alternative remedies in rheumatic disorders

alternative remedies in rheumatic disorders

alternative remedies in rheumatic disorders

Many patients with rheumatic disease suffer physically and emotionally.
they need to learn to address the illness,

“All who drink of this remedy are cured, except those that die. Thus, it’s effective for almost the incurable.” Galen.
What is the role, if any, for “complementary” and “alternative” remedies within the routine therapy of patients with rheumatic diseases? Despite considerable interest in these therapies , I don’t consider that anything truly clinically important has emerged in rheumatology .

“Alternative” or “complementary” therapies in medicine have gained public attention and implied endorsement by the u. s. government:
• A survey of patients followed privately and university-based rheumatology practices found that roughly two-thirds had used some type of complementary or alternative therapy .
• A subsequent survey of 232 consecutive patients in both private and university rheumatology practices found that one-third were actively using one or more of those therapies during the course of 1 year .
• In 1992, Congress established an Office of different Medicine, now renamed the National Center for Complementary and medicine, at the National Institutes of Health (NIH), with an annual budget now in way over $100 million.
It therefore behooves clinicians to be aware of a number of these “complementary” and “alternative” remedies available for rheumatological patients so as to be able to effectively communicate with patients and colleagues.

DEFINITION

 

The American College of Rheumatology (ACR) established a committee in 1993 to handle pertinent issues originally surrounding the efficacy of those remedies.
At that point, the committee deliberately selected the term “questionable,” following the approaches of other groups.
This permitted the avoidance of other terms that euphemized questionable remedies.
to evolve to current trends, the ACR later adopted the terms “complementary” and “alternative.”
There are three forms of therapies:
• Genuine, defined as those proven acceptably safe and effective
• Questionable
• Ineffective
I have come to prefer the terms “mainstream” and “nonmainstream” to best categorize how therapies are conceived.
These names are preferable to other terms for possible remedies, like “unapproved” (eg, by the Federal Drug Administration), “false” (disproven), “unproven” (experimental), “dubious” (very doubtful), “non-standard” (falling wanting practice standards), “irregular” (not employed by mainstream medicine), or perhaps “alternative” or “complementary” (reflecting various questionable or conventional treatment options) .

APPEAL

Many patients with rheumatic disease suffer physically and emotionally.
they need to learn to address the illness, the constraints imposed by the restrictions of medication, and therefore the considerable uncertainty concerning outcome. These adjustments don’t seem to be always easy.
Patients want hope for a cure or for relief.
Nonmainstream approaches offer hope.
Patients may therefore turn from science and seek understanding and relief (and empowerment) from questionable sources .
we will understand this quest and sympathize since we’ve got undoubtedly also sought and used questionable remedies (such as soup for a chilly or a rub for an ache).
Increasingly, many seek “complementary” and “alternative” remedies as a way of life choice .
Recent observations suggest that a lot of patients seeking “complementary” and “alternative” therapies do so in response to psychosocial distress, not necessarily thanks to severe or unresponsive illness .

MEDICAL RESPONSE

 

The medical response to “complementary” and “alternative” remedies therefore remains problematic.
Our different options include:
• We can inform ourselves, which is that the intent of this section.
• We can dismiss them.
• We can establish repositories of data about them, which the American College of Rheumatology and Arthritis Foundation has done .
• We can try and communicate with patients and also the public through the media. However, “Doctor’s diet cures arthritis” makes instant headlines within the lay press; by comparison, “Doctor’s diet doesn’t cure arthritis” takes years of research, writing, and revision before appearing within the rheumatology literature, and has limited impact upon physician and patient practices .
• We can aggressively combat public perceptions within the press and within the courts, as does the National Council Against Health Fraud.
• Although this is often a worthy effort, its success is additionally limited .
Education and communication must suffice until our science improves .

Many physicians have a too frequent impulse to disdain and sometimes to ridicule “complementary” and “alternative” remedies.
we’ve got a conventional intellectual view of science and also the concept that human problems will be understood and solved by the suitable application of science. However, science isn’t proof against superstition, fraud, errors, conservatism, pigheadedness, fashion, and trends (eg, tonsillectomies, adenoidectomies, irradiation for acne or autoimmune disease, and iced saline lavage for GI bleeds).
There are several possible explanations for our dismissal of “complementary” and “alternative” remedies from legitimate study.
Arguably, we not dismiss CAM.
First, non-mainstream approaches evoke discomfort and prejudice, and appear to defy rational explanation.
Second, quackery is purveyed by practitioners whom we sometimes consider unsavory and our intellectual inferiors since we don’t share their belief system, are offended by their audacity, or may feel demeaned if we condescend to contemplate their notions.
It may once have seemed absurd to propose that diet, antibiotics, or red peppers might sometimes help arthritis or that antibiotics would help ulceration disease. However, the outright rejection of “complementary” and “alternative” remedies risks missing potentially beneficial therapies .

HAZARDS

 

Although some may argue that patients should be permitted to do “complementary” and “alternative” therapies because they’re often a minimum of innocuous, I argue that it’s not responsible to use therapies generally not considered acceptably safe and effective.
As examples, some “complementary” and “alternative” therapies aren’t innocuous and are occasionally harmful:
• There are documented instances of patients who received therapies apart from those promised and suffered from adverse results, including marrow aplasia, serious infections from contaminants, and death.
• Patients seeking “complementary” and “alternative” remedies may inappropriately neglect their illness .
• Expenditures on “complementary” and “alternative” remedies may divert scarce health-care resources from more appropriate areas.
I will next consider selective and representative samples of “complementary” and “alternative” remedies.
a close discussion of those remedies is beyond the scope of this presentation, but has been reviewed elsewhere .

alternative remedies in rheumatic disorders

the science or practice of the diagnosis, treatment, and prevention of disease (in technical use often taken to exclude surgery).

