| disease | Pyelonephritis |
| alias | Pyelonephritis |
Pyelonephritis refers to inflammation of the renal pelvis, mostly caused by bacterial infections, often accompanied by lower urinary tract inflammation, and is clinically difficult to strictly distinguish. 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 Pathological Changes
Acute Pyelonephritis: The lesions can be unilateral or bilateral, localized or extensive, and can range from mild to severe. In mild cases, only the renal pelvis mucosa is affected. 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 are widened. In a few severe cases, necrosis of the renal papillae and pyramids can be seen, and the necrotic tissue is excreted with urine, known as necrotizing papillitis. Microscopically, renal interstitial edema and neutrophil infiltration are visible.
Chronic Pyelonephritis: The renal pelvis and calyces show chronic inflammatory changes. The renal pelvis is enlarged and deformed, with scar formation in the renal cortex and papillae. The kidney is smaller than normal, and the lesions on both sides are often asymmetrical. The renal medulla is deformed, and the mucosa of the renal pelvis and calyces, as well as the ureteral wall, are 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, body temperature mostly between 38～39℃, can also reach up to 40℃. The fever pattern varies, generally remittent, but can also be intermittent or continuous. Accompanied by headache, general soreness, and profuse sweating when the fever subsides.2. Urinary symptoms Patients have lumbago, mostly dull or sore pain, varying in intensity, a few may have abdominal cramps radiating along the ureter towards the bladder. Tenderness is present at the upper ureter point (intersection of the lateral border of the rectus abdominis and the umbilical line) or the costovertebral angle (intersection of the lateral border of the psoas major and the twelfth rib), and kidney percussion pain is positive. Patients often have bladder irritation symptoms such as frequent urination, urgency, and dysuria, which may precede systemic symptoms in upper urinary tract infections. In pediatric patients, urinary symptoms are often not obvious, and besides high fever and other systemic symptoms, convulsions and spasms may occur at onset.
3. Gastrointestinal symptoms May include loss of appetite, nausea, vomiting, and some patients may have pain in the upper or entire abdomen.
(2) Chronic Pyelonephritis Symptoms are milder than in the acute phase, sometimes presenting as asymptomatic bacteriuria. More than 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. Previously, a course of more than half a year or one year was considered chronic pyelonephritis, but recently it has been suggested that only those with scar formation in the renal pelvis and calyces, deformation, hydronephrosis, irregular kidney contour, or unequal kidney size on intravenous pyelography are considered chronic pyelonephritis. There may be renal tubular function damage, such as decreased concentration ability, hypoosmotic and low specific gravity urine, increased nocturia, and renal tubular acidosis. In the advanced stage, glomerular function damage, azotemia, and even uremia may occur. Renal hypertension is often caused by chronic pyelonephritis, generally believed to be related to high renin levels, release of vasoconstrictive peptides, and vascular sclerosis and stenosis. In a few patients, hypertension improves after removal of the diseased kidney.
bubble_chart Auxiliary Examination
During the acute phase, signs of acute inflammation may be observed, such as an increase in white blood cell count and a higher percentage of neutrophils. The following tests are of significant importance for diagnosis.
(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/Hp) is termed pyuria. Currently, the leukocyte test strip method, commonly referred to as urine dipstick, is used. The mechanism is based on the presence of esterase in white blood cells, which produces indophenol that reacts with diazonium salt in the test strip to produce a purple color. A positive reaction is observed when white blood cells exceed 10/ml, but preservatives like formaldehyde can cause false positives. The Griess nitrate reduction test is used in the strips, where intestinal bacteria reduce nitrate in urine to nitrite, causing the strip to change color (pink). Gram-positive bacteria and Pseudomonas are not sensitive to this test, and high doses of vitamin C can cause false positives. Patients should collect urine samples at least 10 hours after taking such medication. In acute urinary tract infections, besides pyuria, white blood cell casts, bacteriuria, and sometimes microscopic or gross hematuria may be found, especially in infections caused by Proteus, Nocardia, and Actinomyces (including Mycobacterium). Occasional trace proteinuria may be seen, and significant proteinuria suggests glomerular involvement.
