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

                                                                                                                                                                                                             Trends

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

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

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

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

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

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

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

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

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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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