1. University of Nizwa
College of Pharmacy and Nursing
School of Pharmacy
PHARMACOTHERAPY - I
PHCY 310
Lecture -15 “Renal Failure” Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy University of Nizwa

2. Course Outcome
Upon completion of this lecture the students will be able to
Define and classify acute and chronic renal failures, and its clinical signs and symptoms,
Describe the pathogenesis of both acute and chronic renal failure and its management strategies,
Recommend the treatment for patients with acute and chronic renal failure.

3. Acute Renal Failure
Defined as a decrease in glomerular filtration rate (GFR) occurring over hours to weeks that is associated with an accumulation of waste products, including urea and creatinine.
ARF should be suspected when the kidney is unable to regulate fluid, electrolyte, acid–base, or nitrogen balance, even in the presence of a normal SrCr concentration.
Clinicians use a combination of the serum creatinine (Scr) value with change in either Scr or urine output (UOP) as the primary criteria for diagnosing ARF

4. Clinical Presentation
Oliguric Phase- Urine production of <400 mL/day is termed oliguria, and urine production of <50 mL/day is termed anuria. The oliguric stage may last from days to several weeks.
After the oliguric phase, a period of increased urine production occurs over several days; this is called the diuretic phase.
The recovery phase occurs over several weeks to months, depending on the severity of the patient's ARF.
Symptoms in the outpatient setting include change in urinary habits,weight gain, or flank pain.
Signs include edema, colored or foamy urine, and, in volume-depleted patients, orthostatic hypotension.

5. Pathogenesis ARF can be categorized as
prerenal (resulting from decreased renal perfusion),
intrinsic (resulting from structural damage to the kidney),
postrenal (resulting from obstruction of urine flow from the renal tubule to the urethra),
functional (resulting from hemodynamic changes at the glomerulus independent of decreased perfusion or structural damage)

6. DIAGNOSIS
Thorough medical and medication histories, physical examination, assessment of laboratory values and if needed, imaging studies, are important in the diagnosis of ARF.
Scr and blood urea nitrogen cannot be used alone to diagnose ARF because they are insensitive to rapid changes in GFR and therefore may not reflect current renal function.
Monitoring changes in Urinary Output (UOP) can help diagnose the cause of ARF.

8. PREVENTION OF ACUTE RENAL FAILURE
TREATMENT
PREVENTION OF ACUTE RENAL FAILURE
Risk factors for ARF include advanced age, acute infection, preexisting chronic respiratory or cardiovascular disease, dehydration, and chronic kidney disease (CKD).
Decreased renal perfusion secondary to abdominal or coronary bypass surgery, acute blood loss in trauma, and uric acid nephropathy also increase risk.

9. Non-pharmacologic Approaches
No drugs have been found to accelerate ARF recovery.
Supportive care goals include maintenance of adequate cardiac output and blood pressure to optimize tissue perfusion while restoring renal function to pre-ARF baseline.
Medications associated with diminished renal blood flow should be stopped.
Appropriate fluid replacement should be initiated. Avoidance of nephrotoxins is essential in the management of patients with ARF.
Renal replacement therapy (RRT), such as hemodialysis and peritoneal dialysis, maintains fluid and electrolyte balance while removing waste products.

10. Pharmacologic Approaches
The most effective diuretics are mannitol and loop diuretics.
Mannitol 20% is typically started at a dose of 12.5 to 25 g IV over 3 to 5 minutes.
Disadvantages include IV administration, hyperosmolality risk,and need for monitoring because mannitol can contribute to ARF.
Equipotent doses of loop diuretics (furosemide, bumetanide, torsemide, ethacrynic acid) have similar efficacy.

11. Ethacrynic acid is reserved for sulfa allergic patients.
Continuous infusions of loop diuretics appear to be more effective and to have fewer adverse effects than intermittent boluses.
An initial IV loading dose (equivalent to furosemide 40 to 80 mg) should be administered before starting a continuous infusion (equivalent to furosemide 10 to 20 mg/hour).

12. ELECTROLYTE MANAGEMENT AND NUTRITION THERAPY
Hyperkalemia is the most common and serious electrolyte abnormality in ARF.
Typically, potassium must be restricted to less than 3 g/day and monitored daily.
Hypernatremia and fluid retention commonly occur, necessitating restricting daily sodium intake no more than 3 g.
All sources of sodium, including antibiotics, need to be considered when calculating daily sodium intake.
Phosphorus and magnesium should be monitored; neither is efficiently removed by dialysis.
Enteral, but not parenteral, nutrition has been shown to improve patient outcomes.

13. Chronic Kidney Disease
A progressive loss of function over several months to years, characterized by gradual replacement of normal kidney architecture with interstitial fibrosis.
It is categorized by the level of kidney function, based on glomerular filtration rate (GFR), into stages 1 to 5, with each increasing number indicating a more advanced stage of the disease, as defined by a declining GFR.
CKD stage 5, previously referred to as end-stage renal disease (ESRD), occurs when the GFR falls below 15 mL/min per 1.73 m2 body surface area.
The patient with stage 5 CKD requiring chronic dialysis or renal transplantation for relief of uremic symptoms is said to have ESRD.

14. PATHOPHYSIOLOGY
Susceptibility factors increase the risk for kidney diseaseinclude advanced age, reduced kidney mass and low birth weight, racial or ethnic minority, family history, low income or education, systemic inflammation, and dyslipidemia.
Initiation factors include diabetes mellitus, hypertension, autoimmune disease, polycystic kidney disease, and drug toxicity.
Progression factors include glycemia in diabetics, hypertension, proteinuria, and smoking.

15. CLINICAL PRESENTATION
Patients with stage 1 or 2 CKD usually do not have symptoms or metabolic derangements.
It is seen with stages 3 to 5, such as anemia (decreased production of erythropoietin), secondary hyperparathyroidism, cardiovascular disease, malnutrition, and fluid and electrolyte abnormalities that are more common as kidney function deteriorates.
Uremic symptoms (fatigue, weakness, shortness of breath, mental confusion, nausea, vomiting, bleeding, and anorexia) are generally absent in stages 1 and 2,
It is minimal during stages 3 and 4, and common in patients with stage 5 CKD who may also experience itching, cold intolerance, weight gain, and peripheral neuropathies.

16. NONPHARMACOLOGIC THERAPY
A low-protein diet (0.6 to 0.75 g/kg/day) can delay progression of CKD in patients with or without diabetes, although the benefit is relatively small.

17. PHARMACOLOGIC THERAPY
Hyperglycemia
Intensive therapy in patients with type 1 and type 2 diabetes reduces microvascular complications, including nephropathy.
Intensive therapy can include insulin or oral drugs and involves blood sugar testing at least three times daily.
The progression of CKD can be limited by optimal control of hyperglycemia and hypertension.

18. Hypertension
Adequate blood pressure control can reduce the rate of decline in GFR and albuminuria in patients with or without diabetes.
Antihypertensive therapy should be initiated in diabetic or nondiabetic CKD patients with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker.
Nondihydropyridine calcium channel blockers are generally used as second-line antiproteinuric drugs when ACEIs or angiotensin II receptor blockers are not tolerated.

19. Supportive Therapies
Dietary protein restriction lipid-lowering medications, smoking cessation, and anemia management (Erythropoiesis stimulating agent [ESA] therapy) may help slow the rate of CKD progression.
The primary goal of lipid-lowering therapies in CKD is to decrease the risk for progressive atherosclerotic cardiovascular disease.
A secondary goal is to reduce proteinuria and renal function decline seen with administration of statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors).