Pyelonephritis, acute N10

Acute pyelonephritis (APN) is a tubulointerstitial nephritis usually caused by a urinary tract infection, which in the majority of cases is unilateral (Herold 2020). However, APN can also develop without a previous cystitis (Kasper 2015).

APN is differentiated between the following types:

• 1. uncomplicated APN, these
  • is acquired on an outpatient basis
  • is accompanied by no vomiting
  • predisposing factors do not exist (Keller 2010)
• 2. complicated APN:
  • in this case, there are signs of severe systemic inflammation such as nausea, vomiting, circulatory instability, etc. (Wagenlehner 2017)
  • Risk factors are present such as diabetes mellitus, gravidity, male gender, urinary bladder catheter, anatomical malformations (Manski 2019), weakening of the immune system (Michel 2016), etc.
  • Complications are more frequent during the course of the disease (Suman 2020).
• 3. emphysematous pyelonephritis:
  • It is a necrotizing inflammation, which is caused in > 70% by E. coli. This leads to gas accumulation in the area of the renal parenchyma, the renal pelvic caliceal system and the perinephritic tissue (Kuhlmann 2015/Suman 2020 / Colgan 2011).

APN is more common in women than in men and is particularly common during pregnancy(Michel 2016).

It causes approximately 250,000 physician visits and approximately 200,000 hospitalizations per year in the United States. Women between the ages of 15 - 29 are most commonly affected, followed by infants and the elderly.

APN also occurs in men, but only very rarely. In these cases, functional or anatomical abnormalities are usually present (Kasper 2015 / Colgan 2011).

Approximately 75% of patients with APN have a history of one or more urinary tract infections (Schmelz 2006).

However, in patients with acute cystitis, pyelonephritis develops due to ascension of the pathogens in only < 5 % (Manski 2019 / Schmelz 2014).

In pregnant women, however, PN by ascension occurs in up to 23 %. This can be complicated by concomitant

• anemia (23 %)
• renal dysfunction (7 %)
• respiratory insufficiency (7 %)
• In turn, according to Manski (2019), an APN in pregnant women can lead to:
  • prematurity
  • reduced birth weight
  • increased neonatal mortality
  • pre-eclampsia
• Mycosis pyelonephritis: PN caused by mycosis is rare. It is Candida in up to 90% of cases in Central Europe. Only occasionally molds, Cryptococcus and other fungi are found (Schmelz 2006).
• Emphysematous PN (The emphysematous APN occurs only very rarely. It preferentially affects older women with diabetes mellitus, Suman 2020).

APN can have different causes:

• Ascending

Acute APN primarily results from ascending infections of a urinary tract infection (Manski 2019).

The germs are primarily E. coli (70% - 95%) followed by Staphylococcus saprophyticus with about 5% , very rarely occur Proteus, Klebsiellen, Enterobacteriaceae, Mycoplasma hominis and fungi (Schmelz 2006).

(Keller 2010)

• Hematogenous

Gram-positive germs, fungi, tubercle bacilli, viruses and parasites are predominantly the result of haematogenous spread. However, they are very rarely found as the cause of an APN.

(Michel 2016)

• Vesicoureteral reflux (VUR).

VUR can be congenital or acquired. It causes a pendulum urine in the upper urinary tract, from which recurrent pyelonephritides to terminal renal failure can develop (Manski 2019 / Kuhlmann 2015).

In APN, inflammation leads to edematous swelling of the kidney(s). Subcapsularly, there are pinhead-sized, raised abscesses with hemorrhagic margins, which sometimes confluent. Pus-filled tubules extend as yellow roads from the cortex to the papillae.

The mucosa in the renal pelvis covered with exudate shows thickening.

Scarring healing is likely, especially in children.

(Manski 2019)

In emphysematous APN, intraparenchymal gas formation occurs in the kidney (Colgan 2011). The gas remains within the gerota fascia (connective tissue covering of the kidney [Manski 2019]). The exact mechanism of gas formation is not yet known. Gas formation is thought to occur through fermentation of E. coli (Manski 2019).

Acute APN shows a sudden onset (Kasper 2015). There is a triad of:

• Fever

This shows a typical sawtooth pattern. The fever can be mild to very high, with or without chills (Kasper 2015).

• Dysuria
• palpitation of the renal pelvis (so-called flank pain)

(Herold 2020)

However, these characteristic symptoms may be absent in immunosuppressed patients or hyposensitive patients (e.g., spinal cord injury patients, diabetics) (Michel 2016).

