Significant Decrease In Renal Function Research Articles

Renal distress syndrome in surgery and uronephrology: concept, pathogenesis, basics of prevention and correction

Based on objective criteria of the structural and functional state of the kidneys in various urgent surgical and uronephrological pathologies (peritonitis, pancreonecrosis, intestinal obstruction, urinary peritonitis, acute purulent secondary pyelonephritis) to identify and prove the general pattern of development of renal changes, their influence on the pathogenesis of homeostasis disorders at the organizational level and to form the evidence base of a new symptom complex - renal distress syndrome in surgery and uronephrology; to establish the effectiveness of Remaxol in its correction. Experimentally on 60 mongrel dogs with acute peritonitis, pancreatitis, intestinal obstruction of varying severity, the state of renal function, including detoxification, was assessed based on the assessment of the inflow-outflow difference in the level of toxins and in the parenchyma of organs - the composition of lipids, the activity of peroxidation of membrane lipids and phospholipases. Clinical and laboratory studies included patients with acute peritonitis (48), acute pancreatitis (18), intestinal obstruction (21), acute purulent secondary pyelonephritis (19). Patients with peritonitis (20) underwent standardized therapy (the first subgroup) or with the inclusion of Remaxol (28) (the second subgroup). In the experiment and in the clinic, in acute surgical and some urological diseases with a different nature of the inflammatory process, there is a significant decrease in renal function. The recorded acute renal injury is combined with a pronounced membrane-stabilizing process in the tissue structures of the kidneys, the degree of which is associated with the severity of the disease. In order to correct and stabilize the indicated changes, Remaxol was used. The drug increased kidney tolerance to trigger pathogenetic agents, which improved the functional status of the kidneys. These data confirm the significance of the studied molecular mechanisms in kidney damage in urgent pathology. Experimental and clinical evidence has been obtained for the formation of a new concept - a symptom complex in acute surgical and uronephrological diseases of the abdominal cavity and retroperitoneal space called renal distress syndrome. Renal distress syndrome in surgery and uronephrology is a set of pathological processes of the body, the most important manifestation of which is the progression of endogenous intoxication due to a violation of the functional status of the kidneys as a result of membrane-stabilizing phenomena of organ cells due to oxidative stress and phospholipase activity.

Radical Cystectomy Versus Bladder-Preserving Therapy in Muscle-Invasive Bladder Cancer Patients After Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Multicenter Retrospective Analysis

Purpose: Although radical cystectomy (RC) and concurrent chemoradiotherapy (CCRT) are curative options for muscle-invasive bladder cancer (MIBC), the optimal treatment strategy for MIBC patients with a history of nephroureterectomy for upper tract urothelial carcinoma (UTUC) remains unclear. This retrospective analysis was conducted to compare survival rates and evaluate prognostic factors related to treatment outcomes.Materials and Methods: We conducted a multi-institutional retrospective study of patients with MIBC after nephroureterectomy for UTUC between 2005 to 2023. Out of 75 patients, 30 underwent bladder-preserving therapy (BPT), including 22 patients who underwent radiation therapy (RT) and 8 patients who underwent CCRT, while 45 patients underwent RC. The overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) after BPT and RC were evaluated using Kaplan-Meier curves. Cox regression analysis was used to identify variables associated with OS, CSS, and PFS. Posttreatment changes in renal function were compared.Results: At 3 years, the OS, CSS, and PFS rates in the BPT group were 52.4%, 71.7%, and 31.3%, respectively, with no significant difference compared to RC. In multivariate analysis, bladder cancer T stage was the only predictive factor for OS, CSS, and PFS. Similar results were also observed in the RT group compared to RC. A significant decrease in renal function was detected among patients in the RC group, while patients in the BPT group maintained preserved renal function. Patients in the BPT group experienced a lower grade of toxicity after treatment compared to those in the RC group, and the rates of survival with functional bladder at 1 year, 3 years, and 5 years were 87.0%, 69.9%, and 69.9%, respectively.Conclusions: Bladder-preserving therapy, including RT alone, may be a viable treatment option for patients with MIBC who have undergone nephroureterectomy, as it can achieve comparable oncologic outcomes to RC, while potentially preserving bladder and renal function.

