Chronic pyelonephritis N11.9

Chronic pyelonephritis (CPN) is variously defined in the literature:

• a chronic interstitial nephritis caused by obstruction (Herold 2018)
• a chronic atrophic PN
• an inflammation associated with cortical scarring over plumped renal calices (Hegele 2015)
• chronic smoldering or relapsing PN, always associated with parenchymal damage (Keller 2010)

The following forms are predominantly found in the literature:

Chronic focal destructive pyelonephritis: This is understood to be a persistent or relapsing PN that is always associated with parenchymal damage (Keller 2010).

Xanthogranulomatous pyelonephritis (XPN). A distinction is made in XPN between 2 forms:

- diffuse form (affects about 85%)

- localized form

The localized form is rare and difficult to distinguish from a malignant tumor (Vogl 2011).

XPN is a chronic inflammation with purulent destruction of renal tissue caused by outflow obstruction (Kasper 2015) and occurs predominantly unilaterally. The course is always progressive and leads to granulomatous destruction of both the kidney and renal capsule and surrounding tissues (Kuhlmann 2015).

Ask- Upmark- Kidney: In childhood, APN heals only with scarring parenchymal damage. Mostly children up to the age of 5 are affected, 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).

CPN: CPN is still the most common cause of end-stage renal failure, accounting for up to 20%, although the numbers have been declining for several years: in 2006, they were still 25% (Schmelz 2006 / Manski 2019).

XPN: XPN is a rare disease with an incidence of 1.4 / 100,000 (Pallwein- Prettner 2011). It predominantly affects women (in 66% - 86% of cases). The mean age of onset is around 50 years (Hegele 2015).

The causes of CPN vary widely:

• Recurrent acute pyelonephritis: Most commonly, CPN is caused by recurrent ascending bacterial infections of acute pyelonephritis (Manski 2019). This is usually caused by a mixed infection (Herold 2018).
• Vesicoureteral reflux (VUR): VUR associated with bacteriuria can also lead to CPN and then correlates with the severity of VUR. Sterile reflux alone, on the other hand, does not cause CPN (Manski 2019).
• Neurogenic bladder disorders: Similarly, ascending infections in neurogenic bladder disorders can lead to CPN. Neurogenic bladder disorder alone does not cause CPN, similar to VUR (Manski 2019).
• Ask- Upmark- kidney: Ask- Upmark- kidney is scarring parenchymal damage in childhood after acute pyelonephritis has taken place. These can cause chronic pyelonephritis, the so-called Ask- Upmark- kidney (Manski 2019).
• Xanthogranulomatous pyelonephritis (XPN): In XPN, a complete obstruction in the ureter or a partial obstruction in the area of the renal calices, e.g. due to nephrolithiasis or - much more rarely - due to a tumour, play an aetiological role. The bacterial colonization consists predominantly of germs such as E. coli, Proteus mirabilis, Klebsiellen and Staphylokokken(Manski 2019). An atypical virulence of the pathogens and / or an altered immunological defense situation are additionally important (Kuhlmann 2015).

Immunological and / or toxic influences: In some of the patients with CPN, both the urine and the renal tissue are bacteriologically negative. In such cases, immunological and toxic effects of killed parts of the pathogens, the so-called peptidoglycans (components of the cell wall), which maintain the inflammation, are suspected (Keller 2010).

Risk factors for CPN include:

• recurrent episodes of acute PN
• congenital or acquired vesicoureteral reflux
• neurogenic urinary bladder disorder such as paraplegia, longstanding diabetics, etc. (Kuhlmann 2015, Manski 2019)
• analgesic nephropathy
• Sickle Cell Disease (Kasper 2015).

Risk factors for XPN are(Suman 2020):

• diabetes mellitus
• arterial hypertension
• Dyslipidemia
• immunosuppression (congenital, acquired or drug-induced)
• post renal transplantation
• brachydactyly syndrome

CPN: In this case, the kidney is reduced in size by bumpy retractions, the renal pelvis and the calyx system are usually distorted by scarring.

In bilateral involvement with marked scarring, CPN can lead to chronic renal failure (Manski 2019).

XPN: The exact pathophysiological mechanism of XPN is currently unclear. Primarily, chronic obstruction results in an inflammatory response with destruction of renal and perirenal tissue and replacement of the same by granulomatous tissue (Suman 2020).

The renal pelvis is filled with pus (so-called pyonephrosis). In addition to tissue necrosis, there are also inflammatory yellow-orange foci with small abscesses. The inflammatory process is initially segmentally limited and may later spread diffusely to the entire kidney and the adjacent retroperitoneum or to adjacent structures (Manski 2019).

