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Pyelonephritis

Pyelonephritis is a bacterial infection of the kidney that involves inflammation of the renal pelvis and parenchyma, typically resulting from the ascent of pathogens from a lower urinary tract infection.^[1] It is a serious form of urinary tract infection (UTI) that requires prompt medical attention to prevent complications such as permanent kidney damage or sepsis.^[2]^[3] Common symptoms include fever, chills, flank pain, dysuria, frequent urination, and nausea or vomiting, though presentation can vary by age and severity.^[2]^[4] The primary causative agent is Escherichia coli, accounting for most cases, with other uropathogens like Klebsiella or Proteus species involved less frequently.^[1] Risk factors encompass female gender due to anatomical differences, urinary obstructions, vesicoureteral reflux, diabetes, immunosuppression, and indwelling catheters.^[2]^[5] Diagnosis typically involves urinalysis showing pyuria and bacteriuria, urine culture for pathogen identification, and sometimes imaging to rule out complications like abscesses.^[6]^[1] Treatment generally consists of antibiotics tailored to the suspected or confirmed pathogen, with oral therapy for uncomplicated cases and intravenous administration for severe or complicated infections, often requiring hospitalization.^[7]^[8] If untreated, pyelonephritis can lead to acute kidney injury, chronic renal scarring, hypertension, or life-threatening sepsis.^[9]^[2] Prevention strategies include adequate hydration, prompt treatment of lower UTIs, and managing underlying conditions like diabetes or urinary obstructions.^[10]

Overview and Pathophysiology

Definition and Classification

Pyelonephritis is a bacterial infection involving inflammation of the renal pelvis and parenchyma, typically resulting from an ascending infection originating in the lower urinary tract, such as the bladder (cystitis).^[1] This distinguishes it from lower urinary tract infections by its involvement of the upper urinary tract structures, including the kidneys, where the infection can lead to significant tissue damage if untreated.^[11] The most common causative pathogen is Escherichia coli, though other gram-negative bacteria may also be implicated.^[5] Pyelonephritis is primarily classified into acute and chronic forms based on clinical presentation, duration, and pathological outcomes. Acute pyelonephritis represents a sudden-onset infection characterized by rapid inflammation and systemic symptoms, which is often reversible with prompt antibiotic therapy, though it may cause temporary renal dysfunction.^[1] In contrast, chronic pyelonephritis develops from persistent or recurrent infections, leading to progressive tubulointerstitial inflammation, cortical scarring, and potential long-term renal impairment, frequently associated with underlying conditions like vesicoureteral reflux or urinary tract obstruction.^[12]^[13] Rare variants include emphysematous pyelonephritis, a severe necrotizing infection marked by gas formation within the renal parenchyma due to fermentation by gas-producing bacteria, often seen in diabetics and carrying mortality rates of approximately 13-25%.^[14] Xanthogranulomatous pyelonephritis is another uncommon chronic variant, presenting as a granulomatous destructive process that replaces functional renal tissue with lipid-laden macrophages and fibrosis, typically linked to chronic obstruction by calculi and resulting in a non-functioning kidney.^[15] These variants highlight the spectrum of disease severity and underscore the need for tailored management approaches.

Pathophysiology

Pyelonephritis typically arises through an ascending infection pathway, in which pathogenic bacteria from the lower urinary tract migrate retrograde through the ureters to reach the renal pelvis and parenchyma. This migration is often promoted by vesicoureteral reflux, a condition where urine and bacteria backflow from the bladder into the ureters, bypassing normal antireflux mechanisms at the ureterovesical junction. Less commonly, hematogenous spread from distant sites of bacteremia can seed the kidneys, though this route predominates in neonates or immunocompromised individuals.^[5]^[1] The predominant causative agent is Escherichia coli, responsible for approximately 70-90% of community-acquired cases, with other Gram-negative Enterobacteriaceae such as Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter species accounting for the remainder. These uropathogens express key virulence factors that enhance their ability to colonize and invade the urinary tract; notably, P fimbriae (also known as Pap pili) mediate specific adhesion to glycolipid receptors on uroepithelial cells, facilitating bacterial attachment, biofilm formation, and evasion of urinary flow. Additional factors like type 1 fimbriae, hemolysins, and siderophores further support persistence and tissue invasion by promoting cytotoxicity and iron acquisition in the nutrient-limited urinary environment.^[16]^[17] Once in the renal parenchyma, bacteria elicit a robust host immune response primarily through pattern recognition receptors, including Toll-like receptor 4 (TLR4) for lipopolysaccharide and TLR5 for flagellin, activating NF-κB signaling and the release of proinflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β). This inflammatory cascade recruits neutrophils to the site of infection, resulting in pyuria— the presence of pus in urine—and local edema, which can impair renal blood flow and lead to tubular necrosis. In severe or unresolved infections, the unchecked inflammation may progress to microabscess formation within the cortex or medulla, exacerbating tissue damage.^[17]^[18] Recurrent episodes of pyelonephritis, often in the context of structural abnormalities or persistent bacterial reservoirs, drive a chronic inflammatory state characterized by progressive tubulointerstitial fibrosis. Repeated neutrophil infiltration and cytokine-mediated signaling activate fibroblasts, leading to excessive extracellular matrix deposition and renal scarring, which can distort calyces and impair nephron function over time. This fibrotic remodeling is mediated by transforming growth factor-beta (TGF-β) and contributes to long-term complications such as hypertension and reduced glomerular filtration rate.^[18]