 

 

SELECTED “COMPLEMENTARY” AND “ALTERNATIVE” REMEDIES

 

Prominent “complementary” and “alternative” remedies for rheumatic disorders include
• Diet
• Vitamins and minerals
• Nutritional supplements
• Fish oils
• Antimicrobials (nitroimidazole, rifamycin, ceftriaxone , tetracyclines, ampicillin , and amantadine )
• Biologic therapy (thymopoietin, transfer factor, placenta-derived factors, venoms, and herbal remedies)
• Other pharmacologic agents (cis-retinoic acid, isoprinoside, amiprolose, thalidomide , and dapsone )
• Topical agents ( dimethyl sulfoxide [DMSO])
• Mechanical/instrumental therapies (hyperbaric oxygen, laser irradiation, acupuncture, photopheresis, electromagnetic radiation), chiropractic manipulation, homeopathy, biofeedback, exercise, yoga, et al. (eg, sitting in abandoned uranium mines)
Antimicrobials
A microbial etiology for autoimmune disease (RA) has long been a horny but unproven hypothesis.
However, antimicrobials may well be useful if this hypothesis were true.
The following are instructive clinical experiences concerning therapy using antimicrobial agents for patients with rheumatic disorders .
However, the subsequent reflect largely isolated and unconfirmed observations.
• Nitroimidazole antimicrobial drugs are tried for the treatment of RA due to the efficacy of levamisole, another imidazole derivative, and since of claims that RA was caused by Amoeba limax. Results, however, haven’t been impressive .
• Rifamycin, an antibiotic that blocks DNA-dependent RNA polymerase and inhibits cellular protein synthesis, was promising for the treatment of rheumatoid knee synovitis in preliminary observations .
• Tetracycline therapy has also been tried based upon a putative mycoplasma etiology for RA.
• Such therapy was considered ineffective for several years. This issue has been revisited, however, since later scientific work found that tetracyclines, particularly minocycline , may have significant physiologic effects, including reduced collagenase activity, lessening of bone resorption, and perturbation of T-cell and neutrophil function. additionally, these drugs were found to be antiproliferative, antiinflammatory, and antiarthritic in animal and possibly human arthritis. Thus, tetracycline therapy is not any longer considered “complementary” or “alternative”.
• Patients with chronic inflammatory arthritis and antibody titers to Lime disease spirochete of 1:64 or greater have had encouraging responses to ceftriaxone .
• Ampicillin was reported to be beneficial under certain conditions for patients with RA .
• Amantadine , an medicine, was useful for a gaggle of patients with teenage-onset juvenile idiopathic arthritis who had elevated antibody titers to influenza A and were born during an influenza epidemic .
If observations suggesting a take pleasure in antimicrobial and/or antiviral therapy are consistently confirmed, either chronic arthritis in some patients results from bacterial, spirochete, or infection, or such therapy could also be antirheumatic.

Foods, diet and nutritional supplements
For years, special diets for patients with arthritis were relegated to quackery. it had been shortly ago that the Arthritis Foundation presented “The Truth about Diet and Arthritis,” stating “if there was a relationship between diet and arthritis it’d are discovered way back.
the easy fact is that there’s no scientific evidence that any food has anything to try to to with causing arthritis and no evidence that any food is effective in treating or ‘curing’ it .

We et al have now reexamined this notion.

balanced nutrition

the process of providing or obtaining the food necessary for health and growth

• How might food affect arthritis? First, some patients with rheumatic disease could also be allergic to certain foods and have symptoms that may be a manifestation of allergy.
• Second, certain sorts of diets with particular amounts of calories, protein, and fatty acids may affect the immunologically-mediated inflammation that happens with arthritis .
• Is there a diet for arthritis? there’s no compelling evidence at this time that any diet aside from a healthy, balanced one is consistently helpful to patients with arthritis.
• One study of a well-liked diet (the elimination of beef, additives, preservatives, fruit, dairy products, herbs, spices, and alcohol) for patients with arthritis found no consistent salutary effect on disease activity .
• Is arthritis caused by food hypersensitivity in some patients? Physicians and patients remain intrigued that arthritis may occasionally be the results of hypersensitivity to foods.
• As examples: palindromic rheumatism has been related to sodium nitrate; Behçet’s syndrome with black walnuts; systemic LE (SLE) with canavanine in alfalfa (which may cross-react with native DNA or activate B lymphocytes) and with hydrazine, and RA allegedly with many substances including house dust, tobacco, smoke, petrochemicals, tartrazine, dairy products, wheat, corn, and beef.
• In addition, rheumatoid-like synovitis in rabbits has been induced by dietary milk .

Careful, prospective, placebo-controlled, double-blind studies confirmed (for selected patients) that inflammatory arthritis can be related to foods.
• One patient, for instance, had half-hour of morning stiffness, nine tender joints, and three swollen joints on her regular diet .
• Virtually all of those findings disappeared after a 3 day fast.
• they may then be reproduced by milk challenge but not with other foods.
• The role of fish or plant oils or diets? Nutritional status exerts a profound influence on immune responsiveness and disease expression.
• As an example, mice with SLE or rats with arthritis that are fed diets rich in omega-3 (a present, substituted, polyunsaturated carboxylic acid analog) fared better than did control animals.

Clinical trials of fish oils and plant seed oils have suggested a modest decrease in certain symptoms with therapy in patients with RA but not SLE .
• Beneficial effects of animal oil supplementation could also be enhanced by limiting the dietary intake of polyunsaturated oils (eg, corn, soybean, safflower, sunflower) to 10 grams or less per day .
• Although capsules of animal oil are convenient, the quantity of omega-3 contained in each capsule is corresponding to that found in one mL of cod liver oil; thus, a 20 mL dose of cod liver oil, which is that the usual daily dose, provides roughly the identical amount of such fatty acids as that found in 20 capsules of animal oil.

In comparison to a typical “Western” diet, a Mediterranean diet generally derives fewer calories from animal material and more from cereals and vegetable oils, particularly vegetable oil.
• Liberal intake of fresh fruits and beans yet as a moderate daily consumption of wine is additionally typical of this kind of diet. The possible effects of a Mediterranean diet (MD) was the topic of a study within which 51 patients with RA were randomly assigned to a MD or to an omnivorous cuisine for 12 weeks .
• While those subjects who ate a MD had more improvement in some measures of disease activity, other indicators were unchanged.
• There was little change noted in patient global-assessments within the omnivorous subjects nor in their disease activity scores.
• Since the intervention and assessment weren’t “blinded” in any fashion, a big issue within the group assigned to the Mediterranean diet can not be excluded.

