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Chapter Number
Advanced Chronic Kidney Disease in Context of Familiar Amyloidotic Polyneuropathy Type I
Daniel Martin
Name of University Name of University Country 1. Introduction
Patients with familiar amyloidotic polyneuropathy (FAP) or Andrades disease are a minority among those with a rare condition that can affect many members of the same family through hereditary nature and insidious onset. Documented on many countries, the disease and its variants are associated with a genetic mutation of the TTR, protein transthyretin, synthesized with the liver and the choroid plexus. The deposit of this substance on tissues, like hereditary amyloidosis or other amyloids, causes their destruction and subsequent dysfunction. Initial sensorial polyneuropathy, motor and autonomic peripheral distal-proximal characteristics are some of its clinical manifestations, but not only: gastrointestinal disturbances (such as constipation and diarrhea), heart abnormalities, kidney, eye and skin disorders may also occur. The deposit of amyloid causes a progressive and irreversible loss of the kidney function. At its terminal stage it originates a multitude of signs and symptoms, also known as uremic syndrome. Peritoneal Dialysis and Hemodialysis (HD) are dialytic techniques currently offered for the treatment of advanced chronic kidney disease, Hemodialysis being the most common one. The prevalence of patients with FAP and advanced chronic kidney disease in HD are known and described by the nurses and nephrology nursing, particularly since this it not an exclusively hereditary renal disease. Therefore the nephrology nurse tends to pay special care to renal disease and treatment with HD. It is important to know that, in addition to the problems caused by kidney disease and dialysis, there are those related to the underlying disease, the FAP. Through literature review, it is aimed to gain a deeper knowledge in the observation and study of the FAP in patients on hemodialysis.

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2. Historical development of amyloidosis

The Amyloidosis are a group of diseases with a common characteristic, the deposit of a substance with protein nature and structure of fibers in the extracellular space of one or more tissues, causing organic changes through the amount of deposit and/or body that is affected. These fibers are insoluble; they resist proteolytic digestion and destroy normal tissue deposits (Martnez, 1996). The term "amyloid" was first introduced by the botanist Schleiden, in 1838, to describe a starch constituent of plants (Lobato, 2006). In 1854, Virchow identified the substance as

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"amyloid" due to its color, similar to a starch (a blue color in the presence of iodine) by assuming its hydrocarbon nature (Munar-Qus, 1994). Friedreich and Kekule, by 1859, demonstrated that the substance had a protein origin and concluded that the compound did not contain carbohydrate, contradicting previous assumptions. They have also classified the secondary or unknown primary amyloidosis in inflammatory processes (Lobato, 2006). Benhold in 1922, and later Divry Florkin in 1927, described the methods of diagnosis. For Benhold is the color of Congo red as a marker (at a conventional light microscope, they acquire a pink color), and for Divry Florkin apple green birefringence under polarized light after staining with Congo red (at an optical microscopy polarized light, we get a brownish yellow-green). The combination of these diagnostic methods is currently used due to its simplicity in identifying amyloid deposits in histological preparations (Munar-Qus, 1994; Martnez, 1996; Lobato, 2006). In 1952, the Portuguese Corino de Andrade contributed surpassingly to the classification of amyloidosis. Within the group of systemic amyloidosis he described a type of hereditary amyloidosis, observed in Portuguese families of the north of the country. This type of amyloidosis was associated to a sensory-motor polyneuropathy and autonomic characteristics with a prognosis of life of 10 years (Munar-Qus, 1994; Martnez, 1996; Lobato, 2006). From here, new contributions to the amyloid neuropathies will need another type of classification and terminology. In 1975, Reinmann defined the clinicopathologic classification into 5 types (Sigala; NellenHummel; Rodrguez & Halabe, 2002): 1. Amyloidosis associated with multiple myeloma; 2. Secondary Amyloidosis associated with the underlying inflammatory disease or infection, with deposit of amyloid in the parenchyma. 3. Located Amyloidosis, especially in elderly patients; 4. Senile amyloidosis, cardiovascular disease; 5. Familial amyloidosis, autosomal dominant. On 1978, Pedro Costa identified the pre-albumin (transthyretin, TTR) as the protein involved in amyloid deposits on the familiar amyloid polyneuropathy (FAP), described by Andrade (Buades Reins & Andreu Serra, 2000). Later, in 1983 and 84, Tarawa and Saraiva depicted a mutation of the TTR which replaced the valine for a methionine at position 30 (TTR Val30Met), located on chromosome 18 in families of Japanese, Portuguese and Swedish origin with FAP (Munar-Qus,1994;Lobato, 2006; Conceio, 2006). Holmgren et al on 1990 (Quoted by Munar-Qus, 1994), suggests liver transplantation as a treatment for FAP. That same year, the first two transplants are performed in Sweden and in 1991 he conducts the first liver transplant on Albacete, Spain, followed by 10 more, 9 of them on patients from Mallorca (Munar-Qus, 1994). By May 1998, the Global Registry counts around 300 liver transplants, 35 of them made in Spain, mostly on Mallorca patients (Buades Reins & Andreu Serra, 2000).

