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Pyelonephritis
Pyelonephritis
Pyelonephritis
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Pyelonephritis
Other namesKidney infection[1]
A color photomicrograph, demonstrating macrophages and giant cells in a case of xanthogranulomatous pyelonephritis.
CD68 immunostaining on this photomicrograph shows macrophages and giant cells in a case of xanthogranulomatous pyelonephritis.
Pronunciation
SpecialtyInfectious disease, urology, nephrology
SymptomsFever, flank tenderness, nausea, burning with urination, frequent urination[2]
CausesBacterial infection[2]
Risk factorsSexual intercourse, prior urinary tract infections, diabetes, structural problems of the urinary tract, spermicide use[2][3]
Diagnostic methodBased on symptoms and supported by urinalysis[2]
Differential diagnosisEndometriosis, pelvic inflammatory disease, kidney stones[2]
PreventionUrination after sex, drinking sufficient fluids[1]
MedicationAntibiotics (ciprofloxacin, ceftriaxone)[4]
FrequencyCommon[5]

Pyelonephritis is inflammation of the kidney, typically due to a bacterial infection.[3] Symptoms most often include fever and flank tenderness.[2] Other symptoms may include nausea, burning with urination, and frequent urination.[2] Complications may include pus around the kidney, sepsis, or kidney failure.[3]

It is typically due to a bacterial infection, most commonly Escherichia coli.[2] Risk factors include sexual intercourse, prior urinary tract infections, diabetes, structural problems of the urinary tract, and spermicide use.[2][3] The mechanism of infection is usually spread up the urinary tract.[2] Less often infection occurs through the bloodstream.[1] Diagnosis is typically based on symptoms and supported by urinalysis.[2] If there is no improvement with treatment, medical imaging may be recommended.[2]

Pyelonephritis may be preventable by urination after sex and drinking sufficient fluids.[1] Once present it is generally treated with antibiotics, such as ciprofloxacin or ceftriaxone.[4][6] Those with severe disease may require treatment in hospital.[2] In those with certain structural problems of the urinary tract or kidney stones, surgery may be required.[1][3]

Pyelonephritis affects about 1 to 2 per 1,000 women each year and just under 0.5 per 1,000 males.[5][7] Young adult females are most often affected, followed by the very young and old.[2] With treatment, outcomes are generally good in young adults.[3][5] Among people over the age of 65 the risk of death is about 40%, though this depends on the health of the elderly person, the precise organism involved, and how quickly they can get care through a provider or in hospital.[5]

Signs and symptoms

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Diagram showing the typical location of pain[8]

Signs and symptoms of acute pyelonephritis generally develop rapidly over a few hours or a day. It can cause high fever, pain on passing urine, and abdominal pain that radiates along the flank towards the back. There is often associated vomiting.[9]

Chronic pyelonephritis causes persistent flank or abdominal pain, signs of infection (fever, unintentional weight loss, malaise, decreased appetite), lower urinary tract symptoms and blood in the urine.[10] Chronic pyelonephritis can in addition cause fever of unknown origin. Furthermore, inflammation-related proteins can accumulate in organs and cause the condition AA amyloidosis.[11]

Physical examination may reveal fever and tenderness at the costovertebral angle on the affected side.[12]

Causes

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Most cases of community-acquired pyelonephritis are due to bowel organisms that enter the urinary tract. Common organisms are E. coli (70–80%) and Enterococcus faecalis. Hospital-acquired infections may be due to coliform bacteria and enterococci, as well as other organisms uncommon in the community (e.g., Pseudomonas aeruginosa and various species of Klebsiella). Most cases of pyelonephritis start off as lower urinary tract infections, mainly cystitis and prostatitis.[9] E. coli can invade the superficial umbrella cells of the bladder to form intracellular bacterial communities (IBCs), which can mature into biofilms. These biofilm-producing E. coli are resistant to antibiotic therapy and immune system responses, and present a possible explanation for recurrent urinary tract infections, including pyelonephritis.[13] Risk is increased in the following situations:[9][14]

Diagnosis

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Laboratory examination

[edit]