These observations suggest that dietary factors that modify arachidonic acid-derived prostaglandin or leukotriene generation affect inflammatory and immunologic responses and should therefore ameliorate symptoms of rheumatic diseases.
• The role of nutritional supplements? variety of drugs, including copper, zinc, and vitamin B, are reported to be helpful for patients with arthritis. In general, however, the evidence in support of such claims is scant
• As an example, although copper salts are antirheumatic in clinical trials, their use was related to many adverse effects; as a result, copper salts haven’t evolved as a very important therapeutic agent.
• In another study, some patients with RA benefited from oral zinc; however, the development was modest and inconsistent, and wasn’t confirmed in other studies.
• In addition, although the administration of L-histidine has helped atiny low set of patients with RA, it’s not emerged as a crucial agent. Evidence to support the efficacy of ascorbic acid for arthritis patients is additionally lacking.

While concentrations of pyridoxal are reduced within the serum of patients with RA and levels of pyridoxal 5′ phosphate, the active metabolite of B6, are inversely correlated with disease activity ; there’s at the present no convincing evidence that supplementing the diet with vitamin B has any beneficial effect on disease activity or associated disorders.
A general overview of dietary supplements is provided elsewhere.
Herbal remedies
Various herbal preparations are undergoing investigation for possible benefit for arthritis.
A good example may be a Chinese herbal remedy (an alcohol extract of Tripterygium wilfordii Hook F, TwHF) for autoimmune disease (RA), with suggestive immunosuppressive properties .
A handy study randomly assigned 35 patients with RA to placebo or one in all two doses (180 or 360 mg/day) of an alcohol/ethyl acetate extract of the herb.
A dose-response relation was noted with ACR 20 responses of 80, 40, and 0 percent within the high-dose, low-dose, and placebo groups, respectively; ACR 50 responses were note in 50, 10, and 0 percent.
Self-limited diarrhea developed more often during active treatment than with placebo (in approximately one-third and none, respectively).
Another randomized trial compared TwHF with sulfasalazine in 121 patients with RA; only 62 and 41 percent of these receiving TwHF (60 mg three times/day) and sulfasalazine (1 gm twice/day), respectively, completed the study .
Among those that completed the study, an ACR20 response was achieved significantly more often after 24 weeks of treatment by patients receiving TwHF (68 versus 36 percent).
HAQ scores and IL-6 levels improved more with TwHF, but there was no difference in ESR and CRP.
There was a 2.4 point improvement within the DAS28 with TwHF. Adverse event rates were similar within the two groups.
Additional clinical study and further investigation into the mechanism of the beneficial antiinflammatory effects of this herbal preparation are valuable.
Additional herbs and dietary supplements that are studied in patients with RA include the following;
• Those that showed some promising results: two Ayurvedic mixtures, borage, garlic, Phytodolor, Uncaria tomentosa, fish oil, and selenium
• Others that weren’t related to any clinical improvement, including blackcurrant (Ribes nigrum), Boswellia serrat, herb (eg, from common evening primrose and Oenothera lamarckiana), feverfew (Tanacetum parthenium), and green-lipped mussels.
However, all the studies were small, the results were modest at the best, and wish confirmation in standardized trials.
Other herbal preparations are promoted as treatments for osteoarthritis. One systematic review concluded that there was so far no evidence of a major benefit with Eazmov, Gitadyl, or ginger extract; by comparison, there was some evidence of efficacy (decreased pain) for Reumalex (a combination of willow bark, guaiacum resin, rattle-top, sarsaparilla, and poplar bark), willow bark alone, nettle, Articulin F (a proprietary combination of salai [Indian frankincense], Withania somnifera [winter cherry], turmuric and zinc), devils claw, extract of soybean and avocado unsaponifiables (ASU), Phytodolor (a combination of poplar bark, ash bark, and goldenrod), and capsaicin cream.
These would require rigorous well controlled randomized study to verify putative salutary effects.
A general overview of herbal medicine is provided elsewhere.
Other
Some of the newer biologic agents, like monoclonal antibodies, interleukins, cytokines, and similar products, are exciting due to their potential, and for a few, their established clinical value.
Even those biologic agents whose therapeutic roles are still being evaluated, don’t seem to be usually considered “alternative” remedies .
Additional “complementary” and “alternative” remedies and their possible efficacy include the following:
• Although venoms affect inflammatory and immune responses in vitro, they need no documented clinical utility.
• Indeed, a “beekeepers” arthritis has been reported .
• New pharmacologic approaches are of interest; some (such as dapsone ) may receive further attention.
• Dimethyl sulfoxide (DMSO) and hyperbaric oxygen aren’t of proven value.
• Laser therapy, utilizing low power light sources, has been evaluated for both arthritis and osteoarthritis.
• a scientific review of reported clinical trials reported that laser treatment of the hands of patients with autoimmune disorder provided significant benefits .
• By comparison, consistent trends haven’t been observed in those with osteoarthritis.
• It is difficult to supply any specific recommendations regarding low level laser therapy due to variations in protocols, including laser intensity, duration, wavelength, and frequency of treatments.
• Homeopathy and biofeedback have shown varying degrees of benefit in certain situations; however, these studies haven’t been confirmed.
• The subject of homeopathy is reviewed well elsewhere.
• Acupuncture has not been found effective in patients with RA, and isn’t a risk-free procedure.
• A review of reported complications included two deaths thanks to needle injuries to the center and 90 pneumothoraces, of which two were fatal.
• Although popular, permanent magnets appear to be without benefit in patients with chronic low back pain as demonstrated during a pilot randomized trial of 20 patients .
• They also appear to be no better than placebo in relieving wrist pain in patients with carpal tunnel syndrome .
• Improvement in pain and performance are reported in some studies of patients with osteoarthritis of the knee or hip .
• Blinding could be a problem, as subjects can often discern the difference between magnetic devices and nonmagnetic or weakly magnetic (placebo) controls.
• Pulsed magnetic fields weren’t simpler than a sham treatment for patients with osteoarthritis of the knee .
• Reports have evaluated the possible efficacy sure enough patients with rheumatoid or osteoarthritis of multiple different therapies, including thalidomide , manipulation , electromagnetic wave , photo- (chemo-) pheresis , yoga , mud , prayer or distant healing , Ayurvedic medicine , and maybe soup .

