Hunger in Patients with Kidney Disease – Why it matters and what to do about it?

As a new pediatric nephrology fellow, my first weeks taking care of patients on hemodialysis were overwhelming. Each of my patients had complex problems and intricate physiology, and I initially learned to focus on the numbers – clearance, blood pressures and weight – in order to optimize therapies for each patient’s clinical disease and status. About three months into fellowship, however, I was stumped by a young girl with ESRD whose numbers just didn’t make sense. She was losing weight, admitted repeatedly for infections, and had worsening clinical and laboratory parameters which wouldn’t improve with interventions. Despite nutritional supplements, additional dialysis sessions, and medication adjustments, nothing changed. Finally, the root cause became clear – she was hungry, and her family couldn’t afford to buy food. 

Unfortunately, this isn’t a rare experience in the United States. Food insecurity is common, affecting 16.6% of American households and 7.8% of American children – and appears to be more common in those with chronic illness, such as kidney disease. Food insecurity is defined as limited or uncertain availability of nutritionally adequate and safe foods, or limited or uncertain ability to acquire such foods in socially acceptable ways. I have seen families frequently make trade-offs between buying medication versus food, or choosing inappropriate food for their children’s medical problems due to cost. Parents have told me they often go hungry in order to feed their children – providing a human face to the statistics published by the U.S. Department of Agriculture (USDA) Economic Research Service showing that half of all parents or caregivers experiencing food insecurity shield their children from having to skip meals by skipping meals themselves. 

Why should food insecurity matter to nephrologists? Food insecurity is an essential social determinant of health with significant implications, including poorer overall levels of health, chronic medical conditions, and lower levels of psychosocial and physical functioning. A recent report showed that two-thirds of families with food insecurity have to choose between paying for medical care or food within the past year.These findings in children mirror studies in adult ESRD patients where food insecurity was associated with worse nutritional status and poorer quality of life. Among adults with chronic kidney disease, food insecurity accelerates disease progression, and may increase the risk of ESRD. Patients with food insecurity often use coping strategies which are deleterious for their health, including medication under-use or non-adherence, postponing or forgoing preventive care, or relying on a low-cost diet of energy rich but nutrient-poor foods. 

While awareness of food insecurity has increased in pediatrics and screening for food insecurity is frequently part of general pediatrics care, there no similar recommendations in either pediatric or adult subspecialties. Given the implications for our patients and their diseases, I would argue that all patients with kidney disease, especially those with ESRD, should be screened for food insecurity as part of their routine nephrology and dialysis care. Physicians, dietitians, and other health providers often counsel patients with kidney disease on dietary interventions, and awareness of food security status is paramount in providing optimal care. Many interventions and recommendations (such as a low-salt diet or phosphorus restriction) may be challenging or impossible to implement for patients who are food insecure. Screening should be performed with a standardized screening instrument, with several available and validated by the AAP, AAFP and USDA. Screening should be coupled with timely and appropriate referrals to food resources – an area of intervention that requires innovation, collaboration and community-based solutions. While eliminating food insecurity may be the eventual goal, the first step is to screen patients at risk; as only once we recognize, name, and quantify a problem can we start to identify solutions. 

 Post by Michelle Starr, NSMC Intern Class 2018

Understanding nPCR (Normalized Protein Catabolic Rate)

The normalized protein catabolic rate (nPCR) is a formula commonly used to assess dietary protein intake in dialysis patients, as a means towards determining nutritional adequacy, a major problem in many ESRD patients. For example, say you have a patient on dialysis who has a pre-dialysis BUN of 18 mg/dL--reasonably low, right?. This could mean that the patient is a well-nourished individual who is adequately dialyzed. But it could also mean that the patient is malnourished, which is often linked to poor appetite that is linked to inadequate dialysis. The nPCR helps distinguish between these possibilities.

The nPCR is reported in grams of urea nitrogen per kilogram per day, and can be calculated using several methods. One of them is shown here:

nPCR = 0.22 + (.036 * intradialytic rise in BUN * 24)/(intradialytic interval).

For instance, if the pre-dialysis BUN is 70 and the post-dialysis BUN is 18, and the intradialytic interval is 44 hours (e.g., there is an interval of 44 hours from the end of one dialysis until the beginning of the next), then the nPCR is calculated to be 1.24 g/kg/day. As you can see, a large intradialytic rise in BUN is generally indicative of adequate nutrition. Most guidelines specify maintaining the protein intake above 1.0 - 1.2 g/kg/day in dialysis patients, with values less than 0.8 g/kg/day being equated with malnutrition.

