No abstract available

Acute pyelonephritis (APN), although a common clinical entity, still not much is known about the clinical profile in the Indian scenario. We prospectively collected clinical, biochemical, and radiological data of patients hospitalized with a diagnosis of APN from March 2014 to June 2016. A total of 296 cases were included in the study. Mean age was 53.85 ± 9.78 years. Male to females ratio was 1.93:1. Among the risk factors recognized for complicated pyelonephritis (PN), diabetes mellitus (DM) (54.4%) was the most common factor followed by renal calculi (14.4%), benign prostatic hyperplasia (6.7%), immunocompromised state (3.3%), stricture urethra and meatal stenosis (3.3%), and neurogenic bladder (2%). Urinary culture was negative in 153 (51.7%) and positive in 143 patient (48.3%). Most common organism isolated was Escherichia coli (29.7%), followed by Klebsiella pneumoniae (5.4%), pseudomonas (5.4%), Enterococcus (4.4%), and Proteus in 10 (3.4%). Serum creatinine of more than 1.5 mg/dl at admission was seen in 96.3% patients; 40% of them had underlying chronic kidney disease with DM being the most common. Multiorgan dysfunction either at admission or during the course in hospital stay was seen in 31.8% patients. Twelve (2%) had emphysematous PN. Six patients had Class II, 4 had Class III, 1 with Class I, and another with Class IV. A total of 18 deaths were noted (6.1%). Hemoglobin <10 g/dl, serum creatinine at admission >1.5 mg/dl, HbA1c% >10%, and immunosuppression had statistically significant association with the development of multiorgan dysfunction on univariate analysis, but on multivariate analysis, only hemoglobin, HbA1c%, and immunosuppression reached statistical significance. Even with attributable risk of mortality, only hemoglobin, HbA1c%, and immunosuppression reached statistical significance on multivariate analysis. HbA1c% adds to the predictive parameters to recognize at-risk patients to intensify the treatment and avoid complications.

Emphysematous pyelonephritis (EPN) is a rare, life-threatening necrotizing renal parenchymal infection. Traditional management of EPN with nephrectomy had a mortality of 40-50%. The purpose of this case series was to assess the management, biochemical factors, and outcome of EPN patients.

A specific type of urinary cast has been demonstrated in the urine of patients who have acute pyelonephritis. This cast is characterized by the presence of bacteria in its matrix and appears to be specific for and diagnostic of pyelonephritis. It is easily demonstrated by routine urinalysis.

For unknown reasons, urinary tract infections (UTIs) are clustered in certain individuals. Here we propose a novel, genetically determined cause of susceptibility to acute pyelonephritis, which is the most severe form of UTI. The IL-8 receptor, CXCR1, was identified as a candidate gene when mIL-8Rh mutant mice developed acute pyelonephritis (APN) with severe tissue damage.

Renal scarring after pyelonephritis is linked to long-term health risks for hypertension and chronic kidney disease. Androgen exposure increases susceptibility to, and severity of, uropathogenic Escherichia coli (UPEC) pyelonephritis and resultant scarring in both male and female mice, while anti-androgen therapy is protective against severe urinary tract infection (UTI) in these models. This work employed androgenized female C57BL/6 mice to elucidate the molecular mechanisms of post-infectious renal fibrosis and to determine how these pathways are altered by the presence of androgens. We found that elevated circulating testosterone levels primed the kidney for fibrosis by increasing local production of TGFβ1 before the initiation of UTI, altering the ratio of transcription factors Smad2 and Smad3 and increasing the presence of mesenchymal stem cell (MSC)-like cells and Gli1 + activated myofibroblasts, the cells primarily responsible for deposition of scar components. Increased production of TGFβ1 and aberrations in Smad2:Smad3 were maintained throughout the course of infection in the presence of androgen, correlating with renal scarring that was not observed in non-androgenized female mice. Pharmacologic inhibition of TGFβ1 signaling blunted myofibroblast activation. We conclude that renal fibrosis after pyelonephritis is exacerbated by the presence of androgens and involves activation of the TGFβ1 signaling cascade, leading to increases in cortical populations of MSC-like cells and the Gli1 + activated myofibroblasts that are responsible for scarring.

The clinical significance and appropriate management of graft pyelonephritis diagnosed by biopsy are poorly understood.

