Long-term outcome of pediatric renal transplantation with donors younger than 6 years.

BACKGROUND: Renal transplantation is currently the best treatment option for patients with end-stage renal disease. However, the use of kidneys from donors under 6 years of age as a possibility to increase the organ pool in pediatric recipients remains a controversial matter. We aimed to investigate whether donor age is associated to the long-term functionality of the renal graft. Likewise, we analyzed the adaptation of the graft to the ascending functional requirements in the pediatric patient. METHODS: Retrospective study of the results obtained in pediatric recipients transplanted with grafts from donors between 3 and 6 years of age, comparing them with those of grafts from donors older than 6 years. Among the variables compared are cumulative graft survival, renal size, need for antiproteinuric therapy, GFR, incidence of rejection, pyelonephritis, renal failure and surgical or tumor complications. RESULTS: A total of 43 transplants were performed with donors aged 3-6 years, and 42 transplants with donors older than 6 years. Cumulative graft survival at 5 years was 81% for the younger donor group compared to 98% for the older donor group (p < .05). At 8 years, cumulative graft survival for donors <6 years was 74%. As for the mean estimated graft survival, it was 11.52 years for the younger donor group and 14.51 years for older donors. During follow-up, the younger donor group presented greater renal enlargement and need for antiproteinuric therapy. The older donors group had a higher GFR during the first year of follow-up, which then equalized in both groups. There were no statistically significant differences in the incidence of acute or chronic rejection, acute pyelonephritis, acute renal failure or surgical or tumor complications. CONCLUSIONS: Renal transplants of grafts equal to or less than 6 years old have good short-term and acceptable long-term results in pediatric patients.

A single-centre report of acute pyelonephritis in a patient after kidney transplantation - analyses of risk factors.

BACKGROUND: Urinary tract infections (UTI) are the most common infectious complications after kidney transplantation (KTx) with highest incidence in the first three months of transplantation. UTI in transplant recipients increase morbidity and mortality, risk of graft failure and incidence of acute rejection episodes. According to published data, urinary tract infections significantly affect graft survival. The aim of our study was to identify possible risk factors for the development of UTI. MATERIAL AND METHODS: We retrospectively analyzed a cohort of patients who received kidney transplantation between January 2014 and December 2016 in the Transplant Center of Louis Pasteur University Hospital in Kosice. One hundred and fifty-three patients after kidney transplantation were included in the study. RESULTS: A total of 47 Caucasian patients (30%) developed UTI, namely - acute pyelonephritis after KTx. We identified independent risk factors associated with UTI such as female gender OR (7.98, 95% CI 2.88-22.12, p < 0.001), diabetes mellitus (OR 5.26, 95% CI 2.01-13.74, p = 0.001; 95% CI 4.57-53.82, p < 0.001) urologic complication (OR 15.68, 95% CI 4.57-53.82; p < 0.001) and acute rejection episode (OR 3.15, 95% CI 1.13-8.76, p = 0.027). The most common microbiological agent was Escherichia coli. CONCLUSION: We identified the aforementioned risk factors of urinary tract infections in the files of our patients. Statistically, the most significant risk factors are the female gender, and presence of urological complications. The urological complications and BMI of the patients are considered modifiable factors. Based on our analysis, we confirmed a significantly higher number of ACR patients who overcame infection which is in accordance with the published data on association of UTI with the development of acute cellular rejection (ACR) (Tab. 2, Fig. 1, Ref. 15).

Factors associated with urinary diversion and fatality of hospitalised acute pyelonephritis patients in France: a national cross-sectional study (FUrTIHF-2).

