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Chronic Kidney Disease

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Title: Chronic Kidney Disease


1
Chronic Kidney Disease
  • Sumit Kumar, MD, MPH
  • Presbyterian Hospital, Dallas, TX

2
The Story of Mr. George Lopez
  • 45 yr HM with Diabetes for 10 yrs, reasonably
    well controlled
  • PMH
  • Hypertension for 7 yrs..well controlled
  • BMI of 30
  • Dyslipidemia
  • Fam Hx Diabetes
  • Soc Hx Sedentary non smoker Comedian
  • Exam
  • 139/85 Mild Obesity, rest fairly normal
  • Labs
  • BUN 28, Creatinine 1.8, Urine protein (dipstick)
    2

3
Chronic Kidney Disease
  • Definition
  • Chronic, irreversible loss of kidney function
    attributable to loss of functional nephron mass
    pathophysiologic processes for more than 3
    months.

4
Pathophysiology of CKD
  • Final Common Pathway is loss of nephron mass

Diabetes Hypertension
Chronic GN Cystic Disease
Tubulointerstitial disease
Mediated by vasoactive molecules, cytokines and
growth factors, renin angiotensin axis
5
Estimation of GFR
  • Modification of Diet in Renal Disease (MDRD)
    Formula
  • Estimated GFR 1.86 (Serum Creat) -1.154 X (age)
    -0.203
  • Multiply by 0.742 for women
  • Multiply by 1.21 for African Americans
  • Cockroft Gault Formula
  • (140 age) X Body Weight (Kg)
  • 72 X Serum Creatinine (mg/dL)
  • Multiply by 0.85 for women

6
Staging of Chronic Kidney Disease
7
Who is at Risk for CKD?
  • Family history of heritable renal disease
  • Diabetes
  • Hypertension
  • Auto-immune disease
  • Old age
  • Prior episode of ARF
  • Current evidence of renal damage, even with
    normal or increased GFR

8
MDRD GFR for Mr Lopez
  • Diabetic, Hypertension, Metabolic Syndrome X
  • Stage 3 CKD
  • GFR 44 ml/min/1.73 m2

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10
Etiology and Epidemiology
  • 6 of the US population has CKD (Stage 1 and 2)
  • Additional 4-5 have Stage 3 and 4 CKD
  • Diabetic nephropathy
  • Hypertension chronic ischemic nephropathy
  • Very high CV disease burden

11
Monitoring of CKD
  • Serial measurements of
  • Creatinine
  • GFR
  • Albumin
  • Albumin-creatinine ratio in the 1st morning
    sample
  • Electrolytes including HCO3, Ca, Phos alkaline
    phosphatase, iron studies, intact PTH
  • Renal sonogram
  • Renal biopsy

12
Symptoms of CKD
  • Stage 1 and 2
  • Asymptomatic, hypertension
  • Stage 3 and 4
  • Anemia loss of energy
  • Decreasing appetite poor nutrition
  • Abnormalities in Calcium, Phosphorus metabolism
  • Sodium, water, potassium and acid base
    abnormalities
  • Stage 5
  • All of the above accentuated eventually overt
    uremia

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14
Estimates of Subgroups at Increased Risk for CKD
15
1992-93
1997-98
Steady Rise in the Rate of CKD in Medicare
population over the last decade
2002-03
16
Common Causes and Presentation
17
Genetic Considerations
  • Autosomal dominant PKD
  • Alports hereditary nephritis
  • Familial FSGS
  • Nephronopthisis
  • Medullary cystic kidney disease
  • Fabrys disease

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23
Natural History of CKD
  • Most CKD has a logarithmic progression and is
    predictable

24
Mr. Lopez Progressive Decline
25
Clinical Features of Diabetic CKD
26
Clinical Features of Non-Diabetic CKD
27
Pathophysiology of Uremia
  • Azotemia refers to the retention of nitrogenous
    waste products. Uremia advanced stages of
    azotemia with end organ dysfunction
  • Accumulation of products of protein metabolism
  • Urea anorexia, malaise, vomiting and headaches
  • Loss of other renal functions
  • Erythropoietin deficiency anemia
  • Metabolic bone disease endocrine abnormalities
  • Fluid, electrolyte and acid base disorders

