Renal failure occurs when the kidneys are unable to too maintain a normal internal environment

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1 Leah Molai Diagnosis of Chronic Renal Failure Anatomy The Kidneys are two bean shaped excretory organs that lie against the dorsal abdominal wall at the level of vertebrae T 12 to L 3. The right kidney is slightly lower than the left because of the space occupied by the large right lobe of the liver above it. Each kidney contains ~1, 2 million functional units called nephrons. Kidneys account for only 0.4% of the total body weight, receiving 21% of cardiac output (200 litres) and excretes ~2litres of urine daily. (This emphasises the importance of the kidneys in the regulation of blood volume and composition). The kidneys play key roles in body function, not only by filtering the blood and getting rid of waste products, but also by balancing levels of electrolytes and acid base concentrations in the body, controlling blood pressure, stimulating the production of red blood cells (erythropoietin production), among other functions. The kidneys facilitate removal of waste products of metabolism of drugs, vitamins and supplements, additive without worry that toxic by products will build up to harmful levels, unless they are damaged. Renal failure occurs when the kidneys are unable to too maintain a normal internal environment Case study: A 42 year old woman presented to her GP with a vague history of persistent headaches, muscle weakness, tiredness, nausea and vomiting, unintentional weight loss and energy that lasted for 8 months. On examination she had the following signs and symptoms: Pallor, confusion, decreased sensation in hands and feet, muscle cramps, odourous breath, excessive nighttime urination, and excessive thirst, loss of appetite, seizures and hyperventilation (compensation to metabolic acidosis). Differential diagnosis: Distinguishing acute renal failure (ARF) from chronic renal failure (CRF) is important, yet making the distinction can be difficult. A history of chronic symptoms fatigue, weight loss, anorexia, nocturia, and

2 generalised itching (Symptoms mostly from anaemia or accumulation of waste products in the body) suggest chronic renal failure. Unlike CRF, acute kidney failure develops rapidly, over days or weeks and is often reversible with appropriate treatment and can be classified as pre renal, renal and post renal. Other conditions that may lead to similar symptoms must be eliminated to get to the final diagnosis and causes. Urine output history can be useful. Oliguria (urine production <400ml/Day) generally favours ARF. Abnormally high urine output on the other hand is known as polyuria. The doctor requested: Urea, Creatinine and Electrolytes (UE), Bicarbonate, Albumin, Calcium, Magnesium, Phosphate and Haemoglobin. Diagnosis can be made with tests from the following disciplines: Chemical Pathology Haematology Microbiology Further tests for Confirmation/Exclusion Cellular Pathology Serology Acid base/ Electrolytes: Test Abnormality Results Flag Reference range s Sodium Usually increased in terminal stages renal failure 140 N mmol/l s Chloride 103 N mmol/l s Potassium Hyperkaelaemia occurs when GFR < 20ml/min ; s creatinine > mmol/l Anion gap (Na + K) (Cl+HCO 3 ) Increase seen in Uraemia/Renal failure due to retention of phosphates and sulphates 6.8 H mmol/l 24 H 8 20 mmol/l

3 s Bicarbonate Normally, nearly all the bicarbonate ions are reabsorbed from the tubules, with little lost in the urine. Metabolic acidosis 18 L mmol/l Calcium magnesium phosphate: [s Calcium] Failure to convert vitamin D to active form/hypomagnesaemia 1.86 #L mmol/l Calcium Corrected Renal parenchymal destruction leading to decreased 1,25 vitd production,and/ or phosphate retention 2.06 #L mmol/l s Magnesium Decreased excretion by kidney 1.13 #H mmol/l s Phosphate Decreased excretion. Chronic renal failure patients at greatest risk H mmol/l Excretion of the waste products of protein metabolism: Tests Abnormality Results Flag Reference range s Urea s Creatinine The kidney is the only significant route of excretion for urea. Increase seen in Uraemia/Renal failure Levels remain the same everyday unless muscle mass or renal function changes H mmol/l 1030 *H µmol/l egfr (MDRD) Takes longer to filter waste from essentials. 5 L >60 ml/mim Haematology: Test Abnormality Results Flag Reference range Haemoglobin Loss of erythropoietin production. Peripheral smear reveals Normocytic Normochromic anaemia with fragments and burr cells (typical of kidney failure) *s=serum, *N=Normal, *L=Low, *H=High 10.6 L g/dl Other investigations that may be helpful towards a definite diagnosis include: Kidney Biopsy, Full blood count, Urinalysis, Antinuclear antibodies (ANA), Serum complement levels, Anti glomerular basement membrane (anti GBM) antibodies, Hepatitis B and C, HIV, Venereal Disease Research Laboratory (VDRL), Lipid profile, Liver function tests, Blood Pressure Monitoring and Cardiac profile and markers

4 Specific radiological investigations include: Abdominal Ultrasound Abdominal MRI Abdominal CT Scan X ray of kidneys and abdomen What is chronic renal failure (CRF)? Chronic renal failure (CRF) most often results from any disease that causes gradual loss of kidney function. It can range from mild dysfunction to severe kidney failure. The disease may lead to end stage renal disease (ESRD). Usually occurs over a number of years as the internal structures of the kidney are slowly damaged. In the early stages, there may be no symptoms. In fact, progression may be so slow that symptoms do not occur until kidney function is less than one tenth of normal. Common characteristic biochemical findings in CRF are: Increased Urea, Creatinine. Potassium, Anion Gap, Phosphate, Decreased Calcium and Metabolic acidosis occur especially when the Glomerular filtration rate (GFR) is <20 30 ml/min. Acute renal failure (ARF) or acute kidney injury (AKI), as it is now referred to in the literature, is defined as an abrupt or rapid decline in renal filtration function. This condition is usually marked by a rise in serum creatinine concentration or azotemia (a rise in blood urea nitrogen [BUN] concentration). However, immediately after a kidney injury, BUN or creatinine levels may be normal, and the only sign of a kidney injury may be decreased urine production. A rise in the creatinine level can result from medications (e.g., cimetidine, trimethoprim) that inhibit the kidney s tubular secretion. A rise in the BUN level can occur without renal injury, resulting instead from such sources as GI or mucosal bleeding, steroid use, or protein loading, so a careful inventory must be taken before determining if a kidney injury is present. Creatinine Clearance provides an estimate of the volume (ml) of plasma which could theoretically be completely cleared of a substance per minute. Creatinine is a waste product formed from a high energy storage compound, creatine phosphate stored in the muscle. The amount excreted daily is fairly equal and can thus be used to estimate glomerular filtration by the kidney. A decreased creatinine clearance is a sensitive indicator of a decreased glomerular filtration rate (GFR). An increased value has no clinical significance. Stages of CRF have been standardized as shown in the table below. Stages of Chronic Kidney Failure Stage Description GFR* ml/min/1.73m 2 1 Slight kidney damage with normal or increased filtration More than 90 2 Mild decrease in kidney function 60 89

5 3 Moderate decrease in kidney function Severe decrease in kidney function Kidney failure requiring dialysis or transplantation Less than 15 *GFR is glomerular filtration rate, a measurement of the kidney's function. Causes: Diabetes and high blood pressure are the two most common causes and account for most cases. Other major causes include(among others): Alport syndrome Analgesic nephropathy Glomerulonephritis of any type (one of the most common causes) Kidney stones and infection Obstructive uropathy Polycystic kidney disease Reflux nephropathy Treatment: There is no cure for chronic kidney disease. The four goals of therapy are as follows: 1. Slow the progression of disease: life style and dietary changes e.g. moderate exercise and some food restrictions meat, salt, supplements e.g. VIT D etc 2. Treat underlying causes and contributing factors 3. Treat symptoms and complications of disease like anaemia e.g. erythropoietin injections 4. Regular dialysis or a kidney transplant References: Michael L.B; Edward P.F; Larry E.s, Clinical Chemistry: Principles, Procedures, correlations, 5 th edition. Lippincott Willians & Wikins: Philadelphia, kidney disease Accessed on 22/02/ kidney failure Accessed 22/02/ Accessed 21/02/ Accessed 20/02/2010