(3) Non-invasive infection localization tests
1. Urine concentration ability: Theoretically, acute and chronic pyelonephritis often accompany impaired renal tubular concentration function, possibly related to prostaglandins produced by damaged medulla. Using prostaglandin synthesis inhibitors (indomethacin) can block this phenomenon. After infection clearance, renal tubular concentration function can recover. Bilateral infections are more likely to show impaired urine concentration ability than unilateral infections, but this test is not sensitive enough to be routinely recommended.
2. Urinary enzyme measurement: It has been reported that about 25% of patients with pyelonephritis have higher urinary lactate dehydrogenase (LDH) levels than those with lower urinary tract infections. In pyelonephritis, urinary N-acetyl-β-D-glucosaminidase levels are higher than in lower urinary tract infections, as this enzyme is present in renal tubular epithelial cells. To date, urinary enzymes that can serve as localization diagnostic tools for urinary tract infections are still under study.
3. Urine C-reactive Protein Measurement Literature reports that serum C-reactive protein significantly increases during upper urinary tract infections affecting kidney excess substances. Monitoring the C-reactive protein (CRP) levels every other day during the course of the disease helps estimate the efficacy of treatment, i.e., a decrease in CRP indicates effectiveness, while an increase indicates ineffectiveness. CRP does not rise in acute bladder infections. However, CRP may also increase in other infectious diseases, and the presence of false positives affects the diagnostic significance of this test.
4. Urine Antibody-Coated Bacteria Analysis: Immunofluorescence analysis confirms that bacteria from the kidneys are coated with antibodies, which can bind to fluorescently labeled IgG antibodies, showing a positive reaction. Bacteria from the bladder are not coated with specific antibodies, so in recent years, urine antibody-coated bacteria (ACB) analysis has been more widely used for the localization diagnosis of upper and lower urinary tract infections. Its accuracy is about 83%. However, some cases of prostatitis, bladder inflammation, and massive proteinuria may show false positives.
Additionally, the measurement of urine β2 microglobulin also helps to 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 an increase in urine β2 microglobulin, whereas lower urinary tract infections do not result in an increase in urine β2 microglobulin.
5. Direct Localization Method: Among direct methods, Stamey's ureteral catheterization method has higher accuracy, but it requires cystoscopy or percutaneous renal pelvis puncture with a Skinny needle to collect urine, making it an invasive method and not commonly used. Fairley's bladder irrigation sterilization followed by urine culture method has an accuracy of over 90% and is simple and practical, commonly used in clinical settings. The specific method involves injecting 40ml of 0.2% neomycin solution through a catheter to sterilize the bladder, then rinsing with saline, and collecting the urine flowing into the bladder for culture, taking urine samples every 10 minutes, three times in a row. If it is bladder inflammation, the bacterial culture should be negative after sterilization; if it is pyelonephritis, it will still be positive, and the colony count will increase successively.
(IV) X-ray Examination: Since acute urinary tract infections themselves are prone to cause vesicoureteral reflux, intravenous or retrograde pyelography should be performed 4 to 8 weeks after the infection has been eliminated. Acute pyelonephritis and uncomplicated recurrent urinary tract infections do not advocate for routine pyelography. For chronic or refractory patients, as needed, plain radiographs of the urinary tract, intravenous pyelography, retrograde pyelography, and voiding cystourethrography can be performed to check for obstructions, stones, ureteral strictures or compression, nephroptosis, congenital anomalies of the urinary system, and vesicoureteral reflux. Additionally, it can help understand the formation and function of the renal pelvis and calyces, and differentiate from renal subcutaneous nodes, renal tumors, etc. Chronic pyelonephritis shows grade I dilation or clubbing of the renal pelvis, and may have scar deformities. In cases of renal insufficiency, double or triple the usual dose of iodine contrast agent is required for rapid intravenous infusion, and multiple films are needed to achieve satisfactory imaging results. Renal angiography can show varying degrees of twisting of the small blood vessels in chronic pyelonephritis. If necessary, renal CT or MRI scans can be performed to rule out other kidney diseases.
(V) Isotope Renography: This can provide information on split renal function, urinary tract obstruction, vesicoureteral reflux, and residual urine in the bladder. The renogram characteristics of acute pyelonephritis include a delayed peak, with the secretory phase appearing 0.5 to 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 start of the excretory phase, presenting as a search curve. However, these changes are not highly specific.
(VI) Ultrasound Examination: This is currently the most widely used and simplest method, capable of screening for urinary tract dysplasia, congenital anomalies, polycystic kidneys, uneven kidney size due to renal artery stenosis, stones, hydronephrosis, tumors, and prostate diseases.
1. Medical History A history of acute pyelonephritis can serve as a reference for diagnosis but cannot be used as a definitive basis. This is because many patients with non-obstructive chronic pyelonephritis may not have a history of urinary tract infections or other kidney diseases. The onset is often insidious, and symptoms of azotemia may be the first signs noticed by the patient, which should be taken into consideration during diagnosis.
2. Clinical Manifestations There may be intermittent urinary tract irritation symptoms, which are generally mild and not as pronounced as in acute pyelonephritis. These are often accompanied by lack of strength, loss of appetite, and lower back pain, and may include low-grade fever or no fever. In the advanced stage, symptoms of uremia such as dizziness, headache, nausea, and vomiting may occur due to renal function impairment. Other symptoms may include polyuria, increased nocturia, hypokalemia, hyponatremia, or chronic renal tubular acidosis. Some patients may have insidious or atypical symptoms, which should be noted.
3. Auxiliary Examinations
⑴ Urinalysis: Urine protein is usually trace or small in amount. If urine protein exceeds 3.0/24 hours, it may suggest a condition other than this disease. The urine sediment may contain a small number of red and white blood cells. The presence of white blood cell casts can aid in diagnosis but is not specific to this disease.
⑵ Urine Culture: Similar to acute pyelonephritis, but the positive rate is lower, and sometimes repeated tests are necessary to obtain a positive result. About 20% of patients with negative urine bacterial cultures may have protoplast strains, which are a variant form of pathogenic bacteria that survive adverse conditions such as antibiotics and antibodies. Although the cell membrane is ruptured, the protoplasm remains and can proliferate again once the environment becomes favorable. Positive results from bladder-sterilized urine culture and urine antibody-coated bacteria tests can aid in the diagnosis of this disease and help differentiate it from cystitis.
⑶ Renal Function Tests: There is usually a decrease in renal tubular function (reduced urine concentration ability, decreased phenol red excretion rate, etc.), and there may be increased excretion of sodium and potassium in the urine, as well as metabolic acidosis. Blood potassium may increase when urine output is low. In the advanced stage, glomerular dysfunction, increased blood urea nitrogen and creatinine levels occur, leading to uremia.
⑷ X-ray Imaging: Deformation of the renal pelvis and calyces can be seen, with irregular or even reduced shadows. {|106|}
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 more water and urinate frequently to lower medullary osmotic pressure, enhance the function of phagocytic cells, and flush out cells in the bladder.
Patients are generally encouraged to drink more water and urinate frequently to lower medullary osmotic pressure and enhance the function of phagocytic cells. Those with systemic infection symptoms such as fever should rest in bed. Taking 1g of sodium bicarbonate three times a day can alkalize urine, reduce bladder irritation symptoms, and enhance the efficacy of aminoglycoside antibiotics, penicillin, erythromycin, and sulfonamides, but may reduce the efficacy of tetracycline and nitrofurantoin. Underlying factors such as kidney stones and ureteral abnormalities should be treated. Anti-infective treatment is best conducted under urine bacterial culture and drug sensitivity testing.
