31 PDA303T CHRONIC RENAL FAILURE 1.pptx

Chronic renal failure

1. Lecture- 31 Lecture Title Lecture speaker Mr. Subeesh K Viswam

2. Objectives At the end of this lecture, student will be able to: Explain different treatment options for chronic renal failure Identify suitable lifestyle modification required for chronic renal failure

3. Chronic Renal Failure SIGNS AND SYMPTOMS Most patients experience few symptoms of CKD until less than 25% of normal renal function remains CKD can therefore progress insidiously over months to years, evident only through abnormal biochemical parameters, such as gradually rising levels of BUN and serum creatinine values Nonspecific complaints such as malaise, fatigue, and nocturia may be noted

4. Chronic Renal Failure Urine output may or may not be diminished. Hypertension may develop If discovered, presents a critical opportunity for investigation of renal implications Unless patients are recognized to be at risk of and are monitored for kidney disease They usually do not seek medical attention until the onset of uremic symptoms At this point, interventions to forestall progression to ESKD are largely unfruitful

5. Chronic Renal Failure pharmacotherapy TREATMENT OF DIABETIC NEPHROPATHY Diabetic nephropathy is caused mainly by the presence of hyperglycemia , as has been previously discussed In this situation, the best way to prevent or slow renal damage is to prevent hyperglycemia Several trials have shown that minimizing hyperglycemia can delay the onset and slow the progression of the microvascular and macrovascular complications of diabetes

6. Chronic Renal Failure pharmacotherapy TREATMENT OF DYSLIPIDEMIA The benefits of treating dyslipidemia in patients with CKD have been demonstrated through many studies. Specifically, studies suggest that hydroxymethylglutaryl coenzyme A reductase inhibitors (HMG-CoA, statins) are particularly beneficial Statins may decrease proliferation of mesangial and proximal tubular cells, reducing glomerulosclerosis They may also decrease the inflammatory response stimulated by endothelin-1

7. Chronic Renal Failure They have been shown to have an antiproteinuric effect, as well as the ability to slow progression of renal dysfunction Studies have shown decreases in carotid intimal thickening (a marker of total body atherosclerosis) Statins have also been shown to decrease plasma homocysteine levels; fibrates may have the opposite effect

8. Chronic Renal Failure pharmacotherapy TREATMENT OF METABOLIC AND SYSTEMIC CONSEQUENCES OF CHRONIC KIDNEY DISEASE- DIURETICS AND VOLUME MANAGEMENT Until patients become dialysis dependent, diuretic therapy is a mainstay of fluid and volume management When used as single agents, thiazides lose much of their diuretic efficacy after GFR falls to below 20 to 30 mL per minute At this point, loop diuretics such as furosemide, bumetanide, and torsemide become drugs of choice in maintaining volume balance

9. Chronic Renal Failure These agents enter the urine through tubular secretion, producing dose-dependent diuretic responses that require a “threshold” urinary concentration to be present In patients with CKD, drug entry into urine and at the site of action is impaired Administration of doses two to ten times higher than those given to patients with normal renal function may be required to produce a comparable diuretic response

10. Chronic Renal Failure pharmacotherapy ANEMIA Before the introduction of recombinant human erythropoietin (epoetin alfa [EPO]) in the late 1980s Anabolic steroids and red cell transfusions were the primary modalities by which anemia was treated in the CRD population The synthesis of epoetin revolutionized anemia management in the ESRD population But despite more than a decade of clinical use, opinions are still evolving regarding the most appropriate manner of EPO use, optimal therapeutic hemoglobin (or hematocrit ) goals, and their associated risk-benefit ratios

11. Chronic Renal Failure Epoetin alfa , a recombinant molecule with the same structure as endogenous erythropoietin, is manufactured under two name brands (Procrit, Epogen ) This modification gives darbepoetin [also known as a novel erythropoiesis-stimulating protein (NESP)], an increased half-life compared with epoetin alfa This characteristic allows it to be dosed less frequently than epoetin was traditionally dosed

12. Chronic Renal Failure All three products have the same mechanism of action—stimulation of the production and differentiation of erythrocytes Procrit and Epogen are the same molecule but with different FDA-approved indications Only Epogen and Aranesp are approved for the treatment of patients with anemia of chronic kidney disease