Analysis of the urine may show signs of urinary tract infection. Specifically, the presence of nitrite and white blood cells on a urine test strip in patients with typical symptoms are sufficient for the diagnosis of pyelonephritis, and are an indication for empirical treatment. Blood tests such as a complete blood count may show neutrophilia. Microbiological culture of the urine, with or without blood cultures and antibiotic sensitivity testing are useful for establishing a formal diagnosis,[9] and are considered mandatory.[15]

Imaging studies

[edit]

If a kidney stone is suspected (e.g. on the basis of characteristic colicky pain or the presence of a disproportionate amount of blood in the urine), a kidneys, ureters, and bladder x-ray (KUB film) may assist in identifying radioopaque stones.[9] Where available, a noncontrast helical CT scan with 5 millimeter sections is the diagnostic modality of choice in the radiographic evaluation of suspected nephrolithiasis.[16][17][18] All stones are detectable on CT scans except very rare stones composed of certain drug residues in the urine.[19] In patients with recurrent ascending urinary tract infections, it may be necessary to exclude an anatomical abnormality, such as vesicoureteral reflux or polycystic kidney disease. Investigations used in this setting include kidney ultrasonography or voiding cystourethrography.[9] CT scan or kidney ultrasonography is useful in the diagnosis of xanthogranulomatous pyelonephritis; serial imaging may be useful for differentiating this condition from kidney cancer.[10]

Acute pyelonephritis with increased cortical echogenicity and blurred delineation of the upper pole[20]

Ultrasound findings that indicate pyelonephritis are enlargement of the kidney, edema in the renal sinus or parenchyma, bleeding, loss of corticomedullary differentiation, abscess formation, or an areas of poor blood flow on doppler ultrasound.[21] However, ultrasound findings are seen in only 20–24% of people with pyelonephritis.[21]

A DMSA scan is a radionuclide scan that uses dimercaptosuccinic acid in assessing the kidney morphology. It is now[when?] the most reliable test for the diagnosis of acute pyelonephritis.[22]

Classification

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Acute pyelonephritis

[edit]

Acute pyelonephritis is an exudative purulent localized inflammation of the renal pelvis (collecting system) and kidney. The kidney parenchyma presents in the interstitium abscesses (suppurative necrosis), consisting in purulent exudate (pus): neutrophils, fibrin, cell debris and central germ colonies (hematoxylinophils). Tubules are damaged by exudate and may contain neutrophil casts. In the early stages, the glomerulus and vessels are normal. Gross pathology often reveals pathognomonic radiations of bleeding and suppuration through the renal pelvis to the renal cortex.[citation needed]

Chronic pyelonephritis

[edit]

Chronic pyelonephritis implies recurrent kidney infections and can result in scarring of the renal parenchyma and impaired function, especially in the setting of obstruction. A perinephric abscess (infection around the kidney) and/or pyonephrosis may develop in severe cases of pyelonephritis.[23]

  • Abscess around both kidneys[24]
  • Abscess around both kidneys[24]
  • Chronic pyelonephritis with reduced kidney size and focal cortical thinning. Measurement of kidney length on the US image is illustrated by '+' and a dashed line.[20]
    Chronic pyelonephritis with reduced kidney size and focal cortical thinning. Measurement of kidney length on the US image is illustrated by '+' and a dashed line.[20]
Xanthogranulomatous pyelonephritis
[edit]

Xanthogranulomatous pyelonephritis is an unusual form of chronic pyelonephritis characterized by granulomatous abscess formation, severe kidney destruction, and a clinical picture that may resemble renal cell carcinoma and other inflammatory kidney parenchymal diseases. Most affected individuals present with recurrent fevers and urosepsis, anemia, and a painful kidney mass. Other common manifestations include kidney stones and loss of function of the affected kidney. Bacterial cultures of kidney tissue are almost always positive.[25] Microscopically, there are granulomas and lipid-laden macrophages (hence the term xantho-, which means yellow in ancient Greek). It is found in roughly 20% of specimens from surgically managed cases of pyelonephritis.[10]

Prevention

[edit]

