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2.1
Uremia
Intoxication by Urinary Waste Products

Uremia is clinically defined as the active accumulation of toxic substances like nitrogenous wastes in the serum. This condition is generally brought about by the failure of the kidney to rid-off the body system with nitrogenous wastes by way of the urine. Consequently, uremia results from any medical condition that hampers the renal excretory functions.

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Presentation

The following signs and symptoms are seen in patients with uremia:

  • Peripheral neuropathy
  • Muscular fatigue
  • Seizures 
  • Anorexia and nausea
  • Perennial cramping
  • Sleep disturbances
  • Coma
  • Sexual dysfunction
  • Bone problems
  • Muscle wasting
  • Pruritus
  • Hiccups
  • Bleeding problems
  • Pallor

Entire Body System

  • Fatigue

    Symptoms associated with uremia include nausea, vomiting, fatigue, appetite loss, weight loss, itching, muscle cramps, thirst, visual disturbances, and changes in mental status. [medicinenet.com]

    The thyroid and parathyroid panels will help work up any symptoms of fatigue, as well as determine calcium abnormalities as they relate to uremia vs longstanding or unrelated illness of calcium metabolism. [en.wikipedia.org]

    Symptoms of uremia often initially include fatigue, loss of appetite, edema, excessive thirst, and decreased concentration, and progression of the condition may lead to a rapid pulse, anemia, diarrhea, convulsions, discoloration of the skin, coma, and [microscopyu.com]

    The symptoms of uremia are Fatigue, lassitude, and a loss of mental concentration may be among the first signs. [longdom.org]

  • Weight Loss

    Symptoms associated with uremia include nausea, vomiting, fatigue, appetite loss, weight loss, itching, muscle cramps, thirst, visual disturbances, and changes in mental status. [medicinenet.com]

    However, we also mentioned some of the indications of starting HD in patients with progressive, severe chronic kidney disease: - Refractory Hypertension despite multiple meds - Persistent nausea/vomiting - Signs of malnutrition and weight loss - low albumin [errolozdalga.com]

    Uremic syndrome may affect any part of the body and can cause: Nausea, vomiting, loss of appetite, and weight loss. Changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. [myhealth.alberta.ca]

  • Episodic Pain

    The antibiotics of choice are penicillins, clindamycin, and cephalosporins, which can be administered at normal doses even if the therapeutic range will be extended.[13] For analgesics, paracetamol is the option of choice for cases of episodic pain. [en.wikipedia.org]

    The antibiotics of choice are penicillins, clindamycin, and cephalosporins, which can be administered at normal doses even if the therapeutic range will be extended.42 Regarding painkillers, paracetamol is the option of choice for cases of episodic pain [tandfonline.com]

  • Hypothermia

    […] pathology are: asterixis (tremors) lethargy (prolonged drowsiness) hyperreflexia (increased osteotendinous reflexes) uremic flush (metallic and bitter taste in the mouth) serositis, especially pericarditis (inflammation of the tissue around the heart) hypothermia [topdoctors.co.uk]

    Signs: vomiting, anorexia, lethargy/depression, anemia, weakness, hypothermia, oral ulcers, melena, muscle, tremors, seizures. Diagnosis: signs, blood biochemistry, urinalysis. Prognosis: depends on severity of renal damage. [vetstream.com]

    Subtle signs of malnutrition Increased susceptibility to infection Increased susceptibility to cardiovascular complications Low-grade serositis Impaired vascular reactivity Hypothermia Reduced exercise capacity and O2 utilization Fatigue Subtle psychological [slideshare.net]

Gastrointestinal

  • Nausea

    Symptoms associated with uremia include nausea, vomiting, fatigue, appetite loss, weight loss, itching, muscle cramps, thirst, visual disturbances, and changes in mental status. [medicinenet.com]

    […] fatigue -CV - Hypertension, Arrythmias, LVH, Increased predisposition to MI and SCD, Accelerated atherosclerosis and coronary calcification, Volume overload, Pericardial effusions and pericarditis -Pulm - pulmonary edema due to volume overload -GI - nausea [errolozdalga.com]

    A 28-year-old man was admitted to our hospital with nausea, headache and weakness of the left hand. He had severe uremia without hypertension due to recurrent/chronic pyelonephritis. [ncbi.nlm.nih.gov]

    Loss of appetite progresses to nausea and vomiting; episodes of diarrhea and constipation may occur. [longdom.org]

  • Hiccup

    Other associated symptoms and signs can include low urine output, confusion, hiccups, and high blood pressure. [medicinenet.com]

    Arrythmias, LVH, Increased predisposition to MI and SCD, Accelerated atherosclerosis and coronary calcification, Volume overload, Pericardial effusions and pericarditis -Pulm - pulmonary edema due to volume overload -GI - nausea/vomiting, anorexia, hiccups [errolozdalga.com]

    The following signs and symptoms are seen in patients with uremia: Peripheral neuropathy Muscular fatigue Seizures Anorexia and nausea Perennial cramping Sleep disturbances Coma Sexual dysfunction Bone problems Muscle wasting Pruritus Hiccups Bleeding [symptoma.com]

    […] as if intoxicated Frequent belching Progressive motor dysfunction occurring over hours to days Development of facial asymmetry Heat and pain of the brain Mental confusion with moments of lucidity Inability to fully recover after loss of consciousness Hiccups [americandragon.com]

    […] features of uremia[3][4][5] Area affected Signs and symptoms Central nervous system diurnal somnolence, night insomnia, memory and concentration disorders, asthenia, headache, confusion, fatigue, seizures, coma, encephalopathy, decreased taste and smell, hiccups [en.wikipedia.org]

  • Dyspepsia

    […] hyperparathyroidism, hypogonadism, erectile dysfunction, decreased libido), bone disease (adynamic bone disease, impaired calcitriol metabolism, osteitis fibrosa, osteomalacia, osteoporosis), skin (melanosis, pruritus), gastro-intestinal system (anorexia, dyspepsia [karger.com]

Jaw & Teeth

  • Poor Oral Hygiene

    For example, enamel hypoplasia in the form of white or brown discoloration of primary teeth is commonly seen in young children with early-onset renal disease.[11] Poor oral hygiene, a carbohydrate-rich diet, disease-related debilitation, hypoplastic enamel [en.wikipedia.org]

    In approximately 85% of cases, bad breath is due to intraoral factors that include the following: tongue coating, dry mouth, poor oral hygiene, and the presence of prostheses and periodontitis.30 Approximately 10% of oral halitosis cases derive from the [tandfonline.com]

  • Tooth Erosion

    erosion.[10] Dental Considerations[edit] When treating patients with renal insufficiency, a dentist should collect a complete medical history, with particular attention to ESRD-related illnesses, drugs with prescribed dosages, blood parameters, timing [en.wikipedia.org]

  • Halitosis

    Patients with CRF associated with high levels of urea nitrogen in the blood and salivary production31 report more severe halitosis when the blood urea levels are >55 mg/dL. [tandfonline.com]

    May progress to seizures and coma Dusky yellow-tan or gray skin Uremic halitosis, uremic frost - patient will have urine-smelling breath and skin due to inability to clear waste products from the kidney بی اشتهایی، دلبدی، استفراغ، اسهال، ممکن منتج به [slideus.org]

    May progress to seizures and coma • Dusky yellow-tan or gray skin • Uremic halitosis, uremic frost - patient will have urine-smelling breath and skin due to inability to clear waste products from the kidney • بی اشتهایی، دلبدی، استفراغ، اسهال، ممکن منتج [slideserve.com]

Musculoskeletal

  • Muscle Cramp

    Symptoms associated with uremia include nausea, vomiting, fatigue, appetite loss, weight loss, itching, muscle cramps, thirst, visual disturbances, and changes in mental status. [medicinenet.com]

    Severe malnutrition can contribute to muscle wasting, while electrolyte abnormalities may cause muscle cramping, cardiac arrhythmias, and mental status changes. [emedicine.medscape.com]

    Uremic symptoms include but are not limited to a uriniferous breath smell, metallic taste in the mouth, muscle cramps, changes in mentation, fatigue, itching of the skin, and anemia. Early stages of kidney disease are typically asymptomatic. [atlasofscience.org]