28
Symptoms of Uremia
29
Sodium and water Imbalance
  • Glomerulotubular feedback is disrupted sodium
    retention, contributes to hypertension
    hyponatremia is unusual.
  • Higher than usual doses for diuretics. In
    situations with volume depletion can be severe,
    because of inadequate sodium retention.
  • Treatment Salt restriction high doses of
    diuretics

30
Potassium Imbalance
  • Potassium
  • GI excretion is augmented
  • Constipation, dietary intake, protein catabolism,
    hemolysis, hemorrhage, transfusion of stored
    blood, metabolic acidosis,
  • Drugs ACE inhibitors, ARBs, B blockers, K
    sparing diuretics and NSAIDs
  • Hyporeninemic hypoaldosteronism Diabetes, sickle
    cell disease

31
Acid Base Imbalance
  • Damaged kidneys are unable to excrete the 1
    mEq/kg/d of acid generated by metabolism of
    dietary proteins.
  • NH3 production is limited because of loss of
    nephron mass
  • Decreased filtration of titrable acids
    sulfates, phosphates
  • Decreased proximal tubular bicarb reabsorption,
    decreased positive H ion secretion
  • Arterial pH 7.33 - 7.37 serum HCO3 rarely below
    15 buffering offered by bone calcium carbonate
    and phosphate
  • Should be maintained over 21
  • Treatment Sodium bicarbonate, calcium carbonate,
    sodium citrate

32
Bone Disease
33
Treatment of Secondary Hyperparathyroidism
  • Phosphorus control in diet
  • Phosphate binders
  • Calcium acetate (Phoslo), calcium carbonate
    (TUMS), sevelamer (Renagel) , lanthanum
    (Fosrenol)
  • Oral Vitamin D
  • Calcimemetic agent Cinacalcet (Sensipar)

34
Mineral Metabolism
  • Calciphylaxis
  • Calcemic uremic arteriopathy
  • Extraosseous/metastatic calcification of soft
    tissues and blood vessels
  • Devastating complication
  • Treatment controversial
  • Sodium thiosulfate
  • Parathyroidectomy

35
Cardiovascular Abnormalities
  • Leading cause of morbidity and mortality in
    patients with CKD at all stages
  • Ischemic CAD
  • Hypertension and LVH
  • Congestive heart failure
  • Uremic pericarditis

36
Trends in the interactions of diabetes,
congestive heart failure, CKD 2002-2003
  • LVH and dilated CM are the most ominous risk
    factors for excess mortality and morbidity
  • High cardiac output
  • Extracellular fluid overloa
  • AV shunt
  • Anemia

Medicare general Medicare CKD patients
continuously enrolled in Medicare Parts A B for
two consecutive years (numbers estimated from 5
percent sample)
37
Cardiac Complications
38
Hematological Abnormalities
  • Anemia
  • Chronic blood loss, hemolysis, marrow suppression
    by uremic factors, and reduced renal production
    of EPO
  • Normocytic, normochromic
  • Rx Iron and Epo as needed
  • Coagulopathy
  • Mainly platelet dysfunction decreased activity
    of platelet factor III, abnormal platelet
    aggregation and adhesiveness and impaired
    thrombin consumption
  • Increased propensity to bleed post surgical, GI
    Tract, pericardial sac, intracranial
  • Increased thrombotic tendency nephrotic syndrome

39
Other Abnormalities
  • Neuromuscular
  • Central, peripheral and autonomic neuropathy
  • Peripheral Sensory/Motor Neuropathy
  • Stage 4 for more than 6 months
  • Restless leg syndrome
  • Gastrointestinal
  • Uremic fetor
  • Gastritis, peptic disease, mucosal ulcerations,
    AVMs
  • Endocrine
  • Glucose metabolism
  • Estrogen levels amenorrhea, frequent abortions
  • Male oligospermia, germinal cell dysplasia,
    delayed sexual maturation
  • Dermatologic
  • Pallor, ecchymoses, hematomas, calciphylaxis,
    pruritus, uremic frost

40
Uremic Complications
41
Therapeutics in CKD
  • Non Pharmacologic
  • Risk Factor Modification
  • Pharmacologic
  • Treatment of complications

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43
Therapeutics in CKD
  • Non Pharmacologic
  • Risk Factor Modification
  • Pharmacologic
  • Treatment of complications

44
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45
Therapeutics in CKD
  • Non Pharmacologic
  • Risk Factor Modification
  • Pharmacologic
  • Treatment of complications

46
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