In people who experience recurrent urinary tract infections, additional investigations may identify an underlying abnormality. Occasionally, surgical intervention is necessary to reduce the likelihood of recurrence. If no abnormality is identified, some studies suggest long-term preventive treatment with antibiotics, either daily or after sexual activity.[26] In children at risk for recurrent urinary tract infections, not enough studies have been performed to conclude prescription of long-term antibiotics has a net positive benefit.[27] Cranberry products and drinking cranberry juice appears to provide a benefit in decreasing urinary tract infections for certain groups of individuals.[28]

Management

[edit]

In people suspected of having pyelonephritis, a urine culture and antibiotic sensitivity test is performed, so therapy can eventually be tailored on the basis of the infecting organism.[5] As most cases of pyelonephritis are due to bacterial infections, antibiotics are the mainstay of treatment.[5] The choice of antibiotic depends on the species and antibiotic sensitivity profile of the infecting organism, and may include fluoroquinolones, cephalosporins, aminoglycosides, or trimethoprim/sulfamethoxazole, either alone or in combination.[15]

Simple

[edit]

A 2018 systematic review recommended the use of norfloxacin as it has the lowest rate of side effects with a comparable efficacy to commonly used antibiotics.[29]

In people who do not require hospitalization and live in an area where there is a low prevalence of antibiotic-resistant bacteria, a fluoroquinolone by mouth such as ciprofloxacin or levofloxacin is an appropriate initial choice for therapy.[5] In areas where there is a higher prevalence of fluoroquinolone resistance, it is useful to initiate treatment with a single intravenous dose of a long-acting antibiotic such as ceftriaxone or an aminoglycoside, and then continuing treatment with a fluoroquinolone. Oral trimethoprim/sulfamethoxazole is an appropriate choice for therapy if the bacteria is known to be susceptible.[5] If trimethoprim/sulfamethoxazole is used when the susceptibility is not known, it is useful to initiate treatment with a single intravenous dose of a long-acting antibiotic such as ceftriaxone or an aminoglycoside. Oral beta-lactam antibiotics are less effective than other available agents for treatment of pyelonephritis.[15] Improvement is expected in 48 to 72 hours.[5]

Complicated

[edit]

People with acute pyelonephritis that is accompanied by high fever and leukocytosis are typically admitted to the hospital for intravenous hydration and intravenous antibiotic treatment. Treatment is typically initiated with an intravenous fluoroquinolone, an aminoglycoside, an extended-spectrum penicillin or cephalosporin, or a carbapenem. Combination antibiotic therapy is often used in such situations. The treatment regimen is selected based on local resistance data and the susceptibility profile of the specific infecting organism(s).[15]

During the course of antibiotic treatment, serial white blood cell count and temperature are closely monitored. Typically, the intravenous antibiotics are continued until the person has no fever for at least 24 to 48 hours, then equivalent antibiotics by mouth can be given for a total of two-week duration of treatment.[30] Intravenous fluids may be administered to compensate for the reduced oral intake, insensible losses (due to the raised temperature) and vasodilation and to optimize urine output. Percutaneous nephrostomy or ureteral stent placement may be indicated to relieve obstruction caused by a stone. Children with acute pyelonephritis can be treated effectively with oral antibiotics (cefixime, ceftibuten and amoxicillin/clavulanic acid) or with short courses (2 to 4 days) of intravenous therapy followed by oral therapy.[31] If intravenous therapy is chosen, single daily dosing with aminoglycosides is safe and effective.[31]

Fosfomycin can be used as an efficacious treatment for both UTIs and complicated UTIs including acute pyelonephritis. The standard regimen for complicated UTIs is an oral 3 g dose administered once every 48 or 72 hours for a total of 3 doses or a 6 grams every 8 hours for 7 days to 14 days when fosfomycin is given in IV form.[32]

Treatment of xanthogranulomatous pyelonephritis involves antibiotics as well as surgery. Removal of the kidney is the best surgical treatment in the overwhelming majority of cases, although polar resection (partial nephrectomy) has been effective for some people with localized disease.[10][33] Watchful waiting with serial imaging may be appropriate in rare circumstances.[34]