(2) Anti-infective Treatment
1. Acute Pyelonephritis: The main bacteria causing urinary tract infections are Gram-negative bacteria, predominantly large intestine bacilli. For initial acute pyelonephritis, compound sulfamethoxazole (SMZ-TMP) 2 tablets twice daily, or pipemidic acid 0.5g three to four times daily, or norfloxacin 0.2g three times daily for 7-14 days can be chosen. Severe infections with sepsis should be treated with intravenous medication. Sensitive drugs should be selected based on urine culture results. For example, cefoperazone and amikacin have a sensitivity rate of over 90% against Staphylococcus, Klebsiella, Proteus, Pseudomonas aeruginosa, and large intestine bacilli. The former is administered 1-2g every 8-12 hours, and the latter 0.4g every 8-12 hours. Fluoroquinolones have a sensitivity rate of over 80% against Proteus, Citrobacter, and Klebsiella. Piperacillin, ampicillin, and nitrofurantoin are 100% sensitive against Group D enterococci. The first two are administered 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 can be used.
Acute pyelonephritis in newborns, infants, and children under 5 years old is often accompanied by urinary tract abnormalities and dysfunction, making it difficult to eradicate. However, some dysfunctions such as vesicoureteral reflux may disappear with age. Single or multiple urinary infections can form focal scars in kidney tissue, even affecting kidney development. Recently, it is recommended to perform midstream urine cell culture before medication, and repeat urine culture at the 2nd, 4th, and 6th weeks after stopping medication to detect and manage promptly.
2. Chronic Pyelonephritis: Acute episodes should be treated as acute pyelonephritis. For recurrent episodes, urine bacterial culture should be performed to determine the bacterial type and clarify whether the recurrence is a relapse or a new infection.
Relapse: Refers to the recurrence of the same pathogen within 6 weeks after treatment and negative culture. Common causes of relapse include ① anatomical or functional abnormalities in the urinary tract causing poor urine flow, which can be identified through intravenous pyelography or retrograde pyelography. If significant anatomical abnormalities exist, surgical correction is needed. If obstructive factors are difficult to remove, appropriate antibiotics should be selected based on drug sensitivity for 6 weeks. ② Inappropriate antibiotic selection or insufficient dose and duration often lead to relapse. Antibiotics should be selected based on drug sensitivity for 4 weeks. ③ Due to scar formation in the lesion area, poor blood flow, and insufficient antibiotic concentration in the lesion, larger doses of bactericidal antibiotics such as cephalosporins, ampicillin, carbenicillin, and gentamicin can be tried for 6 weeks.
If urinary tract infections occur three or more times within a year, it is referred to as recurrent urinary tract infection, and long-term low-dose treatment may be considered. Generally, low-toxicity antibacterial drugs are selected, such as compound formula sulfamethoxazole or nitrofurantoin, one tablet every night, taken for one year or longer, with approximately 60% of patients achieving negative bacteriuria. For males with recurrence caused by prostatitis, chronic prostatitis should be treated simultaneously, and fat-soluble antibacterial drugs such as compound formula sulfamethoxazole should be chosen; ciprofloxacin 0.5g, twice daily; rifampin 0.45～0.6g, administered at draught, with a treatment course lasting up to 3 months. If necessary, surgical removal of the diseased (hyperplastic, tumorous) prostate may be performed.
If the urine culture remains positive after two full courses of antibacterial treatment, long-term low-dose therapy may be considered. Generally, a compound formula of co-trimoxazole or nitrofurantoin is taken once every night, which can be continued for 1 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 urine culture has turned negative, usually occurring more than 6 weeks after the urine culture turns negative. In women, 85% of recurrent urinary tract infections are due to new infections, and they can be treated using the same methods as the initial episode, with emphasis on the importance of prevention. A comprehensive examination should also be conducted to identify and eliminate any predisposing factors.