Objective The aim of this study was to identify predictive factors for bacteremia conveniently and quickly among outpatients diagnosed with pyelonephritis. Patients All patients who were diagnosed with pyelonephritis at the outpatient clinic in the Department of General Medicine of Juntendo University Hospital from April 1, 2008, to June 30, 2015, were enrolled. Patients from whom blood cultures had not been taken were excluded. Methods Clinical information was extracted from medical charts. Factors potentially predictive of bacteremia were analyzed using a t-test and Fisher's exact test, followed by a multivariable logistic regression model analysis. Results Blood cultures were drawn from 116 patients, and 25 (22%) presented with bacteremia. A multivariate analysis with the age, chills, platelet count and urine nitrite test results revealed that older age, positive urinary nitrite test results and chills tended to be associated with bacteremia, respectively. [older age: unit odds ratio (OR) 1.02, p=0.052, 95% confidence interval (CI) 1.00-1.05, positive urinary nitrite test findings: OR 2.5, p=0.092, 95% CI 0.86-7.7, chills: OR 2.5, p=0.096, 95% CI 0.84-7.65]. The area under the receiver operating characteristic (ROC) curve of this model was 0.77. Regardless of age, positive urinary nitrite test findings were significantly associated with bacteremia (OR 3.1, p=0.033, 95% CI 1.1-9.2), and chills tended to be associated with bacteremia (OR 2.7, p=0.07, 95% CI 0.93-7.9) The area under the ROC curve of this model was 0.75. Conclusion Bacteremia should be considered in pyelonephritis patients with rapidly assessable factors in outpatient clinic. In particular, a model including a urinary nitrite test has the potential to aid in the prediction of bacteremia.

Carbonic anhydrase 2 regulates acid-base homeostasis, and recent findings have indicated a correlation between cellular control of acid-base status and the innate defense of the kidney. Mice deficient in carbonic anhydrase 2 (Car2(-/-) mice) have metabolic acidosis, impaired urine acidification, and are deficient in normal intercalated cells. The objective of the present study was to evaluate the biological consequences of carbonic anhydrase 2 deficiency in a murine model of pyelonephritis. Infection susceptibility and transcription of bacterial response components in Car2(-/-) mice were compared with wild-type littermate controls. Car2(-/-) mice had increased kidney bacterial burdens along with decreased renal bacterial clearance after inoculation compared with wild-type mice. Standardization of the urine pH and serum HCO(3)(-) levels did not substantially alter kidney infection susceptibility between wild-type and Car2(-/-) mice; thus, factors other than acid-base status are responsible. Car2(-/-) mice had significantly increased neutrophil-gelatinase-associated lipocalin mRNA and protein and expression at baseline and a marked decreased ability to upregulate key bacterial response genes during pyelonephritis. Our findings provide in vivo evidence that supports a role for carbonic anhydrase 2 and intercalated cells in promoting renal bacterial clearance. Decreased carbonic anhydrase expression results in increased antimicrobial peptide production by cells other than renal intercalated cells, which is not sufficient to prevent infection after a bacterial challenge.

C5a receptor 1 (C5aR1) is a G protein-coupled receptor for C5a and also an N-linked glycosylated protein. In addition to myeloid cells, C5aR1 is expressed on epithelial cells. In this study, we examined the role of C5aR1 in bacterial adhesion/colonization of renal tubular epithelium and addressed the underlying mechanisms of this role. We show that acute kidney infection was significantly reduced in mice with genetic deletion or through pharmacologic inhibition of C5aR1 following bladder inoculation with uropathogenic E. coli (UPEC). This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice. Confocal microscopy demonstrated that UPEC bind to Man on the luminal surface of renal tubular epithelium. In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling. Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.

Xanthogranulomatous pyelonephritis (XGP) is an inflammatory condition of the kidney and its treatment most often involves a combination of antibiotics and nephrectomy. This study aimed to define the clinical features and management of XGP, focusing on microbiological aspects and antibiotic therapy.