Clinical Features

Signs and Symptoms

Pyelonephritis manifests differently depending on whether it is acute or chronic, with acute cases typically presenting more dramatically. In acute pyelonephritis, patients commonly experience high fever exceeding 38°C, often accompanied by chills and systemic malaise.^[1] Flank pain, usually unilateral and located in the lower back or side, is a hallmark symptom, frequently radiating to the groin or abdomen.^[2] Additional lower urinary tract symptoms include dysuria, urinary frequency, and urgency, while gastrointestinal complaints such as nausea and vomiting are also prevalent.^[4] Chronic pyelonephritis, often resulting from repeated episodes of acute infection or vesicoureteral reflux, tends to have subtler and more insidious symptoms. Patients may report a dull, persistent flank pain and recurrent urinary tract infections, alongside general fatigue due to progressive renal impairment.^[19] Scarring from ongoing inflammation can lead to secondary hypertension in a significant proportion of cases.^[20] Atypical presentations are particularly common in vulnerable populations, such as the elderly or immunocompromised individuals, where classic signs like fever and flank pain may be absent. Instead, these patients might exhibit nonspecific symptoms, including confusion, altered mental status, or generalized weakness without prominent urinary complaints.^[21]^[22] On physical examination, costovertebral angle tenderness—elicited by percussion or palpation over the affected kidney—is a key finding in both acute and chronic forms, though it may be less pronounced in chronic cases.^[1]

Risk Factors

Pyelonephritis susceptibility is influenced by various anatomical abnormalities that impair normal urine flow and facilitate bacterial ascent to the kidneys. Urinary tract obstructions, such as kidney stones, urethral strictures, or an enlarged prostate in men, create stagnant urine pools that promote bacterial proliferation and increase infection risk.^[2] Vesicoureteral reflux, where urine backflows from the bladder to the ureters and kidneys, is another key anatomical factor, particularly in individuals with congenital or acquired urinary tract malformations, heightening the likelihood of ascending infections.^[1] Indwelling urinary catheters, often used in hospitalized or immobile patients, introduce bacteria directly into the urinary tract and are associated with up to an 80% increased risk of infection with prolonged use.^[23] Demographic factors play a significant role, with females facing a substantially higher risk due to their shorter urethra, which allows easier bacterial entry from the perineal area.^[2] Pregnancy further elevates this vulnerability through physiological changes like ureteral dilation and relative immunosuppression, resulting in an incidence of pyelonephritis of 1-2% among pregnant individuals, compared to lower rates in non-pregnant populations.^[24] Diabetes mellitus, which impairs immune response and glycosuria favors bacterial growth, independently increases pyelonephritis risk more than fourfold in affected individuals.^[25] Behavioral and lifestyle elements also contribute to susceptibility. Frequent sexual activity, especially more than three times per week, is linked to nearly a sixfold increase in pyelonephritis risk among healthy women, likely due to mechanical introduction of uropathogens.^[25] Inadequate personal hygiene practices, such as improper wiping techniques after defecation or insufficient perineal cleaning, can facilitate bacterial colonization of the urethra, though this is more pronounced in combination with other factors.^[26] Medical conditions involving immunosuppression heighten the overall risk by reducing the body's ability to combat ascending infections. Conditions like HIV, ongoing chemotherapy, or post-transplant immunosuppressive therapy compromise host defenses, making pyelonephritis more likely in these populations.^[1] Neurogenic bladder, often resulting from spinal cord injuries or neurological disorders, leads to incomplete bladder emptying and urinary retention, further predisposing individuals to recurrent infections.^[2]

Diagnosis

Laboratory Investigations

Laboratory investigations play a crucial role in confirming the diagnosis of pyelonephritis, identifying the causative pathogen, and assessing disease severity. Initial evaluation often begins with urinalysis, which provides rapid insights into urinary tract inflammation and infection. Key findings include pyuria, characterized by more than 10 white blood cells per high-power field (WBC/hpf) on microscopic examination, indicating an inflammatory response in the urinary tract.^[1] Bacteriuria, the presence of bacteria in the urine, is commonly observed, while positive tests for nitrites suggest infection by nitrate-reducing organisms such as Enterobacteriaceae.^[1] Additionally, leukocyte esterase, an enzyme released by white blood cells, is frequently detected on dipstick testing, further supporting the presence of pyuria and infection.^[6] Urine culture remains the gold standard for microbiological confirmation, allowing identification of the specific pathogen and determination of antimicrobial susceptibilities to guide targeted therapy. A colony count exceeding 10^5 colony-forming units per milliliter (CFU/mL) in a midstream clean-catch specimen is generally considered indicative of significant bacteriuria consistent with pyelonephritis.^[16] Results typically take 24 to 48 hours, emphasizing the importance of empirical treatment initiation while awaiting culture data.^[6] Blood tests are essential for evaluating systemic involvement and complications. Complete blood count often shows leukocytosis, with elevated white blood cell counts reflecting the inflammatory response.^[1] Inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are typically elevated, helping to gauge infection severity and monitor response to treatment.^[16] Blood cultures should be obtained, particularly in hospitalized patients or those with signs of sepsis, as they are positive for bacteremia in approximately 20% to 30% of acute pyelonephritis cases.^[16] Assessment of renal function is critical to detect any impairment associated with the infection. Serum creatinine and blood urea nitrogen (BUN) levels are measured to evaluate kidney function, with elevations indicating potential acute kidney injury due to dehydration, obstruction, or direct renal parenchymal damage.^[6] These tests help stratify risk and inform management decisions in severe cases.^[1]

Imaging Techniques

Imaging techniques are employed in pyelonephritis primarily when the diagnosis is uncertain based on clinical presentation and laboratory tests, or when complications such as urinary obstruction, abscess formation, or underlying structural abnormalities are suspected. According to the American Academy of Family Physicians (AAFP), initial imaging is not recommended for uncomplicated acute pyelonephritis in adults without risk factors, but it is advised for patients with sepsis, suspected urolithiasis, new renal insufficiency, known urologic anomalies, or failure to respond to treatment within 48 to 72 hours.^[16] The American College of Radiology (ACR) Appropriateness Criteria similarly rate imaging as usually not appropriate for first-time uncomplicated cases but highly appropriate for complicated presentations, emphasizing the need to identify precipitating factors like stones or parenchymal involvement.^[27] Ultrasound (US) is the preferred first-line imaging modality due to its non-invasive, bedside availability, lack of ionizing radiation, and cost-effectiveness, making it especially suitable for initial evaluation in pregnant patients or those with contraindications to other modalities.^[28] It effectively detects hydronephrosis indicative of obstruction and renal or perinephric abscesses, appearing as hypoechoic or complex fluid collections.^[29] Typical findings include renal enlargement with loss of corticomedullary differentiation, focal areas of increased or decreased echogenicity due to edema or inflammation, particulate debris in the collecting system, and reduced cortical vascularity on power Doppler imaging, though US sensitivity for uncomplicated pyelonephritis is limited and may appear normal in up to 80% of mild cases.^[30] Contrast-enhanced US can enhance detection of focal involvement or complications like abscesses by highlighting perfusion defects.^[31] Computed tomography (CT) of the abdomen and pelvis with intravenous contrast is the gold standard for evaluating complicated pyelonephritis, providing high sensitivity and specificity for parenchymal involvement and associated complications. It is particularly indicated in immunocompromised patients, those with diabetes, or when empyema or gas-forming infections are suspected, as per ACR guidelines rating it as usually appropriate (rating 8-9) for such scenarios.^[27] Key findings include the striated nephrogram on contrast-enhanced phases, representing alternating areas of hypo- and hyperenhancement due to tubular obstruction and edema; wedge-shaped or focal regions of hypoattenuation; renal enlargement; and perinephric stranding or fluid collections signaling extension of infection.^[30] Non-contrast CT can identify calculi, gas (in emphysematous pyelonephritis), or hemorrhage but is less sensitive for subtle parenchymal changes.^[32] Magnetic resonance imaging (MRI) is reserved for cases where CT is contraindicated, such as in pregnancy, severe contrast allergy, or renal impairment precluding iodinated contrast use, and it offers comparable diagnostic accuracy without radiation exposure.^[29] The ACR rates gadolinium-enhanced MRI as usually appropriate (rating 7-8) for complicated or pregnant patients, while diffusion-weighted imaging (DWI) without contrast is valuable for detecting restricted diffusion in affected cortical areas.^[27] Findings mirror those on CT, including renal swelling, wedge-shaped zones of signal abnormality on T2-weighted images due to cortical edema, and hypointense areas on T1 with corresponding hyperintensity on DWI indicating inflammation or abscesses; it also assesses vascular complications like renal vein thrombosis.^[30] MRI is particularly useful for follow-up in chronic or recurrent cases to evaluate scarring without cumulative radiation risk.^[33]

Differential Diagnosis

The differential diagnosis of pyelonephritis encompasses conditions that mimic its presentation of fever, flank pain, and urinary symptoms, requiring careful clinical evaluation to avoid misdiagnosis. Common mimics include acute cystitis, renal colic due to nephrolithiasis, and glomerulonephritis.^[20] Acute cystitis, a lower urinary tract infection, typically presents with dysuria, frequency, and suprapubic pain without flank tenderness or systemic signs like high fever and chills, which are hallmarks of upper tract involvement in pyelonephritis.^[1] Renal colic from kidney stones causes intermittent, colicky flank pain radiating to the groin, often accompanied by microscopic hematuria but lacking fever and significant pyuria unless secondarily infected; imaging may reveal calculi, while positive urine cultures with leukocyturia strongly support pyelonephritis over uncomplicated nephrolithiasis.^[1] Glomerulonephritis, an inflammatory kidney condition, features gross hematuria, oliguria, periorbital edema, and hypertension, typically without bacterial pathogens in urine cultures, differentiating it from the infectious etiology of pyelonephritis.^[20] Serious alternative diagnoses include appendicitis, diverticulitis, and lower lobe pneumonia, which can present with overlapping abdominal or flank pain and fever. Appendicitis often localizes to the right lower quadrant with rebound tenderness and anorexia, lacking urinary symptoms or positive urine cultures seen in pyelonephritis.^[20] Diverticulitis, more common in older adults, causes left lower quadrant pain, leukocytosis, and possible fever but is distinguished by gastrointestinal symptoms like constipation or diarrhea and absence of flank pain or bacteriuria.^[1] Lower lobe pneumonia may cause referred abdominal pain and fever but is differentiated by respiratory signs such as cough, dyspnea, and abnormal lung auscultation, with chest imaging confirming the diagnosis over renal involvement.^[20] In special populations like children, pyelonephritis must be differentiated from simple lower urinary tract infections and vesicoureteral reflux (VUR), a congenital condition that predisposes to recurrent upper tract infections. Febrile urinary tract infections in children may indicate pyelonephritis or VUR-related involvement, but VUR is identified through voiding cystourethrography showing retrograde urine flow, whereas simple cystitis lacks fever and renal parenchymal signs on ultrasound.^[34] Positive urine cultures with systemic symptoms favor pyelonephritis over uncomplicated VUR without active infection.^[1]

Management

Acute Pyelonephritis Treatment

The treatment of acute pyelonephritis primarily involves antimicrobial therapy tailored to disease severity, alongside supportive measures to alleviate symptoms and prevent complications.^[1] For mild cases without systemic toxicity, outpatient management with oral antibiotics is appropriate, whereas severe cases, such as those with sepsis or inability to tolerate oral intake, necessitate inpatient intravenous therapy.^[20] Hospitalization criteria include persistent vomiting, hemodynamic instability, signs of sepsis, or comorbidities that increase risk of poor response, such as immunosuppression or pregnancy.^[20] Antibiotic selection begins empirically based on local resistance patterns and common pathogens like Escherichia coli, with subsequent de-escalation guided by urine culture and sensitivity results to optimize efficacy and minimize resistance. Adherence to current guidelines, such as the 2025 IDSA recommendations, is advised for stepwise selection considering severity, resistance risk, and patient factors.^[35] For outpatient treatment of uncomplicated acute pyelonephritis, recommended oral regimens include ciprofloxacin 500 mg twice daily for 5-7 days or trimethoprim-sulfamethoxazole 160/800 mg twice daily for 7 days, assuming low local resistance rates (<20% for trimethoprim-sulfamethoxazole).^[36] Inpatient therapy typically starts with intravenous ceftriaxone 1 g daily or a fluoroquinolone like ciprofloxacin 400 mg every 12 hours, transitioning to oral agents once clinically stable.^[20] The total duration of antibiotic therapy is generally 5-7 days for fluoroquinolones or 7 days for non-fluoroquinolone regimens in uncomplicated cases with clinical improvement, as per 2025 IDSA guidelines.^[35] Supportive care is integral, emphasizing adequate hydration to maintain urine output and prevent dehydration, often via oral fluids outpatient or intravenous fluids inpatient until oral intake is tolerated.^[8] Analgesia with nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, addresses flank pain and fever, while antipyretics like acetaminophen control temperature; antiemetics (e.g., ondansetron) are used as needed for nausea and vomiting.^[1]

Chronic Pyelonephritis Treatment

The management of chronic pyelonephritis primarily focuses on preventing recurrent infections, addressing underlying structural or functional abnormalities, and preserving renal function to mitigate progression to end-stage renal disease (ESRD). Long-term antibiotic prophylaxis is a cornerstone for patients with recurrent episodes, particularly those associated with vesicoureteral reflux (VUR) or other predisposing factors. Common regimens include low-dose nitrofurantoin at 50-100 mg administered orally at bedtime, which has been shown to reduce the frequency of recurrent urinary tract infections (UTIs) in adults, with equivalent efficacy between 50 mg and 100 mg daily doses; this may help prevent ascent to pyelonephritis.^[37] Other options, such as trimethoprim-sulfamethoxazole or cephalexin, may be selected based on local antibiogram and susceptibility patterns, typically continued for 6-12 months before reassessment, as prolonged use beyond this period requires weighing benefits against risks like antimicrobial resistance.^[38] Prophylaxis is especially recommended for patients with a history of febrile UTIs and renal scarring, though its efficacy in halting scar progression remains variable.^[39] Correcting underlying causes is essential to interrupt the cycle of infection and scarring. For structural issues like urinary tract obstruction or VUR, surgical interventions are indicated; antireflux surgery, such as ureteral reimplantation, can resolve high-grade VUR and reduce recurrent pyelonephritis risk in affected individuals, particularly children.^[40] Endoscopic injection of dextranomer/hyaluronic acid copolymer offers a less invasive alternative for select cases of VUR, though it may not be as durable as open surgery.^[38] In patients with diabetes, a common comorbidity exacerbating chronic pyelonephritis due to impaired bladder emptying and neuropathy, rigorous glycemic control through lifestyle modifications, oral agents, or insulin therapy is critical to minimize infection susceptibility and support renal protection.^[12] Ongoing monitoring is vital to assess renal function and detect progression of scarring. Regular laboratory evaluations, including serum creatinine, estimated glomerular filtration rate (eGFR), and urinalysis, are performed every 3-6 months or more frequently if function declines, allowing early intervention to preserve remaining nephrons.^[12] Imaging modalities such as renal ultrasound or dimercaptosuccinic acid (DMSA) scintigraphy are used periodically to evaluate for cortical scarring, atrophy, or hydronephrosis, with computed tomography (CT) reserved for complex cases to guide management without routine radiation exposure.^[41] In advanced cases where chronic pyelonephritis leads to ESRD, typically characterized by a progressive decline in eGFR below 15 mL/min/1.73 m², renal replacement therapies become necessary. Hemodialysis or peritoneal dialysis is initiated to manage uremia and fluid balance; historically, chronic pyelonephritis was a more common cause of ESRD (e.g., 13% in 1971 cohorts), but it now represents a minor proportion (<2%) with primary causes being diabetes and hypertension.^[42] ^[43] For suitable candidates, kidney transplantation offers the optimal long-term solution, restoring renal function and improving quality of life, though pre-transplant nephrectomy of the scarred native kidney may be required to prevent recurrent infections in the graft.^[40] Post-transplant immunosuppression must be balanced to avoid heightened infection risk.^[12]

Complications and Follow-up

Pyelonephritis, if untreated or inadequately managed, can lead to acute complications such as sepsis, where the bacterial infection disseminates systemically, potentially causing septic shock and multi-organ failure.^[9] Renal abscess formation represents another critical acute outcome, characterized by localized pus collections within the kidney parenchyma, often arising from persistent infection in the renal pelvis.^[44] Additionally, renal papillary necrosis may occur, involving ischemic death of the renal papillae due to vascular compromise from severe inflammation or associated conditions like diabetes.^[45] In cases progressing to chronic pyelonephritis, long-term complications include hypertension, which develops from renal parenchymal scarring and activation of the renin-angiotensin system.^[40] This condition frequently contributes to chronic kidney disease, with progressive loss of nephron function leading to reduced glomerular filtration rates.^[9] Ultimately, untreated or recurrent chronic pyelonephritis can culminate in end-stage renal failure, necessitating dialysis or transplantation in advanced stages.^[46] Post-treatment follow-up is essential to ensure eradication of infection and monitor for residual effects. A repeat urine culture is typically performed 1 to 2 weeks after completing antibiotic therapy to verify microbiological clearance, particularly in complicated cases.^[20] If symptoms persist or recur, imaging studies such as ultrasound or computed tomography are recommended to assess for structural abnormalities like abscesses or scarring.^[29] The prognosis for acute pyelonephritis is favorable in most uncomplicated cases, with clinical resolution achieved in approximately 90% of patients following appropriate antimicrobial therapy.^[47] In contrast, chronic pyelonephritis carries a poorer outlook, especially when associated with renal scarring, which increases the risk of hypertension, chronic kidney disease progression, and long-term renal impairment.^[46]