    Bangkokerz / Getty Images Symptoms: Skin and Nervous System The toxicity caused by uremia can result in nervous system symptoms such as peripheral neuropathy, cognitive decline, seizures, sensory dysfunction, insomnia, and muscle cramps. [facty.com]

    cramps, tremor, and asterixis.3 In more severe uremia, muscle fasciculations and myoclonus may appear.3 The combination of asterixis and myoclonus may be severe and has been termed uremic twitching.3,5 Chorea and athetosis are sometimes confused with [epilepsy.com]

  • Muscle Twitch

    The patient may experience persistent itching sensations, along with muscle twitching. dry and flaky skin. dry mouth with metallic taste, breath has a distinct ammonia like odour. [longdom.org]

    According to Puschmann, Lundborg distinguished 3 stages of the disorder: Stage 1 began in childhood or early adolescence and consisted of nocturnal attacks of involuntary symmetric muscle twitches, which often were painful, caused anxiety, and reminded [medlink.com]

Ears

  • Tinnitus

    Clinical Manifestations Oliguria Dizziness Vertigo A feeling of distention in the eyes Tinnitus Feverish sensation in the head Irritability Flushed face as if intoxicated Frequent belching Progressive motor dysfunction occurring over hours to days Development [americandragon.com]

    (pseudotumor cerebri) is a condition characterized by increased intracranial pressure. [1] PTS is classically the disease of middleaged obese women and presented with the increased intracranial pressure symptoms such as headache, diplopia, pulsatile tinnitus [sjkdt.org]

Skin

  • Pruritus

    Thus, if pruritus is not adequately treated, hemodialysis patients may be at risk for prolonged sleep deprivation: indeed, lack of sleep may well be a key variable linking uremic pruritus and a higher mortality risk, the authors note. [medscape.com]

    Chronic kidney disease-associated pruritus: impact on quality of life and current management challenges. Int J Nephrol Renovasc Dis. 2017. 10:11-26. [Medline]. [Full Text]. Mettang T, Kremer AE. Uremic pruritus. Kidney Int. 2015 Apr. 87 (4):685-91. [emedicine.medscape.com]

    * ure·mia (u-reґme-ə) [ur- + -emia] 1. azotemia. 2. in current usage, the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting, anorexia, a metallic taste in the mouth, a characteristic odor of the breath, pruritus [medicine.academic.ru]

    All rights reserved. uremia Prerenal azotemia, renal underperfusion Nephrology A constellation of Sx caused by the retention of urea and other products of protein catabolism due to inadequate kidney function in advanced renal failure Clinical N&V, pruritus [medical-dictionary.thefreedictionary.com]

Neurologic

  • Confusion

    Symptoms include low urine output, confusion, loss of consciousness, and excessive thirst. [healthgrades.com]

    Other associated symptoms and signs can include low urine output, confusion, hiccups, and high blood pressure. [medicinenet.com]

    In this report, we have presented a diabetic patient with uremia, in which acute Parkinsonism occurred, coupled with acute mental confusion, after a sudden increase in blood urea nitrogen and serum creatinin levels. [ncbi.nlm.nih.gov]

    Manifestations of this include fatigue, weakness, nausea, poor appetite, reduced concentration, confusion and lethargy. There is not a specific BUN number after which symptoms start to develop. It varies amongst different individuals. [thekidneydr.com]

    Changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury. [myhealth.alberta.ca]

  • Headache

    He reported a remarkable improvement of his headache but would still have an occasional mild to moderate headache. [jmedicalcasereports.biomedcentral.com]

    The clinical course of the disease is generally good, but it can sometimes cause chronic visual disturbances and headaches. [sjkdt.org]

    A 28-year-old man was admitted to our hospital with nausea, headache and weakness of the left hand. He had severe uremia without hypertension due to recurrent/chronic pyelonephritis. [ncbi.nlm.nih.gov]

    Although the symptoms and findings may be multiple and variable, the clinical picture usually includes varying degrees of headache, vomiting, pericarditis, gastrointestinal symptoms, and, finally, coma and death in the late stages. [jamanetwork.com]

