The prognostic value of serum procalcitonin in acute obstructive pyelonephritis.

PURPOSE: To evaluate the prognostic value of procalcitonin (PCT) in the occurrence of infectious complications in the management of acute obstructive pyelonephritis (AOP) compared with other biological parameters (leucocyte count, C-reactive protein [CRP]). METHODS: We conducted a retrospective study including patients who were treated for AOP and performed serum PCT tests in our center between January 1, 2017 and December 31, 2017. Upper urinary tract obstruction was confirmed by either ultrasound or CT urography. Clinical examinations and laboratory tests including leukocyte count, CRP, urine and blood cultures, and serum PCT measurements were performed in the emergency unit. Treatment included early renal decompression using indwelling ureteral stents or nephrostomy and empiric antibiotic therapy. The primary endpoint was occurrence of severe sepsis (SS), a composite criterion including urosepsis and/or septic shock and/or admission to the intensive care unit (ICU) and/or death. RESULTS: A total of 110 patients (median age: 61 years) were included, of whom 56.3% were female. SS occurred in 39 cases (35.4%). Multivariate regression analysis showed that serum PCT (OR 1.08; 95% CI 1.03-1.17; p = 0.01), CRP (OR 1.007; 95% CI 1.001-1.015; p = 0.03), and diabetes mellitus (OR 5.1; 95% CI 1.27-27.24; p = 0.04) were independent predictors for SS. Serum PCT was the biological marker associated with the highest accuracy to predict SS (ROC 0.912 (95% CI 0.861-0.962) and was superior to CRP (p < 0.001): the sensitivity and specificity of PCT to predict SS were 95% and 77%, respectively, with a serum PCT cutoff value of 1.12 µg/L. CONCLUSIONS: PCT levels > 1.12 µg/L could help physicians to identify high-risk patients who could benefit from early and aggressive management in collaboration with intensive care specialists.

The role of urinary NGAL and serum cystatin C in assessing the severity of ureteropelvic junction obstruction in infants.

BACKGROUND: The ideal management of ureteropelvic junction obstruction (UPJO) remains debatable. This prospective case-control study aimed to investigate if urinary levels of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and serum levels of cystatin C could distinguish surgical from non-surgical cases of UPJO and if they could detect earlier impairment of renal function. METHODS: Biomarkers were measured in the following age-matched groups: (a) 22 infants with surgical UPJO, at initial diagnosis and 12 months postoperatively (groups A1 and A2, respectively); (b) 19 infants with non-surgical UPJO (group B); and (c) 17 controls (group C). Based on serum cystatin C levels, estimated glomerular filtration rate (eGFR) was calculated. RESULTS: Urinary NGAL (uNGAL) was significantly higher in group A1 vs. group A2 (p = 0.02) and in group A1 vs. group C (p = 0.03), whereas there was no statistically significant difference between groups A2 and C (p = 0.77). Likewise, cystatin C levels were significantly higher in group A1 vs. group A2 and in group A1 vs. group C (p = 0.004 and p = 0.02, respectively), but no statistically significant difference between groups A2 and C (p = 0.82). uNGAL and serum cystatin C did not differ between groups B and A, nor did they differ between groups B and C. Cystatin C levels and eGFR of group A1 were significantly higher than those of group A2 and group C (p = 0.0001 and p = 0.02, respectively). CONCLUSION: It seems that NGAL and cystatin C are able to distinguish patients who were treated surgically from healthy controls, and their levels appear to improve significantly following surgery.

C1q/tumor necrosis factor-related protein-3 improves renal fibrosis via inhibiting notch signaling pathways.