Acute pyelonephritis (AP) epidemiology has been sparsely described. This study aimed to describe the evolution of AP patients hospitalised in France and identify the factors associated with urinary diversion and fatality, in a cross-sectional study over the 2014-2019 period. Adult patients hospitalised for AP were selected by algorithms of ICD-10 codes (PPV 90.1%) and urinary diversion procedure codes (PPV 100%). 527,671 AP patients were included (76.5% female: mean age 66.1, 48.0% Escherichia coli), with 5.9% of hospital deaths. In 2019, the AP incidence was 19.2/10,000, slightly increasing over the period (17.3/10,000 in 2014). 69,313 urinary diversions (13.1%) were performed (fatality rate 6.7%), mainly in males, increasing over the period (11.7% to 14.9%). Urolithiasis (OR [95% CI] =33.1 [32.3-34.0]), sepsis (1.73 [1.69-1.77]) and a Charlson index ≥3 (1.32 [1.29-1.35]) were significantly associated with urinary diversion, whereas E. coli (0.75 [0.74-0.77]) was less likely associated. The same factors were significantly associated with fatality, plus old age and cancer (2.38 [2.32-2.45]). This nationwide study showed an increase in urolithiasis and identified, for the first time, factors associated with urinary diversion in AP along with death risk factors, which may aid urologists in clinical decision-making.

Outcomes of asymptomatic histologic pyelonephritis of kidney transplant.

BACKGROUND: Urinary Tract Infections are the most common post-transplant infection and can have varied presentations. This study aimed to describe the outcomes of kidney transplant recipients with asymptomatic histologic pyelonephritis on allograft biopsy. Histologic Pyelonephritis was defined as neutrophil cast or neutrophilic tubulitis, interstitial infiltrates with predominant neutrophils, and no evidence of rejection or glomerulonephritis on biopsy. METHODS: The study included 123 kidney transplant recipients, of whom 95 underwent protocol biopsies, and 28 had biopsies for elevated creatinine within the first 2 years of a kidney transplant. RESULTS: The mean age of the cohort was 55.3 years, with 52% females and 78% deceased donor transplants. The risk factors for asymptomatic histologic pyelonephritis were recipient female sex (OR 1.89, 1.3-2.7, diabetes mellitus (OR 2.479, 1.687-3.645), and deceased donation (OR 1.69, 1.098-2.63). The incidence of asymptomatic pyelonephritis on protocol biopsy was 1.7%, with 52% having positive urine cultures and Escherichia coli being the most common bacteria. Subjects with asymptomatic pyelonephritis had inferior graft survival compared to the matched cohort HR 1.88 (1.06-3.35), p = .0281. In addition, of these 123 subjects, 68 (55%) subsequently developed pyelonephritis, and 34 subjects had pyelonephritis within 6 months after this episode. Subjects with recurrent infections exhibited lower survival HR 2.86 (1.36-6.02) and a trend toward higher rejection risk. CONCLUSION: Asymptomatic histologic pyelonephritis can occur in kidney transplant recipients and is associated with inferior graft survival.

[Features of nephrotransplant blood flow during kidney transplant].

INTRODUCTION: Kidney transplantation, which provides a high quality of life for patients with terminal chronic renal failure worldwide, is recognized as one of the main achievements of modern medicine. Graft dysfunction is an urgent problem, the one-year survival rate of renal transplants is from 93% (from cadaveric donors) to 97% (from living donors), the five-year survival rate is on average 95%. The aim of the study consisted in determining the features of renal graft blood flow in the early post-transplantation period. MATERIALS AND METHODS: The results of operative treatment of 110 patients who underwent orthotopic kidney transplantation for various reasons were analyzed. The indication for transplantation was chronic kidney disease of 5 st in the outcome of the main disease: in 70 (64%) in chronic glomerulonephritis, in 22 (20%) patients in autosomal dominant polycystic kidney disease, 10 (9%) patients in diabetic nephropathy, in 8 (7%) patients in chronic pyelonephritis. The five-year survival rate of the renal graft during catamnestic follow-up was 88%. All patients underwent ultrasound dopplerography of a renal graft in dynamics from the first day to discharge. RESULTS: After transplantation of a renal graft, blood flow disorders are caused by swelling in the early postoperative period, but further to discharge there was a normalization of the blood flow rates of the renal graft. Which suggests a satisfactory functional state of the renal graft and is a favorable prognostic feature. Reduced blood flow in the graft and increased resistance index (RI) in ultrasound with dopplerography are signs of developing graft dysfunction. CONCLUSION: In almost all cases, postoperative postoperative renal transplant transplants continued to cause blood flow disturbances due to early postoperative edema. The use of ultrasound and Doppler imaging to assess graft status is a diagnostically valuable non-invasive method.

