Standard Treatment of Diabetic Nephropathy ( EGFR > 30): ACE Inhibitor OR AR Blocker PLUS SGLT-2 Inhibitor

Standard Treatment of Diabetic Nephropathy ( EGFR > 30): ACE Inhibitor OR AR Blocker PLUS SGLT-2 Inhibitor

Dr KK Aggarwal

President CMAAO and HCFI

Diabetic nephropathy or overt proteinuria (macroalbuminuria, or "severely increased albuminuria") is usually present with worse glycemic control, hypertension, glomerular hyperfiltration, or a genetic predisposition.

The earliest clinical manifestation of renal involvement in diabetes is an increase in albumin excretion (microalbuminuria, or "moderately increased albuminuria")

Glycemic control can partially reverse the glomerular hypertrophy and hyperfiltration, delay the development of elevated albumin excretion, stabilize or decrease protein excretion in patients with increased albumin excretion, and \can slow the progression of glomerular filtration rate decline.

ACE inhibitors OR ARBs can reduce the rate of kidney disease progression.

Do not combiner the two.

Also do not combine aliskiren, a direct renin inhibitor with ACE or ARBs.

Diabetic nephropathy with EGFR >30 mL/min per 1.73 m² add SGLT-2 inhibitor canagliflozin or empagliflozin. They can reduce kidney disease progression, end-stage renal disease, and cardiovascular events and can potentially improve survival. However, they increase the rate of urinary tract infections and genital fungal infections and may increase the likelihood of lower limb amputation and fracture. SGLT-2 inhibitors are weak glucose-lowering agents and also costly.

High-Protein Diet May not be Safe

(Excerpts from Medscape): Even a high-protein diet, often recommended to lose weight or build muscles can be harmful to normally functioning kidneys as per two separate new studies from the Netherlands and Korea, published online in Nephrology Dialysis Transplantation. Many earlier studies have shown that a high-protein diet may harm kidney function, and this is why doctors recommend kidney patients a low-protein diet. 

The high-protein culture (Atkins, Zone, South Beach, and Ketogenic diets) involve daily protein intake of 20% to 25% or more of the total daily energy intake.  As per the studies one should avoid recommending high-protein intake for weight loss in obese or diabetic patients, or those with prior cardiovascular events, or a solitary kidney if kidney health cannot be adequately protected.

1.   In the Dutch study, Kevin Esmeijer, MD, of Leiden University Medical Center, the Netherlands collected dietary data using a food frequency questionnaire from 4837 patients 60-80 years of age with a history of heart attack involved in the Alpha Omega Trial. At baseline and 41 months follow-up, serum cystatin C (cysC) and serum creatinine were measured from stored blood samples. The mean age of the cohort was 69 years and mean estimated glomerular filtration rate was 82 mL/min/1.73m². Compared with the general population, patients with a history of heart attack have double the rate of annual decline in kidney function and thus are at higher risk for chronic kidney disease. For the entire cohort, mean total protein intake was 71 g/day, of which approximately two thirds was from animal protein and the remaining third from plants.

Analyses indicated that the total amount of protein intake per day was inversely associated with the annual rate of kidney function decline. The annual change in eGFR was doubled in patients with a total daily protein intake in excess of 1.20 g/kg ideal body weight, compared with an intake less than 0.80 g/kg.

Specifically, the annual change in eGFR in those with the highest total daily protein intake was –1.60 mL/min/1.73m² compared with –0.84 mL/min/1.73m² for those with the lowest total daily protein intake.

And for each extra daily intake of animal protein of 0.1 g/kg ideal body weight, there was an additional decline in eGFR_cysC of –0.12 mL/min/1.73m² per year.

Subgroup analyses also indicated that the association between protein intake and decline in eGFR was threefold stronger in patients with diabetes compared to those without diabetes.

2.   In the Korean study, Jong Hyun Jhee, MD, of the Institute of Kidney Disease Research, Yonsei University, Seoul, and colleagues analyzed the effect that a high-protein diet had on renal hyperfiltration and declining kidney function in 9226 participants from the Korean Genome and Epidemiology Study.

Patients were classified into quartiles of daily protein intake as assessed by a food frequency questionnaire. The mean age of study participants was 52 years and the mean follow-up was 11.5 years.

Among the four quartiles of daily protein intake, the prevalence of renal hyperfiltration was significantly higher among those in the highest quartile of protein intake, at 6%, compared with 5.2% among those in the lowest protein intake quartile.

And the annual mean decline in eGFR was again highest, at –2.34 mL/min/1.73m², among those in the highest quartile of daily protein intake, compared with –2.01 mL/min/1.73m² among those in the lowest quartile of protein intake.

Rapid decline in kidney function is defined as a decrease in eGFR of > 3 mL/min/1.73m² per year. They found that those in the highest quartile of protein intake had a 32% greater risk of experiencing a rapid decline of eGFR per year compared with those in the lowest quartile.

They also found that the faster drop in renal function happened only among those with pre-existing hyperfiltration. These findings indicate that a higher intake of protein may be an independent risk factor for renal hyperfiltration that can accelerate deterioration of kidney function.

