Inhibition of oxalate nephrolithiasis with Ammi visnaga (AI-Khillah)

We investigated the effect of Ammi visnaga seeds on experimentally – induced kidney stones – in male Wistar albino rats. Oxalate nephrolithiasis was experimentally induced by 3% glycolic acid (added in their diet) given for the period of four weeks. A highly significant amount of deposits were found in the kidneys, which were analyzed quantitatively. These deposits were mainly of calcium oxalate in composition.Daily oral (gavage) treatment with Ammi visnaga (500 mg/kg) highly reduced the incidence of nephrolithiasis (calcium oxalate deposition in the kidneys). Ammi visnaga seeds extract showed highly potent diuretic activity. The reduction in body weight, increase in kidneys weight, increase in water intake, decrease in urine output found in glycolic acid control group were prevented to various extent on Ammi visnaga treatment; and the values became to insignificant difference with control group. The changes in weights of liver, heart and lungs of the three groups were insignificant. Uraemia and hyperbilirubinaemia observed in glycolic acid control group were found to be ameliorated by Ammi visnaga seed extract treatment.     

High iron storage levels are associated with increased DNA oxidative injury in patients on regular hemodialysis

Background Accumulating evidence suggests that oxidative stress is enhanced in patients on regular hemodialysis (HD). Iron supplementation is essential for the treatment of renal anemia, but there is a possibility that it could enhance oxidative stress by inducing the Fenton reaction. Here, we report our investigation of the relation between iron storage and DNA oxidative injury in HD patients.Methods The study subjects were 48 patients on regular HD (age, 62.7 ± 12.1 years; HD duration, 67.2 ± 62.5 months; non-diabetic/diabetic; 22:26). Patients who were positive for hepatitis C virus antibody (HCV Ab), or hepatitis B surface antigen (HBsAg), and those with inflammatory or malignant diseases were excluded. The serum 8-hydroxy-2′-deoxyguanosine (8-OHdG) level, a marker of DNA oxidative injury, was measured before the first HD session of the week in all patients, and factors associated with high serum 8-OHdG were investigated. In 9 patients with a serum ferritin level of more than 1000 ng/ml at study entry, serum 8-OHdG levels were followed up for 6 months in the absence of iron supplementation.Results Multivariate analysis showed that the serum ferritin level was a significant and independent determinant of serum 8-OHdG, and serum ferritin correlated significantly with the total dose of iron supplementation during the 6-month period of the study. In the nine patients, without iron supplementation, serum 8-OHdG levels, as well as serum ferritin, decreased significantly during follow-up.Conclusions Our results suggest that increased iron storage may induce DNA oxidative injury in patients on regular HD, and that the serum ferritin level is a surrogate marker for this pathological condition.     

Urinary inhibitors of crystallization in hypercalciuric children with hematuria and nephrolithiasis

Urinary inhibitors are suggested to play a significant role in reducing crystallization in calcium (Ca) stone former and idiopathic hypercalciuria (IH). Urinary inhibitors such as magnesium (Mg), citrate, and glycosaminoglycans (GAGs) were evaluated, as well as urinary Ca and creatinine (Cr), in IH children with nephrolithiasis (LIT) or with hematuria plus IH (HEM) and were compared with a control group. The mean 24-h urinary excretion of Mg was similar in all groups. However, the urine Ca/Mg ratio was significantly increased (P <0.005) in LIT and HEM groups. A higher mean value for GAGs and citrate was found in the HEM group, but a very low level of GAGs (less than 60% of the normal value) and citrate (less than 30% of the normal value) was found in the LIT group. These data suggest that, despite a high urinary Ca excretion (3.6±0.1 mg/kg per day) in the HEM group, elevated urinary GAGs (32.0±1.0 mg/g Cr) and a normal urinary citrate (428.7±62.3 mg/24 h) excretion may prevent Ca crystallization and thus renal stones. In contrast, in the LIT group low urinary GAG (10.3±0.9 mg/g Cr) and citrate (235.2±52.3 mg/24 h) excretion may precipitate stone formation in the presence of a high urinary Ca excretion. Thus, it is reasonable to suggest that patients with hematuria and IH may not develop overt renal stone due to the presence of normal levels of renal stone inhibitors. Received October 30, 1995; accepted December 15, 1995     

Taurine protected kidney from oxidative injury through mitochondrial-linked pathway in a rat model of nephrolithiasis

