1. Chronic Kidney Disease (CKD)
Shiva Seyrafian
IKRC- IUMS
1392/2/19____9/5/2013

2. The Story of Mr. G. L.
45 yr 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. Epidemiology CKD affects about 26 million people in the US
Approximately 19 million adults are in the early stages of the disease
On the rise due to increasing prevalence of diabetes and hypertension
Total cost of ESRD in US was approximately $40 billion in 2008

5. 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

6. Pathophysiology Repeated injury to kidney
The causes of acute or chronic kidney disease are traditionally classified by that portion of the renal anatomy most affected by the disorder
The two major causes of reduced renal perfusion are volume depletion and/or relative hypotension. This may result from true hypoperfusion due to bleeding, gastrointestinal, urinary, or cutaneous losses, or to effective volume depletion in heart failure, shock, or cirrhosis
Various vascular diseases can also lead to kidney disease.
Direct etiologies from kidney: Tubular and interstitial disease, Glomerular disease, Obstructive uropathy
Acute tubular necrosis — 45 percent
Prerenal — 21 percent
Acute or chronic kidney disease — 13 percent (mostly due to acute tubular necrosis and prerenal disease)
Urinary tract obstruction — 10 percent (most often older men with prostatic disease)
Glomerulonephritis or vasculitis — 4 percent
Acute interstitial nephritis — 2 percent
Atheroemboli — 1 percent

7. Staging of Chronic Kidney Disease
Stage
Description
GFR (ml/min/1.73 m2)
At increased risk
90 (with CKD risk factors) 1
Kidney damage with normal or increased GFR 90 2
Kidney damage with Mildly decreased GFR
60-89 3
Moderately decreased GFR
30-59 4
Severely decreased GFR
15-29 5
Renal Failure
<15 (or dialysis)

8. 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

9. Estimation of GFR Modification of Diet in Renal Disease (MDRD) Formula
Estimated GFR = 1.86 (Serum Creat) X (age)
Multiply by 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

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

11. Stages in Progression of CKD and Therapeutic Strategies
AJKD 2002: 39(2)

13. 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

14. Monitoring of CKD Serial measurements of Albumin
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

15. Symptoms of CKD Stage 1 and 2 Stage 3 and 4 Stage 5
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

16. Symptoms Hematuria Flank pain Edema Hypertension Signs of uremia
Lethargy and fatigue
Loss of appetite
If asymptomatic may have elevated serum creatinine concentration or an abnormal urinalysis

17. Common Causes and Presentation
Clinical Presentation
Diabetic kidney disease
History of diabetes, proteinuria and retinopathy
Hypertension
Elevated BP, normal UA, family history
Non diabetic glomerular disease
Nephritic or nephrotic presentations
Cystic kidney disease
Urinary symptoms, abnormal sediment, radiologic findings
Tubulointerstitial disease
UTI, reflux, chronic med use, drugs, imaging abnormalities, urine concentrating defects

19. Risk Factors Age of more than 60 years Hypertension and Diabetes
Responsible for 2/3 of cases
Cardiovascular disease
Family history of the disease.
Race and ethnicity
Highest incidence is for African Americans
Hispanics have higher incidence rates of ESRD than non-Hispanics.
_followed by American Indians and Alaska Natives, then Asian Americans and native Hawaiians and other Pacific Islanders, and finally Caucasians.

20. Convergence of Genetic Factors
Genes for heart and vascular disease
Genes that maintain ionic balance
Genes for glomerulonephritis
Genes for diabetes
Genes that may be involved in inherited renal diseases

21. Genetic Considerations
Autosomal dominant PKD
Alport’s hereditary nephritis
Familial FSGS
Nephronopthisis
Medullary cystic kidney disease
Fabry’s disease

25. Natural History of CKD
Most CKD has a logarithmic progression and is predictable

26. Mr. G. L. – Progressive Decline

27. Clinical Features of Diabetic CKD

28. Symptoms of Uremia Organ System Symptoms Signs General
Fatigue, weakness
Sallow-appearing, chronically ill
Skin
Pruritus, easy bruisability
Pallor, ecchymoses,
excoriations, edema, xerosis
ENT
Metallic taste in mouth, epistaxis
Urinous breath / fetor
Eye
Pale conjunctiva
Pulmonary
Shortness of breath
Rales, pleural effusion
Cardiovascular
Dyspnea on exertion, retrosternal pain on inspiration (pericarditis)
Hypertension, cardiomegaly,
friction rub
Gastrointestinal
Anorexia, nausea, vomiting, hiccups
Genitourinary
Nocturia, impotence
Isosthenuria
Neuromuscular
Restless legs, numbness and cramps in legs
Neurologic
Generalized irritability and inability to concentrate, decreased libido
Stupor, asterixis, myoclonus,
peripheral neuropathy

29. Sodium and water Imbalance
Sodium retention, contributes to hypertension.
Higher than usual doses for diuretics. In situations with volume depletion – can be severe, because of inadequate sodium retention.

