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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 5  |  Issue : 3  |  Page : 104-108

Management of cyst infection in patients with autosomal dominant polycystic kidney disease: A single-center study


1 Kidney Disease Center, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Aichi, Japan
2 Kidney Disease Center, Japanese Red Cross Nagoya Daini Hospital, Nagoya; Department of Nephrology, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan

Date of Web Publication17-Dec-2018

Correspondence Address:
Akihito Tanaka
Kidney Disease Center, Japanese Red Cross Nagoya Daini Hospital, 2-9, Myoken-Cho, Showa-Ku, Nagoya 466–8650
Japan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jina.jina_3_18

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  Abstract 


Background and Objective: Cyst infections often develop as a complication in patients with autosomal dominant polycystic kidney disease (ADPKD). Although this complication has significant clinical implications, reports of cyst infection are extremely limited. Herein, we report on the status of cyst infection in patients with ADPKD to clarify this. Materials and Methods: Among 90 patients with ADPKD admitted to our hospital from 2010 to 2017, we selected those diagnosed with cyst infection. We collected the data from medical record retrospectively. Results: A total of 22 patients, comprising 12 men and 10 women, were included in the study. Infected cysts were identified on imaging in six (27.3%) patients. Bacterial culture was positive in 12 (54.5%) patients. The initial antibiotic treatment was quinolone, cephalosporin, carbapenem, and vancomycin in 7 (31.8%), 11 (50%), 3 (13.6%), and 3 (13.6%) patients, respectively. The mean hospitalization period was 12.0 days (range, 9.25–14.75), while the mean antibiotic treatment period was 26.5 days (range, 21.25–29.50). No patient died. Nine (40.9%) patients had previous episodes of cyst infection, and 11 (50.0%) had recurrence during the study period. The rate of prolonged hospitalization longer than the median of 12 days was higher in patients with maintenance dialysis, although the difference was not significant (80.0% vs. 50.0%, P = 0.1453). In multiple regression analysis, the albumin value showed a negative correlation with the hospitalization period (β-coefficient: −0.4835, 95% confidence interval: −15.5757–−0.9460, P = 0.0290). Conclusion: Patients with ADPKD who have a poor nutritional status may require additional medical attention to avoid prolonged hospitalization.

Keywords: Autosomal dominant polycystic kidney disease, albumin, cyst infection


How to cite this article:
Tanaka A, Inaguma D, Watanabe Y, Mizukawa T, Shinjo H, Koike K, Otsuka Y, Takeda A. Management of cyst infection in patients with autosomal dominant polycystic kidney disease: A single-center study. J Integr Nephrol Androl 2018;5:104-8

How to cite this URL:
Tanaka A, Inaguma D, Watanabe Y, Mizukawa T, Shinjo H, Koike K, Otsuka Y, Takeda A. Management of cyst infection in patients with autosomal dominant polycystic kidney disease: A single-center study. J Integr Nephrol Androl [serial online] 2018 [cited 2024 Mar 29];5:104-8. Available from: http://www.journal-ina.com/text.asp?2018/5/3/104/247695




  Introduction Top


Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal hereditary disorder and often leads to end-stage kidney disease.[1] Patients with ADPKD usually develop various complications, the most common of which is cystic infection. Cystic infection is among the major causes of hospitalization in this patient population. A total of 30%–50% of patients with ADPKD experience cyst infection.[2] Because the cyst is an enclosed space, it often becomes intractable and recurs repeatedly; thus, it may be lethal.[3],[4] Although it has significant clinical implications, only a few studies have been reported.

The number of patients is also limited even in large-scale research. In a relatively large-scale study, Sallée et al. reported approximately 41-episode cyst infection in 33 patients.[5] They described the incidence of cyst infections (0.01 episode per patient per year), and microbiological documentation was available for 31 episodes (75%). In their study,  Escherichia More Details coli (E. coli) accounted for 74% of all cultured bacterial strains.[5] A recent systematic review by Lantinga et al. also included only 85 cases in the meta-analysis.[6] They reported that although first-line treatment of renal cyst infection with antimicrobials is associated with a high rate of failure, the rate of successful treatment has increased in recent years.[6] However, no large-scale study on the treatment situation of cyst infection in patients with ADPKD has been conducted. The type of antibiotics that is available and their indications vary from country to country; thus, the treatment situation in each country is important. Studies on this topic are also limited in Japan.