3. Amyloid structure
The amyloid is a protein substance which, at an optical microscope, acquires a pinkish color in the presence of Congo red and when submitted to a beam of polarized light, produces an apple-green birefringence. The amyloid substance consists of a component P and a fibrillar component at a proportion of 10 and 90%, respectively (Munar-Qus, 1994).

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The amyloid P component (AP) belongs to the glycoprotein pentraxins group, because of its pentagonal shape (hence the designation P). The hydrocarbon fraction explains the staining characteristic, similar to starch, and is responsible for the perpetuation of the name "amyloid". The P component is similar in all types of amyloid. Its precursor, serum amyloid P component (SAP), is present in all individuals, but only deposited in amyloidosis due to the affinity for the fibrillar component to form the AP. The fibrillar component is made available with laminar Beta folded formations and is specific to each type of amyloid, thereby defining the type of disease. The most frequent abnormality is the substitution of one amino acid for another in the polypeptide chain, producing a variant of the normal protein. 3.1 Current classification of amyloidosis In a general, the systemic amyloidosis can be classified into (Munar-Qus, 1994; Sigala, Nellen-Hummel, Rodrguez & Halabe, 2002; Luz Palma, Grnholz & Osorio, 2005; Lobato, 2006): Primary amyloidosis or immunoglobulin light chain (AL): no signs of concurrent disease except for multiple myeloma. Named due to its composition of monoclonal immunoglobulin light chains (whole or portions of them). Munar-Ques, in his update of amyloidosis, defends the end of the term immunoglobulin amyloidosis introduced by Benson and Wallace, more successful due to its composition and preceded by the monoclonal immunoglobulin light chains circulating in the blood characteristics of the plasma cell dyscrasias such as multiple myeloma, Waldenstrom's disease and monoclonal gammopathy of unknown significance. In amyloidosis immunoglobulin, the heart and kidney are the main target organs. It can lead to proteinuria and may also develop the nephrotic syndrome, with impaired renal function tests on the kidney. Mixed predominantly sensory polyneuropathy, proximal disto pattern, and severe autonomic dysfunction, manifested by postural hypotension, impotence and gastrointestinal motility disorders may happen. Macroglossia (on 20% of the cases), changes of taste, and hoarseness due to infiltration of the vocal cords are also some of the symptoms. Hereditary or familial amyloidosis type Andrade (AF): where F stands for Family. Autosomal dominant descent. Very rare and associated with a genetic mutation of the TTR synthesized in the liver and the choroid plexus. The most common clinical manifestation is progressive and has a slow onset, characterized by poly-motor and autonomic sensory neuropathy. Renal involvement is rare. It is on this type of amyloidosis that we shall discuss later. Secondary amyloidosis or serum amyloid protein (AA) in presence of a chronic inflammatory disease, recurrent acute processes, collagen and certain malignancies. Produced in the liver by hepatocytes. The most common illness associated with this type of amyloidosis is the idiopathic rheumatic disease. A cause of renal proteinuria, nephrotic syndrome and advanced chronic kidney disease, being at 40 to 60% of cases, the main cause of death. These are rare gastrointestinal and heart disorders. Diseases associated with secondary amyloidosis are shown in Table 1.

