CASE REPORT published: 12 July 2021 doi: 10.3389/fped.2021.687396 Case Report: Uroenteric Fistula in a Pediatric-en-bloc Kidney Transplant Manifests as Deceptive Watery Diarrhea and Normal Anion Gap Acidosis Malek Al Barbandi 1, Marissa J. Defreitas 1,2, Juan C. Infante 3,4, Mahmoud Morsi 2, Patricia A. Arroyo Parejo Drayer 1, Chryso P. Katsoufis 1, Wacharee Seeherunvong 1, Jayanthi Chandar 1,2, George W. Burke 2 and Carolyn L. Abitbol 1* 1 Division of Pediatric Nephrology, Department of Pediatrics, University of Miami/Holtz Children’s Hospital, Miami, FL, United States, 2 Division of Kidney/Pancreas Transplant, Department of Surgery, Miami Transplant Institute, University of Miami/Jackson Memorial Hospital, Miami, FL, United States, 3 Department of Radiology (Voluntary), University of Miami/Jackson Memorial Hospital, Miami, FL, United States, 4 Department of Radiology, Nemours Children’s Hospital/University of Central Florida, Orlando, FL, United States Edited by: Introduction: The diagnosis of a post–surgical uroenteric fistula can be challenging and Sidharth Kumar Sethi, may be delayed for months after symptoms begin. A normal anion gap metabolic acidosis Medanta The Medicity Hospital, India has been reported in up to 100% of patients after ureterosigmoidostomy, and bladder Reviewed by: Aftab S. Chishti, substitution using small bowel and/or colonic segments. Here, we describe a rare case University of Kentucky, United States of a pediatric patient who developed a uroenteric fistula from the transplant ureters into Enrico Eugenio Verrina, Giannina Gaslini Institute (IRCCS), Italy the small bowel, after an en-bloc kidney transplantation resulting in profound acidosis *Correspondence: and deceptive watery diarrhea. Carolyn L. Abitbol Case Presentation: The patient is an 8-year-old girl with end stage kidney disease [email protected] (ESKD) secondary to focal segmental glomerulosclerosis. Through a right retroperitoneal Specialty section: approach, she underwent a right native nephrectomy and a pediatric deceased donor This article was submitted to en-bloc kidney transplant including two separate ureters. One month later, she had a Pediatric Nephrology, a section of the journal renal allograft biopsy for suspected rejection. During the week after the biopsy, she Frontiers in Pediatrics experienced abdominal pain followed by watery diarrhea and metabolic acidosis requiring Received: 29 March 2021 continuous bicarbonate/acetate infusions. An extensive gastro-intestinal evaluation for Accepted: 16 June 2021 Published: 12 July 2021 the cause of the diarrhea including endoscopy was inconclusive. The urine output < Citation: decreased to 500 ml daily; although, the kidney function remained normal. After 2 Al Barbandi M, Defreitas MJ, weeks of unexplained watery diarrhea a magnetic resonance urogram with contrast was Infante JC, Morsi M, Arroyo Parejo performed which demonstrated extravasation of urine from both ureters with fistulization Drayer PA, Katsoufis P, Seeherunvong W, Chandar J, into the small bowel. She underwent corrective surgery which identified the fistulous Burke GW and Abitbol CL (2021) tract, which was resected and both ureters were re-implanted. The diarrhea and acidosis Case Report: Uroenteric Fistula in a Pediatric-en-bloc Kidney Transplant resolved, and she has maintained normal renal allograft function for over 1 year. Manifests as Deceptive Watery Conclusion: An important aspect in the early diagnosis of a uroenteric fistula is the Diarrhea and Normal Anion Gap Acidosis. Front. Pediatr. 9:687396. sudden onset of severe hyperchloremic metabolic acidosis that results when urine is doi: 10.3389/fped.2021.687396 diverted into the intestinal tract. The mechanism is similar to that described in cases of Frontiers in Pediatrics | www.frontiersin.org 1 July 2021 | Volume 9 | Article 687396 Al Barbandi et al. Uroenteric Fistula After Kidney Transplant urinary diversions and/or bladder augmentation using the intestine. Important diagnostic tools are the measurements of solute excretion and pH in the urine as compared to the “watery diarrhea” or bowel output. Summary: We describe a case of a uroenteric fistula in a pediatric-en-bloc kidney transplant patient that went undiagnosed for almost 3 weeks due to the deceptive nature of the watery diarrhea which was actually urine. A uroenteric fistula should be considered in the differential diagnosis of diarrhea and hyperchloremic metabolic acidosis as a complication of kidney transplant. The simultaneous comparison of stool and urine pH and solute excretions may lead to the diagnosis, appropriate imaging and surgical intervention. Keywords: uroenteric fistula, pediatric-en-bloc transplant, non-anion gap acidosis, urinary diarrhea, CFTR-SLC26 INTRODUCTION lead to serious