Acute pyelonephritis is a common, serious bacterial infection in children. The prevalence of acute pyelonephritis is due at least in part to vesicoureteral reflux (VUR). Although an association between abnormalities in electrolyte and acid-base balance and pyelonephritis is common in young children, the impact of metabolic acidosis (MA) on progression of acute pyelonephritis is not fully understood. In this study, the effect of MA on pyelonephritis was studied in C3H mouse strains prone to VUR. MA induced by ammonium chloride supplementation in food specifically impaired clearance of urinary tract infection with uropathogenic Escherichia. coli (UPEC-UTI) in innate immune competent C3H strains (HeOuJ, HeN), whereas kidney UPEC burden in Tlr-4-deficient HeJ mice was unaffected. Antibody-mediated depletion of myeloid cells (monocytes, neutrophil) markedly increased UPEC burden in the bladder and kidney confirming the pivotal role of neutrophils and tissue-resident macrophages in clearance of UPEC-UTI. MA concurrent with UPEC-UTI markedly increased expression of cytokine (TNFα, IL-1β, IL-6) and chemokine (CXCL 1, 2, and 5) mRNA in isolated kidney CD cells and kidney neutrophil infiltrates were increased four- to fivefold compared to normal, UPEC-infected mice. Thus, MA intensified pyelonephritis and increased the risk of kidney injury by impairing clearance of UPEC-UTI and potentiating renal inflammation characterized by an elevated kidney neutrophil infiltrate.

We present a new preclinical model to study treatment, resolution and sequelae of severe ascending pyelonephritis. Urinary tract infection (UTI), primarily caused by uropathogenic Escherichia coli (UPEC), is a common disease in children. Severe pyelonephritis is the primary cause of acquired renal scarring in childhood, which may eventually lead to hypertension and chronic kidney disease in a small but important fraction of patients. Preclinical modeling of UTI utilizes almost exclusively females, which (in most mouse strains) exhibit inherent resistance to severe ascending kidney infection; consequently, no existing preclinical model has assessed the consequences of recovery from pyelonephritis following antibiotic treatment. We recently published a novel mini-surgical bladder inoculation technique, with which male C3H/HeN mice develop robust ascending pyelonephritis, highly prevalent renal abscesses and evidence of fibrosis. Here, we devised and optimized an antibiotic treatment strategy within this male model to more closely reflect the clinical course of pyelonephritis. A 5-day ceftriaxone regimen initiated at the onset of abscess development achieved resolution of bladder and kidney infection. A minority of treated mice displayed persistent histological abscess at the end of treatment, despite microbiological cure of pyelonephritis; a matching fraction of mice 1 month later exhibited renal scars featuring fibrosis and ongoing inflammatory infiltrates. Successful antibiotic treatment preserved renal function in almost all infected mice, as assessed by biochemical markers 1 and 5 months post-treatment; hydronephrosis was observed as a late effect of treated pyelonephritis. An occasional mouse developed chronic kidney disease, generally reflecting the incidence of this late sequela in humans. In total, this model offers a platform to study the molecular pathogenesis of pyelonephritis, response to antibiotic therapy and emergence of sequelae, including fibrosis and renal scarring. Future studies in this system may inform adjunctive therapies that may reduce the long-term complications of this very common bacterial infection.

Acute pyelonephritis (APN) is an inflammatory disease that leads to kidney malfunction. The objective of this investigation was to evaluate the impact of gentamicin (GEN) and ceftriaxone (CEF) alone and in combination with mycophenolate mofetil (MMF) on experimentally induced APN. Forty two Wistar male rats were assigned into seven groups +APN, APN +GEN, APN+CEF, APN+MMF, APN+GEN+MMF and APN+CEF+MMF. APN was induced by injecting E. coli in the left kidney. The control and +APN groups were treated with normal saline while the other APN groups received GEN, CEF, or MMF alone and/or in combination for 2 weeks. The elevated total white blood cells count and increased level of creatinine and blood urea nitrogen (BUN) in +APN groups returned to normal levels following 14 days treatment with GEN and CEF. Co-administration of GEN with MMF could not recover the APN-induced changes and resulted in a significant (P < 0.05) elevation of creatinine and BUN levels. Histopathological studies supported the biochemical findings as GEN and CEF alone could partly restore the APN-induced degeneration and leukocytic infiltration; however, the combination therapy of GEN plus MMF failed to reduce the APN-induced damages. The antibacterial susceptibility test demonstrated that the strain of E. coli used in this study was susceptible to GEN and CEF and the combination therapy did not change the antibacterial potency. These findings suggest that co-administration of GEN with MMF in APN may enhance kidney damage and the adverse effects of combination therapeutic regimen could be related partly to incompatibility of these compounds.

The current guidelines for the diagnosis of acute pyelonephritis (APN) recommend that APN be diagnosed based on the clinical features and the presence of pyuria. However, we observed that some of the patients who are diagnosed with APN do not have characteristic clinical features or pyuria at the initial examination. We performed this study to investigate the characteristics of APN without pyuria.

