FIDELIO: Type 2 Diabetes & CKD

Kerendia (Finerenone) is an oral non-steroidal mineralocorticoid receptor (MR) antagonist. Excessive activation of mineralocorticoid receptors can result in hypertension, fluid retention, and cardiovascular harm, all of which have been directly linked to the deterioration of kidney function.

Invokana protects the heart and kidneys

Patients with type 2 diabetes receiving Invokana experienced 30% and 20% lower rates of kidney disease progression and cardiovascular events respectively, when compared to the placebo group.

Results were so obvious and significant that the study was terminated early. About 4500 subjects with DM2 were followed for about 2.5 years. No increased rates of fractures or amputations were seen with Invokana.

Dr. Tashko

Newer diabetes medications can prevent heart and kidney disease

About 80,000 diabetes patients were analyzed from 8 clinical trials.

Authors found that GLP1 agonists and SGLT2 inhibitors prevented cardiovascular events (MACE) equally by 14% in those with established CVD. However, both classes of medications did not appear to be effective in reducing MACE in adults with diabetes but without established CVD.

SGLT2 inhibitors showed superior results compared to GLP1 agonists in regard to preventing hospitalizations for heart failure or severe kidney disease progression, such as end-stage-renal disease or death.

If cost, side effects, drug interactions and contraindications allow, diabetes patients would greatly benefit from these therapies on three fronts; glucose control, heart and kidney disease prevention.


Sotagliflozin effects on diabetes type 1

Among patients with type 1 diabetes who were receiving insulin, the proportion of patients who achieved a glycated hemoglobin level lower than 7.0% with no severe hypoglycemia or diabetic ketoacidosis was larger in the group that received sotagliflozin than in the placebo group. However, the rate of diabetic ketoacidosis was higher in the sotagliflozin group.


New FDA approval: retacrit, to improve anemia of kidney disease

Erythropoietin is a key hormone produced by the kidney to stimulate bone marrow production of red blood cells. FDA has now approved the second erythropoietin analog, retacrit, in addition to epogen. It shows similar efficacy and side effects to epogen. This approval allows both medications to be more accessible to patients, at a lower cost. It is indicated for treatment of anemia of chronic kidney disease or from use of chemotherapy and zidovudine. It could also be used preemptively prior to surgeries with expected major blood loss.


Phosphorous balance in chronic kidney disease

In the setting of chronic kidney disease, elevated blood phosphorous levels can increase the risk of death, in addition to cardiovascular, parathyroid and bone disorders. This case shows us that the other extreme is also dangerous: severe oral phosphorous restriction and severe hypophosphatemia lead to profound muscle weakness, ostemalacia, osteoporosis and multiple bone fractures. Arisotle’s aurea mediocritas applies nicely here too.


A case of nephrogenic diabetes insipidus

Although uncommon, lithium can cause endocrinopathies such as hypothyroidism, hyperthyroidism, hyperparathyroidism, and diabetes insipidus. Diabetes insipidus (DI) is of nephrogenic source, resulting in tubulointerstitial anomaly and resistance to vasopressin. 

Vasopressin or ADH is produced in the hypothalamus but released by the posterior pituitary gland. It is responsible for retaining free water by the kidneys. Nephrogenic DI can lead to increased urination and high blood sodium levels.

This case shows a nice correspondence between lithium-induced renal pathoanatomy and pathophysiolgy.


Mineral bone disorder in the setting of kidney disease.

This is a nice summary of the latest guidelines on diagnosis and management of mineral bone disease induced by chronic kidney disease. Kidney anomaly can be classified functionally via estimated GFR or structurally via proteinuria.

Guidelines emphasize the need for bone density scan, bone biopsy, parathyroid hormone, calcium and phosphorus measures in the right context. Vitamin D analogs and phosphate binders are also discussed. See below for detailed recommendations.


Jardiance is also beneficial in mild kidney disease

Patients with type 2 diabetes, cardiovascular illness and kidney disease were randomized to receive jardiance or placebo. Baseline renal parameters were eGFR 30-60 and albuminuria of >300 mg/day.

Study found that jardiance improved outcomes significantly: all-cause mortality by 24%, cardiovascular death by 29%, all-cause hospitalization by 19%, and heart failure hospitalization by 39%.

Findings are overall consistent with prior clinical trial results.


Aldosterone vs. renin, a cardiometabolic cat-and-mouse game

Study results are important from several aspects. It confirms prior findings that excess aldosterone increases cardiometabolic sequelae, like cardiovascular events, diabetes, atrial fibrillation and mortality, independent of high blood pressure.

More importantly the study guides us on how to objectively reduce the above risks: the dose of mineralocorticoid receptor antagonists, such as spironolactone or eplerenone, could be adjusted to achieve higher plasma renin activity of ≥1 μg/L/hr.

Plasma renin activity is clinically available and a good biochemical measure of hyperaldosterone end-product, as shown in the figure below.


Diabetes, albuminuria, salt and vitamin d; what do they have in common?

Macroalbuminuria predicts renal and cardiovascular events in patients with type 2 diabetes. In patients with macroalbuminuria and type 2 diabetes, moderate salt restriction enhances the antialbuminuric effect of losartan, an effect that could be nephroprotective and cardioprotective in the long term.

The finding that paricalcitol prevents a sodium-induced increase in albuminuria provides support for trials to test the long-term risk-benefit profile of paricalcitol add-on therapy in patients with type 2 diabetes and macroalbuminuria refractory to dietary salt restriction, including patients refractory to even moderate salt restriction.