Pyelonephritis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2]

Pyelonephritis is usually an ascending urinary tract infection that has reached the pyelum (pelvis) of the kidney (nephros in Greek). If the infection is severe, the term “urosepsis” is used interchangeably (sepsis being a systemic inflammatory response syndrome due to infection). It requires antibiotics as therapy, and treatment of any underlying causes to prevent recurrence. It is a form of nephritis. It can also be called pyelitis.

Urinary tract infections have been a long time concern with the first documented description in the Ebers Papyrus dated to 1550 BC. In 1836, Philadelphia surgeon Joseph Parrish described three cases of severe lower urinary tract symptoms without the presence of a bladder stone. Pyelonephritis is a type of upper urinary tract infection. The report of complicated pyelonephritis goes back to 1908.

Pyelonephritis is an upper urinary tract infection. Pyelonephritis may be classified according to the duration of disease and etiology into 5 subtypes: acute uncomplicated, acute complicated, chronic, emphysematous, and xanthogranulomatous pyelonephritis. Most cases of Pyelonephritis are acute uncomplicated and occur in normal healthy individuals with no history of a structural urinary tract anomaly or any long-term disease. Classification of pyelonephritis helps understand dynamics and specify treatments according to the duration, severity and the type of pyelonephritis.

Pyelonephritis is caused by the spread of the infection to the renal parenchyma. The infection, which is the most common cause of pyelonephritis, can either be classified as ascending or descending. Ascending infections stem from a urinary tract which can either be a result of urethritis or cystitis. Descending infections from the blood (hematogenous spread) are a less common cause of pyelonephritis than ascending infections. The Urine is normally sterile and the normal flow of urine washes away bacteria, if any, so that they do not accumulate in a significant amount to cause an infection. Any mechanism that disturbs this normal process like the presence of a catheter, a stone or a tumor can result in stasis and abnormal accumulation of bacteria. These bacteria can ascend through the urethra into the urinary bladder and from the bladder through the ureters to the kidneys and their parenchyma. This results in pyelonephritis and its manifestations.

Causes of uncomplicated and complicated pyelonephritis are mostly similar. Common causes of complicated pyelonephritis include infections such as E. coli, Enterococcus faecalis, Proteus, Klebsiella, and Pseudomonas aeruginosa.

Pyelonephritis must be differentiated from other causes of dysuria such as cystitis, urethritis, prostatitis, vulvovaginitis, urethral strictures or diverticula, benign prostatic hyperplasia, STDs and neoplasms such as renal cell carcinoma and from causes of abdominal pain such as ectopic pregnancy, renal stone, peritoneal or iliopsoas abscess, and rib fracture.

Acute pyelonephritis is reported to cause more than 100,000 hospitalizations each year with the number of people acquiring pyelonephritis being closer to 250,000, yearly. Pyelonephritis is very common, with 120-130 cases annually per 100,000 women and 30-40 cases per 100,000 men. Females are more commonly affected with pyelonephritis than males.

Most risk factors of pyelonephritis are similar to those for cystitis and urethritis, since they themselves predispose the individual to pyelonephritis. Common risk factors in the development of pyelonephritis include renal calculi, urinary tract catheterization, pregnancy, diabetes mellitus, and benign prostatic hyperplasia.

There are no known screening tests for pyelonephritis in general population. However, there are few situations that screening for bacteriuria is performed. Asymptomatic bacteriuria must be screened in pregnancy, prior to urologic surgery, and for research purposes.

Pyelonephritis is distressful condition requiring emergent medical management. Most individuals who are treated adequately with antibiotics do not have complications. A surgical management with removal of stone or obstructing tumor may sometimes be required to prevent complications and prevent obstructive pyelonephritis and stop the course of chronic pyelonephritis. The most common complication of pyelonephritis is recurrent infections. Most episodes of pyelonephritis are uncomplicated and are easily treatable. The prognosis of pyelonephritis varies depending on the type of pyelonephritis and on the timing and duration of treatment. The mortality in case of UTI is between 5% to 33%.

Urinalysis and urine culture with susceptibility testing might confirm the diagnosis of pyelonephritis. Pyelonephritis must be suspected if the patient has urinary symptoms including dysuria, urgency, frequency, or suprapubic pain, along with fever, chills, flank pain, pelvic or perineal pain. Imaging would not be necessary for patients with pyelonephritis, unless in patients with severe and refractory illness or suspected urinary tract obstruction.

Pyelonephritis patients usually present in the emergency department with sudden development of pain radiating to the flank in the presence of dysuria and fever. The differentiation of pyelonephritis from other causes of dysuria is based on severity of symptoms and the typical radiation of pain. A thorough history and examination is required to differentiate pyelonephritis from other causes of dysuria and flank pain.

