Renal failure management

Definition and prevalence of renal failure - classification of renal failure - Acute renal failure definition , causes , stages , clinical manifestations, investigations and treatment - Chronic renal failure definition , causes, stages , risk factors , clinical manifestations , investigations and treatment. Drug safety during chronic renal dysfunction - Adverse drug effects during chronic renal dysfunction

1. Renal Failure Management Dr. Sameh Ahmad Muhamad abdelghany Lecturer Of Clinical Pharmacology Mansura Faculty of medicine

2. RENAL FAILURE INTRODUCTION      CLASSIFICATION ACUTE RENAL FAILURE CHRONIC RENAL Failure DRUG SAFETY IN CKD CONTENTS

3. INTRODUCTION

4. Introduction Results when the kidneys cannot remove the body’s metabolic wastes or perform their regulatory functions. It is a systemic disease and is a final common pathway of many different kidney and urinary tract diseases.

5. Introduction Chronic kidney disease affected 753 million people globally in 2016, including 417 million females and 336 million males. In 2015 it resulted in 1.2 million deaths, up from 409,000 in 1990.

6. Acute Renal Failure

7. Acute Renal Failure Definition: is an acute and potentially reversible irritability of the kidneys to perform their normal functions to maintain homeostasis There is a sudden and almost complete loss of kidney function (decreased GFR) over a period of hours to days with failure to excrete nitrogenous waste products and to maintain fluid and electrolyte homeostasis

8. Acute Renal Failure Causes: Pre-renal( Functiona ) Volume Depletion Cardiac Hepatorenal syndrome Drugs: NSAIDs - ACEIs

9. Acute Renal Failure Causes: Intra-renal(Structural) Vascular: e.g Vascular occlusion Interstitial: e.g Interstitial nephritis Glomerular: e.g glomerulonephritis Tubular: e.g ATN

10. Acute Renal Failure Causes: Post-renal(Obstruction) Due to obstruction in Urinary system. Sites of obstruction leading to ARF: Bladder neck obstruction Bilateral ureters Urine volume variable

11. Acute Renal Failure

12. Acute Renal Failure Stages Onset : 1-3 days with increased BUN and creatinine and possible decreased UOP may be Asymptomatic Oliguric : UOP < 400/d, increased BUN, Creatinine, Phosphates, K, may last up to 14 d Impaired glomerular filtration Waste cannot be remove & Uremia develops

13. Acute Renal Failure Stages Diuretic : UOP increased up to as much as 4000 mL/d but no waste products at end of this stage may begin to see improvement dehydration and electrolyte imbalance due to excess urination Recovery : things go back to normal or may remain insufficient and become chronic(takes months)

14. Clinical manifestations Severe oliguria/ Anuria Nausea / Vomiting Lethargy Dehydration Acidotic breathing Altered consciousness Irregular cardiac rate, rhythm Edema Hypertension

15. Clinical manifestations

16. Investigations LAB Blood examination: Anemia Raised serum creatinine level, blood urea Electrolytes: K , Na , Ca PH: Acidosis Complete blood count Urine examination: Protienuria, Hematuria, presence of casts

17. Investigations Radiological USG Structural abnormalizes, calculi IVP Acute tubular necrosis Radionuclide studies Evaluate GFR, renal blood flow Renal biopsy Ultimate cause

18. Investigations

19. Treatment Immediate treatment of pulmonary edema and hyperkaliemia Remove offending cause or treat offending cause Dialysis as needed to control hyperkaliemia, pulmonary edema, metabolic acidosis, and uremic symptoms Adjustment of drug regimen Usually restriction of water, Na, and K intake, but provision of adequate protein Possibly phosphate binders

20. Treatment Medical treatment Fluid and dietary restrictions Use of diuretics Maintain Electrolytes May need dialysis to jump start renal function May need to stimulate production of urine with IV fluids, Dopamine, diuretics, etc. Hemodialysis

21. CHRONIC RENAL FAILURE

22. Chronic Renal Failure Definition: It is a permanent irreversible destruction of nephron leading to severe deterioration of renal function, finally resulting to end stage renal disease Defined as either presence of Kidney damage Pathological abnormalities Glomerular filtration rate (GFR) <60 ml/min for 3 months or longer

