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CKD COMPLICATIONS DONE BY: DIMA SALAH NAHID ARAR CKD COMPLICATIONS #Among these complications are : *fluid and electrolyte abnormalities, *anemia, *hyperphosphatemia, *hyperparathyroidism, *metabolic acidosis, *cardiovascular complications, *poor nutritional status. CKDbCKD CKD Often , these complications go unrecognized or are inadequately managed during the earlier stages of CKD,leading to poor outcomes by the time a patient is in need of dialysis therapy. CKD #Fluid And Electrolyte Abnormalities: Sodium and water #patient with CKD maintain sodium balance but are volume expanded. #the most common manifestation of increasd intravascular volume is systemic hypertension. #the goal in managing sodium and water balance is to maintain a normal serum sodium concentration while preventing fluid overload or volume depletion (i.e.,maintaining hemodynamic stability). #Fluid And Electrolyte Abnormalities: #By achieving these goals , the risk of developing hypertension secondary to volume overload is also reduced , although hypertension is already present in many patients with stage 3 to 4 CKD. Clinical presentation of impaired sodium and water homeostasis General Alterations in sodium and water balance in CKD manifests as increased edema. SYMPTOMS Nocturia can present in stage 3 CKD. Edema generally presents in stage 4 CKD or later. SIGNS Cardiovascular :worsening hypertension,edema. Genitourinary:change in urine volume and consistency. Laboratory tests Increased blood pressure Sodium levels remain within the normal range. Urine osmolality is generally fixed at 300 mOsm/l. management # the ability of the kidney to adjust to abrupt changes in sodium intake is greatly diminished in patients with CKD. 1) Sodium restriction beyond a no-added-salt diet should not be recommended except in the face of hypertension or edema.(2-4 g/day). • Saline –containing IV solutions should be used cautiously in patients with CKD because the ability of kidney to excrete a salt load is impaired and such patients are prone to volume overload. management 2) Fluid restriction is generally unnecessary provided sodium intake is controlled ,although fluid intake between dialysis sessions is generally limited for hemodialysis patients (avoid <2 L/dl) 3) Diuretic therapy is often necessary to control edema or blood pressure. Loop diuretics,particularly when administered by continuous infusion,increase urine volume and renal sodium excretion. management Thiazide diuretics are ineffective in patients with a GFR <30 ml/min.the possible exception is used of the thiazide-like diuretic,metolazone,which may retain its effect at reduced eGFRs. #as kidney failure progresses,manifestations of excess fluid accumulation develop that are resistant to more conventional interventions, and dialysis will be required to control volume status. Potassium homeostasis(hyperkalemia) Hyperkalemia is defined as a serum potassium concentration greater than 5.5mEq/L. Hyperkalemia can result from a combination of factors, including: $ diminished renal potassium excretion, $ redistribution of potassium into the extracellular fluid owing to metabolic acidosis, $ excessive potassium intake. Rare if GFR >15 without an endogenous or exogenous load of potassium. Potassium homeostasis(hyperkalemia) It can be further classified according to its severity: Mild hyperkalemia(serum potassium 5.5-6mEq/L) Moderate hyperkalemia (6.1-6.9mEq/L) Severe hyperkalemia(>7mEq/L) #the chronic goal is to maintain potassium concentrations of approximately 4.5 to 5.5 mEq/L. Hyperkalemia- clinical presentation • Frequently, asymptomatic ,however,the patient may complain of heart palpitations or skipped heartbeats. • the earliest ECG change (serum potassium 5.56mEq/L) is peaked T waves. The sequence of change with further increases is:*prolongation of the PR interval, *widening of the QRS complex, *loss of the P wave, *merging of the QRS complex with the T wave resulting in a sine-wave pattern. Hyperkalemia- clinical presentation Hyperkalemia- clinical presentation • Hyperkalemia ECG changes are uncommon at potassium concentrations of <7 mEq/L,but occur regularly at concentrations>8mEq/L. • Ventricular arrhythmias or cardiac arrest may ensure if no effort to lower serum potassium. • Laboratory tests • Increased serum potassium levels. clinical presentation of hyperkalemia General Hyperkalemia is generally asymptomatic in patients with