As an example, glucosamine hydrochloride and chondroitin sulfate have undergone vigorous long-term evaluation in an exceedingly study sponsored by the NIH. Although generally safe, these remedies should be considered questionable (or investigational) approaches.
• I am also not awake to appropriate evidence-based observations to support recommendations for the employment of methonyl-sulfonyl-methane (MSM) , cetyl myristoleate , ginger , or zinaxin .
• Suggestive observations are available for s-adenosylmethionine (SAM-E) ; however, its use should be considered with caution in patients with RA on methotrexate .
• Pain relief from the appliance of leeches was reported in an exceedingly study of 51 patients with osteoarthritis who were randomly assigned to own leeches (Hirudo medicinalis) or topical diclofenac applied to an affected knee .
• Significantly more pain relief was reported with leeching than with diclofenac when assessed at seven days.
• The benefit persisted for up to twenty-eight days and was related to improvements in stiffness and performance.
• the shortage of blinding of patients and assessors could be a major potential source of bias and diminishes confidence within the results .
• Use of leeches also carries a risk of cellulitis and septicemia thanks to Aeromonas hydrophilia that colonize medicinal leeches.
• A small beneficial effect of whole-body massage employing a Swedish technique was suggested during a pilot study in comparison to wait-listed controls.
It should be noted when reading reports of “complementary” and “alternative” remedies that the consequence may be quite powerful in patients with arthritis. In one preliminary report, for instance, clinical improvement of the maximum amount as 50 percent occurred in up to 45 percent of patients .

 

PERSPECTIVE

At present, I don’t consider that diet or other “complementary” or “alternative” therapies have a job within the routine management of rheumatic diseases.
Nevertheless, examination of the role of diet and other questionable remedies in arthritis reminds us that it’s occasionally salutary to critically reevaluate prevailing notions about therapies.
For antimicrobials, diet, exercise, and maybe others, this reexamination has led to new insights about the pathogenesis and therapy of rheumatic diseases.
We therefore have to balance a healthy skepticism with a willingness to contemplate nontraditional concepts
It is important that we recognize this limitations of science in enabling us to grasp diseases and treat patients.
we should always therefore use caution about being dogmatic in interpreting those notions not thoughtfully scrutinized; however, we should always even be resolute against those ideas we are confident to be false and not questionable, and that we should recognize that the flexibility to differentiate among these possibilities is also difficult. i think that reason will ultimately overcome superstition; as logician wrote, “what science cannot tell us mankind cannot know.”

alternative remedies in rheumatic disorders

Rheumatology

ACR POSITION STATEMENT

 

The following position has been taken by the American College of Rheumatology (ACR) concerning “complementary” and “alternative” therapies (CAM) for rheumatic diseases:
”The ACR recognizes the interest in CAM modalities.
The ACR supports rigorous scientific evaluation of all modalities that improve the treatment of rheumatic diseases.
The ACR understands that certain characteristics of some CAMs and a few conventional medical interventions make it difficult or impossible to conduct standard randomized controlled trials.
For these modalities, innovative methods of evaluation are needed, as are measures and standards for the generation and interpretation of evidence.
The ACR supports the combination of these modalities proven to be safe and effective by scientifically rigorous clinical trials published within the biomedical review literature.
The ACR advises caution for those not studied scientifically.
The ACR believes healthcare providers should learn about the more common CAM modalities, based upon appropriate scientific evaluation as described above, and may be able to discuss them knowledgeably with patients” .

 

SUMMARY and proposals

• Clinicians should be aware of the common complementary and alternative remedies available for arthritis to facilitate effective communication with patients and colleagues.
• Therapies are often separated into those which are genuine (ie, those proven acceptably safe and effective), questionable, or ineffective.
• We distinguish between remedies that are mainstream and nonmainstream within the context of usual practice.
• Various factors contribute to the appeal of complementary and alternative remedies.
• These include seeking hope for understanding and a cure or relief from physical and emotional suffering because of the consequences of the medical illness; as a response to psychosocial distress independent of illness severity; as a way of life choice; thanks to difficulty addressing the constraints of medication, and uncertainty concerning outcome.
• The clinician’s response to use of complementary and alternative remedies should include education of the patient and general public, and maintaining communication with the patient regarding these issues.
• We recommend that clinicians mustn’t support the employment of therapies that are generally not considered acceptably safe and effective.
• Potential harms of such therapies include adverse effects, failure to use accepted effective interventions, and financial cost.
• There are a large style of complementary and alternative remedies for rheumatic disorders

Among the more common are:
• Antimicrobial agents
• Special diets or dietary supplements
• Herbal remedies
• Homeopathy, magnets, acupuncture, Ayurvedic medicine, and others
• Special diets or other “complementary” or “alternative” therapies don’t have a job within the routine management of rheumatic diseases.

malnutrition in dialysis

Pathogenesis and treatment of malnutrition in maintenance dialysis

Malnutrition is a crucial problem in patients treated with chronic hemodialysis or peritoneal dialysis.
It occurs in 20 to 70 percent of patients (depending upon the strategy accustomed measure nutritional status), with an increasing length of your time on dialysis correlating with an increasing decline in nutritional parameters.
There could also be significant differences between countries with reference to some measures of nutritional status, like albumen concentration.
Based upon the Dialysis Outcomes and Practice Patterns Study (DOPPS), as an example, the subsequent mean albumen levels were reported in France (3.87 mg/dL), Germany (4.17 mg/dL), Italy (3.98 mg/dL), Spain (3.98 mg/dL), us (3.6 mg/dL), and also the uk (3.72 mg/dL).
However, since differences in measurement methods cause differences in results, the strategy used from laboratory to laboratory and country to country must be known to assess any true differences in albumin in a private patient or groups of patients.