Follow-up

[edit]

If no improvement is made in one to two days post therapy, inpatients should repeat a urine analysis and imaging. Outpatients should check again with their doctor.[35]

Epidemiology

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There are roughly 12–13 cases annually per 10,000 population in women receiving outpatient treatment and 3–4 cases requiring admission. In men, 2–3 cases per 10,000 are treated as outpatients and 1–2 cases/10,000 require admission.[36] Young women are most often affected. Infants and the elderly are also at increased risk, reflecting anatomical changes and hormonal status.[36] Xanthogranulomatous pyelonephritis is most common in middle-aged women.[25] It can present somewhat differently in children, in whom it may be mistaken for Wilms' tumor.[37]

Research

[edit]

According to a 2015 meta analysis, vitamin A has been shown to alleviate renal damage and/or prevent renal scarring.[38]

Terminology

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The term is from Greek πύελο|ς pýelo|s, "basin" + νεφρ|ός nepʰrós, "kidney" + suffix -itis suggesting "inflammation".[citation needed]

A similar term is "pyelitis", which means inflammation of the renal pelvis and calyces.[39][40] In other words, pyelitis together with nephritis is collectively known as pyelonephritis.[citation needed]

Etymology

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The word pyelonephritis is formed by the Greek roots pyelo- from πύελος (púelos) renal pelvis and nephro- from νεφρός (nephrós) kidney together with the suffix -itis from -ῖτις (-itis) used in medicine to indicate diseases or inflammations.[citation needed]

References

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Pyelonephritis

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from Grokipedia
Pyelonephritis is a bacterial of the that involves of the and , typically resulting from the ascent of pathogens from a lower . It is a serious form of (UTI) that requires prompt medical attention to prevent complications such as permanent damage or . Common symptoms include fever, chills, flank pain, , , and or , though presentation can vary by age and severity. The primary causative agent is , accounting for most cases, with other uropathogens like or species involved less frequently. Risk factors encompass female gender due to anatomical differences, urinary obstructions, , , , and indwelling catheters. Diagnosis typically involves showing and , though a normal urinalysis generally suggests no active acute pyelonephritis, with rare exceptions such as cases without pyuria (occurring in approximately 22% of patients, often due to prior antibiotic use); urine culture for identification, and sometimes to rule out complications like abscesses. Treatment generally consists of antibiotics tailored to the suspected or confirmed , with oral for uncomplicated cases and intravenous administration for severe or complicated infections, often requiring hospitalization. If untreated, pyelonephritis can lead to , chronic renal scarring, , or life-threatening . Prevention strategies include adequate hydration, prompt treatment of lower UTIs, and managing underlying conditions like diabetes or urinary obstructions.

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). 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. The most common causative pathogen is Escherichia coli, though other gram-negative bacteria may also be implicated. Pyelonephritis is primarily classified into acute and chronic forms based on clinical presentation, duration, and pathological outcomes. Acute pyelonephritis represents a sudden-onset characterized by rapid and systemic symptoms, which is often reversible with prompt therapy, though it may cause temporary renal dysfunction. In contrast, chronic pyelonephritis develops from persistent or recurrent s, leading to progressive tubulointerstitial , cortical scarring, and potential long-term renal impairment, frequently associated with underlying conditions like or urinary tract obstruction. Rare variants include emphysematous pyelonephritis, a severe necrotizing marked by gas formation within the renal due to fermentation by gas-producing , often seen in diabetics and carrying mortality rates of approximately 13-25%. Xanthogranulomatous pyelonephritis is another uncommon chronic variant, presenting as a granulomatous destructive process that replaces functional renal tissue with lipid-laden macrophages and , typically linked to chronic obstruction by calculi and resulting in a non-functioning . 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 from the lower urinary tract migrate retrograde through the ureters to reach the and . This migration is often promoted by , a condition where and backflow from the 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. The predominant causative agent is , responsible for approximately 70-90% of community-acquired cases, with other Gram-negative Enterobacteriaceae such as , , and 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, formation, and evasion of urinary flow. Additional factors like type 1 fimbriae, hemolysins, and siderophores further support persistence and tissue invasion by promoting and iron acquisition in the nutrient-limited urinary environment. Once in the renal parenchyma, elicit a robust host immune response primarily through pattern recognition receptors, including (TLR4) for and TLR5 for , activating signaling and the release of proinflammatory cytokines such as interleukin-6 (IL-6), tumor factor-alpha (TNF-α), and interleukin-1β (IL-1β). This inflammatory cascade recruits neutrophils to the site of , resulting in — the presence of in —and local , which can impair renal flow and lead to tubular . In severe or unresolved , the unchecked may progress to microabscess formation within the cortex or medulla, exacerbating tissue damage. Recurrent episodes of pyelonephritis, often in the context of structural abnormalities or persistent bacterial reservoirs, drive a chronic inflammatory state characterized by progressive tubulointerstitial . Repeated infiltration and cytokine-mediated signaling activate fibroblasts, leading to excessive deposition and renal scarring, which can distort calyces and impair function over time. This fibrotic remodeling is mediated by transforming growth factor-beta (TGF-β) and contributes to long-term complications such as and reduced .

