BUKU PEGANGAN TUTOR

Modul MUAL DAN MUNTAH

Diberikan pada mahasiswasemester IV FK UNHAS

SISTEM UROGENITALIAFAKULTAS KEDOKTERAN

UNIVERSITAS HASANUDDINMAKASSAR

2006

PENDAHULUAN

Modul mual dan muntah ini diberikan pada mahasiswa yang mengambil mata

kuliah sistim Urogenitalia di semester IV. TIU dan TIK pada sistim ini disajikan pada

permulaan buku modul agar dapat dimengerti secara menyeluruh tentang konsep dasar

penyakit-penyakit Sistem Urogenitalia yang memberikan gejala mual dan muntah.

Mahasiswa diharapkan mampu menjelaskan semua aspek tentang system Urogenitalia

dan patomekanisme terjadinya penyakit, kelainan jaringan, dan pemeriksaan lain yang

dibutuhkan pada penyakit yang memberikan gejala mual dan muntah.

Sebelum menggunakan modul ini, mahasiswa diharapkan membaca TIU dan TIK

sehingga tidak terjadi penyimpangan pada diskusi dan tujuan serta dapat dicapai

kompetensi minimal yang diharapkan. Bahan untuk diskusi dapat diperoleh dari bacaan

yang tercatum di akhir modul. Kuliah pakar akan diberikan atas permintaan mahasiswa

yang berkaitan dengan penyakit ataupun penjelasan dalam pertemuan konsultasi antara

peserta kelompok diskusi mahasiswa dengan tutor atau ahli yang bersangkutan.

Penyusun mengharapkan modul ini dapat membantu mahasiwa dalam

memecahkan masalah penyakit Urogenitalia yang disajikan.

Makassar, 2 Desember 2005

Penyusun

TUJUAN INSTRUKSIONAL UMUM

Setelah mempelajari modul ini mahasiswa diharapkan dapat menjelaskan penyebab, patomekanisme, gambaran klinik, cara diagnosis, penanganan dan pencegahan penyakit-penyakit sistem urogenitalia yang menyebabkan gejala mual dan muntah.

TUJUAN INSTRUKSIONAL KHUSUS

Setelah pembelajaran dengan modul ini mahasiswa diharapkan dapat:

A. Menyebut penyakit-penyakit yang menyebabkan gejala mual dan muntah.

B. Menjelaskan tentang patomekanisme terjadinya penyakit-penyakit yang

menyebabkan gejala mual dan muntah

1. menguraikan struktur anatomi, histologi dan histofisiologi dari sistim uropoetika

2. menyebutkan fungsi masing-masing bagian dari

nefron, fungsi sel-sel JGA dalam renin angiotensin system,

3. menjelaskan faktor-faktor yang mempengaruhi

GFR, prinsip hukum Starling pada filtrasi ginjal, dan dapat menghitung GFR,

4. menjelaskan mekanisme dan proses reabsorbsi dan

sekresi di tubulus, mengapa ada zat yang mempunyai Tmax, peranan hormon

aldosteron dan ADH pada reabsorbsi, pengaturan reabsorbsi dan sekresi di

tubulus, counter current mechanism, proses reabsorbsi dan sekresi pada keadaan

tertentu seperti dehidrasi dan overhidrasi

5. menjelaskan biokimia urine dan kompensasi ginjal dalam keseimbangan asam

basa

6. menjelaskan tentang penyebab penyakit-penyakit yang menyebabkan gejala nyeri

saat berkamih

7. menjelaskan hubungan antara penyebab, respon dan perubahan jaringan pada

patogenesis terjadinya penyakit yang menyebabkan gejala nyeri saat berkamih

C. menjelaskan tentang gejala-gejala klinik penyakit-penyakit: GNA, BSK, Nefropathy,

dan penyakit non-uropoetik msialnya alergi dan kelainan ginjal akibat rehidrasi.

D. menjelaskan tentang cara-cara diagnosis GNA, BSK, Nefropathy, dan penyakit non-

uropoetik msialnya alergi dan kelainan ginjal akibat rehidrasi.

menjelaskan tentang cara anamnesis terarah pada penderita penyakit-penyakit di

atas

1. menjelaskan tentang cara pemeriksaan fisik penderita penyakit-penyakit di atas ,

menggambarkan perubahan histopatologi penyakit-penyakit di atas

menjelaskan fase pre-analitik, analitik & Post analitik dari prosedur tes/Lab pada

penyakit-penyakit di atas

menganalisa hasil laboratorium pada penderita penyakit-penyakit di atas .

menjelaskan gambaran Rontgen dari saluran kemih yang normal, dan pada

penyakit di atas.

E. menjelaskan tentang penatalaksanaan pada penderita penyakit-penyakit di atas

menyebutkan obat-obatan yang dipakai pada penderita dengan gejala nyeri saat

berkamih,

menjelaskan farmakodinamik dan farmakokinetik obat-obat yang digunakan

dalam terapi penyakit yang menyebabkan gejala nyeri saat berkamih

menjelaskan asuhan nitrizi pada penyakit-penyakit yang menyebabkan gejala

nyeri saat berkamih

F. Menjelaskan tentang aspek epidemiologi penyakit-penyakit yang tersebut di atas

PROBLEM TREE

Lab : Urine Kimia darah UrinalisisPemeriksaan lain :BNOCT Scan, USG

Diagnosis Banding BSKNefropathyTumor UG

Anamnesis :Disuria, pollakisuriaDemam +/-, ada darah diakhir miksi

Fisik Diagnostik :Suhu tubuh subfebrilTampak nyeri

MUAL DAN MUNTAH

AnatomiHistologiFisiologiBiokimiaPatologi Anatomi FarmakologiMikrobiologi

Bedah

Medikamentosa Non MedikamentosaNutrisi

PenatalaksanaanPengendalian

Preventif Promotif Non Bedah

Skenario 1. Mual dan muntah

1. Setelah membaca dengan teliti skenario di atas anda harus mendiskusikan kasus

tersebut pada satu kelompok diskusi terdiri dari 12 – 15 orang, dipimpin oleh seorang

ketua dan seorang penulis yang dipilih oleh anda sendiri. Ketua dan sekretaris ini

sebaiknya berganti-ganti pada setiap kali diskusi. Diskusi kelompok ini bisa dipimpin

oleh seorang tutor atau dilakukan secara mandiri oleh kelompok.

2. Melakukan aktivitas pembelajaran individual di perpustakaan dengan menggunakan

buku ajar, majalah, slide, tape atau video, dan internet, untuk mencari informasi

tambahan.

3. Melakukan diskusi kelompok mandiri (tanpa tutor) , melakukan curah pendapat bebas

antar anggota kelompok untuk menganalisa dan atau mensintese informasi dalam

menyelesaikan masalah.

4. Berkonsultasi pada nara sumber yang ahli pada permasalahan dimaksud untuk

memperoleh pengertian yang lebih mendalam (tanpa pakar).