CKD until serum potassium levels are greater than 5.5 mEQ/L,when cardiac abnormalities present. Symptoms mild hyperkalemia is generally not associated with overt symptoms. Signs Cardiovascular:ECG changes. Hyperkalemia-Management • Generally,treatment is unnecessary if the potassium concentration is<6.5 mEq/L and there are ECG changes. • If potassium concentrations rise above 6.5 mEq/L and especially if they are accompanied by neuromuscular symptoms or changes in the ECG, treatment should be instituted . • Chronic management involves prevention of hyperkalemia by : Hyperkalemia-Management Limiting potassium intake to 50 to 80 mEq/day II. Avoiding the use of agents that could elevate potassium levels III. Constipation in patients with CKD can interfere with colonic potassium excretion ,therefore a good bowel regimen is important I. Hyperkalemia-Management Acute management involves : • reversal of cardiac effects with calcium administration • Reduction of serum potassium which can be achieved by shifting potassium intracellularly with administration of : #glucose and insulin # B-adrenergic agonists # alkali therapy ( if metabolic acidosis is a contributing factor) • Removing excess potassium from the body # loop or thiazide diuretics # exchange resins to remove potassium # dialysis using a low-potassium dialysate bath Metabolic acidosis : A clinically significant metabolic acidosis is commonly seen when the GFR drops below 20-30 ml/min. the major factors responsible for the development of metabolic acidosis in advanced kidney disease:#reduced bicarbonate reabsorption #impaired production of ammonia by the kidney Consequences of metabolic acidosis include: 1. renal bone disease (bone buffering of some of the excess hydrogen ions is associated with the release of calcium and phosphate from bone,ex. Promoting bone resorption), Metabolic acidosis 2.Fatigue and decreased exercise tolerance. 3.Reduced cardiac contractility 4.Increasd vascular irritability 5.Protein catabolism(uremic acidosis can increase skeletal muscle breakdown and diminish albumin synthesis) The goals of therapy for patients with CKD are: to normalize the PH of the blood (PH of approximately 7.35-7.45) maintain the serum bicarbonate within the normal range(2228mEq/L). Metabolic acidosis-management Asymptomatic patient with mild acidosis(bicarbonate of 12-20 mEq/L,PH of 7.2 to 7.4)generally don’t require emergent therapy and gradual correction over days to weeks is appropriate. When plasma bicarbonate less than 20mEq/L, give NAHCO3 orally • each 650 mg tablet of sodium bicarbonate provides 8 mEq of sodium and 8 mEq of bicarbonate. • Dose mEq= 0.5*WT*(24-serum bicarbonate) #the calculated amount of bicarbonate replacement therapy should be administered over several days to prevent volume overload from excessive sodium intake. Metabolic acidosis-management Should be administered over several days to avoid volume overload from Na. Daily dose should not exceed 0.5 mEq/Kg/day and should be given in divided dose. GI distress from CO2 production. Patients with severe acidosis (serum bicarbonate <8 mEq/L, PH<7.2) may require IV therapy. Other Electrolyte and Metabolic Disturbances Of CKD Hypermagnesemia • is due to decreased elimination of magnesium by the kidney. • Magnesium is eliminated by the kidney to the extent required to achieve normal serum magnesium concentratinos(1.7-2.2 mg/dl) until eGFR is <30 ml/minute/1.73 m2). • Serum magnesium concentrations <5 mEq/L rarely cause symptoms. • Higher cons can lead to nausea,vomiting,lethargy,confusion,and diminished tendon reflexes, Other Electrolyte and Metabolic Disturbances Of CKD • Severe hypermagnesemia may depress cardiac conduction. • The risk of hypermagnesemia can reduced by #avoiding magnesium –containing antacids and laxatives. #use of magnesium-free dialysate in patients with stage 5 CKD requiring dialysis. Other Electrolyte and Metabolic Disturbances Of CKD Hyperphosphatemia • Is a result of decreased phosphorus elimination by the kidneys. • Patients should reduce dietary phosphorus to 8001000 mg/day while maintaining adequate nutritional needs. • Phosphorus-containing laxatives and enemas should also be avoided. • Hyperphosphatemia is associated with low serum calcium concentrations. Other Electrolyte and Metabolic Disturbances Of CKD Asymptomatic hyperurecemia. • Happen due to diminished urinary excretion of uric acid. • In the absence of a history of gout or urate