Hyperoxaluria and crystal deposition induce oxidative stress (OS) and renal epithelial cells injury, both mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase are considered as the main sources of reactive oxygen species (ROS). Taurine is known to have antioxidant activity and shows renoprotective effect. We investigate the effect of taurine treatment on renal protection, and the putative source of ROS, in a rat model of calcium oxalate nephrolithiasis. Rats were administered with 2.5% (V/V) ethylene glycol + 2.5% (W/V) ammonium chloride (4 ml/day), with restriction on intake of drinking water (20 ml/day) for 4 weeks. Simultaneous treatment with taurine (2% W/W, mixed with the chow) was performed. At the end of the study, indexes of OS and renal injury were assessed. Renal tubular ultrastructure changes were analyzed under transmission electron microscopy. Crystal deposition in kidney was scored under light microscopy. Angiotensin II in kidney homogenates was determined by radioimmunoassay. Expression of NADPH oxidase subunits p47phox and Nox-4 mRNAs in kidney was evaluated by real time-polymerase chain reaction. The data showed that oxidative injury of the kidney occurred in nephrolithiasis-induced rats. Hyperplasia of mitochondria developed in renal tubular epithelium. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in mitochondria decreased and the mitochondrial membrane showed oxidative injury. Taurine treatment alleviated the oxidative injury of the kidney, improved SOD and GSH-Px activities, as well as the mitochondrial membrane injury, with lesser crystal depositions in the kidney. We could not detect statistical changes in the renal angiotensin II level, and the renal p47phox and Nox-4 mRNAs expression in those rats. The results suggest that mitochondria but not NADPH oxidase may account for the OS and taurine protected kidney from oxidative injury through mitochondrial-linked pathway in this rat model.     

Low bone density in children with hypercalciuria and/or nephrolithiasis

The objective of this study was to identify how many children with hypercalciuria and/or nephrolithiasis have a low bone density and whether the risk of low bone density can be identified by 24-h urine stone-risk profiles and/or growth parameters. A retrospective chart review was performed on 110 idiopathic hypercalciuria and/or kidney stone patients who received both a 24-h urine for stone-risk profile and a dual-energy X-ray densitometry scan. Patients were divided into low bone density vs. normal bone density groups and hypercalcuria verus nephrolithiasis groups and analyzed for differences in growth parameters, urine stone-risk profiles, and bone densities. Overall, 47% had a bone density z score < −1, and 26% had a bone density z score < −2. Patients with a low bone density had a higher body mass index and lower urine creatinine and ammonium than those with a normal bone density. Patients with nephrolithiasis had a lower bone density z score than patients with hypercalcuria and no nephrolithiasis. Clinicians should be aware of the increased incidence of low bone density in children with hypercalciuria and nephrolithiasis. The effect of hypercalciuria and nephrolithiasis treatment on bone density and the natural progression of the bone density in the studied patient population warrants further investigation.     

Effect of repeated intravenous iron administration in haemodialysis patients on serum 8-hydroxy-2'-deoxyguanosine levels.

BACKGROUND: Iron supplementation is a mainstay for management of renal anaemia in patients receiving haemodialysis (HD). Although it is well known that a single intravenous iron (IVIR) administration transiently enhances oxidative stress in HD patients, the consequence of repeated IVIR administration is still unknown. This study aims to clarify the time course of changes in serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative injury, during a period of repeated IVIR administration in HD patients. METHODS: Twenty-seven patients (62+/-14 years and 23 males) on long-term HD participated in this study. All patients had been on HD more than 6 months and none had received a blood transfusion or iron therapy in previous 6 months. The patients were divided into three groups according to the baseline haematocrit (Ht) and serum ferritin (FTN) levels as a marker of body iron stores: IVIR group (Ht<30% and FTN<100 ng/ml; n=7); High FTN group (Ht>or=30% and FTN>or=100 ng/ml; n=11); and low FTN group (Ht>or=30% and FTN<100 ng/ml; n=9). The IVIR group patients received 40 mg of ferric saccharate i.v. after each HD session until Ht increased by 5%. Serum 8-OHdG and other parameters were prospectively monitored for 10 weeks. RESULTS: At baseline, the serum ferritin level was independently associated with 8-OHdG in a multiple regression model (total adjusted R2=0.47, P<0.01). All patients in the IVIR group achieved the target Ht level during the study. IVIR administration resulted in significant increases in 8-OHdG levels (0.22+/-0.07-0.50+/-0.16 ng/ml: baseline to 10 week) as compared with both the high FTN group (0.52+/-0.20-0.58+/-0.28 ng/ml) and the low FTN group (0.39+/-0.11-0.36+/-0.11 ng/ml) (ANOVA for repeated measures P<0.01). Additionally, serum 8-OHdG and serum ferritin changed in the same manner. CONCLUSIONS: Repeated IVIR administration for HD patients was associated with signs of increased oxidative DNA injury, as reflected by increased serum levels of 8-OHdG. As these changes were accompanied by increased serum ferritin levels, excess body iron stores might play an important role in oxidative stress.     