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 H ion secretion
Arterial pH: ; serum HCO3 rarely below 15 – buffering offered by bone calcium carbonate and phosphate
Should be maintained over 21

33. Bone Disease

34. Young boy on HD several years with 2nd hyperpara, brown tumor and cyst, 91/8

35. Mineral Metabolism Calciphylaxis
PTH, P, Ca x P, Active Vitamin D, Fetuin A, Matrix Gla protein ( warfarin)
Calcemic uremic arteriopathy
Extraosseous/metastatic calcification of soft tissues and blood vessels
Devastating complication

38. Reza ahmadi niya –alzahra univ. haospit
Reza ahmadi niya –alzahra univ. haospit. HD, renal osteodystrophy 91/ 7, 69 Y/O

39. Reza ahmadi niya –alzahra univ. haospit
Reza ahmadi niya –alzahra univ. haospit. HD, renal osteodystrophy 91/ 7, 69 Y/O

40. Reza ahmadi niya –alzahra univ. haospit
Reza ahmadi niya –alzahra univ. haospit. HD, renal osteodystrophy 91/ 7, 69 Y/O

41. 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

42. Cardiovascular risks in CKD
Reduced glomerular filtration rate (GFR) and proteinuria are both independently associated with an increased risk of cardiovascular events.
 The increase in cardiovascular risk associated with CKD.
The risk of death, particularly due to cardiovascular disease, is typically higher than the risk of eventually requiring renal replacement therapy.

43. Pericarditis
Uremic pericarditis:There is a correlation with the degree of azotemia (the BUN is usually >60 mg/dL), Except in the case of systemic immune disorders (such as lupus erythematosus or scleroderma), there is no relationship with the underlying cause of renal failure.
Dialysis-associated pericarditis: two causses: inadequate dialysis (ie, the patient has uremic pericarditis) and/or fluid overload.

44. Pericarditis
Unusual feature of uremic pericarditis:  the electrocardiogram does not show the typical diffuse ST and T wave elevations observed with other causes of acute pericarditis. 
With the development of cardiac tamponade, typical ECG changes (eg, electrical alternans) may occur

45. Cardiac Complications

46. Lipid abnormalities
The most common dyslipidemia in CKD patients is hypertriglyceridemia, whereas the total cholesterol concentration can be normal or low, perhaps due in part to malnutrition.
 Some have found that low (not high) serum cholesterol values are associated with increased mortality.

47. Lipid abnormalities
Some have found no association between lipid levels and mortality among patients with CKD.
 Reflect the adverse effect of malnutrition and chronic inflammation upon mortality.

48. Hematological Abnormalities
Anemia: Chronic blood loss, hemolysis, marrow suppression by uremic factors, and reduced renal production of EPO
Normocytic, normochromic
Coagulopathy:
Clinical bleeding in uremia is typically cutaneous, including easy bruising and mucosal bleeding, or may occur in response to injury or invasive procedures.
Less frequent is epistaxis, gingival bleeding, or hematuria.
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

49. Other Abnormalities Neuromuscular
Central, peripheral and autonomic neuropathy
Motor Neuropathy: muscle atrophy, myoclonus, and eventual paralysis.
Mononeurpathy:
Carpal tunnel syndrome
Dysfunction of both the vestibular and cochlear divisions of the eighth cranial nerve 
Polyneuropathy: paresthesias, burning sensations, and pain — tend to precede the motor symptoms. The initial finding in uremic polyneuropathy is loss of position and vibration sense in the toes and decreased deep tendon reflexes, beginning with the Achilles reflex.
The hands may become involved. 
Sensory syndromes: restless leg syndrome, the burning foot syndrome, Paradoxical heat sensation 

50. Other Abnormalities Gastrointestinal Endocrine Uremic fetor
Gastritis, peptic disease, mucosal ulcerations,
Endocrine
Glucose metabolism
Some patients have hyperglycemia in response to oral and intravenous glucose loads, while others are able to maintain normoglycemia by raising plasma insulin levels.  Accumulation of a uremic toxin or toxins and excess parathyroid hormone (PTH), resulting from abnormalities in phosphate and vitamin D metabolism, are thought to be responsible for the insulin resistance

51. Other Abnormalities
HYPOGLYCEMIA   spontaneous hypoglycemia. This complication can be seen in both diabetic and nondiabetic subjects.
Estrogen levels – amenorrhea, frequent abortions
Male: oligospermia, germinal cell dysplasia, delayed sexual maturation
Dermatologic
Pallor, ecchymoses, hematomas, calciphylaxis, pruritus, uremic frost

52. Dermatologic changes of Uremic

53. Uremic Complications

54. What Should Patients and Doctors Know
In general CKD is characterized by a gradual loss of the kidney’s filtration capacity.
Markers Don’t tell everything
Source:

55. What Should Patients and Doctors Know
Prevention
Keep diabetes and blood pressure controlled
If at risk perform screening tests
Reduce exposure to nephrotoxic drugs
Eat right and exercise
Know your family history
If you have a positive family history ask doctor to perform common screening tests for kidney function.

58. Thanksمتشکرم