INTRODUCTION — Approximately 30 to 50 percent of patients with autosomal dominant polycystic kidney disease (ADPKD) will have a urinary tract infection (UTI) during their lifetime. Cyst infections responsible for hospitalization occur much less frequently (approximately 9 percent) [1,2]. An infected cyst and acute pyelonephritis are the most common kidney infections, although complications such as a perinephric abscess and bacteremia can occur [3,4]. Cyst infection incidence rates are approximately 0.01 episode per patient per year [1]. Even nonfunctional end-stage polycystic kidneys may be a source of infection [5]. After transplantation, special attention needs to be paid to the native kidneys and polycystic livers in patients who present with sepsis, fever, or flank or abdominal tenderness.

By convention, UTI is defined either as a lower tract (acute cystitis) or upper tract (acute pyelonephritis) infection. This topic will review issues related to UTIs, particularly upper tract infections, in patients with ADPKD. Discussions related to UTI in patients without ADPKD, as well as the therapy of ADPKD and other renal manifestations of ADPKD, can be found separately. (See "Autosomal dominant polycystic kidney disease (ADPKD): Treatment" and "Autosomal dominant polycystic kidney disease (ADPKD): Kidney manifestations" and "Acute simple cystitis in women" and "Acute complicated urinary tract infection (including pyelonephritis) in adults".)

SOURCE OF INFECTION — As with UTIs in the general population, UTIs in patients with ADPKD are more likely to occur in women [3,6-8]. The infections are typically caused by gram-negative enteric organisms.

With respect to upper tract infections:

●Gram-negative enteric organisms ascend from the bladder among patients with pyelonephritis [3,6-8]. Such infections may be associated with dysuria and frequency due to bladder infection.

●In cyst infection, the source of the organisms is also often a gram-negative enteric organism, with Escherichia coli accounting for approximately 75 percent of cases [1]. However, the causes of cyst infection are often more difficult to document since the cysts may not be in communication with the collecting system, and the urine culture is often negative. Support for hematogenous spread has been documented in a case report in which Staphylococcus aureus bacteremia with cyst fluid cultures positive for the same organism and negative urine cultures were identified in an ADPKD patient with a history of intravenous drug use [9]. (See "Bacterial adherence and other virulence factors for urinary tract infection".)

Urinary tract instrumentation can also be a source of infection and should be avoided whenever possible. In addition, approximately 20 percent of patients with ADPKD develop nephrolithiasis, and stones may be a source of recurrent infections. (See "Autosomal dominant polycystic kidney disease (ADPKD): Kidney manifestations", section on 'Nephrolithiasis'.)

CLINICAL FEATURES — The clinical manifestations of a kidney infection in ADPKD include fever and flank pain and usually nausea and vomiting [10]. These infections may be due either to renal parenchymal infection (acute pyelonephritis) or an infected cyst, and distinguishing between them is often difficult.

With pyelonephritis, the manifestations may be more acute, with features similar to any patient without ADPKD. By comparison, patients with a cyst infection frequently have a more insidious presentation and may have a specific area of tenderness that relates to the location of the cyst infection. Importantly, both pyelonephritis and cyst infection may be present simultaneously in an ADPKD patient.

After kidney transplantation, ADPKD patients are at higher risk for native kidney infections compared with the general population [5]. The classical signs and symptoms of native kidney cyst infection or pyelonephritis (fever, pain, dysuria) can be minimal or absent in such patients [5,11]. (See "Acute simple cystitis in women".)

DIAGNOSIS — The diagnosis of a kidney infection in a patient with ADPKD requires a similar approach as in a patient without ADPKD and includes a thorough physical examination, urinalysis, urine Gram stain, urine culture with antimicrobial susceptibility testing, and, in most cases, a blood culture. (See "Acute simple cystitis in women", section on 'Diagnostic approach'.)

The physical examination and urinary findings are not specific, but certain characteristics may help determine whether the patient has pyelonephritis or a cyst infection:

●Patients with an infected cyst may have a new area of discrete tenderness on physical examination, whereas pyelonephritis tends to be associated with diffuse flank pain.

●The presence of white cell casts is suggestive of acute pyelonephritis, and the urine culture is typically positive. In contrast, the sediment may be bland and the urine culture may be negative in patients with an infected cyst since cysts may not be in contact with the renal collecting system [3,6,7]. Blood cultures may be positive in both pyelonephritis and cyst infections [9].

Pyuria is found in up to 45 percent of uninfected patients with ADPKD [3]. As a result, pyuria without an appropriate clinical picture cannot be used to diagnose UTI.

Traditional radiologic studies (including ultrasound, computed tomography [CT] scan, and magnetic resonance imaging) are generally of little help in the initial evaluation since the cyst changes induced by an infection are similar to those with cyst hemorrhage; thus, many uninfected cysts appear abnormal [3]. Gallium or indium scanning localizes only inflammation and is positive in approximately one-half of cases [7]. However, 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) or a CT-PET scan may identify renal and hepatic cyst infections and help differentiate between a kidney and liver cyst infection [12-14].

Further evaluation will depend upon the response to initial therapy. (See 'Antimicrobial therapy' below.)

DIFFERENTIAL DIAGNOSIS — The principal distinction to be made in a patient with ADPKD presenting with flank pain is among a kidney infection, cyst infection, and cyst hemorrhage. Since the symptoms are similar, distinguishing among these disorders is difficult without a positive urine culture. Flank pain in the absence of fever is more likely to result from bleeding into and gradual enlargement of a cyst. However, cyst hemorrhage can be associated with transient fever and leukocytosis. In this setting, findings suggestive of hemorrhage rather than infection are the abrupt onset of pain and the absence of antecedent dysuria and frequency. In a systematic review of 215 cyst infections, of which 119 were renal infections, abdominal pain, fever, and elevated serum inflammatory markers were consistently present [15]. Urine and blood cultures were frequently negative in this study.

Nephrolithiasis (including staghorn calculi) may also be a source of flank pain in patients with ADPKD, as well as a source of UTIs. Imaging studies will identify the presence of kidney stones. (See "Kidney stones in adults: Diagnosis and acute management of suspected nephrolithiasis", section on 'Diagnostic imaging'.)

ANTIMICROBIAL THERAPY — Patients with a suspected kidney infection and relatively marked systemic symptoms are typically hospitalized and, when necessary, empirically begun on parenteral therapy [3,6]. As previously mentioned, although certain characteristics may help determine whether the patient has pyelonephritis or a cyst infection, it is frequently difficult to initially distinguish between the two.

Thus, a major issue surrounding the choice of initial empiric therapy is whether the antibiotic is able to successfully treat both types of infection. Since cysts larger than 2 cm in diameter are not in communication with a filtering glomerulus, the antimicrobial must enter the cyst by a mechanism other than glomerular filtration [16]. The major mechanism is diffusion, which is more pronounced with lipid-soluble drugs.

Drugs that both achieve therapeutic concentrations within the cysts and are active against gram-negative enteric organisms include ciprofloxacin and levofloxacin (and other fluoroquinolones), trimethoprim-sulfamethoxazole, and chloramphenicol [3,9,17-21]. On the other hand, aminoglycosides and the penicillins frequently do not penetrate cysts and are not predictably effective treatment for infected cysts [3,6,10]. The ability of newer antibiotics used against resistant organisms (eg, linezolid) to penetrate cysts has not been examined.

We most commonly treat initially with intravenous ciprofloxacin (or another intravenous fluoroquinolone). This choice is based upon the rationale that fluoroquinolones penetrate renal cysts and are also recommended parenteral agents for the initial empiric therapy of acute complicated pyelonephritis. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults", section on 'Management'.)

In some centers, however, a fluoroquinolone is not used for initial empiric therapy, since quinolone resistance is an increasing problem. In this setting, empiric therapy is initiated with cefotaxime or ampicillin plus gentamicin.

