Patient 2 is a 66-year-old woman with a history of Crohn's disease and an ileostomy. She presented to the emergency department with profound, debilitating weakness 22 days following her regularly scheduled dose of denosumab. She had received biannual treatments for 5 years at this point. Neurological exam revealed 5-/5 strength in all extremities. She exhibited mild psychomotor slowing. Chvostek sign was absent. Serum chemistries demonstrated a serum total calcium of 4.5 mg/dL, magnesium 1.6 mg/dL, phosphorous of <1.0 mg/dL, ionized calcium 0.89 mmol/L and intact PTH 2,356 pg/mL. 25-hydroxy vitamin D was 4 ng/mL. The last prior vitamin D measurement in our records was 2 years prior and measured <4.0 ng/mL. This measurement was drawn 2 weeks after a dose of denosumab was administered, and the importance of supplementation was reinforced to the patient at that time. This patient had no evidence of CKD with an eGFR of 101 mL/min/1.72m2 and a serum creatinine of 0.7 mg/dL. It should be noted that patient 2 had a history of mild, asymptomatic hypocalcemia (with values ranging from 6.0 to 10.4 mg/dL) in the year prior to admission with an intact PTH ranging between 300 and 500 pg/mL and mildly low serum phosphorous levels. Vitamin D deficiency limiting intestinal phosphorous absorption and denosumab-induced elevated PTH levels causing phosphaturia would account for hypophosphatemia. Patients with vitamin D deficiency in the absence of denosumab treatment typically have mildly elevated PTH levels, though generally no higher than 110 pg/mL []. The laboratory findings upon admission of both patients are presented in Table .
A 17-year-old 6-week-pregnant female was admitted for nausea and vomiting for a suspected morning sickness. At admission patient was found to have a mild fever of 99 F, hemoglobin of 6.5 mg/dL, and serum creatinine at 6.47 mg/dL. Baseline creatinine six months earlier was 0.6 mg/dL. A thrombotic thrombocytopenic purpura was suspected despite normal platelets and hence she was admitted to the hospital for further workup. Vital signs at admission were temperature of 99 F, heart rate of 90–100 beats per minute, respiratory rate of 14 cycles per minute, and blood pressure of 120–130/80 s. Physical exam was consistent with a normal female who was moderately built without any evidence of fluid overload like raised jugular venous distension and facial or leg edema. Heart and lung exam were within normal limits. Patient's neurological exam was intact. Laboratory findings were as follows: hemoglobin 6.51 mg/dL, white blood cell count 10.3 k/mm3, platelets 384 k/mm3, sodium 136 mEq/L, potassium 4.4 mEq/L, chloride 107 mEq/L, bicarbonate 21 mEq/L, blood urea nitrogen 26 mg/dL, and creatinine 6.47 mg/dL. Iron studies showed iron deficiency anemia with iron of 25 mcg/dL, total iron binding capacity of 185 mcg/dL, iron saturation of 14%, and transferrin of 132 mg/dL. Urine analysis at admission showed urine pH of 6.5, specific gravity of 1.009, urine protein of 2+, and urine blood of 3+ with too numerous RBCs to count; urine glucose, ketones, bilirubin, and leukocyte esterase were all negative. Other tests that were ordered were antiglomerular basement membrane antibodies which were high at 156 units. Complement C3 and C4 levels were high at 195 and 57, respectively. Antineutrophil antibody, antineutrophil cytoplasmic antibody, antiproteinase 3, anti-Smith, and ds DNA were negative. Other miscellaneous lab tests like HIV antibody, hepatitis A IgM antibody, hepatitis B surface antigen, hepatitis B core IgM antibody, hepatitis C antibody, and antistreptolysin O Ab were all negative.\nOn the second day of hospitalization the patient underwent a kidney biopsy for a suspected anti-GBM disease. The preliminary biopsy results based on the hematoxylin and eosin stains showed acute necrotizing and crescentic glomerulonephritis. Final pathology results showed acute crescentic glomerulonephritis with no globally obsolescent glomeruli, moderate interstitial inflammation, and mild fibrosis. The final images of the pathology slides are shown in Figures and .\nPatient was given 2 units of PRBC after admission with a posttransfusion Hb at 8.9 mg/dL. Peripheral smear did not show any schistocytes and hence the diagnosis of TTP was ruled out. All the labs and pathology suggested acute anti-GBM disease. On hospital day 3 plasmapheresis and high dose methylprednisolone at 1 gm/day were begun. See for creatinine trend. Creatinine peaked to 7.48 on day 5 and the patient was slowly becoming oliguric, showing sign of fluid overload with pedal edema and lung crackles on physical exam and hence was initiated on intermittent hemodialysis on day 5 of hospitalization. Patient received a total of 3 doses of methylprednisolone at 1 gm/day and then was started on prednisone at 60 mg/day from day 4.\nTo prevent further renal injury the option of adding cyclophosphamide was discussed but was not done due to possible fetal adverse outcomes. On day 17 of hospitalization the patient had a spontaneous abortion. After abortion cyclophosphamide was not started due to patient's request and hence she was managed with plasmapheresis and high dose prednisone. The plasmapheresis sessions were started on day 3 and continued daily until discharge (day 25). Traditional plasmapheresis with albumin replacement and sometimes 70% albumin with 30% normal saline replacement that lasted for 3 hours every day was the technique used. She was never started on cyclophosphamide and slowly became hemodialysis independent in about 2 months from discharge. At about 6 months from discharge the patient lost to follow up. It was deemed that the acute anti-GBM flare-up was pregnancy related.