The Gouty Kidney: A Reappraisal

Abstract

This review re-examines the role of crystal deposition in the kidney in view of recent clinical and experimental findings. The involvement of the renal system in gout seems frequent. Indeed, recent studies showed that approximately 25% of patients with gout experience renal failure, defined by estimated glomerular filtration rate <60 mL/min/1.73 m2. The pathophysiology is complex and involves several factors, their respective roles being difficult to dissect. The role of crystal deposition in the kidney was the first suspected, and the concept of gouty microcrystalline nephropathy, also called gouty nephropathy, has been popular, supported by early autopsy studies demonstrating uric acid and urate crystal deposition in the renal medulla of patients with gout, together with features of tubulointerstitial nephritis. Crystal deposition was first considered an important source of renal involvement in gout. After the introduction of urate-lowering drugs and the performance of kidney biopsies, which mainly involved the renal cortex and did not reveal much crystal deposition but rather vascular changes, this concept has been criticized and even dismissed. Thereafter, kidney involvement in gout was considered mainly vascular, related to hypertension and associated comorbidities and later to hyperuricemia. The toxic effects of non-steroidal anti-inflammatory drugs is also an important factor. Modern imaging, especially renal ultrasonography, allows for atraumatic exploration of the kidney and has revealed hyperechogenicity of the renal medulla, suggesting crystalline deposits, in approximately one-third of patients with tophaceous gout. Experimental models of gouty nephropathy have recently demonstrated the pathogenic role of microcrystal deposition in the collecting ducts and parenchyma of the renal medulla. Taken together, these recent findings lead to the re-examination of the pathogenic role of crystal deposition in the renal medulla and testing the effect of urate-lowering drugs on renal features of gouty patients with evidence of renal crystal deposition.

Gout and Cardiovascular Disease: Mechanisms, Risk Estimations, and the Impact of Therapies

“…This assessment should include an interview to assess the patient's history of CVD, including non-atherosclerotic disorders such as atrial fibrillation or heart valve lesions, as well as a physical exam to record blood pressure, body mass index, and subcutaneous tophi. Laboratory tests measuring fasting lipids and glucose, glycated haemoglobin, and the urinary albumin/creatinine ratio (a marker of target organ damage that can also indicate gouty renal disease [135]), is worthwhile. Based on the findings, cardiovascular risk should be estimated according to the patient's CVD background, renal function, and risk assessment tools (FHS or SCORE).…”

Prediction of renal and cardiometabolic outcomes in gout during urate‐lowering therapy by sonography

“…Renal diseases and cardiometabolic events frequently occur in patients with gout, derived from crystal‐induced inflammation, hyperuricemia, and concurrent comorbidities, leading to significant morbidity and mortality 18–20 . Renal crystal deposition may also have a direct, detrimental role, 21 while consistent artery wall deposition remains a matter of debate 22–24 . In order to tailor preventive strategies, it would be of high interest to identify baseline predictors of subsequent renal and cardiovascular events.…”