. Author has the wrong there for CVD, blaming it on salt, fat, and meat, which the other primates don’t get, and uses the Maori and Aborigines of Australia as examples of those with gout, while missing fructose.

http://europepmc.org/abstract/med/15660328

Seminars in Nephrology Volume 25, Issue 1, January 2005, Pages 3-8

Uric acid, evolution and primitive cultures

Hypertension is epidemic and currently affects 25% of the world’s population and is a major cause of stroke, congestive heart failure, and end-stage renal disease. Interestingly, there is evidence that the increased frequency of hypertension is a recent event in human history and correlates with dietary changes associated with Westernization.[1] In this article, we review the evidence that links uric acid to the cause and epidemiology of hypertension. Specifically, we review the evidence that the mutation of uricase that occurred in the Miocene that resulted in a higher serum uric acid in humans compared with most other mammals may have occurred as a means to increase blood pressure in early hominoids in response to a low-sodium and low-purine diet. [Suspect because higher blood pressure doesn’t have a survival value, though increased antioxidant function of uric acid dose. Secondly there is a balance act between harm caused by uric acid and benefit. The atherogenic role of the high fructose western diet is what has raised BP.] We then review the evidence that the epidemic of hypertension that evolved with Westernization was associated with an increase in the intake of red meat with a marked increase in serum uric acid levels. Indeed, gout and hyperuricemia should be considered a part of the obesity, type 2 diabetes, and hypertension epidemic that is occurring worldwide. Although other mechanisms certainly contribute to the pathogenesis of hypertension, the possibility that serum uric acid level may have a major role is suggested by these studies.

FROM FULL PDF https://s3.amazonaws.com/academia.edu.documents/46082733/Uric_acid_evolution_and_primitive_cultur20160530-19206-vh4w49.pdf?AWSAccessKeyId=AKIAIWOWYYGZ2Y53UL3A&Expires=1515438682&Signature=ozw8c2iZMzlYdKHQ0SACGy89ehY%3D&response-content-disposition=inline%3B%20filename%3DUric_acid_evolution_and_primitive_cultur.pdf

Serum uric acid levels are therefore low (0.5– 2.0 mg/dL) in most mammals. However, during the Miocene epoch (8 –20 million years ago) parallel mutations occurred in our hominoid ancestors that first affected the promoter region and later the whole gene, eventually resulting in complete loss of uricase.6 As a consequence, humans and the Great Apes have higher uric acid levels than most other mammals. In addition, some species of New World monkeys also lost uricase, and many Old World monkeys have lower uricase activity than other mammals,7 suggesting similar processes in these species. The stepwise loss of uricase may have allowed adaptation to the loss of this important gene because the sudden knockout of uricase in mice is lethal owing to dramatic increases in serum uric acid levels that cause acute urate nephropathy and renal failure.8 One likely adaptation was a decrease in xanthine oxidase activity because humans have only 1% activity of this enzyme compared with other mammals.9 It also is possible that alterations in transport mechanisms involved in renal urate excretion may have occurred.

2 A similar antioxidant hypothesis suggests that the uricase mutation occurred as a consequence of the loss of our ability to synthesize vitamin C.13 Our ability to synthesize vitamin C was lost approximately 40 to 50 million years ago owing to a mutation in L-gulono-lactone oxidase.14 This mutation may have occurred because the primates of that period were largely fruit eating and hence were ingesting large quantities of vitamin C, making the mutation harmless.15 However, later there was a selection advantage for those species that could increase their antioxidants, and this was provided by the uricase mutation….

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

http://www.sciencedirect.com/science/article/pii/S0270929504001913 Seminars in Nephrology January 2005 43-49

Uric acid and chronic renal disease: Possible implication of hyperuricemia on progression of renal disease

Abstract

Although hyperuricemia has long been associated with renal disease, uric acid has not been considered as a true mediator of progression of renal disease. The observation that hyperuricemia commonly is associated with other risk factors of cardiovascular and renal disease, especially hypertension, has made it difficult to dissect the effect of uric acid itself. However, recent epidemiologic evidence suggests a significant and independent association between the level of serum uric acid and renal disease progression with beneficial effect of decreasing uric acid levels. Furthermore, our experimental data using hyperuricemic animals and cultured cells have provided robust evidence regarding the role of uric acid on progression of renal disease. Hyperuricemia increased systemic blood pressure, proteinuria, renal dysfunction, vascular disease, and progressive renal scarring in rats. Recent data also suggest hyperuricemia may be one of the key and previously unknown mechanisms for the activation of the renin-angiotensin and cyclooxygenase-2 (COX-2) systems in progressive renal disease. Although we must be cautious in the interpretation of animal models to human disease, these studies provide a mechanism to explain epidemiologic data that show uric acid is an independent risk factor for renal progression. Although there is no concrete evidence yet that uric acid bears a causal or reversible relationship to progressive renal disease in humans, it is time to reevaluate the implication of hyperuricemia as an important player for progression of renal disease and to try to find safe and reasonable therapeutic modalities in individual patients based on their clinical data, medication history, and the presence of cardiovascular complications.

From full PDF Seminar in Nephrology 2005, Supra. 43-49

Increased production of uric acid is the result of interference, by a product of fructose metabolism, in purine metabolism.

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

http://www.sciencedirect.com/science/article/pii/S0270929504001470

Pages 19-24, supra. Seminars in Nephrology, Jan. 2005

Hemodynamics of hyperuricemia

Prolonged hyperuricemia is associated with the development of hypertension, renal arteriolosclerosis, glomerulosclerosis, and tubulointerstitial injury. It confers a greater risk than proteinuria for developing chronic renal disease and is associated with the development of hypertension. Mild chronic hyperuricemia without intrarenal crystal deposition was induced in rats by inhibiting uricase with oxonic acid. Hyperuricemic rats developed hypertension, afferent arteriolar thickening, and mild renal interstitial fibrosis. Additionally, hyperuricemia accelerated renal damage and vascular disease in rats undergoing renal ablation. To better understand the role of hyperuricemia in the kidney, micropuncture studies were performed. Hyperuricemia resulted in renal cortical vasoconstriction (single nephron glomerular filtration rate (SNGFR) ↓ 35%, P < .05) and glomerular hypertension (P < .05). The possibility that hyperuricemia could modify renal hemodynamic disturbances during progression of renal disease was tested in rats with 5/6 nephrectomy. Hyperuricemia accentuated the renal vascular damage and caused cortical vasoconstriction (SNGFR ↓ 40%, P < .05) and persistent glomerular hypertension. In conclusion, hyperuricemia impairs the autoregulatory response of preglomerular vessels, resulting in glomerular hypertension. Lumen obliteration induced by vascular wall thickening results in severe vasoconstriction. The resulting ischemia is a potent stimulus that induces tubulointerstitial inflammation and fibrosis as well as arterial hypertension.

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

http://www.sciencedirect.com/science/article/pii/S0270929504001500 Supra. 39-42

Uric acid as a mediator of endothelial dysfunction, inflammation, and vascular disease

Recent experimental findings have led to renewed interest in the possible role of uric acid in the pathogenesis of both hypertension and vascular disease. Often considered an antioxidant, biochemical and in vitro data indicate that noncrystalline, soluble uric acid also can react to form radicals, increase lipid oxidation, and induce various pro-oxidant effects in vascular cells. In vitro and in vivo findings suggest that uric acid may contribute to endothelial dysfunction by inducing antiproliferative effects on endothelium and impairing nitric oxide production. Proinflammatory and proliferative effects of soluble uric acid have been described on vascular smooth muscle cells (VSMCs), and in animal models of mild hyperuricemia, hypertension develops in association with intrarenal vascular disease. Possible adverse effects of uric acid on the vasculature have been linked to increased chemokine and cytokine expression, induction of the renin-angiotensin system, and to increased vascular C-reactive protein (CRP) expression. Experimental evidence suggests a complex but potentially direct causal role for uric acid in the pathogenesis of hypertension and atherosclerosis.

[1] The 1956 Merck Manual places the US rate at 5%. A large part of the difference is that of the defining blood pressure has been significantly lowered to 140 distolic; however, the world figures include those not on a western diet, for whom hypertension is virtually unknown; thus more than offsetting the increase by defining pressure.