5. Mengikut kuliah khusus (kuliah pakar) dalam kelas untuk masalah yang belum jelas

atau tidak ditemukan jawabannya.

6. Melakukan latihan dilaboratorium keterampilan klinik dan praktikum di laboratorium.

Penderita laki-laki, 45 thn MRS dengan keluhan mual muntah yang dialami sejak beberapa hari sebelumnya. Tiga (3) thn yang lalu penderita pernah mengalami bengkak pada seluruh tubuh. Pada pemeriksaan fisik TD 200/120 mmHg, nadi 120x/mnt reguler, afebris, pernapasan 24x/mnt torakoabdominal.

TUGAS MAHASISWA

PROSES PEMECAHAN MASALAH

Dalam diskusi kelompok dengan menggunakan metode curah pendapat, mahasiswa

diharapkan memecahkan problem yang terdapat dalam skenario ini, yaitu dengan

mengikuti 7 langkah penyelesaian masalah di bawah ini:

1. Klarifikasi istilah yang tidak jelas dalam scenario di atas, dan tentukan kata/ kalimat

kunci skenario diatas.

2. Identifikasi problem dasar scenario diatas dengan, dengan membuat beberapa

pertanyaan penting.

3. Analisa problem-problem tersebut dengan menjawab pertanyaan-pertanyaan diatas.

4. Klasifikasikan jawaban atas pertanyaan-pertanyaan tersebut di atas.

5. Tentukan tujuan pembelajaran yang ingindi capai oleh mahasiswa atas kasus

tersebut diatas.

6. Cari informasi tambahan tentang kasus diatas dari luar kelompok tatap muka.

Langkah 6 dilakukan dengan belajar mandiri.

7. Laporkan hasil diskusi dan sistesis informasi-informasi yang baru ditemukan.

Langkah 7 dilakukan dalm kelompok diskusi dengan tutor.

Penjelasan :

Bila dari hasil evaluasi laporan kelompok ternyata masih ada informasi yang

diperlukan untuk sampai pada kesimpulan akhir, maka proses 6 bisa diulangi, dan

selanjutnya dilakukan lagi langkah 7.

Kedua langkah diatas bisa diulang-ulang di luar tutorial, dan setelah informasi

dirasa cukup maka pelaporan dilakukan dalam diskusi akhir, yang biasanya dilakukan

dalam bentuk diskusi panel dimana semua pakar duduk bersama untuk memberikan

penjelasan atas hal-hal yang belum jelas.

1. Pertemuan pertama dalam kelas besar dengan tatap muka satu arah dan tanya jawab.

Tujuan : menjelaskan tentang modul dan cara menyelesaikan modul, dan membagi

kelompok diskusi. Pada pertemuan pertama buku modul dibagikan.

2. Pertemuan kedua : diskusi mandiri. Tujuan :

* Memilih ketua dan sekretaris kelompok,

* Brain-storming untuk proses 1 – 3,

* Membagi tugas

3. Pertemuan ketiga: diskusi tutorial dipimpin oleh mahasiswa yang terpilih menjadi

ketua dan penulis kelompok, serta difasilitasi oleh tutor. Tujuan: untuk melaporkan

hasil diskusi mandiri dan menyelesaikan proses sampai langkah 5.

4. Anda belajar mandiri baik sendiri-sendiri. Tujuan: untuk mencari informasi baru yang

diperlukan,

5. Pertemuan keempat: adalah diskusi tutorial. Tujuan: untuk melaporkan hasil diskusi

lalu dan mensintese informasi yang baru ditemukan. Bila masih diperlukan informasi

baru dilanjutkan lagi seperti No. 2 dan 3.

6. Pertemuan terakhir: dilakukan dalam kelas besar dengan bentuk diskusi panel untuk

melaporkan hasil diskusi masing-masing kelompok dan menanyakan hal-hal yang

belum terjawab pada ahlinya (temu pakar).

TIME TABLE

PERTEMUANI II III IV V VI VII

Pertemuan I(Penjelasan)

Pertemuan Mandiri(Brain

Stroming)

Tutorial I Pengum-

pulan informasiAnalisa &

sintese

Mandiri

PraktikumCSL

Kuliah kosultasi

Tutorial II(Laporan &

Diskusi)

Pertemuan Terakhir (Laporan)

JADWAL KEGIATAN

STRATEGI PEMBELAJARAN

1. Diskusi kelompok difasilitasi oleh tutor

2. Diskusi kelompok tanpa tutor

3. CSL : Pemeriksaan benjolan pada leher

4. Praktikum PA

5. Konsultasi pada pakar

6. Kuliah khusus dalam kelas

7. Aktivitas pembelajaran individual diperpustakaan dengan menggunakan buku ajar

Majalah,slide,tape atau video dan internet

A. Buku Ajar dan Jurnal

1 Urology : R.W. Barnes, R.T.Bergman, H.Hodley, Toppan Co.(S) PTE-LTD,Singapore2 Davitson VL and Sittman DB : Biochemistry3 Kumar, Contran, Robbins: Pathology Basis of Diseases, 20034 Chandrasoma- Taylor: Concise Pathology, 19995 Kenneth J Rothman, 1986, Modern Epidemiology, Little Brownc and Company, Bon 6 World Health Organization, 1992, International statistical Classification of Diseases

an and related Health Problems, 10th revision, volume 1, WHO, Geneva

7 Goodharmt R : Modern nutrition in health and disease, Lee Ferbeger, 20028 Robinson : Normal and Therapeutic Nutrition, Mac Millian Co., New York9 Lenne EH et al ; Manual of Clinical Microbiology , 4th edition, 1985

10 Prescott LM et al : Microbiology, 2nd edition, Wm.c Brown Publisher, Melbourne, 1993

11 WF. Ganong : Review of Medical Physiology, edisi 20, 200312 Synopsis of analysis of Roentgen sign in general Radiology, Isadore Meschan, 197613 Junguiera LC, Carneiro J : Basic Histology 3th edition, Los Altos California USA,

Lange Medical Publication, 198014 Stites DP, Stobo JD, Fudenberg HH : basic and Clinical Immunology, 4th edition, Los

Altos California, Lange Medical Publication, 1982

15 Schlesinger ER, Sultz HA, Mosher WE, et al. The Nephrotic Syndrome. Its incidence and implications for the community. Am J Dis Child 1968, 116; 623

16 International Study of Kidney Disease in Children. Nephrotic Syndrom in Children. Prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. Kidney Int. 1978, 13: 159.

17 Kher KK. Obstructive uropathy. Dalam : Kher KK, Marker SP, penyunting. Clinical Pediatric Nephrology. New York: Mc Graw – Hill 1992: 447-65.