13. Chronic Renal Failure pharmacotherapy BLEEDING AND HEMOSTATIC DEFECTS In the absence of clinical bleeding or in situations of increased risk for bleeding (e.g., invasive or surgical procedures), no specific therapy is required Bleeding diathesis may be reduced by adequate treatment of patients in the uremic state through hemodialysis or peritoneal dialysis, and by avoidance of unnecessary agents with antiplatelet effects Through EPO therapy (or transfusion), correction of hematocrit to levels to above 30% may help enhance platelet–endothelium interactions Although the benefit has largely been attributed to improved intravascular dispersion of platelets by red blood cell (RBC) mass, EPO has been proposed to increase the expression of platelet membrane GPIIb -IIIa receptors

14. Chronic Renal Failure pharmacotherapy Acute treatment for severe bleeding necessitates RBC transfusion and, in life-threatening circumstances, administration of cryoprecipitate The role of platelet transfusion is more controversial, given that repeated platelet transfusions are likely to promote the development of antiplatelet antibodies Moreover, platelets transfused into uremic environment are thought to become deficient in function, in the manner described in earlier sections for native platelets Relatively rapid improvements in bleeding time can be produced in most uremic patients through the administration of desmopressin (DDAVP) 0.3 µg per kg by IV infusion

15. Chronic Renal Failure pharmacotherapy GASTROINTESTINAL COMPLICATIONS Antacids were once used heavily in patients with CKD for relief of dyspepsia or gastrointestinal irritation In the setting of renal insufficiency, many of these agents present potential problems Bicarbonate-based products may cause the inadvertent administration of large sodium loads, but they may be useful in controlling metabolic acidosis When magnesium-containing antacids or cathartics are given on a long-term basis to patients with renal failure, accumulation of magnesium becomes a concern, as creatinine clearance falls to below 30 mL per minute

16. Chronic Renal Failure pharmacotherapy Serum magnesium levels may rise to above 6 mEq per L (3 mmol /L), leading to central nervous system depression, lethargy, somnolence, and loss of deep tendon reflexes Dialysis removes magnesium effectively and may be indicated in cases of severe toxicity. long-term use of aluminum -based antacids or phosphate binders may lead to aluminum intoxication syndromes

17. Chronic Renal Failure pharmacotherapy UREMIC PRURITUS The uremic milieu and the use of dialyzer membranes that are less biocompatible have been implicated in the pathogenesis of uremic pruritus (UP) This appears to be true, and with the improvements in hemodialysis adequacy and more compatible dialyzer membranes, a decrease in the incidence of pruritus has been reported

18. Chronic Renal Failure pharmacotherapy Still, UP is a significant issue, especially in the dialysis population A variety of topical and systemic therapies have been reported as beneficial in reducing or relieving uremic pruritus Unfortunately, none of these has proved uniformly effective, often necessitating a trial-and-error approach

19. Chronic Renal Failure pharmacotherapy MUSCULOSKELETAL COMPLAINTS Control of acute gouty attacks is often achieved through cautious use of traditional agents such as NSAIDs (e.g., indomethacin) and colchicine. Upon initiation of an NSAID, patients should be monitored closely for bleeding, worsened renal function, and loss of diuretic efficacy Allopurinol, which decreases uric acid production, is the preferred prophylactic agent because it possesses an active metabolite ( oxypurinol ) that is renally eliminated Doses are usually reduced to 100 to 200 mg daily in advanced CKD

20. Chronic renal failure patient education Patients with advanced renal disease are expected to understand and follow complex dietary, medication, and physical care regimens Data indicate that intense educational effort in ESKD is associated with increased patient autonomy, improved quality of life, increased compliance with therapies, and clinician ability to delay initiation of dialysis The need for renal replacement therapy (RRT) can often be predicted more than 1 year in advance, providing ample opportunity for early education of patients who face ESKD (and their caregivers)

21. Chronic Renal Failure patient education Educational programs generally emphasize patient comprehension of : The most common complications of kidney disease ( anemia , bone disease, hypertension) Measures to slow progression of renal disease (if still feasible) Dietary management (protein, phosphorus, potassium, sodium, and fluid restrictions) Medication management (reason for use, manner of use, and precautions) Choice of rrt modality and physical preparation for this ( e.G. , Catheter or fistula placement, transplantation referral), Options for medical care and prescription coverage, and Possibilities for vocational support

22. Summary The presence of CKD confers a markedly increased risk of cardiovascular disease, and people with CKD often have other risk factors for heart disease, such as high blood lipids. The most common cause of death in people with CKD is cardiovascular disease rather than kidney failure. Aggressive treatment of hyperlipidemia is warranted. Apart from controlling other risk factors, the goal of therapy is to slow down or halt the progression of CKD to stage 5. Control of blood pressure and treatment of the original disease, whenever feasible, are the broad principles of management. Generally, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor antagonists (ARBs) are used, as they have been found to slow the progression of CKD to kidney failure