bubble_chart Overview

Pyelonephritis refers to inflammation of the renal pelvis, mostly caused by bacterial infection, often accompanied by lower urinary tract inflammation, making it clinically difficult to strictly differentiate. Based on clinical course and disease progression, pyelonephritis can be divided into acute and chronic stages, with chronic pyelonephritis being a significant cause of chronic renal insufficiency.

bubble_chart Etiology

Acute pyelonephritis The lesions can be unilateral or bilateral, localized or extensive, and range from mild to severe. Mild cases only involve the renal pelvic mucosa. In severe cases, the kidney is enlarged, and the cut surface shows mucosal congestion, ulcers, and small abscess formation. If accompanied by obstruction, the renal calyces become dilated. In a few severe cases, necrosis of the renal papillae and pyramids can be observed, with necrotic tissue being excreted in the urine, known as necrotizing papillitis. Microscopically, renal interstitial edema and infiltration of neutrophils are visible.

Chronic pyelonephritis The renal pelvis and calyces exhibit chronic inflammatory changes. The renal pelvis is dilated and deformed, with scar formation in the renal cortex and papillae. The kidney is smaller than normal, and the lesions are often asymmetrical between the two sides. The renal medulla is deformed, and the mucosa of the renal pelvis and calyces, as well as the ureteral wall, becomes thickened. In severe cases, there is widespread atrophy of the renal parenchyma.

bubble_chart Clinical Manifestations

(1) Acute Pyelonephritis This disease can occur at any age, but is most common in women of childbearing age. The onset is sudden, with the following main symptoms.

1. General symptoms High fever, shivering, with body temperature mostly between 38–39°C, and may reach as high as 40°C. The fever pattern varies, generally being remittent, but it may also be intermittent or continuous. Accompanied by headache, general body aches, and profuse sweating when the fever subsides.

2. Urinary symptoms Patients experience lumbago, mostly dull or aching pain of varying intensity. A few may have colic radiating along the ureter toward the bladder. Physical examination reveals tenderness at the upper ureter point (the intersection of the lateral border of the rectus abdominis and the umbilical line) or the costovertebral angle (the intersection of the lateral border of the psoas major and the 12th rib). Kidney percussion pain is positive. Patients often have bladder irritation symptoms such as frequent urination, urgency, and dysuria. In upper urinary tract infections, these may precede systemic symptoms. In pediatric patients, urinary symptoms are often not obvious; at onset, aside from systemic symptoms like high fever, convulsions and spasms may occur.

3. Gastrointestinal symptoms May include loss of appetite, nausea, vomiting, and some patients may experience mid-upper or generalized abdominal pain.

(2) Chronic Pyelonephritis Symptoms are milder than in the acute phase, and sometimes may present as asymptomatic bacteriuria. Over half of the patients have a history of acute pyelonephritis, followed by symptoms such as lack of strength, low-grade fever, anorexia, and lumbago, accompanied by lower urinary tract irritation symptoms like frequent urination, urgency, and dysuria. Acute episodes may also occur intermittently. Previously, cases lasting over half a year or one year were considered chronic pyelonephritis. In recent years, it has been proposed that chronic pyelonephritis is diagnosed only when there is scar formation in the renal pelvis and calyces, with intravenous pyelography revealing deformities, hydronephrosis, irregular kidney contours, or unequal kidney sizes. Tubular function impairment may occur, such as reduced concentrating ability, hypoosmolar or low-specific-gravity urine, nocturia, and renal tubular acidosis. In the advanced stage, glomerular function impairment may develop, leading to azotemia and eventually uremia. Renal hypertension is often caused by chronic pyelonephritis, generally believed to be related to hyperreninemia, the release of vasoconstrictive peptides, and vascular sclerosis or stenosis. In a few patients, hypertension improves after removal of the affected kidney.

The clinical manifestations of chronic pyelonephritis are complex and prone to recurrence due to: (1) the presence of predisposing factors; (2) scarring and deformation of the renal pelvis, calyces, and renal papillae, which facilitate bacterial persistence; (3) bacterial resistance to medicinal properties or intracellular entry after prolonged antibiotic use, rendering antibiotics ineffective; (4) under humoral immunity or antibiotic pressure, bacterial cell membranes fail to form, existing as protoplasts that remain viable in the medullary osmotic environment. When conditions become favorable, they regenerate membranes and resume virulence—these are the protoplast-type strains (L-forms). Therefore, chronic pyelonephritis is considered a difficult-to-cure and progressively worsening disease.

bubble_chart Auxiliary Examination

During the acute phase, findings of acute inflammation may be present, such as elevated white blood cell count and an increased percentage of neutrophils. The following tests are of greater diagnostic significance.

