This document outlines the topics to be covered in a discussion of chronic kidney disease (CKD) and uremia. It includes sections on the introduction, clinical and laboratory manifestations, evaluation and management of CKD patients, and treatment approaches. Specific subtopics are listed under each main section, such as the pathophysiology and risk factors of CKD, fluid and electrolyte abnormalities seen in uremia, and methods for slowing CKD progression and managing complications. Common etiologies, epidemiology, and definitions of CKD and uremia are also outlined.

1. Topic Outline
• I INTRODUCTION
• II CLINICAL AND LABORATORY MANIFESTATIONS OF
CHRONIC KIDNEY DISEASE AND UREMIA
• III EVALUATION AND MANAGEMENT OF PATIENTS
WITH CKD
• IV TREATMENT

2. Topic Outline
I INTRODUCTION
A. PATHOPHYSIOLOGY OF CHRONIC KIDNEY DISEASE
B. IDENTIFICATION OF RISK FACTORS AND STAGING
OF CKD
C. ETIOLOGY AND EPIDEMIOLOGY
D. PATHOPHYSIOLOGY AND BIOCHEMISTRY OF
UREMIA

3. Topic Outline
II CLINICAL AND LABORATORY MANIFESTATIONS OF
CHRONIC KIDNEY DISEASE AND UREMIA
A. FLUID, ELECTROLYTE, AND ACID-BASE DISORDERS
1. Sodium and water homeostasis
2. Potassium homeostasis
3. Metabolic acidosis
B. DISORDERS OF CALCIUM AND PHOSPHATE METABOLISM
1. Bone manifestations of CKD
2. Calcium, phosphorus, and the cardiovascular system
3. Other complications of abnormal mineral metabolism
C. CARDIOVASCULAR ABNORMALITIES
1. Ischemic vascular disease
2. Heart failure
3. Hypertension and left ventricular hypertrophy
4. Pericardial disease

4. Topic Outline
II CLINICAL AND LABORATORY MANIFESTATIONS
OF CHRONIC KIDNEY DISEASE AND UREMIA
D. HEMATOLOGIC ABNORMALITIES
1. Anemia
2. Abnormal hemostasis
E. NEUROMUSCULAR ABNORMALITIES
F. GASTROINTESTINAL AND NUTRITIONAL ABNORMALITIES
G. ENDOCRINE-METABOLIC DISTURBANCES
H. DERMATOLOGIC ABNORMALITIES

5. Topic Outline
III EVALUATION AND MANAGEMENT OF
PATIENTS WITH CKD
A.INITIAL APPROACH
1.History and physical examination
2.Laboratory investigation
3.Imaging studies
4.Renal biopsy
B.ESTABLISHING THE DIAGNOSIS AND ETIOLOGY
OF CKD

6. Topic Outline
IV TREATMENT
A. SLOWING THE PROGRESSION OF CKD
1. Reducing Intraglomerular Hypertension and Proteinuria
B. SLOWING PROGRESSION OF DIABETIC RENAL DISEASE
1. Control of Blood Glucose
2. Control of Blood Pressure and Proteinuria
3. Protein Restriction
C. MANAGING OTHER COMPLICATIONS OF CHRONIC KIDNEY
DISEASE
1. Medication Dose Adjustment
2. Preparation for Renal Replacement Therapy
3. Patient Education

7. Abbreviations
• NKF - National Kidney Foundation
• KDOQI - Kidney Disease Outcomes Quality Initiative
• KDIGO - Kidney Disease Improving Global Outcomes

8. What is CKD?
• CKD is defined by the
–presence of kidney damage or
decreased kidney function
–for three or more months,
–irrespective of the cause.

9. What is CKD?
• The persistence of the damage or decreased
function for at least three months is necessary to
distinguish CKD from acute kidney disease.
• Kidney damage refers to pathologic
abnormalities, whether established via:
1. renal biopsy or
2. imaging studies, or
3. inferred from markers such as
a) urinary sediment abnormalities or
b) increased rates of urinary albumin excretion.