  • Stupor

    Chronic bladder pain R39.83 Unilateral non-palpable testicle R39.84 Bilateral non-palpable testicles R39.89 Other symptoms and signs involving the genitourinary system R39.9 Unspecified symptoms and signs involving the genitourinary system R40 Somnolence, stupor [icd10data.com]

    In uremia, metabolic acidemia may contribute to other clinical abnormalities, such as hyperventilation, anorexia, stupor, decreased cardiac response (congestive heart failure), and muscle weakness. [emedicine.com]

  • Insomnia

    […] the brain Mental confusion with moments of lucidity Inability to fully recover after loss of consciousness Hiccups Irritable Heat in the Heart Tremors Limited mobility of the limbs Persistent high fever Restlessness Twitching Spasms of the extremities Insomnia [americandragon.com]

    Most commonly, subtle symptoms such as insomnia, restless leg syndrome, decreased memory and concentration, fatigue -CV - Hypertension, Arrythmias, LVH, Increased predisposition to MI and SCD, Accelerated atherosclerosis and coronary calcification, Volume [errolozdalga.com]

    Bangkokerz / Getty Images Symptoms: Skin and Nervous System The toxicity caused by uremia can result in nervous system symptoms such as peripheral neuropathy, cognitive decline, seizures, sensory dysfunction, insomnia, and muscle cramps. [facty.com]

    Clinical features of uremia[3][4][5] Area affected Signs and symptoms Central nervous system diurnal somnolence, night insomnia, memory and concentration disorders, asthenia, headache, confusion, fatigue, seizures, coma, encephalopathy, decreased taste [en.wikipedia.org]

  • Amnesia

    A Case of Posterior Reversible Encephalopathy Syndrome with Similar Symptoms as Transient Global Amnesia Jeongyeon Kim, Young Ik-Jung, 서정희 외 2명 Dementia and Neurocognitive Disorders(대한치매학회지) 대한치매학회 2018 리뷰(0) 도움이 되었어요.0 도움이 안되었어요.0 첫 리뷰를 남겨주세요. [dbpia.co.kr]

Workup

The following diagnostic tests and modalities are used to work up patients suffering from uremia:

  • Isotope clearance: The radioisotope iothalamate is utilized to accurately measure the actual glomerular filtration rate to determine the degree of uremia in a patient.
  • Complete blood count (CBC): This routine laboratory test is used to determine the level of hemoglobin and hematocrit and diagnose anemia of uremia. 
  • Kidney ultrasound: Renal sonograms are used to determine the presence of hydronephrosis and obstruction among patients with signs of uremia. The scan will also measure the relative size of the kidneys. 
  • Computed tomography (CT scan): This radiologic imaging modality can be helpful in identifying hematomas in the kidney due to trauma. 
  • Magnetic resonance imaging (MRI): MRI is sensitive in detecting the presence of vascular stenosis in the kidneys as a cause of uremia.
  • Renal biopsy: Histopathologic studies of the kidney will reveal glomerulosclerosis in cases of long standing renal failure.

Serum

  • Hyponatremia

    His blood pressure was 201/113 mmHg, and laboratory findings revealed renal failure and hyponatremia. On physical examination, disorientation and dysarthria were observed. Hemodialysis was performed the same day. [ncbi.nlm.nih.gov]

    […] photoconvulsive responses to photic stimulation may occur.3 When seizures occur in the context of renal insufficiency, it is necessary to rule out a number of complications other than uremia:3 electrolyte imbalance (water intoxication, hypocalcemia, hyponatremia [epilepsy.com]

    Other conditions associated with CRF that can cause headache include severe anemia, hyponatremia, severe hypertension, and dialysis. Dialysis headaches are frontal, start within a few hours of the procedure, and are not persistent [1, 4]. [jmedicalcasereports.biomedcentral.com]

    Hyponatremia (I) c. Hyperkalemia (I) d. Hyperphosphatemia (I) (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 30. [slideshare.net]

    Insulin resistance (hypoglycemia may also occur) Hypertriglyceridemia Secondary hyperparathyroidism Cyanate Metabolic acidosis Plasma insulin normal or increased Decreased high-density lipoprotein cholesterol Altered thyroxine metabolism Creatinine Hyponatremia [en.wikipedia.org]