Prevention and Epidemiology

Preventive Measures

Preventive measures for pyelonephritis primarily target reducing the risk of urinary tract infections (UTIs) that can ascend to the kidneys, focusing on hygiene, medical interventions, surgical corrections, and population-based screening.^[1] Hygiene practices play a foundational role in prevention. Maintaining adequate fluid intake, typically more than 2 liters per day, promotes frequent urination that flushes bacteria from the urinary tract, thereby lowering the incidence of UTIs and subsequent pyelonephritis.^[1] Urinating after sexual intercourse is recommended to eliminate potential pathogens introduced during activity, as supported by public health guidelines.^[48] Cranberry products, such as juice or supplements, have mixed evidence for efficacy; a Cochrane review indicates they may reduce symptomatic UTIs in women with recurrent infections and certain other groups, though results vary by population and product form. Medical prophylaxis is indicated for high-risk individuals, such as those with recurrent UTIs or post-surgical vulnerabilities. Low-dose antibiotic regimens, including nitrofurantoin or trimethoprim-sulfamethoxazole, administered continuously or postcoitally, effectively reduce recurrence rates in women prone to upper tract involvement. Research into vaccines against uropathogenic Escherichia coli (UPEC), the primary causative agent, shows promise; preclinical studies with siderophore conjugates and other antigens have demonstrated protection against experimental pyelonephritis in animal models, with clinical trials ongoing to evaluate human efficacy.^[49]^[50] Surgical interventions address underlying structural abnormalities that predispose to infection. Correction of vesicoureteral reflux (VUR) through ureteral reimplantation prevents urine backflow and recurrent pyelonephritis, particularly in children with high-grade reflux.^[51] Similarly, removal or management of urinary stones via procedures like lithotripsy reduces stasis and bacterial harboring, mitigating ascent to the kidneys in affected adults.^[38] At the population level, screening for asymptomatic bacteriuria in pregnant individuals is a key strategy. Urine culture screening at 12-16 weeks' gestation, followed by targeted antibiotic treatment, significantly lowers the risk of developing pyelonephritis during pregnancy, as evidenced by multiple cohort studies and endorsed by major obstetric organizations.^[52]^[53]

Global Incidence and Trends

Pyelonephritis affects millions worldwide, with an estimated annual global incidence of 10.5 to 25.9 million cases. In adults, the condition occurs at a rate of approximately 10-15 cases per 10,000 population annually, though rates vary significantly by sex and region. In the United States, around 250,000 to 1.1 million cases are reported each year, many requiring hospitalization.^[54]^[1]^[55] Demographically, pyelonephritis disproportionately impacts females, with incidence rates of 15-25 cases per 10,000 women compared to 3-4 cases per 10,000 men. The highest rates occur among young, sexually active women aged 15-29 years, as well as elderly individuals and children with urinary tract anomalies. These patterns reflect underlying physiological and anatomical differences, such as shorter urethra in females, alongside age-related vulnerabilities like reduced immunity in the elderly.^[56]^[16]^[1] Recent trends indicate a rise in antimicrobial resistance complicating pyelonephritis management, particularly among Escherichia coli isolates, the primary pathogen in over 80% of cases. Extended-spectrum β-lactamase (ESBL)-producing E. coli strains now exceed 20% prevalence in regions like parts of Asia, Europe, and Latin America, with yearly increases of 7-8% observed in some surveillance data from 2010-2023. The COVID-19 pandemic further exacerbated trends, leading to delayed diagnoses and presentations post-2020, with patients arriving at emergency departments 3-4 days later on average and exhibiting higher rates of systemic inflammatory response syndrome.^[57]^[58]^[59] Geographically, incidence is elevated in developing countries due to factors like inadequate sanitation and limited access to clean water, contributing to higher urinary tract infection burdens that progress to pyelonephritis. For instance, prevalence of healthcare-associated urinary tract infections, a precursor, reaches up to 24% in such settings compared to 13-20% in high-income regions. In contrast, developed nations like the US and those in Western Europe report more stable but still significant rates, influenced by better hygiene infrastructure.^[55]^[60]

History and Research

Terminology and Etymology

The term pyelonephritis derives from New Latin, combining the Greek roots pyelo- (from πύελος, pyelos, meaning "pelvis" or "basin," referring to the renal pelvis) with nephro- (from νεφρός, nephros, meaning "kidney") and the suffix -itis (indicating inflammation).^[61]^[62] This nomenclature specifically denotes inflammation involving the renal pelvis and kidney parenchyma, distinguishing it from the broader term nephritis, which historically encompassed various forms of kidney inflammation without emphasizing pelvic involvement.^[63] The term was coined in the 19th century, with its earliest documented use appearing in medical literature around 1837–1839, marking its entry into clinical nosology as a distinct entity.^[63]^[61] Prior to this, conditions now recognized as pyelonephritis were often subsumed under broader classifications such as Bright's disease, a 19th-century term introduced by Richard Bright in 1827 to describe albuminuria and associated renal pathologies, including inflammatory kidney disorders that could encompass pyelonephritic features.^[64]^[65] In contemporary usage, pyelonephritis is subdivided into acute and chronic forms, with acute pyelonephritis referring to sudden-onset bacterial infection of the upper urinary tract and chronic pyelonephritis indicating recurrent or persistent inflammation leading to scarring.^[1] Obsolete terms like "suppurative nephritis," which described pus-forming kidney infections akin to pyelonephritis, are avoided in modern terminology to prevent confusion with more precise classifications.^[66]

