1. Pathophysiology and K-DOQI Guidelines Mahmoud El-Khatib, MD
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) 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 results in measurement of proteinuria
False +ve
-dehydration
-hematuria
-infection
-urine pH> 8
False –ve
-excessive hydration
-Para proteins

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

52. Treatment intervention to slow the progression of CKD
With proven effectiveness: strict glucose control in diabetes, strict Bp control, ACEI, ARB
Inconclusive: dietary protein restriction, lipid lowering therapy, partial correction of anemia

53. Prevention of acute GFR decline in CKD patients
Volume depletion
Intravenous radiographic contrast
Nephrotoxic agents like aminoglycosides, amphotericin B,NSAID’s, cyclosporine, tacrolimus
Obstruction of urinary tract

54. Follow up1
Measurements of serum creatinine for estimation of GFR, at least once a year.
More often measurements: if GFR <60, fast GFR decline>4ml/ year, risk factors for faster progression, ongoing treatment to slow progression, exposure to risk factors for acute GFR decline
Risk factors for faster decline of GFR related to the type of kidney disease, African-American race,lower baseline kidney function, male gender, older age

55. Follow up 2
Higher levels of proteinuria, lower serum albumin, higher Bp level, poor glycemic control, smoking.
Anemia, dyslipidemia are inconclusive risk factors for faster decline

56. CKD as a risk factor for CVD
Patients with CKD irrespective of the diagnosis are at increased risk for CVD
Increase in CAD, cerebro vascular disease, peripheral vascular disease, heart failure
Both traditional and CKD related risk factors may contribute to this increased risk
All patients with CKD should be considered highest risk group irrespective of levels of traditional CVD risk factors