Renal outcomes of gout and hyperuricemia

doi:10.1016/0002-9343(79)90076-7

The American Journal of Medicine

Volume 67, Issue 1, July 1979, Pages 74-82

https://doi.org/10.1016/0002-9343(79)90076-7 Get rights and content

Abstract

Azotemia and urolithiasis as outcomes of gout or hyperuricemia were examined in several ways. Azotemia occurred in two (1.8 per cent) of 113 patients with asymptomatic hyperuricemia followed for eight years and in four (2.1 per cent) of 193 normouricemic control subjects; it was mild in all instances. Azotemia was also mild when it occurred in 168 patients with gout followed for 10 years and was unrelated to the degree of control of serum uric acid levels in these patients. Projected degrees of azotemia after 40 years of sustained hyperuricemia were mild and probably of no clinical significance until levels of serum uric acid reached 10 mg/100 ml in women and 13 mg/100 ml in men. Among 1,356 men, aged 60 to 69 years when serum uric acid was measured, follow-up for 10 years showed no death from renal failure that was attributable to hyperuricemia.

Risks of urolithiasis were small; approximately one stone per 295 patients per year in those with asymptomatic hyperuricemia compared with one stone per 852 patients per year in normouricemic control subjects, and one stone per 114 patients per year in those with established gout. Among the gouty patients, initial level of serum uric acid was not a predictor of stone; significantly more of those in whom urolithiasis developed were taking medication to lower serum uric acid levels than in those not taking such medicine, but the differences between those taking probenecid and those taking allopurinol were not significant. Also, among the gouty patients, the control of serum uric acid levels was similar in those in whom stones developed and in those in whom they did not.

It is concluded that (1) azotemia attributable to hyperuricemia is generally mild and probably of no clinical importance until serum uric acid levels reach 13 mg/100 ml in men and 10 mg/100 ml in women; and (2) the risk of urolithiasis is sufficiently low to justify awaiting the occurrence of the first stone before commencing drug therapy to lower serum uric acid levels.

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Cited by (137)