Two important issues are discussed elsewhere:
• How is nutritional status evaluated
• What is that the relation between nutritional status and survival? Patients with malnutrition, as manifested partly by hypoalbuminemia, measured at the onset of or during maintenance dialysis, have an increased fatality rate ( figure 1A-B ).
• this is often true for patients treated with either maintenance hemodialysis or peritoneal dialysis.
• The pathogenesis, prevention, and treatment of malnutrition in these patients are discussed here.
• Most of the observations are made in patients treated with maintenance hemodialysis, but similar considerations apply in many respects to continuous peritoneal dialysis.
PATHOGENESIS
The most readily treatable reason for inadequate nutrition in many patients is underdialysis, which might result in anorexia and decreased taste acuity.
Patients with a minimally acceptable Kt/V and a coffee mid-week BUN may appear, initially glance, to be dialyzed.
However, many such patients are underdialyzed with poor protein intake being answerable for the low BUN.
This problem eventually led to the appreciation that protein intake must be considered when evaluating the adequacy of dialysis.
Thus, estimation of the normalized protein equivalence of nitrogen appearance (nPNA), as index of protein intake, may be a a part of the dialysis regimen.
This is also called the normalized protein catabolic rate (nPCR).
The PCR is simply valid as a measure of protein intake within the patient in neutral balance.
The relationship between the dose of dialysis and protein intake was demonstrated in a very small group of hemodialysis patients in whom the intensity of dialysis was increased by enhancing dialysis time, blood flow, and/or membrane extent.
As the Kt/V rose from 0.82 to 1.32 over a 3 month period, there was a concurrent elevation in PCR from 0.81 to 1.02 g/kg per day.
the increase in PCR was indicative of increased protein intake (and better nutrition) due, presumably, to improved appetite.
A second group during which the dialysis regimen was unchanged had no increase in either Kt/V or PCR.
Whether there’s a mathematical link between Kt/V and PCR because they’re both calculated from similar measures could be a subject of debate.
Further support for the observation of improved nutritional intake with increased dialysis dose was reported during a study during which improved weight was observed with more frequent daily hemodialysis.
An increased dialysis dose may additionally enhance nutritional status among malnourished peritoneal dialysis patients.

Even within the well-dialyzed patient, however, variety of things can impair nutrition:
• The presence of an acute, chronic, or occult systemic illness resulting in an inflammatory response may adversely impact nutritional status. Markedly increased energy expenditure, proinflammatory cytokine levels, and oxidative stress appear to produce a link between inflammation and malnutrition.
• Nutrients are lost into the dialysate.
• As an example, aminoalkanoic acid losses into dialysate can average 4 to eight g/day with peritoneal dialysis or hemodialysis.
• With peritoneal dialysis, losses rise much higher during episodes of peritonitis.
• With hemodialysis, certain reuse procedures lead to increased losses of protein into dialysate.
• Protein loss as high as 20 grams in one hemodialysis has been reported with polysulfone dialyzers reused with bleach.
• Dietary restrictions can make food less palatable.
• Furthermore, the encouragement to limit fluid intake to attenuate intradialytic weight gain may result in a concurrent decrease in caloric intake.
• Solid food contains a high fluid content and lots of beverages contain a considerable amount of calories.
• The dialysis procedure itself could also be catabolic, thanks to reduced protein synthesis and also the loss of amino acids in dialysate; this effect could also be more prominent with bioincompatible membranes.
• This may be overcome with appropriate nutritional intake.
• As shown in some, but not all, studies, persistent acidosis may enhance protein degradation and aminoalkanoic acid oxidation.
• Gastroparesis (by slowing gastric emptying) or, in peritoneal dialysis, the presence of dialysate within the abdomen may impart a sense of fullness.
• Some medications, like phosphate binders, can impair nutrient absorption.
• Adequate dialysis isn’t a whole substitute for the clearance functions of an intact kidney. specifically, the retention of middle molecules (1000 to 5000 Daltons) may partially contribute to anorexia, possibly by directly affecting the central systema nervosum.
• Serum concentrations of leptin, a hormone that induces satiety via effects upon the hypothalamus, could also be increased thanks to reduced renal or dialysis clearance.
• However, a job for leptin in malnutrition within the dialysis patient remains to be proven.
• Chronic volume overload could also be directly related to malnutrition, with improved fluid status increasing overall nutritional status.
• The presence of both malnutrition and intensely low levels of renal function at the time of dialysis initiation are directly related to subsequent poor nutritional status despite adequate dialysis.
• This observation suggests that dialysis should be begun before the onset of serious malnutrition.

• PREVENTION

• The commencement within the prevention of malnutrition is careful assessment of the patient’s nutritional status at the start of dialysis and each three to 6 months thereafter.

• Early diagnosis and correction can avoid clinical deterioration which will make the patient harder to treat, partially because malnutrition itself may cause anorexia.

• This relationship is recommended by studies within which improved nutritional status led to improved food intake.

• In one report, for instance, malnourished patients on hemodialysis received parenteral nutrition supplements during the dialysis procedure.

• This led to a rise in food intake, which began before any changes can be demonstrated in nutritional status.
Ingestion of an adequate diet is incredibly important if malnutrition is to be prevented. Patients previously on a low-protein diet might have to be reminded to extend protein intake once dialysis begins to counteract protein loss within the dialysate.
Although somewhat controversial, a diet providing 1.0 to 1.2 g/kg per day of high biologic value protein is usually recommended for patients on hemodialysis.
Continuous ambulatory peritoneal dialysis is related to a better level of dialysate protein loss; as a result, protein intake should be a minimum of 1.2 g/kg per day with this treatment modality.
One study demonstrated that the metabolic response to protein intake is normal in hemodialysis patients, further supporting the importance of maintaining adequate dietary protein intake.
Adequate caloric intake also must be emphasized, since it’s required for anabolism.
In one study, for instance, patients on maintenance hemodialysis were studied on different diets.
There was negative balance unless caloric intake was a minimum of 32 kcal/kg ideal weight
For patients treated with peritoneal dialysis, the calories provided by the dialysis solution should be taken under consideration.

TREATMENT
The presence of malnutrition is sometimes suspected from anthropometry or the presence of hypoalbuminemia or decreased creatinine production.
Evaluation should begin with an intensive history to see whether the reduction in food intake is caused by unpalatable dietary restrictions or by changes within the patient’s sense of taste.
The dietary history should include personal or ethnic food preferences.
If limiting such preferences is interfering with food intake, the clinician or dietitian should work with the patient and family to feature more preferred foods to the diet. In cases of severe malnutrition, most or all dietary limitations may must be removed for a limited period of your time.
In general, if malnutrition is diagnosed, we advise the subsequent stepped treatment strategy:
• Evaluation of any source of inflammation should be sought and managed.
• Dietary intake should be assessed and dietary counseling should be undertaken.
• If the patient cannot improve nutrient intake by diet alone, intake should be improved in a very step-wise fashion, starting with oral supplements and ending with total parenteral nutrition if no other nutrient intake methodology is suitable.

