Transient Hyperphosphatasemia in Pediatric Kidney Transplant Patients: An Often Unrecognized and Underappreciated Complication

Illustrative Case 

A 5-year-old male underwent a successful living-donor kidney transplantation as a result of focal segmental glomerulosclerosis. At the 6-month follow-up visit after the transplant, the patient exhibited an incidental finding of an extremely high serum alkaline phosphatase level of 2,800 IU/L without the presence of other laboratory abnormalities. Further testing confirmed the elevated alkaline phosphatase level. The patient’s serum alkaline phosphatase level was within the normal range prior to his kidney transplant and within the context of a well-controlled metabolic bone disease.

Clinical Questions

1. What is the most likely etiology of the elevated alkaline phosphatase in this patient?

2. What further investigation should be done?

3. How common is this condition in renal transplant patients, and what is the natural history of the disorder?

Transient hyperphosphatasemia (TH) is a benign condition in children characterized by laboratory findings of extremely elevated levels of serum alkaline phosphatase (> 1000 IU/L). Many physicians are unfamiliar with this condition, which can lead to unnecessary follow-up investigations and patient anxiety.

UPMC Children’s Hospital of Pittsburgh Division of Pediatric Nephrology former fellow Elisabeth Cole, MD, in conjunction with medical director of the UPMC Children’s pediatric kidney transplant program, Michael L. Moritz, MD, published findings from a new study1 that for the first time investigated the prevalence and natural history of TH in a large series of pediatric kidney transplant patients. The incidence of TH in this patient population has garnered little attention in the past, and its incidence rate has been unclear.

Summary of Key Study Findings

The research team found 11 cases of TH in 178 pediatric kidney transplant cases conducted at UPMC Children’s between the years 2008 and 2019. Interestingly, all of TH cases were  in patients < 12 years of age (12.8%) with a median age of 5 years. The analysis showed that the median time from kidney transplant to diagnosis of TH was 7 months, and the median length of time that TH persisted was 6 months. The median peak alkaline phosphatase level was  > 2300 IU/. The median glomerular filtration rate at the time of diagnosis of TH was 84 mL/min/1.73m2, and no patients had significant abnormalities of calcium and phosphorous metabolism or radiologic abnormalities. No patients had a recurrence of elevated alkaline phosphatase level following resolution.

The investigators conclude from their study that TH is common transplant complication in young children that manifests without symptoms during the first year following a pediatric kidney transplant, and it will typically resolve within a year from onset without recurrence.

Key Learnings for the Clinician

1. Transient hyperphosphatasemia (TH) is a relatively common benign finding following pediatric kidney transplantation.

2. TH primarily occurs in prepubertal children with an incidence of approximately 13% in children < 12 years of age.

3. TH typically presents within the first year after transplantation, and usually resolves within a year without recurrence.

4. TH is a clinical diagnosis and therefore no metabolic or radiologic investigations are indicated.

Study Reference

1. Cole EB, Anslow M, Fadakar P, Miyashita Y, Ganoza A, Moritz ML. Transient Hyperphosphatasemia Following Pediatric Kidney Transplant. Cureus. 2021 Sep 3; 13(9): e17697.