Herein, we retrospectively investigated the treatment situation of patients who were hospitalized for cyst infection in our hospital using medical records. We assessed the current treatment status and also investigated factors related to the success or failure of treatment.


  Materials and Methods Top


Patient registration and data collection

This study was approved by the Ethical Committee of the Institutional Review Board of Japanese Red Cross Nagoya Daini Hospital and conducted under the Declaration of Helsinki.

This was an observational study examining 90 patients with ADPKD who were admitted to our hospital from 2010 to 2017. We collected the patients' data, including medical history, physical examination results, laboratory test results, and medication, by reviewing medical records. We included patients diagnosed with cyst infection. [Figure 1] shows the flowchart of patient recruitment. Cyst infection was diagnosed via cyst puncture, imaging, or clinical findings. We also included patients with conditions clinically compatible to cyst infection and ruled out other focus of infection. For patients who were hospitalized more than once, data on their first hospitalization were analyzed. Patients who underwent kidney transplantation were excluded. Positive culture means that the bacteria could be identified via blood or puncture fluid culture. Recurrence was defined as requiring another hospitalization due to cyst infection within the study period.
Figure 1: Flowchart of patient recruitment. ADPKD: Autosomal dominant polycystic kidney disease

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Statistical analysis

Baseline characteristics were presented as median and interquartile range and tested using the Mann–Whitney U-test or Chi-square test. Risk factors for hospital admission were examined via simple and multiple linear regression analyses. P < 0.05 was considered statistically significant.


  Results Top


Baseline characteristics

We assessed 22 patients comprising 12 men and 10 women with a median age of 65.0 years (range, 56.0–69.8). [Table 1] shows the baseline characteristics of the patients. A total of 14 (63.6%) patients had maintenance dialysis. Only one patient had diabetes. Cyst infection was identified via imaging in six (27.3%) patients. Seven (31.8%) patients underwent magnetic resonance imaging (MRI), and the focus of infection was identified in four (18.2%). Clinically, the site of infected cyst was the kidney and liver in four (18.2%) and seven (31.8%) patients, respectively, while it was unknown in the other patients. The culture was positive in 12 (54.5%) patients. The confirmed bacteria were E. coli (n = 6, 2 of which were levofloxacin resistant), Klebsiella pneumoniae (n = 3), Serratia marcescens (n = 1), Enterobacter cloacae (n = 1), and Raoultella ornithinolytica (n = 1). Initial antibiotic treatment was quinolone, cephalosporin, carbapenem, and vancomycin in 7 (31.8%), 11 (50%), 3 (13.6%), and 3 (13.6%) patients, respectively. Drainage because of refractory cyst infection was performed in only one (4.5%) patient. Because we included patients with dialysis, the level of creatinine in the cohort was high at 5.4 mg/dL (range, 2.6–7.6). The mean hospitalization period was 12.0 days (range, 9.25–14.75), and the mean antibiotic treatment period was 26.5 days (range, 21.25–29.50). No patient died. Nine (40.9%) patients had previous episodes of cyst infection, and 11 (50.0%) had recurrence during the study period. Approximately 50% of the patients had cyst infection before the observation period. Of these, approximately 50% were hospitalized again due to cyst infection during the study period. Because it is a closed cavity, the cysts often become refractory and thus recur repeatedly. However, if properly treated, the short-term prognosis is acceptable.
Table 1: Baseline characteristics of patients (n=22)

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Comparison between patients with long and short hospitalization period

Although recurrence is also an important outcome, it may be difficult to compare simply with the presence or absence of episodes because the interval between recurrence episodes varies widely and ranges from months to years. Therefore, we decided to investigate whether treatment is proceeding accordingly or not with the length of hospitalization period. We categorized the patients into two groups according to the median hospitalization period (12 days). The comparison is shown in [Table 2]. No statistical difference in age, sex, treatment, laboratory data, treatment period, or mortality was noted between the two groups. Meanwhile, the percentage of dialysis therapy was high, the culture-positive rate was low, the platelet count was low, and the albumin (ALB) value was low in the long hospitalization group, although the difference was not statistically significant.
Table 2: Characteristics of patients divided by median days of admission (n=22)

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Relationship between various factors and prolonged hospitalization