Pyelonephritis is a medical emergency and requires a thorough physical examination after getting a detailed history and review of symptoms. Typically the patient has acute onset of high grade fever, dysuria and pain radiating to the flank. A sonopalpation test, which is an ultrasound guided palpation, is usually positive and helpful in detecting the exact anatomical structure and position as the cause of tenderness.

Pyelonephritis can be diagnosed with the help or urinalysis and urine culture. Urine culture should always be obtained before administration of antibiotics if pyelonephritis is suspected. A combination of leukocyte esterase test and nitrite test (with either of the two test being positive) is considered to be very effective with a sensitivity ranging from 75-84 and a specificity ranging from 82-98 percent. A blood culture is usually done but may not necessarily yield any findings.

There are no ECG findings associated with pyelonephritis.

An x-ray may be helpful in the diagnosis of pyelonephritis, its risk factors, and complications. Some patients with pyelonephritis have kidney stone which might be visible on x rays of the kidneys, ureters, and bladder (KUB).

There are no echocardiography findings associated with pyelonephritis. Ultrasonography is an effective non-invasive technique in the diagnosis of pyelonephritis. It is sometimes used as a replacement of cortical scintigraphy in the diagnosis of acute pyelonephritis in children.

A CT scan can be used to detect diffuse or complicated pyelonephritis and its suspected complications. It is used when the suspicion of pyelonephritis is accompanied by other differentials. CT scan is very sensitive and CT urography is sometimes used for imaging of the urinary tract. The extent of damage to the parenchymal tissue can also be witnessed in detail with a CT scan.

MRI is sometimes used to diagnose complicated pyelonephritis. It is the preferred modality for diagnosing complicated pyelonephritis when the patient is allergic to iodinated contrast material. A comprehensive idea of the extent of damage to the kidneys can be estimated with an MRI.

Other investigations might be used to diagnose pyelonephritis. Voiding cystourethrogram (VCUG), contrast nephrograms, intravenous pyelography, and urography are helpful in diagnosing pyelonephritis and its complications.

Other diagnostic studies for pyelonephritis include dimercaptosuccinic acid scintigraphy and histopathological exam.

Treatment of Pyelonephritis is usually medical. In case of any risk factors like catheters or obstructing stones or masses, the management includes removing the risk factors to prevent further progress of the disease and the pathogen accumulation. All patients with pyelonephritis should be treated empirically with antimicrobial therapy. Mild pyelonephritis may be managed with oral antimicrobial therapy, and an initial intravenous dose may be administered depending on local resistance patterns. Patients with dehydration, nausea, vomiting, or signs of sepsis should be admitted and should receive parenteral therapy. Medical therapies for pyelonephritis include fluoroquinolones, TMP-SMX, β-lactams, or aminoglycosides.

Different interventions might be used to diagnose or treat pyelonephritis. Flexible ureteroscopy is done for the treatment of obstructive pyelonephritis. Double J stenting, also known as DJ Stenting, is a conservative management method for emphysematous pyelonephritis. Percutaneous nephrostomy is an effective treatment option for emphysematous pyelonephritis which is characterized by necrotizing damage to the parenchyma of the kidney and its adjoining tissue leading to gas formation. Percutaneous nephrolithotomy or transperitoneal laparoscopic ureterolithotomy (TLU) are effective surgical treatment options for pyelonephritis.

Pyelonephritis is usually managed medically. In recurrent infections, additional investigations may identify an underlying abnormality like a stone, a tumor, or an underlying pathological process that has to be aggressively dealt with. Surgery is usually indicated in a patient who does not improve after 48 hours of IV antibiotics or deteriorates. Occasionally, surgical intervention is necessary to decrease of recurrence and to prevent devastating complications. Various renal conditions like obstructive pyelonephritis with presence of stones in the presence of an infected kidney can be fatal and requires urgent management.

Preventative measures to avoid pyelonephritis include the measures for preventing a urinary tract infection which include voiding after intercourse, use of barrier contraception, increasing fluid intake and frequency of urination, cleaning the urethral meatus after intercourse and use of estrogen (among postmenopausal women). Single-dose prophylactic antimicrobial therapy prior to sexual intercourse may be administered to patients who have recurrent episodes of cystitis that are associated with sexual activity. Prevention of recurrence of cystitis may also be helpful in preventing development of pyelonephritis.

Pyelonephritis can be prevented secondarily in some cases by giving long term prophylactic antibiotics. Correction of a structural defect that leads to the initial episode of pyelonephritis may also be helpful in eliminating chances of recurrence of pyelonephritis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2]

Pyelonephritis is caused by the spread of the infection to the renal parenchyma. The infection, which is the most common cause of pyelonephritis, can either be classified as ascending or descending. Ascending infections stem from a urinary tract which can either be a result of urethritis or cystitis. Descending infections from the blood (hematogenous spread) are a less common cause of pyelonephritis than ascending infections. The Urine is normally sterile and the normal flow of urine washes away bacteria, if any, so that they do not accumulate in a significant amount to cause an infection. Any mechanism that disturbs this normal process like the presence of a catheter, a stone or a tumor can result in stasis and abnormal accumulation of bacteria. These bacteria can ascend through the urethra into the urinary bladder and from the bladder through the ureters to the kidneys and their parenchyma. This results in pyelonephritis and its manifestations.

Following important aspects about the pathophysiology of pyelonephritis need to be understood:^[1][2][3][4]

• Pyelonephritis results mostly from an ascending infection, from the urethra (when colonised by organisms) to bladder and then through the ureters to the renal parenchyma or from a hematogenous spread.
• Uncomplicated pyelonephritis occurs in otherwise healthy individuals and because of the normal defence mechanisms of the body it is easy to treat and requires a shorter duration of therapy.
• Complicated pyelonephritis occurs in otherwise unhealthy individuals, pregnant or post menopausal women or other immunocompromised patients and thus requires aggressive, long term and broad spectrum treatment.
• Acute pyelonephritis is an exudative inflammation of the renal pelvis and the kidney and can be purulent in nature.
• The abscesses in the renal parenchyma depict suppurative necrosis. This may consist of pus which is a purulent exudate and may contain neutrophils, fibrin, cell debris and central germ colonies.
• Neutrophil casts may be found as the damage occurs to the tubules by the neutrophils within it. Initially the glomeruli and vessels are normal.
• A decreased expression of CXCR1 which is a receptor for interleukin 8 is considered to be a reason for pyelonephritis in individuals with positive family history.
• The infection can spread to the peritoneum. The inflammation and infection can irritate the nerve endings resulting in the specific mild costovertebral tenderness that can progress to severe abdominal pain radiating to back.
• Chronic infections may be secondary to kidney stones or a tumor constantly obstructing the normal urinary flow or secondary vesicouretral reflux.
• Chronic or recurrent infections result when pathogens like E.coli invade the epithelium at any place in the urinary tract and avoid body defense mechanism. These reservoirs act as a continuous source of pathogen. Chronic infections can result in fibrosis and scarring of the kidneys.

• Emphysematous pyelonephritis is caused by bacteria following the same pathogenesis as described above. It is a necrotising infection of the renal substance with production of gas. The gas accumulates in the parenchyma of the kidney, the perinephric space and the collecting system. Majority of the patients with emphysematous pyelonephritis have diabetes mellitus.^[5][6][7]
• Emphysematous pyelonephritis can be divided into 2 subtypes:^[8]
  • Type 1: It is the destruction of parenchyma without fluid collection or mottled or streaky gas presence (69% mortality).
  • Type 2: It is the destruction of parenchyma with the collection of fluid in renal or peritoneal area with gas in collecting system or loculated or bubble appearance of gas (18% mortality).

• Xanthogranulomatous pyelonephritis is a rare type of pyelonephritis. It is associated with nephrolithiasis. Many kidney stones are seen and stag horn calculi are very commonly associated with it. Xanthogranulomatous pyelonephritis is usually confused due to its appearance, with a malignancy and aggressive management requiring a surgical resection is done. The histopathology of the specimen confirms xanthogranulomatous pyelonephritis rather than a tumor. The initial presentation can be abdominal distention owing to the formation of a peritoneal abscess. Proteus mirabilis is the most common organism involved in case of a peritoneal abscess associated with xanthogranulomatous pyelonephritis.^[9]

Though the genetics of pyelonephritis have not been studied extensively. It is understood that family history of urinary tract infections is a strong risk factor recurrent urinary infections and pyelonephritis in relatives. This risk is stronger in closer than distant relatives suggesting the role of a genetic component. A decreased expression of CXCR1 which is a receptor for interleukin 8 is considered to be a reason for pyelonephritis in individuals with positive family history.^[4][10][11]

The following conditions are associated with the development of pyelonephritis:^[12][13][14]

• Immunodeficiency
• Diabetes
• Pregnancy
• BPH
• Renal Stones
• Post Menopausal Status
• HIV

Gross pathology of pyelonephritis often reveals pathognomonic radiations of hemorrhage and suppuration through the renal pelvis to the renal cortex.^[15]

• Gross pathology of acute pyelonephritis demonstrates papillary necrosis

• Gross pathology of chronic pyelonephritis demonstrates:
  • Dilated and distorted renal pelvis
  • Papillary necrosis
  • Fibrosis and scarring

The microscopic examination can have the following features:^[15]

• Acute pyelonephritis
  • Neutrophils within the tubules and interstitium
• Chronic pyelonephritis
  • Interstitial fibrosis
  • Renal casts
  • Mononuclear tubulointerstitial infiltarte
• Xanthogranulomatous pyelonephritis
  • Numerous macrophages
  • Interstitial plasma cells
  • Giant cells

• 
  Acute Pyelonephritis with neutrophils within the tables and interstitium. Source: Libre Pathology^[16]
• 
  Xanthogranulomatous Pyelonephritis.Source: Libre Pathology^[17]

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