C1q/tumor necrosis factor-related protein-3 (CTRP3) has been extensively reported as an important role involved in antifibrosis, antiapoptosis, and anti-inflammation. However, the role of CTRP3 involved in renal fibrosis remains unclear. Our current study explored the role of CTRP3 in renal fibrosis and its underlying mechanisms by using serums and renal biopsy specimens from renal fibrosis patients and control subjects, rats models with the surgery of unilateral ureteral obstruction (UUO) and human renal proximal tubular epithelial cells (HRPTEpiCs). We found that circulating levels of CTRP3 had no significant difference between renal fibrosis patients and healthy subjects; however, renal CTRP3 expression was markedly downregulated in the fibrotic region with an abundant expression of collagen-I. In UUO rat models, circulating levels of CTRP3 have not changed with the prolonged obstruction of the kidney; renal CTRP3 expression was decreased with the severity of renal fibrosis; adenovirus-mediated CTRP3 treatment inhibited renal interstitial fibrosis. In vitro experiments revealed that CTRP3 attenuates TGF-ß1 induced tubular epithelial cells fibrotic changes; CTRP3 knockdown facilitates the expression of fibrotic markers in TGF-ß1-induced HRPTEpiCs; recombinant CTRP3 or adenovirus-mediated CTRP3 overexpression significantly inhibited the Notch signaling pathway-associated factors, and knockdown of CTRP3 increased TGF-ß1-mediated activation of the Notch signaling pathways. Collectively, our current study found that CTRP3 could improve renal fibrosis, to some extent, through inhibiting the Notch pathway.

Common clinical markers predict end-stage renal disease in children with obstructive uropathy.

BACKGROUND: Obstructive uropathy (OU) is a common cause of end-stage renal disease (ESRD) in children. Children who escape the newborn period with mild-to-moderate chronic kidney disease (CKD) continue to be at increased risk. The predictive ability of clinically available markers throughout childhood is poorly defined. METHODS: Patients with OU were identified in the Chronic Kidney Disease in Children Study. The primary outcome of interest was renal replacement therapy (RRT) (cases). Controls were age matched and defined as patients within the OU cohort who did not require RRT during study follow-up. RESULTS: In total, 27 cases and 41 age-matched controls were identified. Median age at baseline and age at outcome measurement were 10 vs. 16 years, respectively. First available glomerular filtration rate (GFR) (36.9 vs. 53.5 mL/min per 1.73 m2), urine protein/creatinine (Cr) (0.40 vs. 0.22 mg/mg) and microalbumin/Cr (0.58 vs. 0.03 mg/mg), and serum CO2 (20 vs. 22 mmol/L) and hemoglobin (12.4 vs. 13.2 g/dL) differed significantly between cases and controls, respectively. GFR declined 3.07 mL/min per 1.73 m2/year faster in cases compared to that in controls (p < 0.0001). Urine protein/Cr and microalbumin/Cr increased by 0.16 and 0.11 per year more in cases compared to those in controls, respectively (p ≤ 0.001 for both). Serum phosphate increased by 0.11 mg/dL and serum albumin and hemoglobin decreased by 0.04 (g/dL) and 0.14 (g/dL) per year more for cases compared to those for controls, respectively (p < 0.05 for all). CONCLUSIONS: Age-specific baseline and longitudinal measures of readily available clinical measures predict progression to ESRD in children with mild-to-moderate CKD from OU.

Biomarkers of obstructive nephropathy using a metabolomics approach in rat.

Chronic kidney disease (CKD) has become a major public health problem worldwide and has a great impact on the quality of life of millions of people. Long-term obstructive uropathy is an important cause of CKD. We hypothesized diagnostic biomarkers for early stage obstructive nephropathy can be discovered by metabolomic profiling of biofluid. Unilateral ureteral occlusion (UUO) surgery was performed on rats to induce renal interstitial fibrosis. Sham-operated rats were used as controls. Plasma and urine metabolites were analyzed by UPLC-MS based metabolomic approach. Significant metabolic profiling separations were found between UUO rats and controls at different time points. 13 differential plasma metabolites and 14 differential urine metabolites were identified at the first postoperative day. The altered metabolic pathways included glycerophospholipid metabolism, tryptophan metabolism, glutamate metabolism and purine metabolism. We further identified a panel of five plasma biomarkers which offer good diagnostic performance (areas under the curve of 1.0 in the discovery set and validation set) for early diagnosis of obstructive nephropathy. These findings demonstrate that early stage obstructive nephropathy can be diagnosed in an animal model based on plasma metabolomics which is a powerful tool for characterizing metabolic disturbances. This method has strong potential for clinical translation.

