Malakoplakia in kidney transplant recipients: Three case reports

Abstract

BACKGROUND

Malakoplakia is a rare chronic granulomatous disease associated with gram-negative infection, predominantly by Escherichia coli. It is induced by defective phagolysosomal activity of the macrophages. Malakoplakia commonly affects the urinary bladder but has been shown to affect any solid organ, including the native and transplanted kidney. However, isolated malakoplakia of the kidney allograft is rare. Transplant recipients with compromised immune systems are more likely to develop malakoplakia.

CASE SUMMARY

We report three cases of kidney allograft parenchymal malakoplakia in kidney transplant recipients on immunosuppression that were successfully managed with good outcomes. We described the clinical characteristics of all the kidney allograft malakoplakia cases documented in the literature. A total of 55 cases of malakoplakia were reported in recipients with a history of kidney transplant. A total of 27 recipients had malakoplakia involving the allograft, and others had malakoplakia in other organs. The common presentations included allograft dysfunction, pyelonephritis, and allograft or systemic mass. Most recipients had favorable outcomes with appropriate management that included prolonged antibiotic therapy and adjustment of immunosuppression. We reviewed the published literature on all the cases of malakoplakia in kidney transplant recipients so far and summarized the etiology, management, and outcomes.

CONCLUSION

This case series provides an overview of the etiology, presentation, pathogenesis, and management of malakoplakia in kidney transplant recipients.

Key Words: Renal transplant; Malakoplakia; Allograft malakoplakia; Michaelis-Gutmann bodies; Von Hansemann cells; Transplant malakoplakia; Case report

Core Tip: Patients with an immunosuppressed state, such as renal transplantation, are at increased risk of developing malakoplakia. This disease has varied presentations and is challenging to diagnose. We present our recent experience in the diagnosis and management of malakoplakia in renal transplant recipients. We were able to review the documented cases of malakoplakia among renal transplant recipients in the literature and summarize our findings. We made conclusions concerning its presentation, association with transplant rejection, and management strategies.

INTRODUCTION

Malakoplakia is a rare chronic granulomatous disease associated with gram-negative infection, predominantly by Escherichia coli (E. coli). It is induced by defective phagolysosomal activity of the macrophages. Malakoplakia commonly affects the urinary bladder but has been shown to affect any solid organ, including the native and transplanted kidney. However, isolated malakoplakia of the kidney allograft is rare.

Transplant recipients are more likely to develop malakoplakia due to compromised immune systems. We report three kidney allograft parenchymal malakoplakia cases and describe the pathological lesions of malakoplakia, particularly the pathognomonic Michaelis-Gutmann bodies, and their clinical course. We reviewed the clinical characteristics of all the post-kidney-transplant malakoplakia cases documented in the literature. We summarized recently published reports about the disease's pathogenesis, morphology, and clinical course.

CASE PRESENTATION

Chief complaints

Case 1: A 66-year-old African American (AA) male received a deceased donor kidney transplant (DDKT). The post-transplant course was complicated with E. coli transplant pyelonephritis, low-grade cytomegalovirus (CMV) viremia, and later recurrent urinary tract infections (UTI) within the first six months post-transplant. He was on extended-release tacrolimus (Envarsus) 20 mg daily with a target concentration of 6-8 ng/mL, Mycophenolate Sodium (Myfortic) 360 mg twice daily (due to CMV viremia), and prednisone 5 mg daily.

Six months post-transplant, he developed worsening allograft function, with creatinine concentration elevation to 2.74 mg/dL from a baseline of 1.7 mg/dL. His workup showed asymptomatic E. coli bacteriuria, for which he was prescribed a two-week course of oral cefpodoxime 500 mg daily.

Case 2: A 39-year-old AA female's post-transplant course was complicated by disseminated Nocardia with pulmonary and neurological lesions and ocular involvement eight months post-transplant. She completed a 12-month course of Bactrim + moxifloxacin and was noted to have residual lesions in the lungs and brain. Follow-up imaging was performed to ensure the resolution of Nocardia lesions.

