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REVIEW ARTICLE


Overview of CKD :Diet & Progressive of CKD

A. K. Bhalla

Co-Chairman and Director Dialysis Services, Department of Nephrology Sir Ganga Ram Hospital, New Delhi



Definition of Chronic kidney disease (CKD)

It is defined as Structural or functional abnormalities of the kidney for > 3 months a manifested by either (Table 1).


Table 1 :Abnormalities suggestive of Kidney Damage


Normal Albumin execretion is <30mg/24hours. Microalbuminuria is defined as presence of 20-200ugm/min or 30-300mg/24 hours of albumin in the urine. Presence of microalbuminuria is the first sign of glomerular involvement. Macroalbuminuria isdefined aspresence of >300mg/24hours

albumin/protein in the urine. Nephrotic range Proteinuria is

  1. Kidney damage with or without decreased GFR as defined by

  2. eGFR < 60ml/min/1.73m2 with or without kidney damage. (KJDOQI guidelines)


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Stages of CKD Among patients with chronic kidney disease, the stage of disease should be assigned based on the level of kidney function, level of GFR, with higher stages representing

proteinuria >3.5gm/24hours/1.73m2BSA. Other markers of kidney function are, BUN, Cystatin C ( normal levels 0.5- lmg/l)

Estimation of GFR: Estimation of GFR can be done using following equations:

1. Cockcroft- Gault (1976) equation: (140 - age) & wt (kg)

72 x creatinine

In females the product of the equation is multiple by 0.85

lower GFR levels, irrespective of diagnosis, according to the 2. KDOQI CKD classification (table 2).


Table 2 :Stages of Chronic Kidney Disease

MDRD (1999)

GFR (ml/min per 1.73m2) =186 x (S.creatinine x 0.0113 - 1.154 x (age) - 0.203 x 0.742 if female) x (1.212 if African American)

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Stage Description GFR


I

Kidney damage with normal

or increased GFR

:2: 90ml/min

II

Kidney damage with mild decreased GFR

60-59ml/min

III

Moderate decreased GFR

30-59ml/min

IV

Severe decreased GFR

15-29ml/min

V

Kidney failure

15 ml/min

(or dialysis)

3. Chronic kidney disease Epidemiology Collaboration (CKD- EPI) equation.

Males: 141 x (Creatinine/0.9) x 0.411 x (0.993) x age Female: 141 x (creatinine/ 0.7)x 0.329 x (0.993) x age

Diet & Progression of CKD

Brenner et al suggested 40 years age the theory of hyperfiltration and hyperfunction by animal studies. It was studied in animal studies that high protein diet lead to hyper

filtration and increased GFR and dietary protein intake may

Albuminuria: Albuminuria is not only an early sign of glomerular involvement but also of generalized vascular damage. It is single best predictor of disease progression.

be an important determinant of the rate of decline in renal function inpatient with CKD. Itiswell known factthat protein restriction in CKD alleviates uremic symptoms and slows the progression of CKD. However patient with established CKD

are already having anorexia and malnutrition and what is going to be the impact of pattern restriction on nutritional

Table 4 :Management of BP in CKD (K-DIGO guidelines 2012)

status and clinical outcome of patients of CKD.

Because of these factors, the patient are supplemented with ketoanalogs which improve the protein and Amino acid metabolism and may have a beneficial effect on carbohydrate and lipid metabolism too. In addition, ketoanalog in various

BP Goal Non diabetic Diabetic Medication


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AER < 30 ::;; 140/90 ::;; 140/90 AER 30-300

ARB/ACEI ACEI/ARB

studies have slowed the progression of CKD.

Causes of Malnutrition of CKD: Malnutrition in CKD causes malaise, fatigue, poor rehabilitation, increased susceptibility to infection and increased hospitalizations,

AER >30 ::;; 130/80

::;; 130/80 AER > 300

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ARB/ACEI ACEI/ ARB

also there is impaired healing and all these factors lead to increased mortality in these patients.

Various factors lead to malnutrition in CKD (Table 3)


Table 3 :Causes of malnutrition In CKD


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Uremia and uremic Toxins.

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Protein-energy-malnutrition (PEW) is of two types of in CKD. Type I PEM is due to inadequate protein intake due to anorexia .Causes of anorexia are uremic toxins, inflammation (strong relation with CRP, IL-6, TNF alfa) and hormones like leptin and Gherelin. Type II- PEM is irreversible and is characterized by presence of inflamation related due to increased ytokines, uremic toxins and occult sepsis. The leads to syndrome called malnutrition, inflammation and Atherosclerosis syndrome (MEA).