18 Behrman RE. Nelson textbook of pediatrics; edisi ke 14. Philadelphia: WB Saunders,

BAHAN BACAAN & SUMBER INFORMASI LAIN

1992; 1344-50.19 Homes HD, Weinberg JM. Toxic nephropathies. Dalam: Brenner Rector FC,

penyunting, The Kidney, II; edisi ke-Philadelphia: WB Saunders Co, 1986; 1491-532.20 Barrat TM. Acute renal failure. Dalam: Holliday MA, Barrat TM, Vernier RL,

penyunting. Pediatric nephrology, edisi ke-2. Baltimore: Williams & Wilkins 1987; 766-72.

21 Kher KK. Chronic renal failure. Dalam Kher KK, Marker SP, penyunting, clinical pediatric nephrology. New York: MC Graw-Hill Inc, 1992, 501-41.

22 Karjomanggolo WT, Alatas H. Kelainan congenital ginjal dan saluran kemih. Dalam: Naskah lengkap PKB. IKA XXVI : Penelitian tractor urinarius pada anak. Jakarta 11 – 12 September 1992: 1176-84.

23 Londe S causes of hypertension in the young. Pediatric Clin North Am 1978; 25-55.24 Henry JB : Clinical Diagnosis and Manage,ent by laboratory Methods, 19th ed, 199625 H. Beers and R. Berkow editor : The Merck Manual 17th ed, 199926 Harrison : Disorders of the kidney and Urinary tractus, 15th edition, Volume I, Mc

Graw Hill, 2002, pp : 1535-163027 Ginjal Hipertensi dalam Buku Ajar Ilmu Penyakit Dalam jilid II, edisi III, Balai Penerbit

FKUI Jakarta, 2001

B. Diktat dan hand-out

1. Diktat Anatomi2. Diktat Histologi3. Buku Ajar Fisiologi Ginjal4. Diktat Kuliah Radiologi

C. Sumber lain : VCD, Film, Internet, Slide, Tape

D. Nara sumber (Dosen Pengampu)

DAFTAR NAMA NARA SUMBER

No. NAMA DOSEN BAGIAN TLP. KANTOR

HP/FLEXI

1. Prof.Dr. dr. Syarifuddin Rauf Sp.PA

Anak 0811411109

2. Prof.Dr.dr. Syakib Bakri, Sp.PD

Penyakit Dalam 0816250620

3. Prof.dr. Ahmad M Palinrungi Sp.B, Sp.U

Bedah Urologi 08164384040

4. Prof.Dr.dr. M.Dali Amiruddin, Sp.KK

Kulit Kelamin 08194229858

5. Dr. Irfan Idris, MS Fisiologi 584730 0813426953486. Dr. Theopilus Buranda, MS Anatomi 0813424364447. Dr. Robby Lianury Histologi 08114117238. Dr. Agnes Kwenang, MS Biokimia9. Dr. dr. Gatot Lawrence Patologi 0816255306

Anatomi10. Dr. dr. Nurpudji Astuti,

SpGKGizi 0811443856

11. Dr. dr. Fatmawati Farmakologi 08152412036812. Dr. Randana Bandaso, MS Patologi

Anatomi13. Dr. Nurlaily Idris, Sp.R Radiologi 081144106414. Dr. H, Ibrahim Samad, SpPK Patologi Klinik15. Dr. Baedah Madjid, SpMK Mikrobiologi 081144432616. Dr. Sastri, SpKK Kulit Kelamin 08124217393

Apa yang dimaksud ‘kata kunci’ berikut ini :

o Mual : Perasaan seperti akan muntah, karena terjadi perangsangan pada

pusat muntah

o Muntah : Keluarnya makanan/minuman dari mulut akibat dorongan

antiperistaltik pada lambung/saluran cerna. Dapat disebabkan oleh

perangsangan pada batang otak dan rangsangan pada saluran cerna

o Bengkak seluruh badan 3 thn yang lalu : 3 tahun yang lalu penderita

mengalami udem (anasarka)

o Hipertensi dengan TD 200/120 mmHg : Penderita merupakan penderita

Hipertensi berat

Apa penyebab dan bagaimana pato-mekanisme gejala-gejala yang menjadi kata

kunci tersebut

o Mual dan muntah : Gejala yang disebabkan perangsangan pada pusat

muntah di batang otak (Pons Serebri). Mual dan muntah dapat disebabkan

oleh perangsangan pada saluran cerna dan juga pada kemoreseptor trigger

zone di batang otak. Pada penyakit ginjal yang kronis akan menyebabkan

meningkatnya BUN (Azotemia), sehingga merangsang chemoreseptor

trigger zone untuk merangsang terjadinya muntah.

PETUNJUK UNTUK TUTOR

o Riwayat bengkak seluruh badan 3 tahun yang lalu dapat disebabkan oleh

retensi air dan garam akibat kerusakan yang terjadi pada ginjal.

o Hipertensi yang terjadi dapat disebabkan oleh karena adanya kerusakan

pada ginjal atau sebaliknya Hipertensi berat yang lama akan menyebabkan

kerusakan pada ginjal

Sebutkan beberapa penyakit yang dapat di differential diagnosis

dengan tanda dan gejala pada skenario

Acute Renal Failure Anemia Chronic Renal Failure Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetic Nephropathy Encephalopathy, Uremic Glomerulonephritis, Acute Glomerulonephritis, Chronic Glomerulonephritis, Rapidly Progressive Hypertension Hypertension, Malignant

Metabolic Acidosis

Pemeriksaan penunjang yang dibutuhkan untuk menegakkan diagnosis penyakit

yang termasuk dalam DD penyakit tersebut

1. Darah lengkap

2. Kimia darah : Ureum, kreatinin, elektrolit plasma, analisa gas darah

3. Urinalysis

4. Radiologi : USG, CT scan, MRI

5. Biopsi

Bagaimana cara penatalaksanaan dari penyakit-penyakit yang termasuk dalam

DD penyakit tersebut

1. Medikamentosa

2. Dialisis

3. Bedah ; Transplantasi

4. Diet

Epidemiologi dan cara pencegahan penyakit tersebut

1. Hindari penggunaan berlebihan NSAID, aminoglikosisa, dan zat yang toksik

pada ginjal, penderita Hipertensi dan DM sebaiknya kontrol secara reguler

2. Data prevalensi uremia belum diketahui dengan akurat.

Komplikasi penyakit-penyakit yang termasuk DD pada skenario

1. Kejang-kejang

2. Koma

3. Henti jantung

4. Kematian

Prognosis penyakit-penyakit tersebut

1. Prognosis penderita uremia dengan GGK buruk meskipun 2. Prognosis GGA tergantung waktu diagnosis dan ketepatan terapinya

Uremia

Background: Uremia is a syndrome of clinical and metabolic abnormalities associated with fluid, electrolyte, and hormone imbalances, which develop in parallel with deterioration of renal function. The term uremia, which literally means urine in the blood, was first used by Piorry to describe the clinical condition associated with renal failure. In general, uremia is associated with chronic renal failure (CRF), but it also may occur with acute renal failure (ARF) if loss of renal function is rapid. As yet, no single uremic toxin has been identified that accounts for all of the clinical manifestations of uremia. However, other toxins, such as parathyroid hormone (PTH), beta2 microglobulin, or other middle molecules, are thought to contribute to the clinical syndrome.