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, shivering, night sweats, and systemic malaise. Aching flank pain, usually unilateral and located in the lower back (loin area), side, or groin, often starting on one side, is a hallmark symptom, frequently radiating to the groin or abdomen. Common symptoms include fever, chills, flank pain in the lower back/loin area, nausea, and vomiting. Additional lower urinary tract symptoms include dysuria, urinary frequency, and urgency, as well as cloudy or foul-smelling urine, while prominent gastrointestinal complaints such as nausea and vomiting are also prevalent. Approximately one-third of patients also experience symptoms of concurrent cystitis, such as dysuria (burning on urination) and frequent urination. In toddlers, signs that a urinary tract infection has reached the kidneys include high fever, chills, flank pain, and severe vomiting. Chronic pyelonephritis, often resulting from repeated episodes of acute or , tends to have subtler and more insidious symptoms. Patients may report a dull, persistent flank pain and recurrent urinary tract s, alongside general due to progressive renal impairment. Scarring from ongoing inflammation can lead to in a significant proportion of cases. Atypical presentations are particularly common in vulnerable populations, such as the elderly, children, or immunocompromised individuals, where classic signs like fever and flank pain may be absent. Instead, these patients might exhibit nonspecific symptoms, including general malaise, confusion, altered mental status, or generalized without prominent urinary complaints. On , costovertebral angle tenderness—elicited by percussion or over the affected —is a key finding in both acute and chronic forms, though it may be less pronounced in chronic cases.

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 in men, create stagnant pools that promote bacterial proliferation and increase infection risk. , where 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. Indwelling urinary catheters, often used in hospitalized or immobile patients, introduce directly into the urinary tract and are associated with up to an 80% increased risk of infection with prolonged use. Demographic factors play a significant role, with females facing a substantially higher risk due to their shorter , which allows easier bacterial entry from the perineal area. 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. Diabetes mellitus, which impairs and glycosuria favors bacterial growth, independently increases pyelonephritis risk more than fourfold in affected individuals. 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. Inadequate personal practices, such as improper wiping techniques after or insufficient perineal cleaning, can facilitate bacterial colonization of the , though this is more pronounced in combination with other factors. Medical conditions involving immunosuppression heighten the overall risk by reducing the body's ability to combat ascending infections. Conditions like , ongoing chemotherapy, or post-transplant immunosuppressive therapy compromise host defenses, making pyelonephritis more likely in these populations. Neurogenic bladder, often resulting from spinal cord injuries or neurological disorders, leads to incomplete emptying and , further predisposing individuals to recurrent infections.