(1) Urinalysis: This is the simplest and most reliable method for detecting urinary tract infections. It is advisable to collect the first morning urine for testing. The presence of more than 5 white blood cells per high-power field (>5 WBCs/HPF) is termed pyuria. Currently, leukocyte test strips (commonly referred to as urine dipsticks) are used. The mechanism involves the presence of esterase in leukocytes, which produces indophenol that reacts with diazonium salts on the test strip to yield a purple color. A positive reaction occurs when leukocytes exceed 10 cells/mL, but preservatives like formaldehyde can cause false-positive results. The test strip also employs the Griess nitrite reduction test, where enteric bacteria reduce urinary nitrates to nitrites, causing the strip to turn pink. Gram-positive bacteria and Pseudomonas are less sensitive to this test, and high doses of vitamin C may yield false-positive results. Patients should collect urine samples at least 10 hours after taking such medications. In acute urinary tract infections, in addition to pyuria, leukocyte casts, bacteriuria, and sometimes microscopic or gross hematuria may be observed, particularly in infections caused by Proteus, Nocardia, and Actinomyces (including Mycobacterium). Occasional trace proteinuria may be present, while significant proteinuria suggests glomerular involvement.

(2) Urine Cytology: Previously, a clean-catch midstream urine culture with a colony count exceeding 10^5/mL was considered clinically significant, while counts below 10^4/mL were attributed to contamination. However, extensive evidence now shows that about 92% of Gram-negative bacterial urinary tract infections have colony counts exceeding 10^5/mL, whereas only about 70% of Gram-positive bacterial infections exceed this threshold. Moreover, 20–30% of patients have colony counts as low as 10^3–10^5/mL, especially in most lower urinary tract infections. Reasons for low colony counts include: frequent and urgent urination, which shortens bladder dwell time and hinders bacterial growth; antibiotic therapy; rapid diuresis; highly acidic urine inhibiting bacterial proliferation; urinary tract obstruction; extra-luminal contamination; or infections by bacteria requiring special culture media (e.g., anaerobes). Gram-positive bacteria divide slowly and tend to clump, often resulting in underestimated colony counts. Therefore, even colony counts of 10^3–10^4/mL in symptomatic patients should be considered indicative of infection.

(3) Non-Invasive Localization Tests for Infection

1. Urine Concentration Capacity: Theoretically, acute and chronic pyelonephritis often impair renal tubular concentrating ability, possibly due to prostaglandins produced by damaged medullary tissue. This phenomenon can be blocked by prostaglandin synthesis inhibitors (e.g., indomethacin), and tubular concentrating function may recover after infection clearance. Bilateral infections are more likely to reveal impaired urine concentration than unilateral infections, but this test lacks sensitivity and is not recommended for routine use.

2. Urinary Enzyme Measurement: Reports indicate that about 25% of pyelonephritis patients exhibit higher urinary lactate dehydrogenase (LDH) levels than those with lower urinary tract infections. Urinary N-acetyl-β-D-glucosaminidase levels are also elevated in pyelonephritis, as this enzyme is present in renal tubular epithelial cells. However, urinary enzymes for localizing urinary tract infections remain under investigation.

3. Urinary C-Reactive Protein (CRP) Measurement: Literature suggests that serum CRP levels are significantly elevated in upper urinary tract infections involving the renal parenchyma. Serial CRP measurements every other day during treatment can help assess efficacy—declining CRP indicates effectiveness, while rising levels suggest treatment failure. CRP does not elevate in acute cystitis. However, CRP may also rise in other infectious diseases, and false positives limit its utility for localization.

4. Urinary Antibody-Coated Bacteria Analysis Immunofluorescence analysis confirms that bacteria originating from the kidneys are coated with antibodies, which can bind to fluorescently labeled anti-IgG antibodies, resulting in a positive reaction. Bacteria from the bladder are not coated with specific antibodies. Therefore, in recent years, the analysis of urinary antibody-coated bacteria (ACB) has been widely used for the localization diagnosis of upper and lower urinary tract infections, with an accuracy of approximately 83%. However, false positives may occur in cases of certain prostatitis, cystitis, or significant proteinuria.

Additionally, the measurement of urinary β2-microglobulin can also help differentiate between upper and lower urinary tract infections. Upper urinary tract infections are more likely to affect the reabsorption of molecular proteins by the renal tubules, leading to elevated urinary β2-microglobulin levels, whereas lower urinary tract infections do not result in such an increase.

5. Direct Localization Methods Among the direct methods, Stamey's ureteral catheterization is relatively accurate but involves invasive procedures such as cystoscopy or percutaneous renal pelvis puncture using a Skinny needle to collect urine, making it less commonly used. Fairley's bladder irrigation sterilization urine culture method, with an accuracy rate exceeding 90%, is simpler and more practical, thus widely adopted in clinical practice. The specific procedure involves injecting 40 ml of 0.2% neomycin solution into the bladder via a catheter to sterilize it, followed by saline irrigation. Urine flowing into the bladder is then collected for culture, with samples taken every 10 minutes for a total of three times. In cases of cystitis, bacterial cultures should yield negative results after sterilization, whereas in pyelonephritis, the results remain positive, with bacterial counts progressively increasing.

