Distal Renal Tubular Acidosis Accompanied by Severe Hypophosphatemia Mistaken as Fanconi Syndrome in a Kidney-Transplant Patient

A 64-year-old female visited the emergency department due to general weakness and dyspnea developed suddenly. Her vital signs were unremarkable except of tachypnea. Her laboratory results were as follows: creatinine, 1.96 mg/dL; estimated glomerular filtration rate (eGFR, CKD-EPI), 26.4 mL/min/1.73 m²; bicarbonate 7.1 mM/L; sodium, 148 mEq/L; potassium, 3.2 mEq/L; chloride, 126 mEq/L; total calcium, 5.2 mg/dL; ionized calcium (Ca⁺⁺), 1.76 mg/dL; magnesium, 1.8 mg/dL; phosphorus, 1.9 mg/dL; anti-neutrophil antibody, negative; rheumatic factor, negative; complement 3 and 4, within normal range; urine pH, 7.5; urine glucose, negative; urine heme, trace; urine red blood cell, 2–3/high power field (HPF); urine white blood cell, 1–2/HPF; urine culture, no growth; urine protein-creatinine ratio, 0.66 g/g; urine urea nitrogen, 116.8 mg/dL; urine creatinine, 50.34 mg/dL; urine sodium, 57 mEq/L; urine potassium, 23.1 mEq/L; urine chloride, 55 mEq/L; urine uric acid, 18.2 mg/dL; urine osmolarity, 283 mosmol/kg H₂O. The initial serum and urine anion gap were 14.9 and 24.9 mEq/L, respectively and urine osmolal gap was 81.09 mosmol/kg H₂O. In addition, fractional excretion of sodium and uric acid was 1.4 and 22.14%, respectively. She had received a kidney transplant 15 years earlier due to immunoglobulin A nephropathy and has reveived continuous intake of cyclosporine, steroids, and mycophenolate mofetil. The blood cyclosporine level was 104 ng/mL. Kidney, Ureter, Bladder X-ray showed medullary calcified lesions in the allograft kidney (Fig. 1). These symptoms were aggravated despite an intravenous infusion of potassium and bicarbonate. It was decided to perform emergent dialysis because initial lung congestion also made it difficult to have a continuous infusion of sodium bicarbonate (Fig. 2). The symptoms and signs improved after emergent dialysis, however, hyperchloremic metabolic acidosis, hypokalemia, hypocalcemia, and hypophosphatemia remained after dialysis. The 24-hour urinary phosphorus level was markedly increased despite severe hypophosphatemia and fractional excretion of phosphate was markedly increased (10.3%). Furthermore, the 24-hour urinary calcium was 74.70 mg/day and the urine calcium-creatinine ratio (Uca/cr) was 0.015. The Uca/cr could exclude hypercalciuric hypocalcemia. Furthermore, serum parathyroid hormone (PTH), alkaline phosphatase, 25-hydroxyvitamin D3m and aldosterone levels were 559 pg/ml, 275 IU/L, 9.74 ng/mL and 17.87 ng/dL, respectively. In addition, bone densimetry showed osteopenic features. This case showed severe metabolic acidosis with a slightly increased serum anion gap. Perhaps, the severe metabolic acidosis could result from aggravation of renal dysfunction as well as renal tubular acidosis. Fanconi syndrome was suspected because of hypophosphatemia, hypocalcemia, hypokalemia, and metabolic acidosis. However, supplementation of potassium citrate and calcium during 2 weeks recovered laboratory abnormalities, and her serum creatinine was 1.23 mg/dL. Persistent hypokalemia, hyperchloremic metabolic acidosis, nephrocalcinosis and a high urine pH suggested distal renal tubular acidosis (dRTA) rather than Fanconi syndrome. The renal tubular acidosis late after kidney transplantation can divide into three subtypes, such as classic (secretory), voltage-dependent (usually hyperkalemic) and rate-limited type.1 This case was thought as class dRTA due to persistent hypokalemia and high urine pH. Severe hypophosphatemia was thought to be caused by secondary hyperparathyroidism due to hypocalcemia related with dRTA and inhibition of tubular absorption of phosphate by cyclosporine. Metabolic acidosis and hypokalemia can directly or indirectly attenuate renal tubular calcium absorption and lead to hypocalcemia and secondary hyperparathyroidism.2 In addition, hyperparathyroidism and calcineurin inhibitors (CNIs) can attenuate phosphate reabsorption in proximal tubules.3 Therefore, the dRTA related with CNIs can often show hypocalcemia and hypophosphatemia independent of vitamin D. This case showed severe hypophosphatemia, as well as features of dRTA. Renal wasting of phosphate and hypocalcemia can aggravate decreases in bone density, particularly in setting of increased PTH levels and chronic metabolic acidosis. Therefore, early detection and correction of dRTA accompanied by severe hypophosphatemia may attenuate progression of bone disorders and allograft dysfunction in kidney-transplant patients.

FIG. 1
The white arrows indicate the margin of the allograft kidney and black arrow indicates the medullary calcified lesion in KUB.

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FIG. 2
Initial chest X-ray showed significant increase of pulmonary congestion on both lung fields.

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