A rare case of emphysematous pyelonephritis in a renal transplant patient

Abstract

Emphysematous pyelonephritis (EPN) is a rare life-threatening complication of a properly functioning renal allograft leading to potential graft loss and hemodialysis. Currently, no clear management guidelines exist in these clinically challenging immunosuppressed renal transplant recipients. We report a case of a 62-year-old woman who presented with class 4 EPN and was managed with intravenous antibiotics and nephrectomy at our medical center.

Introduction

Emphysematous pyelonephritis (EPN) is a necrotizing infection that is commonly associated with diabetes mellitus and is most prevalent in middle-aged women [Alhajjaj and Pasha, 2016]. The most common pathogens are Escherichia coli and Klebsiella pneumonia [Bansal and Kapoor, 2016]. Given the presence of anatomic differences in the urinary tract system, lifelong immunosuppression, and high mortality rate, the management of EPN in post-renal transplantation patients can be challenging. We report a case of a 62-year-old renal allograft recipient who developed EPN and was managed with urgent nephrectomy along with intravenous antibiotics.

Case

Sixty two-year-old African American woman presented to our facility with complaints of abdominal pain and diarrhea for the past 5 days. Her medical history was significant for hypertension, well-controlled post-transplant diabetes mellitus, coronary artery disease, and cadaveric right-sided renal transplant (12 years ago secondary to bilateral nephrolithiasis). Review of systems was positive for fatigue, chills, anorexia, diffuse body aches, nausea, vomiting, and bloody diarrhea. The vital signs were as follows: temperature – 39.3°C, heart rate – 68/min, blood pressure – 149/69 mm Hg, and respiratory rate – 24/min. Physical examination was notable for abdominal distention and tenderness in the right lower quadrant over the site of the renal allograft. Labs were relevant for creatinine (in mg/dl): 8.79 (baseline-2), blood urea nitrogen (BUN): 112 mg/dl, white blood cell (WBC): 4.70 cells/ul with 95.1% segmented neutrophils, hemoglobin: 9.21 g/dl, hematocrit: 30.2%, sodium: 142, potassium: 4, bicarbonate: 8, chloride: 116, albumin: 2.3, magnesium: 1.3, lactate dehydrogenase (LDH): 549, lactic acid: 2.5, and hemoglobin A1c: 5.7. Urinalysis showed the following results: moderate blood, 3+ albumin, positive leukocyte esterase, 126/hpf WBC, 25/hpf red blood cells (RBC), and 3+ Bacteria.

She was started on intravenous vancomycin and piperacillin-tazobactum, and received emergent hemodialysis after vascular catheter placement in emergency department. Abdominal ultrasound revealed elevated resistive indices of the transplant renal arteries consistent with rejection and scattered echogenic foci with shadowing possibly representing gas in the collecting system. Abdominal computed tomography (CT) was consistent with right kidney class 4 EPN given the infection was located in the solitary functioning kidney (Figure 1) [Huang and Tseng, 2000]. Initial urine and blood cultures were positive for ampicillin-resistant non-extended spectrum beta lactamase K. pneumoniae. Transplant surgery team performed urgent nephrectomy for definitive treatment on hospital day 3. Surgical cultures were also positive for K. pneumoniae with similar sensitivity profile as initial blood and urine cultures. Repeat blood cultures and abdominal CT were negative for any acute process. Given her clinical improvement, she was de-escalated to oral cefepime and ciprofloxacin from day 10, and subsequently discharged to a nursing home facility on ciprofloxacin for the next 2 weeks and outpatient hemodialysis.

Figure 1.

Abdominal CT showing transplant kidney in right lower quadrant with a large focus of intraparenchymal gas consistent with EPN.

Discussion

EPN is defined as a gas producing, necrotizing bacterial infection that leads to the formation of gas in the renal parenchyma, collecting system, or perinephric tissue. EPN has a strong association with diabetes mellitus, but other risk factors can include non-diabetic urinary obstruction and female gender. Women are more commonly affected with EPN than men in a ratio of 4:1 [Al-Geizawi et al. 2010]. The incidence of EPN as a complication of properly functioning renal allografts is extremely rare, however, the infection requires immediate attention due to its life-threatening potential [Huang and Tseng, 2000]. To date, there have been only around 26 cases of EPN in renal allografts, hence paucity of data leads to unclear guidelines and recommendations for management. In the previous cases of EPN in a renal allograft, gas forming organisms such as E. coli and Klebsiella were the most commonly reported bacterial pathogens [Bansal and Kapoor, 2016].