23. Chronic Renal Failure Causes: Glomerulonephritis (the most common cause in the past) Diabetes mellitus Hypertension Tubulointerstitial nephritis Miscellaneous

24. Chronic Renal Failure Stages: Diminished Renal Reserve Normal BUN, and serum creatinine absence of symptoms Renal Insufficiency GFR is about 25% of normal BUN Creatinine levels increased

25. Chronic Renal Failure Stages: Renal Failure GFR <25% of normal increasing symptoms ESRD or Uremia GFR < 5-10% normal creatinine clearance <5-10ml/min resulting in a cumulative effect

26. Chronic Renal Failure Risk factors: Old age Family history Diabetes Obesity HTN Cardiac diseases Previous acute kidney injury Smoking

27. Chronic Renal Failure

28. Clinical manifestations Early symptoms Weakness Anorexia Nausea Failure to thrive Unexplained anemia Late symptoms Pericarditis Congestive cardiac failure Altered sensorium

29. Complications Azotemia Metabolic acidosis Electrolyte imbalance Chronic cardiac failure HTN Severe anemia

30. Clinical manifestations

31. Clinical manifestations

32. Investigations LAB Blood examination: Decreased hematocrit, Hb%, Na+, Ca++, HCO-3, increased K+ & phosphorus Renal function test Gradual increase in BUN, uric acid & creatinine Urine examination: Variation in specific gravity, increased urine creatinine, change in total urine output

33. Investigations Radiological X-Ray Chest, hands, knees, pelvis, spine to detect bony defect ECG, IVP, MCU, radio nuclide imaging Extent of complications

34. Investigations

35. Treatment Conservative management Correction of reversible component of renal dysfunction Preservation of renal function Treatment of metabolic problems Optimization of growth Preparation for treatment of ESRD Treat for infection, accelerated hypertension, CCF, obstruction of urine flow to improve renal function

36. Treatment Medical treatment IV glucose and insulin Na bicarb, Ca, Vit D, phosphate binders Fluid restriction, diuretics Iron supplements, blood, erythropoietin

37. Treatment Dietary therapy Low protein diet Severe protein restriction may produce protein calorie malnutrition Salt restriction in patients with hypertension and fluid overload

38. Treatment Dietary therapy Patients with salt losing nephropathy should take a liberal amount of salt and water If the GFR falls <10 ml/min/1.73m2, potassium intake should be restricted. (hyperkalemia may develop) Vit D is essential to raise the serum calcium and suppress parathormone secretion

39. Treatment Dialysis Peritoneal dialysis Hemodialysis Renal transplantation

40. Treatment Peritoneal dialysis

41. Treatment Hemodialysis

42. Treatment

43. DRUG SAFETY IN CKD

44. Drug-Related adverse safety events in CKD Occurs in 50% of patients with estimated GFR (eGFR) <60 ml/min Risk factors Non-white Older age ACEIs/ ARB use Diabetes More advanced CKD

45. Drug-Related adverse safety events in CKD Modes of Drug-Related Adverse Events in CKD Direct kidney injury Dosing error Drug-drug interaction

46. Drug Elimination in CKD Adjustments usually needed when >25-30% of active drug/metabolite eliminated renally: Azithromycin 5-12% Moxifloxacin 15-21% Pioglitazone (Actos) 15-30% Ciprofloxacin 30-57% Amoxicillin 50-70% Digoxin 57-80%

47. I- Drugs To avoid in CKD NSAIDs Injure kidneys directly Induce acute kidney injury (AKI) from “pre-renal” or ATN Interstitial nephritis Nephrotic syndrome Decrease kidney potassium excretion → hyperkalemia Decrease sodium excretion → HTN, edema

48. I- Drugs To avoid in CKD Oral Sodium Phosphate Preparations Hyperphosphatemia + volume depletion Acute Phosphate Nephropathy Ca-phosphate deposits in tubules & interstitium Leads to AKI/ CKD within days to months

49. I- Drugs To avoid in CKD Iodinated Contrast Leads to AKI Risk Factors CKD (esp. eGFR <30 ml/min/1.73m2) Diabetes, CHF, gout Dehydration Concurrent use of NSAIDs or RAAS-antagonists

50. I- Drugs To avoid in CKD Gadolinium Linked to nephrogenic systemic fibrosis (NSF) Increased risk with decreased kidney function (AKI, CKD, post-transplant) Avoid gadolinium in patients with eGFR <30 ml/min

51. II- Drugs require cautions in CKD Antihypertensives: RAAS antagonists Can lead to AKI, hyperkalemia Risk management Avoid in patients with renal artery stenosis Assess eGFR and serum K+ 1 week after initiation or ↑dose Prior to contrast, major surgery, conditions that predispose to dehydration - consider temporarily decrease Stop or reduce if SCr increase > 30% or serum K+ > 5.5 mEq /L

52. II- Drugs require cautions in CKD Gabapentin Many cases with GFR < 90 ml/min developed side effects Mostly ESRD patients had side effects

53. II- Drugs require cautions in CKD Antimicrobials Most require renal dose adjustments: Common exceptions: Ceftriaxone, moxifloxacin, macrolides, doxycycline, clindamycin, linezolid Careful monitoring of drug levels needed for: Vancomycin. Aminoglycosides

54. II- Drugs require cautions in CKD Antimicrobials Trimethoprim/ sulfamethoxazole May ↑ SCr slightly due to ↓renal tubular creatinine excretion no change in GFR. Distinguish from AKI due to drug allergic interstitial nephritis Hyperkalemia Imipenem/ cilastatin High seizure risk in CKD patients, use carbapenem in CKD

55. II- Drugs require cautions in CKD Metformin eGFR 45 to 60 mL/min/1.73m2 Continue metformin use and ↑ monitoring of eGFR to every 3 - 6 months eGFR 30 to 45 mL/min/1.73m2 Use metformin with caution with lower dose (50% maximal) eGFR < 30 mL/min/1.73m2 Stop metformin

56. II- Drugs require cautions in CKD Hypoglycemics Sulfonylureas Dose adjustment needed for renally excreted drugs: chlorpropramide , glyburide Avoid above two if eGFR < 50 ml/min Insulin Partially renally excreted and dose adjustment may be needed for eGFR <30 ml/min

57. II- Drugs require cautions in CKD Lipid-lowering drugs Statins Dose adjustments needed when eGFR <30 ml/min for fluvastatin , lovastatin, pravastatin, rosuvastatin and simvistatin Fibrates Associated with AKI esp. in CKD patients May transiently raise SCr by increased creatinine production rather than decreased GFR

58. III- Awareness of drug-drug interactions in patients Rhabdomyolysis with Statins Due to Cytochrome P450 3A4 interactions Azoles (ketoconazole the worst) Diltiazem and Verapamil Clarithro and Erythro >>> Azithro Ritonavir in HIV patients Cyclosporine and Tacrolimus

59. III- Awareness of drug-drug interactions in patients Bisphosphonates Bisphosphonates for eGFR > 30 mL/min/ 1.73 m2 with normal Ca, phosphoate , intact PTH showing osteoporosis . Long term treatment with bisphosphonates may cause or exacerbate adynamic bone disease .

60. Avoiding drug toxicity in CKD Minimizing Risk of Adverse Drug Events Minimize pill burden as possible Review medications carefully for Dosing Potential interactions Educate patient on: OTC meds to avoid (mainly NSAIDs) Signs/symptoms of potential drug adverse effects

61. Avoiding drug toxicity in CKD Dosing Adjustments Don’t rely on SCr alone – calculate eGFR or Cr clearance Cannot rely on eGFR in AKI When in doubt, look up dosing adjustment/ potential interactions

62. 62 CONTACT Email: [email protected] Facebook: Sameh abdelghany (https://www.facebook.com/samghany) SlideShare : Sameh abdelghany (https://www.slideshare.net/samghany) Tel: [phone]

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