Case 3: One-month post-transplant, a 62-year-old White male presented with nausea, vomiting, decreased urine output, and chills. He was on the following immunosuppressive regimen: (1) Tacrolimus 3 mg twice daily; (2) Prednisone 5 mg daily; and (3) Myfortic 500 mg twice daily.

History of present illness

Case 1: He with a past medical history of kidney cell carcinoma, a history of prostate cancer, end stage kidney disease (ESKD) due to hypertensive nephrosclerosis.

Case 2: Her with a history of ESKD secondary to type 2 diabetes mellitus (DM) and arterial hypertension (HTN) had a simultaneous pancreas and kidney transplantation.

Case 3: He with a past medical history of ESKD secondary to diabetic nephropathy and HTN had deceased donor kidney transplantation.

Physical examination upon admission

Case 1: He denied any symptoms during his follow-up in the transplant clinic. Vital signs showed a temperature of 97.3 F, blood pressure of 143 mmHg/82 mmHg, heart rate of 75/minute, and a respiratory rate of 16/minute. Physical examination demonstrated normal cardio-pulmonary findings and no allograft tenderness or peripheral edema.

Case 2: Physical examination demonstrated normal cardio-pulmonary findings. She was noted to have allograft tenderness.

Case 3: On examination, he was febrile at 101F and had dry mucus membranes and right lower quadrant abdominal transplant tenderness.

Laboratory examinations

Case 1: Urine studies demonstrated > 100 white blood cells/high power field and > 100 red blood cells/high power field. Creatinine elevation to 2.74 mg/dL from a baseline of 1.7 mg /dL. Laboratory results are detailed in Table 1.

Table 1 It shows our recipients' complete blood count and chemistry results at the time of evaluation (abnormal values are highlighted in bold).

Laboratory	Case 1	Case 2	Case 3	Normal range
White blood cell	5100	11.7	5.7	4000-11000/mm3
Hemoglobin	10.4	10.7	8.8	12-16 gr/dL
Platelet count	217000	391000	65000	150000-450000/mm3
Na	138	135	127	136-145 mmol/L
K	5.4	4.2	4.7	3.5-5 mmol/L
Cl	106	100	96	96-106 mmol/L
HCO3-	24	17	21	22-26 mmol/L
Blood urea nitrogen	31.4	24.5	33	6-24 mg/dL
Creatinine	2.74	1.82	2.75	0.7-1.1 mg/dL

Case 2: Laboratory evaluation showed an elevation of creatinine to 1.8 mg/dL; the other results are detailed in Table 1. Urine cultures revealed E. coli, and she started on IV cefepime and then switched to cefpodoxime on discharge for two weeks with plans for an outpatient allograft kidney biopsy after completion of antibiotics.

Case 3: His initial workup revealed acute kidney injury with an elevated serum creatinine concentration of 2.75 mg/dL (baseline 1.5-1.8 mg/dL); urinalysis showed pyuria and nitrites. Donor-specific antibodies were negative. Urinalysis revealed a white blood cell of 40/hpf, a red blood cell of 17/hpf, and a positive urine culture for E. coli. Other pertinent results at admission are shown in Table 1. He was followed up in the transplant clinic two weeks later and had an elevated serum creatine concentration of 3.01 mg/dL.

Imaging examinations

Case 1: The allograft ultrasound (US) demonstrated a 2.4 cm nodular area in the inferior pole of the kidney transplant. He subsequently underwent an initial kidney biopsy, which was positive for acute tubular injury but negative for rejection and minimal interstitial fibrosis and tubular atrophy. A magnetic resonance imaging (MRI) of the abdomen was performed for the lesion, and three complex masses within the lower pole of the right kidney transplanted pole were demonstrated.