4 chronic microbial infections Leprosy Tuberculosis

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Chronic inflammatory disorders Familial Mediterranean fever. (Inherited autosomal recessive) Rheumatoid arthritis and juvenile chronic arthritis Ankylosing Spondylitis

Malignancies Hodgkin's Disease Renal carcinoma

Bronchiectasis Psoriasis and psoriatic arthropathy Decubitus ulcers Chronic pyelonephritis Osteomyelitis Whipple's disease

Carcinoma of the intestine, lung or genitourinary tract

Basal cell carcinoma

Reiter syndrome Stills disease on adults Behcet Syndrome Crohn's disease

Hairy cell leukemia

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Table 1. Diseases related to secondary amyloidosis. Amyloidosis of hemodialysis or mediated by protein -2 microglobulin. Caused by the deposit of fibrils produced by the -2 microglobulin (light chain proteins that have the class I histocompatibility antigen), it is present in all nucleated cells. Observed in most renal patients on HD, the amyloid deposits are found primarily in joints, bones and peri-articular tissues. Clinical manifestations can be arthralgia, carpal tunnel syndrome and bone cysts. Deposits on other tissues are rarely found. Located amyloidosis, hereditary or acquired. It is associated to a body with no signs of generalized disease and commonly located on the skin or the respiratory and genitourinary system, the Alzheimer's disease being the most important one from a clinical point of view. According to Lobato, 10 to 20% of cases are clearly inherited (Lobato, 2006).The precursors of localized forms of amyloidosis are presented on Table 2. Senile amyloidosis: the most common forms described in this type of amyloidosis are the aortic involvement and the choroid plexus. Lobato makes a complete and current classification of amyloidosis (Lobato, 2006) where she quotes an article of the Nomenclature Committee of the International Society of Amyloidosis from March 2005. According to the author, since the second International Symposium on Amyloidosis, the committee meets every three years to review the guidelines of the nomenclature. On the other hand, this author emphasizes the

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recommendations of the nomenclature for the classification of amyloidosis by amino acid substitutions and not according to geographical origin (Portuguese, Finnish, Indian ...). Table 2 shows the classification of amyloidosis adapted by Lobato (Lobato, 2006), who describes the protein amyloid fibrils and their precursors, the diseases unrelated to transthyretin and precursors of localized forms of amyloidosis. Amyloid protein AL Precursor Immuno light chains Immunoglobulin heavy chain Transthyretin 2-microglobulin (Apo) serum AA Apolipoprotein AI Apolipoprotein AII Apolipoprotein AIV Gelsolin Lysozyme A chain of fibrinogen Cystatin C Abripp Adanpp A Precursor protein Prian protein (Pro) calcitonin Amyloid polypeptide of the islands Atrial natriuretic factor Prolactin Systemic (S) Localized (L) S, L Illness or tissues affected Primary (no criteiros myeloma) or in association with myeloma Primary (no criteiros myeloma) or in association with myeloma Family, peripheral nerves, heart, kidney, eye, senile systemic tenosynovial Chronic kidney disease, hemodialysis, articulate Secondary, reactive (inflammatory), Family (FMF, TRAPS, SMW, FCAS, HIDS) * Family, kidney, heart, aorta Family, renal, cardiac Sporadic, associated elements to aging, renal Family, peripheral nerves, cornea Family, renal Family, renal, hepatic Family, central nervous system (cns) Family, CNS, dementia Family, CNS, dementia Alzheimer's disease associated with aging Spongiform encephalopathy Tumors of the thyroid Islets of Langerhans, diabetes mellitus, insulinotas Atrial, heart Pituitary, prolactinomas associated with aging

AH

S, L

ATTR A2M AA ApoAI ApoAII ApoAIV AGel ALys AFib ACys ABri ADan A APrP Acalc AIAPP AANF APro

S, L? S, L S S, L S S S S S S S L L L L L L L

6 AIns AMed Aker Insulin Lactaderina L L

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Iatrogenic Senile aortic

Keratoconjunctivitis L Family, cornea epitelina ALac Lactoferrin L Cornea tbn A(tbn)** L Odontogenic tumors *.FLF: Family landlocked fever. TRAPS: periodic fever syndrome associated with the receptor of a necrosis tumor factor; MWS: Muckle-Wells syndrome FCAS, cold auto inflammatory syndrome HIDS: hyperimmunoglobulinemia D periodic fever. **.Wait nomenclature. Adapted from: Westmark P, Benson MD, Buxbaum JN, Chen AS, Frangione B, Ikeda S, Masters G, Saraiva MJ & Sipe JD. Amyloid: Toward terminology clarification. Report from the Nomenclature Committee of the International Society of Amyloidosis. Amyloid, March 2005; 12 (1):1-4.

