A 28-year-old Caucasian man with the past medical history of ESRD NYD underwent living unrelated kidney transplantation overseas in March 2012. He was admitted to our nephrology ward with elevated serum creatinine. His baseline creatinine was around 2 mg/dL. He had CMV enteritis in May 2013.
In September 2013, he went on another trip to overseas and felt weak and had a poor appetite, and his controlled serum creatinine level was 4 mg/dL. He underwent a kidney biopsy, which showed acute cellular rejection, but no C4d staining was done. He returned to Canada and was admitted to our ward. On admission he complained of weakness, but nothing else. At admission, he was on tacrolimus, mycophenolate mofetil, steroid, nifedipine, pantoprazole, and trimethoprim/sulphamethoxazole. His vital signs were BP 130/70 mm Hg, HR 85/min, RR 14/min, and temperature 97° F. A repeat kidney biopsy showed ACR-type 2A with tubulitis (Slide 1) and AMR with C4d positivity (Slide 2).
In addition, he had severe interstitial fibrosis/tubular atrophy, no arteriolar hyalinosis and moderate arterial sclerosis, but none of the glomeruli (n=22) was sclerosed.
At admission, his laboratory results revealed a serum creatinine level of 4.5 mg/dL, serum sodium level of 131 mmol/L, serum potassium level of 4.4 mmol/L, serum chloride level of 110 mmol/L, serum bicarbonate level of 14 mmol/L, and serum albumin of 4.6 g/L. This metabolic acidosis was a new finding.
He received a steroid bolus, five doses of plasma exchange, total of 5 mg/kg thymoglobulin treatment and 2 g/kg IVIG. He responded the treatment his graft function improved. Oral sodium bicarbonate was started, but his serum bicarbonate level decreased even more to 10 mmol/L.
At that point, a urinalysis revealed a urine sodium level of 76 mmol/L, urine potassium level of 16 mmol/L, urine chloride level 72 mmol/L, urine urea level of 131 mmol/L, urine glucose level of 14 mmol/L and urine osmolality of 346 mmol/kg.
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He had non-anion gap metabolic acidosis most likely secondary to tubulitis due to ACR+AMR. He had normal corrected anion gap: (131+4)-(110+14)= 11 with serum albumin 4.6 g/L. Measurement of the urine osmolal gap (UOG) is helpful in evaluating patients with a normal anion gap (hyperchloremic) metabolic acidosis by providing an estimate of urinary ammonium (NH4) excretion.
The normal renal response to metabolic acidosis is to increase urinary NH4 excretion along with generation of new bicarbonate. He had no history of diarrhea and his urine osmolar gap was: (measured osmolality-(sodium+potassium)*2+glucose+urea= 346- (76+16)*2+14+131= 346-329) only 17 mosmol/kg. When the UOG is less than 150 mosmol/kg in a patient with metabolic acidosis, it is likely that NH4 excretion is impaired, as with a distal renal tubular acidosis (RTA). The proximal type of RTA usually does not result in severe acidosis, such as serum bicarbonate concentration of 10 mmol/L with oral bicarbonate supplementation.
However, the diagnosis of distal RTA can be made if the patient has preserved renal function, but in this case the improving graft function along with the worsening acidosis indicates that distal RTA can play role. Treatment of tubulitis with rejection regimen can result improvement of acidosis as happened in our case, too.
Answer: Non-anion gap metabolic acidosis secondary to distal RTA secondary to ACR+AMR
The case was prepared by Miklos Z Molnar, MD, PhD, Clinical Fellow, University of Toronto, Toronto, ON, Canada.
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