Long term renal outcome and risk of elevated blood pressure in children undergoing complete primary repair of bladder exstrophy (CPRE).

INTRODUCTION: Since the initiation of staged reconstruction for bladder exstrophy (BE), hypertension has been a known complication of the procedure. Hypertension is a well-established risk factor for chronic kidney disease (CKD) progression and associated with cardiovascular/cerebrovascular morbidity and mortality. Few studies exist evaluating the risk of developing hypertension among patients with bladder exstrophy who underwent CPRE. We hypothesized that long-term blood pressure levels may be elevated in males vs females, and may be correlated with presence of hydronephrosis, bladder neck reconstruction, or continence status. OBJECTIVE: We sought to revisit our long-term experience with CPRE and determine factors associated with incidence of elevated blood pressures. METHODS: We reviewed all BE patients undergoing CPRE at our institution from 1999 to 2019. Patients were considered eligible for inclusion if last renal ultrasound was obtained at least 5 years after repair. Upper tract outcomes based on imaging, history of pyelonephritis and renal function tests measured by serum creatinine and estimated glomerular filtration rate (eGFR, Schwartz formula) were reviewed. Systolic/diastolic blood pressures (SBP/DBP) from all encounters were captured. All blood pressure values were age adjusted by percentile. RESULTS: A total of 36 patients were considered eligible for review. Median follow-up of this cohort was 10.01 (5.16-21.47) years. The mean creatinine for the patients available was 0.58 mg/dL (SD = 0.20), at mean age of 8.90 years Neither SBP or DBP were significantly elevated in males vs females, but had lower odds of elevation >90th percentile for those with higher eGFR, lower renal length, and reimplantation. Pyelonephritis incidence was 38% (n = 14) with first episode at mean age of 8.8 years, and mean of 3.7 episodes per patient. DISCUSSION: At long term follow up, blood pressures following CPRE were not significantly elevated, despite the relatively frequent occurrence of CKD, and hydronephrosis. Male gender does appear to suggest higher risk for long-term deterioration in this regard. Higher eGFR, higher renal length, and presence of ureteral reimplantation were associated with lower likelihood of systolic/diastolic blood pressure elevation. Continence status and bladder neck reconstruction were not associated with likelihood of blood pressure elevation. CONCLUSIONS: Blood pressure and upper-tract outcomes for patients undergoing CPRE at birth are positive for the majority of patients. To avoid complications from hypertension, patients should be closely evaluated as the risks associated with elevated blood pressure are significant. Ultimately, larger-scale prospective and multi-institutional studies are further needed to characterize risks of hypertension in this complex patient population.

A comparison of adverse pregnancy events between ureteral stents and percutaneous nephrostomy tubes in the treatment of nephrolithiasis during pregnancy: A propensity score-matched analysis of a large multi-institutional research network.

PURPOSE: To investigate rates of adverse pregnancy events associated with the use of percutaneous nephrostomy tubes (PCN) versus ureteral stents in the treatment of nephrolithiasis during pregnancy. METHODS: We queried the TriNetX Diamond Network database to evaluate pregnant women (ICD-10 Z34, O09) with a history of nephrolithiasis (N20-23) who underwent a PCN (CPT 50432) or ureteral stent (52332) placement up to 6 months before delivery (O80-82). We controlled for the following potentially confounding variables through propensity score matching: age, race, ethnicity, acute pyelonephritis (N10), infections of the genitourinary tract in pregnancy (O23.0), and other sepsis (A41) at the time of stent or PCN placement. RESULTS: We identified 2,999 pregnant women who underwent ureteral stent placement and 321 who underwent PCN. Following propensity score matching, we found there to be no significant difference in the rate of premature labor or delivery (aOR 1.08, 95% CI 0.735-1.588), premature rupture of membranes (0.889, 0.453-1.743), intrauterine infection (0.906, 0.379-2.165), or c-Sect. (0.825, 0.408-1.667). Within 6 months of their initial procedure, women with a ureteral stent experienced a significantly decreased rate of subsequent urinary tract infection (UTI) or pyelonephritis (0.52, 0.38-0.71), inpatient hospital stay (0.40, 0.26-0.64), emergency department visit (0.65, 0.48-0.89), and repeat exchange procedure (0.70, 0.51-0.96). CONCLUSION: In the treatment of nephrolithiasis during pregnancy, PCN versus ureteral stent placement does not confer a significant difference in rates of adverse pregnancy events. However, ureteral stent placement was associated with a lower incidence of hospital admissions, emergency department visits, exchange procedures, and new UTIs or pyelonephritis.