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Table 2. Amyloidosis classification: amyloid protein fibers and their precursors in men. Lobato, adapted from the Nomenclature Committee of the International Society of Amyloidosis. 3.2 Diagnosis of amyloidosis Differential diagnosis can be made by taking a sample of tissue, usually the saphenous or femoral nerve through biopsy, following an application of Congo red staining and then subjecting it to a beam of polarized light. The amyloid gets, exclusively on these patients, a brownish pink when submitted to Congo red and an apple green birefringence under polarized light. In addition to the histic examination, other methods are increasingly being used nowadays, mainly since the fact that the biopsy does not provide a conclusive diagnosis. Other procedures include the study of biochemical and DNA testing, where one can identify the gene where the mutation has occurred (Munar-Qus, 1994).

4. Hereditary systemic amyloidosis

In 1939, Corino de Andrade, a neurologist at the Hospital General de Santo Antonio in OPorto, noticed a 37-year-old patient from the city of Povoa do Varzim with an interesting medical presentation. This patient showed clinical signs of cachexia, accompanied by loss of thermal sensitivity, pain on the lower extremities, gastrointestinal disorders and lost of his sphincters control. According to Andrade, the disease began insidiously a year ago with lower limb numbness, diarrhea and weight loss. In this region this condition was known by the popular term doena dos pezinhos (feet disease). The author noted that more patients with the same disease could be found among families and discovered a genetic association between them since they all developed the same clinical signs and symptoms. In 1952 a comprehensive clinical and anatomical study based on 74 cases was published, which emphasized the family nature of the disease and demonstrated the need for a genetic research. As a result, a genetic study is initiated with 64 individuals, revealing a high

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incidence of the disease among generations of families in the city of Povoa de Varzim and proximities. The existence of the disease in several generations assumed the character of autosomal dominant genetic inheritance that had, as a common feature, a sensory-motor neuropathy associated with multiple signs and symptoms as sexual dysfunction, diarrhea, orthostatic hypotension, cardiac arrhythmias among others. In this study, the new entity described by Andrade became known as FAP (Andrade, Canijo, Klein & Kaelin, 1969; Conceio, 2006). Since Andrade described this new amyloidosis, three types with similar characteristics were reported by the author. According to the chronological order of their discovery, they proceeded to the first classification of hereditary amyloidosis (Munar-Qus, 1994; Conceio, 2006): I or Andrade type FAP FAP type II or type Rukavina Indiana FAP type III or type Iowa Van Allen FAP type IV or type Meretoja Finnish Two new amyloidosis types associated with cardiomyopathy were added, with symptoms like senile systemic amyloidosis and familial amyloid cardiomyopathy. The Danish proposals are for these new types are a CM acronym, numbered according to the standards of GMP (Munar-Qus, 1994). In 1973, Weiss and Page, referred by Munar-Ques, described another type of amyloidosis, characterized by the presence of a kidney disease named Ostertag disease (first described in 1932 by the author that named it) (Munar-Qus, 1994). Finally, Munar-Ques (Munar-Qus, 1994) and then Lobato (Lobato, 2006), reviewed other classifications of amyloidosis with different hereditary characteristics: renal amyloidosis associated with familial Mediterranean fever and hyperglobulinemia D, autosomal recessive. According to Lobato, they are characterized by periods of fever, located inflammation affecting the chest, abdomen, musculoskeletal system and skin and separated by periods without any symptoms. Since the first classification of hereditary amyloidosis, more than 500 families have been identified and described in Portugal, putting the country at the top of the outbreaks (Conceio, 2006). Other countries, like Japan (Misu et al, 1999) and Sweden (Nowak, Sur, Wikstrm, Wilczek & Ericzon, 2005) are in the second and third places, respectively, in the description of the disease. Among national territory, Mallorca (Sastre, Bernabu, Gasc, 2008; Ballesteros Fernndez, 2004) is the main focus, occupying the 5th place worldwide. On the other hand, there are reports of the disease in Portuguese populations that emigrated to France (Snanoudj, et al. 2004). In 1990 Holmgreen proposed the liver transplantation as a form of therapeutic after the discovery of the protein TTR as the major constituent of amyloid deposits in FAP and the conclusion that 90% of it was produced on the liver, changing the course of a disease that undoubtedly led to death and enabling a radical change on the stabilization and improvement of signs and symptoms associated with FAP (Conceio, 2006). According to Lobato, the TTR mutation most common so far is the V30M, although there are other pathological mutations already identified (more than 80 mutations of the TTR). The author claims that the most frequent manifestations of familial amyloidosis TTR mutations are peripheral neuropathy, autonomic, vitreous opacities, carpal tunnel syndrome, leptomeningeal involvement, and heart and kidney disease (Lobato, 2006).