CPN: Apart from acute episodes, chronic PN is asymptomatic. Only in the further course do secondary symptoms develop, e.g. arterial hypertension, anaemia and / or uraemia (Manski 2019).

XPN:XPN progresses with symptoms such as:

• Fever (in about 70% [Manski 2019]) In this, a typical sawtooth pattern is seen. The fever can be mild to very high, with or without chills (Kasper 2015)
• Palpitating renal pelvis (so-called flank pain; occurs in about 70% [Manski 2019]; Herold 2020).

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

• persistent bacteriuria
• often weight loss
• general feeling of illness
• palpable tumor in the area of one flank (Manski 2019).

Anamnestic questions should be asked in particular (Kuhlmann 2015 / Manski 2019 / Kasper 2015):

• previous acute pyelonephritides
• nephrolithiasis
• vesicoureteral reflux
• diabetes mellitus
• arterial hypertension
• dyslipidemia
• analgesic nephropathy
• brachydactyly syndrome
• sickle cell disease
• Immunosuppression
• Z. n. kidney transplantation

Sonography: In CPN, the kidneys appear small on sonography, with focally thin, echogenic cortex (Manski 2019).

In XPN, a kidney can be visualized enlarged and shows an echogenic spatial structure indistinguishable from a (renal) tumor . Sometimes a nephrolithiasis may be presentable (Manski 2019). For further clarification, a CT scan is recommended. (Kuhlmann 2015)

i. v. pyelogram: The i. v. pyelogram (also called urogram) is now rarely used. CT or MRI have taken its place (Manski 2019).

CPN: In chronic PN, calyx deformities often exist in the i. v. pyelogram. These can show different degrees of severity. Plump calyxes are found with necks approaching each other. Often there is already a loss of parenchyma (Keller 2010). Especially at the renal poles, the cortex appears thin and the kidneys are small overall (Manski 2019).

XPN: In XPN, nephrolithiasis is found in the urogram in 40 % - 70 %.

Contrast of the affected side is absent in 30 % - 80 % of patients. The renal shadow appears predominantly enlarged (Manski 2019).

Contrast-enhanced CT (CPN): In CPN, changes found on CT include:

- Plumping of the renal calices

- Deformities of the renal calices

- Narrowing of the parenchyma (Herold 2020).

XPN: XPN shows a mass with inhomogeneous accumulation of contrast medium. Sometimes the presence of renal cell carcinoma cannot be excluded.

Lithiasis is detected much more frequently. The renal function itself is usually reduced in the affected kidney (Manski 2019).

Magnetic resonance imaging: MRI is superior to CT in:

- Questioning extrarenal spread.

- Evaluation of changes in the area of the renal pelvic caliceal system (Pallwein- Prettner 2011).

It can also be used as an alternative to CT- examination, especially in cases of contrast agent intolerance ((Pallwein- Prettner 2011)) and pre-existing renal insufficiency (Manski 2019). In this case, MRI offers an additional possibility of differentiation between inflammatory and neoplastic processes with the help of diffusion-weighted MR imaging (Pallwein- Prettner 2011).

Renal scintigraphy (also called isotope nephrogram = ING)

With this examination method, a side-separated function of the kidney tissue can be performed.

ING is the most sensitive method to detect scarring parenchymal destruction (Manski 2019).

• Urinalysis (Schmelz 2006):
  • Leukocyturia (in 57 % - 100 % [Schmelz 2006])
  • Haematuria (in XPN in 10 % - 33 % macrohaematuria and approx. 50 % microhaematuria [Schmelz 2006])
  • Proteinuria (typical in CPN is tubular proteinuria [Hofmann 2001]; in XPN proteinuria is found in 60 % - 80 % [Schmelz 2006];
  • Nitrite positive
  • Leukocyte cylinder (found in over 80% of patients with CPN [Herold 2018]).
  • Isosthenuria (inability to change urine concentrate [Keller 2010]).
  • Low specific gravity (most commonly found between 1.008 - 1.012)
  • Urine culture (in XPN positive in 63 % - 69 %)
• Blood test:
  • Creatinine elevated (in CPN)
  • Cystatin C elevated (in CPN) (Manski 2019).
  • ESR (elevated in 74 % on XPN)
  • Anemia (elevated in XPN 57 % - 63 %)
  • Leukocyturia (elevated in XPN 41 % - 57 %)
  • C- reactive protein elevated (Suman 2020)
  • Electrolytes (sodium loss)
  • Retention values increased such as.
    • Creatinine
    • Cystatin C (Manski 2019)
  • Renal clearance decreased
  • Liver values increased (in 25%-50% in XPN) (Schmelz 2006).

