A RARE CASE OF AN INHERITED CRYSTALLINE NEPHROPATHY

Introduction:

Crystalline nephropathies are a unique form of kidney disease. They can be classified by the etiology, for example- medication-induced, paraproteinemia-induced, and those associated with inherited disorders. They are frequently an underdiagnosed cause of kidney disease and are characterized by the pathological finding of intrarenal crystal deposition predominantly involving the tubulointerstitium.

Adenine phosphoribosyltransferase (APRT) deficiency is a disease with variable presentation.  The disease can manifest not only as recurrent kidney stones but also as crystalline nephropathy. Due to its rarity and variable clinical presentation, the diagnosis is often delayed by years after symptom onset, resulting in irretrievable kidney damage in many patients.  Here we present a case of a 45-year-old woman who presented with kidney dysfunction and pancytopenia. On kidney biopsy, the patient was diagnosed with 2,8- dihydroxyadenine (DHA) crystalline nephropathy

Methods:

A 45-year-old woman, born to consanguineous parents, with no known comorbidity, presented with complaints of pain in the left upper abdomen, early satiety, and occasional vomiting. There was no history of fever, trauma, jaundice, loose stools, or weight loss. On examination her blood pressure was normal. She had pallor. Abdominal examination revealed moderate splenomegaly. The rest of the examination was unremarkable

Results:

Investigations revealed pancytopenia and increased serum urea and creatinine.  Investigations are shown in Table 1.

Table 1: Table showing various investigations of the patient

Peripheral blood film showed pancytopenia with a reticulocyte production index of 1%. Bone marrow examination revealed dimorphic red cell morphology. No other abnormal cells or parasites were seen. Serum vitamin B12 was low, 123 pg/ml (190-950 pg/ml).

Urine examination revealed 1+ protein, no red blood cells or casts, and occasional white blood cells. 24-hour urine protein excretion was 406 mg. In view of kidney dysfunction, antinuclear antibodies, anti-myeloperoxidase antibodies, anti-proteinase 3, and anti-glomerular basement membrane antibodies were done, which were all negative. Serum complement levels were within normal limits. Serum electrophoresis, serum immunofixation, and free light chain assays were negative for paraprotein. Viral serology was negative for hepatitis B, C, and HIV. In view of unexplained kidney dysfunction, a CT-guided percutaneous kidney biopsy was done.

Light microscopy revealed 8 glomeruli, and none globally sclerosed. One glomerulus showed segmental tuft sclerosis. There was no evidence of any hypercellularity, deposition, or thrombi. Interstitial fibrosis and tubular atrophy (IFTA) was 8-10%. Tubules showed focal acute tubular injury. Several tubular lumina showed brown to brownish-green strongly birefringent crystals with focal giant cell reaction. These crystals are stained black with methenamine silver. Immunofluorescence was negative (Figure 1).

Urine examination under polarising light revealed DHA crystals. The final diagnosis of DHA crystalline nephropathy with concomitant Vitamin B12 deficiency was made in this patient and she was started on febuxostat and vitamin B12 supplementation.  Her kidney function improved after the treatment and her most recent serum creatinine decreased to 2 mg/dL. Also her pancytopenia resolved after vitamin B12 therapy.

Conclusions:

APRT deficiency can manifest at any age. The age of presentation varies from infancy to 8th decade of life. The disease is diagnosed late because it may remain asymptomatic for many years. Moreover, the lack of clinical suspicion, even in patients who have nephrolithiasis, further causes delay in diagnosis. True to its heterogeneous clinical presentation, our patient remained asymptomatic until 45 years of age. There was no personal or family history of urolithiasis. It has been seen that DHA nephropathy may present as an acute disease leading to renal failure in a few days or weeks or, more frequently, develop slowly and cause progressive decline of renal function during a period of several years. Acute renal failure may be triggered by dehydration, which causes urine supersaturation, and precipitation of DHA leading to acute kidney injury which if undiagnosed frequently leads to chronic kidney disease. Our patient who was previously asymptomatic presented with acute kidney injury. We hypothesize that recurrent vomiting lead to dehydration in our patient which caused DHA crystallization leading to kidney dysfunction. Treatment of APRT deficiency relies on allopurinol therapy, which acts by blocking xanthine oxidase. In patients with DHA nephropathy, allopurinol therapy usually allows renal function to stabilize or improve and prevents recurrence after renal transplantation. 

APRT deficiency should be considered in all cases of urolithiasis in children, recurrent urolithiasis (especially if the stones are radiolucent), and urolithiasis associated with unexplained renal dysfunction. Whenever possible, a thorough stone analysis should be conducted. Crystalluria can be particularly useful, especially when no stone is available for analysis. An APRT activity assay is useful when no stone is available and crystalluria cannot be studied in a patient with crystalline nephropathy, such as in cases of anuria, especially for patients undergoing a kidney transplant.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.