Embolization of Renal Pseudoaneurysm Following Partial Nephrectomy of Localized Tumour and Preserving Renal Function: Clinical Case and Review of Literature

Surgical procedures in highly vascularized renal parenchyma sometimes can cause iatrogenic vascular complications. Although incidence renal pseudoaneurysms after partial nephrectomy is low, around 1%, clinical presentation of these patients can be quite severe – hematuria, lumbar pain, dizziness, weakness. Prompt and precise diagnostics and treatment are essential. Ultrasound and Computed Tomography are two most common diagnostic approaches for the assessment of pseudoaneurysms or arteriovenous fistulas following partial nephrectomy. Endovascular selective microcoil embolization is a safe and effective kidney-preserving procedure for treating iatrogenic vascular complications. Although when embolizing renal arteries some of renal parenchyma loses perfusion and becomes fibrotic, no significant decrease in renal function in early post-embolization period was noted. Comparing open surgery to endovascular treatment of pseudoaneurysms, latter one allows shorter average hospital stay and less frequent cardiac and peripheral vascular complications. The article discusses a case of a patient that had developed renal pseudoaneurysm after partial nephrectomy. During a routine check-up of a middle-aged woman a presumable renal cyst was found. On more throughout examination the cyst was ruled as a tumour and partial nephrectomy was performed. After 12 days from surgery patient was admitted to hospital complaining macrohematuria, lower abdomen pain, episodic right-side ache. Urgent contrast enhanced computed tomography was performed, which confirmed that patient was bleeding from the operated kidney. Patient was admitted to interventional radiology departament and perform embolization of bleeding vessel. After embolization of pseudoaneurysm, bleeding was controlled and patient was completely treated.

Association of reduced renal function with different phase of chronic hepatitis B virus infection

Background: The association between chronic hepatitis B virus (HBV) infection and the development of chronic kidney disease (CKD) remains controversial, and whether the cause is related to the different phases of chronic HBV infection remains unclear. Methods: A large cross-sectional study was performed to show the prevalence of reduced renal function during chronic HBV infection in adults from 7 multi-centers of Shenzhen City in China. Estimated glomerular filtration rate (eGFR) was used to evaluate the effect of HBV infection on the risk of renal impairment. Results: 33.04% HBsAg (+) patients had eGFR < 90, while patients without HBV exposure, 32.73% had eGFR < 90, showing no significant difference. There was no significant difference between those with elevated and normal alanine aminotransferase (ALT) in chronic hepatitis B (CHB) groups. Moreover, according to stratified statistics of different phases of the disease, liver cirrhosis, especially decompensated liver cirrhosis, hepatocellular carcinoma (HCC) showed a significant decrease in renal function compared with CBH (P = 0). Multivariate logistic regression analysis showed that liver disease different phases independently associated with reduced renal function. Conclusion: During the early CHB phase of chronic HBV infection (either elevated ALT or normal) did not increase the risk of renal dysfunction compares no exposure to HBV. However, when CHB progress to end-stage liver disease were associated with reduced kidney function. Additionally, Hoek formula should be recommended for patients with end-stage liver disease.

Glycine Betaine Relieves Lead-Induced Hepatic and Renal Toxicity in Albino Rats.

Lead (Pb) is a widespread and nondegradable environmental pollutant and affects several organs through oxidative mechanisms. This study was conducted to investigate the antioxidant protective effect of glycine betaine (GB) against Pb-induced renal and hepatic injury. Male albino rats (n = 45) were divided into three groups: G1 untreated control, G2 Pb-acetate (50 mg/kg/day), and G3 Pb-acetate (50 mg/kg/day) plus GB (250 mg/kg/day) administered for 6 weeks. For G3, Pb-acetate was administered first and followed by GB at least 4 h after. Pb-acetate treatment (G2) resulted in a significant decrease in renal function, including elevated creatinine and urea levels by 17.4% and 23.7%, respectively, and nonsignificant changes in serum uric acid levels. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphates (ALP) activities were significantly increased with Pb treatment by 37.6%, 59.3%, and 55.1%, respectively. Lipid peroxidation level was significantly increased by 7.8 times after 6 weeks of Pb-acetate treatment. The level of reduced glutathione (GSH-R) significantly declined after Pb-acetate treatment. Pb-acetate treatment also reduced the activities of superoxide dismutase (SOD), glutathione-S-transferase (GST), and glutathione peroxidase (GSH-PX) by 74.1%, 85.0%, and 40.8%, respectively. Treatment of Pb-intoxicated rats with GB resulted in a significant reduction in creatinine, urea, ALT, AST, and lipid peroxidation, as well as a significant increase in the level of GSH-R and in the activities of ALP, SOD, GST, and GSH-PX. The molecular interaction between GB and GSH-PX indicated that the activation of GSH-PX in Pb-intoxicated rats was not the result of GB binding to the catalytic site of GSH-PX. The affinity of GB to bind to the catalytic site of GSH-PX is lower than that of H2O2. Thus, GB significantly mitigates Pb-induced renal and liver injury through the activation of antioxidant enzymes and the prevention of Pb-induced oxidative damage in the kidney and liver.

