K+ channels (K-ATP) account for most of the recycling of K+ which enters the proximal tubules cell via Na, K-ATPase. In the mitochondrial membrane, opening of these channels preserves mitochondrial viability and matrix volume during ischemia. We examined KATP channel modulation in renal ischemia-reperfusion injury (IRI), using an isolated perfused rat kidney (IPRK) model, in control, IRI, IRI + 200 muM diazoxide (a K-ATP opener), IRI + 10 muM glibenclamide (a K-ATP blocker) and IRI + 200 muM diazoxide + 10 muM glibenclamide groups. IRI was induced by 2 periods of warm ischemia, followed by 45 min of reperfusion. IRI significantly decreased glomerular filtration rate (GFR) and increased fractional excretion of sodium (FENa) (p < 0.01). Neither diazoxide nor glibenclamide had an effect on control kidney function other than an increase in renal vascular resistance produced by glibenclamide. Pretreatment with 200 muM diazoxide reduced the postischemic increase in FENa (p < 0.05). Adding 10 muM glibenclamide inhibited the diazoxide effect on postischemic FENa (p < 0.01). Histology showed that kidneys pretreated with glibenclamide demonstrated an increase in injure in the thick ascending limb of outer medulla (p < 0.05). Glibenclamide significantly decreased post ischemic renal vascular resistance (p < 0.05). but had no significant effect on other renal function parameters. Our results suggest that sodium reabsorption is improved by K-ATP activation and blockade of K-ATP channels during IRI has an injury enhancing effect on renal epithelial function and histology. This may be mediated through K-ATP modulation in cell and or mitochondrial inner membrane.

Kidney volume, blood pressure, and albuminuria: Findings in an Australian Aboriginal community

Background. Australian Aborigines are experiencing epidemic proportions of renal disease, marked by albuminuria and, variably, hematuria. They also have high rates of low birth weight, which have been associated with lower kidney volumes and higher blood pressures. The authors evaluated relationships between kidney volume, blood pressure, albuminuria, and hematuria in 1 homogeneous group. Methods Forty-three percent (672 of 1,560) of the population in a remote coastal Australian Aboriginal community aged 4.4 to 72.1 years participated in the study. Results: Kidney size correlated closely with body size. Systolic blood pressure (SBP) was correlated inversely with kidney length and kidney volume, after adjusting for age, sex, and body surface area (BSA); a 1-cm increase in mean kidney length was associated with a 2.2-mm Hg decrease in SBP, and a 10-mL increase in mean kidney volume was associated with a 0.6-mm Hg decrease in SBP (P = 0.001). Mean kidney volume explained 10% of the variance in SBP in a multivariate model containing age, sex, and BSA. In addition to higher SBP, adults who had the lowest quartiles of kidney volume also had the highest levels of overt albuminuria (P = 0.044). Conclusion: Smaller kidneys predispose to higher blood pressures and albuminuria in this population. The lower volumes possibly represent kidneys with reduced nephron numbers, which might be related to an adverse intrauterine environment. Susceptibility to renal disease could be a direct consequence of reduced nephron numbers; the higher blood pressures with which they are associated could also contribute to, as well as derive from, this association.

Carboplatin pharmacokinetics following a single-dose infusion in sulphur-crested cockatoos (Cacatua galerita)

Objective To determine the pharmacokinetics of carboplatin in sulphur-crested cockatoos, so that its use in clinical studies in birds can be considered. Design A pharmacokinetic study of carboplatin, following a single intravenous (IV) or intraosseus (10) infusion over 3 min, was performed in six healthy sulphur-crested cockatoos (Cacatua galerita). Procedure Birds were anaesthetised and a jugular vein cannulated for blood collection. Carboplatin (5 mg/kg) was infused over 3 min by the IV route in four birds via the contralateral jugular vein, and by the 10 route in two birds via the ulna. Serial blood samples were collected for 96 h after initiation of the infusion. Tissue samples from 11 organs were obtained at necropsy, 96 h after carboplatin administration. Total Pt and filterable Pt in plasma and tissue Pt concentrations were assayed by inductively coupled plasma-mass spectrometry. A noncompartmental pharmacokinetic analysis was performed on the plasma data. Results The mean +/- SD for the C-max of filterable Pt was 27.3 +/- 4.06 mg/L and in all six birds occurred at the end of the 3 min infusion, thenceforth declining exponentially over the next 6 h to an average concentration of 0.128 +/- 0.065 mg/L. The terminal half-life (T-1/2) was 1.0 +/- 0.17 h, the systemic clearance (CI) was 5.50 +/- 1.06 mL/min/kg and the volume of distribution (Vss) was 0.378 +/- 0.073 L/kg. The extrapolated area under the curve (AUC(0-x)) was 0.903 +/- 0.127 mg/mL.min; the area extrapolated past the last (6 h) data point to infinite time averaged only 1.25% of the total AUC(0-x). The kidneys had the greatest accumulation of Pt (7.04 +/- 3.006 mug/g), followed by the liver (3.08 +/- 1.785 mug/g DM). Conclusions and clinical relevance Carboplatin infusion in sulphur-crested cockatoos produced mild, transient alimentary tract signs and the Pt plasma concentration was similar whether carboplatin was given intravenously or intraosseously. Filterable plasma Pt concentrations for carboplatin persisted longer than for cisplatin, due mostly to the difference in systemic clearance between these drugs in sulphur-crested cockatoos. The distribution of tissue Pt after carboplatin administration was similar to that reported for cisplatin in sulphur-crested cockatoos. Despite anatomical, physiological and biochemical differences among animal species, the pharmacokinetic disposition of filterable Pt in the sulphur-crested cockatoo shares some features with the kinetics reported previously in other animals and human beings.

