Clinical Pharmacy in Pediatric Nephrology: Optimizing Medication Therapy for Children with Kidney Conditions

1. بسم الله الرحمن الرحيم

2. Clinical Pharmacy in Pediatric Nephrology Ihab El-Hakim

3. Clinical Pharmacy Is the branch of pharmacy in which pharmacists provide patient care that optimizes medication therapy and promotes health, wellness, and disease prevention. Its practice is centered inside the hospitals and clinics in company with physicians for the purpose of ensuring optimal medications’ prescription. A clinical pharmacist should have a foundational understanding of the biomedical, pharmaceutical, socio-behavioral, and clinical sciences(American College of Clinical Pharmacy, www.accp.com).

5. Pediatric Nephrology • Functional anatomy of the kidney • Physiological roles of the kidney and UT • Drug handling by the kidney • Clinical conditions (presentations, investigations, therapy) • Glomerular: AGN, MLNS • Tubular: deToni-Debré-Fanconi syndrome • Hypertension • UTI • Chronic renal failure, drugs in CRF • Dialysis, drugs and dialysis • Transplantation

6. Functional anatomy of the kidney

7. Functional anatomy of the kidney

8. Functional anatomy of the kidney

9. Functional anatomy of the kidney

10. Functional anatomy of the kidney

11. Functional anatomy of the kidney

12. Functional anatomy of the kidney

13. Functional anatomy of the kidney

14. Functional anatomy of the kidney

15. Functional anatomy of the UT

17. Physiology • 1.3 million nephrons in each kidney • The total area of the glomerular capillary endothelium across which filtration occurs is about 0.8 m2. • The filtration slits are approximately 25 nm wide and each is closed by a thin membrane. They permit passage of neutral substances up to 4 nm diameter and almost totally exclude substances with 8 nm or greater diameter. Also charges on the molecules affect their passage.

18. Physiology • Glomerular function FILTRATION • Renal blood flow (RBF) about 25% of cardiac output. More in cortex than medulla. • Glomerular capillary pressure 40% of systemic arterial pressure. • Various substances affect the afferent or efferent arterioles differently hence the net effect on glomerular filtration pressure varies. • Clearance of a substance: is the volume of plasma cleared from that substance per minute. Most commonly used is creatinine. Clearance = (Ucrx V)/(Pcr) (mg/ml x ml/min)/(mg/ml)

19. Physiology • Tubular functions REABSORPTION and SECRETION

20. Physiology

21. Physiology • Bladder function STORAGE and MICTURITION

22. Drug handling by the kidney • Kidneys are involved in the process of elimination of drugs. • Drugs may be filtered, reabsorbed or secreted by glomeruli and tubules in an active or inactive form. • Filtrtation is passive and nonsaturable. Protein-bound drugs are poorly filtered. • Weak acid drugs are secreted in PCT. • Lipid soluble drugs are rapidly reabsorbed. • Some drugs may be metabolized in the kidney.

24. Some Clinical Conditions Glomerular diseases Acute glomerulonephritis • Commonest cause is post streptococcal • Triad of oliguria, gross hematuria and hypertension. • In some cases there may be proteinuria or renal impairment. • Investigations: urine analysis, renal functions, ASOT, serum electrolytes, serum C3. • Therapy includes fluid and salt restriction, antihypertensive drugs, antistreptococcal antibiotics. In rare conditions dialysis may be required.

25. Some Clinical Conditions Glomerular diseases Minimal lesion nephrotic syndrome • Age 2-8 years • Albuminuria, hypoalbuminemia, hypercholoesterolemia, generalized edema. • In some cases there may be hematuria, hypertension or renal impairment. • Investigations: urine analysis, renal functions, serum lipids and proteins, CBC. • Therapy includes ample fluid intake, high protein diet, diuretics and albumin transfusion are controversial, corticosteroids in max dose except in presence of hypertension or infection

26. Some Clinical Conditions Tubular diseases De Toni-Debré-Fanconi syndrome • Generalized proximal renal tubular dysfunction with impaired reabsorption of aa, bicarbonate, glucose, P, urate, Na, K, Mg, Ca and low molecualr weight proteins • Either priamary or secondary. • Polyuria, dehydration, metabolic acidosis and glucosuria. Growth retardation and rickets • Investigations: urine analysis, serum electrolytes, ABG. • Therapy includes replacement of all substances lost in urine to keep their serum levels within normal.

27. Some Clinical Conditions Systemic hypertension

28. Some Clinical Conditions Systemic hypertension • Non-pharmacological treatment • Pharmacological treatment • Investigations, prevention and treatment of complications

29. Some Clinical Conditions Urinary tract infection • May be lower or upper UTI • Symptoms of lower UTI include dysuria, frequency, hematuria, suprapubic pain. Upper UTI presents with fever, loin pain. • Investigations: urine analysis, culture and antibiotic sensitivity, CBC. • Recurrence warrants investigation for predisposing factors.

31. Chronic Renal Failure • Progressive and usually irreversible loss of renal function. GFR <= 60 ml/min/1.73m2 • End stage renal disease (ESRD) ehen life cannot be maintained without renal replacement therapy (dialysis or transplantation). GFR<10-15 ml/min/1.73m2 • Clinical symptoms: • Oligo-polyhydramnios • Failure to thrive • Anorexia, nausea, vomiting, fatigue • Pruritis • Oliguria, polyuria • Delayed puberty • Pallor • Bone deformities • Hypertension • Edema

32. Chronic Renal Failure • Metabolic abnormalities • Hyponatremia • Hyperkalemia • Metabolic acidosis • Hyperuricemia • Hypocalcemia • Hyperphosphatemia • Renal osteodystrophy • Hypovitaminosis D • Hyperparathyroidism • Anemia • Growth failure • Delayed puberty • Cardiovascular disease • GI bleeding • Platelet dysfunction Treat hypertension Reduce proteinuria Correct anemia Reduce salt and fluid intake Control hyperlipidemia Control hyperphosphatemia Control hyperkalemia Treat renal osteodystrophy Revise drugs and their doses

34. Dialysis • Principle • Indications • Clinical manifestations (encephalopathy, pericarditis) • Metabolic problems not responding to medical treatment • Fluid overload • Rapid rise in parameters of renal function. • Modalities • Peritoneal dialysis (PD) • Hemodialysis (HD)

35. Dialysis

36. Dialysis

38. Drugs in Chronic Renal Failure and Dialysis

39. Drugs in Chronic Renal Failure and Dialysis

40. Renal Transplantation • Team • Donor • Recipient • Preparation • Procedure • Protocol • Follow up • Complications • Rejection