Kidney

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

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.

GT

Phosphorous balance in chronic kidney disease

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.

GT

A case of nephrogenic diabetes insipidus

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.

GT

Mineral bone disorder in the setting of kidney disease.

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.

GT

Jardiance is also beneficial in mild kidney disease

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.

GT

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

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.

GT

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

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.

Lancet

Albumin excretion during puberty in the setting of type 1 diabetes.

Albumin excretion during puberty in the setting of type 1 diabetes.

The use of an ACE inhibitor and a statin did not change the albumin-to-creatinine ratio over time among adolescents with type 1 diabetes. Neither drug had significant effects on carotid intima–media thickness, other cardiovascular markers, the glomerular filtration rate, or progression of retinopathy.

NEJM

Uric acid and renal failure

Uric acid and renal failure

Uric acid elevation is frequently seen in patient with metabolic syndrome. It can lead to gout and kidney stones. In the current study, researchers monitored and analyzed a group of 4,000 participants suffering from chronic kidney disease, stages 2-4.

Authors found that higher baseline uric acid levels were a strong independent predictor of renal failure in adults with initial eGFR > 45 (stage 3a CKD), marginally in those with eGFR 30-45 (stage 3b), and not a predictor at all in subjects with eGFR < 30 (stage 4).

Future interventional studies would be useful in determinining if hyperuricemia is a causative and modifiable risk factor.

GT

Obesity and kidney disease

Obesity and kidney disease

This is a nice review showing how obesity contributes to kidney disease, particularly in the setting of metabolic syndrome, diabetes and hypertension.

The process starts with glomerular hyperfiltration, and made worse by high sodium and animal protein intake. I suspect that inflammation from visceral adiposity plays a major role too.

It appears that the risk for kidney disease accumulates over time, as prognosis is worse in childhood-onset vs. adult-onset obesity.

GT

How the diabetes drug protects the heart

How the diabetes drug protects the heart

EMPA-REG trial found that jardiance, an inhibitor of sodium-glucose cotransporter, lowered the risk of heart failure in patients with diabetes. Many pathways have been proposed for such benefits.

Authors propose that reduced activity of the sodium-hydrogen exchanger in the heart and kidneys is the main inciting factor in preventing heart failure. Decreased blood pressure, body weight, fluid retention, and kidney function preservation also play a role. 

Further research would be needed to clarify the molecular, cellular, metabolic, and hemodynamic intricacies of the SGLT2-inhibitor as an armour of the heart.

GT

Victoza and kidney prevention in type 2 diabetes

Victoza and kidney prevention in type 2 diabetes

LEADER trial showed that victoza reduced mortality and cardiovascular outcomes in type 2 diabetes patients at high baseline CVD risk. About 9,000 participants were followed for 4 years.

Secondary analysis of the trial now uncovers that liraglutide also reduces renal events, primarily by preventing macro-albuminuria. Urinary protein leak, technically called albuminuria, is a well known independent risk factor for both cardiovascular illness and chronic kidney disease.

Important to be aware of these findings as they have direct clinical implications.

GT

Diabetes medication and acute kidney injury

Diabetes medication and acute kidney injury

Type 2 diabetes patients treated with or without SGLT-2 inhibitors were followed for about one year. In the Mount Sinai cohort, authors found that acute kidney injury (AKI) was 60% less common in those receiving SGLT-2 inhibitors than nonusers. On the secon (Geisinger) cohort, adjusted AKI risk was no different among the two experimental groups. All SGLT-2 inhibitors were included in the study; invokana, farxiga and jardiance.

Authors conclude that in a real-world setting, unlike the FDA warning, decreased renal sodium-glucose co-transporting does not cause acute kidney injury in patients with type 2 diabetes.

GT

Resistant hypertension, review

Resistant hypertension, review

This article reviews recent advances in resistant hypertension: poor therapy adherence, undertreatment with chlorthaladone and spironolactone, precise patient selection for renal nerve denervation (knowledge of accessory renal arteries and possible reinnervation), baroreflex activation therapy via unilateral carotid sinus stimulation, and refractory hypertension (a severe form, defined as uncontrolled blood pressure in spite of using ≥5 agens, including the long-acting thiazide and aldosterone antagonist).

Resistant hypertension is thought to be from salt-sensitivity upregulation (renal), while refractory HTN from sympathetic overdrive (neurogenic). Both types of severe hypertension increase the risk of clinical events strikingly; heart failure, stroke, coronary heart disease, end-stage nephropathy, and all-cause mortality.

GT

Invokana, Diabetes, Heart, Kidney and Amputations.

Invokana, Diabetes, Heart, Kidney and Amputations.

Invokana reduced cardiovascular events in patients with type 2 diabetes and CVD. The medication also showed possible kidney benefits by retarding albuminuria rise and estimated GFR decline. Unexpectedly, higher rates of toe and metatarsal amputations were seen in adults receiving invokana vs. placebo. More research is needed to confirm or elucidate the mechanism of such adverse events. About 10,000 participants were followed for 3.5 years.

GT

Physiological Effects of SGLT-2 inhibition in Type II Diabetes

Physiological Effects of SGLT-2 inhibition in Type II Diabetes

"Recently, episodes of ketoacidosis have been reported in some patients receiving SGLT-2 inhibitors, especially on the background of insulin treatment. Though infrequent, this serious complication of SGLT-2 inhibition has led both the US FDA and European Medicines Agency to include a warning on the product label.

In summary, we found that the physiological response to SGLT-2 inhibition in patients with type 2 diabetes and preserved renal function, as well as in subjects without diabetes includes an increase in the absolute and fractional excretion of β-HB, lactate, and sodium, which quantitatively track with glycosuria. .

These findings, and the increase in EPO production, indicate that substantial glucose loss through joint inhibition of glucose and sodium reabsorption in the proximal tubule induces multiple changes in renal metabolism that, taken together, may be beneficial for kidney function in the long term."

Diabetes Care

Osteoporotic Drugs in Kidney Disease, who knows?

Osteoporotic Drugs in Kidney Disease, who knows?

This systematic review and meta-analysis included 13 randomized clinical trials from 2006-2016. Bisphosphonates, teriparatide (forteo), raloxifene, and denosumab (prolia) were compared with non-pharmacological therapy in patients with kidney disease: transplant, dialysis or simply stage 3-5. No clear benefit or harm of antiosteoporotic agents was found in individuals with CKD.

GT