Vesico-ureteric reflux in children and young people undergoing kidney transplantation.

Vesico-ureteric reflux (VUR) into transplanted kidneys in children and young people is a common occurrence, found in 19 to 60% of those who had an anti-reflux procedure and up to 79% in the absence of such a procedure. While VUR is unlikely to be of concern without evidence of symptomatic urinary tract infections, less certainty exists regarding outcomes when the VUR is associated with urinary tract infection (UTI) and transplant pyelonephritis. Issues explored will include additional risk factors that might predispose to UTI, any effect of pyelonephritis on acute and long-term kidney allograft function and practical strategies that may reduce the prevalence of infection.

Risk factors for Infectious Complications of Ureteroscopy after Obstructive Acute Pyelonephritis.

OBJECTIVES: To identify risk factors for infectious complication of ureteroscopy after obstructive acute pyelonephritis (OAPN). PATIENTS AND METHODS: This single-center, retrospective cohort study (#20200002, retrospectively registered in February 1st, 2020) included patients who underwent emergency drainage for OAPN and subsequently underwent ureteroscopic stone removal between January 2006 and December 2020. Multivariable analysis was conducted using demographic and stone-related factors to determine those that could predict postoperative febrile urinary tract infection (UTI). RESULTS: Overall, 432 patients underwent ureteroscopy after OAPN. The stone-free rate was 84.3%, whereas the overall and major complication rates were 17.6% and 3.2%, respectively. A total of 70 (16.2%) patient developed febrile UTI, among whom 34 (7.9%) and 11 (2.5%) developed sepsis and severe sepsis, respectively. Multivariable analysis identified diabetes mellitus [odds ratio (OR) 1.98, 95% confidence interval (CI) 1.05-3.74], duration from drainage to surgery >1 month (OR 2.28, 95% CI 1.20-4.74), and simultaneous retrograde intrarenal surgery (OR 2.96, 95% CI 1.35-6.48) as significant risk factors for UTI. After dividing patients into low- (0), intermediate- (1), and high- (2-3) risk groups according to the number of factors they had, the risk of postoperative UTI was 6.3%, 14.5%, and 27.7%, respectively (p for trend <0.001). CONCLUSIONS: Patients who underwent ureteroscopy after OAPN were at risk for postoperative UTI, despite its efficacy. Simultaneous retrograde intrarenal surgery should be carefully planned, especially for patients with diabetes mellitus or extended surgery wait times.

[Risk factors and mechanisms of acute pyelonephritis development after contact ureterolithotripsy].

