Hyperuricemia can affect the kidneys, and it is clinically manifested as proteinuria, uric acid stones, etc. Its pathological manifestation is urate deposition in renal interstitial and renal tubular , and birefringent needle-shaped urate crystals can be seen. The above crystals cause infiltration of renal interstitial and mononuclear cells around the renal tubular, resulting in necrosis of tubular epithelial cells, tubular atrophy, lumen occlusion, interstitial fibrosis, and even nephron necrosis¹.
serum amyloid A (AA) amyloidosis is mainly related to the immune system and is commonly found in patients with chronic inflammatory arthritis, chronic sepsis, periodic fever syndrome, and malignant tumors. Previous studies and cases show that AA amyloidosis rarely occurs in joints with hyperuricemia and arthritis.
On November 8, 2022, doctors from Turkey found that patients with kidney disease with hyperuricemia may develop AA amyloidosis. Compared with the pathological changes in urate crystallization, the treatment methods of AA amyloid gouty nephropathy have certain special characteristics².
case report
basic information: the patient is male, 28 years old. Due to swelling of the right knee and difficulty walking, he was admitted to the hospital 10 days ago.
has a medical history: 3 years ago, the right big toe was swollen, painful, and exudated, and was diagnosed with hyperuricemia. To date, patients have repeated hyperuricemia and arthritis, and non-steroidal anti-inflammatory drugs are used in pain.
Physical examination: right hand (first, second, fourth) and left hand (second, third, fifth) finger arthritis, multiple gout stones on both hands, and edema of the right knee joint. No angiokeratoma or neuropathy was detected, but there were mild intellectual disability. Other test results are normal.
Family history: Family analysis shows that the patient meets X linkage recessive genetic , and his brother has premature hyperuricemia and gouty nephropathy .
laboratory examination: blood uric acid 12.3mg/dL (reference range: 3.4~7.0mg/dL), erythrocyte sedimentation rate 64mm/h (0~10mm/h), C reactive protein 25.5mg/L (0.0~5.0mg/L), estimated glomerular filtration rate (eGFR) >90ml/min/1.73㎡ (>60 ml/min/1.73㎡), serum creatinine 0.69mg/dL (0.7~1.20mg/dL), asparagus aminotransferase 17U/L (0~37U/L), alanine aminotransferase 29U/L (0~41U/L), cholesterol 185mg/dL (130~199mg/dL). Both anti-cyclic citrulline peptide and rheumatoid factor were negative.
urine test: urine protein 2+, 24h urine protein 2230.5mg (0~167mg/24h), urine albumin 1874.7mg/24h (0~30mg/24h), uric acid in urine 16.5mg/dL (37~92mg/dL), urine density 1007 (1015~1025), urine pH value 5.5 (5.5~8).
The patient underwent genetic screening due to the patient's family history of hyperuricemia and renal disease, but the results of mutation tests for hypoxanthine phosphoribotransferase 1 (HPRT1) and uromodulin (UMOD) genes were negative.
imaging examination: abdominal ultrasound indicates strong echo foci in the pyramidal area of both renal, suggesting medullary sponge kidney.
renal biopsy results: Due to a large amount of proteinuria, the patient underwent a renal biopsy. A total of 24 glomeruluses were collected, of which 11 were necrotic. The appearance of intragromerules and segmental eosinophilic aggregation of arterioles (Fig. 1 A), crystal violet and Congo red staining were positive (Fig. 1 B), and the chemical labeling of amyloid immunoprotein confirmed AA amyloidosis (Fig. 1 C). Immunofluorescence showed no accumulation, mild chronic inflammatory cell infiltration in other areas, focal interstitial mild fibrosis, and mild tubular atrophy.
Figure 1 Renal biopsy results
was initially diagnosed with gouty nephropathy. The patient took colchicine (2×0.5mg), allopurinol (1×300mg) and prednisolone (1×8mg) before hospitalization. However, because the patient was in the acute stage of hyperuricemia, allopurinol was stopped and allopurinol was started to take febutasi (1×80mg). In addition, due to insufficient uric acid excretion, the patient received losartan (1×50 mg). Shortly after receiving treatment, the acute phase of biomarker subsided, C-reactive protein 2.5 mg/L, erythrocyte sedimentation rate was 31 mm/h, and no complications occurred².
Discussion
Although inflammatory arthritis is a common complication of hyperuricemia, AA amyloidosis rarely occurs in patients with hyperuricemia.There are two main reasons for this condition. First, compared with other chronic inflammations, inflammation caused by hyperuricemia is usually short-term and intense. Second, drugs that patients with hyperuricemia often take, such as colchicine, have the ability to prevent AA amyloid transformation. Therefore, AA amyloidosis is rarely seen in patients with hyperuricemia.
Review of previous literatures found that there are currently only 16 cases (if this case is included, there are 17 cases) in patients with hyperuricemia who have AA amyloid changes. Their age range is 23 to 85 years old, most of them are male (15/16), and the duration of hyperuricemia ranges from 1 to 36 years. Most patients (12/16) have an AA amyloid change location in the kidneys. It is worth noting that proteinuria is the earliest and most common clinical symptom of AA amyloid transformation, and up to 97% of patients with AA amyloid transformation may have proteinuria.
cases have shown that uric acid crystals can cause hematuria and infection in patients, which in turn causes medullary sponge kidney and AA amyloid degeneration. However, in this case, the patient did not experience hematuria and kidney repeated infection. Therefore, repeated renal infections caused by hyperuric acid crystals may not be related to AA amyloidosis.
Since patients experience AA amyloidosis, patients also need to receive related treatment for AA amyloidosis. There are two major categories of basic therapies for the treatment of AA amyloidosis, colchicine and cytokine blockers (such as anti-interleukin-1, anti-interleukin-6, etc.). Recently, scholars have shown that cannamab combined with prednisone, colchicine and allopurinol can be used as drugs for patients with AA amyloid lesions and hyperuricemia.
In short, patients with hyperuricemia rarely experience AA amyloid lesions, but this does not mean that it is impossible. It is worth noting that for patients with AA amyloid gouty nephropathy, the treatment method of nephropathy may be different from those with gouty nephropathy with high uric acid crystals².
References:
1. Yuan Ying. Gouty nephropathy[J]. Shandong Medicine, 2010.
2. Yilmaz F, Acikalin MF, Kasifoglu T. Amyloid A amyloidosis on medullary sponge kidney in a 28-year-old male with gout: A case report and literature review. Int J Rheum Dis. 2022 Nov 8.
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