A 42-year-old man was hospitalized with sudden-onset weakness in both lower extremities. The patient had been treated with isoniazid 300 mg, rifampin 450 mg, and ethambutol 800 mg daily for pulmonary tuberculosis during the past two months. He had no history of exposure to antituberculosis antibiotics before beginning therapy. His compliance to antibiotics was excellent after the treatment for pulmonary tuberculosis and he denied the interruption on these regimens. He reported no constitutional symptoms, history of hyperthyroidism or paralysis.
A physical examination indicated that the muscle strength of the lower extremities was 2/5 of normal. The rest of the physical examination was unremarkable. A chest radiograph revealed reticular opacities on the bilateral upper lung fields, consistent with pulmonary tuberculosis. His laboratory data included hemoglobin 13.0 mg/dL, leukocyte count 9900/muL, and platelet count 290,000/muL. His biochemical data for serum and urine on admission are shown in Table 1. Profound hypokalemia, hypophosphatemia, and hypouricemia were present. Serum pH, bicarbonate level and anion gap indicated hyperchloremic metabolic acidosis with normal anion gap. The urinary anion gap was positive (10.2 mEq/L), suggesting the presence of renal tubular acidosis. Urinalysis showed normoglycemic glucosuria, beta2-microglobulinuria, pH 5.5, 2.5 g/day proteinuria and microscopic hematuria. The fractional excretion of potassium was 29.3% (normal range, 4%-16%); the calculated ratio of the maximal tubular transport of phosphate reabsorption to the glomerular filtration rate (TmP/GFR) was 0.24 mg/dL (normal range, 2.3-4.3 mg/dL); and the fractional excretion of uric acid was 77.4% (normal range, 6%-20%). Generalized hyperaminoaciduria was detected with liquid chromatography-tandem mass spectrometry. These findings suggest generalized proximal tubular dysfunction with wasting of bicarbonate, glucose, protein, potassium, phosphate, and uric acid.
Additional blood tests were performed to determine other possible causes of the patient's hypokalemia. His plasma renin activity and serum level of aldosterone were 21.6 ng/mL/h and 30.5 ng/dL, respectively. His thyroid-stimulating hormone and free thyroxine levels were within the normal ranges. Serum and urinary protein immunoelectrophoresis showed no evidence of monoclonal gammopathy, and immunological surveys of autoantibodies were negative. The patient's reticulocyte count, serum lactate dehydrogenase, and liver enzymes levels were within the normal ranges.
An ultrasonographic examination showed a normal-sized kidney, with slightly increased echogenicity in the bilateral renal parenchyma. A renal biopsy showed extensive mononuclear cell infiltrates, including epithelioid histiocytes and eosinophils, mild interstitial fibrosis, and tubular atrophy (Figure 1A and B). Ziehl-Neelsen staining for acid-fast bacilli and PCR detection of Mycobacterium tuberculosis in the renal biopsy specimen were negative. Focal granular deposits of immunoglobulin A (IgA) and complement 3 (C3) were demonstrated in the tubules (Figure 1C and D). The same immunofluorescent positivity was also shown in glomerular mesangium, and electron microscopy showed electron-dense deposits in the subendothelial and mesangial spaces (Figure 1E and F). These findings were consistent with IgA nephropathy accompanied by focal immune deposits along the tubules. Half the epithelial foot processes were effaced, and there were no pathological findings in the mitochondria.
Potassium chloride supplementation was given to treat the patient's hypokalemic paralysis. His muscle strength increased one day after potassium chloride supplementation. We substituted rifampin with levofloxacin, but his other antituberculosis antibiotics remained the same. Supplementation with potassium chloride and sodium bicarbonate was continued, and the patient was discharged on hospital day 14. The biochemical markers associated with Fanconi syndrome were significantly resolved, and he experienced no paralytic symptoms after discharge. His proteinuria and microscopic hematuria was also improved, and we discontinued supplementation with potassium chloride and sodium bicarbonate at the three-month follow-up. The patient's renal function and proximal tubular function remained stable at the last follow-up.