Hematoxylin and eosin stain of the kidney showing brown deposits within the tubules of the kidney.
Urine microscopy showing brown crystals characteristic of APRT deficiency.
A 52-year-old woman presented for nephrologic consultation due to progressive chronic kidney failure. One year previously, her estimated glomerular filtration rate (eGFR) was 55 mL/min/1.73m2. She continued to follow up with her primary doctor and was found to have an eGFR of 40 mL/min/1.73m2 6 months later. The patient’s past medical history was significant for the spontaneous passage of 1 kidney stone 10 years previously. Five years ago, she had been seen in the emergency department for renal colic and again went home and passed a kidney stone. Family history was significant for a brother on dialysis who also had passed several kidney stones. Two other siblings and both parents had normal kidney function and no history of kidney stones. The patient is a professor of Icelandic history at a local university.
Physical examination revealed a healthy woman in no acute distress. Her blood pressure was 140/90 mm Hg with heart rate 50 bpm. Physical examination was unremarkable. Renal ultrasonography revealed no kidney stones or obstruction. The right kidney was 9.5 cm and the left kidney was 10 cm. A urinalysis performed by the laboratory revealed no urinary protein. Microscopy revealed an inactive sediment without blood or urine.
Given the fall in the patient’s eGFR, the nephrologist pursued kidney biopsy (Figure 1).
The nephrologist then performed his own urinalysis and saw similar brown crystals (Figure 2).
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This case was prepared by Anthony J Bleyer, MD, MS, Professor, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem NC. Dr Bleyer also serves on the editorial advisory board of Renal & Urology News.
- Cochran B, Kovačíková T, Kateřina Hodaňová K, et al. Case report: Chronic tubulointerstitial kidney disease in untreated adenine phosphoribosyl transferase (APRT) deficiency. Clin Nephrol. 2018; published online ahead print.
- Bollée G, Dollinger C, Boutaud L, et al.: Phenotype and genotype characterization of APRT deficiency. J Am Soc Nephrol. 2010;21:679-688.
- Runolfsdottir HL, Palsson R, Agustsdottir IM, et al. Kidney disease in APRT deficiency. Am J Kidney Dis. 2016;67:431-438.
Adenine phosphoribosyl transferase (APRT) deficiency is an autosomal recessive kidney disease caused by mutations in the corresponding gene.1,2 These mutations result in an inability to metabolize adenine and the development of elevated serum concentrations of 2,8-dihydroxy-adenine (DHA). DHA deposition leads to the formation of DHA kidney stones. In addition, DHA can precipitate within the renal tubules and lead to slowly progressive chronic kidney disease. Allopurinol prevents the conversion of adenine to DHA and is a very effective treatment for this disorder.
There are 4 common clinical presentations of this disorder:
- Some infants and young children present with massive DHA precipitation and stone formation leading to AKI. These patients are treated with stone removal and prescription of allopurinol with recovery of kidney function.
- Patients may present with kidney stones at any age. These stones are radio-dense and appear similar to calcium oxalate stones on radiologic tests. When the stone is passed or removed surgically, stone analysis will reveal the presence of DHA. However, if the stone is not sent for analysis, a diagnosis will not be made. A routine 24-hour urine collection to determine urinary stone constituents does NOT include an analysis for DHA and thus will not identify DHA stones.
- Patients develop chronic kidney failure and proceed to dialysis without a diagnosis being made. The patients then develop acute kidney injury post-transplant, undergo kidney biopsy, and DHA crystals are identified.
- Chronic kidney failure with little or no history of nephrolithiasis is becoming increasingly identified as a presentation of APRT deficiency.2,3 Patients without stones usually proceed to the need for dialysis between the ages of 38 and 65 years, with a mean age of end-stage renal disease onset of approximately 50 years.
As kidney failure from APRT deficiency is totally preventable with allopurinol, it is imperative to diagnose APRT deficiency. However, the diagnosis of this condition remains exceedingly difficult for the following reasons: a) many patients present with CKD of unknown cause, with a bland urinary sediment and low grade proteinuria. Most of these individuals will not undergo kidney biopsy. Only rarely will these patients have APRT deficiency; b) there is no urinary chemical test available for DHA; c) the best way to diagnose APRT deficiency is through identification of brown crystals in the urine. However, identification of these crystals requires careful evaluation. In most cases, nephrologists and laboratory technicians likewise will dismiss these crystals as debris in the urine. Only in retrospect are these crystals usually identified; d) concerted efforts to make sure all nephrologists can identify these crystals would be beneficial, but the rarity of this condition and the infrequency that a nephrologist will see this condition would make such training likely ineffective. Whole genome testing for causes of kidney failure may be a good alternative in the future.