Urinary marker for oxidative stress in kidneys in cisplatin-induced acute renal failure in rats.

BACKGROUND: Establishment of non-invasive urinary biomarkers for the prediction of acute renal failure (ARF) is important. We evaluated whether urinary oxidative stress markers reflect intrarenal oxidative stress in cisplatin (CDDP)-induced ARF, and whether these markers can be used for the prediction of future ARF. METHODS: Urinary malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured up to day 14 post-CDDP (6 mg/kg) injection in rats. MDA and 8-OHdG expressions were examined in kidneys. RESULTS: CDDP induced an increase in serum creatinine (Scr), blood urea nitrogen (BUN), and tubular damage at day 5, increased urinary MDA excretion and MDA expression in kidneys at day 1 (but returned to basal values by day 3), increased urinary excretion of 8-OHdG at day 5 till day 14 (though the number of 8-OHdG-positive tubular cells increased at day 5 and then gradually decreased). Urinary MDA levels at day 1 correlated significantly with Scr (rho = 0.721, P < 0.01) and tubular damage score (rho = 0.840, P < 0.01) at day 5. CONCLUSION: Our findings demonstrated divergent changes of urinary oxidative stress markers in CDDP-induced ARF, and suggested that urinary MDA may be a useful marker for the prediction of the development of CDDP-induced ARF.     

High perirenal fat thickness predicts a greater risk of recurrence in Chinese patients with unilateral nephrolithiasis

IntroductionThe aim of this study was to evaluate the association between recurrence-free survival (RFS) and perirenal fat thickness (PFT) in a cohort of Chinese population with unilateral nephrolithiasis.MethodsWe retrospectively reviewed the medical records of 81 patients with unilateral nephrolithiasis in our center from January 2019 to June 2019. PFT measured on computed tomography (CT) scans was evaluated. Kaplan-Meier curves and log-rank tests were used to assess significant differences in RSF between high-PFT and low-PFT groups within sexes. Univariable and multivariable Cox regression analyses were used to evaluate the potential risk factors for renal stone recurrence.ResultsHigh PFT was significantly associated with high BMI and hyperlipidemia (p = .003 and.047, respectively). The PFT of stone-bearing kidney was significantly greater than PFT of non-stone-bearing kidney (0.77 ± 0.60 cm vs. 0.67 ± 0.58 cm, p = .002) . During the follow-up periods (median 31 months), 21 (25.9%) patients experienced ipsilateral renal stone recurrence. In addition, Kaplan–Meier survival curves showed that patients with low PFT had a significant better RFS than those with high PFT (p = .012). In the univariable Cox analyses, male sex and high PFT were significantly associated with a poor RFS (p = .042 and .018, respectively). Moreover, both male sex and high PFT retained significance in the multivariable analyses (p = .045 and .020, respectively).ConclusionsOur findings suggested that PFT is a noninvasive and feasible parameter, which may help in the risk stratification of renal stone recurrence in the follow-up periods.     

Crystallization conditions in urine of patients with idiopathic recurrent calcium nephrolithiasis and with hyperparathyroidism

