Nephrologists recommendations

[Guest guest]

Hi there. I have been in contact with a doctor at the Mayo clinic in

MN. He sent me some documents that I thought was interesting. I left

his name out. He is also sending me a new report just finished from

the Seminars in Nephrology that he did. I believe its coming via

snail mail. Will let you know when I get it. I will try to upload

the ordering form in the files page of this group. Let me know what

you think. I'm gonna order some Friday.

The health benefits of omega-3 polyunsaturated fatty acids (n-3

PUFA) have gained wide attention both in the medical literature and

lay press. Favorable effects of n-3 PUFA in a variety of

cardiovascular and autoimmune diseases are supported by an

impressive number of studies reported over the past decade (Table

1). The evidence for these beneficial effects is based largely on

epidemiological studies and randomized clinical trials in which both

fish consumption and fish oil supplements were tested for efficacy.

The safety and content of dietary supplements containing

eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two

major n-3 PUFA, has recently been reviewed(3). The usual fish oil

supplements available over-the-counter in pharmacies and health food

stores are not standardized by refinement, composition or

encapsulation procedures. One does not know what they contain in

the way of contaminants or oxidation products. We can recommend a

product which is a pharmaceutical-grade fish oil concentrate,

Coromega„·, manufactured by European Reference Botanical

Laboratories, Carlsbad, CA. Pronova Biocare, Oslo, Norway, provides

the fish oil used in Coromega„· which, in turn, is manufactured in a

pharmaceutically qualified facility in Carlsbad, CA, using the

highest quality ingredients and pharmaceutical Good Manufacturing

Procedures. The oil is produced from raw fish oil through a three-

stage process of purification and concentration that complies with

European standards of Good Manufacturing Practice (22). This

process yields oils that are highly refined and therefore represent

a pharmaceutical preparation in which potential impurities, such as

polychlorinated biphenyls, heavy metals and dioxins, are effectively

removed, as are pesticide residues, unwanted fatty acids and

oxidation products.

Coromega„· is formulated in emulsified pouches of an orange-flavored

mixture. Each pouch contains a 650 mg concentrate of very long

chain polyunsaturated n-3 fatty acids, providing 350 mg of EPA and

230 mg of DHA, and 3 I.U. of d-alpha tocopherol serving as an

antioxidant.

Referring to the cardiovascular diseases listed in Table 1, eating

oily fish to increase omega-3 fatty acid intake is preferable.

However, for patients with coronary heart disease, the dose of omega-

3 PUFA of approximately 1 g/day may not be practical to achieve

through diet alone. This also applies to persons who need to lower

serum triglyceride levels. Clinical trials have shown that n-3 PUFA

supplements can reduce cardiac events, including death, non-fatal

myocardial infarction and stroke, hypertension and arrhythmias

(Table 1). Under a physician¡¦s care, n-3 PUFA supplements can

become a component of the total management of patients with coronary

heart disease, and can be useful as a preventive measure in persons

without a history of heart disease. Coromega„· may be prescribed in

doses of two pouches per day for the cardiac event risk reductions,

and three pouches per day for reduction of hypertriglyceridemia.

Adding n-3 PUFA supplements in patients with end-stage renal disease

who require renal replacement treatment with either chronic,

repetitive dialysis or renal transplantation is also supported in

clinical trials (Table 1). For the various conditions listed in the

chronic dialysis population, we recommend Coromega„· in a dose of two

pouches per day for the cardiovascular event risks, and 5 pouches

per day for prevention of vascular access graft thrombosis,

reduction in EPO requirements, and relief of uremic pruritis. In

the renal transplant patients, we recommend 5 pouches of Coromega„·

per day to reduce cyclosporine toxicities and rejection episodes.

In rheumatoid arthritis, prescribing 5 pouches per day of Coromega„·

may be beneficial in reducing arthritic symptoms and lowering the

requirement for nonsteroidal anti-inflammatory drugs (Table 1).

In IgA nephropathy, the most common form of primary

glomerulonephritis in the world, efficacy of n-3 PUFA in fish oil

supplements has been tested with varying results. The largest

randomized clinical trials, performed by our collaborative group (19-

21), provided strong evidence that treatment for two years with 1.8

g of EPA and 1.2 g of DHA slowed the progression of renal disease in

high-risk patients. These benefits persisted after 6.4 years of

follow-up. A prescription of Coromega„· of five pouches per day in

adults, and 2 pouches per day in children up to the age of 12 years,

provides our recommended doses of EPA and DHA for treating patients

with IgA nephropathy.

