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2015 International Society of Nephrology
Kidney International (2015) 88, 14591460; doi:10.1038/ki.2015.127

The Case | Azotemia without renal failure

Laura E. Hesemann1 and Aubrey R. Morrison2
1

Divisions of Pediatric Nephrology and Nephrology, University of Missouri Health Care, Columbia, Missouri, USA and 2Division of Nephrology,
Washington University School of Medicine, St Louis, Missouri, USA
Correspondence: Laura E. Hesemann, Divisions of Pediatric Nephrology and Nephrology, University of Missouri Health Care, 400 N Keene
Street, Suite 102, DC058.00, Columbia, Missouri 65201, USA. E-mail: hesemannl@health.missouri.edu

3 cm

3 cm

Figure 1 | Computed tomography of the abdomen and pelvis. Left; pneumobilia

(arrow). Right; gas in the right renal pelvis (arrow).

A 75-year-old male was transferred to our facility from an

outside hospital for the management of complications of
acute pancreatitis. There he was diagnosed with a common
bile duct stone and underwent endoscopic retrograde
cholangiopancreatography 6 weeks before transfer. His
course was complicated by acute pancreatitis with a
pseudocyst compressing the right ureter requiring ureteral
stenting and by Clostridium difficile infection. All nutrition
and hydration was given by tube feeds via a gastrojejunostomy tube, including 3 g/kg/day of protein in an attempt to
reverse his 14 kg weight loss. At the time of transfer,
laboratory abnormalities included blood urea nitrogen

(BUN) concentration of 96 mg/dl, creatinine (Cr) of

0.88 mg/dl, albumin 2.8 g/dl, alkaline phosphatase of
238 U/l, and lipase 197 U/l. Other electrolytes were normal.
At the time of admission to the outside hospital his BUN was
16 mg/dl, and Cr was 0.8 mg/dl. Three days before transfer
his BUN was 77 mg/dl. The patient reported that his urine
output was significantly reduced such that he was voiding
very small amounts once or twice per day. Computed
tomography at our facility showed pneumobilia and gas in
the right renal collecting system (Figure 1), not seen on
imaging 2 weeks prior. When asked directly, the patient
admitted to pneumaturia.

What is the cause of the azotemia?

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Kidney International (2015) 88, 14591460

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make your diagnosis

LE Hesemann and AR Morrison: Azotemia without renal failure

The Diagnosis | Ureterocolic fistula

100

Placement of
peritoneal drain

90
80
BUN, mg%

60

50
40

30
20

Creatinine, mg%

70

10
0

0
0

5
10
Day of hospitalization

15

Figure 2 | Clinical course of the patient at our facility. BUN

open circles (red) and Cr open triangles (green). BUN, blood urea
nitrogen; Cr, creatinine.

Computed tomography showed an intraperitoneal abscess and

another in the right retroperitoneum with colonic necrosis and
pneumatosis, intraperitoneal free air, and air in the right renal
collecting system attributed to a ureterocolic fistula as the right
mid-ureter traversed the collection. The right ureter drained
into the ascending colon. The day after admission to our
facility, a drain was placed in the retroperitoneal abscess. The
following day, BUN fell to 60 mg/dl. Twelve days later, BUN
was 21 mg/dl and Cr 0.57 mg/dl (figure 2).
Disproportionate elevations in BUN relative to Cr are not
uncommon and are often multifactorial. Causes include
volume depletion with decreased glomerular filtration rate
(GFR) per nephron, hypercatabolism, high-dose glucocorticosteroids, and excessive protein intake.
Made clear by the marked improvement following drain
placement, the dominant cause of our patients azotemia was
colonic urea recycling as it drained via the fistula into the
colon where it was metabolized and absorbed. Circulating
urea is normally transported into the intestinal lumen by urea
transporters UT-A, UT-B, and UT-A6, where it undergoes
hydrolysis by bacteria-derived urease.1 However, sepsis and
infectious diarrhea are thought to alter this process by
cytokine-induced downregulation of these urea transporters.2
Experimental models have demonstrated the uptake of urea

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instilled directly into the human colon, confirming the

clinical consequences of this series of events in our patient.3
Drain placement allowed for reestablishment of right renal
excretory function, stopping the cycle of recirculation. In
essence, he went from one functioning kidney to two.
After the initial fall in BUN, further decline was due to
optimization of nutrition and increasing glomerular filtration.
However, at the outside hospital, his daily protein intake far
exceeded his nutritional needs. Even in intensive care unit
patients, sufficient daily protein intake is 1.2 g/kg/day, far
o3 g/kg/day our patient received. Furthermore, his Cr also
improved as a result of right ureteral external drainage. His
estimated GFR at the time of admission was 57 ml/min per
1.73 m2, which improved to 107 ml/min per 1.73 m2 by day
12, underscoring the limitation of assuming equivalence of
the estimated GFR with Cr clearance.
REFERENCES
1.

Smith CP, Potter EA, Fenton RA. Characterization of a human colonic cDNA
encoding a structurally novel urea transporter, hUT-A6. Am J Physiol Cell
Physiol 2004; 287(4): C1087C1093.
2. Schmidt C, Hocherl K, Bucher M. Cytokine-mediated regulation of urea
transporters during experimental endotoxemia. Am J Physiol Renal Physiol
2007; 292: F1479F1489.
3. Moran BJ, Jackson AA. 15N-urea metabolism in the functioning human
colon: luminal hydrolysis and mucosal permeability. Gut 1990; 31: 454457.

Kidney International (2015) 88, 14591460