Atypical symptoms also occur-especially in children and the elderly-such as:

• Nausea
• Vomiting
• abdominal pain
• Subileus
• headache

(Herold 2020)

• diarrhea
• strong feeling of sickness
• Tachycardia
• Hypotension

(Manski 2019)

Physical examination

Typical of acute APN is a palpitating renal bed; in rare cases, both renal beds are palpitating.

In men, a rectal examination should always be performed to rule out concomitant prostatitis.

(Michel 2016)

• Sonography

Sonography is obligatory in the presence of APN (Manski 2019). The kidneys may be enlarged, the parenchyma is usually widened and appears less echoic. The wall thickness of the renal pelvis is increased with a cut-off value of 2.0 mm (Michel 2016).

In addition, sonography reveals any existing urinary outflow obstruction.

Air pockets in the parenchyma of the kidney may be evidence of emphysematous PN.

If there is evidence of an echo-deficient mass in the renal area, it is most likely a renal abscess.

In all these cases, CT should be performed for further diagnosis.

In PN caused by fungi, solid echoic structures without acoustic shadow, the so-called fungal balls, are seen sonographically (Schmelz 2006).

Sonography is also the diagnostic tool of choice in cases of vesicoureteral reflux in children with APN. In adults, reflux is found in only about 2% of cases.

(Manski 2019)

• i. v. pyelogram

If sonographically there is a suspicion of urinary outflow obstruction, emphysematous PN or nephrolithiasis, an i. v. pyelogram (also known as urogram) can be performed for further diagnosis.

Nowadays, however, further diagnostics are usually performed by CT.

In emphysematous PN, gas inclusions are seen within the gerota fascia. These should not be confused with a gas accumulation of the renal pelvic caliceal system, which is less severe.

(Manski 2019)

• Contrast-enhanced CT.

In acute APN, CT is indicated if.

• there has been no resolution of fever after 72 h
• with sonographic V. a.
  • an abscess
  • an emphysematous PN
  • Obstruction

(Manski 2019)

CT should always be performed as a multiphase CT:

• native spiral CT for exclusion of concrements
• KM-series to exclude
  • Abscesses
  • obstruction
  • focal inflammation
• late series in case of a possible outflow obstruction

(Schmelz 2006)

The CT shows:

• no contrast uptake: abscess
• wedge-shaped homogeneous attenuation of the contrast medium: uncomplicated focal disease
• heterogeneous contrast medium attenuation: complicated focal event
• Assessment of the extent of possible perirenal fungal abscesses

(Schmelz 2006)

Blood test

The following changes are usually found in APN:

• Blood count: Leukocytosis
• BSG: elevated
• CRP: elevated

(Manski 2019)

• Procalcitonin: elevated (Michel 2016)

It should also be checked for signs of renal failure in severe courses such as:

• Creatinine
• Cystatin C to determine GFR (Manski 2019).
• Electrolytes such as:
  • Sodium
  • Potassium
  • Chlorine
• Blood gas analysis

(Michel 2016)

In very severe cases and especially if sepsis is suspected, it is necessary to check for a consumption coagulopathy (anemia, decrease in platelets, Quick, fibrinogen and coagulation factors [factor V, VIII, XI]).

Sepsis is suspected with:

• Increase in INR (International Normalized Ratio)
• decrease of the Quick- value
• Increase in C-reactive protein or (faster responding) procalcitonin
• decrease in platelets
• Leukocytosis

(Michel 2016)

In severe cases and/or if sepsis is suspected, blood cultures should be taken immediately (Herold 2020). In acute APN, these are positive in 10 % - 20 % (Keller 2010).

If there is a suspicion of PN caused by mycoses, fungal cultures should be taken from:

• Urine
• blood
• sputum
• possible intraoperative interventions

(Schmelz 2006)

Urine sediment

• Urine mostly flocculent and turbid
• Leukocyturia (always an indication of pyelonephritis [Herold 2020])
• Pyuria (if this is absent, there is doubt about the diagnosis of PN)
• Bacteriuria (in 80 % - 90 % > 10 5 CFU / ml [colony forming units])
• Hematuria
• Leukocyte cylinder
• mild proteinuria

(Keller 2010 / Manski 2019)

In the acute form, wedge-shaped abscess streets with striated collections of granulocytes are found in the renal parenchyma between the papilla and the cortex (Herold 2020).