AIM: of the study is to identify risk factors for the development of acute pyelonephritis after contact urethrolithotripsy (URLLT) and to establish the mechanisms for maintaining inflammation after the withdrawal of NSAIDs. MATERIAL AND METHODS: The study included 21 patients who underwent contact ureterolithotripsy (URLT). The severity of leukocyturia was assessed 1 day after URLT, 2 days (the last appointment of NSAIDs, the total duration of the drug was 9 days) and 3 days (24 hours after NSAID discontinuation). The number of circulating platelet-leukocyte aggregates (PLA) was calculated by microscopy of stained blood smears. Analysis of the functional activity of platelet receptors involved in the modulation of the acute inflammatory response was performed by the turbidimetric method on a ChronoLog analyzer (USA).Statistical analysis was performed using the MedCalc package. RESULTS: After URSL, when NSAIDs were prescribed to patients, the level of leukocyturia decreased (p<0.05) compared to that at the time of hospitalization. A similar dynamics was found by analyzing the amount of TLA in the blood. Similar dynamics was found in the analysis of the amount of TLA in the blood. After 24 hours of NSAIDs cancellation, an increase in the severity of leukocyturia was detected (p<0.001). At the same time, normoreactivity of the 2-adrenergic receptor, GPVI receptor, AT1 receptor, PAT receptor, P2X1 receptor and A2A receptor, as well as hyporeactivity of the 2-adrenergic receptor and P2Y receptors, were revealed. An analysis of correlations made it possible to establish that the 2-adrenoreceptor, AT1 receptor, and GPVI receptor play a key role in the formation of TPA. Incubation of blood cells in vitro with agonists made it possible to establish that the maximum effect of TLA formation was reproduced during the interaction of the 2-adrenergic receptor and the AT1 receptor. CONCLUSION: With the abolition of NSAIDs, activation of the sympathetic-adrenal and renin-angiotensin systems, as well as remodeling of the basement membrane of the vascular wall are risk factors for the development of acute pyelonephritis after URLS.

[Blebbing of plasma membrane of lymphocytes in infectious complications of urolithiasis].

INTRODUCTION: About 200 thousand operations for urolithiasis are performed annually in Russia, but the frequency of postoperative complications reaches 30%. Infectious complications occur with a frequency of up to 40% in the form of various forms of pyelonephritis, urosepsis is recorded in 3% of patients. The aim of the study determine the intensity of blebbing of the plasma membrane of lymphocytes in infectious complications of urolithiasis. MATERIALS AND METHODS: A prospective study examined 1,240 patients with urolithiasis. Inflammatory complications were characterized by the development of bacteriuria, serous pyelonephritis, purulent pyelonephritis and urosepsis. Complications of infectious nature were characterized by the development of bacteriuria, serous pyelonephritis, purulent pyelonephritis and urosepsis. During the study, complications of an infectious nature were detected in 148 patients, which amounted to 11,93% of cases. The control group consisted of - 25 persons with urolithiasis and a favorable course of the postoperative period. Lymphocyte membrane condition was evaluated by phase contrast microscopy. RESULTS: Changes in plasma membrane structure were more frequently reported in patients with postoperative purulent pyelonephritis and urosepsis. When assessing the presence of circulating microparticles, the highest number was recorded in patients with urolithiasis complicated by purulent pyelonephritis or urosepsis - 1318 [982; 2007] and 1531 [1028; 1963], respectively. A relationship was established between the degree of severity of terminal blebbing of the plasma membrane of lymphocytes and the nature of inflammatory complications in urolithiasis.

[X-ray endoscopic treatment in patients with ureteral anastomotic obliteration after orthotopic neobladder formation].

INTRODUCTION: Strictures and obliterations of ureteral anastomosis after radical cystectomy with orthotopic neobladder reconstruction occur in 8-13% of cases, mainly in the first 2 years after surgery. According to the European Association of Urology guidelines, open reconstruction is considered the "gold standard" for the treatment of those patients. At the same time, according to various publications, X-ray endoscopic treatment of ureteral anastomotic strictures can be performed, especially in patients who have undergone orthotopic neobladder reconstruction. MATERIALS AND METHODS: Three clinical cases of endoscopic treatment of ureteral anastomotic obliteration after orthotopic neobladder formation are presented. In all patients, nephrostomy tube was initially put due to acute pyelonephritis. Obliteration of the ureteral anastomosis was diagnosed by contrast-enhanced multispiral computed tomography and antegrade pyelography. The length of obliteration in all patients did not exceed 1.0 cm. The recurrence of the bladder cancer was excluded. After percutaneous opacification of the pelvicalyceal system and advancement of two guidewires ("working" and "safety") to the level of ureteral obliteration, a catheter with a built-in fiber optic light source was put in antegrade fashion along the "working" guidewire to the area of obliteration. During transurethral inspection of the reservoir, the distal end of the light source was visualized and the reservoir wall was cut "to the light" using electrosurgery (n=2) and a thulium fiber laser (one case). For adequate kidney drainage, two internal stents of 6 Fr were put for a period of 6 months in two patients and for 2 months in another case. RESULTS: All patients had an adequate diameter of the ureteral anastomosis after removal of the stents. In two cases, an adequate passage of the contrast agent through both ureters was maintained for 42 and 37 months after procedure (according to the follow-up computed tomography and excretory urography). One patient had an attack of acute pyelonephritis 2 months after the removal of internal stents due to recurrent stricture. After repeated endoscopic ureteral recanalization with putting of two internal stents for a period of 6 months, no recurrence of the stricture was observed during 28 months of follow-up. CONCLUSION: Endoscopic treatment of both primary and recurrent short ureteral anastomotic obliterations in patients with orthotopic neobladder allows for adequate ureteral patency, provided that two internal stents are left in place for 6 months.