Diagnosis

Laboratory Investigations

Laboratory investigations play a crucial role in confirming the of pyelonephritis, identifying the causative , and assessing severity. Initial evaluation often begins with , which provides rapid insights into urinary tract and . Key findings include , characterized by more than 20 per high-power field (WBC/hpf) on microscopic examination, indicating an inflammatory response in the urinary tract. , the presence of in the , is commonly observed, with bacteria often visible on Gram stain or microscopy, while positive tests for nitrites suggest by nitrate-reducing organisms such as . Additionally, , an enzyme released by , is frequently detected on testing, further supporting the presence of and . Urinalysis may also reveal possible microscopic , the presence of blood in the urine, protein (proteinuria), or WBC casts (specific to kidney involvement, though rare), as well as gross findings such as cloudy appearance or foul odor, which are indicative of infection. However, a normal urinalysis with no signs of infection such as white blood cells, nitrites, or bacteria generally suggests the absence of active acute pyelonephritis, although rare cases without pyuria exist, particularly in patients with prior antibiotic use; in such instances, diagnosis should not rely solely on urinalysis. Urine culture remains the gold standard for microbiological confirmation, allowing identification of the specific and determination of susceptibilities to guide . A colony count exceeding 10^5 -forming units per milliliter (CFU/mL) in a midstream clean-catch specimen is generally considered indicative of significant consistent with pyelonephritis. Results typically take 24 to 48 hours, emphasizing the importance of empirical treatment initiation while awaiting culture data. Blood tests are essential for evaluating systemic involvement and complications. often shows , with elevated counts reflecting the inflammatory response. Inflammatory markers such as (CRP) and (ESR) are typically elevated, helping to gauge infection severity and monitor response to treatment. Blood cultures should be obtained, particularly in hospitalized patients or those with signs of , as they are positive for bacteremia in approximately 20% to 30% of acute pyelonephritis cases. 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. These tests help stratify risk and inform management decisions in severe cases.

Imaging Techniques

Imaging techniques are employed in pyelonephritis primarily when the is uncertain based on clinical and laboratory tests, or when complications such as urinary obstruction, formation, or underlying structural abnormalities are suspected. According to the (AAFP), initial imaging is not recommended for uncomplicated acute pyelonephritis in adults without risk factors, but it is advised for patients with , suspected urolithiasis, new renal insufficiency, known urologic anomalies, or failure to respond to treatment within 48 to 72 hours. 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. Ultrasound (US) is the preferred first-line imaging modality due to its non-invasive, bedside availability, lack of , and cost-effectiveness, making it especially suitable for initial evaluation in pregnant patients or those with contraindications to other modalities. It effectively detects indicative of obstruction and renal or perinephric abscesses, appearing as hypoechoic or complex fluid collections. Typical findings include renal enlargement with loss of corticomedullary differentiation, focal areas of increased or decreased echogenicity due to or , particulate debris in the collecting system, and reduced cortical vascularity on power Doppler , though US sensitivity for uncomplicated pyelonephritis is limited and may appear normal in up to 80% of mild cases. Contrast-enhanced US can enhance detection of focal involvement or complications like abscesses by highlighting perfusion defects. Computed tomography (CT) of the and with intravenous contrast is the gold standard for evaluating complicated pyelonephritis, providing high for parenchymal involvement and associated complications. It is particularly indicated in immunocompromised patients, those with , or when or gas-forming infections are suspected, as per ACR guidelines rating it as usually appropriate (rating 8-9) for such scenarios. Key findings include the striated nephrogram on contrast-enhanced phases, representing alternating areas of hypo- and hyperenhancement due to tubular obstruction and ; wedge-shaped or focal regions of hypoattenuation; renal enlargement; and perinephric stranding or collections signaling extension of infection. Non-contrast CT can identify calculi, gas (in emphysematous pyelonephritis), or hemorrhage but is less sensitive for subtle parenchymal changes. 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. 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. 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. MRI is particularly useful for follow-up in chronic or recurrent cases to evaluate scarring without cumulative radiation risk.

