A 57-year-old Caucasian woman presented to our institution with severe muscle weakness, fatigue, and weight loss for the past 2 years. Her medical history included well-controlled migraines and depression, which were treated with sumatriptan and citalopram, respectively. In addition, she had chronic hypokalemia leading to multiple visits to the emergency department for muscle weakness. These episodes were treated with potassium supplementation, with only transient improvement. She denied smoking, drinking alcohol, or using recreational drugs. On further questioning, she complained about dry eyes and dry mouth for the past 5 months. Also, she mentioned unintentional weight loss of 8 pounds during the same time. Upon examination, her vital signs were within acceptable limits. She was cachectic, with marked temporal wasting, dry mouth, and poor dentition. No thrush was noticed. Her cardiopulmonary evaluation was unremarkable, and no organomegaly was palpated. Her neurological examination revealed decreased muscle strength in upper and lower extremities, both proximally and distally. Furthermore, her tendon reflexes were decreased throughout. However, her sensory and vibratory function was intact.
Biochemical studies showed hyperchloremia (122 mEq/L), nonanion gap (non-AG) metabolic acidosis (HCO3 −, 16 mEq/L; AG corrected for albumin, 7.8 mEq/L), and severe hypokalemia (2.5 mEq/L). In addition, her serum creatinine (Cr) was 1.3 mg/dl (estimated glomerular filtration rate [eGFR], 42 ml/min/1.73 m2 per the Modification of Diet in Renal Disease formula [MDRD]), and her blood urea nitrogen was 16 mg/dl. The remaining electrolytes, including calcium, magnesium, and phosphorus, were within normal limits. Her arterial blood gas showed pH 7.29, partial pressure of carbon dioxide 26 mmHg, and partial pressure of oxygen 134 mmHg. Her urine biochemistry revealed specific gravity 1.004, urine osmolality 175 mOsm/L, and pH 7.0. On further evaluation, the patient had a high urine anion gap (UAG) of + 23 and an inappropriately high potassium-to-creatinine ratio (K/Cr) of 3.9 mEq/mg. Repeated urine studies showed persistent alkaline urine (pH range, 6.5–7) with no evidence of glycosuria or phosphaturia. These findings were concerning for dRTA complicated with severe symptomatic hypokalemia. Additionally, her urine sediment was notable for sterile pyuria, as well as the presence of eosinophils, which suggested an ongoing tubulointerstitial process.
She had mild polyclonal gammopathy with predominance of immunoglobulin G (IgG) antibodies and undetectable IgG4 levels. Furthermore, antinuclear antibody titers (1:1280, speckled pattern), antibodies against Sjögren's syndrome antigen A (116.4; reference, 0–19.9), and antibodies against Sjögren's syndrome antigen B (58.3; reference, 19.9) were very high, suggesting Sjögren's syndrome (SS). The patient had no antibodies against salivary protein 1 or parotid-specific proteins. Antibodies against carbonic anhydrase (CA) type VI were negative as well. A renal biopsy was conducted, which revealed acute tubulointerstitial nephritis (TIN) with abundant eosinophils and significant lymphocytic and plasmatic cell infiltration (Figure 1a and b). We concluded that our patient had primary SS with acute TIN.
a Periodic acid-Schiff stain showing tubular atrophy, interstitial fibrosis, and inflammatory infiltrate in the glomeruli. b H&E stain showing eosinophil infiltrate in the interstitium, tubular atrophy, and intact glomeruli
Treatment and Outcome
The patient received aggressive therapy with potassium chloride (180 mEq/day), sodium bicarbonate (1960 mg/day), and amiloride (10 mg/day). In addition, she was treated with immunomodulatory therapy, including hydroxychloroquine (HCQ; 300 mg/day), azathioprine (50–100 mg/day), and a taper of prednisone. The patient tolerated the therapy and was reevaluated as an outpatient. After 2 weeks of inpatient treatment, her potassium level remained stable (3–3.5 mEq/dl), and she was minimally symptomatic. She was discharged with close follow-up.
Her strength and weight increased over the following 5 months. However, her renal function remained decreased with a serum Cr of 1.3–1.5 mg/dl, mild hypokalemia (K+, 3.1–3.4 mEq/dl), and mild metabolic acidosis (HCO3 −, 20 mEq/L), punctuated by recurrent episodes of severe hypokalemia and acidosis when she was unable to maintain the high-dose potassium and bicarbonate supplementation. Figure 3 shows the trajectories of serum potassium levels and renal function as well as the influence of medical therapy during the clinical course of the patient. Her clinical course was affected by her intermittent compliance with prednisone owing to its side effects, most importantly edema and lipodystrophy. She developed chronic kidney disease (CKD) in the setting of TIN.
J Med Case Reports. 2019;13(103) © 2019 BioMed Central, Ltd.