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4.1 Clinical manifestations of FAP type I. Several authors organized these manifestations in groups (Falco de Freitas, 1976; Martnez, 1996; Guevara, Barrientos, Flores & Idiquez, 2003; Conceio, 2006): 4.1.1 Peripheral sensory-motor polyneuropathy and autonomic Especially common in hereditary amyloidosis. The clinical onsets are always characterized by subjective manifestations (Falco de Freitas, 1976) that have early expressions and usually dominate the clinical picture, such as a loss of thermal sensitivity and pain (predominantly distal-proximal and symmetrical) accompanied by paresthesia and dysesthesia which contributes to the onset of plantar ulcers and Charcot joint. Motor followed by sensitive disorders occur. Patients may acquire a characteristic way of walking, named "steppage", due to muscular paresis and atrophy, making it difficult or impossible to place the heel on the floor due to a difficulty on flexing the torso. In more advanced stages, patients will be on wheelchairs and in the final ones theyll be beat down by a motor sensory deficit that prevents them from moving. An atrophy of the interosseous muscles gives the hands a claw setting. 4.1.2 Sexual dysfunction Mainly, a decrease of bulbo-cavernous reflex and decreased semen volume are the first manifestations of the disease in men. In women, a loss of libido and orgasms are registered. 4.1.3 Sphincter disorders Related to a reduced ability to control anal continence (accentuated especially after the appearance of sensorimotor neuropathy), bladder detrusor hipocontractibility or paresis in urination and vesico-ureteral reflux (Guevara, Barrientos, Flores & Idiquez, 2003; Conceio, 2006; Saraiva, 2006). 4.1.4 Gastrointestinal disorders Are common in this disease and observed in most patients. Of all these, dysphagia and xerostomia is present in 50% and 60% of cases (16). The feeling of fullness (gastroparesis) causes anorexia, which may be accompanied by nausea and vomiting resulting from gastric retention. On patients with sensorimotor neuropathy, you may have those with constipation or patients with chronic diarrhea, which on later stages evolutes to fecal incontinence, responsible for the decreased absorption of nutrients (Falco de Freitas, 1976; Conceio, 2006; Saraiva, 2006). Secondary to the disease progression and as a result of multiple factors (reduced intake of nutrients by anorexia, structural alterations, functional, intestinal motility and malabsorption) is generated in the body an imbalance between intake, absorption nutrition and daily nutritional needs. The result is a nutritional deficiency, malnutrition, accompanied by a progressive weight loss. Consequently, there is a decrease on the body mass index (BMI), preexisting a common feature on all: a skinny looking (Fonseca, 2006). 4.1.5 Cardiac disorders: Arrhythmias are the most common disorders of the disease. A normal systolic blood pressure is below 100mmHg in 50% of patients. It is a common finding of orthostatic hypotension.