Drug toxicity
Drugs that may impair appetite or make meals less palatable should be reduced or eliminated.
In severe cases, the patient may have the benefit of temporary cessation of oral phosphate binders.
Hyperphosphatemia may be a lesser risk during this setting, since the low protein intake itself will lower the plasma phosphate concentration.
In fact, hypophosphatemia is also an extra clue to the presence of malnutrition.
Gastroparesis
Gastroparesis may be contributing factor to decreased food intake by delaying gastric emptying, thereby increasing the sensation of fullness.
This complication is most typical in diabetics (possibly affecting as many as 20 to 30 percent of diabetics with end-stage renal disease), but can even occur in nondiabetics.
If gastroparesis is suspected from the history, the speed of gastric emptying may be accurately assessed by various methods, like ingestion of a radiolabeled test meal with simultaneous gastric scanning.
If slow or delayed gastric emptying is documented, several therapeutic modalities is also beneficial:
• Metoclopramide are often given, but the dose must be limited in patients with end-stage renal disease.
• Patients are successfully treated with erythromycin
• Patients not awake to erythromycin may answer other agents, like cisapride.
• However, the utilization of cisapride is now restricted per the manufacturer’s and Federal Drug Administration’s recommendations thanks to the chance of arrhythmias.
• As of August 2000, prescriptions for the drug can only be filled directly through the manufacturer after providing documentation on need for the drug and assessment of risk factors for cardiac arrhythmias within the individual patient (including a protracted QTc on the EKG or use of medicines known to change the drug’s metabolism like macrolide antibiotics, antifungals and phenothiazines).
If gastroparesis is detected via gastric emptying scans, the optimal therapeutic agent is also chosen based upon the prokinetic response to an intravenous test dose.
As an example, the gastric emptying response to intravenous doses of metoclopramide (5 mg) and erythromycin (200 mg) was assessed in 6 dialysis patients with hypoalbuminemia and occult gastroparesis.
Subsequent oral therapy based upon a successful gastric response significantly improved albumen levels (from 3.3 to 3.7 g/dL).
Nutritional supplements
If attention to the preceding problems doesn’t improve appetite and food intake, then nutritional supplementation could also be necessary.
Oral supplementation, enteral tube feeding, and parenteral nutrition are all possibilities.
A 2005 systematic review and meta-analysis of 18 studies (including five randomized controlled trials) found that enteral nutritional support increased total intake and albumin concentration (0.23 g/dL).
Clinical outcomes were evaluated in precisely some studies, while data was inadequate to check both disease-specific versus standard formulae and enteral versus parenteral nutrition.
Oral supplements are the simplest and cheapest to use.
Several supplements are intended primarily for the patient with end-stage renal disease.
They are low in potassium and fairly dense in nutrients, thereby providing adequate calories and protein, while minimizing the danger of hyperkalemia and fluid overload.
However, these supplements have the disadvantage of being more costly than less specific preparations, thereby making compliance a difficulty.
Oral supplements provided at the time of dialysis treatments could also be an efficient therapy.
This was suggested by a matched cohort study of maintenance hemodialysis patients with albumin concentrations ≤3.5 g/dL who were given oral nutritional supplements at the time of dialysis.
By 15 months of follow-up, improved survival was demonstrated among patients given oral nutritional supplements compared with untreated matched control patients by both as-treated and intention-to-treat analysis. the best advantage of oral supplements was observed among patients with rock bottom baseline albumen concentration (≤3.2 g/dL).
These observations, although potentially clinically significant, are limited by the absence of random allocation of patients; although control patients were matched by propensity score, residual confounding remains possible.
Another study analyzed the effect of providing oral supplements (taken at non-dialysis times) to patients with albumin ≤3.8 mg/dL.
This was a retrospective analysis of knowledge provided by Fresinius Medical Health Care Plan’s disease management program, during which eligible patients (ie, defined as those with albumin ≤3.8 mg/dL for 2 or more months) were given 24 cans of oral supplement per month.
Among eligible patients, 276 received supplements and 194 failed to, either because it absolutely was deemed inappropriate for unspecified reasons, or because they refused.
After multiple adjustments, compared with no supplements, the employment of oral supplements was related to a lower rate of hospitalization (89 versus 68 percent respectively), and with a nonsignificant trend toward improved survival at one year (p = 0.09).
This study was limited by the possible presence of unadjusted differences within the patient populations.
Despite the constraints related to both studies cited above, oral nutritional supplements administered during the dialysis treatment is also a useful intervention for a few patients with very low albumen.
Compared with intravenous nutritional supplementation, oral supplementation has fewer side effects, is cheaper, and appears to be an affordable start within the nutrition management of those patients.
The general supplements will be tried in patients ready to tolerate the rise in potassium and fluid intake.
We limit the precise “renal failure” supplements to patients with preexisting hyperkalemia or fluid overload due, for instance, to failure. Although some evidence suggests that oral essential amino acids is also modestly beneficial to patients with significant hypoalbuminemia, further study is required before any recommendation concerning their use.
Patient compliance is vital to the success of oral nutrient supplements.
A different regimen is required in patients with severe anorexia who are unable to extend their oral intake.
Overnight supplementation by nasoenteral feeding tube could also be effective during this setting.
A short course of overnight tube feeding can result in a sufficient improvement in nutritional status and overall well-being that adequate dietary oral is resumed.
Patients with severe gastroparesis could also be unable to tolerate any kind of oral supplementation.
Intradialytic parenteral nutrition (IDPN) could also be beneficial during this setting if the malnutrition isn’t too severe. IDPN solutions are similar those used for total parenteral nutrition : a typical solution contains 10 percent amino acids and 40 to 50 percent glucose, 10 to twenty percent lipids, or a mix of carbohydrate or lipids depending upon the wants of the patient.
However, IDPN has certain limitations:
• It is that the costliest and least efficient nutritional supplement. IDPN often costs twice the maximum amount as dialysis itself, and only 70 percent of the nutrients are literally delivered to the patient due to loss into the dialysate.
• Malnutrition may persist, since IDPN is run only three days per week for roughly 4 hours.
• It could also be related to a below expected delivered dose of dialysis, due possibly to increased urea generation.
Despite these shortcomings, IDPN is convenient (because it’s delivered during dialysis) and is probably going to be beneficial in some patients.
However, although variety of studies suggest that IDPN provides substantial benefit, most were case reports, retrospective, or poorly designed.
To better assess the consequences of IDPN, 186 malnourished hemodialysis patients were randomly assigned to oral nutritional supplements, with or without one year of IDPN.
At two years, there was no difference in mortality, hospitalization rate, and nutritional status between the 2 groups.
With statistical procedure, however, improved nutrition defined as a rise in prealbumin level of greater than 30 mg/L within the primary three months correlated with an approximately 50 percent decrease in mortality at two years.
The optimal indications for IDPN haven’t been established.
We consider use of this modality within the malnourished dialysis patient who cannot tolerate oral supplements but who can consume a minimum of 50 percent of the prescribed caloric intake.
This is in step with the 2007 European best practice guidelines for hemodialysis.
If this degree of oral intake can not be reached, we first try a nasoenteral feeding tube with nighttime enteral nutrition or, if oral intake isn’t tolerated, the institution of total parenteral nutrition should be considered.
Total parenteral nutrition (TPN) is required within the rare patient with severe malabsorption, severe malnutrition, or severe intolerance of oral supplements. Although generally well tolerated, TPN solutions typically contain added potassium, phosphorus, and magnesium.
Thus, patients with end-stage renal disease receiving TPN are in danger for the event of hyperkalemia, hyperphosphatemia, and hypermagnesemia. Elimination of the added electrolytes can prevent these problems but carries the reverse risk of electrolyte deficiencies with prolonged therapy.
We generally recommend that TPN be started with solutions containing little or no added electrolytes.
The patient should then be carefully monitored, and electrolytes should be added if the plasma levels fall below the conventional range.
Dialysis prescription
The dialysis prescription should be reassessed in terms of Kt/V and also the protein catabolic rate.
In a trial to handle the question of optimal dialysis dose and membrane flux for hemodialysis patients, an oversized test, called the Hemodialysis (HEMO) Study, was performed.
Patients were randomly assigned to a regular (single-pool Kt/V of 1.25) or high dose of dialysis (single-pool Kt/V of 1.65) and a low- or high-flux dialyzer.
Similar outcomes in terms of survival were observed with high and standard dialysis doses likewise as dialysis using high and low flux membranes.
Subsequent analysis of the HEMO trial also found that nutritional parameters, like albumin and anthropometric measures, were the identical with the various dose and flux interventions.
Current minimum recommendations are 1.3 to 1.4 for Kt/V in hemodialysis, at least 1.7 for weekly Kt/V in continuous ambulatory peritoneal dialysis, and 1.0 to 1.2 g/kg per day for the nPNA.
there’s also some preliminary evidence that, compared with Kt/V, Kt alone (which is that the non-normalized dialysis dose) could also be more closely related to albumen levels.
Although further study is required, daily in center and nocturnal hemodialysis are used as a rescue therapy for patients with severe malnutrition complicating uremia, with patients generally reporting increased appetite after switching from conventional to daily dialysis.
The effects on nutrition of short daily and nocturnal hemodialysis are presented separately.
Recombinant human STH
Some studies suggest that administration of recombinant human somatotropic hormone can reduce wasting and catabolism, improve nutritional status, and lower the BUN in hemodialysis patients, even within the elderly.
• In one study, 139 adult dialysis patients with albumin levels but 4 g/dL were randomly assigned to 6 months of therapy with different doses of recombinant somatotrophin or placebo.
• Lean body mass significantly increased in the least dose levels (2.5 kg versus –0.4 kg) for placebo, while albumen levels attended increase.
• In another prospective, cross-over study, improvements in protein metabolism were observed with administration of recombinant human somatotropin in comparison to no hormone therapy, as shown by a decrease in BUN (55 versus 40 mg/dL [19.6 versus 14.3 mmol/L]) and a decrease in protein catabolic rate (0.82 versus 0.67 g/kg per day). Follow-up evaluation of those patients revealed that the improved protein metabolism resulted from the increased ability to utilize essential amino acids. Similar improvements in protein metabolism were noted in other studies during which the like recombinant human STH could largely be explained by a rise in free insulin-like growth factor-1 levels.
Recombinant human endocrine has also been reported to boost nutritional status in malnourished patients on hemodialysis treated with IDPN; the latter was ineffective when given alone.
Recombinant insulin-like growth factor-1 (IGF-1) has also been shown to markedly increase balance in patients treated with CAPD.
Despite evidence suggesting that recombinant human somatotrophic hormone provides short term benefits ,significant long-term nutritional benefits with this agent aren’t consistently observed.
additionally, the consequences of recombinant human human growth hormone on malnutrition associated morbidity and mortality are unclear.
One additional major limitation of the utilization of recombinant therapy for the treatment of malnutrition in patients with ESRD is its very high cost.
To best assess the advantages and adverse effects related to recombinant human somatotropic hormone , the chance trial will assess the effect of this hormone on survival in hypoalbuminemic dialysis patients and its effect upon morbidity, markers of body protein mass, inflammation, exercise capacity, and quality of life.
Correction of acidosis
Uremic acidosis can increase muscle breakdown and diminish albumin synthesis, resulting in muscle wasting and muscle weakness.
Recommendations concerning correction of acidosis are presented separately.