For patients with chronic pyelonephritis, it is essential to strengthen their constitution and enhance the body's defense capabilities. Eliminate various predisposing factors such as diabetes, kidney stones, and urinary tract obstructions. Actively search for and remove inflammatory foci, including sexually transmitted diseases, such as prostatitis in men, and paraurethral gland inflammation, vaginitis, and cervicitis in women. Minimize unnecessary catheterization and urinary tract instrumentation. If catheter retention is necessary, prophylactic use of antibacterial drugs should be considered. Women who have had destructive sexual activity should urinate immediately after intercourse and take a dose of SMZ-TMP orally. Pay extra attention to vulvar hygiene during pregnancy and menstruation. Postmenopausal women should take Nilestriol 1-2mg, once or twice a month, to enhance local resistance.
Acute pyelonephritis generally presents with typical symptoms and abnormal urine findings, making diagnosis straightforward. For cases with only high fever and inconspicuous urinary symptoms, differentiation from various fever-related diseases is necessary. For those with significant abdominal pain and lumbago, differentiation from cholecystitis, appendicitis, pelvic inflammation, and perinephric abscess is required. Generally, a definitive diagnosis can be made after multiple urine tests. Chronic pyelonephritis often lacks obvious urinary symptoms, and routine urine tests may show no significant changes or intermittent abnormalities, leading to misdiagnosis. In women, the possibility of this disease should be considered in cases of unexplained fever, backache, lack of strength, and grade I urinary symptoms. Repeated urine routine and culture tests are necessary to find evidence. Chronic pyelonephritis accompanied by hypertension needs to be differentiated from hypertension. Additionally, differentiation from the following diseases is required.
(1) Renal subcutaneous node: Urogenital subcutaneous nodes often occur simultaneously and are the most common extrapulmonary subcutaneous nodes, usually caused by hematogenous infection. Acute phase symptoms include fever (low-grade), night sweating, lack of strength, lumbago, frequent urination, urgency, dysuria, and hematuria. About 20% of cases may be asymptomatic, known as silent urinary tract infection. After several years, the renal parenchyma is destroyed, and the granulomas and caseous changes of the subcutaneous nodes first affect the medulla and papillary region, followed by papillary necrosis, deformation of the renal pelvis and calyces, thinning of the cortex, and occasionally involvement of perirenal tissues. In the late stage [third stage], renal function is impaired, and bladder contracture occurs. Chest X-ray, prostate, epididymis, and pelvic subcutaneous node detection aid in diagnosis. Urine tests show hematuria (microscopic or gross), pyuria, positive skin test (PPD), and high detection rate of urine subcutaneous node culture (over 90%). Intravenous pyelography can only detect more advanced cases. Recently, polymerase chain reaction (PCR) for detecting Mycobacterium tuberculosis DNA in urine has been widely used in diagnosis, with specificity and positive rates as high as 95%.
(2) Chronic glomerulonephritis: Differentiation is straightforward if there is edema and significant proteinuria. The proteinuria in pyelonephritis is generally below 1-2g/d; if it exceeds 3g, it is more likely to be glomerular disease. However, differentiation from latent nephritis is difficult, as the latter shows more red blood cells in routine urine tests, while pyelonephritis is dominated by white blood cells. Additionally, urine culture and long-term observation for symptoms like low fever and frequent urination aid in differentiation. Advanced nephritis with secondary urinary tract infection is difficult to differentiate; detailed history and clinical features should be analyzed.
(3) Prostatitis: Men over 50 years old are prone to this disease due to prostatic hyperplasia, hypertrophy, urethral catheterization, and cystoscopy. Acute prostatitis, besides chills and fever, elevated white blood cell count, causes lumbosacral and perineal pain, restlessness, frequent urination, dysuria, and pyuria in urine tests, easily confused with acute cystitis. Chronic prostatitis often lacks obvious clinical symptoms besides abnormal urine tests. Prostatic massage fluid examination showing white blood cells >10/HP and B-ultrasound aid in differential diagnosis.
