The Case | Azotemia without renal failure
Authors: Laura E. Hesemann, Aubrey R. Morrison
Journal: Kidney International (2015)

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? 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 patient’s 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.Smith C.P. Potter E.A. Fenton R.A. Characterization of a human colonic cDNA encoding a structurally novel urea transporter, hUT-A6.Am J Physiol Cell Physiol. 2004; 287: C1087-C1093Crossref PubMed Scopus (62) Google Scholar However, sepsis and infectious diarrhea are thought to alter this process by cytokine-induced downregulation of these urea transporters.2.Schmidt C. Hocherl K. Bucher M. Cytokine-mediated regulation of urea transporters during experimental endotoxemia.Am J Physiol Renal Physiol. 2007; 292: F1479-F1489Crossref PubMed Scopus (44) Google Scholar Experimental models have demonstrated the uptake of urea instilled directly into the human colon, confirming the clinical consequences of this series of events in our patient.3.Moran B.J. Jackson A.A. 15N-urea metabolism in the functioning human colon: luminal hydrolysis and mucosal permeability.Gut. 1990; 31: 454-457Crossref PubMed Scopus (42) Google Scholar 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 <3 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.