nephropathy , asymptomatic hyperuricemia doesn’t require treatment . Anemia Anemia appears as early as stage 3 CKD. Usually is normochromic and normocytic. The primary cause of anemia in patient with CKD is erythropoietin(EPO) defeciency. Other factors include: Decreased lifespan of red blood cells secondary to uremia, Blood loss from frequent phlebotomy and HD,GI bleeding, Severe hyperparathyroidism ,protein malnutrition,severe infections,and inflammatory conditions Uremic toxins may inhibit the production of EPO, the bone marrow response to EPO,and the synthesis of heme. Anemia Iron deficiency Vitamin B12 and folate deficiency ,occurs more frequently in dialyzed patients since folic acid is removed by dialysis. Aluminium intoxication(RBCs are typically microcytic).the major source is aluminium-containing antacids. Anemia the recommended thresholds for diagnosis and evaluation of anemia should not be interpreted as being thresholds for treatment of anemia but simply for the identification of this complication. Practice preferences with respect to treatment strategies should be directed according to local resources. Evaluation of anemia in people with CKD #to identify anemia in people with CKD measure Hb concentration: • When clinically indicated in people with GFR<60 ml/min/1.73m2. • At least annually in people with GFR 30-59 ml/min/1.73m2. • At least twice per year in people with GFR<30 ml/min/1.73m2. Anemia-clinical presentation and diagnosis Pallor and fatigue are the earliest clinical signs,with other manifestations(exertional dyspnea,dizziness,headache)developing as anemia worsens progressively with declining kidney function. A significant consequence of anemia is development of left ventricular hypertrophy (LVH), further contributing to cardiovascular complications and mortality in patients with CKD >>>CHF,angina. >>>Early and aggressive treatment of anemia of CKD before the development of stage 5CKD is important. Anemia-clinical presentation and diagnosis A more complete and regular workup for nemia of CKD is recommended for patients with eGFR <60 ml/min/1.73m2.this workup includes: Monitoring of hemoglobin and hematocrit, Assessment of iron indices with correction if iron deficiency is present, Evaluation for sources of blood loss,such as bleeding from the GI tract. Clinical presentation of anemia of CKD General Anemia of CKD generally presents with fatigue and decreased quality of life. Symptoms Anemia of CKD is associated with symptoms of cold intolerence, shortness of breath,and decreased exercise capacity. Signs Cardiovascular:left ventricular hypertrophy,ECG changes,congestive heart failure. Neurologic:impaired mental cognition Genitourinary:sexual dysfunction. Clinical presentation of anemia of CKD Laboratory tests Decreased RBC count,Hgb,and Hct Decreased serum iron level,TIBC,serrum ferritin ,and TSAT. Decreased erythropoietin levels relative to the degree of hypoxia that is present. TIBC:total iron binding capacity TSAT:transferrin saturation Goals of Anemia therapy: 1-increase oxygen-carrying capacity 2-decrease signs and symptoms of anemia like Easy fatigue, rapid heat beat, particularly with exercise, headache Difficulty concentrating ,Dizziness , Pale skin ,Leg cramps Insomnia 3-improve the patient’s quality of life 4-decrease the need for blood transfusions oTo achieve this goals we must combine ESA with iron supplement oHb is the preferred parametet to moniter blood cell production because it is not affected by storage condition Initiation of ESA therapy should be considered in all CKD patients when Hb is between 9 and 10 g/dL ESA dose should be decreased or interrupted when Hb is above 10 g/dL in CKD patients not receiving dialysis or above 11 g/dL in patients receiving dialysis. As CKD worsens, a progressive decline in Hb despite ESA therapy may be observed so we must add iron supplement Parameters used to monitor iron level: TSat, an indicator of iron immediately available for delivery to the bone marrow (Transferrin is the carrier protein for iron and, as a protein, may be affected by nutritional status) serum ferritin, an indirect measure of storage iron. *Serum ferritin is an acute-phase reactant, meaning it may be elevated under certain inflammatory conditions and give a false indication of storage iron. The content of hemoglobin in reticulocytes (CHr) is also recommended as a parameter to assess iron status in hemodialysis patients Anemia management : Nonpharmacologic