Pathophysiology: Normally, the kidney is the site of hormone production and secretion, acid-base metabolism and regulation, fluid and electrolyte regulation, and waste-product elimination. In the presence of renal failure, these functions are not performed adequately and metabolic abnormalities, such as anemia, acidemia, hyperkalemia, hyperparathyroidism, malnutrition, and hypertension, occur. Uremia is clinically apparent once creatinine clearance is less than 10-20 mL/min, although some patients may be symptomatic at higher clearance levels. The syndrome may be heralded by the clinical onset of nausea, vomiting, fatigue, anorexia, weight loss, muscle cramps, pruritus, and change in mental status.

Anemia

Anemia-induced fatigue is thought to be one of the major contributors to the uremic syndrome. Erythropoietin (EPO), a hormone necessary for red blood cell production in bone marrow, is produced by peritubular cells in the kidney in response to hypoxia. Anemia associated with renal failure can be observed when the glomerular filtration rate (GFR) is less than 30 mL/min or when the serum creatinine clearance is greater than 2 mg/dL. Diabetic patients may experience anemia with a GFR of less than 45 mL/min. Anemia associated with chronic kidney disease is characteristically normocytic, normochromic, and hypoproliferative. Reduced EPO production leads to a low reticulocyte count, a characteristic that distinguishes anemia of chronic kidney disease from anemia of chronic disease. In contrast, anemia of chronic disease is typically normochromic, normocytic, hyperproliferative, and associated with elevated EPO levels, which leads to an elevated reticulocyte count.

In the setting of CRF, anemia may be due to other clinical factors or diseases such as iron deficiency, vitamin deficiency secondary to poor appetite, or elevated PTH levels. Iron deficiency may occur as a result of occult GI bleeding due to elevated BUN, inhibition of platelet aggregation, or frequent blood draws in a patient with chronic renal insufficiency or renal failure. However, if the stool is guaiac-positive, a GI cause for blood loss, such as from a tumor or ulcer, must be investigated. In addition to the above causes, decreased levels of folic acid or vitamin B-12 may contribute to anemia. Also, elevated PTH levels are thought to be associated with marrow calcification, which may suppress red blood cell production and lead to a hypoproliferative anemia. Parathyroid-induced marrow calcification tends to regress after parathyroidectomy.

Acidosis

Acidosis is another major metabolic abnormality associated with uremia. Metabolic acid-base regulation is controlled primarily by tubular cells located in the kidney, while respiratory compensation is accomplished in the lungs. Accumulation of hydrogen ions occurs in the setting of CRF or urinary bicarbonate wasting, which occurs with interstitial renal disease, and may contribute to metabolic acidosis. Accumulation of phosphate and other organic acids, such as uric acid, hippuric acid, and lactic acid, contribute to the increased ion-gap metabolic acidosis. Hyperchloremic nongap metabolic acidosis occurs when chloride ions are retained in exchange for urinary bicarbonate excretion. In uremia, metabolic acidemia may contribute to other clinical

abnormalities, such as hyperventilation, anorexia, stupor, decreased cardiac response (congestive heart failure), and muscle weakness.

Hyperkalemia

Hyperkalemia (potassium, >6.5 mEq/L) may be an acute or chronic manifestation of renal failure, but regardless of the etiology, a potassium level of greater than 6.5 mEq/L is a clinical emergency. As renal function declines, the nephron is unable to excrete a normal potassium load, which can lead to hyperkalemia if dietary intake remains constant. In addition, other metabolic abnormalities, such as acidemia or type IV renal tubular acidosis, may contribute to decreased potassium excretion and lead to hyperkalemia. However, remember that most cases of hyperkalemia are multifactorial in etiology.

Hyperkalemia can occur in several instances, which include (1) excessive potassium intake in patients with a creatinine clearance of less than 30 mL/min, (2) hyporeninemic hypoaldosteronism or type IV renal tubular acidosis in older patients with diabetes or patients with interstitial nephritis, (3) hypercatabolic states, (4) significant acidemia, or (5) with drug therapy. Hyperkalemia is common when drugs, such as potassium-sparing diuretics (eg, spironolactone, amiloride, triamterene), ACE inhibitors, angiotensin-receptor blockers, beta-blockers, or nonsteroidal anti-inflammatory drugs are used in the setting of renal insufficiency or renal failure.

Calcium, parathyroid, and vitamin D abnormalities

Abnormalities of the calcium–vitamin D metabolic pathway associated with renal failure result in elevated PTH levels (secondary hyperparathyroidism), which ultimately leads to renal bone disease (osteodystrophy). After exposure to the sun, vitamin D-3 is produced in the skin and transported to the liver for hydroxylation (25[OH] vitamin D-3). Hydroxylated vitamin D-3 is then transported to the kidney, where a second hydroxylation occurs, and 1,25(OH)2 vitamin D-3 is formed. As the clinically active form of vitamin D, 1,25(OH)2 vitamin D-3 is responsible for GI absorption of calcium and suppression of PTH. During renal failure, 1,25(OH)2 vitamin D-3 levels are reduced secondary to decreased production in renal tissue, which leads to decreased calcium absorption from the GI tract and results in low serum calcium levels. Hypocalcemia stimulates the parathyroid gland to excrete PTH, a process termed secondary hyperparathyroidism.

In this setting, 1,25(OH)2 vitamin D-3 can be replaced orally as calcitriol or intravenously as Calcijex or the newer vitamin D analogue agent Zemplar (both are trade names for forms of calcitriol), which suppress the parathyroid gland in a negative feedback loop.

In addition to the calcium abnormalities, hyperphosphatemia occurs as excretion of phosphate decreases with progressive renal failure. Hyperphosphatemia is a major stimulant for PTH release and a major stimulant for the direct synthesis and secretion of PTH. Hyperphosphatemia also stimulates parathyroid gland hypertrophy and stimulates increased production and secretion of PTH. Elevated PTH levels have been associated with uremic neuropathy and other metabolic disturbances, which include altered pancreatic response, erythropoiesis, and cardiac and liver function abnormalities. The direct deposit of calcium and phosphate in the skin, blood vessels, and other tissue, termed metastatic calcification, occurs when the calcium-phosphate product is greater than 70.

Endocrine abnormalities

Other endocrine abnormalities that may occur in the setting of uremia include changes in carbohydrate metabolism, decreased thyroid hormone excretion, abnormal sexual hormone regulation, and abnormal growth hormone metabolism. Changes in carbohydrate metabolism result in glucose-induced pancreatic insulin secretion and insulin sensitivity, which can lead to

increased episodes of hypoglycemia and normalization of hyperglycemia in diabetic patients. Glycemic control may appear to be improved; however, this may be an ominous sign of renal function decline. Consider appropriate decreases in doses of antihyperglycemia medications (ie, insulin and oral antihyperglycemic medications) as renal function declines to avoid hypoglycemic reactions.