If the patient has significant residual renal function, then one must add a term that takes into account endogenous urea clearance. Importantly, these equations are only valid for individuals in steady state, and are not as helpful in the setting of acute illness. Separate equations exist for peritoneal dialysis, since the BUN levels are relatively constant and therefore pre- and post- levels cannot be used to estimate nPCR; rather urea levels in serum and peritoneal filtrate can be compared. Nutritional status can be especially important to assess in patients on peritoneal dialysis, since these patients are at high risk of losing albumin in the peritoneal filtrate. There is a nice discussion of this topic in Up-To-Date ("Protein catabolic rate in maintenance dialysis"), which includes alternative formulas for nPCR that incorporate Kt/V.

Survival Rule of Threes

I recently learned the "Survival Rule of Threes"--which gives a rough estimate of how long a person can live in various extreme survival conditions.  For example....

...you can expect to live for 3 minutes without air.

...you can expect to live for 3 hours without shelter (in an extreme condition like Antarctica for example).

...you can expect to live for 3 days without water.

...you can expect to live for 3 weeks without food.

Obviously these are only rough estimates (and I don't encourage you to find out whether or not you can beat these various marks) and there is a wide variability between human beings.  Gandhi was able to fast for 3 weeks while already in his 70s.  One member of the Irish Republican Army, Thomas McElwee, successfully survived for 73 days during a hunger strike.   The infamous case of Terry Schiavo in 2005 ended with her death about 2 weeks following the court-ordered removal of her feeding tube.  

Not surprisingly, one can last a lot longer without food than without water, a testament to (a) how much water one loses with just the normal processes of breathing and sweating, and (b) the potentially lethal complications of hypernatremia and the importance of maintaining appropriate water concentration.

Vitamin D Basics

Sometimes the formulations of vitamin D can get confusing. Here's a few key points:

1. The terms "vitamin D2" and "vitamin D3" do not refer to the hydroxylation status of vitamin D--either D2 or D3 can exist in the (1,25-OH), (25-OH), and unhydroxylated varieties--rather, they refer to whether or not the vitamin D derives from animal (D3, also called cholecalciferol) or plant (D2, also called ergocalciferol).

2. Ergocalciferol (Vit D2) is the least expensive, is the type of vitamin D with which milk is fortified, and can be given in large enough oral doses to correct vitamin D deficiency relatively rapidly (e.g., 50000 units of ergocalciferol po qweek x 12 weeks).

3. Cholecalciferol (Vit D3) is better absorbed orally than Vit D2, but is not available as a high dose form like D2 (e.g., 400-800 units po qd of cholecalciferol).

4. Calcitriol refers to the activated form of vitamin D, which is hydroxylated at both the (1) and (25) positions, and may be either D2 or D3; the medication calcitriol is the D3 form.

5. Cholecalciferol (VitD3) is produced in the human skin in response to UV light and is initially unhydroxylated at both the (1) and (25) position. Hydroxylation occurs at the (25) position in the liver (an efficient process which generally occurs even in the setting of advanced liver disease) and occurs at the (1) position in the kidney.

6. Paricalcitol (Zemplar) is a vitamin D2 analogue which is hydroxylated at both (1) and (25) positions.

7. doxercalciferol (Hectorol) is another vitamin D2 analogue which is hydroxylated only at the (1) position.

MDRD II

Continuing on with a brief discussion of the landmark MDRD Study: at the time of the study, several smaller studies suggested that a low protein diet would prolong time to ESRD for patients with CKD. The theory was that low dietary protein would lead to (a) less buildup of nitrogenous wastes which might contribute to uremia, (b) improved acidosis normally associated with advanced CKD, and (c) less proteinuria and thus less ongoing renal damage.

The MDRD Study took several hundred patients with moderate CKD (GFR = 25-55 cc/min) and advanced CKD (GFR = 13-24 cc/min) and subjected them to a 2x2 prospective randomized control design. They tested the effect of both usual-protein versus a low-protein diet (defined as 0.58 g of protein per kg of body weight per day) as well as having both high BP target and low BP target groups. The average follow-up time in this study was just over 2 years. For the most part, there were no major differences in any of the groups in terms of rate of progression to ESRD. Effects of the low-protein diet were seen, however: in the moderate CKD group, those randomized to the low protein diet actually showed a transiently DECREASED GFR over the first 4 months of the study, only to demonstrate a slower rate of decline at later time points. The authors described this graph by stating that the initial decrease in GFR is due to hemodynamic effects which over the long run actually have beneficial effects (kind of like ACE-inhibitors' effect on the kidneys). So although the results of the trial were essentially negative for any effect of a low-protein diet on slowing CKD progression, there are many who believe that had the patients been followed out for an even longer period of time, the benefit would ultimately manifest.