therapy maintain adequate dietary intake of iron as well as folate and B12 like chicken , tuna ,salmon Peanut Butter Spinach Cereal ,Nuts ,Dried frutit Patients on hemodialysis or peritoneal dialysis should be routinely supplemented with water-soluble vitamins (vitamins B, C, and folic acid) as these vitamins are often depleted with dialysis therapy. small amount of dietary iron , approximately 1 to 2 mg is absorbed so oral intake from dietary sources alone is insufficient to meet the increased iron requirements Pharmacologic Therapy Pharmacologic therapy for anemia of CKD is based on a foundation of ESA therapy to correct erythropoietin deficiency and iron supplementation to correct and prevent iron deficiency caused by ongoing blood loss and increased iron demands associated with the initiation of erythropoietic therapy. Erythropoietin: a glycoprotein hormone secreted by the kidney in the adult and by the liver in the fetus, which acts on stem cells of the bone marrow to stimulate red blood cell production and hemoglobin in the bone marrow, in response to low levels of oxygen in the tissues. Iron supplementation is first-line therapy for anemia of CKD if iron deficiency is diagnosed 1) Iron (Parenteral and Oral Form) Anemia in CKD patient must be treated by iron agents depending on iron test iron therapy appears not to be limited to patient iron deficiency. Goals of iron therapy are: 1)avoid storage iron depletion 2) prevent iron-deficient erythropoietin 3) achieve and maintain target Hgb levels Monitoring iron level Every month during initial ESA treatment At least every 3 months during stable ESA treatment Oral Iron Preparation Oral ferrous sulphate (glutamate, fumarate) 200mg/day of elemental iron is taken on empty stomach in 2-3 doses to maximize absorption, unless no side effects in GI In case of GI side effect: I. oral iron can be taken with small snack II. ferrous sulphate solution, iron polysaccharide complex or sustained-release preparation may be used but with the latter two bioavailability is the problem GI side effects ( nausea, abdominal pain, diarrhea, constipation, dark stools). drug interactions with oral iron (e.g., antacids, quinolones) Food and CaCO3 delay iron absorption iron should be taken 1 hr before or 2 hr after CaCO3 •The ferrous form of iron is absorbed three times more readily than the ferric form •Drugs that decrease iron absorption: 1)Mg , Al, and Ca containing antacid 2)Tetracycline and doxycycline 3)Histamine2 antagonist 4)Proton pump inhibitor 5)Cholestyramine Iron drug interaction: 1-levodopa (chelate with iron) 2-methyldopa ( decrease efficacy) 3-levothyroxine (decrease efficacy) 4-penicillamine (chelate with iron) 5-fluoroquinolones (form complex) 6-mycophenolate (decrease absorption) Parental iron preparation: 1- iron dextran •100mg during each HD session by IV push over 2 min for 10 session 50 mg each week during dialysis for 10 weeks •ADR:(Arthralgias, myalgias, serum sickness-like syndrome, hypotension. •25mg in adults should be administered IV before initiating therapy to detect small risk of anaphylaxis 2- ferric gluconate 3- iron sucrose 4- Ferumoxytol ( these agents have less ADR compared to dextran) 2) Folic Acid 1 mg/day 3) Blood Transfusion: may result in iron overload, infections, suppression of erythropoietin . Only use it in persistent anemia . 4) Erythropoiesis- Stimulating Agent (ESA): The erythropoietin deficiency evident in patients with CKD can be corrected by the exogenous administration of ESA . Two such agents are currently available: A- Epoetinalfa (recombinant human erythropoietin) B- Darbepoetin Alfa The benefits of ESA: 1- improvements in quality of life 2- increased energy levels 3- greater capacity for work and exercise 4- improved appetite and participation in social activities 5- reduced depression and fatigue oEpoetin Alfa: SC administration is preferred because cost is lower than with IV administration and less frequency •the half-life of epoetin alfa (8.5 hours IV, 24.4 hours SC), so administered one to three times per week with SC and three times per week for IV oDarbepoetin alfa: • has a longer half life and prolonged biological activity •Starting dose in patients not previously receiving epoietin-alpha therapy is 0.45 mcg/kg IV or SC once weekly. •In dialysis and nondialysis patients with CKD receiving ESA therapy, the selected Hgb target should generally be in the range of 11.0 to 12.0 g/dL and not be greater