The epidemiology of acute pyelonephritis (APN) has changed with time. Therefore we investigated the current clinical characteristics of APN and the significance of proper surgical management for treatment of 1,026 APN patients in South Korea for the past 5 yr. The male-to-female ratio was about 1:8. The peak ages of female patients were 20s (21.3%) and over 60s (23.7%), while that of male was over 60s (38.1%). The occurrence of sepsis was 10.1%. Complicated APN patients were 35.4%. Ninety-four patients (9.2%) needed urological procedures. The duration of the flank pain and of the costovertebral angle tenderness in complicated APN patients was statistically significantly longer than that with simple APN patients (4.3 vs. 3.4 days, 4.4 vs. 4.0 days). If flank pain and costovertebral angle tenderness sustain over 4 days, proper radiologic studies should be performed immediately with the consideration of surgical procedure. Also the resistance to antibiotics was increasing. As the sensitivities to ampicillin (27.2%) and trimethoprim/sulfamethoxazole (44.7%) of Escherichia coli and Klebsiella pneumoniae were very low, it is necessary to take the careful choice of antibiotics into consideration.

No abstract available

To determine whether treatment for urinary tract infections in children could be individualized using biomarkers for acute pyelonephritis.

Objective  Group B Streptococcus (GBS) colonization of the lower urinary tract in pregnancy is associated with severe infections such as chorioamnionitis, endometritis, and pyelonephritis. The objective of this study was to compare rates of progression to pyelonephritis between GBS and Escherichia coli lower urinary tract infections (LUTIs), as well as compare infectious and obstetric morbidity secondary to these pathogens. Study Design  Retrospective cohort of pregnant women with LUTIs (asymptomatic bacteria or acute cystitis [AC]) from a single health system between July 2013 and May 2019. Demographic, infectious, antepartum, and intrapartum data were abstracted from medical records of women with GBS or E. coli LUTI. The primary outcome was progression to pyelonephritis. Secondary outcomes included pyelonephritis-related anemia, sepsis, pyelonephritis length of stay (LOS), median gestational age (GA) at delivery, preterm delivery, and low birth weight (LBW). Logistic regression was used to calculate the adjusted odds of the primary outcome. Results  Of 729 pregnant women with urinary colonization, 433 were culture positive for one of the aforementioned bacteria, with 189 (43.6%) having GBS and 244 (56.4%) having E. coli. Women with E. coli were more likely to be younger, use tobacco, have a history of AC, and have a history of preterm birth. Rates of progression to pyelonephritis were markedly higher with E. coli (15.6%) than with GBS (1.1%; p  < 0.001). Median LOS for pyelonephritis and pyelonephritis-related morbidities did not differ. Median GA at delivery, preterm delivery, and LBW rates also did not differ. In adjusted analysis, controlling for history of AC, insurance status, tobacco use, prior preterm birth, primary infection type, and maternal age, women with GBS LUTI had markedly decreased odds of developing pyelonephritis in pregnancy compared with those with E. coli (adjusted odds ratio: 0.04, 95% confidence interval: 0.01-0.28). Conclusion   Escherichia coli infections progress to pyelonephritis in pregnancy at markedly higher rates than GBS, although obstetric outcomes are similar.

Type 1 pili have long been considered the major virulence factor enabling colonization of the urinary bladder by uropathogenic Escherichia coli (UPEC). The molecular pathogenesis of pyelonephritis is less well characterized, due to previous limitations in preclinical modeling of kidney infection. Here, we demonstrate in a recently developed mouse model that beyond bladder infection, type 1 pili also are critical for establishment of ascending pyelonephritis. Bacterial mutants lacking the type 1 pilus adhesin (FimH) were unable to establish kidney infection in male C3H/HeN mice. We developed an in vitro model of FimH-dependent UPEC binding to renal collecting duct cells, and performed a CRISPR screen in these cells, identifying desmoglein-2 as a primary renal epithelial receptor for FimH. The mannosylated extracellular domain of human DSG2 bound directly to the lectin domain of FimH in vitro, and introduction of a mutation in the FimH mannose-binding pocket abolished binding to DSG2. In infected C3H/HeN mice, type 1-piliated UPEC and Dsg2 were co-localized within collecting ducts, and administration of mannoside FIM1033, a potent small-molecule inhibitor of FimH, significantly attenuated bacterial loads in pyelonephritis. Our results broaden the biological importance of FimH, specify the first renal FimH receptor, and indicate that FimH-targeted therapeutics will also have application in pyelonephritis.