Levels of thyroid hormones, such as thyroxine, become depressed or are low-normal, while reverse triiodothyronine levels increase because of impaired conversion of triiodothyronine to thyroxine. However, patients may not be clinically hypothyroid, and replacement therapy should be considered with elevated thyroid-stimulating hormone levels. In addition to thyroid hormone abnormalities, levels of growth hormone and growth hormone–binding protein can increase, which can cause growth hormone hyporesponsiveness. These abnormalities can lead to growth retardation in children, but they appear to have little or no affect on adults.

Reproductive hormone dysfunction is common and can cause impotence in men and infertility in women. Renal failure is associated with decreased spermatogenesis, reduced testosterone levels, increased estrogen levels, and elevated luteinizing hormone levels in men, all of which contribute to impotence and decreased libido. In women, uremia reduces the cyclic luteinizing hormone surge, which results in anovulation and amenorrhea. Infertility is common and pregnancy is rare in women with advanced uremia and renal failure, the process of which may be reversed with renal transplantation.

Cardiovascular abnormalities

Cardiovascular abnormalities and associated hypertension are common occurrences in persons with chronic uremia. Cardiovascular abnormalities include uremic pericarditis, pericardial effusions, calcium and phosphate–associated worsening of underlying valvular disorders, and uremic suppression of myocardial contractility. Left ventricular hypertrophy is a common disorder found in approximately 75% of patients who have not yet undergone dialysis. Left ventricular hypertrophy is associated with ventricular dilatation, arterial stiffening, coronary atherosclerosis, and/or coronary artery calcification. Commonly, cardiac arrhythmias are due to underlying electrolyte and acid-base abnormalities. Renal dysfunction may contribute to associated fluid retention, which may lead to uncontrolled hypertension and congestive heart failure.

Malnutrition

Malnutrition usually occurs as renal failure progresses and is manifested by anorexia, acidemia, and insulin resistance. Clinical indicators of malnutrition include weight loss, loss of muscle mass, low cholesterol levels, low BUN levels in the setting of an elevated creatinine level, low serum transferrin levels, and hypoalbuminemia. However, whether uremia stimulates protein catabolism directly remains controversial. Other mechanisms of malnutrition include anorexia, which can be induced by the impaired taste and decreased olfactory function commonly associated with elevated levels of urea and other retained toxins.

Comorbid diseases, such as diabetes, congestive heart failure, or other diseases, that require reduced food intake or restrictions of certain foods may contribute to anorexia. Leptin, a 16-kilodalton plasma protein that suppresses appetite, has been associated with low level of protein intake and loss of lean tissue. Leptin is retained with renal failure and is also thought to contribute to uremia-associated anorexia.

Frequency:

In the US: The prevalence of uremia has not been evaluated specifically, but uremia is thought to occur when the creatinine clearance is less than 10 mL/min or less than 15

mL/min in diabetic patients. Presently, the majority of patients begin dialysis after the onset of uremia or when the creatinine clearance is less than 10 mL/min. When the prevalence of delayed initiation of dialysis from was evaluated in the United States Renal Data System, most dialysis patients were found to have started dialysis when their calculated GFRs were 5-10 mL/min (62.5%) and almost one quarter of patients started dialysis when their calculated GFRs were less than 5 mL/min (23.5%). The current unadjusted crude prevalence of end-stage renal disease (ESRD) in the United States is 320 cases per 1 million persons. As of 1998, 319,515 patients were on dialysis in the United States.

Internationally: The prevalence of ESRD in other countries is 2- to 3-fold lower than that of the United States. This difference most likely represents the increased rate of diabetes and hypertension in US minority populations, such as in African Americans and Native Americans.

Mortality/Morbidity: Information on patients prior to the initiation of dialysis is not readily available. Thus, data regarding morbidity and mortality associated with uremia are inferred indirectly from data available from new dialysis patients. Dialysis is a life-saving measure in uremic patients, for whom death is imminent if renal replacement therapy is not performed.

The first-year age-adjusted mortality rate of patients on dialysis is 9.4%, the second-year mortality rate is 32.3%, and the 5-year mortality rate is 60.8%. In contrast, diabetic ESRD patients have a first-year mortality rate of 23%.

In patients with ESRD, cardiovascular disease, which is followed by sepsis and cerebrovascular disease, is the primary cause of death. The survival rate for the general population with renal insufficiency prior to the initiation of dialysis is not known, but the prevalence of cardiovascular disease is thought to be significant in predialysis patients, particularly older diabetic patients who are thought to have a high mortality rate related to cardiovascular disease prior to the initiation of dialysis therapy.

Morbidity is significant for patients with uremia, although not much is known regarding the risk of hospitalization or comorbid disease prior to the initiation of dialysis. Using United States Renal Data System data, investigators found that patients who had delayed initiation of dialysis had 1.5-fold higher risk of a low serum albumin level and 1.8-fold higher risk of starting dialysis with a hematocrit value lower than 28% compared with those who did not have a low creatinine clearance. Patients with delayed onset of dialysis were not more likely to have prevalent cardiac disease, peripheral vascular disease, hypertension, or poor functional status than those without a delayed onset of dialysis. Prospective studies have shown that in patients with CRF, cardiovascular disease is progressive and may manifest clinically as left ventricular dilatation, arterial and aortic calcification, coronary atherosclerosis, and congestive heart failure.

Race: ESRD disproportionately affects minority populations. Whites represent the majority of the ESRD population (59.8%), while African Americans (33.2%), Asians (3.6%) and Native Americans (1.6%) comprise the rest of the ESRD population. Note that African Americans comprise only 12.2% of the US general population but account for a third of the ESRD population.

Minority populations are more likely to have delayed onset of dialysis care and are more likely to start dialysis when their GFRs are significantly decreased.

Compared with whites, Hispanic patients were 1.5-fold more likely to have delayed access to dialysis, while Asian Americans were 1.7-fold more likely and other minority populations were 1.9-fold more likely than whites to have delayed access. However,

African Americans were not more likely to have a delayed onset of dialysis after adjustment for other comorbidities.

Whether a certain racial or ethnic background predisposes patients to symptoms of uremia more so than another racial or ethnic background in patients with equivalent GFRs remains unknown.

Sex: ESRD is slightly more prevalent in men than in women (male-to-female ratio, 1.2:1).

Women are 1.7-fold more likely to have delayed initiation of dialysis than men.

In general, men have higher baseline creatinine levels than women, which is due to the higher muscle mass found in men.

Women may be more likely to develop uremic symptoms at a lower level of creatinine.

Age: ESRD is more prevalent in older adults, but the prevalence of uremia in the CRF population is not known.