Case 2: Computed tomography of the abdomen revealed findings consistent with acute pyelonephritis of the right lower quadrant of the kidney transplant with mild transplant hydronephrosis. A transplant kidney US showed a 3.2 cm hypoechoic mass-like area in the lower pole of the kidney transplant with hydronephrosis.

Case 3: A kidney transplant US showed a minimally complex 6.0 cm peri-transplant collection, which required placement of a drain, and the workup was consistent with a urinoma.

FINAL DIAGNOSIS

Case 1

He underwent a biopsy of the kidney mass, which demonstrated malakoplakia. Urine cultures were again positive for E. coli.

Case 2

She had a biopsy from the allograft kidney a month later due to worsening kidney function, which showed Banff type IA grade acute cellular rejection and malakoplakia. For case 2, histological examination showed segmental sclerosed and extensive about 70% interstitial fibrosis with proportional tubular atrophy, findings diagnostic of acute T-cell mediated rejection, grade 1A with moderate-to-severe interstitial inflammatory cells with abundant plasma cells and lymphocytes. In addition, there were focal interstitial neutrophils in addition to the plasma cells that showed rimming around tubules, neutrophilic tubulitis, and focal neutrophilic casts. These findings in this recipient with a recent history of E. coli urinary tract infection are diagnostic of focal acute pyelonephritis. Moreover, there were focal sheets of macrophages adjacent to the area with acute pyelonephritis that have abundant PAS-positive granular eosinophilic cytoplasm (Von Hansemann cells) and basophilic inclusions that show focal targetoid appearance characteristic of Michaelis-Gutmann bodies and stained positive for calcium and iron, findings diagnostic of malakoplakia.

Case 3

The allograft biopsy was negative for rejection but showed malakoplakia.

Case 1 and Case 3

For cases 1 and 3, histological examination from the transplant biopsy showed chronic inflammatory sheets of macrophages, lymphocytes, and occasional plasma cells. Multiple intracytoplasmic inclusions with focal targetoid appearances within the macrophages were noted. These inclusions were positive for calcium on the Von Kossa stain and focally positive for Iron on the Prussian blue stain, consistent with Michaelis–Gutmann bodies pathognomonic for malakoplakia, as shown in Figure 1.

Figure 1 Von Kossa stain. A: Variable lymphoplasmacytic infiltrate and sheets of macrophages were noted on the haematoxylin and eosin stain(marked with arrows); B: Periodic acid Schiff (PAS) stain highlighting PAS positive intracytoplasmic inclusions (Michaelis-Gutmann bodies) marked with an arrow that focally has a targetoid appearance; C: Von-Kossa stain highlighting the mineralized cytoplasmic inclusions; D: Prussian blue stain for iron that is focally positive(marked with an arrow).

TREATMENT

Case 1

He was started on intravenous (IV) cefepime for a week and then discharged on oral Trimethoprim/Sulfamethoxazole (TMP/SMX) and the repeat imaging showed persistent biopsy-proven kidney malakoplakia three months later. He was given IV Cefepime for a week and continued on oral cefuroxime therapy for six months.

Case 2

Rejection was treated with IV thymoglobulin. Repeat urine cultures grew Acinetobacter. She was treated with IV ceftriaxone for pyelonephritis and was discharged to continue with oral TMP/SMX DS until the resolution of imaging findings.

Case 3

He was given cefuroxime for 6 months.

OUTCOME AND FOLLOW-UP

Case 1

A repeat MRI later showed decreased size in the kidney lesions, and serum creatinine concentration reached a nadir of 1.2 mg/dL.

Case 2

A follow-up MRI three months later showed complete resolution in malakoplakia and complete resolution of hydronephrosis.

Case 3

A repeat kidney imaging three months later demonstrated a resolution of malakoplakia.

