​How much do you know about kidney damage caused by gout?

*For medical professionals to read and refer to the summary of knowledge about gout-related kidney disease, full of dry goods~ Gout is a crystal-related arthropathy caused by the deposition of monosodium urate in the joints, which is related to purine metabolism disorders and/or reduced uric acid excretion The resulting hyperuricemia is directly related to metabolic rheumatism.

Gout can be complicated by kidney disease and other groups of metabolic syndrome, such as abdominal obesity, hyperlipidemia, hypertension, type 2 diabetes, and cardiovascular disease.

Primary gout is caused by genetic factors and environmental factors, and has a certain family susceptibility.

The origin of gout and kidney disease, let’s start with the pathogenesis of hyperuricemia and kidney damage~ Its occurrence mechanism mainly includes the direct and indirect damage of hyperuricemia that cause changes in the structure and function of the kidney, leading to end-stage kidney disease.
The occurrence of (see Figure 1).

Current research hotspots mainly focus on the indirect damage of hyperuricemia, including the damage of hyperuricemia to the vascular endothelium, activation of the renin-angiotensin-aldosterone system, stimulation of the inflammatory cascade, occurrence of metabolic syndrome, and Cause the renal tubular epithelial cells to transdifferentiate into renal interstitial fibroblasts, etc.
, and aggravate the progression of chronic kidney disease.

During the onset of gout, urate can be deposited in the urinary system, leading to acute or chronic urate nephropathy and uric acid urinary tract stones.

Figure 1.
The mutual promotion of hyperuricemia and chronic kidney disease (picture source: Chinese Journal of Nephrology, October 2014, Volume 30, Issue 10 "Research Progress on Hyperuricemia Kidney Damage") Next, we Let’s take a look at the common manifestations of gout-related kidney disease~ When chronic urate nephropathy persists with hyperuricemia, sodium urate crystals are deposited in the distal collecting duct and renal interstitium, leading to chronic tubular-interstitial nephritis and renal tubular atrophy.
Deformation, interstitial fibrosis, severe cases can cause glomerular ischemic sclerosis.

The clinical manifestations include decreased urine concentration, increased nocturia, low specific gravity urine, small molecule proteinuria, leukocyte urine, mild hematuria, and casts.

The late stage can lead to a decline in glomerular filtration function, renal insufficiency, hypertension, edema, anemia and other manifestations.

Uric acid urinary tract stones The concentration of uric acid in the urine increases in a state of supersaturation, which deposits and forms stones in the urinary system.
The incidence in gout patients is more than 20%, which can occur before the occurrence of gout arthritis.

Smaller stones may have no obvious symptoms, and larger ones may block the urinary tract, causing renal colic, hematuria, dysuria, urinary tract infection, renal pelvis dilatation, and hydrops.

Acute uric acid nephropathy blood and urine uric acid levels rise sharply, a large number of uric acid crystals are deposited in the renal tubules, collecting ducts, etc.
, causing acute urinary tract obstruction.

The clinical manifestations are oliguria, anuria, and acute renal failure; a large number of uric acid crystals can be seen in the urine.

This condition is rare in primary gout and is mostly caused by secondary causes such as malignant tumors and their radiotherapy and chemotherapy.

With the continuous update of the guidelines, the treatment strategies for gout combined with chronic kidney disease are becoming more standardized and perfect.
Finally, let’s learn about the relevant opinions of the recent domestic guidelines~The Chinese Journal of Rheumatology published the "Diagnosis and Treatment of Primary Gout" in 2011 "Guide", which mentions the treatment of gout-related kidney disease.

Gout-related kidney disease is an indication for uric acid-lowering drug therapy.

At present, commonly used uric acid-lowering drugs in China include inhibition of uric acid synthesis (allopurinol and febuxostat) and promotion of uric acid excretion (benzbromarone).

Both allopurinol and febuxostat inhibit the activity of xanthine oxidase and reduce the synthesis of uric acid, thereby reducing blood uric acid levels.

Benzbromarone promotes uric acid excretion and reduces blood uric acid levels by inhibiting renal tubular uric acid transporter-1 and inhibiting renal tubular uric acid reabsorption.

When chronic urate nephropathy requires diuresis, avoid the use of thiazide diuretics and furosemide that affect uric acid excretion.

For uric acid urinary tract stones, after reasonable uric acid-lowering treatment, most of them can be dissolved or discharged spontaneously, and those with large and fixed size can be used for extracorporeal impact lithotripsy and endoscopic stone removal.

For acute uric acid nephropathy, the sudden increase in blood uric acid should be quickly and effectively reduced.

The "Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout in China" issued by the Endocrinology Branch of the Chinese Medical Association in 2019 mentions the choice of uric acid-lowering drugs when hyperuricemia and gout are combined with chronic kidney disease.

It is recommended to select uric acid-lowering drugs and dosages individually according to the stage of chronic kidney disease.
It is recommended that uric acid-lowering drugs should be given priority to febuxostat when eGFR<30ml/min.

Chronic kidney disease is a common complication of patients with hyperuricemia and gout.
In order to avoid impaired renal function affecting drug metabolism and excretion, leading to drug accumulation and poisoning, experts at home and abroad suggest that uric acid-lowering drugs should be rationally selected according to renal function stages and adjusted in time The starting and maximum dose of the drug.

According to the "Guidelines for Diagnosis and Treatment of Gout" published by the Chinese Journal of Internal Medicine in 2020, based on the cardiovascular safety (CARES) study of febuxostat and allopurinol in gout patients with cardiovascular disease, febuxostat may cause complications Gout patients with cardiovascular disease have an increased risk of death.
Although there is no conclusion, those with a history of cardiovascular disease or new cardiovascular disease should be used with caution and follow-up monitoring to be alert to the occurrence of cardiovascular thrombotic events.

As a first-line treatment option, allopurinol should be cautious for patients with renal insufficiency.

HLA-B*5801 gene positive is a risk factor for adverse reactions to allopurinol.
It is recommended to perform HLA-B*5801 gene testing before treatment if conditions permit.

Conclusion: Since hyperuricemia can have no symptoms or signs, early diagnosis and treatment are easily overlooked.

As the incidence of hyperuricemia has been increasing year by year, it has received more and more attention now.

The damage of hyperuricemia to the kidney involves the participation of multiple mechanisms, which are greatly affected by environmental factors, and there are many risk factors, and are closely related to a variety of diseases.
More in-depth research is still needed in the future. References: 1.
Xu Dong, Zhu Xiaoxia, Zeng Xuejun, et al.
Standards for diagnosis and treatment of gout[J].
Chinese Journal of Internal Medicine, 2020,59(06):421-426.
2.
Rheumatology Branch of Chinese Medical Association.
Diagnosis and Treatment of Primary Gout Treatment guidelines[J].
Chinese Journal of Rheumatology,2011,15(6):410-413.
3.
Endocrinology Branch of Chinese Medical Association.
Guidelines for the diagnosis and treatment of hyperuricemia and gout in China (2019)[J].
Chinese Journal of Endocrinology and Metabolism ,2020,036(001):1-13.
4.
Shi Yingfeng, Wang Li, Xu Liuqing, Zhuang Shougang, Yan Haidong, Liu Na.
Research progress of hyperuricemia kidney damage[J].
Chinese Journal of Nephrology,2014(30):798.