Information from the United States Renal Data System indicates that older adults are 31% less likely to have delayed initiation of dialysis than patients on dialysis who were younger than 40 years at the initiation of dialysis.

Making the diagnosis of uremia may be difficult in young children because of the nonspecificity of clinical symptoms.

CLINICAL

History:

Uremia can occur once the creatinine clearance is below 10-20 mL/min, and it is heralded by the clinical onset of nausea, vomiting, fatigue, anorexia, weight loss, muscle cramps, pruritus, mental status changes, visual disturbances, and increased thirst.

Uremic encephalopathy can progress to seizures, stupor, coma, and, eventually, death.

Patients may report of nonspecific symptoms, which become chronic and progressive over time because of the gradual onset of the disease.

Metabolic abnormalities such as anemia, acidemia, and electrolyte abnormalities are prominent.

Cardiovascular abnormalities such as hypertension, atherosclerosis, valvular stenosis and insufficiency, congestive heart failure, and angina accelerate as renal function declines. These abnormalities may contribute to clinical symptoms of uremia if not treated appropriately.

Diabetic patients may appear to be in better glycemic control but may tend to have more hypoglycemic episodes as renal function declines. This paradoxical improvement in glycemic control is a result of increased insulin sensitivity and insulin half-life, both of which occur as renal function declines.

Physical: Typical physical findings found in persons with uremia are those associated with fluid retention, anemia, and acidemia. Severe malnutrition can contribute to muscle wasting, while electrolyte abnormalities may cause muscle cramping, cardiac arrhythmias, and mental status changes.

Skin: The classic skin finding in persons with uremia is uremic frost, which is a fine residue thought to consist of excreted urea left on the skin after evaporation of water. The skin may have a velvety appearance and feel, particularly in patients who are pigmented. Patients who are uremic also may have a sallow coloration of the skin due to urochrome, the pigment that gives urine its color. Patients may become hyperpigmented as uremia worsens (melanosis).

Head, ears, eyes, nose, and throat: Sclera may become slightly icteric. The oral pharynx may be dry. Stomatitis may be present. Calcium deposition in the sclera can cause "red eye."

Cardiovascular system: Uremic pericarditis can be associated with a pericardial rub or a pericardial effusion. Increased fluid retention results in an aortic flow murmur, diastolic dysfunction, and severe hypertension. Valvular calcification may cause aortic stenosis or accelerate underlying disease.

Lungs: Fluid retention may result in pulmonary edema and corresponding crackles in the lungs. Plural rubs occur in the setting of uremic lungs.

Gastrointestinal system: Occult GI bleeding may occur. Nausea and vomiting are common in those with severe uremia. Uremic fetor (ammonia or urinelike odor to the breath) also may be present.

Extremities: Fluid retention, pruritus associated with calcium phosphate deposition, and nail atrophy are common in persons with uremia.

Neurologic system: Uremic encephalopathy symptoms include fatigue, muscle weakness, malaise, headache, restless legs, asterixis, polyneuritis, mental status changes, muscle cramps, seizures, stupor, and coma. Amyloid deposits may result in medial nerve neuropathy, carpal tunnel syndrome, or other nerve entrapment syndromes.

Causes: The etiologies of CRF range from a primary glomerular disease (eg, glomerulonephritis, focal segmental glomerulosclerosis, rapidly progressive glomerulonephritis) to systemic disorders affecting the glomerulus (eg, diabetes, lupus, amyloidosis, Goodpasture disease, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome).

ARF may be caused by multiple etiologies but is associated with uremia when a rapid rise in urea or creatinine occurs.

Diabetes is the primary cause of ESRD in the United States and accounts for 40% of new dialysis patients, followed by hypertension (25.2%), glomerulonephritis (11.3%), interstitial disease (3.8%), cystitis (2.8%), and neoplasms (1.7%).

Diabetes is the primary cause of renal disease in most other countries; however, other glomerulonephropathies, particularly immunoglobulin A nephropathy, may be the primary cause of ESRD, depending upon the country

DIFFERENTIAL

Acute Renal Failure Anemia Chronic Renal Failure Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetic Nephropathy Encephalopathy, Uremic Glomerulonephritis, Acute Glomerulonephritis, Chronic Glomerulonephritis, Rapidly Progressive Hyperchloremic Acidosis Hyperkalemia Hypermagnesemia Hyperparathyroidism Hyperphosphatemia Hypertension Hypertension, Malignant Hypoalbuminemia Hypocalcemia IgA Nephropathy Iron Deficiency Anemia Metabolic Acidosis Pericardial Effusion Pleural Effusion

Other Problems to be Considered:

End-stage renal disease

Lab Studies:

The diagnosis of renal failure is primarily based on abnormal serum laboratory test results, specifically elevated BUN level, serum creatinine level, and CBC count.

Other laboratory tests to consider for abnormalities prevalent with clinical uremia include calcium, phosphate, PTH, magnesium, potassium, and serum bicarbonate values.

Perform an arterial blood gas determination to assess acid-base status.

Urinalysis should be completed by the provider to evaluate for the presence of protein, red blood cell casts, ketones, hemoglobin, myoglobin, and pH.

o The presence of hemoglobin positivity in the absence of red blood cells in a microscopic urine evaluation is an indication of free hemoglobin or myoglobin being filtered by the kidney. This abnormality is commonly associated with renal failure of any etiology and, less commonly, can be associated with hemolytic anemia or rhabdomyolysis.

o Perform a microscopic evaluation of the urine to evaluate for the presence of red blood cell casts, white blood cell casts, bacteria, chronic casts, oval fat bodies, and evidence of papillary necrosis.

o To perform a urinalysis, spin down the urine using the following method: Place 10 mL of urine in a centrifuge tube and spin it at 5000 revolutions per minute for 5 minutes. Discard all of the supernatant, and resuspend the remaining pellet in the centrifuge tube. A plastic or glass pipet is used to gently aspirate the pellet, which is placed with the remaining urine onto a slide. Evaluate the urine pellet under low power with a microscope. Scan the entire slide for casts or cells and go to higher magnification to identify cellular material.

Staging is determined by the GFR (creatinine clearance) and/or a renal biopsy results if renal function decline is rapid and thought to be treatable or reversible.

GFR determination can be accomplished by 24-hour urine collection for creatinine clearance, although creatinine clearance is thought to be less accurate in persons with CRF. In this setting, the average of the combined creatinine clearance and urea clearance is a more accurate determination of the GFR.

Imaging Studies:

A renal ultrasound study is indicated to estimate the size of the kidneys and to evaluate for hydronephrosis or obstruction.

o Hydronephrosis can occur with ureteral or bladder obstruction, retroperitoneal fibrosis, massive abdominal tumors due to cervical or prostate cancers, and other structural abnormalities.

o Renal ultrasound is performed to determine the size and shape of the kidneys; large kidneys are associated with diseases such as diabetes, multiple myeloma, polycystic kidney disease, or acute glomerulonephritis, while small kidneys may indicate chronic diseases such as hypertensive nephrosclerosis, focal segmental glomerulosclerosis, or other chronic kidney diseases.

o A renal ultrasound should be the initial test ordered if pregnancy is a concern.