10. What is CKD?
• Chronic kidney disease is defined based on the
presence of either kidney damage or decreased
kidney function for three or more months,
irrespective of cause.
• Criteria:
Duration ≥3 months, based on documentation or
inference
Glomerular filtration rate (GFR) <60 mL/min/1.73 m2
Kidney damage, as defined by structural abnormalities or
functional abnormalities other than decreased GFR

11. CHRONIC KIDNEY DISEASE
Duration ≥3 months, based on documentation or
inference
Duration is necessary to distinguish chronic from acute kidney
diseases.
1. Clinical evaluation can often suggest duration
2. Documentation of duration is usually not available in
epidemiologic studies

12. CHRONIC KIDNEY DISEASE
GFR is the best overall index of kidney function in health and
disease.
1. The normal GFR in young adults is approximately 125
mL/min/1.73 m2; GFR <15 mL/min/1.73 m2 is defined as
kidney failure
2. Decreased GFR can be detected by current estimating
equations for GFR based on serum creatinine (estimated
GFR) but not by serum creatinine alone
3. Decreased estimated GFR can be confirmed by measured
GFR
Glomerular filtration rate (GFR) <60 mL/min/1.73 m2

13. CHRONIC KIDNEY DISEASE
A) Pathologic abnormalities (examples). Cause is based on
underlying illness and pathology. Markers of kidney damage may
reflect pathology.
1. Glomerular diseases (diabetes, autoimmune diseases, systemic
infections, drugs, neoplasia)
2. Vascular diseases (atherosclerosis, hypertension, ischemia,
vasculitis, thrombotic microangiopathy)
3. Tubulointerstitial diseases (urinary tract infections, stones,
obstruction, drug toxicity)
4. Cystic disease (polycystic kidney disease)
Kidney damage, as defined by structural abnormalities or functional
abnormalities other than decreased GFR

14. CHRONIC KIDNEY DISEASE
B) History of kidney transplantation. In addition to pathologic
abnormalities observed in native kidneys, common pathologic
abnormalities include the following:
1. Chronic allograft nephropathy (non-specific findings of tubular
atrophy, interstitial fibrosis, vascular and glomerular sclerosis)
2. Rejection
3. Drug toxicity (calcineurin inhibitors)
4. BK virus nephropathy
5. Recurrent disease (glomerular disease, oxalosis, Fabry disease)
Kidney damage, as defined by structural abnormalities or functional
abnormalities other than decreased GFR

15. CHRONIC KIDNEY DISEASE
C) Albuminuria as a marker of kidney damage (increased glomerular
permeability, urine albumin-to-creatinine ratio [ACR] >30 mg/g).*
1. The normal urine ACR in young adults is <10 mg/g. Urine ACR
categories 10-29, 30-300 and >300 mg are termed "high normal,
high, and very high" respectively. Urine ACR >2200 mg/g is
accompanied by signs and symptoms of nephrotic syndrome
2. Threshold value corresponds approximately to urine dipstick
values of trace or 1+
3. High urine ACR can be confirmed by urine albumin excretion in a
timed urine collection
Kidney damage, as defined by structural abnormalities or functional
abnormalities other than decreased GFR

16. CHRONIC KIDNEY DISEASE
D) Urinary sediment abnormalities as markers of kidney
damage
1. RBC casts in proliferative glomerulonephritis
2. WBC casts in pyelonephritis or interstitial nephritis
3. Oval fat bodies or fatty casts in diseases with proteinuria
4. Granular casts and renal tubular epithelial cells in many
parenchymal diseases (non-specific)
Kidney damage, as defined by structural abnormalities or functional
abnormalities other than decreased GFR

17. CHRONIC KIDNEY DISEASE
E) Imaging abnormalities as markers of kidney damage (ultrasound,
computed tomography and magnetic resonance imaging with or
without contrast, isotope scans, angiography).
1. Polycystic kidneys
2. Hydronephrosis due to obstruction
3. Cortical scarring due to infarcts, pyelonephritis or vesicoureteral
reflux
4. Renal masses or enlarged kidneys due to infiltrative diseases
5. Renal artery stenosis
6. Small and echogenic kidneys (common in later stages of CKD
due to many parenchymal diseases)
Kidney damage, as defined by structural abnormalities or functional
abnormalities other than decreased GFR

18. PATHOPHYSIOLOGY OF
CHRONIC KIDNEY DISEASE
Two broad sets of mechanisms
of damage:
1. initiating mechanisms specific to the underlying
etiology
2. a set of progressive mechanisms
- hyperfiltration and hypertrophy of the
remaining viable nephrons

19. PATHOPHYSIOLOGY OF
CHRONIC KIDNEY DISEASE
Two broad sets of mechanisms
of damage:
1. initiating mechanisms specific to the underlying
etiology
2. a set of progressive mechanisms
- hyperfiltration and hypertrophy of the
remaining viable nephrons

20. PATHOPHYSIOLOGY OF
CHRONIC KIDNEY DISEASE
Increased intrarenal activity of the renin-
angiotensin axis appears to contribute
both to:
initial adaptive hyperfiltration
the subsequent maladaptive hypertrophy
and sclerosis (TGF-β)