A Novel Antioxidant Protects Against Contrast Medium-Induced Acute Kidney Injury in Rats.

Many studies proposed that oxidative stress and apoptosis are key mechanisms in the pathogenesis of contrast-induced acute kidney injury (CI-AKI). Xylose-pyrogallol conjugate (XP) is an original effective antioxidant that showed decent antioxidant and anti-apoptosis effect before. Thus the therapeutic effect and mechanism of XP in preventing CI-AKI in the short and long term were investigated in this research. Renal function and histological grade were evaluated to determine the severity of renal injury. Kidney samples were then collected for the measurement of oxidative stress markers and the detection of apoptosis. Transmission electron microscopy (TEM) and western blot of mitochondrial protein were utilized for the analysis of the mitochondrial conditions. The results demonstrated that the CI-AKI rats caused a significant decrease in renal function accompanied by a remarkable increase in Malondialdehyde (MDA), bax, caspase-3, cytochrome c (Cyt C) level, TdT-mediated dUTP nick end labeling (TUNEL) positive apoptotic cells, and damaged mitochondria, while a decline in antioxidase activities and mitochondrial superoxide dismutase 2 (SOD2) expression compared with the control rats. However, when XP (50 or 100 or 200 mg/kg/day) was given orally for consecutive 7 days before CI-AKI modeling, XP (200 mg/kg) showed a better capability to restore renal dysfunction, histopathological appearance, the level of apoptosis, mitochondrial damage, oxidative stress, and fibrosis generation without interference in computed tomographic imaging. Our study indicated that antioxidant XP played a nephroprotective role probably via antiapoptotic and antioxidant mechanisms. Besides, XP may regulate the mitochondria pathway via decreasing the ratio of bax/bcl-2, inhibiting caspase-3 expression, cytochrome c release, and superoxide dismutase 2 activity. Overall, XP as a high-efficient antioxidant may have the potentials to prevent CI-AKI.

Scutellarin Ameliorates Renal Injury via Increasing CCN1 Expression and Suppressing NLRP3 Inflammasome Activation in Hyperuricemic Mice.

Considerable evidences have indicated that elevated uric acid (UA) was involved in renal tubular injury leading to hyperuricemic nephropathy (HN). Scutellarin is a biologically active flavonoid derived from the Chinese traditional herb Erigeron breviscapus Hand-Mazz, which has been widely used in the treatment of cardiovascular and cerebrovascular diseases. In the present study, we analyzed the effect of scutellarin on HN, by using C57BL/6 mice and human renal tubular epithelial cell line HK-2 which was subjected to adenine/potassium oxonate and UA to mimic a HN injury. The HN mice showed a significant decrease in renal function with the increased SCr and blood urea nitrogen (BUN) (p < 0.05). Hematoxylin–eosin staining results showed a histological injury in HN mice kidney tissues with severe tubular damage. Scutellarin dose dependently alleviated the renal injury of the HN model (p < 0.05), and a dose of 20 mg/kg/day remarkably reduced the Scr level (26.10 ± 3.23 μmol/ml vs. 48.39 ± 7.51 μmol/ml, p < 0.05) and BUN (151.12 ± 30.24 mmol/L vs. 210.43 ± 45.67 mmol/L, p < 0.05) compared with the HN model group. Similarly, scutellarin decreased NGAL, Kim-1, cystatin C, and IL-18 protein expression levels in HN mouse (p < 0.05). Overexpressed CCN1 could not induce NLRP3 inflammasome activation, with no change of mRNA and protein expression levels of NLRP3, ASC, and pro-caspase-1 compared with the control HK-2. However, HK-2 showed a significant NLRP3 inflammasome activation and apoptosis. Importantly, knockdown of CCN1 not only aggravated NLRP3 inflammasome activation and apoptosis but also abrogated the protective effect of scutellarin in UA-induced HK-2 injury. Thus, scutellarin might alleviate HN progression via a mechanism involved in CCN1 regulation on NLRP3 inflammasome activation.

Long-term evaluation of renal function and neurogenic bladder following radical hysterectomy in patients with uterine cervical cancer.

