A 58-year-old Thai woman developed end-stage renal disease from lupus nephritis and had been on hemodialysis for 2 years. She had markedly elevated serum intact parathyroid hormone (iPTH) of 113.8 pmol/L (1.6–6.9 pmol/L), increased serum calcium (Ca) of 2.65 mmol/L (2.10–2.37 mmol/L), and a phosphorus (P) level of 1.39 mmol/L (1.13–1.78 mmol/L). She was on Lanthanum carbonate, later converted to aluminum hydroxide, but was not on 1 alpha cholecalciferol, vitamin D analogs or calcium supplements. Daily urine output was 130 mL and her urine pH was high at 7.5 without urinary tract infection or sodium bicarbonate use. On 26 March 2014, our patient received a renal transplant from her haplo-identical and compatible blood group 35-year-old son. The radionuclide renogram demonstrated normal function of both of the donor’s kidneys. Pretransplant luminex crossmatch and panel reactive antibody tests were negative. Parathyroid sestamibi scan was not done because the doctor and patient did not want to do a parathyroidectomy. Cinacalcet (50 mg, once a day), a calcimimetic agent, and aluminum hydroxide (Al(OH)3) (1000 mg, three times a day) were prescribed for 2 days prior to transplantation. Serum Ca, P, and iPTH were decreased to 2.20, 1.74 mmol/L, and 92 pmol/L at the time of transplantation, respectively (Fig. 1). Induction therapy consisted of tacrolimus, mycophenolate mofetil, and steroid without interleukin-2 receptor antagonists as indicated in institutional protocol.
The patient had immediate graft function with 3000 mL of urine during day 1 after transplantation. However, urine output decreased to 1150 mL on day 2, with serum Ca, P, and iPTH levels increased to 2.33 mmol/L, 1.65 mmol/L, and 137.4 pmol/L, respectively (Fig. 1). Serum creatinine (SCr) was significantly elevated to 280 µmol/L on day 4. Doppler ultrasound of the transplanted kidney showed no hydronephrosis or vessel-related problems. Cinacalcet (25 mg) and Al(OH)3 were restarted again on day 2. Intravenous furosemide was also prescribed to enhance urine output. Tacrolimus level were 6.5–11.9 ng/mL. Hemodialysis was started and allograft biopsy was performed on day 2 after transplantation. The graft biopsy contained 25 glomeruli with no presence of glomerulitis or fibrin thrombi. There were, however, more than 20 foci of intratubular basophilic crystals (Fig. 2a). The crystals were positive for von Kossa stain, indicating calcium phosphate precipitation (Fig. 2b). Under polarized light, crystals showed no birefringence that is characteristic of calcium oxalate. Interestingly, all of the crystals were located in the distal tubules. There was no evidence of tubular injury or rejection. Immunofluorescence studies for IgG, IgA, IgM, C3, C1q, kappa, lambda, fibrinogen, and C4d were all negative. The histopathological diagnosis was nephrocalcinosis caused by intratubular precipitation of calcium phosphate crystals, most likely due to severe hyperparathyroidism. Urine pH before and 1 day after transplantation was 7.5 and 6.0, respectively. Our patient did not use any phosphate-containing laxatives. We withheld the cinacalcet for 24 h due to a high urine calcium/creatinine (Ca/Cr) ratio (0.57 mmol/mmol), but restarted later after the ratio was decreased to 0.08 and continued for 1 week without any change in immunosuppressive agents. SCr and iPTH declined to less than 176.8 µmol/L and 21.2 pmol/L, respectively, while serum Ca, P, and urine pH were maintained between 2.10–2.25 mg/dL, 0.87–1.32 mmol/L, and 5.5–6.0, respectively. Only one hemodialysis treatment was required.
At 2 years after transplantation, our patient has slightly high serum iPTH (13.8–21.2 pmol/L) and Ca (2.65 mmol/L) levels, with low level of serum P (0.84 mmol/L). Current immunosuppressive agents include tacrolimus, mycophenolate mofetil, and prednisolone.