We make antibiotic adjustments based upon results of the urine culture, which is usually available within 48 hours. Vancomycin or erythromycin should be substituted if the patient has a streptococcal or staphylococcal infection [17]. Levofloxacin is also a good alternative for resistant group A streptococcal infections [21]. Metronidazole or clindamycin should be used if anaerobic organisms are recovered.

The patient should respond rapidly if the appropriate intravenous antimicrobial is administered. Patients with an infected cyst presenting with only mild or local symptoms can be treated primarily with oral therapy (eg, trimethoprim-sulfamethoxazole or a fluoroquinolone, such as ciprofloxacin).

In those who do not respond to antibiotic therapy with improvement in symptoms within 72 hours or have continued fevers for more than one week, one of the following may be present:

●Untreated micro-organisms are playing a pathogenic role

●Stone or obstruction of the urinary tract will not permit successful treatment

●The infected cyst is too large to respond to parenteral antibiotics

●Other causes of fever are present including drug-related fevers

In this setting, we suggest renal imaging. We prefer a spiral computed tomography (CT) scan to help determine the size of a possible infected cyst and to detect a stone or urinary tract obstruction. In situations of nonresponse to therapy or a deteriorating clinical condition, diagnostic information may be derived via percutaneous drainage of the suspicious cyst for documentation of the infecting organisms and/or drainage of the abscess cavity.

The duration of therapy will depend upon the response and the presence of pyelonephritis or an infected cyst:

●For patients with acute pyelonephritis (and no evidence of infected cyst or abscess), we continue with an oral antibiotic, based upon the results of the urine culture, for a total course of therapy of a minimum of 10 to 14 days.

●The optimal duration of therapy for infected cysts is unclear. Patients with a presumed cyst infection are usually treated for at least four weeks and sometimes for up to six weeks. If the infection recurs after withdrawal of antimicrobials, therapy may have to be reinstituted and continued for two to three months or longer [7]. In cases of an extremely large cyst infection, antibiotic therapy alone may not be sufficient to successfully treat the infection, and cyst drainage may be indicated. (See 'Other interventions' below.)

A perinephric abscess may also be present if the patient shows little or an incomplete response to antibiotic therapy within five to seven days. The management of perinephric abscesses is discussed separately. (See "Renal and perinephric abscess", section on 'Management'.)

Gas-forming organisms resulting in an emphysematous cyst are a rare complication of renal cyst infections in ADPKD. However, when present, a high mortality rate is associated, and urgent nephrectomy should be considered [22].

OTHER INTERVENTIONS — The majority of patients will eventually respond to the administration of appropriate antimicrobials. Large infected cysts (greater than 3 to 5 centimeters in diameter) are more likely to fail medical therapy and, therefore, to require other interventions [9].

Percutaneous or surgical drainage of the cyst is both infrequently necessary and hard to perform since it is usually difficult to ascertain radiologically which of the many cysts is infected. Case reports and a limited case series of percutaneous drainage of infected cysts have demonstrated a high success rate [9,23]. However, a prospective, randomized study comparing medical and interventional therapy has not been performed.

In contrast to the limited role of cyst drainage for cyst infection, drainage may be indicated for a perinephric abscess, which is diagnosed by ultrasonography or computed tomography (CT) scan. (See "Renal and perinephric abscess".)

Stone removal procedures may be required if nephrolithiasis is contributing to recurrent UTIs. (See "Kidney stones in adults: Struvite (infection) stones" and "Kidney stones in adults: Surgical management of kidney and ureteral stones".)

Surgical nephrectomy is the treatment of last resort because of potential complications and the potential adverse effects of removing a partially functioning kidney [3]. However, there are a few settings in which nephrectomy is sometimes considered:

●In patients infected with gas-forming organisms [22].

●Patients with recurrent, recent, or refractory infections who are about to undergo kidney transplantation [24]. In this setting, nephrectomy will minimize the risk of posttransplant infection when immunosuppressive agents are administered to prevent rejection [3]. In the absence of recurrent infections, however, posttransplant rates of UTI are comparable between nephrectomized and non-nephrectomized polycystic kidney disease patients [11].