DISCUSSION

Malakoplakia is a rare chronic granulomatous infectious disease involving the skin and other organs[1,2]. Malakoplakia was first described by von Hansemann in 1901 and 1902 by Michaelis and Gutmann[3]. It is most frequently reported to occur in the genitourinary system. The first case of malakoplakia reported outside the genitourinary system was in 1958[4]. Malakoplakia is believed to result from the inadequate killing of bacteria by macrophages or monocytes that exhibit defective phagolysosomal activity[5]. Reduced monocytic cyclic guanosine monophosphate (cGMP) levels and decreased release of ß-glucuronidase lead to impaired lysosomal clearance, leading to bacterial residues in macrophages. Partially digested bacteria accumulate in monocytes or macrophages and lead to the deposition of calcium and iron on residual bacterial glycolipids. The presence of the resulting basophilic inclusion structure, the Michaelis-Gutmann body, is considered pathognomonic for malakoplakia[5-7]. These macrophages with pathological Michaelis-Gutmann bodies are called Von Hansemann cells.

The most common organism isolated was E. coli. Other organisms isolated include Klebsiella and Proteus species. Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa, and Rhodococcus equi are rarely encountered in recipients with malakoplakia[8].

An immunodeficient state favors the increased incidence of malakoplakia in immunocompromised states, including post-organ transplantation, DM, chronic alcohol intake, acquired immune deficiency syndrome, malignancy, and immunosuppressive therapy, which suggests that an impaired function of T lymphocytes may play a role in the pathogenesis of malakoplakia[3,6,7]. Partial or complete resolution of phagocytic cell dysfunction has been shown to occur in recipients with malakoplakia after cessation of immunosuppressive therapy[2,6-9].

We report these cases because of the rarity of isolated malakoplakia on kidney allografts and the scarcity of medical literature regarding management. Immunosuppression predisposes and increases kidney transplant recipients to gram-negative bacterial infections and subsequently to the development of malakoplakia. The differential diagnosis of malakoplakia includes other chronic inflammatory processes such as mycobacterium avium infections and xanthogranulomatous pyelonephritis.

In all of our cases, malakoplakia was diagnosed by biopsy, and two showed resolution of malakoplakia with TMP/SMX DS confirmed by serial imaging modalities. The other case demonstrates the complexity of managing and the need for therapy adjustments to achieve curative treatment.

Methods

We reviewed the literature in PubMed for cases of malakoplakia among kidney transplant recipients. Publications not in English were excluded, and we identified 55 cases (Figure 2) published among kidney transplant recipients (including the current 3 cases). Of the 55 reported cases, 27 involved the kidney allograft (Table 2)[7,10-30], and 28 involved other internal organs instead of the kidney allograft (Table 3)[6,9,31-54]. Out of these 28 cases of Malakoplakia involving other organs, nine involved the gastrointestinal tract, 6 involved the bladder, 5 involved the groin or perineum, 2 involved the lung, 2 involved the skin, 1 involved the prostate, 1 involved the abdominal wall, 1 involved the tongue, and 1 involved the native kidney (Table 3)[6,9,31-54].

Figure 2  It shows the location of malakoplakia diagnosis in kidney transplant recipients so far documented in the literature.

Table 2 Depicts the clinical characteristics of recipients with kidney allograft malakoplakia.