• Nephrolithiasis
• Kidney tumor
• Renal infarction
• papillary necrosis (Michel 2016)
• Pancreatitis
• Pleurisy
• basal pneumonia
• Adnexitis
• acute appendicitis
• acute cholecystitis
• lumbago / lumbar spine syndrome
• (Sigma-) diverticulitis
• renal or perirenal abscess

(Herold 2020 / Manski 2019)

• Urosepsis (life-threatening complication; occurs in up to 65% after instrumental procedures in the setting of APN).
  • Early symptoms of urosepsis are:
    • tachypnea (> 20 breaths/min)
    • tachycardia (> 90 beats / min)
    • hyperthermia (> 38 ° C)
    • Hypothermia (< 36 ° C, alternating with fevers)

(Schmelz 2006)

• hydronephrosis or pyonephrosis (in case of obstruction)
• paranephritic or intraparenchymal abscess
• pyelonephritic shrinkage (n)
• purulent nephritis
• chronic renal insufficiency
• renal carbuncle
• renal parenchymal damage
• Partial tubular dysfunction such as:
  • Sodium-losing kidney
  • Potassium-losing kidney
• Disturbances in the ability to concentrate with polyuria and polydipsia

(Herold 2020 / Kasper 2015 / Manski 2015)

Mild to moderate APN can usually be treated as an outpatient. However, the patient should remain on bed rest.

In case of systemic accompanying symptoms such as vomiting, circulatory instability, etc. (Wagenlehner 2017), inpatient treatment for parenteral antibiosis is recommended.

(Kuhlmann 2015)

Analgesia

Metamizol, for example, is suitable as an analgesic (with simultaneous antipyretic effect).

Dosage recommendation: Metamizol 1 g - max. 4 g / d (Frölich 2003).

(Kuhlmann 2015)

Antibiosis

Before starting antibiosis, a urine culture should be obtained and after receipt, the antibiosis should be adjusted if necessary (Manski 2019).

• Uncomplicated acute PN in pre-menopausal women.

In this case, antibiotics can usually be administered orally. The pathogen spectrum corresponds approximately to that of uncomplicated cystitis.

Medications of first choice for uncomplicated acute APN are e.g.:

• Ciprofloxacin

Recommended dosage: 500 mg 2 x / d for 7 - 10 days.

Dose adjustment required from a GFR of < 60 ml / min / 1.73 m² KOF

(Herold 2020 / Kuhlmann 2015)

• Fluoroquinolones such as levofloxacin

Dosage recommendation: 500 mg 1 x / d for 7 - 10 days.

Dose adjustment required from a GFR of < 50 ml / min / 1.73 m² KOF

(Manski 2019 / Herold 2020)

• Cefpodoxin- Proxetil

Dosage recommendation: 200 mg 2 x / d for 10 days.

(Wagenlehner 2017)

Dose adjustment required from a creatinine clearance < 50 ml (Frölich 2003).

• Severe course of acute PN

In the case of a severe course with accompanying systemic symptoms such as vomiting, circulatory instability, etc., inpatient treatment and initial administration of parenteral antibiotics are required (Wagenlehner 2017).

The recommended 1st-line agents are:

• Ceftriaxone (3rd generation):

Dosage recommendation: 50 mg / kg bw / d as a single dose i. v.

(Manski 2019)

Dose adjustment in renal insufficiency NOT required (Frölich 2003).

• Cefepime (4th generation):

Dosage recommendation: 50 mg / kg bw / d every 8 - 12 hours i. v.

Dose adjustment required from a creatinine clearance < 50 ml (Frölich 2003).

(Manski 2019)

• Ceftazidime (3rd generation):

Dosage recommendation: 50 mg / kg bw / d every 8 hours i. v.

Dose adjustment required from a creatinine clearance < 50 ml (Frölich 2003).

(Manski 2019)

As soon as fever is removed, it can be switched to oral medication, e.g.:

• Ceftibuten 9 mg / kg bw 1- 0- 0 or.
• Cefixime 4 mg - 8 mg / kg bw 1- 0- 1.

(Manski 2019)

The duration of therapy should be 14 days in total, up to 21 days in severe courses (Michel 2016).

• Pregnant patients

Pregnant women are at significantly increased risk for serious complications. For this reason, antibiotics should always be administered parenterally (Herness 2020).

Medications that may be considered are:

- 2nd or 3rd generation cephalosporins.

