A 26-year-old woman presented to a nephrology office in Virginia for a reevaluation and second opinion regarding her history of kidney stones. This condition had led to uremia and acute kidney failure, requiring hemodialysis.
Her history was significant for recurrent kidney stones and infections, beginning at age 12. Over the next six years, she passed at least five stones and underwent three lithotripsy procedures; according to the patient, however, neither she nor her parents were ever informed of any decrease in her kidney function. The patient said she had been told that her stones were composed of calcium oxalate, and she was placed on potassium citrate therapy but did not take the medication on a regular basis.
After high school, she left the area for college and for several years she frequently and spontaneously passed gravel and stones. She was a runner in high school and college and had two children without experiencing any hypertension, proteinuria, or stone problems during her pregnancies. She had been treated for numerous recurrent urinary tract infections in outpatient clinics and private offices during the 10 years leading up to her current presentation. She had a distant history of a cholecystectomy.
In May 2009, the patient was hospitalized for a kidney infection and underwent cystoscopy with a finding of left ureteral obstruction caused by a stone. A stent was placed, followed by lithotripsy. Her serum creatinine level was measured at 2.2 mg/dL at that time (normal range, 0.6 to 1.5 mg/dL). In August 2009, she was treated again for a kidney infection; a right-sided stone obstruction was noted at that time, and again a stent was placed and lithotripsy was performed. Her serum creatinine level was then 3.3 mg/dL. During these episodes, the patient’s calcium level ranged from 8.2 to 10.1 mg/dL (normal, 4.5 to 5.2 mg/dL). Her phosphorus level was noted to range from 2.6 to 9.5 mg/dL (normal, 2.5 to 4.5 mg/dL). Her intact parathyroid level was 354 pg/mL (normal, 10 to 60 pg/mL). Thus, she had documented secondary hyperparathyroidism, which was treated with paricalcitol and a phosphate binder.
In February 2010, the patient was “feeling poorly” and was taken to a local hospital in South Carolina. She was admitted in acute renal failure and started on dialysis. She did well on hemodialysis with little to no fluid gain and good urine volume. She returned to Virginia temporarily for treatment, to be closer to her family and to prepare for kidney transplantation. She had family members who were willing to donate an organ.
The patient’s family history was negative for gout, kidney disease, or kidney stones. No family member was known to have hypertension, diabetes, or enuresis.
Physical examination showed a thin white woman with a runner’s lean look. She denied laxative use. Her blood pressure was measured at 120/84 mm Hg, and her pulse, 96 beats/min. Findings in the skin/head/eyes/ears/nose/throat exam were within normal limits except for the presence of contact lenses and a subclavicular dialysis indwelling catheter. Neither thyroid enlargement nor supraclavicular adenopathy was noted. Her heart rate was regular without murmurs. The abdomen was soft and nontender without rebound. The extremities showed no edema. Neurologic and vascular findings were intact.
The most recent 24-hour urine study showed a urine creatinine clearance of 4 mL/min (normal, 85 to 125 mL/min), despite a very large urine volume. Renal ultrasonography revealed two small kidneys that were highly echogenic, with evidence of medullary nephrocalcinosis without obstruction bilaterally.
The presentation of a woman with a kidney stone load high enough to cause full kidney failure by age 26 led the nephrologist to suspect the presence of hyperoxaluria type 1 (primary) or type 2 (secondary). The patient’s urine oxalate level was 158 mcmol/L (normal, < 57 mcmol/L), and her plasma oxalate level was 73 mcmol/L (normal, < 10 mcmol/L).
In response to the patient’s high blood and urine oxalate levels and her interest in kidney transplantation, genetic testing was performed to determine whether she had type 1 or type 2 hyperoxaluria. If she was found to have type 1 hyperoxaluria, she would need a liver transplant before her body showered a newly transplanted kidney with stones, causing recurrent kidney failure.
Discussion
Primary hyperoxaluria (PHO) type 1 is a very rare recessive hereditary disease with a prevalence of one to three cases per one million persons.1 Patients typically present with kidney stones at an early age (as did the case patient) or in full kidney failure. It is calculated that PHO is responsible for 1% of all end-stage renal disease among pediatric patients.2,3