Klotho and activin A in kidney injury: plasma Klotho is maintained in unilateral obstruction despite no upregulation of Klotho biosynthesis in the contralateral kidney.

In a new paradigm of etiology related to chronic kidney disease-mineral and bone disorder (CKD-MBD), kidney injury may cause induction of factors in the injured kidney that are released into the circulation and thereby initiate and maintain renal fibrosis and CKD-MBD. Klotho is believed to ameliorate renal fibrosis and CKD-MBD, while activin A might have detrimental effects. The unilateral ureter obstruction (UUO) model is used here to examine this concept by investigating early changes related to renal fibrosis in the obstructed kidney, untouched contralateral kidney, and vasculature which might be affected by secreted factors from the obstructed kidney, and comparing with unilateral nephrectomized controls (UNX). Obstructed kidneys showed early Klotho gene and protein depletion, whereas plasma Klotho increased in both UUO and UNX rats, indicating an altered metabolism of Klotho. Contralateral kidneys had no compensatory upregulation of Klotho and maintained normal expression of the examined fibrosis-related genes, as did remnant UNX kidneys. UUO caused upregulation of transforming growth factor-ß and induction of periostin and activin A in obstructed kidneys without changes in the contralateral kidneys. Plasma activin A doubled in UUO rats after 10 days while no changes were seen in UNX rats, suggesting secretion of activin A from the obstructed kidney with potentially systemic effects on CKD-MBD. As such, increased aortic sclerostin was observed in UUO rats compared with UNX and normal controls. The present results are in line with the new paradigm and show very early vascular effects of unilateral kidney fibrosis, supporting the existence of a new kidney-vasculature axis.

Attenuation of partial unilateral ureteral obstruction - induced renal damage with hyperbaric oxygen therapy in a rat model

ABSTRACT Objective: The objective of the present study was to evaluate the effectiveness of HBO therapy on biochemical parameters, renal morphology and renal scintigraphy in rats undergoing chronic unilateral partial ureteral obstruction (UPUO). Material and methods: Thirty-five rats were divided into five equal groups: Control group; Sham group; HBO group; UPUO group and UPUO/HBO group. The effects of HBO therapy were examined using biochemical parameters and histopathological changes. After calculating the score for each histopathological change, the total histopathological score was obtained by adding all the scores. In addition, dynamic renal scintigraphy findings were evaluated. Results: Serum parameters indicating inflammation, serum tumor necrosis factor- alpha, ischemia modified-albumin, IMA/albumin ratio and Pentraxin-3 levels, were observed to be high in the UPUO group and low in the UPUO/HBO treatment group. Similarly, in the treatment group, the reduction in malondialdehyde, total oxidant status and oxidative stress index levels and increase in total antioxidant capacity values were observed to be statistically significant compared to the UPUO group (p<0.001, p=0.007, p<0.001, p=0.001, respectively). The total score and apoptosis index significantly decreased after administration of HBO treatment. Dynamic 99mTc-MAG3 renal scintigraphy also showed convincing evidence regarding the protective nature of HBO against kidney injury. In the UPUO/HBO therapy group, the percentage contribution of each operated kidney increased significantly compared to the UPUO group (41.73% versus 32.72%). Conclusion: The findings of this study indicate that HBO therapy had a reno-protective effect by reducing inflammation and oxidative stress, and preserving renal function after renal tissue damage due to induction of UPUO.

Perioperative serum creatinine changes and ureteral injury.

PURPOSE: To illustrate a simple method that screens for ureteral injury in the acute postoperative period after urogynecologic surgeries. METHODS: Serum creatinine measurements in the preoperative (baseline) and postoperative periods of urogynecologic surgeries were determined and the correlation of the change to ureteral injury and/or obstruction analyzed. The sample size calculation showed 7 cases and 28 controls were sufficient to detect significant changes in creatinine. Each of the seven cases was matched for age and type of surgery with a control patient in a 1:4 ratio following standard protocol. RESULTS: Chart review of patients (273 cases) undergoing urogynecologic surgeries from October 2009 to June 2014 were undertaken. There were 7 cases of ureteral injury and 28 matching control cases. All cases had intraoperative cystoscopy confirming bilateral ureteral flow. In the ureteral injury group, blockage of ureter was confirmed by CT scan with IV contrast. There was a 59.8% increase in serum creatinine levels postoperative in the ureteral injury group versus a 3.8% decrease in controls. A difference of creatinine levels greater than or equal to 0.3 mg/dL over baseline was evident in ureteral injury cases. CONCLUSION: A small change in serum creatinine level over baseline after urogynecologic surgery alerted the possibility of ureteral injury or obstruction. A simple and inexpensive evaluation of perioperative creatinine levels can promptly diagnose ureteral damage in the acute postoperative period for gynecologic reconstructive surgeries.

