While diabetes, hypertension (high blood pressure) and other medical conditions have long been on the list of causes of chronic kidney disease, obesity has only more recently been recognized as an independent cause of kidney disease.
A recent review article helps us understand how obesity can cause chronic kidney disease, also termed ‘obesity related glomerulopathy’.
(A little background: ‘Glomeruli’ are the precious microscopic filters of the kidneys. They are kind of like little baskets with tiny holes in it, which allow the substances we want filtered from the blood into the urine to get through, and to keep the stuff we want in the blood, in the blood. (Some substances we want to keep actually get filtered through and then resorbed by the kidney’s tubules back to the blood, but that’s a story for another day). What is important for this discussion is that if the glomeruli get damaged, think of it like the filters becoming more leaky than they should be.)
There are many ways that obesity can result in kidney damage, including:
- Hemodynamic changes and hyperfiltration. Vasodilation of the afferent arteriole leads to increased renal plasma flow and intraglomerular pressure (In english: increased blood flow to the basket filters puts pressure on the baskets.)
- Renin-angiotensin-aldosterone system (RAAS) overactivation: Mechanisms include compression of the kidneys by fat tissue and higher pressures in the abdomen (intra abdominal pressure), and increased production of the hormone aldosterone.
- Insulin resistance: Mechanisms include the impact of high insulin levels on hemodynamic changes, promotion of chronic inflammation, and glomerular hypertension (high pressure in the basket filters).
- Inflammation: obesity is a state of chronic low-grade inflammation, which can have adverse effects on every organ system, including the kidneys.
- Fat accumulation (fatty kidney): Excess fat accumulated around organs is called ‘ectopic fat’. Ectopic fat around the kidneys compresses blood vessels and puts physical pressure on the kidneys. Ectopic fat also produces inflammatory chemicals and other substances , and exposure of the kidneys to these substances can be damaging.
- Increased production of other hormones in fat cells that may be damaging to kidneys (eg leptin).
Kidney function is assessed with a blood test called serum creatinine, which is used to calculate the GFR, or ‘glomerular filtration rate’. As blogged previously, an important test than can often detect kidney damage years before the kidney function declines, is with a urine test called the ‘albumin:creatinine ratio’. When the glomeruli are in the early stages of damage, they often become a bit leaky, leaking albumin into the urine. This usually starts years before kidney function starts to decline (though some people do develop decreased kidney function without albumin in the urine). Kidney ultrasound, while not a routine part of evaluation in most parts of the world currently, may ultimately come to be more standard in the evaluation of kidneys in people with elevated weight (similar to how ultrasounds can be done to evaluate for fatty liver disease). Other biomarkers of early glomerular injury may also be of interest (check out the article for more on this).
Good news: there are treatments that can provide powerful protection of the kidneys in people with elevated weight.
Weight loss is a key component of treatment, and we have an expanding armamentarium of approaches (including weight loss medications) that can help. (search up this topic in my search box at the top right for more reading!)
Blockade of the RAAS system (see above) can be accomplished with medications including ACE inhibitors or angiotensin II receptor blockers (ARBs), and/or mineralocorticoid receptor antagonists.
The SGLT2 inhibitors can be beneficial by reducing glomerular hyperfiltration, providing some weight loss, and reducing inflammation. They have been shown to be of renal (kidney) benefit in people with type 2 diabetes and chronic kidney disease. Dapagliflozin has also been shown to protect the kidneys of people with chronic kidney disease who don’t have type 2 diabetes. These benefit are seen across the spectrum of body mass index, including people of healthy weight and people with obesity (see here and here and here).
GLP-1 receptor agonists have been shown to reduce albumin in the urine in people with type 2 diabetes. Two GLP1 receptor agonists, liraglutide and semaglutide, are also approved as obesity medications, but we don’t have studies evaluating their benefit to the kidneys in people who don’t have diabetes.
BOTTOM LINE: Obesity can cause chronic kidney disease, even in the absence of other health issues known to cause kidney damage (like diabetes or hypertension). Regular screening for kidney disease is important, with urine testing often showing the first signs of damage. Talk to your doctor about treatment strategies to help manage weight and provide important kidney protection!
Disclaimer: I receive honoraria as a continuing medical education speaker and consultant from the makers of the SGLT2 inhibitors, including medications mentioned above: dapagliflozin (Astra Zeneca), as well as the GLP1 receptor agonists, including liraglutide and semaglutide (Novo Nordisk). I have been involved as an investigator in clinical trials of GLP1 receptor agonists and SGLT2 inhibitors.
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