This study aimed to determine whether radical hysterectomy (RH) affects renal function. Renal function was followed up in 83 patients with stage IB1-IIB cervical cancer who underwent RH during 2006-2015. Serum creatinine (sCre) levels were measured preoperatively and every year postoperatively. Estimated glomerular filtration rate (eGFR) was calculated using sCre levels. Patients who were unable to urinate by themselves or whose residual urine was ≥100 mL were referred to a urologist with the diagnosis of neurogenic bladder (NB). The relationship between NB occurrence and changes in sCre level or eGFR was evaluated respectively. Urological intervention was required in 45 patients (54.2%), and self-urethral catheterization was performed in 41 (49.3%) patients. The NB and clean intermittent catheterization (CIC) groups exhibited significant increases in sCre levels, which were not observed in the non-NB or non-CIC groups. In the non-NB group, eGFR did not change following surgery. However, in the NB group, significant decreases in eGFRs were observed at postoperative 2 and 3 years and at final follow-up. There was no difference in the incidence of cardiovascular events between patients with and without NB. In patients with NB following RH, a significant decrease in renal function was observed after postoperative 2 years.

Transcatheter aortic valve implantation versus conservative treatment in chronic kidney disease patients.

There are no studies comparing transcatheter aortic valve implantation (TAVI) to conservative management in patients with chronic kidney disease stage 3-5 and severe aortic stenosis. We sought to compare the mortality rate and change in renal function in this patient population. This was a single-centre retrospective cohort study that included all patients with chronic kidney disease stage 3-5 and severe aortic stenosis who underwent TAVI or were treated conservatively between 2010 and 2015. Three hundred and sixty patients were included (162 TAVI and 198 conservatively treated patients). Several statistical methods were used, including propensity score matching and inverse probability weighting. Mean follow-up was 1.9 years. Conservative management was associated with a hazard ratio of 3.95 (95% CI: 2.59-6.02) for mortality compared with TAVI. After one year there was a significant decrease in renal function in the control group (39.6±13.9 ml/min to 34.4±15.3 ml/min), but not in the TAVI group (41.7±13 ml/min to 42.9±14.5 ml/min) (p-value=0.001). TAVI is associated with improved survival in patients with aortic stenosis and chronic kidney disease stage 3-5 compared to conservative management and protects from further decline in renal function up to one-year follow-up.

Histopathological analysis of the non - tumour parenchyma following radical nephrectomy: can it predict renal functional outcome?

ABSTRACTIntroduction Radical nephrectomy (RN), a recommended treatment option for patients with Renal cell carcinoma (RCC) leads to an inevitable decline in global renal function. Pathological changes in the non-tumour parenchyma of the kidney may help predict the function of the remaining kidney.Materials and Methods Aim of this prospective, observational study was to find histopathological factors in the non-tumor renal parenchyma that could predict the decline in global renal function postoperatively and its association with co-morbidities like diabetes (DM). Data of consecutive patients undergoing RN from December-2013 to January-2015 was collected. Non-tumor parenchyma of the specimen was reported by a dedicated histopathologist. eGFR was calculated using Cockcroft-Gault formula before the surgery and at last follow up of at least 12 months.Results 73 RN specimens were analyzed. Mean follow up was 12.3 months. The mean decrease in eGFR was 22% (p=.0001). Percent decrease in eGFR did not show association with any of the histopathological parameters studied. DM was significantly associated with decrease in percent eGFR (p<0.05) and increase in arteriolar hyalinosis (p=0.004), Glomerulosclerosis (p=0.03) and Interstitial fibrosis/ Tubular atrophy (p=.0001). Maximum size of the tumor showed a negative correlation with percentage change in eGFR (p=.028).Conclusion Histological parameters in the non-tumour portion of the RN specimen may not be able to predict renal function outcome over a short follow up. However, presence of DM was associated with adverse pathological changes and significant decrease in renal function postoperatively.

Systematic renal function evaluation using iohexol or inuline clearance before lung transplantation in adult CF patients