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4.1.6 Eye disorders Keratoconjunctivitis sicca, vascular disorders of the conjunctiva, pupillary changes, glaucoma and vitreous opacities are the most common ones (Lobato, 2006). 4.1.7 Renal disorders In short term, they can be detected from microalbuminuria to nephrotic syndrome and chronic kidney disease. Since renal impairment is the subject of the study in the approach to the FAP, we shall dedicate a subchapter to the subject. 4.2 Renal disorders in type I FAP Renal amyloidosis is a common complication of amyloidosis, as it appears in 76% of the cases of renal disease. In secondary amyloidosis and familial Mediterranean fever, renal involvement is common, between 75 to 95% and 25%, respectively (Darnell, Torrellas, 1997). In the review carried out by several publications describing amyloidosis, it is suggested that primary amyloidosis is associated with a high incidence of kidney disease(Tena & Oliv, 1994). In a family with amyloidosis several mutations can occur. Andrade described that the genes encoded different plasma proteins (fibrinogen A or lysozyme, among others) as mentioned on Table 2. Renal impairment as in the heart and liver, are revealed as major manifestations associated with such mutations (Mousson et al. 2006; Gillmore, Booth, Madhoo, Pepsys & Hawkins, 1999). In the glomeruli, the amyloid deposits in the mesangium and capillary walls are well diffused and generalized without cell proliferation. At an optic microscope, it appears as a cottony-looking material, amorphous, eosinophilic, gradually infiltrating glomerular structures. The presence of amyloid is confirmed by the apple green birefringence under a polarized light examination after the Congo red staining. The most common sign of kidney disease is a proteinuria that can remain isolated for years. The diagnosis is confirmed by a renal biopsy (Darnell & Torrellas, 1997). At an article (Falco de Freitas, 1976) about the clinical aspects of Andrades FAP type, published in 1976, Falco de Freitas, a professor at the Faculty of Medicine of Oporto, based on the observations of Dr. Corino de Andrade and his colleagues said: "... By principal, and related with other forms of primary and secondary amyloidosis, renal alterations in FAP are very rare. They merely repeat signs of urinary infection, and in all are likelihood related to neuropathic bladder disturbances. While in the terminal phase, very rarely albuminuria in intensity is viewed... Albuminuria solid and other signs that characterize the nephrotic syndrome were never seen ... Or even clear renal failure revealed by the glomerular or tubular function tests also found in this form of amyloidosis In contrast, recent studies (Lobato et al. 1998; Snanoudj et al. 2004) based on histopathological examination of the kidney tissue maintain that there are extensive amyloid deposits in the glomeruli and renal medulla at an early stage, being present in all patients. Lesser amounts of amyloid deposits were also found in the distal convoluted tubule, loop of Henle. There may be the involvement of the cortical arterioles and interlobular arteries. On the other hand, the degree of the kidney disease depends in large measure to the amount of the amyloid deposit (Lobato L, 2006). In a study where microalbuminuria was assessed as a predictor of neuropathy and nephropathy, the most early signs of onset and possibly the most important one are stated,

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the microalbuminuria (albuminuria 20g/min) which may precede the neurologic symptoms. The presence of microalbuminuria in asymptomatic carriers increased by 4.8 the risk of developing neuropathy when compared with those with a normal albumin excretion. These authors assumed that the progression of renal disease is associated with albumin excretion above 30 mg / min (Lobato et al. 2003).

5. Transplantation in FAP
Liver (Lobato et al. 2003; Munar-Qus, 2003; Lobato, 2006) and hepato-renal (Tena & Oliv, 1994; Lobato, 2006) transplantation has established itself as an efficient and growing therapy, according to the latest figures from the International Register quoted by Munar-Ques and is proposed as a treatment for the stabilization of symptoms of FAP, specially in patients with the Val30Met variant since it interrupts the course of the disease and promotes a slow start (Munar-Qus, 2003). The best results were obtained in young patients, and when the transplant occurs during the first year of the disease, if possible (Munar-Qus, 2003). On the other hand, it seems that the liver transplantation changes the progression of renal damage caused by amyloid deposition in the kidney (Snanoudj et al. 2004; Nowak, Sur, Wikstrm, Wilczek & Ericzon, 2005; Lobato, 2006). Several authors suggest risk factors with statistical significance (older age and non-use of mycophenolate mofetil after a transplant) on patients with FAP and liver transplantation, and frequently present commitment of renal function with a tendency for progression to Advanced Chronic Kidney Disease (ACKD) (Pessegueiro, Sampaio, Viana, Nolasco, Santos & Barroso, 2005).

6. Replacement therapy in advanced chronic kidney disease in the context of FAP

On the chronic kidney disease (CKD), there is a slow and progressive loss, usually irreversible, of the kidney function to excrete, result of the destruction of the nephrons. In practice, it is expressed by a glomerular filtration rate (GFR) or an estimated creatinine clearance less than 60 ml/min/1, 73 m2, or the presence of a kidney damage with both persistent disturbances for at least 3 months (Garca Garca, 1997; Soriano Cabrera, 2004). There is also an altered regulatory function and an endocrine-metabolic-dependent kidney (Dmaso & Botella, 1997). Stage 5 of kidney disease, also known as kidney failure, is reflected by the decline in GFR below 15 ml/min/1, 73m23 and the inability of the kidney to maintain a balanced internal environment and eliminate the result of an accumulation of the toxic nitrogen metabolism. Such renal failure leads to a syndrome named uremic syndrome. Garcias (Garca Garca, 1997, pp. 889) definition is: "... The final stage of the evolution of renal ER and is manifested by a multisystemic failure due to the retention of substances (uremic toxins), hormonal disturbances, metabolic changes and electrolyte disorders in the body. Before the introduction of dialysis and transplantation, uremic syndrome can lead to death quickly. The accumulation of uremic toxins in the body is incompatible with life in the ACKD with a GFR inferior to 15 ml/min/1, 73m2. With symptoms of uremic syndrome, the institution of therapeutic alternatives to improve renal function is indispensable (Soriano Cabrera, 2004). The HD, its variants and the peritoneal dialysis are the most common dialytic techniques used nowadays. They are responsible for a partial replacement of the kidney functions, like