Emergency Ureteral Stone Treatment Score Predicts Outcomes of Ureteroscopic Intervention in Acute Obstructive Uropathy Secondary to Urolithiasis.

INTRODUCTION: Immediate ureteroscopic treatment for patients presenting to the emergency room with symptomatic ureterolithiasis is more commonly being utilized. Recent reports demonstrate good efficacy for emergency ureteroscopy (URS); however, preoperative predictors of treatment success have not been described. In this study, we report our multicenter experience with emergency URS and identify predictors of successful treatment. We also describe the Emergency Ureteral Stone Treatment (EUST) score, which integrates these predictors and stratifies patients into those that are likely and unlikely to have successful treatment. MATERIALS AND METHODS: Laboratory and radiographic data for all patients who underwent emergency URS for acute symptomatic ureterolithiasis from 2010 to 2015 were reviewed. Statistical difference among parameters for patients who were stone free (SF) and not SF was assessed with the Student's t-test. Cutoff values for significant predictors were determined using sensitivity and specificity analysis. The EUST score was determined based on the number of cutoffs a patient was below. RESULTS: Two hundred two of 247 patients (81.8%) were SF. Two complications (ureteral perforation) occurred. Stone size, duration of symptoms before presentation, and serum white blood count at presentation did not affect SF rates. 95.5% of the treatment failures were attributed to a tight ureter preventing stone access. Patients who received alpha blockers before treatment were more likely to be SF (98.0% vs 55.5%, p < 0.01). Periureteral density (PUD) was lower in SF patients (2.8 HU vs 19.6 HU, p < 0.01), whereas the increase in serum creatinine from baseline (ΔCr) was greater in non-SF patients (0.44 mg/dL vs 0.20 mg/dL, p < 0.01). EUST score of 0, 1, and 2 correlated with SF rates of 20.6%, 81.9%, and 99.2%, respectively. CONCLUSIONS: Combined consideration of PUD and ΔCr with the EUST score can assist in selecting optimal candidates for immediate ureteroscopic management. Administration of alpha blockers before surgery may improve success rates by providing preoperative ureteral dilation.

Attenuation of partial unilateral ureteral obstruction - induced renal damage with hyperbaric oxygen therapy in a rat model.

OBJECTIVE: The objective of the present study was to evaluate the effectiveness of HBO therapy on biochemical parameters, renal morphology and renal scintigraphy in rats undergoing chronic unilateral partial ureteral obstruction (UPUO). MATERIAL AND METHODS: Thirty-five rats were divided into five equal groups: Control group; Sham group; HBO group; UPUO group and UPUO/HBO group. The effects of HBO therapy were examined using biochemical parameters and histopathological changes. After calculating the score for each histopathological change, the total histopathological score was obtained by adding all the scores. In addition, dynamic renal scintigraphy findings were evaluated. RESULTS: Serum parameters indicating inflammation, serum tumor necrosis factoralpha, ischemia modified-albumin, IMA/albumin ratio and Pentraxin-3 levels, were observed to be high in the UPUO group and low in the UPUO/HBO treatment group. Similarly, in the treatment group, the reduction in malondialdehyde, total oxidant status and oxidative stress index levels and increase in total antioxidant capacity values were observed to be statistically significant compared to the UPUO group (p<0.001, p=0.007, p<0.001, p=0.001, respectively). The total score and apoptosis index significantly decreased after administration of HBO treatment. Dynamic 99mTc-MAG3 renal scintigraphy also showed convincing evidence regarding the protective nature of HBO against kidney injury. In the UPUO/HBO therapy group, the percentage contribution of each operated kidney increased significantly compared to the UPUO group (41.73% versus 32.72%). CONCLUSION: The findings of this study indicate that HBO therapy had a reno-protective effect by reducing inflammation and oxidative stress, and preserving renal function after renal tissue damage due to induction of UPUO.