Introduction Cystic fibrosis (CF) patients are at risk for kidney injury even before undergoing lung transplantation because of prolonged exposure to aminoglycoside and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR) such as Cockroft or MDRD Formula are not adapted in CF population due to patients’ low body weight [1] . The aim of our study was to measure precisely the GFR of CF adult patients before lung transplantation. Materiels et methodes Iohexol or Inuline clearance was realized in 21 adult CF patients, when they entered the lung transplant waiting list ( n = 17) or when the patient was considered by the clinician at high risk for renal disease ( n = 4). No patient was treated with aminoglycoside at the time of GFR measurement. BMI, history of diabetes mellitus and high blood pressure were recorded. Exposure to intravenous aminoglycoside within the 5 years before GFR measurement was calculated. Urines samples were collected to check for proteinuria and albuminuria. Resultats Our population was predominantly male (57%). Mean age at GFR measurement was 31 years old. Mean BMI was 19 kg/m 2 . Only one patient had a history of high blood pressure, and 43% of patients were diabetic. Fourteen percent of patients had albuminuria of more than 30 mg/L and none of them had proteinuria. Mean days of exposure to IV aminoglycoside therapy within the 5 years before GFR evaluation was 169 days (Ranging from 60 to 280 days). Tobramycin was the most used aminoglycoside at the mean posology of 7.6 mg/kg/day. GFR was measured using iohexol for 15 patients and inuline was used for the remaining 6 patients. Mean measured GFR was 107 mL/min/1.73m 2 . Only 2 patients had a measured GFR 2 for which GFR estimation using CKD EPI was unable to detect the moderate decline in kidney function (estimated GFR >90 mL/min/1.73m 2 ). Discussion Our sample was representative of the CF population. Despite prolonged exposition to high dose of aminoglycoside associated with a high prevalence of diabetes mellitus, no major decline in GFR is observed in our cohort. Conclusion There is no significant decrease in renal function in CF patients before lung transplantation.

Renal function in bladder cancer patients after trimodality therapy: Long-term results of a large institutional experience.

453 Background: Maintenance of renal function following treatment of bladder cancer presents an ongoing challenge. The decline following radical cystectomy is well documented. However, in patients undergoing trimodality bladder-sparing therapy consisting of transurethral resection (TURBT) and concurrent chemoradiation followed by adjuvant chemotherapy, renal function is poorly understood. Methods: We performed a retrospective review of 178 patients with muscle-invasive bladder cancer who underwent bladder-sparing therapy between 2001 and 2013 and collected nadir creatinine values in the month preceding TURBT and at 1, 3, 5, 7, and 9 years post treatment initiation. Wilcoxon signed-rank test and mixed effects analysis were performed to compare the pre-treatment and post-treatment levels of creatinine and EGFR and to analyze their temporal change. Results: Median follow-up was 48 months (range: 1 to 162 months). The mean pre-treatment creatinine and EGFR were 1.12 mg/dl and 71 mg/dl, respectively. Cr increased to 1.21 mg/dl and EGFR decreased to 65 mg/dl at 1 year following treatment initiation (p = 0.001, p = 0.002). All post-treatment values were also significantly different from pre-treatment values (all p values &lt; 0.002), but there was no significant difference between the post-treatment values over time. Conclusions: Following bladder-sparing therapy for muscle invasive bladder cancer, renal function was generally well preserved in the long term. Although there was a modest yet statistically significant decrease in renal function that occurred during the first year, there was no further decline up to 9 years. While this initial decrease in function is of unknown clinical significance, the lack of further decline after 1 year is different from similar studies following cystectomy.

ASSESSMENT OF PARAMETERS OF RENAL FUNCTION IN PATIENTS WITH ARTERIAL HYPERTENSION AND ABDOMINAL OBESITY WITH A HISTORY OF ACUTE CEREBROVASCULAR ACCIDENT, DEPENDING ON THE TARGET LEVELS OF SYSTOLIC BLOOD PRESSURE IN THE RECOVERY PERIOD OF THE STROKE