Additional trials in all of the disorders listed in Table 1 are

needed, and are being conducted in most, to further define the

health benefits of n-3 fatty acid supplements.

Table 1. The Beneficial Effects of n-3 PUFA in Cardiovascular and

Autoimmune Diseases

Disease Beneficial Effects

Coronary heart disease Reduce the risk of death from cardiac and

non-cardiac causes in persons with (1-3) and without (4) a history

of coronary heart disease.

Hypertension Improve blood pressure especially in hypertensive

patients and those with clinical atherosclerotic disease or

hypercholesterolemia (5).

Arrhythmias Reduce risk of sudden cardiac death (1, 3, 6) by

stabilizing the myocardium (3).

Stroke Reduce the incidence of stroke (7).

Hypertriglyceridemia Lower serum triglyceride levels (8); fasting

hypertriglyceridemia has been identified as an independent risk for

ischemic heart disease (9).

End-stage renal disease

--Chronic dialysis patients

Decrease the risk of death from cardiovascular disease (1, 2, 10);

lower blood pressure in hypertensive patients (11); prevent vascular

access graft (PTFE*) thrombosis (12); reduce EPO** requirements

(13); relieve uremic pruritis (14).

--Transplant patients Reduce cyclosporine-induced hypertension and

renal function impairment in solid-organ transplanted patients

receiving this drug for immunosuppression (15); reduce rejection

episodes and shorten hospitalizations in renal transplant recipients

(16).

Rheumatoid arthritis Ameliorate arthritic symptoms (17) and

reduce nonsteroidal anti-inflammatory drug therapy (18).

IgA nephropathy Reduce renal disease progression in high-risk

patients (19-21).

*PTFE -- polytetrafluoroethylene (Teflon)

**EPO ¡V erythropoietin

TABLE OF CONTENTS

1. DESCRIPTION OF THE DISEASE

1.1)

Definition

1

1.2) Clinical

Features

1

1.3) Disease

Outcome

2

2. REASON FOR

THERAPY

3

3. DESCRIPTION OF COROMEGA AND SCIENTIFIC RATIONALE FOR ITS USE

IN IgA NEPHROPATHY

3.1) Product Composition And

Formulation 3

3.2) Rationale For The Use Of Coromega In The Treatment Of

Patients With

IgA

Nephropathy

4

3.3)

Dosage

5

4. HOW TO OBTAIN COROMEGA AND

PRICING 5

5.

REFERENCES

6

ii

Page 1

1. DESCRIPTION OF THE DISEASE

1.1)Definition ¡V Immunoglobulin A (IgA) nephropathy, first described

in 1968

by Berger and Hinglais, is now recognized as the most common

form of

primary (cause unknown) glomerulonephritis in the world(1).

Primary IgA nephropathy is an immune complex-mediated

glomerulo-

nephritis defined on immunohistologic examination by the

presence of

glomerular IgA deposits accompanied by a variety of

histopathologic

lesions(2).

For many years, primary IgA nephropathy was considered to

be a benign

condition. It is now clear, however, that a large number of

cases eventually

progress to renal failure. It is the main cause of end-stage

renal disease in

patients with primary glomerular disease requiring renal

replacement therapy

with either renal transplantation or chronic, repetitive

dialysis(3,4).

1.2)Clinical Features ¡V In the early stages of the disease, many

patients have

no obvious outward symptoms and are usually unaware of any

problems. In

these patients, IgA nephropathy may only be suspected during routine

screening or investigation of another condition. However, some

patients may

present with aggressive disease.

In general, there are few characteristic clinical signs;

however, micro-

scopic hematuria and proteinuria may be persistently or

intermittently

Page 2

detected for many years. Patients with IgA nephropathy usually

present with

one of the following: (1) episodes of macroscopic hematuria (tea-

colored

urine) that may coincide with an upper respiratory tract

infection. This pre-

sentation usually occurs in patients under 40 years of age. Loin

pain often

accompanies hematuria; (2) abnormal urine sediment and

proteinuria in

asymptomatic patients, usually more common in older patients, but

this

presentation is observed in all ages.

It is important to emphasize that a definitive diagnosis of

IgA nephropathy

can only be made by renal biopsy and immunohistological examination.

Up to 20 percent of patients with IgA nephropathy present with

severe

azotemia that represents long-standing disease that differs from the

classic

presentation either because the patient did not come to early

medical at-

tention or was referred late without an established diagnosis.

