Acute Renal Failure

Pharmacotherapeutics of Acute Renal Failure

1. Dr. V. S. Swathi Assistant Professor

2. Definition It is critical condition where excretory function of kidney declines rapidly over a period of hours/ days which is associated with accumulation of metabolic waste products and water

3. Epidemiology In the world, it affects 13.3 million cases every year In India, half of the 13.3 million people are affected every year

4. Types Pre renal failure Responsible for 40-80% cases of acute kidney injury Results due to decreased renal perfusion Intra renal failure Responsible for 10-50% cases of acute kidney injury Results due to renal parenchymal injury Post renal failure Responsible for less than 10% cases of acute kidney injury Results due to urinary tract obstruction

5. RIFLE Classification Condition Serum Creatinine(mg/dl) GFR(ml/min) Urine output(ml/hour) Risk Increased Se. Creatinine by 1.5 times Decreased GFR by greater than 25% Less than 0.5ml/kg/hour in 6 hours Injury Increased Se. Creatinine by 2 times Decreased GFR by greater than 50% Less than 0.5ml/kg/hour in 12 hours Failure Increased Se. Creatinine by 3 times Decreased GFR by greater than 75% Less than 0.3ml/kg/hour in 24 hours Loss Persistent renal failure for more than one month End stage renal disease Persistent renal failure for more than three months

6. Risk factors Advanced age Peripheral artery disease Hypertension Diabetes Previous kidney injury Liver disease Cancer Morbid obesity

7. Etiology Hypoperfusion of kidney Renal parenchymal damage Urinary tract obstruction

8. Pathogenesis Pre renal failure

9. Pathogenesis of Intra renal failure Hypoperfusion due to decreased oxygen and nutrient supply to kidney Renal vasoconstriction due to radiocontrast media Renal vasoconstriction due to hepatorenal syndrome Direct renal cell damage due to Rhadmyolysis Immune reactions due to renal transplantation Direct cell damage, Disturbing renal tubular permeability of tubular cells and intra renal vasoconstriction due to drugs (Aminoglycosides, Amphotericin B, Immunosupressants) Damage of tubules of nephron  Decreased excretion of wastes   Accumulation of wastes Damage to kidney 

10. Pathogenesis of Post renal failure Calculi or clots in Ureter Excessive decompression of Ureter due to benign strictures Retroperitoneal tumors Urine obstruction Accumulation of wastes in kidney Damage of kidney  

11. Clinical Presentation Volume loss signs and symptoms Thirst Vomiting Diarrhea Dry mucosa Decreased elasticity of skin Tachycardia Decreased blood pressure Decreased jugular venous pressure

12. Clinical Presentation continued… Volume over load signs and symptoms Weight gain Orthopnea Nocturnal dyspnoea Ankle swelling Oedema Jugular venous distension Pulmonary crackles Shortness of breath

13. Complications Hyperkalemia Metabolic acidosis Hypocalcaemia Hyperphosphatemia Infections Uraemic gastro intestinal erosions Pleural effusion Heart failure Bleeding problems

14. Diagnosis Medical history Family history Clinical presentation Renal function tests Complete blood count Urine microscopy Renal biopsy Computed Tomography of kidney Magnetic Resonance imaging of kidney Ultrasound of kidney

15. Diagnosis continued…. Renal Immunology screening of : Anti neutrophil cytoplasmic antibodies Antiglomerular basement membrane antibodies Serum and urine electrophoresis Immunoglobulins Anti nuclear antibodies

16. Non Pharmacological Treatment Oxygen therapy Ventilation Urinary catheterisation Central line procedure Water restriction –less than 1L per day Sodium restriction- less than 2-3g/ day Restriction of potassium rich diet Dialysis Renal transplantation

17. Treatment Algorithm Acute kidney injury Loop diuretics+ Thiazide diuretics Hyperkalemia Restriction of potassium rich food Calcium Gluconate Glucose + Insulin Nebulised Salbutamol Uraemia Parentral nutrition Volume overload Water and sodium restriction Dialysis

18. Treatment Algorithm continued… Metabolic acidosis Sodium bicarbonate Dialysis Hypocalcaemia Calcium carbonate Vitamin D Hyperphosphatemia Calcium carbonate Calcium acetate Infections Broad spectrum antibiotics Gastric erosions Proton pump inhibitors H 2 receptor antagonists

19. Drugs used in treatment of acute renal failure Drug Category Mode of action Dose Adverse effects Furosemide Loop diuretic Inhibit reabsorption of sodium and water at proximal and distal convoluted tubule 100mg/hour-IF Hypokalemia Hypocalcaemia Hypomagnesaemia Hypotension Hyperurecemia Metalazone Thiazide diuretic Inhibit reabsorption of sodium and water at distal convoluted tubule 2.5-10mg-PO-OD Chest pain Hyperurecemia Hypocalcaemia Hypomagnesaemia Glucosuria Calcium Gluconate (10%) Antidote for Hyperkalemia Stabilises myocardial instability due to high potassium levels 10-30ml-IF for 5-10 min Bradycardia Hypotension Hypomagnesaemia Hyperphosphatemia GI disturbances

20. Drugs used in treatment of acute renal failure continued… Glucose (50%) Glucose elevating agent Stimulate intracellular potassium uptake 50ml with 8-12 units of insulin –IF for 10 minutes Hyperosmolarity Oedema Venous thrombosis Tachypnea Phlebitis Sodium bicarbonate Alkalinising agent Reacts with excess H + ions and decreases acidity 50MEQ-IV for 5 min Aggravated Congestive heart failure Oedema Hypernatremia Metabolic alkalosis Gastric distension Calcium carbonate Mineral supplement balances negative calcium ion levels in the blood 1g-OD-PO Anorexia Constipation Flatulence Hypercalcemia Milk alkali syndrome Vitamin D Vitamin supplement Stimulate calcium and phosphorus absorption from intestine, stimulate calcium secretion from bone in to blood 600-IU-OD-PO Arrhythmias Confusion Constipation Hypercalcemia Dry mouth

21. Drugs used in treatment of acute renal failure continued… Calcium acetate Calcium supplement Balances negative calcium ions levels in the body 1334 mg-OD-PO Arrhythmias Hypomagnesaemia Hyperphosphatemia Hypotension Hypercalcemia

22. Resources https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322747/pdf/pone.0210360.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303942/pdf/12882_2018_Article_1169.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915682/pdf/pone.0196088.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096658/pdf/11255_2018_Article_1836.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827600/?report=printable