Acute Pyelonephritis

Acute pyelonephritis is a condition incited by a bacterial infection that affects the parenchymal tissue of the kidneys. It is, most frequently, a complication of a lower urinary tract infection that has allowed pathogens to further infiltrate the kidneys; alternatively, bacteria can access the kidney through the bloodstream. Acute pyelonephritis can eventuate in septic phenomena, abscess of the kidney or a chronic state of inflammation and secondarily, kidney failure


Presentation

An episode of acute pyelonephritis typically presents with three symptoms: fever, nausea and costovertebral angle pain. Although this is termed as the classic symptomatology of pyelonephritis, these three symptoms may not be simultaneously present or some may not be manifested at all. Fluctuation in the severity of the symptoms is naturally expected, and may even develop gradually, instead of acutely. Even though acute pyelonephritis usually develops as a result of a prior, complicated lower UTI infection, the latter's symptoms may not be present at the time of diagnosis.

A lower UTI infection exhibits a characteristic symptomatology, including hematuria, fever, dysuria and frequent, urgent urination. Approximately 1/3 of female patients with pyelonephritis exhibit the symptom of hematuria; should the patient be male, an investigation of other causes of hematuria should promptly be investigated. Febrile patients commonly exhibit chills or rigor as well, alongside fatigue and weakness. Temperature is not expected to exceed an average of 103°F (39.4°C).

The pain felt at the costovertebral angle is characteristically triggered by percussion and it is usually experienced at the side of the affected kidney. Gastrointestinal symptoms, such as vomiting or anorexia may also be present.

Children may lack the typical symptoms of acute pyelonephritis, a fact which renders the diagnosis considerably more difficult. Particularly infants or neonates who cannot yet express themselves verbally may evince anorexia, lethargy, fever and vomiting. Senior patients may experience symptoms that are identical to those of a lower UTI infection, or clinical manifestations that include a mental status impairment, fever and organ failure.

Workup

A detailed medical history and clinical examination, alongside confirmation by urinalysis usually suffice in order to diagnose acute pyelonephritis. Radiologic depiction is usually employed in infants and children or adults who do not manifest characteristic symptoms. Should the symptomatology match the typical clinical picture of acute pyelonephritis, the analysis of the urine is expected to produce the following results to confirm an infection:

A nitrite test can also be used; nevertheless, it can be falsely negative in various cases. A urine culture is also mandatory in order to eliminate antibiotic resistance. A blood culture can confirm the bacterial strain, should the pathogens have reached the renal parenchyma through the bloodstream.

A physician may perform imaging techniques if a patient continues to deteriorate despite treatment, if toxicity persists for >72 hours and if fever does not subside after 2 days. The optimal imaging technique is considered to be the contrast-enhanced helical/spiral computed tomography (CECT). Should it reveal a possible nephrolithiasis, a computed tomography (CT) scan and urogram need to be carried out for fear of hydronephrosis [9].

Treatment

Prompt treatment of acute pyelonephritis is the key to achieving optimal therapeutic results. Since blood and urine cultures need some days to produce the results and pyelonephritis should be treated as early as possible, empirical treatment is usually administered from the start, which may be subject to adaptations if the cultures show a resistant microorganism. Local studies of pathogen resistance should be consulted prior to choosing the antimicrobial agent. Patients may need to be hospitalized, receive parenteral treatment and then complete their regime with oral agents [10] or could be treated at home from the beginning. A patient can be allowed to remain at home and receive oral treatment if they are in a good health status other than pyelonephritis, if they can abide by the doctor's direction, they display no septic phenomena or further complications.

Empirical treatment includes the administration of a selection of the following agents:

• Meropenem 
• Imipenem
• Ampicillin and an aminoglycoside
• Piperacillin-tazobactam
• Ticarcillin-clavulanate

A penicillin allergy prompts its replacement with vancomycin. Hospital therapy is continued for 10 to 14 days, starting with IV administration of antibiotics fro at least 1 or 2 days or until the patient's condition ameliorates.

Prognosis

An episode of acute pyelonephritis is a treatable condition, which, if addressed appropriately, can heal completely; if mistreated or untreated, however, it can cause serious damage and threaten the kidney and potentially the life of the patient as well.

Healthy individuals, both men and non-pregnant women, tend to recover to a full extent with no renal impairment, given that their health status is other than that normal. On the other hand, pregnant women do run a higher risk of going into labor prematurely and patients over the age of 65, immunodeficient people and people with a generally poor status of health display an increased mortality. Patients with an underlying diabetes mellitus were also shown to suffer from severer attacks of pyelonephritis and have increased mortality [8].