Acute Allograft Pyelonephritis: Vague Symptoms, Indeterminate Laboratory Results, and the Necessity of Indication Biopsy.

OBJECTIVES: In this study, we examined the clinical and biochemical features of biopsy-proven acute pyelonephritis among 769 kidney transplant recipients. MATERIALS AND METHODS: This cohort study was performed between January 2003 and December 2019 at the University of Health Sciences (Izmir, Turkey). Acute pyelonephritis refers to urinary tract infection with acute graft dysfunction. All patients with suspected acute pyelonephritis underwent diagnostic biopsy and received antibiotic treatment for an average of 14 to 21 days. Patients with acute pyelonephritis (18/769, 2.3%) were categorized into groups of 9 patients each: group 1 developed acute pyelonephritis in the first 6 months, and group 2 developed acute pyelonephritis >6 months posttransplant. RESULTS: All patients in group 1 had acute graft dysfunction; only 2 (22%) were symptomatic. All patients recovered baseline graft function after treatment. Patients in group 2 had at least 2 laboratory findings that included leukocytosis, neutrophilia, and high C-reactive protein values. Six patients had urine culture positivity. Recurrent pyelonephritis occurred in 3 patients. Four patients had graft loss. Over the mean follow-up of 48.0 ± 28.4 months, 14 patients (78%) were alive with a functioning graft. CONCLUSIONS: Diagnostic biopsy is of great importance in patients with urinary tract infection accompanied by acute graft dysfunction in the first 6 months after transplant.

Histologic acute graft pyelonephritis after kidney transplantation: Incidence, clinical characteristics, risk factors, and association with graft loss.

BACKGROUND: Histologic acute graft pyelonephritis (HAGPN) after kidney transplantation (KT) has been assessed less frequently than urinary tract infections (UTIs) or clinical acute graft pyelonephritis. Risk factors for HAGPN, its association with graft loss, and measures that might prevent it are not known. METHODS: We performed a retrospective review of HAGPN cases identified from KT occurring between January 2008 and December 2017 at our institution. We compared the HAGPN cases to a randomly selected control group of KTs to identify risk factors using univariate and multivariate Cox regression models. The association between HAGPN and graft loss was also assessed, similarly. RESULTS: HAGPN was identified in 46 of 1391 patients (cumulative incidence, 5% [95% CI, 3%-7%]) undergoing KT at a single center from January 2008 through December 2017 (median time to diagnosis, 241 days after KT; interquartile range, 122-755 days). Indications for biopsy were follow-up of treated rejection (n = 20 [43%]), KT protocol biopsy (n = 19 [41%]), and acute kidney injury (n = 7 [15%]). Histologic rejection, UTI, and asymptomatic bacteriuria (ASB) were present in 23 (50%), 9 (20%), and 16 (35%). Multivariate Cox proportional hazards models comparing KT recipients with or without HAGPN (n = 46 and n = 138, respectively) showed that HAGPN was associated with urologic complication by day 30, delayed graft function, previous UTI or ASB, and a history of rejection. In the univariate and multivariate analyses, HAGPN was associated with an increased risk of graft loss. CONCLUSION: HAGPN is an infrequent, unanticipated, and clinically significant complication of KT.

Usefulness of computed tomography in the diagnosis of acute pyelonephritis in older patients suspected of infection with unknown focus.