  • Phosphate Decreased

    Hyperphosphatemia occurs as excretion of phosphate decreases with progressive renal failure. Hyperphosphatemia stimulates parathyroid gland hypertrophy and stimulates increased production and secretion of PTH. [emedicine.com]

  • Luteinizing Hormone Decreased

    […] erythropoietin production Hypermagnesemia Gonadal dysfunction (increased prolactin and luteinizing hormone, decreased testosterone) Decreased sodium-potassium ATPase activity Increased serum gastrin and melanocyte-stimulating hormone History[edit] Urea [en.wikipedia.org]

Treatment

The following treatment modalities are available for the management of uremic diseases:

  • Dialysis: The use of peritoneal and hemodialysis are also implored to treat uremic states in patients. Peritoneal dialysis is usually indicated among patients with other cardiovascular conditions [7]. Hemodialysis are used for other cases but may require an arterio-venous access [8]. 
  • Intravenous calcium gluconate: The infusion of calcium gluconate in the venous system active controls the hyperkalemic state that causes cardiac disturbances among uremic patients.
  • Erythropoietic stimulating agents (ESA): These agents are arbitrarily given to promote the production of red blood cells in the bone marrows.
  • Parathyroid hormone (PTH) replacement therapy: A PTH level of 150-600 pg/ml is targeted to correct the conditions of parathyroidism among ESRD patients with uremia [9].
  • Oral calcium supplements: Exogenous calcium and phosphates are given to correct varying degrees of hypocalcemia and hypophosphatemia among patients with uremia.
  • Diet: Studies have shown that the administration of a low protein diet among patients with uremia can lower the rate of nephron death and subsequently delay the progression to ESRD [10]. 
  • Renal transplant: This surgical option is the definitive treatment of choice of ESRD patients with severe signs of uremia.

Prognosis

In general, uremia among ESRD patients has a very poor prognosis unless hemodialysis or renal transplantation is done promptly. However, uremia brought about by acute renal insufficiency from reversible causes like thrombocytopenic purpura, Wegener disease, and Goodpasture syndrome can have a better prognosis if diagnosed and treated early in the course of the disease. Uremic disease carries a high morbidity rating in almost all patients with concomitant diseases like diabetes mellitus and hypertension.

Etiology

Uremia usually results from chronic renal diseases caused by the following illnesses [3]:

  • Polycystic kidney disease
  • IgA nephropathy
  • Multiple myeloma
  • Uncontrolled hypertension
  • Hemolytic uremic syndrome
  • Goodpasture syndrome
  • Thrombocytopenic purpura
  • Diabetes mellitus
  • Systemic lupus erythematosus
  • Amyloidosis

Acute cases of renal diseases can also lead to uremia when there is a rapid rise in creatinine or urea concentrations in the blood.

Epidemiology

The actual prevalence of uremia is hard to determine because the expression of the signs and symptoms of the disease varies in some disease conditions. In normal individuals, uremic signs starts to appear at creatinine clearance level of less than 10ml/min while diabetics can have the onset of symptoms in as early as 15ml/min of creatinine clearance. Concurrently, uremia exists in patients treated as end stage renal disease (ESRD).

Almost 58% of the world’s ESRD populace resides in Brazil, Japan, Germany, USA, and Italy. The white race has higher predisposition for ESRD representing almost 60% of cases. ESRD has a slight predilection in males than their female counterparts. Mean age of onset is usually on the late adulthood stage. Patients beyond 70 years old are least likely to tolerate any delays in renal treatment for uremic signs compared to their younger counterparts.

Pathophysiology

Uremia generally develops as a complication of renal failure in most patients. There is a progressive decline in the kidney functioning during this phase where its capacity to produce adequate vital hormones, fluid and electrolyte regulation, water elimination, and acid-base homeostasis is significantly impaired. When creatinine levels go beyond 2mg/dl, the peritubular cells of the kidney fail to secrete erythropoietin that induces red blood cell formation leading to progressive anemia. By statistics, 39% of patients presenting with anemia has an associated renal dysfunction at hand [4].

The gradual accumulation of uremic toxins hampers the adhesion capacity of the thrombocytes. This impairment leads to bleeding diasthesis making ESRD patients on oral coagulopathy susceptible to pathologic bleeding in the face of uremia [5]. The breakdown in the acid-base balance by the kidney leads to the failure in the secretion of hydrogen ions and excretion of ammonium from the serum resulting to metabolic acidosis. The decreasing serum pH leads to compensatory respiration presenting as tachypnea. The accumulation of potassium secondary to tubular acidosis leads to hyperkalemia.

This is an offshoot in uremic states especially when the creatinine clearance falls below 20 mL/min. There is an imbalance in the calcium and phosphate metabolism due to the uncontrolled secretion of parathyroid hormones caused by uremia. The calcium and phosphate accumulation in the serum leads to abnormal deposition of calcium plaques in the skin, blood vessels, and other tissues in the body [6]. The uremic state will also lead to abnormal carbohydrate metabolism, sexual hormone release, and thyroid hormone secretions.

Prevention

Patients with diagnosed diabetes and hypertension should comply religiously with their maintenance medications to prevent renal complications in the future. High risk patients should avoid nephrotoxic drugs like ibuprofen and naproxen to prevent nephrotoxicity and uremia.

Summary

Uremia is a medical illness that accompanies renal failure caused by the abnormal accumulation of organic waste products normally excreted by the kidneys. Uremic symptoms clinically manifests when the glomerular filtration rate (GFR) of the kidneys fall below 60 ml per minute per 1.73 meter squared of body area [1]. Early uremic signs are usually constitutional and non-specific, thus mild uremia is oftentimes underdiagnosed. Severe uremia is corrected by renal transplant; however, the supply of kidney donors is almost always eclipsed by the demand for kidney transplant. Because of this, hemodialysis is the leading modality utilized to control and subvert this medical illness [2].

Patient Information

  • Definition: Uremia is a medical condition associated with renal failure causing an abnormal accumulation of organic waste products normally excreted by the kidneys.
  • Cause: Uremia can typically arise from any etiologic conditions that results in renal failure like diabetes, hypertension, multiple myeloma and SLE.
  • Symptoms: Uremia will present with muscular fatigue, seizure, numbness, anorexia, and sleep disturbances.
  • Diagnosis: Isotope clearance, anemia work-up, and imaging studies are diagnostic tests and modalities used in the work up of patients with uremia.
  • Treatment and follow-up: Uremia can effectively be treated with dialysis and kidney transplantation. 

References

  1. Coresh J, Byrd-Holt D, Astor BC, et al. Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000. J Am Soc Nephrol 2005; 16:180-188.
  2. USRDS 2006 annual data report: atlas of end-stage renal disease in the United States. Bethesda, MD: U.S. Renal Data System, 2006.
  3. Fakhouri F, Roumenina L, Provot F, et al. Pregnancy-Associated Hemolytic Uremic Syndrome Revisited in the Era of Complement Gene Mutations. J Am Soc Nephrol. Mar 4 2010.
  4. Almoznino-Sarafian D, Shteinshnaider M, Tzur I, et al. Anemia in diabetic patients at an internal medicine ward: Clinical correlates and prognostic significance. Eur J Intern Med. Apr 2010; 21(2):91-96.
  5. Boccardo P et al. (2004) Platelet dysfunction in renal failure. Semin Thromb Hemost 30: 579–589.
  6. Schlieper G, Aretz A, Verberckmoes SC, et al. Ultrastructural Analysis of Vascular Calcifications in Uremia.J Am Soc Nephrol. Mar 4 2010.
  7. Chuang YW, Shu KH, Yu TM, et al. Hypokalaemia: an independent risk factor of Enterobacteriaceae peritonitis in CAPD patients. Nephrol Dial Transplant. May 2009; 24(5):1603-8.
  8. Vinsonneau C, Camus C, Combes A, et al. Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial. Lancet2006; 368:379-385.
  9. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. Aug 2009; S1-130.
  10. Fouque D, Laville M. Low protein diets for chronic kidney disease in non-diabetic adults. Cochrane Database Syst Rev. Jul 8 2009; CD001892.
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