CT scan of the abdomen may be indicated to rule out retroperitoneal fibrosis, pelvic masses, lymphadenopathy, or lymphoma if bilateral hydronephrosis is found on ultrasound images and no obvious etiology is present (eg, stone, bladder mass, ureteral mass).

Renal duplex Doppler studies can be used to evaluate the renal arteries for areas of stenosis, while evaluation of the renal vein can identify renal vein thrombosis. ARF or CRF can occur with bilateral renal artery stenosis, particularly after the use of ACE inhibitors or nonsteroidal anti-inflammatory agents.

MRI arteriograms can be used to assess the kidneys for acute arterial thrombosis or aortic dissection involving the aorta and renal arteries.

A renal artery duplex Doppler or nuclear medicine renal scan with an ACE inhibitor (ie, mercaptotriglycylglycine renogram, captopril renogram) may be considered if renal artery stenosis is thought to be present. Importantly, consider this abnormality in the differential because it is one cause of renal failure that is potentially reversible by angioplasty or bypass surgery of the affected renal artery.

Consider a brain CT scan in the event of a significant change in mental status, especially if the change occurs after a fall or in association with mild trauma. Spontaneous subdural hematomas occur in patients with uremia, particularly if the BUN level is greater than 150-200 mg/dL.

Other Tests:

Nuclear medicine radioisotope (iothalamate) clearances can also be obtained but are more expensive.

Procedures:

In order to make an accurate diagnosis of ARF or CRF, a renal biopsy is necessary. However, if the renal failure has been slowly progressive and the kidneys are small, renal biopsy results are of little benefit. In the setting of rapidly progressive renal failure or ARF for which the etiology is not known, a renal biopsy is indicated to determine if potentially reversible or treatable renal disorders are present.

Histologic Findings: Histologic findings vary depending on the underlying etiology. However, in the setting of CRF and uremia in which renal function has deteriorated over a prolonged period and the kidneys are relatively small, renal biopsy results may show significant glomerulosclerosis and obsolescent glomeruli (completely scarred and sclerosed) with significant interstitial fibrosis. Renal function decline may be an indication of progressive interstitial fibrosis, particularly in diabetic nephropathy or other glomerular diseases. In the setting of uremia, performing a renal biopsy in a patient with small kidneys may be dangerous because of comorbid disease and the increased risk of bleeding. Consider this procedure if a reversible cause of renal function is in the differential.

Staging: Staging is determined by the GFR (creatinine clearance), renal biopsy results, or both

TREATMENT

Medical Care: The ultimate treatment for uremia is dialysis. Initiate dialysis when signs or symptoms of uremia (eg, nausea, vomiting, volume overload, hyperkalemia, severe acidosis) are present and are not treatable by other medical means. Patients with uremia must have dialysis initiated when their creatinine clearance is 10 mL/min (creatinine level of 8-10 mg/dL) or less or, for diabetic patients, when their creatinine clearance is 15 mL/min (creatinine level of 6 mg/dL). Early referral to a nephrologist for evaluation (when creatinine level is >3 mg/dL) is essential for patient education and preparation for dialysis or transplantation.

Patients may decide on peritoneal dialysis or hemodialysis, a decision dependent on their preference and level of motivation. Peritoneal dialysis is preferred for patients who are highly motivated, need flexibility in their dialysis schedule, and who may have underlying cardiovascular disease. Hemodialysis requires a functioning arterial venous dialysis access and may be accomplished at home or in a center. Regardless of whether a patient choses peritoneal dialysis or hemodialysis, dialysis access must be discussed and placed early. Newer methods of dialysis include daily hemodialysis and nocturnal hemodialysis, the advantages of which include improved volume control, improved calcium-phosphate balance, and improved dietary parameters.

Renal transplantation is the best renal replacement therapy and results in better survival and quality of life. Transplants from living, related donors are best, but transplants from living, unrelated donors also may be considered. Consider transplantation prior to the need for dialysis because the waiting list for cadaver transplants may exceed 1-2 years.

Hyperkalemia: Patients with renal failure associated hyperkalemia of 7 mEq/L or greater are candidates for emergent dialysis therapy, particularly if the hyperkalemia is associated with ECG changes (eg, peaked T waves, atrioventricular block, bradycardia). Short-term measures include intravenous infusion of calcium gluconate, bicarbonate, insulin, and glucose solution or inhaled or intravenous beta-agonists, which are used more in the pediatric population and less in adults because of the concern for precipitating cardiac arrhythmias. Nonemergent hyperkalemia can be treated with oral potassium binders (eg, sodium polystyrene sulfonate [Kayexalate]). Correction of acidemia may improve potassium balance. Also, consider discontinuation of ACE inhibitors, angiotensin-receptor blockers, beta-blockers, potassium-sparing diuretics, and nonsteroidal anti-inflammatory drugs.

Anemia: Begin the workup for anemia when the hemoglobin level is less than 11 g/dL or the hematocrit value is less than 33% in premenopausal females and prepubertal patients or when the hemoglobin level is less than 12 g/dL or the hematocrit value is less than 37% in men and postmenopausal women. In patients found to have anemia of chronic kidney disease, begin the initial treatment with iron replacement. If the anemia is not corrected, then begin treatment with subcutaneous EPO injections. The serum ferritin level should be greater than 100 mcg/mL. Current US National Kidney Foundation guidelines recommend treatment as follows:

o Initiate iron therapy concurrently with dialysis therapy. o Start either ferrous gluconate (slightly better tolerated) or ferrous sulfate at 325

mg orally 3 times a day at the time of EPO therapy. o For significant iron deficiency, intravenous iron (InFeD Injection) may be

administered slowly (500 mg over 4-6 h) after the administration of a test dose (25 mg) or in divided doses with dialysis runs after initiation of dialysis.

Hyperparathyroidism, hypocalcemia, hyperphosphatemia, and renal osteodystrophy: Evaluate and treat secondary hyperparathyroidism, manifested by low calcium levels, high phosphate levels, and low levels of 1,25(OH)2 vitamin D-3, early because it is one of the first manifestations of renal osteodystrophy. Hypocalcemia can be treated with oral calcium carbonate at a dose of 500 mg to 1 gram orally 3 times a day with meals, or calcium acetate can be administered; both agents also bind phosphate in foods. If 1,25(OH)2 vitamin D-3 levels are depressed, calcium levels are decreased, and parathyroid levels are elevated (>300), consider initiating oral calcitriol therapy. The dosage of calcitriol is 0.25 mcg orally once daily or 3 times a week, depending on the levels of 1,25(OH)2 vitamin D-3 and PTH.