- Penicillin derivatives

(Kuhlmann 2015)

• Cephalosporins such as:

- Cefuroxime (2nd generation)

Recommended dosage 750 mg 3 x /d i.v.

Dose reduction from a creatinine clearance of < 30 ml/ min

(Manski 2019)

- Cefotaxime (3rd generation)

Dosage recommendation 3 - 6 g / kg bw i.v. 3 x / d i. v.

Dose reduction from a creatinine clearance of < 5 ml /min

(Manski 2019)

• Penicillin derivatives such as e.g.

- amoxicillin

Dosage recommendation: 1 - 2 g 4 x / d i. v.

Dose reduction from a creatinine clearance of < 30 ml/ min

(Furger 2003)

The duration of therapy should be at least 14 days.

If no therapeutic success is apparent after 3 - 5 days, further diagnostics are recommended. In the majority of cases, a renal abscess is present, which should be drained immediately.

(Briese 2015)

• Mycosis pyelonephritis

In PN caused by mycosis, systemic antifungals should be used for treatment such as:

- Amphotericin B

After a test dose of 1 mg / 100 ml over a period of 30 min, the initial dose of 0.1 mg / kg bw / d can be increased daily up to 1 mg - 5 mg / kg bw / d.

The single doses should be applied every 4 h. The maximum dose is 4 g. This should not be exceeded in at least 6 weeks.

(Schmelz 2006)

- 5- Flucytosine

Dosage recommendation: Every 4 - 6 h administration of single doses of 100 mg - 150 mg / kg bw / d (Schmelz 2006).

- Fluconazole

After i.v. administration of the antimycotics, treatment with fluconazole (e.g. triazole) should follow for 10 - 30 days.

Recommended dosage: 50 mg - 400 mg / d orally.

This allows 94 % - 95 % of urogenital mycoses or candiduria to be remediated.

(Schmelz 2006)

• Transplant kidney

Pyelonephritis of a transplant kidney can lead to a significant deterioration of graft function, which only partially regresses even after successful treatment (Kuhlmann 2015).

• Follow-up

On the 4th day of therapy and approx. 7 days after the end of antibiotic treatment, the urine cultures should be checked with regard to the course (Hegele 2015) .

In APN, there are situations that require surgical treatment, such as:

• possible anomalies of the urinary tract (Schmelz 2006)

• an infected urinary stasis kidney
  • it is a life-threatening emergency due to the threat of urosepsis. In this case, immediate drainage or percutaneous nephrostomy should be performed (Manski 2019).

• an abscess
  • this requires percutaneous abscess drainage (Schmelz 2006).

• mycosis- pyelonephritis
  • in patients with pyelonephritis caused by mycosis, surgical intervention is required in approximately 50%.
  • if fungal balls lead to a urinary retention kidney, an immediate urinary drainage is recommended
  • in the case of bilateral infestation without a tendency to regression, the fungal material should be removed surgically (endurologically or openly).

(Schmelz 2006)

• Nephrectomy

Nephrectomy may also be required in the setting of APN, as in:

- development of sepsis originating from the kidney, which cannot be stabilised with intensive medical measures

- An emphysematous PN that cannot be managed by conservative measures.

(Manski 2019)

- complete destruction of the kidney in the course of mycosis (Enamel)

a. o.

In childhood, APN heals only with scarring parenchymal damage. Mostly it affects children up to the age of 5, but cases up to puberty have also been described. The parenchymal damage can lead to the development of chronic pyelonephritis - the so-called Ask- Upmark- kidney (Manski 2019).

In the majority of women, uncomplicated APN heals completely under adequate and early therapy, and there is no subsequent deterioration in renal function. However, in the case of severe infections or a delayed start of therapy, scarring may occur.

(Kuhlmann 2015)

Acute renal failure is extremely rare in the context of APN (Schmelz 2006).

In complicated PN, recurrence occurs in approximately 10%-30% of patients treated with antibiotics for 14 days. This should be treated again with antibiotics for 14 days (Schmelz 2006).

Patients on the waiting list for a kidney transplant have between 15 % - 25 % infectious diseases as (co-)cause of terminal renal failure.

(Michel 2016)

• Mortality

The mortality of pyelonephritis is 0.4 / 100,000, which corresponds to about 320 deaths per year in Germany (Hegele 2015).

In contrast, emphysematous PN has a very high lethality of 43% (Manski 2019).

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