BACKGROUND: In older adults, the diagnosis of acute pyelonephritis is challenging because of non-specific symptoms and false-positive urine test results. Few studies have investigated the diagnostic performance of computed tomography (CT) signs. PURPOSE: To evaluate the diagnostic performance of CT signs for acute pyelonephritis in older patients suspected of infection with unknown focus. MATERIAL AND METHODS: This cross-sectional study was conducted between 2015 and 2018. Patients aged ≥65 years who underwent blood cultures, urine culture, and non-contrast or contrast-enhanced CT on admission were included. Cases with clinically presumable infection focus before CT were excluded. Two radiologists blinded to clinical information independently reviewed five CT signs: perirenal fat stranding; pelvicalyceal wall thickening and enhancement; renal enlargement; thickening of Gerota's fascia; and area(s) of decreased attenuation. The final diagnoses were made by a clinical expert panel. RESULTS: Among 473 eligible patients, 61 were diagnosed with acute pyelonephritis. When the laterality of findings between the left and right kidneys were considered, the positive and negative likelihood ratios of perirenal fat stranding were 4.0 (95% confidence interval [CI] = 2.3-7.0) and 0.8 (95% CI = 0.7-0.9) in non-contrast CT, respectively. The other signs in non-contrast CT showed similar diagnostic performance with positive and negative likelihood ratios of 3.5-11.3 and 0.8-0.9, respectively. CONCLUSION: CT signs can help physicians diagnose acute pyelonephritis in older patients suspected of infection with unknown focus.

Antibacterial activity of apramycin at acidic pH warrants wide therapeutic window in the treatment of complicated urinary tract infections and acute pyelonephritis.

BACKGROUND: The clinical-stage drug candidate EBL-1003 (apramycin) represents a distinct new subclass of aminoglycoside antibiotics for the treatment of drug-resistant infections. It has demonstrated best-in-class coverage of resistant isolates, and preclinical efficacy in lung infection models. However, preclinical evidence for its utility in other disease indications has yet to be provided. Here we studied the therapeutic potential of EBL-1003 in the treatment of complicated urinary tract infection and acute pyelonephritis (cUTI/AP). METHODS: A combination of data-base mining, antimicrobial susceptibility testing, time-kill experiments, and four murine infection models was used in a comprehensive assessment of the microbiological coverage and efficacy of EBL-1003 against Gram-negative uropathogens. The pharmacokinetics and renal toxicology of EBL-1003 in rats was studied to assess the therapeutic window of EBL-1003 in the treatment of cUTI/AP. FINDINGS: EBL-1003 demonstrated broad-spectrum activity and rapid multi-log CFU reduction against a phenotypic variety of bacterial uropathogens including aminoglycoside-resistant clinical isolates. The basicity of amines in the apramycin molecule suggested a higher increase in positive charge at urinary pH when compared to gentamicin or amikacin, resulting in sustained drug uptake and bactericidal activity, and consequently in potent efficacy in mouse infection models. Renal pharmacokinetics, biomarkers for toxicity, and kidney histopathology in adult rats all indicated a significantly lower nephrotoxicity of EBL-1003 than of gentamicin. INTERPRETATION: This study provides preclinical proof-of-concept for the efficacy of EBL-1003 in cUTI/AP. Similar efficacy but lower nephrotoxicity of EBL-1003 in comparison to gentamicin may thus translate into a higher safety margin and a wider therapeutic window in the treatment of cUTI/API. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Clinical and microbiological characteristics of men with nonobstructive acute pyelonephritis: A multicenter retrospective observational study.