Sequential fetal serum ß2-microglobulin to predict postnatal renal function in bilateral or low urinary tract obstruction.

OBJECTIVE: Fetal serum ß2-microglobulin has been shown to predict postnatal renal outcome in cases of fetal obstructive uropathy. We assessed the value of serial measurements of fetal serum ß2-microglobulin in the prediction of postnatal renal outcome. METHODS: We retrospectively studied renal outcome in 42 fetuses with bilateral or low urinary tract obstruction that had fetal blood sampling on at least two occasions to assay serum levels of ß2-microglobulin. Amniotic fluid volume at the time of each sampling was recorded. We classified renal outcome as either favorable (when postnatal renal function was normal) or adverse (when postnatal chronic renal failure occurred or when renal dysplasia at autopsy was noted). A ß2-microglobulin cut-off of 5 mg/L and amniotic fluid index of 5 cm were used to predict postnatal renal outcome. RESULTS: Renal outcome was adverse in 28 cases and favorable in 14. In 12 (28.6%) cases, fetal serum ß2-microglobulin concentration differed between the first and last measurement. Prediction of postnatal renal outcome was correct in 11 of these cases based on the last ß2-microglobulin measurement. The sensitivity of ß2-microglobulin in predicting renal outcome was significantly higher (P = 0.005) when using the last rather than the first measurement (96.4% vs 64.3%), with similar specificity for both measurements (85.7% vs 78.6%, non-significant). The sensitivity of amniotic fluid volume was also significantly higher (P = 0.005) when using the last rather than the first measurement (75.0% vs 35.7%), with similar specificity for both measurements (64.3% vs 71.4%, non-significant). CONCLUSION: Sequential measurement of serum ß2-microglobulin, performed for adverse ultrasound findings, such as renal parenchymal abnormality or decreasing amniotic fluid volume, predicts postnatal renal outcome more accurately than does a single assay. This may be due to possible worsening of renal injury with increasing duration of urinary tract obstruction. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

The role of serum and urinary carbohydrate antigen 19-9 in predicting renal injury associated with ureteral stone.

This study was designed to evaluate the role of urinary and serum carbohydrate antigen 19-9 (CA19-9) as a biomarker in the assessment of patients with ureteral stone. A total of 38 patients with ureteral stone and hydronephrosis who underwent transurethral lithotripsy (TUL) (Group A) and 24 age-matched healthy controls (Group B) were evaluated in this study. Urinary and serum CA19-9 concentrations were measured in group A patients before TUL as well as 4 and 8 weeks following the operation. Urinary and serum CA19-9 concentrations were also measured in group B participants. Median concentration of urinary and serum CA19-9 was 34.0 and 15.0 kU/L in group A patients and 16.1 and 5.3 kU/L in group B, respectively (p < 0.001). Medians of CA19-9 concentration in urine and serum reduced to 12.5 and 4.5 kU/L 8 weeks after TUL (p < 0.001). Following successful TUL and hydronephrosis resolution, a significant decline was detected in serum and urinary CA19-9. We also noted that duration of ureteral obstruction was associated with serum and urinary CA19-9 concentrations, suggesting the potential role of this marker in predicting renal damage associated with urinary tract obstruction and determining the appropriate timing of interventions.

Inhibitory effect of NH4Cl treatment on renal Tgfß1 signaling following unilateral ureteral obstruction.