1.3) Disease Outcome ¡V Primary IgA nephropathy is characterized by a

highly variable course ranging from a totally benign condition

to rapidly

progressive renal failure. From 15 percent to 40 percent of

patients will

eventually suffer end-stage renal failure(5). Most of these

patients

develop a chronic, slowly progressive renal failure.

Over the past decade or so, numerous studies from around

the world

have reported clinical, laboratory and pathologic

characteristics that predict

progressive renal disease(5-7). Both in children and adults,

hypertension,

high glomerular histopathologic scores, persistent microscopic

hematuria and

Page 3

proteinuria exceeding 1 g/24 hr, and impaired renal function

at the time of

diagnosis stand out as consistent and strong predictors of

poor renal survival.

Although not exacting on a case-by-case basis, it is

useful to establish a

profile of clinicopathologic features to establish which

patients are more at

risk for progressing to renal failure, and for whom treatment

strategies can be

designed in an attempt to slow or halt renal progression.

2. REASON FOR THERAPY

Until recently, there was no effective treatment available for

patients with

IgA nephropathy. Although there remains no cure, treatment

options are

becoming available that slow disease progression. Knowing that

IgA

nephropathy may affect up to 1.3 percent of the population, it

is clear

there is need for novel therapeutics agents capable of

preserving renal

function.

3. DESCRIPTION OF COROMEGA AND SCIENTIFIC RATIONALE FOR

ITS USE IN IgA NEPHROPATHY

3.1) Product Composition And Formulation -- Coromega is

formulated in

emulsified packets of an orange flavored mixture. Each packet

contains a

650 mg concentrate of very long chain polyunsaturated n-3 fatty

acids and 3

I.U. of d-alpha-tocopherol. The concentrate is produced from

premium grade

fish oil and each packet contains 350mg of eicosapentanoic acid

(EPA) and

230 mg of docosahexanoic acid (DHA).

Page 4

3.2)Rationale For The Use Of Coromega In The Treatment Of

Patients

with IgA Nephropathy -- Causes of glomerular diseases, such as

IgA

nephropathy, or how to prevent them are unknown. Current

interventions in glomerular disease are aimed at retarding

progression

and, thus, preserving renal function. In IgA

nephropathy, treatment

should be prescribed for patients who are at risk for developing

progressive renal disease rather than treating asymptomatic diseases

which may result in giving unnecessary therapy to patients who might

remit spontaneously. A risk profile for patients with IgA

nephropathy is

presented in 1.3 Disease Outcome.

The rationale for prescribing Coromega in IgA nephropathy

involves

potential mechanisms that reduce renal inflammation and glomerulo-

sclerosis, hallmarks of progressive renal disease(8).

Fish oil preparations containing a daily intake of 1.8 g EPA

and 1.2 g

DHA have been shown to reduce significantly renal disease progression

in high-risk patients with primary IgA nephropathy in a multicenter,

randomized, placebo-controlled, 2-year clinical trial(9). In a

follow-up

observational study extending beyond the 2-year trial, long-term

treatment

with n-3 fatty acids consistently retarded renal disease progression

(10).

More recently, the effects of high-dose n-3 fatty acids (3.76 g

EPA,2.94 g

DHA) were compared with standard-dose n-3 fattyacids (1.88 g EPA,1.47

g DHA)(11). Both doses showed similar effects in slowing of the

rate of

Page 5

renal function loss particularly in those patients with

moderately advanced

renal disease defined as having serum creatinine levels

up to 3.0 mg/dL

and proteinuria greater than 500 mg/24 hr.

3.3) Dosage ¡V We previously determined that a daily dose of n-3

fatty acids composed of 1.8 g EPA and 1.2 g DHA efficiently en-

hanced EPA and DHA and total n-3 polyunsaturated fatty acids of

plasma phospholipids(12). This dose can be recommended on the

strength of the findings in the clinical trials outlined in 3.2

Rationale For

The Use Of Coromega(9-11).

A daily dose of 5 packets for adults and 2 packets for children

under

age 12 years with or without food is recommended. This provides a

daily

dose of 1.75 g EPA and 1.15 g DHA for adults, and 0.7 g EPA and 0.46

g

DHA for children. Each packet should be torn or cut along the

perforation

and squeezed directly into the mouth or onto a spoon. Coromega may

be

added to cold food, such as yogurt, or mixed with a beverage

(electric

blending required). Coromega packets should be stored in a cool,

dry

place and not frozen or heated.