Acute pyelonephritis refers to an acute bacterial inflammation of the renal pelvis and renal parenchyma. The primary pathogens include Escherichia coli and other Enterobacteriaceae, as well as Gram-positive bacteria such as Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis, and Staphylococcus species. In rare cases, fungi and viruses may also serve as causative agents. The microorganisms typically ascend from the urethra to the bladder and then travel via the ureters to the kidney, though hematogenous dissemination to the kidney may also occur. The incidence of this condition is higher in females than in males, particularly during childhood, the honeymoon phase, pregnancy, and old age. Secondary pyelonephritis may occur in association with urinary tract obstruction, vesicoureteral reflux, or urinary retention.
Pathology
Acute pyelonephritis often leads to renal enlargement and edema, with the kidney becoming relatively soft. The renal surface may exhibit scattered abscesses of varying sizes, appearing yellow or yellow-white with surrounding purplish-red congestive halos. The cross-section of the kidney reveals irregularly distributed small purulent foci in various parts of the renal parenchyma. The mucosa of the renal pelvis appears edematous and congested, with scattered petechial hemorrhages. Microscopically, there is marked infiltration of neutrophils accompanied by hemorrhage. Early in the disease, the glomeruli are typically unaffected, but severe cases may show damage to the renal tubules and glomeruli. Purulent lesions that heal may form small fibrotic scars, which do not impair renal function after resolution. However, extensive and severe lesions can result in the loss of function in some renal units. Failure to eradicate the pathogens or resolve the underlying causes of infection may lead to chronic pyelonephritis through persistent or recurrent disease progression.
Clinical Manifestations
Fever
Patients may experience sudden onset of chills, high fever with temperatures exceeding 39°C, headaches, generalized body pain, nausea, and vomiting. The fever pattern resembles that of sepsis, with sweating followed by temperature normalization before subsequent rises, and it often persists for about one week.
Flank Pain
Unilateral or bilateral flank pain may occur, often accompanied by significant renal pressure tenderness and costovertebral angle tenderness.
Bladder Irritative Symptoms
Symptoms of bladder irritation include urinary frequency, urgency, and dysuria. In cases of ascending infection, onset typically begins with bladder irritative symptoms and/or hematuria, followed by systemic manifestations. Hematogenous infections often present with high fever as the initial symptom, with bladder irritation occurring later and sometimes being less pronounced.
Diagnosis
Diagnosis relies on typical clinical features and laboratory findings, including the presence of white blood cells, red blood cells, proteins, casts, and bacteria in the urine. A bacterial colony count exceeding 105/ml in urine culture and an elevated white blood cell count predominantly consisting of neutrophils are supportive findings. Symptoms in older adults may be atypical.
Acute pyelonephritis frequently coexists with cystitis, which may also present with fever and lower back pain. Distinguishing between these conditions can be challenging since lower urinary tract infections can ascend to affect the kidneys. However, lower urinary tract infections are primarily characterized by bladder irritative symptoms, including lower abdominal discomfort or distension, while systemic signs such as chills and fever are usually absent. Further evaluation for predisposing factors, including urinary tract obstruction, diabetes, and vesicoureteral reflux, is suggested after acute symptoms are controlled for effective long-term management.
Treatment
General Management
Management includes bed rest, fluid infusion, antipyretic measures, and increased water intake to maintain a daily urine output of at least 1.5 liters, which facilitates the excretion of inflammatory products. The diet should comprise easily digestible foods rich in calories and vitamins. Broad-spectrum antibiotic therapy is typically initiated before pathogen culture and antibiotic susceptibility testing results are available. The list of potential antibiotics includes:
Quinolones
These drugs offer broad-spectrum activity, high efficacy, and low toxicity. They are widely used but are not appropriate for children or pregnant women.
Penicillins
First- and Second-Generation Cephalosporins
These are effective against enzyme-producing staphylococcal infections. Second- and third-generation cephalosporins are highly efficacious for severe Gram-negative bacterial infections. Their combination with aminoglycosides may yield synergistic effects. Agents such as piperacillin, cefoperazone, ceftazidime, amikacin, and tobramycin are useful against Pseudomonas aeruginosa and other pseudomonal infections.
Norvancomycin
This is suitable for methicillin-resistant staphylococcal infections, multidrug-resistant enterococcal infections, or Gram-positive cocci infections in patients allergic to penicillin.
Trimethoprim-Sulfamethoxazole
This combination is effective against Gram-positive and Gram-negative bacteria except Pseudomonas aeruginosa.
Imipenem-Cilastatin
This combination has a broad spectrum of activity and is bactericidal for Gram-negative bacilli, making it particularly beneficial for refractory nosocomial infections and pyelonephritis in immunocompromised patients.
Treatment regimens should be individualized, with a typical duration of 7–14 days. Intravenous antibiotics can be transitioned to oral formulations after clinical improvement, resolution of fever, and negative urine cultures.
Symptomatic Treatment
Alkalizing agents such as sodium bicarbonate or potassium citrate may reduce the irritation caused by acidic urine, alleviating bladder-related symptoms. Calcium channel blockers such as verapamil or flavoxate hydrochloride may relieve bladder spasms and associated discomfort.