Acidemia: Acidemia may be treated with oral bicarbonate solution, but use this therapy cautiously in persons with significant fluid retention and hypertension because of the risk of worsening the fluid retention. In addition, some liquid bicarbonate preparations contain potassium as the associated carrier cation; thus, proceed cautiously if used in patients with hypervolemia and hyperkalemia.

Surgical Care: Surgical referral is necessary for dialysis access placement after the decision regarding dialysis has been made. Renal replacement therapy can be accomplished by hemodialysis, peritoneal dialysis, or transplantation. Referral to an appropriate surgeon (ie, vascular, general, transplant) is made after the modality for renal replacement therapy has been determined.

In general, referral to a vascular surgeon for consideration of dialysis access is initiated by the nephrologist early in the patient's course of renal failure to avoid emergent dialysis access placement. Dialysis access can be conducted through either an arteriovenous fistula for

hemodialysis or a peritoneal dialysis catheter for chronic ambulatory peritoneal dialysis or continuous cycling peritoneal dialysis.

Arteriovenous fistulas are the dialysis access of choice for hemodialysis.

o Avoid arteriovenous Gore-Tex grafts if at all possible because of their poor longevity. Avoid long-term use of tunneled catheters because of the increased risk of infection and poor dialysis adequacy. Avoid subclavian catheters because of their association with increased venous stenosis, thrombosis, or both.

o A novel method of hemodialysis access includes CryoVein transplants, a method that can be used after failure of a native arteriovenous fistula.

Peritoneal dialysis access can be accomplished by the placement of Tenckhoff peritoneal dialysis catheter by either an experienced nephrologist or a surgeon. Direct visualization of the peritoneum is associated with fewer complications and better function of the catheter. Peritoneal dialysis allows patients more control and flexibility with their dialysis treatment regimen.

Consider any surgery carefully in uremic patients because of the increased risk for uremic bleeding, cardiovascular events, ARF, CRF, respiratory depression, and decreased metabolism of certain drugs. Vasopressin may be considered if uremic bleeding is substantial.

Consultations: Consider consulting a nephrologist as soon as possible in the course of the patient's disease, particularly when renal function test results are only mildly abnormal. Acute hyperkalemia, volume overload, severe acidemia, or a change in mental status, which can progress to stupor or coma, requires emergent consultation with a nephrologist and, possibly, initiation of dialysis.

Diet: Dietary changes should be made only with the help of a dietitian knowledgeable in renal diet treatment, particularly in patients who have not yet started dialysis therapy.

A low-protein diet has been advocated for persons with mild-to-moderate renal failure. Low-protein diets may alleviate some of the symptoms of uremia, such as nausea, however, low-protein diets can cause the patient to become malnourished, which has been associated with higher mortality upon initiation of dialysis.

Current recommendations for a low-protein diet prior to the initiation of dialysis are 0.8 gram of protein/kg of weight, with an additional gram of protein added for each gram of protein lost in the urine (for patients with nephrotic syndrome).

Patients with advanced uremia or malnutrition are not candidates for a low-protein diet.

Patients with CRF are placed on a low-potassium (2-3 g/d), low-phosphate (2 g/d), and low-sodium (2 g/d) diet.

Activity: Activity for patients with uremia is self-restricted based on their level of fatigue.

Early treatment of anemia with iron and EPO improves the quality of life and energy levels even before the patient needs dialysis.

Bleeding secondary to uremia may occur; dangerous activities may need to be restricted and potential bleeding sites assessed in the event of a fall (eg, for a subdural hematoma).

Usually, medications used for uremia are indicated to treat associated metabolic and electrolyte abnormalities (ie, anemia, hyperkalemia, hypocalcemia, hyperparathyroidism, iron deficiency). Medication selection and dosage depend on the patient's clinical state, which may change with the acute clinical setting. Dialysis is the primary treatment for uremia, but medications can effectively treat some of the associated symptoms and clinical abnormalities (eg, anemia, hypocalcemia).

Drug Category: Colony-stimulating factors -- Increase reticulocyte count, hematocrit value, and hemoglobin levels.

Drug Category: Calcium supplements -- Used to correct hypocalcemia and improve symptoms associated with renal osteodystrophy. Also may be used to bind phosphate in patients with hyperphosphatemia

Drug Category: Vitamins -- Essential for normal metabolism of proteins, carbohydrates, and fats and normal DNA synthesis. Used in the treatment of hyperparathyroidism, vitamin D deficiency, and renal osteodystrophy

Drug Category: Iron salts -- Used to correct iron deficiency symptomsDrug Category: Antidotes -- Used to reduce serum potassium levelsDrug Category: Antidiabetic agents -- Stimulate cellular uptake of potassiumDrug Category: Phosphate binders -- Used to bind phosphate when calcium carbonate or acetate cannot be used because of a high serum calcium level.

Deterrence/Prevention:

Avoid nephrotoxic medications such as nonsteroidal anti-inflammatory drugs, renal toxic aminoglycoside antibiotics, and other potential renal toxins.

N-acetyl-cystine can be administered before and after radiologic imaging that requires intravenous contrast (eg, CT scan, renal angiogram, intravenous pyelogram) to avoid nephrotoxicity. However, consider an alternative method of imaging (eg, ultrasound, MRI) in this setting to avoid ARF, particularly in patients with diabetes.

Complications:

Severe complications of untreated uremia include seizure, coma, cardiac arrest, and death.

Spontaneous bleeding can occur with severe uremia and may include GI bleeding, spontaneous subdural hematomas, bleeding associated with the underlying disorder, or bleeding associated with trauma.

Cardiac arrest may occur from severe underlying electrolyte abnormalities such as hyperkalemia, metabolic acidosis, or hypocalcemia.

Severe hypoglycemic reactions may occur in diabetic patients if hyperglycemic medications are not adjusted for their decreased creatinine clearance.

Renal failure associated bone disease (renal osteodystrophy) may lead to an increased risk of osteoporosis or bone fracture with trauma. Medication clearance is decreased in persons with renal failure and may lead to untoward adverse effects such as a digoxin overdose, increased sensitivity to narcotics, and decreased excretion of normal medications.

Prognosis:

The prognosis for patients with uremia of CRF is poor unless the uremia is treated with renal replacement therapy such as dialysis or transplantation.

The prognosis for ARF and renal failure secondary to a reversible or treatable cause, such as rapidly progressive glomerulonephritis (eg, lupus nephritis, Wegner disease, Goodpasture disease, thrombotic thrombocytopenic purpura and hemolytic uremia syndrome, multiple myeloma) depend on the timing of diagnosis and rapidity of appropriate treatment (eg, steroids, chemotherapeutic agents, plasmapheresis).

Patient Education:

Patients should be sent to the nephrologist early for education regarding renal disease and renal replacement therapy options and for evaluation and diagnosis of their underlying renal disease process.

Inform diabetic patients about potential changes in insulin or oral hypoglycemic medication needs.

Inform patients and their families regarding dialysis to avoid the shock of emergent dialysis and the decreased quality of life that occurs with this disease.

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