Others
Androgenic anabolic steroids and anti inflammatory drugs are utilized in dialysis patients with malnutrition.
• Only limited data have evaluated the efficacy and adverse effects of androgenic anabolic steroids in dialysis patients.
• Although a rise in weight, muscle mass, and albumin are reported, the long-term efficacy and risk for adverse effects with these agents is unclear. These agents therefore can not be recommended during this setting.
• The use of anti-inflammatory agents in patients with malnutrition-inflammation syndrome complex is reviewed separately.
• Dialysis patients often have decreased taste acuity, which is controversially related to deficiency disease.
• If present, diminished taste acuity can result in decreased intake and anorexia.
• The role of deficiency disease has never been established and that we don’t routinely measure plasma zinc levels or administer zinc supplements.
MALNUTRITION IN CONTINUOUS AMBULATORY PERITONEAL DIALYSIS
Much of the foregoing discussion applies to both hemodialysis and peritoneal dialysis.
As previously noted, however, there are several problems unique to peritoneal dialysis, including increased dialysate protein losses and a sense of fullness because of dialysate within the abdomen.
Gastroparesis is additionally more common, since many CAPD patients are diabetic.
The management of malnutrition in these patients again focuses on prevention and treatment.
The approach is comparable thereto noted above, but there are variety of specific recommendations:
• Patients with loss of appetite should drain the dialysate just before meals in order that the abdomen is empty at mealtime.
• They may additionally tolerate frequent, small meals better than the standard three large meals.
• Peritoneal dialysis patients generally have fewer dietary restrictions than those treated with hemodialysis, since they’re continuously dialyzed. However, some patients consume excessive amounts of fluid that are removed by the utilization of high-dextrose dialysate. the following increase in glucose absorption can, in susceptible subjects, cause hyperglycemia, which might directly suppress appetite.
• Avoidance of excess fluid intake is therefore desirable, since it limits the requirement to be used of hypertonic dialysis solutions.
• Persistent malnutrition is treated with oral supplements or TPN. Limited data, however, have reported mixed results with oral nutritional supplementation; this can be possibly the results of poor compliance, small sample size, and reliance upon albumen concentration because the principal outcome measure.
• Clearly, IDPN isn’t feasible thanks to continuous dialysis.
Amino acid dialysate
Dialysate containing amino acids because the osmotic agent, instead of glucose, may minimize a number of these above problems, increasing net protein intake, allowing the attainment of positive balance and net anabolism and improving the plasma albumin concentration and overall nutrition.
In a prospective three month study, 105 malnourished peritoneal dialysis patients were randomly assigned to 1 or two exchanges per day with a 1.1 percent organic compound dialysate, or to usual therapy.
Benefits observed within the group receiving the protein dialysate included increases in insulin-like growth factor-1, and reduces in serum potassium and inorganic phosphorus, findings indicative of a general anabolic response.
The combination of organic compound plus glucose dialysate might also improve the nutritional status of malnourished patients. in a very random order crossover study of eight patients undergoing nocturnal automated peritoneal dialysis, protein kinetics was markedly superior over a 1 week period with dialysate containing organic compound plus glucose versus that observed during every week with the control dialysate.
Further study in a very larger number of patients is required to adequately evaluate this approach.
Dialysate containing amino acids because the osmotic agent is now commercially available in Europe, Canada and other regions, although they’re not commercially available within the us.
Patients who are treated with aminoalkanoic acid containing dialysate should be monitored closely for the subsequent reasons:
• To avoid aminoalkanoic acid imbalance, organic compound dialysate mustn’t be used for over one or at the most two exchanges per day.
• As the osmotic agent, a 1.1 percent solution of amino acids has an ultrafiltration profile kind of like dialysis solutions containing 1.5 percent dextrose.
• Thus, aminoalkanoic acid dialysate mustn’t be used for the overnight dwell because most of the amino acids are absorbed, thereby limiting the degree of fluid removal.
• There is concern that amino acids will raise urea nitrogen appearance and urea production if they’re not used for anabolism.
• organic compound dialysate may result in acidosis which is primarily thanks to the proton contained in cationic amino acids (such as lysine).
• Thus, both the BUN, and plasma bicarbonate concentration should be monitored.
The European Best Practice Guidelines suggest that an aminoalkanoic acid containing solution should be considered in malnourished patients.
They also state that this solution should only be used once daily.
Malnourished patients who don’t tolerate oral supplements are possibly to profit.
A response — improved appetite, increased plasma albumin concentration, weight gain — should be seen within three months; at now, we switch back to traditional dialysate.