Creation of an adequate animal model of hyperuricemia (acute and chronic hyperuricemia); study of its reversibility and its maintenance
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Hyperuricemia is defined by the European Rheumatology Society as a uric acid level greater than 6 mg/dl (60 mg/l or 360 μmol/l). Our goal was to evaluate the hypouricemic effect of nettle. For this reason, we have first of all try to create an hyperuricemic animal model which is very suitable because at the level of literature there is not an exact model, there are many models and our objective is to set an adequate model.
An attempt has been made to test acute and chronic hyperuricemia by varying the duration and method of induction of potassium oxonate. Similarly, attempts have been made to induce chronic hyperuricemia through an animal and vegetable diet. The reversibility of hyperuricemia was tested with a maintenance protocol.
For the creation of the hyperuricemia model, it has been shown that acute hyperuricemia cannot be induced by short administration of potassium oxonate and persistent chronic hyperuricemia can be induced only after daily administration of oxonate of potassium by intraperitoneal injection for 15 days. Indeed, hyperuricemia was reversible after stopping the administration of potassium oxonate. The high-purine diet is also capable of inducing chronic hyperuricemia but to a less extent.
After creating an adequate model of hyperuricemia while setting the dose of potassium oxonate, route of administration and duration. A maintenance protocol was followed which subsequently made it possible to deduce that the daily administration of potassium oxonate must be continued to maintain the hyperuricemia.
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The association between uric acid (UA) on one side and systemic hypertension (Htn), dyslipidemia, glucose intolerance, overweight, fatty liver, renal disease and cardiovascular disease (CVD) on the other side is well recognized. However, the causal relationship between UA and these different clinical problems is still debatable. The recent years have witnessed hundreds of experimental and clinical trials that favored the opinion that UA is a probable player in the pathogenesis of these disease entities. These studies disclosed the strong association between hyperuricemia and metabolic syndrome (MS), obesity, Htn, type 2 diabetes mellitus (DM), non-alcoholic fatty liver disease, hypertriglyceridemia, acute kidney injury, chronic kidney disease (CKD), coronary heart disease (CHD), heart failure and increased mortality among cardiac and CKD patients. The association between UA and nephrolithiasis or preeclampsia is a non-debatable association. Recent experimental trials have disclosed different changes in enzyme activities induced by UA. Nitric oxide (NO) synthase, adenosine monophosphate kinase (AMPK), adenosine monophosphate dehydrogenase (AMPD), and nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase are affected by UA. These changes in enzymatic activities can lead to the observed biochemical and pathological changes associated with UA. The recent experimental, clinical, interventional, and epidemiologic trials favor the concept of a causative role of UA in the pathogenesis of MS, renal, and CVDs.
Clinical Features and Treatment of Gout
2016, Kelley and Firestein's Textbook of Rheumatology: Volumes 1-2, Tenth Edition
Epidemiology of gout
2014, Rheumatic Disease Clinics of North America
Citation Excerpt :
The association between gout and renal disease is complex and could be bidirectional, that is, although renal disease predisposes to the development of gout, gout and its treatment are themselves thought to lead to renal impairment and chronic kidney disease. Such associations have been recognized for many years, yet early studies were undertaken in specialist secondary care populations,74–76 which may not be representative of most patients with gout who are managed exclusively in primary care. More recently, 2 population-based epidemiologic studies have provided convincing evidence that renal disease is a risk factor for gout.
Serum uric acid and the risk of mortality during 23 years follow-up in the Scottish heart health extended cohort study
2014, Atherosclerosis
Citation Excerpt :
Despite accounting for only a small proportion of deaths (5.6%), we found that uric acid was highly predictive of kidney-related mortality independent of eGFR. These findings are distinct from other observational studies [61,62]. Although uric acid is highly associated with existing kidney injury [27,29], its relationship with kidney disease is controversial.
Elevated uric acid is a prevalent condition with controversial health consequences. Observational studies disagree with regard to the relationship of uric acid with mortality, and with factors modifying this relationship.
We examined the association of serum uric acid with mortality in 15,083 participants in the Scottish Heart Health Extended Cohort (SHHEC) Study.
Serum uric acid was measured at study enrollment. Death was ascertained using both the Scottish death register and record linkage.
During a median follow-up of 23 years, there were 3980 deaths. In Cox proportional hazards models with sexes combined, those in the highest fifth of uric acid had significantly greater mortality (HR 1.18, 95% CI: 1.06, 1.31) compared with the second fifth, after adjustment for traditional cardiovascular risk factors. This relationship was modified by sex (P-interaction = 0.002) with adjusted HRs of 1.69 (95% CI: 1.40, 2.04) and 0.99 (95% CI: 0.86, 1.14) in women and men, respectively. Compared with the second fifth, the highest fifth of uric acid was most associated with kidney-related death (HR: 2.08, 95% CI: 1.31, 3.32).
Elevated uric acid is associated with earlier mortality, especially in women. Future studies should evaluate mechanisms for these interactions and explore the strong association with renal-related mortality.
Management of asymptomatic hyperuricemia: Integrated Diabetes & Endocrine Academy (IDEA) consensus statement
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Citation Excerpt :
Untreated hyperuricemia is also a risk factor for renal calculi. In a study of 1386 subjects with asymptomatic hyperuricemia followed up for 10 years showed that 0.3% of patients with asymptomatic hyperuricemia developed renal calculi as compared to 0.1% in normouricemic patients [15]. A study on Korean population found that there was a linear relationship between elevated sUA and the risk of developing nephrolithiasis in males which was 1.06 (95% CI, 1.02–1.11) when sUA was 7.0–7.9 mg/dl, which increased to 1.72 (95% CI, 1.44–2.06) for a sUA ≥10 mg/dl [16].
The definition and management of asymptomatic hyperuricemia has been an area of controversy for many decades. Debate persists regarding the benefit of treating all cases of asymptomatic hyperuricemia and hence, unsurprisingly there are no clear clinical practice guidelines from our country.
Ten members consisting of eminent physicians, endocrinologists, nephrologist and a rheumatologist were selected by the Integrated Diabetes & Endocrine Academy (IDEA) for a closed meeting with the aim to come to a consensus.
A literature search was performed using PubMed and Cochrane library following which published articles in indexed peer review journals were selected.
Each participant voiced their opinion after reviewing the available data and a consensus was reached after three meetings by voting.
Recommendations were made on important areas such as definition, investigation and management of asymptomatic hyperuricemia.

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^☆: This research was supported by the Community Service Program of Kaiser Foundation Hospitals.

¹: From the Division of Rheumatology, Department of Medicine, Kaiser-Permanente Medical Center, San Francisco, California.

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Clinical studyRenal outcomes of gout and hyperuricemia☆

Abstract

Am J Med

Am J Med

Correlates and consequences of asymptomatic hyperuricemia

Arch Intern Med

Statistical Methods for Rates and Proportions

Hyperuricemia in health and disease

The kidney in gout

Medicine (Baltimore)

Rein goutteux et ponction-biopsie

J Urol Med Chir