Background: Essential arterial hypertension is one of the most common causes of chronic kidney disease. Timely identification of asymptomatic chronic kidney disease may help to prevent development of renal failure and maintain kidney functioning. Aim: To assess changes in renal function parameters in patients with arterial hypertension and abdominal obesity with a history of a stroke, depending on the target levels of systolic blood pressure (SBP) during the recovery period of stroke. Materials and methods: We assessed 88 patients with arterial hypertension with a history of an acute cerebrovascular accident within the last 1 to 6 months (mean age, 58.8±9.5 years). During 2 to 4 weeks of their hospital stay, their antihypertensive treatments were titrated to reach the chosen target levels of blood pressure. Thereafter, the patients were followed up for 8 to 12 months with baseline and follow-up measurements of their antropometric and clinical chemistry parameters including blood urea nitrogen and serum creatinine and estimated glomerular filtration rate (CKD-EPI). Chronic kidney disease was diagnosed by albumin and creatinine measurements with calculation of albumin/creatinine ratio in the morning urine portion. Results: There was a positive correlation between office SBP and serum creatinine (r=0.5, р=0.01), serum albumin (r=0.4, р=0.003) and creatinine in the morning urine portion (r=0,5, р=0.0001). Hip circumference negatively correlated with serum creatinine and albumin/creatinine ration at the end of the follow-up (r=-0.3, р=0.04 and r=-0.3, р=0.04, respectively). Bodyweight correlated positively with the glomerular filtration rate (r=0.3, р=0.04), whereas waist to hip ration correlated with urine albumin at the end of the follow-up (r=0.3, р=0.01). Multiple regression analysis showed an association between mean office SBP and serum creatinine (β=0.43, р=0.04), urine albumin (β=0.33, р=0.02) and urine creatinine level (β=0.39, р=0.005). Conclusion: We found an association between SBP and renal function. SBP levels below 135 mm Hg are associated with an improvement of the renal function, whereas SBP levels below 124 mm Hg are associated with a significant decrease in renal function assessed by glomerular filtration rate and albumin/creatinine ratio. The efficacy of antihypertensive treatment in the recovery period after an acute cerebrovascular accident should be assessed with consideration of renal function measured by glomerular filtration rate and microalbuminuria levels.

Reply to Letter to the Editor

Previous studies show that chronic pyelonephritis and end stage renal disease may follow acute pyelonephritis in children and adolescents when improperly or inadequately treated. Our study shows that there is a significant decrease in renal function following untreated acute bacterial pyelonephritis due to nephron loss. The acute inflammatory response is responsible for much of the renal damage, although damage from renal ischemia is an additional significant factor. The present study used a combination of an antibiotic and a xanthine oxidase inhibitor (allopurinol) as compared to antibiotic therapy alone begun 72 hours after infection. Both were successful in eradicating the infection rapidly, but did not entirely prevent renal damage. Treatment prior to 72 hours thus is important. It appears that the combined treatment, designed to eradicate the bacteria as well as reduce the post-ischemic reperfusion damage and the phagocytic burst of phagocytosis is ideal, as this combined treatment was effective in preventing almost all renal damage and loss of renal function.

Decompression of Inflammatory Edema along with Endothelial Cell Therapy Expedites Regeneration after Renal Ischemia-Reperfusion Injury

Increased pressure due to postischemic edema aggravates renal ischemia-reperfusion injury (IRI). Prophylactic surgical decompression using microcapsulotomy improves kidney dysfunction after IRI. Supportive cell therapy in combination with microcapsulotomy might act synergistically protecting kidney function against IRI. The effects of therapeutic endothelial cell application alone and in combination with microcapsulotomy were investigated in a xenogenic murine model of 45-min warm renal ischemia. Renal function and perfusion were determined before as well as 2 and 18 days postischemia by (99m)Tc-MAG3 imaging and laser Doppler. Histological analysis included H&E stains and immunohistology for endothelial marker MECA-32, cell proliferation marker Ki-67, and macrophage marker F4/80. Histomorphological changes were quantified using a tubular injury score. Ischemia of 45 min led to severe tissue damage and a significant decrease in renal function and perfusion. Microcapsulotomy and cell therapy alone had no significant effect on renal function, while only surgical decompression significantly increased blood flow in ischemic kidneys. However, the combination of both microcapsulotomy and cell therapy significantly improved kidney function and perfusion. Combination therapy significantly reduced morphological injury of ischemic kidneys as determined by a tubular injury score and MECA-32 staining. Macrophage infiltration evidenced by F4/80 staining was significantly reduced. The Ki-67 proliferation index was increased, suggesting a regenerative environment. While microcapsulotomy and cell therapy alone have limited effect on renal recovery after IRI, combination therapy showed synergistic improvement of renal function, perfusion, and structural damage. Microcapsulotomy may create a permissive environment for cell therapy to work.

Nephrotoxicity and Efficacy Assessment of Polymyxin Use in 92 Transplant Patients

Polymyxins are old antimicrobials, discontinued for many years because of nephrotoxicity and neurotoxicity reports and reintroduced recently due to the increasing frequency of multiresistant Gram-negative bacterial infections. There are very few data related to toxicity and efficacy from transplanted patients, the major subjects of this study. All solid-organ-transplanted patients from our institution during January 2001 to December 2007 who used polymyxins were retrospectively assessed for nephrotoxicity and treatment efficacy. Microbiological and clinical cure rates were 100% and 77.2%, respectively. Only transplant patients subjected to at least 72 h of intravenous polymyxin were entered in the study. Overall, 92 transplant patients were included, and the nephrotoxicity rate was 32.6%. Multivariate analysis showed a statistically significant association between duration of polymyxin treatment (P = 0.037; odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00 to 1.12) and significant renal dysfunction. Polymyxin use is associated with very high rates of significant decrease in renal function; therefore, polymyxin must be used only when no other option is available and for as briefly as possible in the solid organ transplant setting.

