Chronic Renal Failure

1. Chronic Renal Failure Pathophysiology and K-DOQI Guidelines Mahmoud El-Khatib, MD

2. Trends

5. Evaluation of CKD patients • Diagnosis • Co morbid conditions • Severity, assessed by level of kidney function • Complications related to level of kidney function • Risk of loss of kidney function • Risk for cardiovascular disease

6. Management of CKD patients • Specific therapy based on diagnosis • Evaluation and management of co morbid conditions • Slowing the loss of kidney function • Prevention and treatment of cardiovascular disease • Prevention and treatment of complications of decreased kidney function • Preparation for kidney failure and kidney replacement therapy • Replacement of kidney function by dialysis and transplantation, if signs and symptoms of uremia are present

8. Other management plan • Dosage adjustment based on level of kidney function • Detection of potentially adverse effects on kidney function or complications of CKD • Detection of drug interaction • Therapeutic drug monitoring, if possible • Self management behaviors should be incorporated to the plan • Referral to Nephrologist , when GFR < 30 ml/1.73m2

9. Individuals at increased risk of CKD • They should be assessed as part of routine health encounters, to determine whether they are at increased risk of developing CKD, based on clinical and sociodemographic factors • Individuals at increased risk of developing CKD should undergo testing for markers of kidney damage and to estimate GFR • Individuals at increased risk, but found not to have CKD, should be advised to follow a program of risk factors reduction, and if appropriate undergo repeat periodic evaluation

11. Clinical evaluation of patients with increased risk for CKD • All patients -Measurement of blood pressure -Serum creatinine to estimate GFR -Prot/ Cr or Alb/ Cr ratio in first morning or random spot urine -Examination of urine sediment

12. Selected patients -Ultrasound imaging -Serum electrolytes -Urinary concentration or dilution -Urinary acidification

13. Laboratory evaluation of patients with CKD • Serum creatinine to estimate GFR • Prot/ Cr or Alb/ Cr ratio in a morning or random spot urine • Examination of urine sediment • Imaging of the kidney. Usually by ultrasound • Serum electrolytes

14. Estimation of GFR • GFR should be estimated from prediction equations which take into account : serum creatinine, age, gender,race, body size • For adults: MDRD study, Cockcroft- Gault equations • For children: Schwartz and Counahan- Barratt equations • The serum creatinine alone should not be used to assess the level of kidney function

15. Estimation of GFR *MDRD GFR= 170x(sCr)-0.999x (age)-0.176x (BUN)-0.170 x(Alb)+0.38x (0.762 if female)x (1.180 if black) *Abbreviated MDRD GFR= 186x (sCr)-0.58x (Age)-0.28x (0.742 if female)x (1.120 if black)

16. Estimation of GFR *Cockcroft-Gault Crc= (140- age)x weight/ 72x sCR( 0.85 if female *Schwartz Crc= 0.55x length/ sCr *Counahan-Barratt GFR= 0.43xlength/sCr

17. Creatinine Clearance • Measurement of CrC using 24 hours urine collections does not improve the estimated GFR over that provided by prediction equations • It is useful is certain situations: patients with exceptional dietary intake like vegetarian diet, creatine supplements, amputation, malnutrition,muscle wasting, extremes of age and body size, obesity, disease of skeletal muscles, paraplegia or quadriplegia • Assessment of diet and nutritional status • Need to start dialysis

21. Assessment of proteinuria • It is usually not necessary to obtain a timed urine collection( 24 hrs) • First morning specimens are preferred, Random samples are acceptable • Patients with a positive dipstick test should have quantitative protein measurement. • Protein/ creatinine ratio, Albumin/ creatinine ratio are acceptable methods • Patients with +ve two tests spaced by 1 to 2 weeks are diagnosed to have persistent proteinuria

22. Assessment of proteinuria 2 • Albumin/creatinine ratio rather than protein/ creatinine ratio should be used if albumin excretion less than 500mg/ g of creatinine • Orthostatic proteinuria must be excluded by repeat measurement on a first morning specimen

25. False +ve -dehydration -hematuria -infection -urine pH> 8 False –ve -excessive hydration -Para proteins False results in measurement of proteinuria

26. Proteinuria as a risk factor • Proteinuria as a risk factor for cardiovascular disease • Proteinuria as a mediator and a marker of progressive kidney disease • Persistent massive proteinuria as the inciting factor that leads to nephritic syndrome

27. Markers for CKD other than protein • Abnormalities in the urine sediment • Abnormalities in the imaging studies • Tubular low-molecular weight proteins, specific mononuclear cells.

30. Level of GFR and Hypertension • High Bp is both a cause and complication of CKD • May develop early during the course of CKD and is associated with adverse outcomes • Faster loss of kidney function • Development of cardiovascular disease • Optimal Bp of <130/85 • Multi drug therapy is the rule

32. Level of GFR and Anemia • Patients with GFR < 60 should be evaluated for anemia • Anemia of CKD should be evaluated and treated • The main cause is Erythropoietin deficiency • Other causes of anemia should be evaluated

35. Level of GFR and nutritional status • Malnutrition develops during the course of CKD and associated with adverse outcomes • Low protein and calorie intake is an important cause of malnutrition in CKD • Patients with GFR of <60 should undergo assessment of dietary protein and energy intake and nutritional status • Patients with GFR <20 should be evaluated by serial measurements of albumin, edema-free body weight, nPNA • BMI < 23.6 is indicative of malnutrition

41. Level of GFR and bone disease • Bone disease and disorders of calcium and phosphorus metabolism develop during the course of CKD • Patients with GFR <60 should be evaluated • Elevated PTH seems to be an early marker of abnormal bone mineral metabolism

45. Neuropathy • Neuropathy develops during the course of CKD and may become symptomatic • May be manifested as encephalopathy, peripheral polyneuropathy, autonomic dysfunction, sleep disorders, peripheral mononeuropathy • There is insufficient evidence to define a specific threshold level of GFR that is associated with an increased prevalence or severity of neuropathy

47. Level of GFR and indices of functioning and well-being • Impairments in domains of functioning and well-being develop during the course of CKD • May be related to socio-demographic factors, conditions causing CKD, complication of kidney disease or possibly directly related to reduced GFR • Patients with GFR<60 should undergo regular assessment for impairment of functioning and well-being • Establish a baseline and monitor changes • Assess the effect of interventions

50. Factors affecting functioning and well-being of CKD patients • Late referral and inadequate pre-dialysis care • Effect of illness on physical,psychological and social functioning • Satisfaction with health and care • Complications of CKD: anemia, malnutrition,bone disease, neuropathy • Co morbid conditions: diabetes, cardiovascular disease