Enteral tube feeding
Some PD patients with malnutrition who are unable to ingest adequate amounts of nutrition are successfully treated with enteral tube feedings, particularly with gastrostomy or gastrojejunostomy tubes.
A paucity of knowledge exists concerning the utilization of this method of feeding in adults, but it appears to end in improved nutrition in malnourished children.

Others
Limited evidence suggests that improved control of acidosis may enhance the nutritional status in peritoneal dialysis patients.
In one study, 200 consecutive patients initiating peritoneal dialysis were randomized to high (lactate of 40 meq/L) or low (35 meq/L) alkali dialysate for one year.
Correction of acidosis with carbonate and sodium hydrogen carbonate was also utilized within the high alkali group.
At one year, the serum bicarbonate within the high alkali group was 27 meq/L versus 23 meq/L within the low alkali group.
Compared to the low alkali group, benefits observed with high alkali therapy included a greater increase in weight (6.1 versus 3.7 kg, P<0.05) and lower morbidity (16.4 versus 21.2 days spent within the hospital, P<0.05).
A preliminary study found that administration of ghrelin, a hormone that functions as an appetite enhancer, may enhance food intake acutely in malnourished patients undergoing peritoneal dialysis.
Longer term study is required to higher characterize the consequences of ghrelin during this setting.

INFORMATION FOR PATIENTS
UpToDate offers two sorts of patient education materials, “The Basics” and “Beyond the fundamentals.
” the fundamentals patient education pieces are written in plain language, at the 5 th to six th grade reading level, and that they answer the four or five key questions a patient might need a couple of given condition.
These articles are best for patients who need a general overview and preferring short, easy-to-read materials.
Beyond the fundamentals patient education pieces are longer, more sophisticated, and more detailed.
These articles are written at the ten th to 12 th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to the present topic.
We encourage you to print or e-mail these topics to your patients.
(You may also locate patient education articles on a spread of subjects by searching on “patient info” and also the keyword(s) of interest.)
• Basics topic

• SUMMARY and proposals

• Malnutrition is common in patients treated with maintenance dialysis. Principal causes include inadequate dialysis dose, inflammation, dietary restrictions, nutrients lost via dialysate, catabolic properties of dialysis, and other factors.
• The beginning within the prevention of malnutrition is careful assessment of the patient’s nutritional status at the start of dialysis and each three to 6 months thereafter.
• Ingestion of an adequate diet is incredibly important if malnutrition is to be prevented.
• If malnutrition is diagnosed, it’s important to undertake treatment strategies as follows:
• Evaluation of any source of inflammation should be sought and managed.
• Dietary intake should be assessed and dietary counseling should be undertaken.
• If the patient cannot improve nutrient intake by diet alone, intake should be improved during a step-wise fashion, starting with oral supplements and ending with total parenteral nutrition if no other nutrient intake methodology is acceptable.
• Much of the discussion associated with malnutrition during this topic review applies to both hemodialysis and peritoneal dialysis.
• However, since there are several problems unique to peritoneal dialysis, variety of specific recommendations may be made in these patients.
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