Sandra Amaral, MD, MHS, Rebecca L. Ruebner, MD, MSCE, Benjamin Lewis Laskin, MD, MS
An 8-year-old male with a history of bilateral ptosis and narrow external auditory canals presented to his pediatrician with a 5-month history of decreased appetite and weight loss. He also complained of fatigue, polyuria, and polydipsia. He was on no medications, and there was no significant family history. One year prior, his weight and height were at the 10th percentile for age. On presentation, his weight and height had both fallen below the 5th percentile. He had normal blood pressure. Urinalysis had a specific gravity of 1.005 with no blood, protein, or glucose. Metabolic panel was significant for sodium 142 mmol/L, potassium 3.9 mmol/L, chloride 102 mmol/L, bicarbonate 21 mmol/L, BUN 94 mg/dL, creatinine 5.4 mg/dL, calcium 7.9 mg/dL, and phosphorous 8.2 mg/dL. Additional labs included hemoglobin 7.4 g/dL with normal mean corpuscular volume and parathyroid hormone level 1289 pg/ mL. Renal ultrasound showed normal size kidneys with increased echogenicity bilaterally.
Discussion: This patient was found to have kidney failure due to juvenile nephronophthisis. Given his history of poor growth, fatigue, and polyuria/polydipsia, chronic kidney disease (CKD) is more likely than an acute kidney injury (AKI). The presence of normocytic anemia (from impaired renal production of erythropoietin) and hyperparathyroidism (from hyperphosphatemia and impaired renal activation of vitamin D) also support an underlying chronic kidney disease process. The creatinine of 5.4 mg/dL corresponds to an estimated glomerular filtration rate of <10 mL/min/1.73 m2, classifying him as end-stage kidney disease (ESKD). His primary care practice promptly referred him to CHOP Nephrology.
Causes of CKD in children include congenital and acquired disorders. In this case, congenital anomalies are ruled out by a normal kidney ultrasound. The history of polyuria/polydipsia and the low urine specific gravity suggest impaired renal concentrating ability. The dilute urine without hematuria or proteinuria is consistent with a “bland urine” typical for tubulointerstitial nephritis (TIN) rather than an underlying glomerular disorder. As the underlying process appears to be both chronic and a tubulointerstitial process, one must consider the causes of chronic TIN in the different diagnosis. Chronic TIN can be secondary to inflammatory, autoimmune, and genetic conditions, including a group of disorders known as nephronophthisis (NPHP). NPHP is an autosomal recessive disorder affecting proteins involved in primary cilia function and is characterized by early onset CKD with progression to ESKD by 20 years of age. Extrarenal manifestations are present in 10% to 20% of patients, and include retinitis pigmentosa, hepatic fibrosis, neurologic abnormalities, and skeletal defects. NPHP can occur as an isolated kidney process, or as part of Joubert, Meckel-Gruber, Senior-Loken, and Cogan syndromes.
A kidney biopsy showed chronic interstitial fibrosis. An ophthalmologic examination ruled out entities like cystinosis or the syndrome of TIN and uveitis. Genetic testing identified a homozygous deletion in NPHP1, confirming the final diagnosis of juvenile nephronophthisis.
Next, the CHOP Nephrology team, including physicians, nurse practitioners, social workers, psychologists, pharmacists, and dialysis nurses, and the patient’s caregivers had extensive discussions to review renal replacement therapy treatment options, namely dialysis vs. transplant.
Physician-scientists at CHOP participate in a number of clinical studies that can help families assess the long-term outcomes of kidney disease, and which form of renal replacement therapy is best for their children. One recent study explored how outcomes have changed for children with ESKD over the last two decades. Despite improvements in overall mortality rates for children with kidney failure on dialysis in the United States, children on dialysis experience mortality rates at least 30 times higher than healthy children. Dialysis is associated with an increased risk for infection, anemia, impaired growth, and cardiovascular disease. For all these reasons, early kidney transplantation is the preferred renal replacement therapy for most children. Children who are transplanted grow better, learn better, and can lead more normal lives compared with children on dialysis.
The evaluation of a potential kidney transplant recipient and identification of a suitable donor take time. Thus, prompt recognition of disease and early referral to pediatric nephrology are crucial. First, transplant candidates must be evaluated by a multidisciplinary team and often must undergo special laboratory studies and imaging to complete their work-up. The ability of the patient and/or caregiver to adhere to the medical regimen of life-long immunosuppressive medications is an important consideration. Vaccinations must also be up to date. Second, we explore potential living kidney donors or the necessity of being placed on the waiting list for a deceased donor. When possible, living related donation is preferred as it generally permits better immunocompatibility. However, children who are placed on the national deceased donor waiting list do receive pediatric priority for kidney donors younger than 35 years of age.
This patient was promptly evaluated for transplant eligibility. His mother was found to be an excellent, healthy, and immunocompatible donor. The child received a preemptive kidney transplant within a few months of his diagnosis. He is now thriving, playing baseball, and enjoying his new “gift of life.”
References and Suggested Readings
Mitsnefes MM, Laskin BL, Dahhou M, Zhang X, Foster BJ. Mortality risk among children initially treated with dialysis for end-stage kidney disease, 1990-2010. JAMA. 2013;309(18):1921-1929.
To make a referral to or learn more about Nephrology, the Pediatric Stone Center and the Hypertension and Vascular Evaluation (HAVE) Program at CHOP, call 215-590-2449.