Category Archives: Kidney Disease

Particular Diabetes Drugs May Protect Your Heart and Kidneys

 

Blood pressure control is also extremely important for protection of heart and kidneys

I’ve been reticent to tout the putative heart-protective effects of diabetes drugs in the classes called SGLT2 inhibitors and GLP-1 receptor agonists. Frankly, their supposed kidney-protective effects haven’t even been on my radar. My hesitation to report on these matters stems from:

Maybe if Big Pharma sent me a nice check….

The GLP-1 receptor agonists seem to have beneficial effects on both heart and kidney. With SGLT2 inhibitors, renal benefits may be more prominent than cardiac. Also note that any beneficial heart or renal effects may be attributable only to certain drug within the class, and not a class effect.

For what it’s worth, the American Diabetes Association recently hosted a conference on these issues. I assume the ADA endorses the report written by three experts, two of whom have received some sort of compensation from pharmaceutical companies. This doesn’t necessarily mean they are biased. Some excerpts:

Since patients with diabetes are at increased risk for CV [cardiovascular] and renal events, reducing the risk of these events is of primary interest to improve outcomes in the long-term. [Cardiovascular events usually refers to heart attacks, strokes, and death from those. Renal events would be high loss of protein through the kidneys, impaired kidney function or chronic kidney disease, or the need for dialysis.]

SGLT2 inhibitors and GLP-1 RAs have dramatically changed the treatment landscape of type 2 diabetes due to their established CV benefits, and the observed improvements in renal function seen with these classes of agents are currently undergoing intense investigation.

***

It is now apparent that both SGLT2 inhibitors and GLP-1 RAs show consistent reductions in major adverse cardiovascular events for patients with established cardiovascular (CV) disease, and both appear to have renal benefits as well.

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The nephron is the microscopic structural and functional unit of the kidney.

Renal effects of GLP-1 receptor agonists

These drugs may exert their beneficial actions on the kidneys through their effects on lowering blood glucose and blood pressure and by reducing the levels of insulin.

For GLP-1RAs, these [studies] include ELIXA with lixisenatide, LEADER with liraglutide, SUSTAIN-6 with semaglutide, EXCSEL with exenatide once-weekly, HARMONY with albiglutide, and REWIND with dulaglutide.

All these studies indicate that albuminuria [protein loss through urine] is reduced during treatment with GLP-1 RAs, and eGFR [estimated glomerular filtration rate, a measure of kidney function] appears to be stabilized.

These benefits are seen independently of HbA1c, weight, and blood pressure variations.

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Heart attack is only one type of cardiovascular event

Cardiovascular effects of GLP-1 receptor agonists

Large CV outcomes trials with GLP-1 RAs have shown that these agents can reduce the risk of major adverse CV events, CV mortality, and all-cause mortality.

These CV benefits appear to be related to four distinct mechanisms:

    • Improve myocardial [heart muscle] performance in ischemic heart failure [caused by poor blood flow to heart]
    • Improve myocardial survival in ischemic heart disease
    • Ameliorate endothelial dysfunction [endothelium is the lining of arteries]
    • Decrease markers of CV risk.

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Renal effects of SGLT2 inhibitors

  • However, many potential mechanisms have been linked to the renoprotective effects of SGLT2 inhibitors.
  • These include reduction of blood pressure, improved metabolic parameters, reduced volume overload, reduction in albuminuria, and glomerular pressure.
  • For the latter, SGLT2 inhibition appears to reduce hyperfiltration via a tubuloglomerular feedback mechanism.
  • Clinical data from CV outcomes trials have shown consistent variations in eGFR and reduction in death from renal causes with empagliflozin, canagliflozin, and dapagliflozin.
  • However, to gain more information about the renal effects of these agents, dedicated renal outcomes trials are needed to study reductions in albuminuria, changes in eGFR, number of patients reaching end-stage renal disease, need for dialysis, and deaths due to kidney failure.

***

Key Messages from the authors

Large CV outcomes trials have shown that both SGLT2 inhibitors and GLP-1 RAs are associated with significant reductions in CV events in patients with elevated CV risk.

From CV outcomes trials both classes of agents also appear to have renal benefits, although large dedicated studies are needed to establish the magnitude of this potential benefit

The mechanism of action at the basis of CV and renal benefits of SGLT2 inhibitors and GLP-1 RAs is complex, multifactorial, and still not completely understood.

I’m still skeptical but will keep an open mind.

Steve Parker, M.D.

PS: Bold emphasis above is mine.

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Diet Can Prevent Chronic Kidney Disease and Albuminuria

Folks with diabetes are at risk for chronic kidney disease, often heralded by albumin (a protein) in the urine.

The heathy diet describe in this Renal and Urology News article sounds like the Mediterranean diet to me, not a typical paleo diet. It will be years, if ever, before the paleo diet is tested as a preventative for chronic kidney disease. But anyway…

Adhering to a healthy diet may reduce the risk of chronic kidney disease (CKD) and albuminuria, according to a new systematic review and meta-analysis.

Such a diet is rich in vegetables, fruit, legumes, nuts, whole grains, fish, and low-fat dairy products and low in red and processed meats, sodium, and sugar-sweetened beverages.

Jaimon T. Kelly, PhD, of Bond University in Australia, and collaborators, analyzed 18 studies that included a total of 630,108 healthy adults followed for a mean 10.4 years. Their meta-analysis of low to moderate grade studies found that a healthy dietary pattern was associated with a 30% lower incidence of CKD and a 23% lower incidence of albuminuria, according to results published in the Clinical Journal of the American Society of Nephrology.

The dietary patterns that were most frequently studied included the Mediterranean diet, DASH (Dietary Approaches to Stop Hypertension) diet, and US dietary guidelines.

Source: Healthy Diet May Prevent CKD, Albuminuria – Renal and Urology News

Steve Parker, M.D.

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Is Protein Restriction Necessary If You Have Diabetic Kidney Disease?

Steak is high in protein but it ultimately depends on serving size

From a Diabetes Care Consensus panel:

Consensus recommendation:

In individuals with diabetes and non–dialysis-dependent diabetic kidney disease (DKD), reducing the amount of dietary protein below the recommended daily allowance (0.8 g/kg body weight/day) does not meaningfully alter glycemic measures, cardiovascular risk measures, or the course of glomerular filtration rate decline and may increase risk for malnutrition.

Are protein needs different for people with diabetes and kidney disease? Historically, low-protein eating plans were advised to reduce albuminuria and progression of chronic kidney disease in people with DKD, typically with improvements in albuminuria but no clear effect on estimated glomerular filtration rate. In addition, there is some indication that a low-protein eating plan may lead to malnutrition in individuals with DKD. The average daily level of protein intake for people with diabetes without kidney disease is typically 1–1.5 g/kg body weight/day or 15–20% of total calories. Evidence does not suggest that people with DKD need to restrict protein intake to less than the average protein intake.

Source: Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report | Diabetes Care

Steve Parker, M.D.

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