than 13g/dL. • We prefer SC in non-hemodialysis-CKD patients and IV in HD (hemodialysis)-CKD patients ESA resistance causes: 1-Fe,folate and B12 deficiency 2-inflammtion (less Fe delivered) 3-Hyperparathydism KDIGO guideline: oESAs not be started in adult non-dialysis CKD patients with Hgb concentrations ≥10 g/dL. For non-dialysis CKD patient with Hgb <10 g/dL, the treatment individualized depend on: the rate of fall in Hgb concentration, response to iron therapy, In dialysis patients, KDIGO suggests initiating ESAs when the Hgb concentration is below 10 g/dL. The KDIGO 2012 guidelines suggest that ESAs should generally not be used to maintain Hgb concentrations above 11.5 g/dL, but that individualization of therapy will be necessary as some patients may have improvements in quality of life at Hgb ≥11.5 g/dL and will be prepared to accept the risks The KDIGO guidelines recommended that ESAs not be used to maintain Hgb ≥13 g/dL. The 2012 KDIGO guidelines recommended that ESAs be used in caution with malignancy, or with a history of stroke • Calcium–phosphorus balance play an important role parathyroid gland by on bone, GI tract, kidney, and many hormones like *PTH (↑ serum calcium, ↓ serum phosphate( *Vitamin D: ↑ Ca and P *fibroblast growth factor 23:inhibits the production of 1,25(OH)2D )↓serum phosphate) by the kidney The major sequelae of CKD is its impact on bone mineral homeostasis: deficient 1,25(OH)2D production retention of phosphate reduction in ionized calcium levels secondary hyperparathyroidism that results from the parathyroid gland response to lowered serum ionized calcium and low 1,25(OH)2D. FGF23 levels are also increased in part due to the increased phosphate, which further reduce 1,25(OH)2D production by the kidney *Kidney produce vitamin D and when kidney disease progresses, renal activation of vitamin D is impaired , which reduces gut absorption of calcium ,which lead to low blood calcium concentration resulting in increase secretion of Parathyroid hormone (PTH) When renal function declines, serum calcium balance can be maintained only at the expense of increased bone resorption Which leads to change in bone morphology bone pain and fractures. 1)altered lipid metabolism and insulin secretion 2)impaired neurologic and immune functions 3)Resistance to erythropoietic therapy 4)Increase mortality 1-Osteitis Fibrosa cystica : bone become deformed and soft because of high bone turnover 2-osteomalacia:softening of bone 3-adynamic bone disease: inactive bone *When symptoms appears the disease will not be easily treated The desired ranges of calcium , phosphorus, calcium-phosphorus product and PTH based on K/DOQI parameter Stage 3 Stage 4 stage 5 Corrected calcium (mg/dl) Normal” Normal” 8.4-9.5 Phosphorus(mg/dl ) 2.7-4.6 2.7-4.6 3.5-5.5 Ca*p(mg^2/dl^2) <55 <55 <55 Intact PTH (pg/ml) 35-70 70-110 150-300 MONITERING: Lab tests should be repeated every 12 months for stage 3 patient and every 3 month for stage 4 patient and monthly for stage 5 Patient The KDIGO guideline recommend measuring of bone-specific alkaline phosphate which is useful for diagnosis and assessment of severity of metabolic bone disease including Paget disease, osteomalacia, and other states of high bone turnover Bone biopsy: gold standard and invasive test that is not easily performed for diagnosis of bone architecture, this test recommended when symptoms is not clear or in patient with more biochemical abnormalities *including patient with fractures, persistent hypercalcemia and aluminum toxicity. However when aluminum concentration (60-200mcg/L)a Deferoxamine test should be done (test used for diagnosis of aluminum-related osteodystrophy) Bone biopsy test described turnover rate ,volume and miniralization Bone mineral density test is not recommended in advanced CKD stages because has not been shown to predict the fracture risk *Electron Beam computed tomography(EBCT): noninvasive and sensitive method for detecting cardiovascular calcification and used in CKD studies Calcification: build up of calcium in body tissue where there normally is not any calcium leading to organ dysfunction or vessel defect, calcification occur by aging,surgery,radiation and infection Management of renalosteodystrophy: Dietary phosphate restriction Phosphate binder (calcium and non-calcium) Vitamin D analogues Calcium supplement Calimimetic(not approved for CKD patients) 1)Oral calcium supplement: are first line for controlling both