639 PREOPERATIVE PREDICTORS OF RENAL FUNCTION DECLINE FOLLOWING RADICAL NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyUrothelial Cancer: Upper Tract Tumors1 Apr 2012639 PREOPERATIVE PREDICTORS OF RENAL FUNCTION DECLINE FOLLOWING RADICAL NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA Matthew Kaag, Landon Trost, R. Houston Thompson, Ricardo Favaretto, Vanessa Elliott, Shahrokh Shariat, Ally Maschino, Jay Raman, and Guido Dalbagni Matthew KaagMatthew Kaag Hershey, PA More articles by this author , Landon TrostLandon Trost Rochester, MN More articles by this author , R. Houston ThompsonR. Houston Thompson Rochester, MN More articles by this author , Ricardo FavarettoRicardo Favaretto New York, NY More articles by this author , Vanessa ElliottVanessa Elliott Hershey, PA More articles by this author , Shahrokh ShariatShahrokh Shariat New York, NY More articles by this author , Ally MaschinoAlly Maschino New York, NY More articles by this author , Jay RamanJay Raman Hershey, PA More articles by this author , and Guido DalbagniGuido Dalbagni New York, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.718AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Radical nephroureterectomy (NU) for upper tract urothelial carcinoma (UTUC) may result in a clinically significant decrease in renal function. This loss of glomerular filtration rate (GFR) may impact the ability to adequately deliver postoperative chemotherapy. We developed a model to predict GFR based on interval from NU, and assessed predictors of GFR after surgery. METHODS We identified 370 patients treated with NU for UTUC at 3 centers between 1995 and 2010 who had post-operative laboratory data. Only patients deemed eligible for cisplatin-based chemotherapy before NU (pre-operative GFR>60 ml/min/m2) were included. We created a generalized estimating equations linear model to predict GFR based on the time from surgery. We used univariate linear regression to identify predictors of GFR after NU at early post-operative (1-5 months after NU) and late post-operative (>5 months after NU) time points. RESULTS 163 patients had an eligible early post-NU GFR measurement and 172 had an eligible late post-NU GFR measurement. The median age was 67 (IQR 59, 73) and 154 (72%) were male. The median GFR prior to NU was 72 ml/min/m2 (IQR 64, 80). When modeling GFR after surgery, we did not see evidence that post-NU GFR values changed significantly over time, despite allowing for a possible non-linear relationship in the model. At 2 months the predicted GFR was 52 ml/min/m2 (95% CI: 51, 54); at 6 months it was 51 ml/min/m2 (95% CI: 49, 53). On univariate analysis, age and preoperative GFR were both significant predictors of early (per year: β= -0.4; 95% CI: -0.6, -0.2; p<0.0005 and per 10 ml/min/m2: β= 5.4; 95% CI: 3.7, 7.2; p<0.0005) and late GFR outcomes (per year: β= -0.4; 95% CI: -0.5, -0.2; p<0.0005 and per 10 ml/min/m2: β= 4.1; 95% CI: 2.6, 5.6; p<0.0005). On multivariate analysis, preoperative GFR and age remained significant predictors of both early (p<0.0005 and p=0.004) and late (p=0.001 and p=0.007) GFR after NU. Charlson score was also an independent predictor of late GFR post-NU on multivariate analysis (p=0.004). CONCLUSIONS Renal function decreases after NU and does not show evidence of recovery over time. Pre-NU GFR and patient age are independent predictors of post-NU GFR at early and late time points, while Charlson score predicts only late post-operative GFR. Diminished GFR following NU is likely to limit utilization of adjuvant cisplatin-based chemotherapy. These data underscore the need for clinical trials evaluating neoadjuvant chemotherapy in well-selected patients. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e260 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew Kaag Hershey, PA More articles by this author Landon Trost Rochester, MN More articles by this author R. Houston Thompson Rochester, MN More articles by this author Ricardo Favaretto New York, NY More articles by this author Vanessa Elliott Hershey, PA More articles by this author Shahrokh Shariat New York, NY More articles by this author Ally Maschino New York, NY More articles by this author Jay Raman Hershey, PA More articles by this author Guido Dalbagni New York, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Partial Nephrectomy After Previous Radio Frequency Ablation: The National Cancer Institute Experience

