Category Archives: kidney disease

Finerenon: New Hope for Prevention of Kidney Disease and Cardiac Death in Type 2 Diabetes

Your friendly neighborhood drug supplier

Verbatim from the FDA press release:

FDA has approved Kerendia (finerenone) tablets to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalization for heart failure in adults with chronic kidney disease associated with type 2 diabetes.

Diabetes is the leading cause of chronic kidney disease and kidney failure in the United States. Chronic kidney disease occurs when the kidneys are damaged and cannot filter blood normally. Because of defective filtering, patients can have complications related to fluid, electrolytes (minerals required for many bodily processes), and waste build-up in the body. Chronic kidney disease sometimes can progress to kidney failure. Patients also are at high risk of heart disease.

The ultimate role of finerenone in our armamentarium against disease and suffering will probably depend on cost and the number needed to treat.

The efficacy of Kerendia to improve kidney and heart outcomes was evaluated in a randomized, multicenter, double-blind, placebo-controlled study in adults with chronic kidney disease associated with type 2 diabetes. In this study, 5,674 patients were randomly assigned to receive either Kerendia or a placebo.

The study compared the two groups for the number of patients whose disease progressed to a composite (or combined) endpoint that included at least a 40% reduction in kidney function, progression to kidney failure, or kidney death. Results showed that 504 of the 2,833 patients who received Kerendia had at least one of the events in the composite endpoint compared to 600 of the 2,841 patients who received a placebo.

The study also compared the two groups for the number of patients who experienced cardiovascular death, a non-fatal heart attack, non-fatal stroke, or hospitalization for heart failure. Results showed that 367 of the 2,833 patients receiving Kerendia had at least one of the events in the composite endpoint compared to 420 of the 2,841 patients who received a placebo, with the treatment showing a reduction in the risk of cardiovascular death, non-fatal heart attack, and hospitalization for heart failure.

Side effects of Kerendia include hyperkalemia (high levels of potassium), hypotension (low blood pressure), and hyponatremia (low levels of sodium). Patients with adrenal insufficiency (when the body does not produce enough of certain hormones) and those receiving simultaneous treatment with strong CYP3A4 inhibitors should not take Kerendia.

Kerendia received priority review and fast track designations for this application.

FDA granted the approval of Kerendia to Bayer Healthcare.


Click for prescribing information.


Parker here.

Just offhand, finerenone doesn’t look like a great drug. Helpful, maybe. Chronic kidney disease can end up at ESRD (end stage renal disease), which requires thrice weekly hemodialysis if the patient wants to stay alive. (Yes, peritoneal dialysis is an alternative.) Preventing ESRD is an incredible benefit for an individual.

Finerenone seems to be a well-tolerated daily pill. The main adverse effect is elevated blood potassium level, which can cause palpitations, and death infrequently. Less commonly, the drug can cause low blood pressure.

Steve Parker, M.D.

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Filed under Drugs for Diabetes, Heart Disease, kidney disease, Longevity, Stroke

Does Salt Restriction Lower Blood Pressure in Type 2 Diabetes?

Yes, according to an article in Nutrition, Metabolism & Cardiovascular Disease. The systolic pressure lowering is 5-6 points, but only 1-2 points on average for diastolic pressure. This degree of BP lowering is not dramatic, but might prevent an escalation of antihypertensive drug dosing or initiation of an additional drug.

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

Steve Parker, M.D.

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Gastric Bypass Surgery Improves Heart and Kidney Outcomes in Type 2 Diabetes

Steve Parker MD, bariatric surgery, gastric bypass

Band Gastric Bypass Surgery

From a recent Diabetes Care article:

Our data suggest robust benefits for renal outcomes, heart failure, and CV mortality after GBP in individuals with obesity and T2DM. These results suggest that marked weight loss yields important benefits, particularly on the cardiorenal axis (including slowing progression to end-stage renal disease), whatever the baseline renal function status.

Source: Renal and Cardiovascular Outcomes After Weight Loss From Gastric Bypass Surgery in Type 2 Diabetes: Cardiorenal Risk Reductions Exceed Atherosclerotic Benefits | Diabetes Care

Because of the risk of surgery, I’d make sure first that diet modification was seriously tried and failed.

Steve Parker, M.D.

low-carb mediterranean diet

Click the pic to purchase at Amazon.com. E-book versions also available at Smashwords.com.

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Do Certain Diabetes Drugs Protect the 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.

***

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.

***

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.

***

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.

low-carb mediterranean diet

Click the pic to purchase at Amazon.com. E-book versions also available at Smashwords.com.

 

 

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Filed under coronary heart disease, Drugs for Diabetes, Heart Disease, kidney disease, Stroke