●Patients with a staghorn calculus causing recurrent UTIs in a relatively nonfunctioning kidney. (See "Kidney stones in adults: Struvite (infection) stones".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic kidney disease in adults".)

SUMMARY AND RECOMMENDATIONS

●Approximately 30 to 50 percent of patients with autosomal dominant polycystic kidney disease (ADPKD) will have one or more kidney infections during their lifetime. As in urinary tract infections (UTIs) in patients without ADPKD, it is typically caused by gram-negative enteric organisms, which ascend from the bladder. Vesicoureteral reflux, nephrolithiasis, and urinary tract instrumentation can be contributory.

●Infected cysts and acute pyelonephritis are the most common causes of upper UTI in ADPKD. In each of these, flank pain and fever are typically present. Acute pyelonephritis is suggested by the presence of white cell casts, whereas an infected cyst may present with a new area of discrete tenderness and a bland urine sediment. In addition, both parenchymal and cyst infection may be present in any given patient. (See 'Clinical features' above.)

●In patients suspected of having a kidney infection, a complete history and physical examination should be performed, and a urinalysis, urine culture with antimicrobial susceptibility testing, and blood cultures should be obtained. Imaging studies such as ultrasound, computed tomography (CT), or magnetic resonance imaging are generally nonspecific. However, 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) or a CT-PET scan may identify renal and hepatic cyst infections and help differentiate between a kidney and liver cyst infection. (See 'Diagnosis' above.)

●Hemorrhage into a cyst and nephrolithiasis can also cause flank pain. Although fever can be present with cyst hemorrhage alone, they are not typically associated with pyuria or a positive urine or blood culture. (See 'Differential diagnosis' above.)

●We recommend initiating therapy of all patients with acute pyelonephritis and/or cyst infection who have marked systemic symptoms (eg, high fever, flank pain, nausea, and vomiting) with intravenous antibiotics (Grade 1B). We propose the following approach (see 'Antimicrobial therapy' above):

•For the therapy of either acute pyelonephritis or an infected cyst, we recommend initial treatment with intravenous ciprofloxacin (or other intravenous fluoroquinolone), unless fluoroquinolone resistance is an issue. This is based upon the rationale that fluoroquinolones penetrate renal cysts and are also recommended parenteral agents for the initial empiric therapy of acute complicated pyelonephritis. Therapy is modified based upon the urine culture. Intravenous therapy is discontinued once systemic symptoms resolve.

•In some centers where quinolone resistance is an increasing problem, empiric therapy may be initiated with cefotaxime or ampicillin plus gentamicin.

•For patients with acute pyelonephritis (and no evidence of infected cyst or abscess), we continue with an oral antibiotic based upon the results of the urine culture for a total course of therapy of a minimum of 10 to 14 days.

•For patients with infected cysts, we continue a fluoroquinolone orally for a minimum of four and up to six weeks.

●For the therapy of an infected cyst in patients with minimal or no systemic symptoms, we treat with an oral antibiotic that has demonstrated cyst penetration. Either a fluoroquinolone (eg, ciprofloxacin) or trimethoprim-sulfamethoxazole is a reasonable alternative, but the local bacterial susceptibility patterns must be considered.

●In those who do not respond to antibiotic therapy with improvement in symptoms within 72 hours or have continued fevers for more than one week, we perform a spiral CT scan without contrast to evaluate for the presence of stones or a perinephric abscess and to establish the size of the infected cyst. If indicated, diagnostic information may also be derived via percutaneous drainage. (See 'Antimicrobial therapy' above.)

●A perinephric abscess may require more prolonged therapy with intravenous antibiotics with activity against the likely organisms (typically gram-negative organisms). Drainage may be indicated. (See "Renal and perinephric abscess".)

●Percutaneous or surgical drainage and nephrectomy are rarely necessary; however, cysts larger than 5 cm in diameter have been shown not to respond to long-term parenteral antibiotic therapy. (See 'Other interventions' above.)

●The possibility of native kidney infections should be considered in kidney transplant recipients with nonfunctional polycystic kidneys. (See 'Clinical features' above.)