Ref.	Age (years)	Sex	Native disease	Time after transplant	Prior rejection	Organism	Antibiotic duration	Outcome
Case 1	66	M	HTN	8 months	No	E. coli	8 months	Improved
Case 2	39	F	HTN, DM	33 months	Yes	E. coli	3 months	Improved
Case 3	62	M	HTN, DM	1 month	No	E. coli	6 months	Improved
Vishwajeet et al[10], 2023	49	F	NR	12 years	Yes	E. coli	NR	Improved
Rustom et al[11], 2023	55	M	HTN	5 months	NR	E. coli	Long-term	Improved
Triozzi et al[12], 2022	40	F	Hemolytic uremic syndrome	4 months	No	E. coli	30 days	Improved
Yim et el[7], 2022	33	F	GN	6 months	Yes	E. coli	22 days	Improved
Park et al[13], 2020	59	F	DKD	6 months	NR	NR	Long-term	Improved
Lee et al[14], 2022	59	F	NR	18 months	Yes	E. coli	NR	Improved
Patel et al[15], 2021	45	F	GN	16 months	Yes	E. coli, Klebsiella pneumoniae	Long-term	Improved
Kalimuthu et al[16], 2021	41	F	NR	1 year	NR	Culture negative	NR	NR
Kinsella et al[17], 2021	63	F	NR	7 months	NR	E. coli	3 months	Improved
Kinsella et al[17], 2021	52	F	NR	4 months	NR	E. coli	6 months	Improved
Tan et al[18], 2021	55	F	Lithium	NR	NR	E. coli	4 months	NR
Khojah[19], 2020	74	F	NR	2 years	No	E. coli, Enterobacter aerogenes	Long-term	Improved
Khojah[19], 2020	62	F	NR	6 years	No	Culture-negative	6 months	Improved
Yasin et al[20], 2018	36	F	NR	4 years	NR	E. coli	14 weeks	Improved
Mookerji et al[21], 2018	58	M	Polycystic kidney disease	6 months	Yes	E. coli, Enterobacter cloacae	1 month	Kidney failure
Pirojsakul et al[22], 2015	14	F	Vesico-ureteral reflux	1 year	NR	E. coli	NR	NR
Keitel et al[23], 2014	23	F	GN	36 days	Yes	E. coli	28 days	Kidney failure
Honsova et al[24], 2012	31	F	DKD	12 years	Yes	E. coli, Staphylococcus aureus	NR	Improved
Augusto et al[25], 2008	56	F	Unknown	11 months	No, prior transplant	E. coli	10 weeks	Improved
Puerto et al[26], 2007	45	F	NR	2 years	NR	E. coli	None	Kidney failure
Pusl et al[27], 2006	43	F	DKD	2 years	NR	E. coli	2 months	Improved
McKenzie et al[28], 1996	29	F	GN	8 years	NR	NR	Long-term	Improved
Stern et al[29], 1994	55	F	GN	3 years	No	E. coli	Long-term	Improved
Osborn et al[30], 1977	46	F	Pyelonephritis	15 months	No	E. coli, psoriasis vulgaris	1 month	Improved

DKD: Diabetic kidney disease; DM: Diabetes mellitus; E. coli: Escherichia coli; F: Female; GN: Glomerulonephritis; HTN: Hypertensive kidney disease; M: Male; NR: Not reported.

Table 3 depicts the clinical characteristics of kidney transplant recipients with malakoplakia involving other organs.