BACKGROUND/AIMS: Consequences of obstructive nephropathy include tissue fibrosis, a major pathophysiological mechanism contributing to development of end-stage renal disease. Transforming growth factor ß 1 (Tgfß1) is involved in the progression of renal fibrosis. According to recent observations, ammonium chloride (NH4Cl) prevented phosphate-induced vascular remodeling, effects involving decrease of Tgfß1 expression and inhibition of Tgfß1-dependent signaling. The present study, thus, explored whether NH4Cl influences renal Tgfß1-induced pro-fibrotic signaling in obstructive nephropathy induced by unilateral ureteral obstruction (UUO). METHODS: UUO was induced for seven days in C57Bl6 mice with or without additional treatment with NH4Cl (0.28 M in drinking water). Transcript levels were determined by RT-PCR as well as protein abundance by Western blotting, blood pH was determined utilizing a blood gas and chemistry analyser. RESULTS: UUO increased renal mRNA expression of Tgfb1, Tgfß-activated kinase 1 (Tak1) protein abundance and Smad2 phosphorylation in the nuclear fraction of the obstructed kidney tissues, effects blunted in NH4Cl treated mice as compared to control treated mice. The mRNA levels of the transcription factors nuclear factor of activated T cells 5 (Nfat5) and SRY (sex determining region Y)-box 9 (Sox9) as well as of tumor necrosis factor α (Tnfα), interleukin 6 (Il6), plasminogen activator inhibitor 1 (Pai1) and Snai1 were up-regulated in the obstructed kidney tissues following UUO, effects again significantly ameliorated following NH4Cl treatment. Furthermore, the increased protein and mRNA expression of α-smooth muscle actin (α-Sma), fibronectin and collagen type I in the obstructed kidney tissues following UUO were significantly attenuated following NH4Cl treatment. CONCLUSION: NH4Cl treatment ameliorates Tgfß1-dependent pro-fibrotic signaling and renal tissue fibrosis markers following obstructive nephropathy.

Serum metabonomic analysis of protective effects of Curcuma aromatica oil on renal fibrosis rats.

BACKGROUND: Curcuma aromatica oil is a traditional herbal medicine demonstrating protective and anti-fibrosis activities in renal fibrosis patients. However, study of its mechanism of action is challenged by its multiple components and multiple targets that its active agent acts on. METHODOLOGY/PRINCIPAL FINDINGS: Nuclear magnetic resonance (NMR)-based metabonomics combined with clinical chemistry and histopathology examination were performed to evaluate intervening effects of Curcuma aromatica oil on renal interstitial fibrosis rats induced by unilateral ureteral obstruction. The metabolite levels were compared based on integral values of serum 1H NMR spectra from rats on 3, 7, 14, and 28 days after the medicine administration. Time trajectory analysis demonstrated that metabolic profiles of the agent-treated rats were restored to control levels after 7 days of dosage. The results confirmed that the agent would be an effective anti-fibrosis medicine in a time-dependent manner, especially in early renal fibrosis stage. Targeted metabolite analysis showed that the medicine could lower levels of lipid, acetoacetate, glucose, phosphorylcholine/choline, trimethylamine oxide and raise levels of pyruvate, glycine in the serum of the rats. Serum clinical chemistry and kidney histopathology examination dovetailed well with the metabonomics data. CONCLUSIONS/SIGNIFICANCES: The results substantiated that Curcuma aromatica oil administration can ameliorate renal fibrosis symptoms by inhibiting some metabolic pathways, including lipids metabolism, glycolysis and methylamine metabolism, which are dominating targets of the agent working in vivo. This study further strengthens the novel analytical approach for evaluating the effect of traditional herbal medicine and elucidating its molecular mechanism.

Urinary and serum biomarkers in ureteropelvic junction obstruction: a systematic review.

CONTEXT: Ureteropelvic junction obstruction (UPJO) constitutes a predominant cause of obstructive hydronephrosis. Fundamental questions regarding the assessment and treatment of infants and children with obstructive nephropathy remain unanswered. OBJECTIVE: Several studies have investigated the usefulness of substances that could serve as potential diagnostic and prognostic biomarkers in children with UPJO. Aim of the present study is to systematically review the literature on biomarkers that have been studied to date in patients with UPJO. METHODS: The main search was conducted in the electronic databases MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) from inception through March 2014 using various combinations of Medical Subject Headings (MeSH). RESULTS: The 14 included studies reported data on 380 UPJO patients who underwent surgery, 174 who were treated conservatively and 213 controls. CONCLUSION: Some biomarkers offer promising results however more multicenter, prospective carefully designed studies are needed to evaluate their diagnostic and prognostic value.

