3 Types of Gout Not 2 is my review of gout studies showing there is an extra type of gout. Because 2 types of gout causes have been recognized in the past: over-producers and under-excreters. But now we should consider a third reason for gout.

This is important as it is the foundation of all gout treatment. If you change that foundation, you create a new view of gout treatment, with new opportunities.

This is a layman’s summary of a report that changes the foundation of gout causes. It is a highly technical investigation, and I will omit much of the scientific detail from this review. The full review is widely available on the Internet, so simply search for the title.

Gout Causes Report

Title:
Decreased extra-renal urate excretion is a common cause of hyperuricemia
Authors:
Ichida K, Matsuo H, Takada T, Nakayama A, Murakami K, Shimizu T, Yamanashi Y, Kasuga H, Nakashima H, Nakamura T, Takada Y, Kawamura Y, Inoue H, Okada C, Utsumi Y, Ikebuchi Y, Ito K, Nakamura M, Shinohara Y, Hosoyamada M, Sakurai Y, Shinomiya N, Hosoya T, Suzuki H.
Published:
Nat Commun. 2012 Apr 3;3:764.

This gout causes report is not presented in the usual methods, results, conclusion sequence, and I have followed the sub-headings used.

Extra-renal urate excretion is the excretion of uric acid through pathways other than the kidney – primarily the gut.

Hyperuricemia is the British English spelling of hyperuricemia, meaning high uric acid. This usually is 7mg/dL (0.42mmol/L) or higher.

Gout Causes Report Introduction

The report introduces high uric acid as the reason for gout and some kidney stones, noting that it also increases kidney and heart disease.[1,2]. It explains that humans do not have the enzyme, uricase, that other mammals degrade uric acid with.[3] Therefore we have two pathways to remove excess uric acid, with two-thirds excreted through the kidneys, leaving one-third non-kidney extraction that is mainly through the gut.[4,5] The cause of high uric acid has been described as either overproduction or underexcretion, but underexcretion has always referred to the kidneys alone.[6-9]

The kidney is the main regulator of uric acid in the blood, with the net extraction rate determined by the amount of uric acid extracted from the blood, less the amount that is returned to the blood. These processes are controlled by genes, and the report describes details of several genes involved in the control of uric acid. Gout is commonly caused by a combination of more than one genetic disorder.[10-21]

The study investigates the relationship between a genetic disorder (specifically, ABCG2 dysfunction) and uric acid excretion in humans with high uric acid and in mice.

Gout Causes Report Results

In the human analysis, 644 males were analyzed. They were grouped according to the specific genetic disorder[21] as full function, 3/4 function (mild dysfunction), 1/2 function (moderate dysfunction) and up to 1/4 function (severe dysfunction). 75.6% of these high uric acid patients had the genetic disorder.

Further analysis revealed that the disorder was associated with higher uric acid excretion through the kidneys. However, it was also associated with uric acid overproduction. The authors note a paradox in the conventional overproducer/underexcreter view, suggesting that excretion outside the kidney would account for this.

The investigators were loath to dissect their humans to investigate uric acid excretion in the gut, and so they introduced a mouse model.[22] They satisfied themselves that the profile for uric acid excretion through the kidneys matched the human model, then turned to analyze uric acid excretion through the gut. They found that the genetic disorder significantly decreased uric acid excretion through the gut. They examined excretion through the bile duct and confirmed earlier investigations that it was insignificant.[23] For patients with this genetic disorder, increased uric acid in the blood, despite higher uric acid excretion through the kidneys, is explained by decreased uric acid excretion from the gut.

Gout Causes Report Discussion

The investigation shows that this genetic disorder, previously assumed to cause overproduction of uric acid, is actually responsible for decreased non-kidney excretion.

They apply this finding to other investigations.[24-28]

In keeping with the importance of this new view of uric acid control, the authors include a lengthy interpretation of the concept noting that most overproduction explanations have been inadequate.[29] They suggest that high uric acid should now be reclassified, with overproduction split between non-kidney underexcretion and genuine overproduction.

This new concept will help pinpoint the reasons for hyperuricemia more accurately and provide a more effective therapeutic strategy for hyperuricemia and gout, leading to a good model of personalized medicine for common diseases.

Gout Causes Report Methods

The report ends with an extensive explanation of the methods used in different parts of the investigation.[30-41] The description of measuring uric acid excretion through the gut explains why the investigators were loath to test their theories on humans.

Gout Causes Report: Next Steps

Development of Gout Overview
Types of gout from uric acid: overproduction in the liver; and underexcretion from the kidneys or gut

What does this new classification of types of gout causes mean to us gout patients?

In the short-term, probably very little, though it might see renewed interest in Montmorillonite (Calcium Bentonite clay). I’m still waiting for some more research on Montmorillonite, but you can see some facts on my uricase page. Long-term, we should hope to see new approaches to gout control as researchers target gout caused by under-excretion of uric acid by the gut.

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Gout Causes Report References

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