(IV) X-ray Examination Since acute urinary tract infections themselves can easily induce vesicoureteral reflux, intravenous or retrograde pyelography should be performed 4–8 weeks after the infection has resolved. Acute pyelonephritis and uncomplicated recurrent urinary tract infections do not typically require routine pyelography. For chronic or refractory cases, plain radiography of the urinary tract, intravenous pyelography, retrograde pyelography, or voiding cystourethrography may be performed as needed to check for obstructions, stones, ureteral strictures or compression, nephroptosis, congenital urinary tract abnormalities, or vesicoureteral reflux. Additionally, these methods can assess the structure and function of the renal pelvis and calyces, aiding in differentiation from conditions such as renal subcutaneous nodules or renal tumors. Chronic pyelonephritis may present with grade I dilation or clubbing of the renal pelvis, along with scar-related deformities. In cases of renal insufficiency, a double or triple dose of iodinated contrast agent may be required for rapid intravenous infusion, with multiple imaging sessions to achieve satisfactory results. Renal angiography may reveal varying degrees of vascular distortion in chronic pyelonephritis. If necessary, renal CT or MRI scans can be performed to rule out other renal diseases.

(V) Radionuclide Renal Imaging This test provides insights into split renal function, urinary tract obstruction, vesicoureteral reflux, and residual bladder urine volume. The characteristic findings of acute pyelonephritis on renal imaging include a delayed peak, with the secretory phase appearing 0.5–1.0 minutes later than normal and a slow decline in the excretory phase. Chronic pyelonephritis shows a reduced slope in the secretory phase, a blunted or widened and delayed peak, and a delayed onset of the excretory phase, presenting a parabolic curve. However, these changes are not highly specific.

(VI) Ultrasonography Currently the most widely used and simplest method, ultrasonography can screen for urinary tract hypoplasia, congenital malformations, polycystic kidneys, uneven kidney size due to renal artery stenosis, stones, hydronephrosis, tumors, and prostate diseases.

bubble_chart Diagnosis

1. Medical History A history of acute pyelonephritis can serve as a reference for diagnosis but cannot be the sole basis. Most patients with non-obstructive chronic pyelonephritis may have no prior history of urinary tract infections or other kidney diseases. The onset is often insidious, and symptoms of azotemia may be the first presenting symptoms, which should be noted during diagnosis.

2. Clinical Manifestations There may be intermittent urinary tract irritation symptoms, which are generally mild and less pronounced than in acute pyelonephritis. These are often accompanied by lack of strength, loss of appetite, and dull lower back pain, with possible low-grade fever or no fever. In the advanced stage, symptoms of uremia such as dizziness, headache, nausea, and vomiting may occur due to impaired renal function. Other manifestations may include polyuria, increased nocturia, hypokalemia, hyponatremia, or chronic renal tubular acidosis. Some patients may have an insidious or atypical disease course, which should be noted.

3. Auxiliary Examinations

(1) Urinalysis: Urinary protein is usually trace or minimal. If urinary protein exceeds 3.0 g/24 hours, it suggests an alternative diagnosis. The urine sediment may show a small number of red and white blood cells. The presence of white blood cell casts aids in diagnosis but is not specific to this condition.

(2) Urine Culture: Similar to acute pyelonephritis, but the positive rate is lower. Repeated testing may sometimes be required to obtain a positive result. Among patients with negative urine bacterial cultures, about 20% may show protoplast-type strains. These are pathogenic bacteria that, under the influence of antibiotics or antibodies, develop a survival mechanism by adapting to adverse conditions. Although the cell membrane ruptures, the protoplasm remains intact and can resume proliferation once conditions become favorable. A positive urine culture after bladder sterilization or a positive urine antibody-coated bacteria test supports the diagnosis of this condition and helps differentiate it from cystitis.

(3) Renal Function Tests: Typically, there is reduced tubular function (e.g., impaired urine concentration, decreased phenol red excretion rate), increased urinary sodium and potassium excretion, and metabolic acidosis. In cases of oliguria, serum potassium may rise. In the advanced stage, glomerular dysfunction may develop, with elevated blood urea nitrogen and creatinine levels, leading to uremia.

(4) X-ray Imaging: Deformities of the renal pelvis and calyces may be observed, with irregular or even reduced shadows.

bubble_chart Treatment Measures

(1) General Treatment

The aim is to alleviate symptoms, prevent recurrence, and reduce damage to kidney excess. Patients should be encouraged to drink plenty of fluids and urinate frequently to lower medullary osmotic pressure, enhance the function of phagocytic cells, and flush out cells in the bladder.