Ongoing Research and Advances

Recent research has focused on combating antibiotic resistance in pyelonephritis, particularly from multidrug-resistant (MDR) Gram-negative bacteria such as Escherichia coli. Cefiderocol, a novel siderophore cephalosporin, has demonstrated efficacy against carbapenem-resistant strains in complicated urinary tract infections (cUTIs), including pyelonephritis, through its unique iron-chelating mechanism that facilitates bacterial uptake.^[67] The U.S. Food and Drug Administration approved cefiderocol for cUTIs and pyelonephritis in 2020, with retrospective studies from 2023–2025 confirming its clinical success in real-world MDR cases, achieving microbiological eradication rates of approximately 70–80% in hospitalized patients.^[68] The PERSEUS study, published in 2025, further evaluated cefiderocol's safety and effectiveness in serious Gram-negative infections, including urinary sources, highlighting its role in empirical therapy for resistant pathogens.^[69] Vaccine development represents a promising preventive strategy against pyelonephritis caused by uropathogenic E. coli (UPEC), which accounts for most cases. FimH-targeted vaccines aim to block bacterial adhesion to uroepithelial cells via the type 1 pilus adhesin. Preclinical studies, including a 2024 cynomolgus monkey model of UPEC urinary tract infection, confirmed that FimH vaccine candidates elicit strong serum IgG and adhesin-blocking antibodies, reducing bacterial burden in the bladder and kidneys.^[70] As of 2025, an mRNA-based FimH nanoparticle vaccine showed high immunogenicity in rodents, paving the way for human translation.^[71] A related FimCH complex vaccine completed phase 1A/1B trials by 2025, demonstrating a 73% reduction in recurrent UTIs from UPEC or Klebsiella species, with ongoing efforts toward phase II for broader pyelonephritis prevention.^[72] Diagnostic advances emphasize faster pathogen identification to guide therapy and curb resistance. Rapid polymerase chain reaction (PCR) assays detect bacterial DNA in urine within hours, compared to traditional culture methods that require 24–48 hours, enabling earlier targeted antibiotics.^[73] A 2025 narrative review highlighted PCR's superior sensitivity for polymicrobial infections and resistance gene profiling in pyelonephritis, improving diagnostic accuracy over conventional tests.^[74] These molecular tools, including targeted next-generation sequencing, have been integrated into point-of-care settings post-2020, reducing empirical broad-spectrum antibiotic use.^[75] Emerging research addresses gaps in understanding recurrence and detection through microbiome analysis. Studies indicate that dysbiosis in the gut, urinary, and vaginal microbiomes contributes to pyelonephritis relapse by serving as reservoirs for UPEC colonization and antibiotic resistance genes.^[76] A 2024 analysis linked low-diversity gut microbiomes to increased recurrent UTI risk, suggesting probiotic interventions could restore balance and lower incidence.^[77]

