Case Presentation: Our patient is a 62 year-old gentleman with PMH significant for HTN, moderate-severe bilateral RAS and stage IIIa CKD who was transferred to our hospital for AKI requiring dialysis. 1 month prior to presentation, spironolactone was added to his antihypertensive medications of amlodipine, carvedilol, azilsartan and furosemide. He was in his usual state of health until four days prior to presentation when he had a day of non-bloody, non-melenic diarrhea that self-resolved. He subsequently developed nausea, anorexia, and generalized weakness.At presentation, he was afebrile, hypertensive with BP 164/70 mmHg, bradycardic to 56/min, respiratory rate of 16/min, with normal oxygen saturation. He had a neutrophilic predominant leukocytosis of 14.7K and platelet count of 161,000. Basic metabolic profile was significant for a sodium of 122 mmol/L, potassium of 6.2 mmol/L, total carbon dioxide 13 mmol/L with an anion gap of 15, BUN was elevated to 99 mg/dL, and serum creatinine was 11.5 mg/dL. Urinalysis was significant for microscopic hematuria (2/HPF), occasional urine squamous epithelial cells, small leukocyte esterase and negative nitrites. Renal ultrasound was negative for obstruction. CT abdomen/pelvis without contrast revealed severe atherosclerosis and non-obstructing renal calculi. He underwent emergent hemodialysis and was treated with ceftriaxone for possible UTI. Urine culture grew E. Coli sensitive to ceftriaxone <100,000 CFU. Repeat UA was unremarkable and microscopy revealed a bland sediment. Renal biopsy revealed findings as highly suggestive of thrombotic microangiopathy and diffuse tubular injury. Further studies showed mildly elevated LDH at 287 IU/L, but otherwise no signs of hemolysis. C3 and C4 levels and ADAMSTS13 were within normal limits. A stool sample 14 days after resolution of diarrhea was negative for salmonella, shigella, E-coli Shiga toxin, and campylobacter. A peripheral smear was significant for normal RBC and platelet morphology, without schistocytes. Genetic testing revealed no signs of inherited complement-mediated TMA.He was discharged dependent on hemodialysis with no further interventions. He had some renal recovery and two months after discharge and has remained dialysis independent with resultant stage IV CKD.
Discussion: This case suggests two major differential categories: local renal injury with renal artery stenosis (RAS) in the setting of transient hypoperfusion, or renal-limited TMA versus a resolving systemic TMA syndrome.Given the extensive secondary testing, the TMA or renal-limited TMA, if present likely would have been due to Shiga-toxin-mediated TMA, severe HTN-associated TMA, or less likely complement-mediated TMA. Renal-limited TMA, although only rarely described, is most commonly found to be drug-mediated or related to rheumatologic diseases, neither of which were found in this patient. More likely, however, is that this patient had diffuse ATN from volume depletion in setting of renin-angiotensin-aldosterone inhibition and severe bilateral RAS which masqueraded as a microangiopathy due to shearing of RBCs along the stenotic renal arteries with showering into the territory of the renal biopsy. Thus the biopsy revealed signs of both ATN and microangiopathy.
Conclusions: In the setting of severe renal artery stenosis, pathology may show signs of microangiopathy without a systemic TMA syndrome. This diagnosis can be considered only if the TMA workup is otherwise negative.