Oral glucose tolerance test in children and adolescents: Positives and pitfalls

Objectives: To describe the glycaemic status (assessed by an oral glucose tolerance test (OGTT)) and associated comorbidities in a cohort of Australian children and adolescents at risk of insulin resistance and impaired glucose homeostasis (IGH). Methods: Twenty-one children and adolescents (three male, 18 female) (18 Caucasian, one Indigenous, two Asian) (20 obese, one lipodystrophy) referred to the Paediatric Endocrinology and Diabetes Clinic underwent a 2-h OGTT with plasma glucose and insulin measured at baseline, + 60 and + 120 min. If abnormal, the OGTT was repeated. Results: The mean (SD) age was 14.2 (1.6) years, BMI 38.8 (7.0) kg/m(2) and BMI-SDS 3.6 (0.6). Fourteen patients had fasting insulin levels >21 mU/L. Type 2 diabetes mellitus was diagnosed in one patient, impaired glucose tolerance (IGT) in four patients and impaired fasting glycaemia (IFG) in one patient. Despite no weight loss, only one patient had a persistently abnormal OGTT on repeat testing. Three patients with IGH were medicated with risperidone at the time of the initial OGTT. One patient who had persistent IGT had continued risperidone. The other two patients had initial OGTT results of IGT and diabetes mellitus type 2. They both ceased risperidone between tests and repeat OGTT showed normal glycaemic status. Conclusions: Use of fasting glucose alone may miss cases of IGH. Diagnosis of IGT should not be made on one test alone. Interpretation of glucose and insulin responses in young people is limited by lack of normative data. Larger studies are needed to generate Australian screening recommendations. Further assessment of the potential adverse effects of atypical antipsychotic medication on glucose homeostasis in this at-risk group is important.

Indexes of insulin resistance and secretion in obese children and adolescents

OBJECTIVE - To assess the concurrent validity of fasting indexes of insulin sensitivity and secretion in - obese prepubertal (Tanner stage 1) children and pubertal (Tanner stages 2-5) glucose tolerance test (FSIVGTT) as a criterion measure. RESEARCH DESIGN AND METHODS - Eighteen obese children and adolescents (11 girls and 7 boys, mean age 12.2 +/- 2.4 years, mean BMI 35.4 +/- 6.2 kg/m(2), mean BMI-SDS 3.5 +/- 0.5, 7 prepubertal and I I pubertal) participated in the study. All participants underwent an insulin-modified FSIVGTT on two occasions, and 15 repeated this test a third time (mean 12.9 and 12.0 weeks apart). S-i measured by the FSIVGTT was compared with homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), fasting glucose-to-insulin ratio (FGIR), and fasting insulin (estimates of insulin sensitivity derived from fasting samples). The acute insulin response (AIR) measured by the FSIVGTT was compared with HOMA of percent beta-cell function (HOMA-beta%), FGIR, and fasting insulin (estimates of insulin secretion derived from fasting samples). RESULTS - There was a significant negative correlation between HOMA-IR and S-i (r = -0.89, r = -0.90, and r = -0.81, P < 0.01) and a significant positive correlation between QUICKI and S-i (r = 0.89, r = 0.90, and r = 0.81, P < 0.01) at each time point. There was a significant positive correlation between FGIR and S-i (r = 0.91, r = 0.91, and r = 0.82, P < 0.01) and a significant negative correlation between fasting insulin and S-i (r = -90, r = -0.90, and r = -0.88, P < 0.01). HOMA-beta% was not as strongly correlated with AIR (r = 0.60, r = 0.54, and r = 0.61, P < 0.05). CONCLUSIONS - HOMA-IR, QUICKI, FGIR, and fasting insulin correlate strongly with S-i assessed by the FSIVGTT in obese children and adolescents. Correlations between HOMA-β% FGIR and fasting insulin, and AIR were not as strong. Indexes derived from fasting samples are a valid tool for assessing insulin sensitivity in prepubertal and pubertal obese children.

Echocardiographic parameters in 14 healthy English Bull Terriers

Objective To determine the range of various cardiac parameters using echocardiography in apparently normal, healthy English Bull Terriers. Design Fourteen English Bull Terriers were selected for study. Cardiac auscultation of the parents of these dogs was normal. Echocardiographic examination of one parent of each animal showed: no mitral or aortic valve abnormalities; no myocardial lesions; no two dimensional evidence of fixed or dynamic left ventricular outflow tract obstruction; and no systolic aortic or left ventricular outflow tract turbulence on colour flow Doppler examination. The 14 selected dogs did not have arrhythmias or murmurs, and on echocardiographic examination had similar findings to their parents. Systolic blood pressure was measured in all dogs and they had no clinical evidence of Bull Terrier polycystic kidney disease or Bull Terrier hereditary nephritis. Procedure All dogs were auscultated and subjected to a sequential global echocardiographic assessment of the heart, including two dimensional long and short axis, and colour flow Doppler interrogation of the mitral and aortic valves. Dimensional measurements, including those from the left atrium, aortic annulus and left ventricle, were taken from a right parasternal window, and derived values such as fractional shortening, stroke volume and left atrial to aortic annulus ratio were calculated. Peak systolic aortic velocity was measured from the left parasternal window using two dimensional-guided pulsed wave Doppler with angle correction. Systolic blood pressure was measured using a Doppler monitor. The absence of Bull Terrier polycystic kidney disease was determined using renal ultrasonography, and of Bull Terrier hereditary nephritis using urinary protein to creatinine ratio. Results These 14 dogs had greater left ventricular wall thickness and smaller aortic root diameters than those reported as normal for other breeds of comparable body size. Left atrial dimensions were also larger, however this may have been due to the maximising method of measurement. These apparently normal English Bull Terriers also had higher aortic velocities than those reported for other breeds, possibly due to a smaller aortic root diameter or other anatomic substrate of the left ventricular outflow tract, lower systemic vascular resistance, or breed-specific normal left ventricular hypertrophy. While these dogs were selected to be as close to normal as possible, the breed may have a particular anatomy that produces abnormal left ventricular echocardiographic parameters. Conclusion These echocardiographic parameters may be used to diagnose left ventricular outflow tract obstruction and left ventricular hypertrophy, and inaccurate diagnoses may result if breed-specific values are not used.

Selective approach for transperitoneal and extraperitoneal endoscopic nephrectomy in children

Purpose: From the experience of a large combined series of transperitoneal. (TP) and retroperitoneal (RP) endoscopic complete and partial nephroureterectornies in children, we present a logical selective endoscopic approach to benign renal pathology. Materials and Methods: During a 5-year period 122 complete nephrectomies and nephroureterectomies (bilateral 2, invisible ectopic 8) and 63 partial nephroureterectomies for duplex (52 upper, 8 lower) or singleton polar disease (xanthogranulomatous pyelonephritis 1, cyst 2) were performed. Of the partial nephrectomies, ureterectomy, bladder repair and lower moiety reimplantation were performed in 8. Patient age ranged from 2.7 months to 14 years (mean 2.9 years). Preoperative weight ranged from 2.7 to 98 kg (mean 12.3). The position of the renal remnant, the presence or absence of a refluxing ureter and the need for ureterectomy were the major determining factors affecting choice of endoscopic approach. Results: A total of 179 (96.7%) procedures were successfully completed endoscopically. The 6 open conversions (3.2%) occurred early in our experience. The operating time reflected the complexity of the excision and lower urinary reconstruction (lateral and posterior RP 25 to 145 minutes [mean 921) TP with ureterocelectomy and bladder neck repair 105 to 355 minutes [mean 153]. Hospital stay for RP and simple TP was 1.5 days (mean 1 to 4) and for complicated TP 2 to 8 days (mean 3.5). Conclusions: We suggest a posterior retroperitoneal approach with isolated renal excision without extended ureterectomy. The lateral retroperitoneal approach allows complete ureterectomy as well as better exposure to horseshoe and pelvic kidneys and, therefore, avoids exposure to intraperitoneal. structures. Finally, the transperitoneal approach is recommended when complete moiety excision with lower urinary reconstruction is anticipated.