Ref.	Anatomical location	Age, gender	Native disease	Time after transplant	Prior rejection	Organism
Boo et al[31], 2023	Native kidney	40, F	End stage kidney disease	32 weeks	No	E. coli
Coulibaly et al[32], 2023	Colon	62, M	GN	NR	NR	NR
Biggar et al[6], 1985	Abdominal wall	32, M	Reflux	16 months	Yes	E. coli
Nieto-Ríos et al[33], 2017	Bladder	45, F	Preeclampsia	2 years	NR	E. coli
Graves et al[9], 2014	Bladder	56, F	GN	1 year	Yes	E. coli
Merritt et al[34], 1985	Bladder	64, F	NR	3 years	NR	NR
Deguchi et al[35], 1985	Bladder	22, F	GN	1 year	NR	E. coli, Proteus mirabilis, K. pneumoniae
Sian et al[36], 1981	Bladder	52, F	PKD	17 months	No	NR
Arnesen et al[37], 1977	Bladder	37, F	NR	6 months	No	E. coli, Corynebacterium spp.
Mitchell et al[38], 2019	Gastrointestinal	72, F	FSGS	10 months	NR	NR
Ghaith et al[39], 2018	Gastrointestinal	75, M	DKD, HTN	NR	Yes	NR
Koklu et al[40], 2018	Gastrointestinal	51, F	HTN	11 years	NR	NR
Mousa et al[41], 2017	Gastrointestinal	68, M	NR	NR	NR	NR
Bae et al[42], 2013	Gastrointestinal	55, F	GN	11 years	No	NR
Shah et al[43], 2010	Gastrointestinal	45, M	DKD	3 years	Yes	NR
Yousif et al[44], 2006	Gastrointestinal	40, M	PKD	15 months	NR	E. coli
Berney et al[45], 1999	Gastrointestinal	52, M	PKD	9 years	No	E. coli
Macdonald et al[46], 2019	Groin	48, M	Reflex	5 months	No	E. coli
Afonso et al[47], 2013	Groin	51, M	FSGS	2 years	NR	Providentia spp., Candida albicans
Olivier et al[48], 2022	Groin	70, M	DKD, HTN	2 years	NR	E. coli, Pseudomonas aeruginosa
Lowitt et al[49], 1996	Perineum	51, M	Cervical intraepithelial neoplasia	14 months	NR	Streptococci spp., K. pneumoniae, Enterococcus spp.
Leão et al[50], 2012	Perineum	37, M	Reflux	15 years	Yes	Burkholderia cepacia
Ifudu and Delaney[51], 1994	Prostate	60, M	HTN	1 year	NR	E. coli, Serratia marcescens
Lococo et al[52], 2016	Pulmonary	67, M	NR	1 year	NR	Rhodococcus equi
Biggar et al[6], 1985	Pulmonary	44, M	GN	31 months	NR	E. coli
Addison[53], 1986	Skin (eyelid)	35, M	Pyelonephritis	3.5 years	Yes	E. coli
Lowitt et al[49], 1996	Skin (temple)	67, M	DKD, HTN	1 year	NR	E. coli, Streptococcus spp.
Schwob et al[54], 2015	Tongue	70, M	NR	NR	NR	E. coli

DKD: Diabetic kidney disease; E. coli: Escherichia coli; F: Female; FSGS: Focal segmental glomerulosclerosi; GN: Glomerulonephritis; HTN: Hypertensive kidney disease; K. pneumoniae: Klebsiella pneumoniae; M: Male; NR: Not reported; PKD: Polycystic kidney disease.

Literature review

We noted several trends and observations based on the Malakoplakia cases involving the kidney allograft. E. coli was the most common organism, accounting for infections in 23 out of 27 cases (85.1%). Organisms such as Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, psoriasis vulgaris, and S. aureus were found in a few cases, along with E. coli. In two cases, the organism was not reported.

Malakoplakia was more likely to affect the kidney allografts in female recipients (23/27 cases), while it was more likely to occur in locations other than the kidney allograft in male recipients. The recipients' age varied between 14 and 74 in the literature.

The clinical presentation of malakoplakia varied based on its location and severity. When occurring in the kidney allograft, malakoplakia can present with unilateral kidney dysfunction, allograft pain, dysuria, lower urinary tract symptoms, or a palpable mass.

Recipients may also develop perinephric abscesses, hydronephrosis, or pyelonephritis. Laboratory results that may clue clinicians toward malakoplakia include elevated creatinine, decreased glomerular filtration rate, elevated white blood cell count, urinalysis suggestive of UTI, and a urine culture positive for bacterial organisms. As Patel et al[15] reported, hypercalcemia may rarely be seen. Imaging may show an enlarged allograft with a possible mass.

Biopsy serves as the best diagnostic tool for malakoplakia diagnosis. On gross examination, malakoplakia will appear as white or yellow patches, calcified plaques, or masses of the kidney autograft. Histopathologic examination reveals von Hansemann cells, enlarged macrophages with eosinophilic cytoplasm, and Michaelis-Gutmann bodies, 2-10 mm lesions within the cytoplasm of macrophages with a “bird’s eye” appearance, on light microscopy (Figure 1)[15]. The presence of periodic acid Schiff positive granules in the macrophages and CD 68 positivity can also confirm the diagnosis if the lesions stain negative for calcium in the von Kossa stain[7]. Sometimes, a repeat biopsy may be considered as these lesions may not be apparent early in the disease course[8].