Considering the above results, a simple linear regression analysis was performed using dialysis therapy, culture positivity, platelet count, and ALB level as explanatory variables and hospitalization period as an objective variable [Table 3]. Our results showed a negative correlation between the level of ALB and hospitalization period (β-coefficient: −0.4820, 95% confidence interval [CI]: −15.2186–−1.2529, P = 0.0231). Further, multivariate analysis was also performed with adjustment for age and sex, and it showed the same correlation (β-coefficient: −0.4835, 95% CI: −15.5757–−0.9460, P = 0.0290) [Table 4].
Table 3: Simple linear regression analysis of various parameters for duration of hospitalization (n=22)

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Table 4: Multiple linear regression analysis of various parameters for duration of hospitalization (n=22)

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  Discussion Top


We retrospectively investigated the management of patients with ADPKD who developed cyst infection as complication and admitted to our hospital. Dialysis therapy was performed in more than 50% of the patients. The rate of infected foci being identified on imaging modalities was low at <30%. More than 50% of positive culture was observed, and the most commonly detected bacterium was E. coli. Meanwhile, the most common antibiotics used for treatment were quinolone and cephalosporin. No patient died, but several incidences of recurrence were noted. Hypoalbuminemia was found to be associated with prolonged hospitalization.

The rate of hospitalization was high in patients in maintenance dialysis (n = 14 patients, 63.6%). Some papers reported varying causes of cyst infection, including bloodstream infection[7] and retrograde urinary tract infection.[8] Based on the retrograde infection mechanism, patients who undergo maintenance dialysis may be at a higher risk of cyst infection because of their incapability to produce urine.

The rate of infected cysts identified on imaging was low at only 6 patients out of 22 (27.3%) showing infection. Previous studies reported that MRI[9] and positron-emission tomography (PET)[10] are useful for identifying the infected lesion. However, our hospital does not have PET, and the probability of accurate diagnosis may have increased if it was used. Among patients whose sites of infected cyst were not identified on plain or contrast-enhanced computed tomography, seven underwent MRI. Of these seven patients, the infected site was identified in four. Diagnosis is also difficult in patients with multiple cysts. The effectiveness of gallium scintigraphy has also been reported,[11] and one patient in our study was diagnosed using such modality.

The rate of positive blood or puncture fluid culture was 54.5%. The most common bacterium that was cultured was E. coli (n = 6 cases), a finding that is similar to that in a previous report.[5] Two of these six cases were levofloxacin resistant, indicating that we have to take care of that when performing empirical treatment with quinolone.

Quinolone is a fat-soluble antibiotic and is considered to be excellent in cystic migration. Several studies have reported its effectiveness for cyst infection.[12],[13],[14] Therefore, physicians tended to prefer quinolone. However, cephalosporin is the most commonly used antibiotic medication in this study. If the initial treatment is not effective, drainage and surgical treatment are performed.[5] However, in this study, drainage was performed in only one case, and no patient died. Cyst infection can be fatal[3] and has significant clinical implications. In this study, it had good short-term prognosis.

However, several patients had recurrence. Fatal cyst infections may develop from antibiotic-resistant bacteria or decreased immune capability due to repeated recurrence. Hypoalbuminemia is associated with prolonged hospitalization. Because malnutrition compromises wound healing,[15],[16] the nutritional status may play important roles in prognosis.

The high incidence of recurrences indicates the need for evaluating clinical factors such as the period of antibiotic use. In this study, several patients received antibiotics for approximately 4 weeks, which is the recommended period in Japanese guidelines (evidence-based clinical practice guidelines for polycystic kidney disease, 2014, in Japanese). Although immediate death was not observed, the problem is recurrence due to antibiotic resistance that results from prolonged antibiotic use. Thus, surgical treatment may be better in terms of relapse prevention. However, no evidence-based guideline for surgical treatment of cyst infection has been published.[17] Although a recent systematic review reported favorable outcomes, the study included only a small number of patients (N = 85);[6] thus, the result cannot be generalized. Accumulating additional cases in the future is important.

Our study has some limitations. First, this was a single-center study. Our hospital is a general hospital, and clinical practice may be different from other specialized centers. Second, this was a retrospective study. Identification of the infected foci and selection of antibiotics depend on the judgment of the attending physician. Thus, there may be some bias.