Etiology

The greater majority of pyelonephritis cases are triggered by bacteria, which have infiltrated the renal parenchyma via the lower parts of the urinary tract. A crucial risk factor that increases susceptibility to such a condition is anatomic variability: strictures at any part of the lower tract or ureters increase the possibility of developing a renal inflammation. This risk factor primarily affects men. The condition frequently affects young women and women who have undergone catheterization.

Another pathway, through which bacteria can infiltrate the kidney, is the bloodstream itself. Aggressive pathogens such as Staphylococcus aureus, pseudomonas aeruginosa and various Candida species are known to posses the ability to enter the renal parenchyma in such a way.

Epidemiology

Studies conducted in the USA confirmed that women tend to be more frequently affected by pyelonephritis than men. Researchers observed that, per year, around 16 cases of acute pyelonephritis were diagnosed amongst 10,000 women, in contradistinction to a considerably lower number, 3-4, per 10,000 men [3]. Even in women, the susceptibility to pyelonephritis varies with age: incidence increases at the periods of 0-4 years old, 15 to 35 years old and then again after the 80th year of age [3]. Treatment of acute pyelonephritis costs approximately $2.14 billion annually [3] [4].

Pregnant women run a higher risk of being affected by acute pyelonephritis. Data exhibited a staggering 20-30% of pyelonephritis cases in pregnant women, resulting from asymptomatic bacteriuria, for which the patients received no therapy. Women are also more frequently hospitalized with acute pyelonephritis than men, at a rate of 5:1, but do, however, maintain a lower mortality rate [5].

Pyelonephritis affects people of all ethnicities and its incidence seems to fluctuate additionally, according to the season. July, August and September were shown to be the months with an increased incidence of acute pyelonephritis, according to a study conducted in the state of Washington.

Sex distribution
Age distribution

Pathophysiology

A lower urinary tract infection (lower UTI) that is complicated with the ascendance of bacteria to the kidneys causes acute pyelonephritis; it is possible to outline a partial profile of patients who are in higher risk of developing such a condition, based on patient characteristics and bacterial traits [6].

The bloodstream pathway is another possibility for bacterial infiltration of the kidney. Bacteremia due to gram (+) pathogens, combined with other underlying systemic conditions or iatrogenic immunosuppression can lead to acute pyelonephritis, where the bacteria have been transferred to the kidney parenchyma through the bloodstream. This pathway, however, is reserved almost exclusively for the immunodeficient.

Most cases of lower or upper UTI can be traced back to the Escherichia coli pathogen, and more specifically, the uropathogenic E. coli (UPEC), which is one of the bacterium's strains. This bacterium latches on to the epithelial layers, causing a glycosphingolipid- and TLR4-mediated inflammation. This results to the activation of the immune system; chemokines such as IL-8 are activated, and connect to the interleukin 8 receptor (CXCR1). As a result, polymorphonuclear leukocytes are allowed to access the urine.

Infection is initiated at the pelvis, proceeding to the medulla and the cortex as it expands, while separate non-infected regions may still appear inbetween. An abscess may form and other papillary necrosis is reserved for patients with an underlying systemic disease (diabetes, analgesic neuropathy, sickle cell disease). Men who have an anatomic urinary tract obstruction, including prostatitis and hypertrophy, are in increased danger of suffering from acute pyelonephritis [7].

Prevention

Pyelonephritis can be prevented by adaptations in one's routine and behavior, in order to eliminate the possibility of being affected by a urinary tract infection. Contraceptive behavior should be reevaluated, frequent urination is encouraged and any case of cystitis should be identified and treated early, so as to avoid its being complicated with acute pyelonephritis. Patients who do proceed to these adaptations but still experience recurrent phenomena of UTI or pyelonephritis or do not respond to appropriate treatment should be examined for the existence of an obstructing anatomic variation.

Specifically women who are affected by a urinary tract infection more than three times per year should consider the following measures:

  • Drinking larger amounts of fluids, preferably water.
  • Urinating frequently.
  • Urinating before and after coitus.
  • Avoiding the use of a diaphragm or spermicide.
  • Wiping from the front to the back after defecation.
  • Prophylactic antibiotics administered either continuously or after sexual intercourse. This scheme is recommended after failure of the aforementioned methods.