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, due to nephrolithiasis, and . Acute cystitis, a lower , typically presents with , frequency, and suprapubic pain without flank tenderness or systemic signs like high fever and chills, which are hallmarks of upper tract involvement in pyelonephritis. Renal colic from kidney stones causes intermittent, colicky flank pain radiating to the groin, often accompanied by microscopic but lacking fever and significant unless secondarily infected; imaging may reveal calculi, while positive urine cultures with leukocyturia strongly support pyelonephritis over uncomplicated nephrolithiasis. , an inflammatory kidney condition, features gross , , periorbital , and , typically without bacterial pathogens in urine cultures, differentiating it from the infectious of pyelonephritis. Serious alternative diagnoses include , , and lower lobe , which can present with overlapping abdominal or flank pain and fever. often localizes to the right lower quadrant with rebound tenderness and anorexia, lacking urinary symptoms or positive cultures seen in pyelonephritis. , more common in older adults, causes left lower quadrant pain, , and possible fever but is distinguished by gastrointestinal symptoms like or and absence of flank pain or . Lower lobe may cause referred and fever but is differentiated by respiratory signs such as , dyspnea, and abnormal lung auscultation, with chest imaging confirming the diagnosis over renal involvement. In special populations like children, pyelonephritis must be differentiated from simple lower urinary tract infections and (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 showing retrograde flow, whereas simple cystitis lacks fever and renal parenchymal signs on . Positive cultures with systemic symptoms favor pyelonephritis over uncomplicated VUR without active infection.

Management

Acute Pyelonephritis Treatment

The treatment of acute pyelonephritis primarily involves prompt antimicrobial therapy tailored to disease severity, alongside supportive measures to alleviate symptoms and prevent complications. It is important to seek medical attention quickly if experiencing fever and back pain, as prompt treatment reduces the risk of complications. For mild cases without systemic toxicity, outpatient management with oral antibiotics is appropriate, whereas severe cases, such as those with or inability to tolerate oral intake, necessitate inpatient . Hospitalization criteria include persistent , hemodynamic instability, signs of , or comorbidities that increase risk of poor response, such as or . Most patients are treated at home with oral tablets, but severe cases (e.g., affected general condition or high risk) require hospitalization and intravenous antibiotics. Antibiotic selection begins empirically based on local resistance patterns and common pathogens like , with subsequent guided by culture and sensitivity results to optimize efficacy and minimize resistance. A urine sample for culture is taken, and treatment is adjusted according to resistance patterns. Adherence to current guidelines, such as the 2025 IDSA recommendations, is advised for stepwise selection considering severity, resistance risk, and patient factors. For outpatient treatment of uncomplicated acute pyelonephritis, recommended oral regimens include pivmecillinam 400 mg three times daily for 7-10 days (as recommended in Danish guidelines), 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); ciprofloxacin is often used in cases of penicillin allergy. Inpatient therapy typically starts with intravenous 1 g daily or a fluoroquinolone like 400 mg every 12 hours, transitioning to oral agents once clinically stable. The total duration of antibiotic therapy is generally 7-10 days, though recent IDSA guidelines recommend shorter courses of 5-7 days for fluoroquinolones or 7 days for non-fluoroquinolone regimens in uncomplicated cases with clinical improvement. Supportive care is integral, emphasizing adequate hydration to maintain urine output and prevent , often via oral fluids outpatient or intravenous fluids inpatient until oral is tolerated. Analgesia with nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, addresses flank pain and fever, while antipyretics like acetaminophen control temperature; antiemetics (e.g., ) are used as needed for and vomiting.

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 (VUR) or other predisposing factors. Common regimens include low-dose 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. 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 . Prophylaxis is especially recommended for patients with a history of febrile UTIs and renal scarring, though its efficacy in halting scar progression remains variable. 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 , such as ureteral reimplantation, can resolve high-grade VUR and reduce recurrent pyelonephritis risk in affected individuals, particularly children. Endoscopic injection of dextranomer/ copolymer offers a less invasive alternative for select cases of VUR, though it may not be as durable as open . In patients with , a common exacerbating chronic pyelonephritis due to impaired emptying and neuropathy, rigorous glycemic control through lifestyle modifications, oral agents, or insulin therapy is critical to minimize infection susceptibility and support renal protection. Ongoing monitoring is vital to assess renal function and detect progression of scarring. Regular laboratory evaluations, including serum creatinine, , and , are performed every 3-6 months or more frequently if function declines, allowing early intervention to preserve remaining nephrons. Imaging modalities such as renal ultrasound or dimercaptosuccinic acid (DMSA) scintigraphy are used periodically to evaluate for cortical scarring, , or , with computed tomography (CT) reserved for complex cases to guide management without routine radiation exposure. 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. 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. Post-transplant immunosuppression must be balanced to avoid heightened infection risk.