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Care resulting from the implementation of medical orders Vascular access care (according to the protocol of each unit) Body treatment: HD Pharmacotherapy Control of vital signs. Control condition of the patient With respect to pathological condition Potential Secondary to: complication: Orthostatic hypotension, arrhythmias, dysrhythmias. Cardiovascular Hypertension, heart failure, pericarditis. Skin lesions and polyneuropathy. Itching, calcium deposit, Cutaneous hematomas. Hematologic: anemia anorexia, fatigue Impotence loss of libido. Infertility, amenorrhea, Endocrine hyperparathyroidism. Diarrhea, fecal incontinence, weight loss, decreased BMI. Gastrointestinal Nausea, vomiting, anorexia, bleeding. Motor sensory and autonomic polyneuropathy. Irritability, Neurological lethargy, headaches, sleep disturbances. Decreased eye visual acuity, vitreous opacities. Keratopathy, Ocular retinopathy Electrolyte Dehydration, Convulsions, nausea, headache, arrhythmias. disturbances Infectious fever, local catheter infection or FAV Bone Osteomalacy, artropathy, hyperparathyroidism Regarding the effects of treatment Potential Secondary to: complication: Hypotension, hypovolemia, vascular status of the patient Nausea and vomiting early manifestation of "disequilibrium syndrome, hypotension Fever / sepsis reaction to pyrogens, infection Extracorporeal circuit inadequate anticoagulation clotting muscle contractures Hyponatremia bleeding inadequate anticoagulation, extracorporeal circuit break dialysis bath temperature too hot, hypotonic dialysis solution Hemolysis or contaminated with bleach, chloramines, copper, nitrates. Headache Caffeine Withdrawal (Daurguidas) hypersensitivity to components of the dialyzer and blood Pruritus circuit Brachialgia prolonged immobilization, trauma to the puncture site Air embolism Air in the circuit Angina Hypotension, vascular status of the patient Table 4. Most common complications associated with treatment with HD

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the excretion of toxic substances, the regulation of acid - base and the elimination of excess fluid in the patients body (Garca Garca & Gri Boira, 1997; Andru & Forc, 2001). The replacement therapy on renal functions allows the survival and active life of patients with renal failure (Garca Garca & Gri Boira, 1997). The peritoneal dialysis, despite the benefits in increasing patient autonomy and tolerance, may become more difficult to implement due to gastrointestinal problems and motor limitations. This technique requires help of the family or caregiver. Through the references quoted, only one presents patients with peritoneal dialysis, a case in Portugal (Gillmore, Booth, Madhoo, Pepsys & Hawkins, 1999) and another in Mallorca (Sastre, Bernabu & Gasc, 2008).

7. Nurse approach in Type I FAP

As mentioned, FAP type I (also called Andrades disease) is a rare inherited autosomic dominant disease. It has been described as the largest existing disease in the region of Povoa de Varzim and Vila do Conde, north of Portugal, followed by Sweden and Japan. In Spain, the disease is scarcely understood. In 2003, 83 patients were diagnosed with FAP in 9 regions of the Peninsula and 148 in Mallorca, considered the largest known Spanish outbreak (Munar-Qus, 1994; Munar-Qus, 2003). In the FAP, as well as in other amyloidosis, there is a deposit of the amyloid in the extracellular space of one or more tissues, causing organic changes through the amount of deposit and / or organ affected. These fibers are insoluble, resist proteolytic digestion and destroy the tissues deposits (Martnez, 1996). In the kidney, the deposit of this substance can cause various states of renal disease, from microalbuminuria to nephrotic syndrome and ACKD4. Microalbuminuria is considered the first clinical stage of nephropathology, predating even the neuropathic symptoms. In carriers, microalbuminuria has a risk 4.8 higher than in those with more than 25 years of age and normal albumin excretion (Lobato, 2006). The need for a replacement therapy of renal functions on patients with FAP is usually done in HD. The peritoneal dialysis is not recommended because of the limitations that these patients have due to their underlying disease and dependence (almost) mandatory on relatives or caregivers (Lobato, 2006). Therefore, the inclusion of these patients on a regular HD program implies an extra caution, in addition to the problems related to the underlying disease, with those that are associated with kidney disease and dialysis treatment.In general, renal patients care is fundamental and essential to know the underlying disease in order to provide specific and individualized care. These patients undergo a radical lifestyle modification that includes physical, psychological and social life changes (Torres, Velasco & Lla, 2006). Patients with FAP are no exception to this rule, and it is particularly necessary to know the "natural evolution" of the disease in order to provide personalized and differentiated care to each patient. The extensive bibliographic search revealed no reference on nursing care in patients with FAP in HD, which shows that this group of patients is poorly studied and documented by the nephrology nursing. Nursing care should be individually targeted, prioritized and according to the specific needs of these patients. The standardization of care plans does not mean equal plans to all patients with FAP in HD. Results and interventions may be similar or not, depending on the needs felt by each individual at the time of evaluation.

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The use of the North American Nursing Diagnosis Association (NANDA) Taxonomy II, the Nursing Outcomes Classification (NOC) and the Nursing Interventions Classification (NIC), unifies criteria and highlights the work of nursing in the HD unit, ensuring a comprehensive care. It also promotes a daily monitoring of the care receiver, improves a better acceptance of their disease, and fosters a therapeutic relationship with health professionals (Torres, Velasco & Lla, 2006). The development of a care plan is a systematic method that directs nursing practice to achieve more efficient objectives (independent or collaborative) (Ruiz, Roman, Serarols, Diez de los Rios, 2001; Garca Palacios et al. 2002). To do this we need equal involvement of all professionals in the institution. It is necessary to use consistent terminology, which allows direct communication, clear and effective care with other teams and the applicability in all areas where nursing takes place (research, teaching, management and support) (Ruiz, Roman, Serarols, Diez de los Rios, 2001). The evaluation model for functional health patterns and taxonomy NANDA, NOC, NIC are widely used and validated by nurses worldwide. The physiological evolution of the disease is very similar in patients with FAP. However, the psychological aspect varies largely, according to each persons perception of the disease (changes in the body image, disability) and their impact on social status, employment, family economic situation and added difficulty in the use of community resources. Despite liver transplantation contributes for the remission of some symptoms associated with the FAP, the incurable nature of the disease continues to be a reality for others (Lopes, 2006). Modifications on the body image may limit the activities of daily living. On the other hand, treatment with HD, the construction of vascular access, GI disturbances, weight loss and other manifestations of the disease, can lead to an abandon of the working life due to the disability imposed by the disease. In Portugal there is a particular association of social solidarity that contributes to the study of FAP, headquartered in the region of Vila do Conde, Northern Portugal. This association currently has ten centers throughout the Portuguese territory. One of those is in Lisbon, where FAP patients may benefit from the services this organization offers. In Spanish territory, Mallorca hosts the Study Group of FAP. For patients with FAP who initiate HD, we must note that this type of treatment involves a greater sense of loss of independence, as well as time constraints, recreational and labor constraints and imposes the need to go to hemodialysis to maintain life (Lpez Alonso, Gmez Jarabe, Gonzlez Garca, 2000). The dependency of a machine is seen as a stressful situation for the patient, mostly because of the fear of death and the fear of being dependent of an HD monitor (Rudnicki, 2006). During the HD session, there are several complications that may arise from the implementation of medical orders or the evolution of the pathological condition (Table 4) (Ruiz, Roman, Serarols, Diez de los Rios, 2001).

8. Conclusion
FAP is a disease that is well documented by the medical community worldwide but it is little known and described by nurses who provide care in the area of nephrology in our environment. On the other hand, there is a need to create a specific care plan specifically designed to patients with FAP in HD, taking into account the symptoms that may occur. Thus it is acceptable to raise the results and address the activities to be as adapted as possible to the needs of each patient.

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9. References
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