Metallic ureteral stents in malignant ureteral obstruction: clinical factors predicting stent failure.

PURPOSE: To provide clinical outcomes of the Resonance metallic ureteral stent in patients with malignant ureteral obstruction, as well as clinical factors predicting stent failure. METHODS: Cancer patients who have received Resonance stents from July 2009 to March 2012 for ureteral obstruction were included for chart review. Stent failure was detected by clinical symptoms, image studies, and renal function tests. Survival analysis for stent duration was used to estimate patency rate and factors predicting stent failure. RESULTS: A total of 117 stents were inserted successfully into 94 ureteral units in 79 patients. There were no major complications. These stents underwent survival analysis and proportional hazard regression. The median duration for the stents was 5.77 months. In multivariate analysis, age (P=0.043), preoperative serum creatinine level (P=0.0174), and cancer type (P=0.0494) were significant factors associated with stent failure. Cancer treatment before and after stent insertion had no effect on stent duration. CONCLUSIONS: Resonance stents are effective and safe in relieving malignant ureteral obstructions. Old age and high serum creatinine level are predictors for stent failure. Stents in patients with lower gastrointestinal cancers have longer functional duration.

[Ectopic production of calcitriol by non-Hodgkin lymphoma as a cause of hypercalcemic crisis]. / Ektope Calcitriol-Produktion durch ein Non-Hodgkin-Lymphom als Ursache einer hyperkalzämischen Krise.

HISTORY AND ADMISSION FINDINGS: A 92-year-old woman was admitted because her general condition had deteriorated during the last two weeks and acute kidney injury had developed. Moreover, she suffered from periods of disorientation and confusion while heretofore she was autonomous. INVESTIGATION, TREATMENT AND COURSE: Clinical and biochemical evaluation revealed a hypercalcemic crisis with markedly increased serum levels of calcium (3.77 mmol/l; reference values 2.2-2.65), an acute kidney injury and neuropsychiatric disturbances. Ultrasound scan and magnetic resonance imaging of a palpable mass in the right abdomen showed a tumor in the retroperitoneal space. Histological evaluation specified the tumor as non-Hodgkin lymphoma. Further investigation revealed no other reason for the hypercalcemia but enhanced levels of calcitriol. Since serum levels of calcidiol were increased while levels of calcidiol were normal, we assumed ectopic production of calcitriol by non-Hodgkin lymphoma as the cause of hypercalcemic crises. This could been proven by the decrease of calcium and calcitriol levels during the course of lymphoma treatment. CONCLUSION: Hypercalcemia of malignancy is the most common cause of hypercalcemia in the inpatient setting. The evaluation of these cases should consider ectopic production of calcitriol a cause of hypercalcemia.

Alpha-lipoic acid attenuates renal injury in rats with obstructive nephropathy.

This study was established to determine the possible protective effects of alpha-lipoic acid (ALA), a powerful antioxidant, on renal injury in obstructive nephropathy. Male Sprague-Dawley rats were assigned into sham-operated unilateral ureteral obstruction (UUO) and UUO treated with ALA groups. ALA 60 mg/kg was injected intraperitoneally 2 days before UUO induction and continued afterward for 7 days. Renal function, oxidative stress markers, nitric oxide, transforming growth factor-1 (TGF-ß1), and histological changes were evaluated at the end of the experiment. Obstruction of the ureter resulted in renal dysfunction as indicated by significant increases in blood urea nitrogen and serum creatinine. Nonobstructed contralateral kidneys in all groups examined did not show any morphological or biochemical alterations. In untreated UUO group, the obstructed kidney developed marked hydronephrosis, leukocyte infiltration, and severe interstitial fibrosis. These functional and structural changes were associated with significant increases in tissue levels of malondialdehyde, nitric oxide, and TGF- ß 1 but decreases in reduced glutathione and total antioxidant capacity. Pretreatment with ALA significantly minimized all the changes elicited by ureteral obstruction. These findings demonstrate that ALA supplementation attenuates renal injury in rats with obstructive nephropathy and further suggest that oxidative stress inhibition is likely to be involved in the beneficial effects of this compound.