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Xanthogranulomatous pyelonephritis | Radiology Reference Article
Jun 1, 2010 · Xanthogranulomatous pyelonephritis (XGP) is a rare form of chronic pyelonephritis and represents a chronic granulomatous disease resulting in a non-functioning ...
[16]
Acute Pyelonephritis in Adults: Rapid Evidence Review - AAFP
Aug 1, 2020 · Acute pyelonephritis is a bacterial infection of the kidney and renal pelvis and should be suspected in patients with flank pain and laboratory evidence of ...Abstract · Epidemiology and Microbiology · Diagnosis · Treatment
[17]
Uropathogen and host responses in pyelonephritis - PMC - NIH
Risk factors for cystitis, such as sexual activity, personal history of UTI or family history of UTI also predispose individuals to pyelonephritis.Upec Virulence Factors · Host Responses To Upec... · Regulation Of Immunity
[18]
Integrated Pathophysiology of Pyelonephritis | Microbiology Spectrum
It involves a combination of factors originating from the infection as well as from physiological injuries, such as ischemia and obstruction.
[19]
Reflux Nephropathy - StatPearls - NCBI Bookshelf
Reflux nephropathy was previously called chronic pyelonephritis as it was believed to result from childhood recurrent urinary tract infections (UTIs). It occurs ...
[20]
Diagnosis and Management of Acute Pyelonephritis in Adults - AAFP
Mar 1, 2005 · Acute pyelonephritis is an infection of the upper urinary tract, specifically the renal parenchyma and renal pelvis.Abstract · Pathogenesis · Clinical Presentation · Diagnostic Testing<|control11|><|separator|>
[21]
Sepsis and other Infectious Disease Emergencies in the Elderly - PMC
Atypical presentations including altered mental status and gastrointestinal symptoms also abound in elders with pyelonephritis, but fever and chills are more ...<|control11|><|separator|>
[22]
Comprehensive Review of Urinary Tract Infections in Renal ...
Feb 8, 2024 · Notably, in elderly or immunocompromised transplant recipients, UTIs can present with non-specific symptoms such as altered mental status, ...
[23]
Pathophysiology, Treatment, and Prevention of Catheter-Associated ...
Even short-term urinary catheterization increases the risk of developing CAUTI and other complications up to 80%, and prolonged catheterization can increase the ...
[24]
Antenatal pyelonephritis: a three-year retrospective cohort study of ...
May 1, 2023 · Pyelonephritis affects 1–2% of pregnant women, and is associated with significant maternal and fetal morbidity. Antenatal pyelonephritis has ...
[25]
Risk Factors Associated with Acute Pyelonephritis in Healthy Women
Pyelonephritis risk increased nearly 6-fold for recent frequent sexual intercourse and more than 4-fold for UTI history and diabetes.
[26]
Risk factors and predisposing conditions for urinary tract infection
Poor hand hygiene, poor aseptic technique, and poor catheter placement all predispose towards UTIs. Unnecessary or overlong catheterization is a further risk ...
[27]
Acute Pyelonephritis - AC Search
Studies in adults have shown that DWI can be useful in the diagnosis of pyelonephritis [28-30]. APN, renal abscesses, and pyonephrosis have lower ADC values ...
[28]
When does acute pyelonephritis require imaging?
Aug 1, 2019 · The recommended imaging study is computed tomography of the abdomen and pelvis with contrast, or computed tomography without and with contrast.
[29]
Acute Pyelonephritis Workup - Medscape Reference
Aug 20, 2025 · Magnetic resonance imaging (MRI) can detect kidney infection or masses and urinary obstruction, and it can evaluate the kidney vasculature.
[30]
Acute pyelonephritis | Radiology Reference Article | Radiopaedia.org
Sep 8, 2025 · Ultrasound · particulate matter/debris in the collecting system · reduced areas of cortical vascularity by using power Doppler · gas bubbles ( ...Emphysematous pyelonephritis · Striated nephrogram · Lobar nephronia
[31]
Ultrasound, contrast-enhanced ultrasound and pyelonephritis
Focal pyelonephritis typically presents as a hyperechoic focal lesion with cortical bulging on grey-scale ultrasound, related to the high number of inflammatory ...
[32]
CT Imaging in Pyelonephritis: Pearls & Pitfalls - emDocs
Aug 10, 2020 · CT imaging without contrast can visualize gas, calculi, hemorrhage, renal enlargement, inflammatory masses, and obstruction accurately.22 ...
[33]
CT and MRI in Urinary Tract Infections: A Spectrum of Different ...
MRI signs of acute pyelonephritis are similar to those detected at CT scan; renal enlargement, alterations of signal intensity due to hemorrhage or edema, ...2.2. Renal And Perinephric... · 2.3. Pyonephrosis · 2.6. Emphysematous Urinary...<|separator|>
[34]
Pediatric Pyelonephritis Differential Diagnoses - Medscape Reference
Aug 4, 2024 · Conditions to be considered in the differential diagnosis of pyelonephritis include the following: ... Vesicoureteral reflux. Ureteropelvic ...
[35]
Diagnosis and Treatment of Acute Pyelonephritis in Women - AAFP
Sep 1, 2011 · Acute pyelonephritis: the differential diagnosis and workup. March 5, 2010. http://emedicine.medscape.com/article/245559. Accessed January ...
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Ciprofloxacin for 7 days versus 14 days in women with ... - PubMed
Aug 4, 2012 · Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled ...
[37]
Recurrent Uncomplicated Urinary Tract Infections in Women
Aug 1, 2019 · Dosing and Duration ; Nitrofurantoin, 50 mg daily, 100 mg daily ; Cephalexin, 125 mg once daily, 250 mg once daily ; Fosfomycin, 3 gm every 10 days.
[38]
Chronic Pyelonephritis Treatment & Management
Jun 19, 2023 · Preventive strategies include the administration of prophylactic antibiotics, endoscopic injection of dextranomer hyaluronic acid, and antireflux surgery.
[39]
Chronic Pyelonephritis Guidelines - Medscape Reference
Jun 19, 2023 · The guidelines make the following treatment recommendations : In the absence of BBD, recurrent febrile UTI, or renal cortical ...
[40]
Chronic Pyelonephritis - Medscape Reference
Jun 19, 2023 · Chronic pyelonephritis is characterized by inflammation and scarring induced by recurrent or persistent kidney infection, vesicoureteral reflux, or other ...
[41]
Chronic pyelonephritis | Radiology Reference Article
May 17, 2020 · Chronic pyelonephritis is a form of pyelonephritis where there are longstanding sequelae of renal infection.Missing: classification | Show results with:classification
[42]
Chronic Pyelonephritis as a Cause of Renal Failure in Dialysis ...
Chronic pyelonephritis was found to be the primary cause of end-stage renal failure in 22 (13%) of 173 dialysis candidates and was almost always.
[43]
Renal Abscess - StatPearls - NCBI Bookshelf
Apr 11, 2025 · Renal abscesses are a rare but critical complication of urinary tract infections (UTIs) and bacteremia, often arising from inadequately managed pyelonephritis.
[44]
Acute pyelonephritis can have serious complications - PubMed
Acute pyelonephritis may be uncomplicated and resolve without serious sequelae. A minority of episodes may be complicated by acute kidney injury.
[45]
Development of hypertension and uraemia after pyelonephritis in ...
Conclusions: Children with focal renal scarring due to pyelonephritis are at high risk of serious long term consequences. It is essential that they are given ...