complications, including peritonitis, sepsis, malabsorption, electrolyte abnormalities, acute kidney injury, Uroenteric fistula represents an abnormal communication metabolic acidosis, and hyperammonemia (1, 2). Here, we between the urinary and enteral tracts. Although such fistulas are describe the rare case of a patient who developed a urinoma uncommon, they cause significant morbidity and may markedly following pediatric-en-bloc kidney transplant with extravasation affect the patient’s quality of life. Uroenteric fistulas most of urine from both ureters and fistulization into the small bowel. frequently occur as a consequence of abdominal malignancies, This resulted in severe hyperchloremic metabolic acidosis and traumatic or iatrogenic injuries (1, 2). Untreated fistulas can persistent deceptive watery diarrhea. FIGURE 1 | Timeline from deceased pediatric donor en-bloc kidney transplant (DDKT), renal allograft biopsy with subsequent development of uroenteric fistula which manifested as normal anion gap acidosis and watery diarrhea which was diagnosed by magnetic resonance imaging urogram (MRU), followed by surgical repair and discharge after 8 weeks of hospitalization. The daily fluid balance with urine and stool volumes are color coded. Frontiers in Pediatrics | www.frontiersin.org 2 July 2021 | Volume 9 | Article 687396 Al Barbandi et al. Uroenteric Fistula After Kidney Transplant CASE PRESENTATION TABLE 1 | Comparison of blood, bowel and bladder solutes during hyperchloremic acidosis induced by uroenteric fistula. An 8-year-old girl with a history of end stage kidney disease Blood acid/Base balance Bowel Bladder (ESKD) secondary to steroid resistant nephrotic syndrome and focal segmental glomerulosclerosis (FSGS), underwent right Acidosis Normo- Watery Urine native nephrectomy, with a pediatric-en-bloc deceased donor acidemia stool kidney transplant. The transplant operation was performed pH 7.20 7.36 9.0 6.0 in a retro-peritoneal fashion. The right native kidney was Sodiummmol/L 137 136 98 67 excised to create space for the two en-bloc pediatric kidneys. Potassium mmol/L 4.4 4.2 5.7 3.0 The arterial anastomosis was performed in an end-to-side Chloride mmol/L 116 110 31 48 fashion between the distal donor aorta and the distal recipient − aorta. The venous anastomosis was performed in an end- HCO3 mmol/L 7 20 to-side fashion between the inferior aspect of the donor Serum anion gap 18 10 (mmol/L) (Normal 6–22) inferior vena cava (IVC) and the distal recipient IVC. Creatinine mg/dL 0.29 0.29 17.65 5.44 The bladder was small, but of sufficient size to permit Osmolarity (mOsm/L) 273 273 242 131 the placement of two separate extravesicular (Lich-Gregoire Total protein mg/dL 5.1 5.6 55 14 technique) uretero-vesical anastomoses, performed without Albumin mg/dL 2.9 3.2 3.3 <1.2 tension, and without stents. Her post-operative course was complicated by recurrence of FSGS manifesting as heavy Urine Pr/Cr (mg/mg) 3.11 2.57 (Normal <0.2) proteinuria within 24 h following the transplant. She was Urine alb/cr (mg/g) 187 220 treated with therapeutic plasma exchange and rituximab with (Normal <30) resolution of the proteinuria. Four weeks after the transplant, Urine anion gap (HCO3) +72.7 +22 she suffered refractory abdominal pain with fever and elevated Urine osmolar gap +134 +61 serum creatinine. Serial abdominal ultrasounds showed resolving (NH4) postoperative perinephric collections around each kidney with FeNa% 1.6% 3.6% stable moderate hydronephrosis of the lateral kidney. She FeK% 2.0% 3.5% underwent a kidney biopsy for suspected rejection. The FeCl% 0.58% 2.9% biopsy revealed borderline T-cell mediated rejection which Tubular reabsorption of 99.4% 97.1% was treated with solumedrol given as a rapid taper over 10 Chloride % days from 300 to 5 mg for a total dose of 750 mg. Although Abnormal values are in bold. mmol/L, millimoles/liter; mOsm/L, milliosmoles/ liter; mg/dl, the fever resolved and the abdominal pain improved, she milligrams/deciliter; U Pr/Cr, Urine Protein/Creatinine ratio (Nl <0.2 mg/mg; Nephrotic developed watery diarrhea (1–2 liters daily without mucus or >2.0 mg/mg); Ualb/cr, Urine albumin/creatinine ratio (Nl <30 mg/g; nephrotic > 1,000 blood) with a hyperchloremic normal anion gap metabolic mg/g). HCO3, bicarbonate; NH4, ammonium; FeNa%, Percent fractional excretion of acidosis. Clinical examination revealed abdominal distension sodium; FeK%, Percent fractional excretion of potassium; FeCl%, Percent fractional excretion of chloride. Please see the schematic in Figure 3 (3, 4). with generalized tenderness. Abdominal ultrasound showed a new complex collection involving the pouch of Douglas measuring 6.8 × 6.4 × 3.3 cm. As a result, she was started on (Table 1). Notably, the analysis of the solutes from the