Summary (1) The highest degree of urinary supersaturation with respect to calcium oxalate monohydrate (COM) and brushite at which secondary nucleation and growth of small amounts of COM and hydroxyapatite (HAP) are inhibited was determined by new and simple methods. There were 39 subjects who produced 24 h-urine collections 11 idiopathic stone formers (ISF), 12 patients suffereing from primary hyperparathyroidism (HPT) and 16 healthy controls (HC). These subjects had a moderate calcium and low oxalate intake. The results obtained were compared with the state of urinary saturation and with urine chemistry. The measurements of crystallization conditions with respect to COM were repeated in 26 subjects (11 ISF, 5 HPT, 10 HC) after a dietary oxalate load. (2) In 24 h-urines of HC diluted to 2.4 1/24 h the degree of supersaturation necessary to induce crystallization of COM and HAP was 2–5 times higher than the state of urinary saturation measured under the same test conditions. (3) ISF showed a decreased pyrophosphate concentration and a decreased inhibitory activity to HAP crystallization in their 24 h-urine. (4) The urinary inhibitory activity towards crystallization of HAP showed a positive correlation to urinary pyrophosphate concentration. (5) In the 24 h-urine of HPT hypercalciuria and increased saturation with respect to brushite which reached values to induce HAP crystallization were found. (6) After a dietary oxalate load urinary supersaturation with respect to COM reached values to induce COM crystallization in ISF and HPT but not in HC.Abbreviations COM Calcium oxalate monohydrate - CP Concentration product - CPR Concentration product ratio - HAP Hydroxy apatite - HC Healthy controls - HPT Patients suffereing from primary hyperparathyroidism - ISF Idiopathic stone formers     

维生素K对肾结石患者尿抑制作用的影响

为了解维生素Ｋ在尿石形成中作用，用超滤法分离正常人和草酸钙肾结石患者尿中大分子物；结合草酸耐受试验，检测肾结石患者应用维生素Ｋ前后尿不同分子量物质的草酸耐受量。结果：正常人及肾结石患者尿分子量１００００～３００００大分子物草酸耐受量最高；肾结石患者较正常人草酸耐受量低（分别为２．７２±０．７４ｍｌ和３．７５±０．３５ｍｌ，Ｐ＜０．０５）；肾结石患者应用维生素Ｋ后尿１００００～３００００大分子物草酸耐受量增加（３．１９±０．５７ｍｌ，Ｐ＜０．０５）。提示尿中草酸钙结石抑制物主要为分子量１００００～３００００的大分子物，维生素Ｋ应用后明显改善肾结石患者尿抑制作用     

Kidney stone inhibitors in patients with renal stones and endemic renal tubular acidosis in northeast Thailand

Distal renal tubular acidosis (dRTA) is generally associated with hypercalciuria, hypocitraturia, and nephrolithiasis. Our intention was to study glycosaminoglycans (GAGS) and nephrocalcin (NC), two well-known crystal growth inhibitors, in a population with endemic dRTA and nephrolithiasis in northeast (NE) Thailand. We studied 13 patients, six with dRTA and seven with nephrolithiasis with normal or undefined acidification function. Six healthy adults living in the same area as the patients and another six from the Bangkok (BKK) area were used as controls. We measured urinary pH, ammonia, calcium, citrate, magnesium, oxalate, potassium, sodium and uric acid. GAGS were determined by an Alcian blue precipitation method and were qualitated by agarose gel electrophoresis after being isolated using 5% cetyltrimethylammonium bromide at pH 6.0. NC isoforms were isolated as previously described by Nakagawa et al. Citrate was higher in BKK controls (p<0.04). There was a striking difference among GAGS from BKK when compared with other groups (103.85±10.70 vs. 23.52±8.11 for dRTA, 22.36±14.98 for kidney stone patients and 14.73±2.87 mg/ml in controls from the NE region, (p<0.0001). dRTA and stone-forming patients excrete proportionally more (C+D) than (A+B) NC isoforms (p<0.05). Also, their NC showed a 100-fold weaker binding capacity of calcium oxalate monohydrate crystals. The ratio of chondroitin sulfate/heparin sulfate in GAGS was approximately 9/1. In addition to the traditional risk factors for nephrolithiasis in dRTA, GAGS and NC might play an important role in the pathogenesis of stone formation in this population.     

Phyllanthus niruri normalizes elevated urinary calcium levels in calcium stone forming (CSF) patients

Phyllanthus niruri is a plant used for years in Brazil to treat urinary calculi. We prospectively evaluated the effect of P. niruri intake on 24 h urinary biochemical parameters in an attempt to assess its in vivo effect in calcium stone forming (CSF) patients. A total of 69 CSF patients (39 males and 30 females, 38±8 years old) were randomized to take either P. niruri (n=33) (450 mg capsules, td) or placebo (n=36) for 3 months. Blood calcium, uric acid, citrate, magnesium, oxalate, sodium and potassium were determined at baseline and at the end of the study. A subset analysis was made in patients classified according to the presence of metabolic abnormalities (hypercalciuria, hyperuricosuria, hyperoxaluria, hypocitraturia and hypomagnesiuria). Overall, there were no significant differences in the mean values of urinary parameters between the urine samples before and after P. niruri intake, except for a slight reduction in mean urinary magnesium after P. niruri, which was within the normal range. However, in the subset analysis, we observed that P. niruri induced a significant reduction in the mean urinary calcium in hypercalciuric patients (4.8±1.0 vs 3.4±1.1 mg/kg/24 h, P<0.05). In this short-term follow-up, no significant differences in calculi voiding and/or pain relief between the groups taking P. niruri or the placebo were detected. Our data suggest that P. niruri intake reduces urinary calcium based on the analysis of a subset of patients presenting with hypercalciuria. Larger trials including primary hypercalciuric stone formers should be performed in order to confirm these findings and to determine the possible clinical consequences of urinary calcium reduction during P. niruri administration.     

