Chronic Kidney Disease

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Chronic Kidney Disease

• Sumit Kumar, MD, MPH
• Presbyterian Hospital, Dallas, TX

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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)
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Chronic Kidney Disease

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

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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
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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

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Staging of Chronic Kidney Disease
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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

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MDRD GFR for Mr Lopez

• Diabetic, Hypertension, Metabolic Syndrome X
• Stage 3 CKD
• GFR 44 ml/min/1.73 m2

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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

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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

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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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Estimates of Subgroups at Increased Risk for CKD
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1992-93
1997-98
Steady Rise in the Rate of CKD in Medicare
population over the last decade
2002-03
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Common Causes and Presentation
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Genetic Considerations

• Autosomal dominant PKD
• Alports hereditary nephritis
• Familial FSGS
• Nephronopthisis
• Medullary cystic kidney disease
• Fabrys disease

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Natural History of CKD

• Most CKD has a logarithmic progression and is
  predictable

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Mr. Lopez Progressive Decline
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Clinical Features of Diabetic CKD
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Clinical Features of Non-Diabetic CKD
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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

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Symptoms of Uremia
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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

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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

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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

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Bone Disease
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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)

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Mineral Metabolism

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

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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

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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)
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Cardiac Complications
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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

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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

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Uremic Complications
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Therapeutics in CKD

• Non Pharmacologic
• Risk Factor Modification
• Pharmacologic
• Treatment of complications

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Therapeutics in CKD

• Non Pharmacologic
• Risk Factor Modification
• Pharmacologic
• Treatment of complications

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Therapeutics in CKD

• Non Pharmacologic
• Risk Factor Modification
• Pharmacologic
• Treatment of complications

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