ABSTRACT: To investigate the differences in clinical and microbiological features in men hospitalized with community-acquired (CA) and healthcare-associated (HA) nonobstructive acute pyelonephritis (APN), as well as the predictive factors associated with bacteremia.Men discharged from urological centers with nonobstructive APN were identified using an electronic medical records system. We compared the clinical and microbiological data between subjects with CA-APN and HA-APN.Of the 245 men with nonobstructive APN, 175 had CA-APN, and 70 had HA-APN. The HA group was significantly older, had a longer hospital stay, and had more underlying diseases, bacteremia, and intensive care unit admissions than the CA group. The most commonly cultured microorganism was Escherichia coli. The susceptibility of the cultured bacteria to fluoroquinolone was 68.7% in the CA group and 45.3% in the HA group (P = .005). The proportion of extended-spectrum beta-lactamase-producing bacteria was 22.7% for CA and 53.5% for HA (P < .001). The sensitivity to piperacillin/tazobactam was 94.9% for CA and 90.0% for HA, and the sensitivity to amikacin was more than 95% for both groups. The multivariate analysis revealed that an age ≥65 years and chronic liver disease were independent predictive factors for bacteremia.The incidence of antibiotic resistance and bacteremia was higher in the HA group than in the CA group. However, resistance to fluoroquinolone and the presence of extended-spectrum beta-lactamase-producing bacteria were high in both groups. Piperacillin/tazobactam and amikacin may be suitable treatment options in men with nonobstructive APN.

Optimal duration of preoperative antibiotic treatment prior to ureteroscopic lithotripsy to prevent postoperative systemic inflammatory response syndrome in patients presenting with urolithiasis-induced obstructive acute pyelonephritis.

PURPOSE: There is no consensus on the optimal duration of preoperative antibiotic treatment prior to ureteroscopic lithotripsy in patients presenting with urolithiasis-induced obstructive acute pyelonephritis (APN). We aimed to identify surgeon-modifiable, preoperative risk factors associated with postoperative systemic inflammatory response syndrome (SIRS) in these patients. MATERIALS AND METHODS: This multicenter retrospective study evaluated 115 patients who presented with urolithiasis-induced obstructive APN between January 2008 and December 2019. All patients were administered intravenous third-generation cephalosporin until culture sensitivity confirmation or until ureteroscopic lithotripsy. Data were collected for age, sex, diabetes mellitus, performance status, stone features, hydronephrosis grade, preoperative renal collecting system drainage, laboratory data, operative time, and duration of preoperative antibiotic treatment. Sensitivity analysis using Youden's index and logistic regression analysis were used to assess risk factors of postoperative SIRS. RESULTS: Postoperative SIRS was identified in 32 (27.8%) patients. The incidence of postoperative SIRS was higher in patients who received preoperative antibiotic treatment for fewer than 14 days (38.8% vs. 12.5%; p=0.001). Backward variable selection logistic regression analysis revealed maximal stone diameter ≥15 mm, duration of preoperative antibiotic treatment <14 days, and preoperative C-reactive protein (CRP) level ≥6.0 mg/L to be associated with higher risk of postoperative SIRS. CONCLUSIONS: Patients with urolithiasis-induced obstructive APN planned for ureteroscopic lithotripsy should be administered at least 14 days of preoperative antibiotic administration and achieve a serum CRP level ≤6.0 mg/L to minimize the risk of postoperative SIRS.

Association between acute graft pyelonephritis and kidney graft survival: A single-center observational study.

The association between acute graft pyelonephritis (AGPN) and graft failure in kidney transplant recipients (KTR) remains controversial. In this single-center observational study, we aimed to assess the incidence of AGPN as a time-dependent posttransplantation event. We also examined the association between the diagnosis of AGPN and graft outcomes. In total, we evaluated 1480 patients who underwent kidney transplantation between January 2007 and December 2017. During a median follow-up of 5.04 years, we observed 297 AGPN episodes that occurred in 158 KTR. To evaluate the association between AGPN and clinical outcomes, we performed Cox proportional hazards regression analyses in which AGPN was entered as a time-dependent covariate. AGPN was independently associated with an increased risk of graft loss (hazard ratio = 1.66; 95% confidence interval [CI]: 1.05-2.64, p < .03) and a persistently decreased eGFR (fixed effect on intercept: -2.29 ml/min/1.73 m2 ; 95% CI: from -3.23 to -1.35, p < .01). However, neither mortality nor biopsy-proven acute rejection was found to correlate with AGPN. Moreover, recurrent AGPN episodes did not appear to have an additive detrimental impact on graft loss. These data represent a promising step in understanding whether AGPN prevention may decrease the risk of graft loss in KTR.