For systemic infection symptoms such as fever, bed rest is recommended. Taking 1g of sodium bicarbonate three times a day can alkalize the urine, alleviate bladder irritation symptoms, and enhance the efficacy of aminoglycoside antibiotics, penicillin, erythromycin, and sulfonamides, but it may reduce the effectiveness of tetracycline and nitrofurantoin. Underlying factors such as kidney stones or ureteral abnormalities should be treated. Anti-infective therapy is best conducted based on urine bacterial culture and drug sensitivity tests.

(2) Anti-infective Therapy

1. Acute Pyelonephritis: The primary bacteria causing urinary tract infections are Gram-negative, with large intestine bacilli being the most common. For initial acute pyelonephritis, compound sulfamethoxazole (SMZ-TMP) 2 tablets twice daily, pipemidic acid 0.5g 3–4 times daily, or norfloxacin 0.2g three times daily for 7–14 days may be used. Severe infections with sepsis require intravenous administration. Sensitive drugs should be selected based on urine culture results. For example, cefoperazone and amikacin have sensitivity rates exceeding 90% against Staphylococcus, Klebsiella, Proteus, Pseudomonas aeruginosa, and large intestine bacilli. The former is administered 1–2g every 8–12 hours, while the latter is given 0.4g every 8–12 hours. Fluoroquinolones have sensitivity rates above 80% against Proteus, Citrobacter, and Klebsiella. Piperacillin, ampicillin, and nitrofurantoin are 100% effective against Group D enterococci. The first two are given 1–2g every 6 hours, and the latter 0.1g three times daily. For fungal infections, ketoconazole 0.2g three times daily or fluconazole 50mg twice daily may be used.

In newborns, infants, and children under 5 years old, acute pyelonephritis is often associated with urinary tract abnormalities and dysfunction, making it difficult to eradicate. However, some dysfunctions, such as vesicoureteral reflux, may resolve with age. Single or multiple urinary infections can lead to focal scarring in kidney tissue, even affecting kidney development. Recent guidelines recommend performing midstream urine cell culture before treatment and rechecking urine cultures at weeks 2, 4, and 6 after discontinuation to detect and manage issues promptly.

2. Chronic Pyelonephritis: Acute episodes should be treated as acute pyelonephritis. For recurrent cases, urine bacterial culture should identify the strain to determine whether the recurrence is a relapse or a new infection.

Relapse: Refers to the recurrence of the same pathogen within 6 weeks after treatment, despite initial negative results. Common causes include: (1) Anatomical or functional abnormalities in the urinary tract causing poor urine flow. Intravenous pyelography or retrograde pyelography can confirm this. If significant anatomical abnormalities exist, surgical correction may be needed. If obstruction cannot be resolved, a 6-week course of appropriate antibiotics based on sensitivity tests is recommended. (2) Inappropriate antibiotic selection or insufficient dose and duration often lead to relapse. A 4-week course of drugs selected by sensitivity testing is advised. (3) Due to scar formation in the affected area, poor blood flow, and insufficient antibiotic concentration, high-dose bactericidal antibiotics such as cephalosporins, ampicillin, carbenicillin, or tobramycin may be tried for 6 weeks.

If urinary tract infections recur three or more times within a year, it is referred to as recurrent urinary tract infection, and long-term low-dose therapy may be considered. Generally, low-toxicity antibacterial drugs are selected, such as compound sulfamethoxazole or nitrofurantoin, one tablet nightly for one year or longer. Approximately 60% of patients achieve negative bacteriuria. For males with recurrence due to prostatitis, concurrent treatment of chronic prostatitis is advisable, using fat-soluble antibacterial drugs such as compound sulfamethoxazole; ciprofloxacin 0.5g twice daily; or rifampin 0.45–0.6g administered at draught. The treatment course should last up to three months. If necessary, surgical removal of pathological (hyperplastic or neoplastic) prostate tissue may be performed.

If the urine culture remains positive after two full courses of antibacterial therapy, long-term low-dose treatment may be considered. Generally, a compound formula of co-trimoxazole or nitrofurantoin is taken once nightly for one year or longer, with approximately 60% of patients achieving negative bacterial conversion.

Reinfection: Refers to an infection caused by a different pathogen invading the urinary tract after the initial bacteriuria has cleared, typically recurring six weeks after the urine culture turns negative. Among women with recurrent urinary tract infections, 85% are due to new contraction infections and can be treated using the same approach as for the initial episode, while emphasizing the importance of prevention. Additionally, a comprehensive examination should be conducted to identify and eliminate any predisposing factors.

bubble_chart Prevention

For patients with chronic pyelonephritis, it is essential to enhance their physical constitution and improve the body's defense capabilities. Eliminate various predisposing factors such as diabetes, kidney stones, and urinary tract obstruction.