Complications and Follow-up

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

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 , medical interventions, surgical corrections, and population-based screening. practices play a foundational role in prevention. Maintaining adequate fluid intake, typically more than 2 liters per day, promotes that flushes from the urinary tract, thereby lowering the incidence of UTIs and subsequent pyelonephritis. Urinating after is recommended to eliminate potential pathogens introduced during activity, as supported by guidelines. 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 or trimethoprim-sulfamethoxazole, administered continuously or postcoitally, effectively reduce recurrence rates in women prone to upper tract involvement. Research into vaccines against uropathogenic (UPEC), the primary causative agent, shows promise; preclinical studies with conjugates and other antigens have demonstrated protection against experimental pyelonephritis in animal models, with clinical trials ongoing to evaluate . Surgical interventions address underlying structural abnormalities that predispose to infection. Correction of (VUR) through ureteral reimplantation prevents urine backflow and recurrent pyelonephritis, particularly in children with high-grade reflux. Similarly, removal or management of urinary stones via procedures like reduces stasis and bacterial harboring, mitigating ascent to the kidneys in affected adults. At the population level, screening for asymptomatic in pregnant individuals is a key strategy. Urine culture screening at 12-16 weeks' , followed by targeted treatment, significantly lowers the risk of developing pyelonephritis during , as evidenced by multiple cohort studies and endorsed by major obstetric organizations. 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 annually, though rates vary significantly by and . , around 250,000 to 1.1 million cases are reported each year, many requiring hospitalization. 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 in females, alongside age-related vulnerabilities like reduced immunity in the elderly. Recent trends indicate a rise in complicating pyelonephritis management, particularly among 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 , , and , with yearly increases of 7-8% observed in some surveillance data from 2010-2023. The 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 . Geographically, incidence is elevated in developing countries due to factors like inadequate and limited access to clean water, contributing to higher 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 and those in report more stable but still significant rates, influenced by better hygiene infrastructure.

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). 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. The term was coined in the 19th century, with its earliest documented use appearing in around 1837–1839, marking its entry into clinical as a distinct entity. Prior to this, conditions now recognized as pyelonephritis were often subsumed under broader classifications such as , a 19th-century term introduced by Richard Bright in 1827 to describe and associated renal pathologies, including inflammatory kidney disorders that could encompass pyelonephritic features. 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. Obsolete terms like "suppurative nephritis," which described pus-forming infections akin to pyelonephritis, are avoided in modern terminology to prevent confusion with more precise classifications.

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. 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. 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. Vaccine development represents a promising preventive strategy against pyelonephritis caused by uropathogenic E. coli (UPEC), which accounts for most cases. FimH-targeted s aim to block bacterial adhesion to uroepithelial cells via the type 1 adhesin. Preclinical studies, including a 2024 cynomolgus monkey model of UPEC , confirmed that FimH candidates elicit strong serum IgG and adhesin-blocking antibodies, reducing bacterial burden in the and kidneys. As of 2025, an mRNA-based FimH showed high in , paving the way for translation. A related FimCH complex completed phase 1A/1B trials by 2025, demonstrating a 73% reduction in recurrent UTIs from UPEC or species, with ongoing efforts toward phase II for broader pyelonephritis prevention. 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. A 2025 narrative review highlighted PCR's superior sensitivity for polymicrobial infections and resistance gene profiling in pyelonephritis, improving diagnostic accuracy over conventional tests. These molecular tools, including targeted next-generation sequencing, have been integrated into point-of-care settings post-2020, reducing empirical broad-spectrum antibiotic use. 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. A 2024 analysis linked low-diversity gut microbiomes to increased recurrent UTI risk, suggesting probiotic interventions could restore balance and lower incidence.

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