The clinical presentation of EPN is very similar to that of severe pyelonephritis, with flank pain, fever, vomiting, and dysuria as the most common presenting complaints. The infection has the potential to rapidly progress to multi-organ failure. Patients with renal allografts have a higher probability of infection spread due to the lack of an investing fascia (Gerota’s fascia) on the transplant kidney. This fascia has been thought to act as a barrier preventing rapid spread of infection in healthy kidneys but is removed in the renal transplant process [Al-Geizawi et al. 2010]. The mortality rate has been reported to be as high as 15% which might be a possible underestimate given EPN is vastly underreported [Al-Geizawi et al. 2010].

Because of the risk of disseminated infection and poor prognosis, prompt diagnosis and treatment are critical. CT scan is the gold standard for diagnosing EPN because of its ability to differentiate EPN from the similar more common abdominal conditions [Alhajjaj and Pasha, 2016]. Even though ultrasound can help in diagnosing urinary retention and obstruction, it has proven ineffective in showing gas production in the renal parenchyma. CT scan is capable of locating areas of gas production and dead tissue [Fujita et al. 2005]. This is important in the commonly used staging system set in place by Huang et al. (Table 1). This classification system, which is generally used in most cases of EPN, focuses on the extension of gas and abscess in relation to their prognosis. Different management strategies depending on the EPN class have been proposed by Huang et al. Class 1 or 2 EPN has been suggested to be managed with aggressive medical management and percutaneous catheter drainage (PCD), while class 3 or 4 is managed with PCD initially followed by nephrectomy if drainage is unsuccessful [Huang and Tseng, 2000].

Table 1.

Classification system for EPN based on Huang and Tseng [2000].

Class 1	Gas limited in the collecting system
Class 2	Gas limited to the renal parenchyma
Class 3A	Gas extending to the perinephric space
Class 3B	Gas extending to the pararenal space
Class 4	Bilateral EPN or solitary kidney with EPN

EPN, emphysematous pyelonephritis.

However, this classification system did not comment on cases involving renal transplant. All renal allograft patients by this classification system would be considered class 4 because the infection involves the only functioning kidney in the patient. This classification suggests aggressive management despite the belief that only 50% of the functioning renal parenchyma is needed to maintain function in a transplant [Huang and Tseng, 2000]. In a study by Al-Geizawi et al. [2010], they proposed staging system for EPN in renal allografts (Table 2) that focused on the lack of Gerota’s fascia and proportion of renal parenchyma involved in the necrotizing process with a potential strategy to salvage the renal allograft. Also they described successful management of stages 1 and 2 EPN in renal allografts using intravenous medicines and PCD, and thus preventing the patient from becoming hemodialysis dependent.

Table 2.

Staging system for EPN in renal allografts proposed by Al-Geizawi et al. [2010].

Stage 1	Gas in the collecting system
Stage 2	Gas in <50% of renal parenchyma, with minimal spread to surrounding tissues and sepsis rapidly controlled
Stage 3	Gas in >50% of renal parenchyma, extensive spread of infection in perinephric area, or evidence of multi-organ failure, uncontrolled sepsis, or refractory shock

Management of EPN in renal allografts still lacks a real consensus in the literature. The treatment is more difficult with lack of clear staging, immunosuppression, and a solitary functioning kidney in most cases. Misgar et al. [2016] recommend early and aggressive medical treatment, including PCD, with nephrectomy as a last resort in patients who deteriorate or do not improve on conservative treatment. Other reports have supported the use of nephrectomy in cases where early medical management was unsuccessful in renal allograft recipients [Alhajjaj and Pasha, 2016].

In our case, medical management with aggressive intravenous antibiotic treatment was attempted. Also our patient was non-compliant with her immunosuppressive medication. Based on the two staging systems, our case of EPN was class 4 and stage 3, which both would have suggested aggressive treatment with medical management, PCD, and nephrectomy if other treatments failed. Because of her acute renal allograft rejection and bacteremia, an urgent nephrectomy was performed for definitive treatment with no attempts at PCD. Also, it is notable that our patient had azotemia, hematuria, albuminuria, hypoalbumenia, and acute renal dysfunction and required emergent hemodialysis. These have been previously reported with poorer outcome and failure of conservative treatment in EPN [Al-Geizawi et al. 2010]. Although the clinical picture eventually improved with our treatment strategy, it is not clear whether the patient would have been successfully managed with PCD alone.

Conclusion

Early diagnosis and treatment in cases of EPN are critical to have better overall outcomes for patients. Because of the rare nature of this disease in renal transplant patients, no specific guidelines exist. Most investigators believe early treatment with medical management and PCD should be practiced, but similar to our experience, others have also reported that early nephrectomy might be essential. Also, lack of validation of the staging systems makes management of the disease more difficult. Further studies are required for deciding optimal management and classification of EPN in a renal allograft patient.