calcium and phosphate level, but elemental calcium should not more than 1500mg/day *IF Ca x P >55mg^2/dl^2 according to K/DOQI high risk for soft tissue formation and calcification leading to calcific uremic artereopathy (CUF) However KDIGO guideline suggest no clinical information of Ca * P than individual value in treatment 2)Dietary phosphate restriction: The normal level of phosphate from 2.4-4.1mg/dl in all CKD stages according to KDIGO. However K/DOQI allow phosphate eve from 3.5-5.5 mg/dl in stage 5 patient Dietary phosphorus restriction (800 to 1,000 mg/day) should be first-line intervention for stage 3 or higher CKD Sources of phosphate: Protein rich food Organic phosphate (plant seeds,nuts,legumes,meat) 50% absorbed Inorganic phosphate(preservative and additive salts found in processed food) should be minimized because 90% absorbed Dark carbonated beverage should be discouraged Some phosphate are removed by dialysis 3) Phosphate-Binding Agents: •Dietary phosphate restriction is difficult to achieve specially when GFR <30ml/minute/1.73m so phosphate-binding agents are necessary •These agents reduce phosphate absorption from the gut and should be administered with meals to maximize the effect •These agents are first-line agents for controlling both serum phosphorus and calcium Concentrations •K/DOQI guidelines recommend that elemental calcium from calcium containing binders should not exceed 1,500 mg/day and the total daily intake from all sources should not exceed 2,000 mg. This may necessitate combination of calcium- and noncalcium-containing products Adverse effects of calcium-containing phosphate binders: 1) constipation, 2) nausea, vomiting, 3)abdominal pain. oTo avoid potential drug interactions, phosphate binders should be administered 1 hour before or 3 hours after other oral medications. 4) Vitamin D Therapy: Calcium (less than 9.5 mg/dl) and phosphorus (less than 4.6 mg/dl) must be controlled before vitamin D therapy is initiated. Calcitriol (1,25-dihydroxyvitamin D3) directly suppresses PTH synthesis and secretion and up regulates vitamin D receptors, which ultimately may reduce parathyroid hyperplasia. The dose depends on the stage of CKD and type of dialysis. If hypercalcemia withhold treatment . Ergocalciferol:in stage 3 and 4 if 25-hydroxyvitamin D is less than 30 ng/dl Ergocalciferol is recommended •The recommended dose between 600-800 units per day 5)Calcimimetics Cinacalcet •reduces PTH secretion by increasing the sensitivity of the calcium-sensing receptor. The most common adverse events are nausea and vomiting. • The starting dose is 30 mg daily, which can be titrated to the desired PTH and calcium concentrations every 3 to 4 weeks and to a maximum of 180 mg daily *Sensipar (cinacalcet) is the first calcimimetic FDA approved Cinacalet lowers serum calcium and may cause hypocalcemia so this agent should not be used if serum level is less than 8.4mg/dl Step 1 The initial focus in managing sHPT should be the management of hyperphosphatemia. Among patients with hyperphosphatemia restricting dietary phosphate intake. Step 2 Among patients with hyperphosphatemia despite dietary phosphorus restriction after two to four months phosphate binders should be administred For patients with an initial serum calcium levels less than 9.5 mg/dl (<2.37 mmol/L), a calcium containing phosphate binder should be administered as long as hypercalcemia does not develop. For patients with an initial serum calcium level greater than 9.5 mg/dl (<2.37 mmol/L), a non-calcium based phosphate binder rather than a calcium-containing phosphate binder. Either sevelamer or lanthanum carbonate can be given in this setting Treatment with ergocalciferol should be initiated if vitamin D deficiency exists, as demonstrated by a 25(OH)-vitamin D (calcidiol) level of less than 30 ng/ml if elevated PTH levels remain despite ergocalciferol and phosphate binder therapy over a six-month period , low dose of active vitamin D analog should be adminidtered If the serum level of corrected total calcium exceeds 10.2 mg/dL (2.54 mmol/L) ergocalciferol therapy and all forms of vitamin D therapy should be discontinued Step 3 Decide whether phosphate binder therapy is sufficient or whether a vitamin D analogue should be added. This is based upon calcium, phosphate, and PTH levels that are measured when administering optimal phosphate binder therapy. Step 4 Among predialysis patients with sHPT, the use of cinacalcet