Comments

The recommended dietary allowance for protein intake is only 0.8 g/kg/day and the requirement for protein is likely even lower, at only about 0.6 g/kg/day, provided adequate essential amino acids are consumed. However, most adults in Western societies eat 1.0 to 1.4 g/kg/day of protein. Protein intake may be as high as 20% to 25% or more of the total energy source they add — considerably higher than the 10% to 15% recommended by most guidelines.

Emerging data across individuals and populations suggest that glomerular hyperfiltration associated with a high-protein diet may lead to a higher risk of de novo CKD or may accelerate progression of pre-existing CKD.

Dr KK Aggarwal

Padma Shri Awardee

President Confederation of Medical Associations in Asia and Oceania (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

World Kidney Day: Same serum creatinine value may mean different eGFR for persons of different body weight

Serum creatinine is a commonly used test to evaluate kidney function. And, if the creatinine value falls within the lab reference range, then all is considered well. However, this is not so because the creatinine level is affected by age, race, gender and also the body weight. Hence, serum creatinine level alone is an unreliable marker for impaired kidney function or chronic kidney disease.

The GFR or glomerular filtration rate is the best measure to assess the function of the kidneys.

There are several ways to calculate the GFR.

The most common is Cockcroft Gault equation. It calculates creatinine clearance (mL/min) as a surrogate for GFR. It provides an estimate of GFR based on serum creatinine, age, gender and body weight. 

The formula is:

Estimated or eGFR = 140 – age x body weight (in kg)/72 × serum creatinine (in mg/dL)

·         A value of 60 or higher is normal (GFR decreases with age). 

·         A value less than 60 is low and may indicate kidney disease.

·         A value of 15 or lower may mean kidney failure.

The same serum creatinine value may mean different GFR for similarly aged persons of different body weight.

·         A 40 kg man, aged 40 years, with serum creatinine of 1, the GFR is 55.

·         A 50 kg man, aged 40 years, with serum creatinine of 1, the GFR is 69.

·         A 60 kg man, aged 40 years, with serum creatinine of 1, the GFR is 83.

·         A 70 kg man, aged 40 years, with serum creatinine of 1, the GFR is 97.

·         A 80 kg man, aged 40 years, with serum creatinine of 1, the GFR is 111.

If you are at increased risk for kidney disease i.e. if you have diabetes, high blood pressure, or family history of diabetes, high blood pressure or kidney disease, then calculate your GFR to know if you have kidney disease.

The GFR may show impaired kidney function, even if the serum creatinine level is in the normal range.

Another important point to take note of is that instead of looking at a single test result, one should look for trends in the results. 

Always compare the results of a particular test with previous reports even when a result is normal. Results that show change over time i.e. show a rising or declining trend by 0.3 are important and should not be ignored.

Any result which has been in the low normal range for the last many years, but is now in the high normal range even though still within normal limits, should be investigated accordingly.

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

CKD in India: Early detection is the key to its prevention

Chronic kidney disease or CKD is becoming a major public health problem globally, including in India.

The exact burden of CKD in India is not known, but CKD is becoming an epidemic in the country.  The prevalence of CKD in India is estimated to be 800 per million people. Every year about 2.2 Lakh new patients of end stage renal disease (ESRD) get added in India resulting in additional demand for 3.4 crore dialysis every year.

The two commonest causes of CKD are diabetes and hypertension. With the growing population of persons with diabetes and hypertension coupled with increasing life expectancy, this number is only going to further increase.  

CKD has poor outcomes and entails high treatment costs. It is gradually progressive disease, but since it is asymptomatic in early stages, CKD is often detected when the disease is in an advanced stage and most kidney damage that has occurred is irreversible.

How well the kidneys are functioning can be estimated by the eGFR or estimated glomerular filtration rate. Based on the eGFR number, CKD can be divided into five stages.

Stage 1: Normal or high GFR (eGFR > 90 mL/min/1.73 m2)

Stage 2: Mild CKD (eGFR = 60-89 mL/min/1.73 m2)

Stage 3a: Moderate CKD (eGFR = 45-59 mL/min/1.73 m2)

Stage 3b: Moderate CKD (eGFR = 30-44 mL/min/1.73 m2)

Stage 4: Severe CKD (eGFR = 15-30 mL/min/1.73 m2)

Stage 5: End Stage CKD (eGFR <15 mL/min/1.73 m2)

Stage 3 chronic kidney disease (CKD) is the first stage that is identifiable from a blood test alone (Br J Gen Pract. 2010 Jun 1; 60(575): e266–e276). Most patients are detected at this stage of the disease. Stage 5 CKD means the patient is undergoing dialysis or needs to undergo dialysis.

In India, CKD is a part of the National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS) and noncommunicable diseases (NCDs) such as heart disease, cancer, diabetes have been in the spotlight. However, the rising incidence of CKD to epidemic proportions merits a dedicated national program for prevention and management of CKD.

There is no cure for CKD … early detection is the key to its prevention.

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA