Chronic Renal Failure PDF

Chronic Renal Failure Prof. Sahar El-Haggar Professor of Clinical Pharmacy 1  CHRONIC RENAL FAILURE Slowly progressive irreversible decrease of renal function over 3months or years which may lead to end stages of renal failure. ESRD (E...

Chronic Renal Failure Prof. Sahar El-Haggar Professor of Clinical Pharmacy 1  CHRONIC RENAL FAILURE Slowly progressive irreversible decrease of renal function over 3months or years which may lead to end stages of renal failure. ESRD (End stage renal disease):consider when renal failure is so severe and the patient can't live without dialysis. 2  CHRONIC RENAL FAILURE Recently the term of CRF or Chronic kidney impairment is replaced by the term of chronic kidney disease "CKD". CKD is defined as kidney damage for more than 3 months with or without a decrease in GFR. Damage may be functionally detected by tests such as CrCL, proteinuria or hematuria, or structurally detected by kidney biopsy or radiology. 3  ADOPTIVE MECHANISM (HYPER-FILTERATION OR INTACT NEPHRON) THEORY - Although total kidney glomerular filtration rate (GFR) falls, the GFR of Remnant nephron rises. - This allows remnant nephron to increase excretion proportionally. - This adaptation blunts the drop in whole kidney GFR Unfortunately, this adaptive process ultimately results in: 1- Glomerular hypertension 2- Glomerular hypertrophy This results in further glomerular injury or damage. 4 STAGES OF CKD 5 ETIOLOGY OF CHRONIC RENAL FAILURE The causes of chronic renal failure (CRF) vary globally, but the most common causing CRF and endstage renal disease (ESRD) are: 1- Diabetes mellitus type 1 and type 2: Diabetic nephropathy is more common in IDDM than NIDDM  Nephropathy is characterized by:  Persistent albuminuria (> 300 mg/24 h)  An increase in blood pressure or HTN  ↓ GFR All of these cause progressions of renal disease to ESRD. 6  Accumulation of glucose in your blood and blood vessels damage kidneys ‘filters so your kidneys overtime become damaged and not doing good at filtering wastes and extra fluid from your blood which result (proteinuria = persistent albuminuria) which is the first sign of kidney disease from diabetes.  So, when the filters are damaged, albumin passes out of your blood and into your urine.  A healthy kidney doesn’t let albumin pass from the blood into the urine. So, this syndrome is called Diabetic nephropathy. 7 -Oxidative stress may also play an important role in cellular injury from hyperglycemia. - High glucose levels can stimulate free radical production and reactive oxygen species formation that induce nephropathy. - Additionally, hyperglycemia stimulates RAS which plays a role in microvascular disease because it can alter glomerular hemodynamics and promotes diabetic nephropathy. 8 2- Hypertension: High blood pressure can damage blood vessels in the kidneys so they don’t function well to remove wastes and extra fluid from your body. This increase in Extra fluid in the blood vessels may then raise blood pressure Ven more, creating a dangerous cycle. Approximately 25-28% of ESRD patients are secondary to HTN 9  The major mechanisms include ischemia in the renal tubule, causing: 1- Reduction of renal mass 2- Increased glomerular capillary pressure with subsequent damage 10 3- Hyperlipidemia: - Alone is not considered a significant risk factor, but if it is associated with DM, it leads to ESRD - The major mechanism involves glomerular sclerosis (Hardening of glomeruli) 4- Primary and secondary glomerulonephritis which is an inflammation of the kidney’s filtering units (glomeruli). 5- Chronic tubulointerstitial nephritis which is an inflammation of kidney’s tubules and surrounding structures. 6- Polycystic kidney disease (genetic disease that causes kidney cysts to grow) or other inherited kidney diseases. 11 7- Prolonged obstruction of urinary tract which may be result from conditions like enlarged prostate or kidney stones or some cancers. 8- Pyelonephritis which is Recurrent kidney infection 9- Vesicoureteral reflux which is a condition that causes urine to back up into your kidneys. 10- Sickle cell nephropathy (very low percentage). 12 Chronic kidney disease may result from disease processes leading to acute renal failure and over time and years results chronic renal failure. It could be: Prerenal Disease: Decreased renal perfusion pressure Chronic prerenal disease: -Occurs in patients with chronic heart failure or cirrhosis with persistently decreased renal perfusion. -This leads to progressive loss of renal function over time. 13 Intrinsic Renal Vascular Disease: (Pathology of the vessels, glomeruli, or tubules) -The most common chronic renal vascular disease is nephrosclerosis, which causes chronic damage to bloodvessels, glomeruli, and tubules. -The other renal vascular diseases are renal artery stenosis from atherosclerosis. Postrenal (Obstructive Nephropathy): Chronic obstruction may be due to prostatic disease, nephrolithiasis or abdominal/pelvic tumor with mass effect on ureter(s) are the common causes. 14  RISK FACTORS Modifiable Non-modifiable High blood pressure Older age Family history of kidney disease Male gender Heart (cardiovascular) diseases Being black or native Abnormal kidney structure American or Asian Smoking American Obesity Frequent use of medications that could damage your kidneys (nephrotoxic drugs) 15 PREVENTION OF CHRONIC RENAL FAILURE To reduce your risk of progression of chronic renal failure you should: - Manage your medical conditions (Manage diabetes, high blood pressure, and heart disease): You should 1- Keep blood glucose numbers close to your goal. 2- Keep your blood pressure numbers close to your goal. The blood pressure goal for most people with diabetes is below 140/90 mm Hg. 16 3- Take all your medicines as prescribed. 4- To help prevent heart attacks and stroke, keep your cholesterol levels in the target range. -There are two kinds of cholesterol in your blood: LDL and HDL. - LDL or “bad” cholesterol can build up and clog your blood vessels, which can cause a heart attack or stroke. - HDL or “good” cholesterol helps remove the “bad” cholesterol from your blood vessels.  Follow instructions on OTC medications. - When using nonprescription pain relievers, such as aspirin, ibuprofen and acetaminophen, follow the instructions on the package. - Taking too many pain relievers for a long time could lead to kidney damage. 17  LIFE STYLE MODIFICATIONS You should change your habits as followed:  Maintain a healthy weight.  Stop smoking: Cigarette smoking can damage your kidneys and make existing kidney damage worse.  Stop alcohol consumption: Drinking too much alcohol can increase your blood pressure and add extra calories, which can lead to weight gain.  Make healthy food choices: Choose foods that are healthy for your heart and your entire body: fresh fruits, fresh or frozen vegetables, whole grains, and low-fat or fat-free dairy products. - Eat healthy meals, and cut back on salt and added sugars. 18 Symptoms can include: Weight loss and poor appetite Swollen ankles, feet or hands as a result of water retention (edema) Shortness of breath - Tiredness Blood in your urine Difficulty sleeping (insomnia) Itchy skin - Muscle cramps Feeling sick - Headaches 19  TESTS & DIAGNOSIS - Early kidney disease usually doesn’t have any symptoms. - Testing is the only way to know how well kidneys are working. Get checked for kidney disease if with: Diabetes High blood pressure Heart disease A family history of kidney failure 20  BLOOD TEST FOR GFR - Some patients may excrete proteins other than albumin and urine protein-creatinine ratio (PCR) may be more useful for certain conditions. - Use a blood test to check kidney function. The results of the test mean the following: GFR of 60 or more is in the normal range. GFR of less than 60 may mean you have kidney disease. GFR of 15 or less is called kidney failure. Most people below this level need dialysis or a kidney transplant. 21 Lipid profile: -Patients with CKD have an increased risk of cardiovascular disease Evidence of renal bone disease can be derived from the following tests: Serum calcium and phosphate 25-hydroxyvitamin D Alkaline phosphatase Intact parathyroid hormone (PTH) levels 22  Urine Test for Albumin: - A damaged kidney lets some albumin pass into the urine. - The less albumin in urine, the better. - Having albumin in the urine is called albuminuria.  Urine albumin-to-creatinine ratio (UACR): - This test measures and compares the amount of albumin with the amount of creatinine in urine sample. - It's used to estimate how much albumin would pass into urine over 24 hours. A urine albumin result of: 30 mg/g or less is normal More than 30 mg/g may be a sign of kidney disease If albuminuria, the urine test can be repeated to confirm the results. 23 Evaluation/Establishing Chronicity: - When an eGFR of less than 60 ml/min/1.73m is detected in a patient, attention needs to be paid to the previous blood and urine test results and clinical history to determine whether this is a result of AKI or CKD that has been present but asymptomatic. The following factors would be helpful. History of long-standing chronic hypertension, proteinuria, microhematuria, and symptoms of the prostatic disease Skin pigmentation, scratch marks, left ventricular hypertrophy, and hypertensive fundal changes 24 CONT,The following factors would be helpful. Low serum calcium and high phosphorus levels have little discriminatory value, but normal Parathyroid hormone levels suggest AKI rather than CKD Patients who have very high blood urea nitrogen (BUN) values greater than 140 mg/dl, serum creatinine greater than 1.5 mg/dl, who appear relatively well and still passing normal volumes of urine are much more likely to have CKD than acute kidney disease. 25 Assessment of Glomerular Filtration Rate - For patients in whom the distinction between AKI and CKD is unclear, kidney function tests should be repeated in 2 weeks of the initial finding of low eGFR below 60 ml/min/1.73 m. - If previous tests confirm that the low eGFR is chronic or the repeat blood test results over 3 months are consistent, CKD is confirmed. - If eGFR based on serum creatinine is known to be less accurate, then other markers like cystatin-c or an isotope-clearance measurement can be undertaken. 26 Treatment of chronic kidney disease  General Management: - Adjusting drug doses for the level of estimated glomerular filtration rate (GFR) - Preparation of renal replacement therapy Treat the Reversible Causes of Renal Failure - The potentially reversible causes of acute kidney injury like infection, drugs that reduce the GFR, hypotension such as from shock, instances that cause hypovolemia such as vomiting, diarrhea should be identified and intervened. - Other nephrotoxic agents such as aminoglycoside antibiotics and NSAIDs should be avoided. 27 Retarding the Progression of CKD - The factors which result in progression of CKD should be addressed such as hypertension, proteinuria, metabolic acidosis, and hyperlipidemia. - Multiple studies have shown that smoking is associated with the risk of developing nephrosclerosis and smoking cessation retards the progression of CKD. - Protein restriction has also been shown to slow CKD progression. 28 Bicarbonate supplementation - for the treatment of chronic metabolic acidosis has been shown to delay the CKD progression as well. - Also, intensive glucose control in diabetics has been shown to delay the development of albuminuria and also the progression of albuminuria to overt proteinuria. 29 Preparation and Initiation of Renal Replacement Therapy Once the CKD progression is noted, the patient should be offered various options for renal replacement therapy. Hemodialysis (home or in-center) Peritoneal dialysis (continuous or intermittent) Kidney transplantation: It is the treatment of choice for ESRD given better long-term outcomes. 30 Renal transplantation is the best treatment option of ESRD due to its survival benefit compared to long-term dialysis therapy. -The patients with CKD become eligible to be listed for the renal transplant program when the eGFR is less than 20 ml/min/1.73m2. 31 Complications of chronic kidney disease  Anemia: - Anemia happens when kidneys don’t make enough erythropoietin (EPO). - This affects their ability to make red blood cells. You may also have anemia due to low levels of:  Iron  Vitamin B12  Folic acid - Anemia can cause hypoxia. If you have anemia, it can damage organs like your heart and brain. - It can also worsen kidney function. 32  Signs and symptoms of Anemia:  Fatigue, exertion dyspnea, dizziness, headache, and pallor  Decreased hematocrit (HCT)value 33  Therapeutic management Treatment can include: Erythropoietin (erythropoiesis-stimulating agents) results in dose-dependent increases in erythropoiesis. Prior to initiation of Epoetin, iron balance should be assessed because iron deficiency is the most common cause of suboptimal response to Erythropoietin. When hemoglobin reaches to 12 g/l, Erythropoietin therapy should be stopped to avoid CVS complications secondary to increased blood viscosity. Multivitamin containing iron, folic acid, vitamin B12Blood transfusions 34 Renal osteodystrophy, and soft tissue calcification - Phosphorus retention due to increased phosphate reabsorption → increase phosphate conc.→ affect calcium conc. by inhibition of renal activation of vitamin D → reduction gut absorption of calcium → decreases blood ionized (free) calcium → Low blood calcium concentrations → stimulation of parathyroid hormone (PTH) secretion → PTH decreases proximal tubular phosphate reabsorption → decrease Phosphorous conc. → decrease effect of phosphate on calcium. Also, PTH regains calcium from bone to replenish shortage of calcium in blood → osteoporosis. 35  Signs and symptoms: - Muscle spasms Mouth numbness and tingling Itchy skin  Treatment can include: Phosphate-Binding Agents as Mg salts. Calcium Supplementation Vitamin D Therapy Parathyroidectomy 36 Cardiovascular complications: - Excess sodium and fluid contribute to not only edema, which may negatively affect the quality of life but also hypertension and thereby CVD. - Hypertension can lead to worsening kidney function, which can cause fluid retention and worsening hypertension.  Signs and symptoms: - Swelling of the limbs (edema) High blood pressure Fluid in the lungs 37 Therapeutic management of hypertension - The mainstay of therapy is adherence to simple fluid balance (intake vs. output) concepts, restriction of dietary salt intake (2-3 grams per day). - Thiazides and loop diuretics are widely available at low cost and could be used more widely to alleviate symptomatic edema in CKD patients with the potential to improve cardiovascular outcomes. - Massive doses of loop diuretics are generally ineffective in promoting diuresis and expose the patient to risks of ototoxicity, GI upset, muscle Cramps. 38 Therapeutic management of hypertension - ACE inhibition is optimal first-line agents in patients with proteinuria (> 1 gm/24h). - Controlling blood pressure control using KDIGO guidelines (BP goal