is controversial. Some experts and the KDIGO working group recommend NOT giving cinacalcet given the paucity of data concerning efficacy and safety in predialysis patient with CKD Bisphosphonate: We do not describe it if GFR<30ml/min/1.73m^2 Note: •Indication of bisphoohonate are osteoporosis, corticosteroid therapy and Paget disease. •In CKD patient if GFR >60ml/min/1.73m^2 with osteoporosis and at high risk for fracture also if GFR between 30-60ml/min/1.73m^2 with normal PTH,osteoporosis or high risk for fracture treatment should be as normal population Hyperlipidemia: The prevalence of hyperlipidemia increases as renal function declines Target LDL-C in people with diabetes and CKD stages 1-4 should be < 100 mg/dl; <70 mg/dl is a therapeutic option People with diabetes, CKD stages 1-4, and LDL-C ≥ 100 mg/dl should be treated with a statin. Treatment with a statin should not be initiated in patients with type 2 diabetes on maintenance hemodialysis who do not have a specific cardiovascular indication for treatment Lipid profile should be reassessed at least annually and 2 to 3 months after changing treatment HMG-CoA reductase inhibitors may have some other advantages that may help to reduce kidney disease progression in addition to lipid reduction, such as: reduction of monocyte infiltration, mesangial cell proliferation, mesangial matrix expansion, and tubulointerstitial inflammation and fibrosis ATP III suggests that chronic kidney failure is a contraindication to fibrates. New phosphate-binding agent sevelamer hydrochloride appears to lower lipid levels by mechanisms similar to those of bile acid sequestrants. KDIGO guidelines for lipid management in CKD recommend treatment with a statin in adults aged 50 and older with stage 1 to 5 CKD (not on dialysis) The statin/ezetimibe combination may be used in patients in stage 3 to 5 CKD (not on dialysis) KDIGO only recommends statins in adults aged 18 to 49 years with stage 1 to 5 CKD (not on dialysis) who have one or more of the following: known coronary disease, diabetes mellitus, prior ischemic stroke, and an estimated 10- year incidence of coronary death or nonfatal myocardial infarction >10% It is not recommended that statins or statin/ezetimibe be initiated in patients with stage 5 CKD on dialysis; however, therapy with theseagents may be continued if patients were receiving these medications at the time of dialysis initiation. Due to the risk of adverse events with statins with stage 3 to 5 CKD, KDIGO recommends using statins at doses shown to be beneficial (atorvastatin 20 mg, fluvastatin 80 mg, rosuvastatin 10 mg, simvastatin 20 mg) Patients who are on hemodialysis with type 2 diabetes will not be improved by atorvastatin according to study results Some medication increase the level of statin so should be avoided or reduce statin dose Hypertension The pathogenesis of hypertension in patient with CKD is multifactorial. Hypertension Anorexia and malnutrition Limited data defining CKD stage where malnutrition develops Malnutrition is common in patients with advanced chronic renal disease because of:a lower food intake(principally due to anorexia),decreased intestinal absorption and digestion, and metabolic acidosis. Studies have shown a strong correlation between malnutrition and death in maintenance dialysis patients. Anorexia and malnutrition It is desirable to monitor the nutritional status of patients with chronic kidney disease. NKF K/DOQI guidelines:evaluate for signs of malnutrition when GFR<60 ml/min/1.73 m2. A low plasma concentration of albumin and/or creatinine(which varies with muscle mass as well as GFR) may be indicative of malnutrition. Nutrition assessment • • • • dietry protein Calorie intake Serum albumin Urine protein Malnutrition -Management Protein-energy malnutrition is common in patient with stage 4 or 5 CKD. Daily protein intake should be 1.2g/Kg for patient undergoing hemodialysis and 1.2 to 1.3g/kg for those undergoing peritoneal dialysis. Daily energy intake should be 35 Kcal/kg for patients undergoing any type of dialysis, the intake should be lowered to 30-35 kcal/kg for patients older than 60 years. Malnutrition -Management Water-soluble vitamins should be supplemented to replace dialysis-induced loss. L-carnitine is not recommended for patients with ESKD unless the disordes for which it has shown benefit(eg:hypertriglyceridemia,hypercholesterimia,a nd anemia) don’t respond to standard therapies. Questions??