肾结石肾小球病变中细胞外基质变化的研究

应用免疫组织化学ＳＰ法和计算机图像分析系统对１７例肾结石肾小球病变标本细胞外基质中Ⅳ型胶原、纤粘连蛋白（ＦＮ）和层粘连蛋白（ＬＮ）的变化进行定量分析。结果发现硬化的肾小球中Ⅳ型胶原、ＦＮ和ＬＮ均较正常增多，且以Ⅳ型胶原增多为显著，说明肾结石肾小球硬化的发生与细胞外基质的过量积累有关，另外，我们还发现在肾小球、肾小管上皮细胞及间质细胞中有ＨＬＡ－ＤＲ抗原表达，提示肾结石肾小球病变是一种与局部免疫因素     

Oxidative stress in children with kidney disease

The aim of this work was to study the dynamics of oxidative stress in the blood and urine of children with kidney diseases: glomerulonephritis (GN), pyelonephritis (PN), renal failure (RF), and lower urinary tract infections (LUTI). The concentration of conjugated dienes is increased in blood: GN 4 times and RF up to 2 times; and extremely increased in urine: GN 12 times and RF 4 times. The concentration of thiobarbituric acid reactive substances in urine shows a similar trend: GN 7 times, PN 2 times, RF 1.5 times, and LUTI almost 3 times. Urine chemiluminescence is also increased: GN 5 times, PN and LUTI 3 times, and RF 6 times. Kidney disease leads to 2.5-fold inhibition of antioxidant catalase activity in blood and 10-fold in urine. Total antioxidant activity of urine is induced in all groups: GN 18 times, PN 2 times, RF 1.5 times, and almost 4 times in the LUTI group. Experimental data confirm that products of lipid peroxidation, intensity of chemiluminescence, and total and enzyme antioxidant capacity in combination with clinical parameters are a proper test for the dynamics of oxidative stress and markers of intoxication in children with inflammatory and immunological active parenchymal kidney disorders. These data could be helpful for the optimization of complex and effective antioxidant therapy of children with kidney disease.     

Significance of 8-hydroxy-2'-deoxyguanosine levels in patients with chronic renal failure

SUMMARY:     The aim of this study was to determine the significance of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is known as a marker of oxidative stress in vivo , in patients with chronic renal failure (CRF). Fifty-one non-dialysed CRF patients (29 men and 22 women; mean ± SD age, 57.8 ± 12.8 years) who were under dietary therapy for at least 6 months were enrolled in the study. Both serum and urinary 8-OHdG levels were measured by using high-sensitive enzyme-linked immunosorbent assay (ELISA) kits. We examined the relationship between 8-OHdG levels and clinical indices in patients with CRF. As a result, the serum 8-OHdG level was strongly correlated with serum levels of urea nitrogen (UN; r  = 0.58; P  < 0.0001), creatinine (Cr; r  = 0.53; P  < 0.0001), and β2-microglobulin (β2-MG; r  = 0.54; P  < 0.0001). Furthermore, the serum 8-OHdG level was inversely correlated with creatinine clearance (Ccr; r  = −0.54; P  < 0.0001). In contrast, urinary 8-OHdG level was not correlated with any of the clinical parameters. This is the first report of 8-OHdG level determination in patients with CRF. It is suggested that serum 8-OHdG level is not sufficient as a marker of oxidative damage in patients with CRF, and it should be corrected according to the residual renal function to estimate the accurate degree of oxidative stress.     

Blood 8-hydroxy-2'-deoxyguanosine is associated with erythropoietin resistance in haemodialysis patients.