  Conclusion Top


In this paper, we reported on the clinical picture of cyst infection in patients with ADPKD. Although no death was observed, recurrence was frequent. Patients who have poor nutritional status may require additional medical attention to avoid prolonged hospitalization.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Grantham JJ, Mulamalla S, Swenson-Fields KI. Why kidneys fail in autosomal dominant polycystic kidney disease. Nat Rev Nephrol 2011;7:556-66.  Back to cited text no. 1
    
2.
Elzinga LW, Bennett WM. Miscellaneous renal and systemic complications of autosomal dominant polycystic kidney disease including infection. In: Watson ML, Torres VE, editors. Polycystic Kidney Disease. Oxford: Oxford Medical Publications; 1996. p. 483-99.  Back to cited text no. 2
    
3.
Suwabe T, Araoka H, Ubara Y, Kikuchi K, Hazue R, Mise K, et al. Cyst infection in autosomal dominant polycystic kidney disease: Causative microorganisms and susceptibility to lipid-soluble antibiotics. Eur J Clin Microbiol Infect Dis 2015;34:1369-79.  Back to cited text no. 3
    
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Fick GM, Johnson AM, Hammond WS, Gabow PA. Causes of death in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1995;5:2048-56.  Back to cited text no. 4
    
5.
Sallée M, Rafat C, Zahar JR, Paulmier B, Grünfeld JP, Knebelmann B, et al. Cyst infections in patients with autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 2009;4:1183-9.  Back to cited text no. 5
    
6.
Lantinga MA, Casteleijn NF, Geudens A, de Sévaux RG, van Assen S, Leliveld AM, et al. Management of renal cyst infection in patients with autosomal dominant polycystic kidney disease: A systematic review. Nephrol Dial Transplant 2017;32:144-50.  Back to cited text no. 6
    
7.
Suwabe T, Ubara Y, Higa Y, Nakanishi S, Sogawa Y, Nomura K, et al. Infected hepatic and renal cysts: Differential impact on outcome in autosomal dominant polycystic kidney disease. Nephron Clin Pract 2009;112:c157-63.  Back to cited text no. 7
    
8.
Idrizi A, Barbullushi M, Koroshi A, Dibra M, Bolleku E, Bajrami V, et al. Urinary tract infections in polycystic kidney disease. Med Arh 2011;65:213-5.  Back to cited text no. 8
    
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Suwabe T, Ubara Y, Ueno T, Hayami N, Hoshino J, Imafuku A, et al. Intracystic magnetic resonance imaging in patients with autosomal dominant polycystic kidney disease: Features of severe cyst infection in a case-control study. BMC Nephrol 2016;17:170.  Back to cited text no. 9
    
10.
Albano D, Bosio G, Bertagna F 18F-FDG PET/CT demonstrated renal and hepatic cyst infection in a patient with autosomal dominant polycystic kidney disease. Nucl Med Rev Cent East Eur 2016;19:26-8.  Back to cited text no. 10
    
11.
Jiménez-Bonilla JF, Quirce R, Calabia ER, Banzo I, Martínez-Rodríguez I, Carril JM, et al. Hepatorenal polycystic disease and fever: Diagnostic contribution of gallium citrate Ga 67 scan and fluorine F 18 FDG-PET/CT. Eur Urol 2011;59:297-9.  Back to cited text no. 11
    
12.
Elzinga LW, Golper TA, Rashad AL, Carr ME, Bennett WM. Ciprofloxacin activity in cyst fluid from polycystic kidneys. Antimicrob Agents Chemother 1988;32:844-7.  Back to cited text no. 12
    
13.
Telenti A, Torres VE, Gross JB Jr., Van Scoy RE, Brown ML, Hattery RR. Hepatic cyst infection in autosomal dominant polycystic kidney disease. Mayo Clin Proc 1990;65:933-942.  Back to cited text no. 13
    
14.
Hiyama L, Tang A, Miller LG. Levofloxacin penetration into a renal cyst in a patient with autosomal dominant polycystic kidney disease. Am J Kidney Dis 2006;47:e9-13.  Back to cited text no. 14
    
15.
Chandra RK. Nutritional regulation of immunity and risk of infection in old age. Immunology 1989;67:141-7.  Back to cited text no. 15
    
16.
Pifer TB, McCullough KP, Port FK, Goodkin DA, Maroni BJ, Held PJ, et al. Mortality risk in hemodialysis patients and changes in nutritional indicators: DOPPS. Kidney Int 2002;62:2238-45.  Back to cited text no. 16
    
17.
Chapman AB, Devuyst O, Eckardt KU, Gansevoort RT, Harris T, Horie S, et al. Autosomal-dominant polycystic kidney disease (ADPKD): Executive summary from a kidney disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2015;88:17-27.  Back to cited text no. 17
    


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