The data reports a mix of recipient outcomes based on the recipient’s history of prior transplant rejection episodes among recipients with kidney allograft malakoplakia. Eight out of 27 cases reported prior transplant rejection or concomitant rejection, Eight out of 27 did not report prior rejection, and eleven out of 27 did not report this data. Regardless of a recipient’s history of transplant rejection, similar outcomes were noted in improvement vs kidney decline. Thus, prior or concurrent rejection may not present any clinical value in predicting recipient outcomes.

The time from kidney transplant to the onset of malakoplakia was variable among the cases, from 36 days to 12 years. No trends were found in linking infection to time after transplant, and thus, it is essential to note that infections can occur at any point, with a need for long-term surveillance.

Most recipients exhibited clinical improvement after successfully identifying kidney allograft malakoplakia, with 21 out of 27 cases (77.7%) showing improvement following treatment. Two of the cases reported no outcome, and 4/27 of the cases resulted in kidney failure. In the four cases where recipients developed kidney failure, the causes were often multifactorial, with recipients experiencing recurrent infections, advanced malakoplakia, unresponsive to medical therapy, and advanced disease presentation. Understanding these cases of malakoplakia post-kidney transplant underscores the importance of tailored management strategies to achieve favorable outcomes, as the majority of post-transplant infections exhibited positive results with appropriate treatment.

Among the relevant cases, treatment of the condition included initiating antibiotics, reduced immunosuppression therapy, and, rarely surgery. Antibiotics were selected based on susceptibility. TMP/SMX and fluoroquinolones are the preferred antibiotic choices in managing malakoplakia due to their ability to accumulate inside the macrophages. Bethanechol chloride has been shown to increase cGMP levels and can be considered an additive treatment in addition to antibiotics[7]. The antibiotic duration was based on treatment response, and the treatment response to antibiotics varied amongst the reported cases, ranging from 22 days to long-term therapy. Recipients were continued on long-term antibiotics even after response to a short-term treatment. Antibiotic therapy may be insufficient in advanced cases, and surgical intervention may be appropriate[55]. Such cases are rare and present as pseudotumor with mass effect. Antibiotics are crucial in the appropriate management of malakoplakia, and the recipients need to be maintained on prolonged antibiotic therapy even after the surgical resection of the lesions.

In some cases, it was found that reducing immunosuppression therapy may improve the response to antibiotic therapy[7]. Some immunosuppressive therapies may lead to malakoplakia due to leukotoxicity. Leukocyte toxic immunosuppressive agents such as azathioprine can increase the risk for malakoplakia. Purine synthesis inhibitors such as mycophenolate mofetil should be limited during the active treatment of malakoplakia. Episodes of rejection requiring heightened immunosuppression also increase the risk of malakoplakia. Overall, malakoplakia has a good prognosis with early identification and treatment. Proper management of immunosuppression and appropriate antibiotic therapy are crucial for resolving this condition[7,12,15].

CONCLUSION

Due to its rarity, atypical presentation, and progression, malakoplakia is challenging to diagnose. It should be considered in the differential diagnosis of unexplained kidney allograft dysfunction, allograft, or systemic mass in recipients with kidney transplants. Biopsy and histological examinations, such as those presented in this case series, are crucial for diagnosing Malakoplakia.

E. coli is the most common infection associated with malakoplakia in kidney transplant recipients. Malakoplakia involving the kidney allograft is common in females, whereas malakoplakia involving other internal organs is more common in males. Most recipients had favorable outcomes with appropriate management that involved administering antibiotics, adjusting immunosuppression, and, rarely resection.

Overall, this paper emphasizes the importance of having awareness and continued research in transplant nephrology as the risk for malakoplakia and its complications increases dramatically. It should be assessed in recipients with recurrent infections and unexplained loss of allograft function post-transplant. There is an increased need for guideline-based principles to address malakoplakia in kidney transplant recipients.