BACKGROUND: 8-Hydroxy-2'-deoxyguanosine (8-OHdG), a product of oxidized DNA, is increased in haemodialysis (HD) patients, but the clinical relevance of enhanced 8-OHdG production in these patients remains unknown. METHODS: We cross-sectionally measured serum 8-OHdG in 73 patients on maintenance HD (age 68+/-2 years, time on HD 85+/-11 months, male/female=42/31), and examined the relationship between blood 8-OHdG and the severity of renal anaemia and the weekly dosage of recombinant human erythropoietin (rHuEPO). RESULTS: There was a significant increase in serum 8-OHdG in HD patients compared with normal subjects. Serum 8-OHdG was positively correlated with the patients' age (r=0.231, P<0.05) but not with the duration of HD. Serum 8-OHdG was significantly higher in diabetic subjects than in non-diabetic subjects (P<0.05). Serum 8-OHdG had a significant inverse correlation with haemoglobin (Hb) (r=-0.526, P<0.01) but a positive correlation with the rHuEPO dose (r=0.443, P<0.01) and the ratio of the weekly rHuEPO dose divided by Hb (r=0.487, P<0.01). Serum 8-OHdG was not correlated with inflammatory and nutritional parameters. CONCLUSIONS: These findings suggest that the elevation of circulating 8-OHdG may be associated, at least in part, with rHuEPO resistance in HD patients.     

Promotion of oxidative stress in kidney of rats loaded with cystine dimethyl ester

Cystinosis is a systemic genetic disease caused by a lysosomal transport deficiency accumulating cystine in most tissues. Although tissue damage might depend on cystine accumulation, the mechanisms of tissue damage are not fully understood. Studies performed in fibroblasts of cystinotic patients and in kidney cells loaded with cystine dimethyl ester (CDME) suggest that apoptosis is enhanced in this disease. Considering that oxidative stress is a known apoptosis inducer, our main objective was to investigate the effects of CDME loading on several parameters of oxidative stress in the kidney of young rats. Animals were injected twice a day with 1.6 μmol/g body weight CDME and/or 0.26 μmol/g body weight cysteamine (CSH) from the 16th to the 20th postpartum day and killed after 1 or 12 h. CDME induced lipoperoxidation and protein carbonylation and stimulated superoxide dismutase, glutathione peroxidase (GPx), and catalase activities, probably through the formation of superoxide anions, hydrogen peroxide, and hydroxyl free radicals. Coadministration of CSH, the drug used to treat cystinotic patients, prevented, at least in part, those effects, possibly acting as a scavenger of free radicals. These results suggest that the induction of oxidative stress might be one of the mechanisms leading to tissue damage in cystinotic patients.     

Urinary interleukin-6 and interleukin-8 in children with urinary tract infection

Urinary interleukin-6 (UIL-6) and urinary interleukin-8 (UIL-8) concentrations were measured by immunoassay in 39 and 34 patients respectively, hospitalized with febrile urinary tract infection (UTI), and in 37 and 32 age-, race- and sex-matched febrile control children respectively, with negative urine cultures. UIL-6 and UIL-8 concentrations, measured in picograms per milliliter and corrected for creatinine, were compared with clinical and laboratory indicators of inflammation and bacterial virulence factors of Escherichia coli. Median UIL-6 concentrations at the time of admission were 397 pg/ml (range 0–65,789 pg/ml) in the 37 patients compared to 0 pg/ml (range 0–473.8 pg/ml) in the 37 controls (P<0.0001). Median UIL-8 concentrations at the time of admission were 5809 pg/ml (range 0–347,368 pg/ml) in the 32 patients compared to 0 pg/ml (range 0–2231 pg/ml) in the 32 controls (P<0.0001). UIL-6 and UIL-8 concentrations were lower (P<0.0001 for UIL-6 and P=0.0005 for UIL-8) in follow-up urine samples from UTI patients, obtained 48 h after the initiation of antibiotic therapy. UIL-6 and UIL-8 concentrations were statistically significantly correlated with urine white blood cells (WBC). UIL-8 concentrations were elevated in patients with E. coli organisms producing hemolysin. UIL-6 and UIL-8 are elevated in children with febrile UTI and decrease in response to antibiotic therapy. Magnitude of UIL-8 response is associated with hemolysin production, a bacterial virulence factor of E. coli. UIL-6 and UIL-8 concentrations are statistically correlated with urine WBC. UIL-6 and UIL-8 may be mediators of inflammation in children with febrile UTI. Received: 30 June 1999 / Revised: 29 June 2000 / Accepted: 5 July 2000