[46]
Outpatient treatment in women with acute pyelonephritis after ... - NIH
Of 222 patients receiving appropriate empiric antibiotic therapy, 48 (92.3%) of 52 discharged patients showed clinical success at the first outpatient visit and ...
[47]
Urinary Tract Infection Basics - CDC
Jan 22, 2024 · Signs and symptoms · Pain or burning while urinating · Frequent urination · Feeling the need to urinate despite having an empty bladder · Bloody ...
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Siderophore vaccine conjugates protect against uropathogenic ...
Nov 7, 2016 · Siderophore vaccine conjugates protect against uropathogenic Escherichia coli urinary tract infection. Laura A. Mike, Sara N. Smith ...Siderophore Vaccine... · Sign Up For Pnas Alerts · Results
[49]
Development of a Vaccine against Escherichia coli Urinary Tract ...
Our laboratory has made progress toward development of a preventive vaccine against UPEC. The long-term research goal is to prevent UTIs in women with ...
[50]
Vesicoureteral Reflux Guideline - American Urological Association
This clinical guideline covers assessment, initial management, surgical treatment, and follow-up management of pediatric patients with such disorders.
[51]
Urinary Tract Infections in Pregnant Individuals - ACOG
Since ASB screening and treatment became routine practice, the incidence of pyelonephritis in pregnancy has decreased 20–35%, to 1–4% 3.
[52]
Archived: Asymptomatic Bacteriuria in Adults: Screening - uspstf
Jul 15, 2008 · The USPSTF recommends screening for asymptomatic bacteriuria with urine culture for pregnant women at 12 to 16 weeks' gestation or at their ...
[53]
Acute Pyelonephritis in Patients Presenting Only with Lower Urinary ...
The estimated annual incidence of pyelonephritis is 459,000–1,138,000 cases in the United States and 10.5 million to 25.9 million cases globally. It is one of ...
[54]
An introduction to the epidemiology and burden of urinary tract ... - NIH
There are an estimated 250,000 cases of pyelonephritis annually in the US, with a higher frequency among females. In women aged 18−49 years, the estimated ...
[55]
Population-Based Epidemiologic Analysis of Acute Pyelonephritis
Overall rates of acute pyelonephritis at GH were 15–17 cases per 10,000 females and 3–4 cases per 10,000 males and were stable from year to year. Incidence ...
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Antimicrobial Resistance Trends in Urine Escherichia coli Isolates ...
Jun 18, 2021 · Modeling demonstrated a relative average yearly increase of 7.7% (95% confidence interval [CI], 7.2–8.2%) for ESBL+ isolates and 2.7% (95% CI, ...
[57]
Increasing proportions of extended-spectrum β-lactamase ...
Oct 26, 2023 · In urine cultures, the proportion of ESBL-producing E. coli isolates increased from 2.2% (239/10,806) to 7.2% (1,098/15,297) among males (8.8%; ...
[58]
COVID-19 pandemic impact on clinical outcomes of patients with ...
Nov 21, 2020 · During the COVID-19 pandemic, patients with acute obstructive pyelonephritis presented later for evaluation at the ER, had higher disease severity and longer ...
[59]
Epidemiological trends and predictions of urinary tract infections in ...
Feb 8, 2025 · From 1990 to 2019, the global incidence of UTIs rose significantly, from 2,698,152,261 (95% UI: 241,706,586–299,288,509) to 4,491,022,288 (95% ...
[60]
PYELONEPHRITIS Definition & Meaning - Merriam-Webster
The meaning of PYELONEPHRITIS is inflammation of both the lining of the renal pelvis and the parenchyma of the kidney especially due to bacterial infection.
[61]
pyelonephritis, n. meanings, etymology and more | Oxford English ...
The earliest known use of the noun pyelonephritis is in the 1830s. OED's earliest evidence for pyelonephritis is from 1839, in British & Foreign Medical Review.
[62]
Pyelonephritis: A Historical Reappraisal - PMC - NIH
Apr 26, 2019 · Additionally, unlike its acute form, chronic pyelonephritis usually was a low-grade, relatively asymptomatic infection with periods of remission ...Missing: symptoms | Show results with:symptoms
[63]
CONCEPTS OF PYELONEPHRITIS: EXPERIENCE WITH RENAL ...
The differentiation of pyelonephritis from the causes of Bright's disease, and the concepts of its pathogenesis, course and sequelae, constitute serial ...
[64]
Bright's Disease - JAMA Network
He excludes acute pyelonephritis from this classification but includes chronic pyelonephritis ... Bright's disease secondary to pyelonephritis." This he justifies.
[65]
Acute pyelonephritis - Pathology Outlines
Mar 31, 2021 · Kidney nontumor - Acute pyelonephritis is an acute suppurative (pus forming) infection of kidney collecting system as well as renal parenchyma.
[66]
Cefiderocol for the Treatment of Multidrug-Resistant Gram-Negative ...
Clinical trials demonstrated that cefiderocol was non-inferiority to the comparator drugs in treating complicated urinary tract infection and nosocomial ...
[67]
A Retrospective Study of Cefiderocol Utilization and Associated ...
Cefiderocol is a cephalosporin antibiotic with FDA-approved indications for complicated urinary tract infection (cUTI), pyelonephritis, hospital-acquired ...
[68]
Effectiveness and safety of cefiderocol treatment in patients with ...
Mar 25, 2025 · The main objectives of the PERSEUS study were to describe the use of cefiderocol in hospitalised patients with serious Gram-negative bacterial ...Missing: pyelonephritis | Show results with:pyelonephritis
[69]
A cynomolgus monkey E. coli urinary tract infection model confirms ...
Sep 19, 2024 · Both vaccines elicited high levels of serum FimH IgG and adhesin blocking antibodies at the time of bacterial challenge and, for the combination ...
[70]
https://pmc.ncbi.nlm.nih.gov/articles/PMC11475676/
[71]
Monoclonal antibodies targeting the FimH adhesin protect against ...
Jun 20, 2025 · A vaccine against UPEC FimCH has revealed an 73% reduction in recurrent UTIs caused by UPEC or Klebsiella spp. in a phase 1A/1B clinical trial, ...
[72]
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[73]
Advances in the Diagnosis of Urinary Tract Infection: A Narrative ...
Apr 30, 2025 · Molecular assays, such as polymerase chain reaction (PCR), allow for the rapid detection of bacterial DNA, offering higher sensitivity and ...
[74]
Rapid and accurate diagnosis of urinary tract infections using ...
tNGS demonstrates advantages in rapid and accurate UTI diagnosis, particularly in detecting polymicrobial infections and analyzing antibiotic resistance genes.
[75]
Role of the Gut, Urine, and Vaginal Microbiomes in the ...
Aug 19, 2024 · The gut, urine, and vaginal microbiomes play significant roles in the pathogenesis of recurrent urinary tract infections (rUTIs).
[76]
https://academic.oup.com/ofid/article/11/9/ofae471/7735779
[77]
Use of Artificial Intelligence Methods for Improved Diagnosis of ... - NIH
Jul 12, 2025 · This article analyzes AI's role in detecting UTIs' etiologic agents and its potential in managing urolithiasis to enhance early diagnosis ...
[78]
Emerging Insights Into Microbiome Therapeutics for Urinary Tract ...
Apr 30, 2025 · Clinical trials have documented significant reductions in UTI recurrence rates among patients treated with microbiome therapeutics compared to ...