Development of new renal tumors or recurrence after radio frequency ablation not amendable for repeat ablation presents a difficult therapeutic dilemma. We report on the outcomes of partial nephrectomy on kidneys previously treated with radio frequency ablation. We performed a chart review of 13 patients who underwent 16 attempted partial nephrectomies following radio frequency ablation. Hospital records and operative reports were reviewed for demographic data, perioperative data and outcomes. The outcomes of the present series were compared to historical controls of published studies in similar patient populations. No cases were converted to radical nephrectomy. Median time from radio frequency ablation to surgery was 2.75 years (range 1 to 7.1). A median of 7 tumors (range 2 to 40) were removed with a median estimated blood loss of 1,500 ml (range 500 to 3,500) and a median operative time of 7.8 hours (range 5 to 10.7). Operative notes commented on the presence of severe fibrosis in the operative field in 12 of 16 cases (75%). There was a modest but statistically significant decrease in renal function. Partial nephrectomy after radio frequency ablation had a higher reoperation rate compared to other series of primary or repeat partial nephrectomies but had the lowest rate of vascular or visceral injuries. Partial nephrectomy on kidneys previously treated with radio frequency ablation is a technically challenging but feasible procedure. Residual or metachronous disease after radio frequency ablation may be salvaged with partial nephrectomy with a modest decrease in renal function. A trend toward a higher chance of reoperation and urine leak after partial nephrectomy after radio frequency ablation may be useful information for the planning and discussion of treatment decisions.

Transfusion en néphrologie

Population-based study suggests that chronic kidney disease is frequent. Almost one third of people older than 70 years of age would have a significant decrease in renal function. Anemia appears when glomerular filtration rate falls under 40 mL per minute per 1.73 m 2. Concurrently with supplementary iron, erythropoiesis-stimulating agents (ESA) allow a strict control of hemoglobin. However, incomplete responses to ESA are possible. The following conditions — inflammatory disorders, chronic blood loss, hyperparathyroidism, surgical process, chronic diseases, adverse effects of immunosuppressive agents — may cause apparent resistance to ESA therapy. All these conditions may request transfusion.

Low-dose dexamethasone and thalidomide with higher frequency zoledronic acid (dtZ) for newly diagnosed multiple myeloma

18506 Background: Although dexamethasone (Dex), thalidomide (Thal) and zoledronic acid (Zol) have frequently been combined for the treatment of multiple myeloma (MM), the ideal dosing schedule is unknown. We previously reported that lower doses of Dex and Thal can be effectively combined with high-frequency dosing of Zol (Haematologica 2005). Methods: This “dtZ” regimen - which comprises weekly Dex 20 mg OM for 4 days, Thal 50 mg ON, and 3-weekly Zol 4 mg - resulted in an impressive response rate (RR) of 61.6% and near complete remission (nCR)/complete remission (CR) rate of 7.7% in 26 patients with relapsed/refractory MM. Results: In this present study, we treated 22 newly diagnosed MM patients with “dtZ” and report an even more impressive RR of 100.0% and nCR/CR rate of 20–35%. The median time to response was 1.8 months and median time to maximum response was 2.2 months. The median time to progression (TTP) has not been achieved yet. As expected, low-dose Dex/Thal resulted in lower (18.1%) grade 3 or 4 toxicities. These were all infections; which lead to further dose-reduction of Dex. There were no thromboembolic events, despite the fact that aspirin was not routinely given. Of particular interest, 3- weekly Zol was not associated with any significant decrease in renal function, and none of our patients developed osteonecrosis of the jaw (ONJ). In fact, at the time of writing of this abstract, more than 1,000 doses of Zol had been administered in a 3-weekly fashion to these as well as other patients, and only 1 patient developed ONJ. This patient who had already received greater than 20 doses of Zol healed uneventfully after receiving appropriate outpatient dental treatment, and subsequently received another 8 doses of Zol with no recurrence of ONJ. Conclusion: In conclusion, the Zol-based “dtZ” regimen is potentially a highly-effective and safe frontline regimen for MM. Using Zol every 3 weeks with lower doses of Dex and Thal does not appear to increase the rate or severity of nephrotoxicity or ONJ. Although we do not know exactly why every patient responded to “dtZ”, we speculate that this could be due to a critical balance that has been achieved between the anti-MM, anti-osteoclastic and immunostimulatory effects of the individual drugs of the combination. No significant financial relationships to disclose.