Management of Progression and Complications of CKD

Strategies which can slow progression of slow CKD are

  1. Blood pressure control & RAAS interruption

  2. Good glycemic control

    Protein Intake and progression of CKD

    In MDRD study (Saulo klahar et al NEIM, 1994), total number of patient (N=840) were assigned to diet three types of diets High protein, low protein and very low protein diet along with ketoanalogues and BP groups (Table 5). The mean follow up was 2.2 years. In study 1, 585 patients with glomerular filtration rates of 25 to 55 ml per minute per 1.73 m2 of body-surface area were randomly assigned to a usual­ protein diet or a low-protein diet (1.3 or 0.58 g of protein per kilogram of body weight per day) and to a usual- or a low-blood-pressure group (mean arterial pressure, 107 or 92 mm Hg). In study 2, 255 patients with glomerular filtration rates of 13 to 24 ml per minute per 1.73 m2 were randomly assigned to the low-protein diet (0.58 g per kilogram per day) or a very-low-protein diet (0.28 g per kilogram per day) with a keto acid-amino acid supplement, and a usual- or a low-blood-pressure group (same values as those in study 1). An 18-to-45-month follow-up was planned, with monthly evaluations of the patients. The rate of change in the GFR (the slope) was the primary outcome measure. Conditions requiring withdrawal from the study included malnutrition (weight loss to a level below 75 percent of standard body weight or a serum albumin < 3.0 g per deciliter despite corrective measures), a rapid decline in the glomerular filtration rate in study 1 only (to a value <50 percent of the base-line rate, if that value was ::;; 40 ml per minute per 1.73 m2, or to a value of ::;; 20 ml per minute per 1.73 m2, if the base-line rate was >40 ml per minute per 1.73m2), end-stage renal disease requiring dialysis or transplantation, and the development of other serious medical conditions. (Saulo klahar et al NEIM, 1994).


    Table 5 :Study Design of MDRD Study


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    Study 1N=585 Study 2 N=255

  3. Low protein intake

  4. Control of hyperurecemia

  5. Restricted salt intake

Complication associated with CKD include: anaemia, CKD- mineral bone disease (MBD) and acidosis. For good glycemic control the target HBAlc should be < 7.0% (ADA)

GFR- 25-55ml/min

Usual Mean Arterial pressure (MAP) 107mmHg VS 92mmHg

Target protein intake : l.3gm/kg/d

Low protein diet - 0.58gm/kg/d.

GFR 13ml/min

Usual Mean Arterial pressure (MAP)


Target protein intake : 0.58gm/kg / 0.28gm/kg +

Keto-analog (equal 0.28gm/kg of protein)


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The study shoed that initial reduction in GFR in low BP and low protein group was due to hemodynamic changes in 1st four months. Long term rate of loss of GFR was reduced in low MAP and low dietary protein group however this was offset by the increased early loss so at the end there was no significant long term difference among the groups. Patient with greater degree of proteinuria in both groups had more rapid loss of GFR. Baseline proteinuria was the strongest predictor of progression. Patient with proteinuria of > lgm/ day had more beneficial effect with reduction of MAP.

On Secondary outcome analysis, if was found that there was variability in patient depending upon basic cause. Like PKD patient had higher fall of GFR followed by glomerular disease and slowest in tubule interstitial disease.

Schematic analysis of most of the studies on diet and CKD studies such as Ihle et al (1989), Rosman et all (1989), Locateli et all (1991) Williams et al (1991) and Klahr et al (1994) tend to favour low protein diet on effect on progression of non diabetic kidney disease and also the reducing protein intake in patients with CKD reduces the occurrence of renal death by 40% compared to higher/ unrestricted protein intake and on reanalysis of MDRD study, it was seen that very low protein diets with keto­ analogs had slowed the progression of advance renal disease more than supplemented diet with EAA mix. Multi-study analysis showed that by reducing protein intake in patients with CKD, we could delay dialysis in 40% of patient.

KDIGO recommendation for protein intake in CKD are: lower protein intake to 0.8gm/kg/day in adult with diabetes or without diabetes with GFR < 30ml/min/1.73m2 with appropriate education and avoid high protein intake > 1.3gm/kg/day in adult with CKD at risk of progression. Beneficial effects of protein control are given in Table 6.


Table 6 :Reasons To Control Protein Intake Of Patients With CKD


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  1. Adequate adaptation to a reduction in proteins intake

  2. Decreased load on remaining nephrons.

  3. Improve Insulin resistance

  4. Decrease oxidant stress

  5. Decreased ameliorate proteinuria

  6. Decrease serum parathyroid levels

  7. Improve lipid profile

    Calories inCKD :

    The energy intake should be 35 k cal /kg/day who are <60 years of age and 30-35 k cal/kg/day for individual > 60 years. This amount of energy intake will spare body proteins and promote higher serum albumin levels. Low calories are given to patients who are >60 years of age as they are more sedentary.