Proper hydration is generally the key to avoiding frequent urinary tract infections and reducing the risk of acute pyelonephritis.

Summary

Acute pyelonephritis poses a considerable threat on the life of the affected patient and the functionality of the kidneys, as it can induce severe renal impairment. Possible complications resulting from acute pyelonephritis include septic phenomena or even septic shock, renal scarring, abscesses located on the kidney or on adjacent tissue and failure of multiple organs. Individuals who are immunosuppressed run a significantly higher risk of developing any of those complications [1] [2].

In the majority of the cases, acute pyelonephritis is preceded by an episode of infection of the urinary tract's lower parts. Patients report the classic symptomatology: frequent and urgent urination, pain during the action, hematuria and suprapubic pain. It is also possible that a patient first becomes symptomatic with symptoms originating from the acute pyelonephritis itself, such as back pain at the renal level and flank pain. General signs of inflammation may accompany both cases and patients may be febrile and experience nausea, frequent vomiting and chills. Acute pyelonephritis may also present with symptoms that are non-specific; therefore, clinical doctors should be always suspicious in cases of inflammations which are hard to trace. 

Patient Information

Acute pyelonephritis is an inflammation of one or both kidneys, caused by a bacterial infection. The bacteria may ascend to the kidneys from lower parts of the urinary tract, such as the bladder, due to a previous infection affecting those parts (cystitis).

The bacterium that most commonly causes cystitis and subsequent pyelonephritis is the Escherichia coli, normally found in the intestines, excrement and transiently the anal area. Poor genital hygiene or wrong toilet habits may lead to these bacteria entering the bladder and further moving up to the kidneys.

Women tend to be more frequently affected by pyelonephritis that men. Generally, there are sub-categories of people who run a higher risk of developing pyelonephritis, such as people who suffer from diabetes mellitus, transplant receivers, HIV patients, people who receive medication that weakens their immune system and pregnant women.

Pyelonephritis produces symptoms that involve fever with chills, pain at the back (low), nausea and vomiting. The condition will be diagnosed based on the symptomatology, urine test and urine culture. A urine test helps to confirm the inflammation, as it can detect the number of white blood cells currently present in the urine and the red blood cells. A urine culture will reveal the bacterium responsible for the inflammation. Treatment should be administered promptly in order to avoid possible complications and may be carried out in a hospital or at home, depending on the person's general health status and clinical manifestations. Treatment regimes last for 6-14 days.

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References

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  2. Bergeron MG. Treatment of pyelonephritis in adults. Med Clin North Am. 1995;79:619–49.
  3. Czaja CA, Scholes D, Hooton TM, Stamm WE. Population-based epidemiologic analysis of acute pyelonephritis. Clin Infect Dis. 2007 Aug 1. 45(3):273-80.
  4. National Kidney & Urologic Diseases Information Clearinghouse (NKUDIC). Kidney and Urologic Diseases Statistics for the United States. Available at http://kidney.niddk.nih.gov/kudiseases/pubs/kustats/#urologic. Accessed: October 31, 2011.
  5. Foxman B, Klemstine KL, Brown PD. Acute pyelonephritis in US hospitals in 1997: hospitalization and in-hospital mortality. Ann Epidemiol. 2003;13:144–50.
  6. Mazaki-Tovi S, Vaisbuch E, Romero R, et al. Maternal plasma concentration of the pro-inflammatory adipokine pre-B-cell-enhancing factor (PBEF)/visfatin is elevated in pregnant patients with acute pyelonephritis. Am J Reprod Immunol. 2010 Mar 1. 63(3):252-62.
  7. Stamm WE. Urinary tract infections and pyelonephritis. In: Harrison TR, Braunwald E, eds. Harrison’s Principles of internal medicine. 15th ed. New York: McGraw-Hill, 2001:1620–6.
  8. Kofteridis DP, Papadimitraki E, Mantadakis E, et al. Effect of diabetes mellitus on the clinical and microbiological features of hospitalized elderly patients with acute pyelonephritis. J Am Geriatr Soc. 2009 Nov. 57(11):2125-8.
  9. Abrahamian FM, Moran GJ, Talan DA. Urinary tract infections in the emergency department. Infect Dis Clin North Am. 2008 Mar. 22(1):73-87, vi.
  10. van Nieuwkoop C, van't Wout JW, Spelt IC, et al. Prospective cohort study of acute pyelonephritis in adults: safety of triage towards home based oral antimicrobial treatment. J Infect. 2010 Feb. 60(2):114-21.

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