CPN: In chronic focal destructive pyelonephritis, there is wedge-shaped scarring leading to retraction of the renal surface. In addition, there are often deformities of the renal calices and occasionally necrosis of the papillae.

XPN (Manski 2019): In XPN, in addition to lymphocytes, plasma cells and neutrophils, the inflamed tissue also contains the typical large macrophages filled with foamy, lipid-containing cytoplasm, also called foam or xanthoma cells.

CPN:

• Uro- tuberculosis (Kuhlmann 2015)
• chronic recurrent cystitis (Hofstetter 2013)

XPN - xanthogranulomatous pyelonephritis (Suman 2020):

• Clear cell renal cell carcinoma
• Papillary renal cell carcinoma
• Sarcoid renal cell carcinoma
• Renal tuberculosis
• Angiomyolipoma of the kidney
• Megalocytic interstitial nephritis
• Renal abscesses

In chronic PN, CPN may occur during the course (Manski 2019):

• Anemia
• arterial hypertension (found in 30 % - 50 % of patients [Herold 2020])
• chronic renal failure (Keil 2008)
• subacute pyonephrosis
• abscessing acute pyelonephritis (Keller 2010)

XPN: The following complications may occur in XPN (Suman 2020).

• perinephritic abscess
• psoas abscess
• nephro-cutaneous fistula
• pyelo-duodenal fistula
• secondary amyloidosis
• nephrotic syndrome
• Sepsis

In XPN, a renal tumor may also be detectable in 10% of cases (Hegele 2015). An undifferentiated number of patients with XPN also suffer from urogenital tuberculosis (Kuhlmann 2015).

CPN:

In chronic PN, risk factors such as vesicoureteral reflux, analgesic nephropathy, neurogenic bladder dysfunction, etc. should be eliminated or treated as much as possible (Michel 2016).

Any new onset of urinary tract infection should be promptly treated with targeted antibiotics. In case of constant recurrences, a low-dose long-term antibiotic treatment may be necessary with e.g.

• nitrofurantoin 50 mg - 100 mg / d or
• cotrimoxazole 240 mg - 480 mg / d

The duration of treatment should be 3 - 6 months.

(Manski 2019)

For other options for the treatment of CPN, see "Surgical therapy".

(Manski 2019)

XPN:

Patients with segmental or focal involvement of the kidney can be treated initially with antibiotic treatment plus percutaneous drainage in individual cases. If this does not result in healing, a (partial) nephrectomy is required (see "Surgical therapy").

(Suman 2020)

CPN: If CPN is a unilateral involvement with absent renal function, nephrectomy may be appropriate for uncontrollable hypertension or to prevent further urinary tract infections and recurrent acute pyelonephritis (Manski 2019).

XPN: Patients with segmental or focal involvement of the kidney may be treated initially with antibiotic treatment plus percutaneous drainage. If this does not result in healing, (partial) nephrectomy is required (Suman 2020).

In cases of diffuse or advanced XPN, partial or complete nephrectomy is initially indicated. To avoid sepsis, these patients should receive antibiotics preoperatively and postoperatively (Suman 2020). For this purpose, swabs should be taken intraoperatively and the antibiosis adjusted if necessary after obtaining the antibiogram (Manski 2019).

The surgical procedure itself can be difficult with regard to existing adhesions. Laparoscopic surgery is therefore not recommended (Kuhlmann 2015), especially as it has been shown that the conversion rate from laparoscopic to open surgery is approximately 50% ((Suman 2020).

Cases of bilateral XPN also require nephrectomy followed by dialysis (Suman 2020).

CPN: In CPN, pyelonephritic scarring predisposes to the development of:

• arterial hypertension
• proteinuria
• focal glomerulosclerosis
• progressive renal insufficiency

Unilateral involvement or reflux alone without scarring does not cause progressive renal failure (Keller 2010).

Patients on a waiting list for kidney transplantation show infectious diseases as (co-)cause of terminal renal failure in up to 15 % - 25 % (Michel 2016).

Gravidity: Patients with bilateral scars and compensated retention are at risk of developing EPH-gestosis during pregnancy (Keller 2010).

XPN: The prognosis of unilateral XPN is good with appropriate therapy, whereas bilateral involvement is often lethal (Suman 2020).

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