    Potassium inCKD :

    Potassium should be restricted if urine output is less than 1 litre/day and GFR is <lOml/min or patient is on ACE inhibitors and ARB/Blockers or if patient is having hyperglycemia and serum potassium is >5mEq/l. Goal is to maintain serum potassium between 3.5-5mEq/l


    Phosphorus Restriction:

    Target phosphorus levels is 3.5-5.0mgo/o.

    When GFR declines to 40-45ml/min/1.73m2, urinary execretion of phosphorus decreases and hyperphosphaetemia ensues. Higher dietary phosphorus intake might be associated with increased mortality in non diabetic CKD. Increased phosphorus leads to increased atherosclerosis and increased FG- 23 and increased chance of left ventricular hypertrophy (LVH). High dietary phosphorus intake could also worsen kidney disease progression.


    Salt Intake and CKD:

    KDIGO recommends <2gm/day of sodium (1 teaspoon is 5gm of sodium chloride and 2.5 g of Na) in adults.


    Uric Acid and CKD

    Elevated subjective global assessment (SGA) score (>7 in men and >6 in women), elevated uric acid may lead to progression of CKD, increase cardiovascular (CV) and all cause mortality. CKD can improve with specific uric acid lowering therapy. Small studies of control of uric acid show benefit in reduced LV mass, improved endothelial function, decreased CV events and decreased hospitalization.


    Lipid metabolism in CKD

    Plasma lipid abnormalities are worsened with progression of the renal failure (GFR <40-60ml/min). Cardiovascular disease represents 25-50% of death after initiating dialysis therapy and various risk factor are given in Table 7.


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    Table 7 :Risk Factors for Cardiovascular Disease After Initiation of Dialysis

  8. Additive effect of ACE inhibitors.

    Traditional CV

    Risk Factor

    Factor Peculiar Emerging Risk

    To CKD Factor

  9. Decreased likelihood of patient death or delay

initiation of dialysis by 40%.

  1. Decreased number needed to treat (one patient saved from death or initiation of dialysis every year for every 18 patients)

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  2. Lack of serious objective reasons for not recommending a low protein diet to most patients with CKD

Hypertension

Diabetes positive family history


Smoking Hyperlipidemia

Anaemia

Hyperpara­ thyroidism (HPTH)

Homocysteine CRP


Malnutrition (MIA syndrome) Assymetric demethyl arginine (ADMA)


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Obesity and CKD :

Although obesity may be risk factor for CVD, however this is reversed epidemiological effect of obesity in hemodialysis patients. Patient who are obese at initiation of hemodialysis, have survival advantage over underweight patients. There


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References:

1. KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification Guideline 1. Definition and Stages of Chronic Kidney Disease 2002 National Kidney Foundation, Inc

could be resistance to catabolic state of CKD. Simultaneously, 2.

patients with high LDL levels and high total cholesterol may have less mortality in hemodialysis patients.

3.

Summary:

  1. Malnutrition & wasting is common in CKD and is a negative prognostic factor.

  2. Protein intake- CKD stages 3 and stage 4- 0.8gm/kg/ 4.

    day.

  3. There is role of protein restriction in showing the progression of CKDand delaying the start of dialysis 5. and improving quality of life by alleviating uremic symptoms. However repeated detail assessment of

    nutritional status shouldbe doneto avoid malnutrition.

    6.

  4. In addition to protein restriction, there is role adequate calories phosphorus and salt intake in progress of CKD.

    7.

  5. Very low protein diet supplemented with ketoanalogs slows the progression of CKD.

Keane WF, Eknoyan G: Proteinuria, albuminuria, risk, assessment,

detection, elimination (PARADE): A position paper of the National Kidney Foundation. Am J Kidney Dis 33:1004-1010, 1999

Levey AS, Beto JA, Coronado BE, Eknoyan G, Foley RN, Kasiske RL, Klag MJ, Mailloux LU, Manske CL, Meyer KB, Parfrey PS, Pfeffer MA, Wenger NK, Wilson PW, Wright JT Jr: Controlling the epidemic of cardiovascular disease in chronic renal disease: What do we know? What do we need to learn? Where do we go from here? Am J Kidney Disease 32:853-905, 1998

Saulo Klahr, Andrew S. Levey, Gerald J. Beck, Arlene W. Caggiula The Effects of Dietary Protein Restriction and Blood-Pressure Control on the Progression of Chronic Renal Disease N Engl J Med 1994; 330:877- 884 March 31, 1994

KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification Guideline 10.Association of Level of GFR With Bone Disease and Disorders of Calcium and Phosphorus Metabolism 2002 National Kidney Foundation, Inc

KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification Guideline 13. Factors Associated With Loss of Kidney Function in Chronic Kidney Disease 2002 National Kidney Foundation, Inc

KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification Guideline 10.Association of Level of GFR With Bone Disease and Disorders of Calcium and Phosphorus Metabolism 2002 National Kidney Foundation, Inc