21. Left: Schema of the normal glomerular
architecture.
Right: Secondary glomerular changes

22. IDENTIFICATION OF RISK FACTORS AND
STAGING OF CKD
Risk factors:
1. hypertension,
2. diabetes mellitus,
3. autoimmune disease,
4. older age,
5. African ancestry,
6. a family history of renal disease,
7. a previous episode of acute kidney injury,
8. and the presence of
a. proteinuria,
b. abnormal urinary sediment, or
c. structural abnormalities of the urinary tract

23. Recommended Equations for Estimation of Glomerular
Filtration Rate (GFR) Using
Serum Creatinine Concentration (PCr), Age, Sex, Race, and
Body Weight
1) Equation from the Modification of Diet in Renal
Disease study∗ (MDRD)
2) Cockcroft-Gault equation

24. CKD

29. IDENTIFICATION OF RISK FACTORS AND
STAGING OF CKD
Chronic renal damage
Persistence in the urine of:
 >17 mg of albumin per gram of creatinine in
adult males and
 25 mg albumin per gram of creatinine in adult
females

30. ETIOLOGY AND EPIDEMIOLOGY
Leading Categories of Etiologies
of CKD∗
 Diabetic glomerular disease
 Glomerulonephritis
 Hypertensive nephropathy
 Primary glomerulopathy with hypertension
 Vascular and ischemic renal disease
 Autosomal dominant polycystic kidney disease
 Other cystic and tubulointerstitial nephropathy

31. ETIOLOGY AND EPIDEMIOLOGY
Newly diagnosed CKD:
present with hypertension
CKD is often attributed to hypertension:
When no overt evidence for a primary
glomerular or tubulointerstitial kidney disease process
is present

32. ETIOLOGY AND EPIDEMIOLOGY
Two Categories:
1) patients with a silent primary
glomerulopathy
2) patients in whom progressive
nephrosclerosis and hypertension is
the renal correlate of a systemic vascular
disease

33. Multiple Functions of the Kidneys
1) Excretion of metabolic waste products
and foreign chemicals
2) Regulation of water and electrolyte
balances
3) Regulation of body fluid osmolality and
electrolyte concentrations
4) Regulation of arterial pressure
5) Regulation of acid-base balance
6) Secretion, metabolism, and excretion
of hormones
7) Gluconeogenesis

34. PATHOPHYSIOLOGY AND BIOCHEMISTRY
OF UREMIA
Elevated waste products:
Hundreds of toxins, water-soluble,
hydrophobic, protein- bound, charged, and uncharged
compounds, guanidino
compounds, urates and hippurates, products of
nucleic acid metabolism, polyamines, myoinositol,
phenols, benzoates,
and indoles
‘middle molecules’

35. PATHOPHYSIOLOGY AND BIOCHEMISTRY
OF UREMIA
A host of metabolic and endocrine
functions normally performed by the
kidneys is also impaired or suppressed:
 anemia,
 malnutrition,
 and abnormal metabolism of
carbohydrates, fats, and proteins

36. PATHOPHYSIOLOGY AND BIOCHEMISTRY
OF UREMIA
Urinary retention, decreased degradation,
or abnormal regulation of hormones
PTH,
FGF-23,
insulin,
glucagon,
steroid hormones including vitamin D and sex
hormones, and
prolactin

37. 3 Spheres of dysfunction of Uremic Syndrome
Toxins
Homeostasis
Progressive
systemic
inflammation
URE
M

38. CLINICAL AND LABORATORY
MANIFESTATIONS OF
CHRONIC KIDNEY DISEASE
AND UREMIA

39. CLINICAL ABNORMALITIES IN UREMIA
1. Fluid and electrolyte disturbances
2. Endocrine-metabolic disturbances
3. Neuromuscular disturbances
4. Cardiovascular and pulmonary disturbances
5. Dermatologic disturbances
6. Gastrointestinal disturbances
7. Hematologic and immunologic disturbances
(I) improves with an optimal program of dialysis and related
therapy;
(P) persist or even progress, despite an optimal program; (D)
develops only after initiation of dialysis therapy.

40. CLINICAL ABNORMALITIES IN UREMIA
1. Fluid and electrolyte disturbances
a. Volume expansion (I)
b. Hyponatremia (I)
c. Hyperkalemia (I)
d. Hyperphosphatemia (I)
(I) improves with an optimal program of dialysis and related therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.

41. CLINICAL ABNORMALITIES IN UREMIA
1. Secondary
hyperparathyroidism (I or P)
2. Adynamic bone (D)
3. Vitamin D–deficient
osteomalacia (I)
4. Carbohydrate resistance (I)
5. Hyperuricemia (I or P)
6. Hypertriglyceridemia (I or P)
7. Increased Lp(a) level (P)
8. Decreased high-density
lipoprotein level (P)
9. Protein-energy malnutrition (I
or P)
10.Impaired growth and
development (P)
11.Infertility and sexual
dysfunction (P)
12.Amenorrhea (I/P)
13.β2-Microglobulin–associated
amyloidosis (P or D)
(I) improves with an optimal program of dialysis and related
therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
2. Endocrine-metabolic disturbances

42. CLINICAL ABNORMALITIES IN UREMIA
1. Fatigue (I)b
2. Sleep disorders (P)
3. Headache (P)
4. Impaired mentation (I)b
5. Lethargy (I)b
6. Asterixis (I)
7. Muscular irritability
8. Peripheral neuropathy (I or
P)
9. Restless legs syndrome (I
or P)
10.Myoclonus (I)
11.Seizures (I or P)
12.Coma (I)
13.Muscle cramps (P or D)
14.Dialysis disequilibrium
syndrome (D)
15.Myopathy (P or D)
(I) improves with an optimal program of dialysis and related
therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
3. Neuromuscular disturbances

43. CLINICAL ABNORMALITIES IN UREMIA
1. Arterial hypertension (I or
P)
2. Congestive heart failure or
pulmonary edema (I)
3. Pericarditis (I)
4. Hypertrophic or dilated
cardiomyopathy (I, P, or D)
5. Uremic lung (I)
6. Accelerated
atherosclerosis (P or D)
7. Hypotension and
arrhythmias (D)
8. Vascular calcification (P or
D)
(I) improves with an optimal program of dialysis and related
therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
4. Cardiovascular and pulmonary disturbances

44. CLINICAL ABNORMALITIES IN UREMIA
1.Pallor (I)b
2.Hyperpigmentation (I, P, or D)
3.Pruritus (P)
4.Ecchymoses (I)
5.Nephrogenic fibrosing dermopathy (D)
6.Uremic frost (I)
(I) improves with an optimal program of dialysis and related
therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
5. Dermatologic disturbances

45. CLINICAL ABNORMALITIES IN UREMIA
1.Anorexia (I)
2.Nausea and vomiting (I)
3.Gastroenteritis (I)
4.Peptic ulcer (I or P)
5.Gastrointestinal bleeding (I, P, or D)
6.Idiopathic ascites (D)
7.Peritonitis (D)
(I) improves with an optimal program of dialysis and related
therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
6. Gastrointestinal disturbances

46. CLINICAL ABNORMALITIES IN UREMIA
1.Anemia (I)b
2.Lymphocytopenia (P)
3.Bleeding diathesis (I or D)b
4.Increased susceptibility to infection
5.(I or P)
6.Leukopenia (D)
7.Thrombocytopenia (D)
(I) improves with an optimal program of dialysis and related
therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
7. Hematologic and immunologic disturbances

47. FLUID, ELECTROLYTE, AND ACID-BASE
DISORDERS
S
O
D
I
U
M

48. FLUID, ELECTROLYTE, AND ACID-BASE
DISORDERS
Hyponatremia – water restriction
ECFV expansion – salt restriction
Thiazides – limited utility in stages 3-5 CKD
- loop diuretics needed
Loop Diuretics resistance – Higher doses
Metolazone – combined with loop diuretics, which inhibits the
sodium chloride co-transporter of the distal convoluted tubule, can
help effect renal salt excretion
S
O
D
I
U
M

49. FLUID, ELECTROLYTE, AND ACID-BASE
DISORDERS
• HYPERKALEMIA
• Precipitated by
• increased dietary potassium intake,
• protein catabolism,
• hemolysis,
• hemorrhage,
• transfusion of stored red blood cells,
• and metabolic acidosis
• Medications
P
O
T
A
S
S
I
U
M

50. RenalPotassiumHandling

51. FLUID, ELECTROLYTE, AND ACID-BASE
DISORDERS
Hypokalemia:
• Not common in CKD
• reduced dietary potassium intake
• GI losses
• Diuretic therapy
• Fanconi’s syndrome
• RTA
• Hereditary or acquired Tubulointerstitial disease
P
O
T
A
S
S
I
U
M

52. FLUID, ELECTROLYTE, AND ACID-BASE
DISORDERS
Metabolic acidosis
• common disturbance in advanced CKD
• combination of hyperkalemia and hyperchloremic
metabolic acidosis is often present, even at earlier
stages of CKD (stages 1–3)
• Treat hyperkalemia
• the pH is rarely <7.35
• usually be corrected with oral sodium bicarbonate
supplementation
M
E
T
A
C
I
D
O
S
I
S

53. FLUID, ELECTROLYTE, AND ACID-BASE
DISORDERS
Renal Control of Acid-Base Balance
1) Secretion of H+ and Reabsorption of HCO3 by the Renal
Tubules
a. H+ is Secreted by Secondary Active Transport in the Early Tubular
Segments
b. Filtered HCO3 is Reabsorbed by Interaction with H+ in the Tubules
c. Primary Active Secretion of H+ in the Intercalated Cells of Late Distal
and Collecting Tubules
2) Combination of Excess H+ with Phosphate and Ammonia
Buffers in the Tubule Generates “New” HCO3
a. Phosphate Buffer System Carries Excess H+ into the Urine and
Generates New HCO3
b. Excretion of Excess H+ and Generation of New HCO3 by the
Ammonia Buffer System
M
E
T
A
C
I
D
O
S
I
S

54. RenalHandlingofAcid
Excretion

55. • To maintain euvolemia:
• Adjustments in the dietary intake of salt
• and use of loop diuretics, occasionally in combination with
metolazone
• Hyponatremia:
• water restriction
• Hyperkalemia
• responds to dietary restriction of potassium,
• avoidance of potassium supplements
• use of kaliuretic diuretics
• potassium-binding resins, such as calcium resonium or sodium
polystyrene
• The renal tubular acidosis and subsequent anion-
gap metabolic acidosis
• alkali supplementation, typically
with sodium bicarbonate

56. DISORDERS OF CALCIUM AND PHOSPHATE
METABOLISM
The principal complications of abnormalities of
calcium and phosphate metabolism in CKD
1. occur in the skeleton and
2. the vascular bed,
3. with occasional severe involvement of
extraosseous soft tissues
Bone manifestations of CKD, classified as:
• associated with high bone turnover with increased
PTH levels
• low bone turnover with low or normal PTH levels

57. DISORDERS OF CALCIUM AND PHOSPHATE
METABOLISM
The pathophysiology of secondary
hyperparathyroidism:
1. Declining GFR leads to reduced excretion of phosphate
2. increased synthesis of PTH and growth of parathyroid
gland mass
3. decreased levels of ionized calcium, resulting from
diminished calcitriol production by the failing kidney
Fibroblast growth factor 23 (FGF-23)
(1) increased renal phosphate excretion;
(2) stimulation of PTH, which also increases renal
phosphate excretion; and
(3) suppression of the formation of 1,25(OH)2D3, leading
to diminished phosphorus absorption from the gastrointestinal tract

58. DISORDERS OF CALCIUM AND PHOSPHATE
METABOLISM
Osteitis fibrosa cystica
 bone turnover
 abnormal histology
 brown tumor
Low-turnover bone disease can be
grouped into two categories:
1. adynamic bone disease
2. and osteomalacia

59. DISORDERS OF CALCIUM AND PHOSPHATE
METABOLISM
Calcium, phosphorus, and the cardiovascular
system:
• Hyperphosphatemia and hypercalcemia are
associated with increased vascular
calcification
• calcification of the media in coronary arteries
and even heart valves
• ingested calcium cannot be deposited in
bones with low turnover
• osteoporosis and vascular calcification
• hyperphosphatemia can induce a change in
gene expression in vascular cells

60. DISORDERS OF CALCIUM AND PHOSPHATE
METABOLISM
Other complications of abnormal mineral
metabolism:
• Calciphylaxis (calcific uremic arteriolopathy)
• Other etiologies
• use of oral calcium as a phosphate binder
• Warfarin

61. Sevelamer and lanthanum – non calcium containing
polymers
Calcitriol exerts a direct suppressive effect on PTH
secretion and also indirectly suppresses PTH secretion by raising
the concentration of ionized calcium
recommended target PTH level between 150 and 300
pg/mL

62. CARDIOVASCULAR ABNORMALITIES
1) Ischemic vascular disease
The CKD-related risk factors comprise
1. anemia,
2. hyperphosphatemia,
3. hyperparathyroidism,
4. sleep apnea, and
5. generalized inflammation
Cardiac troponin levels are frequently elevated in
CKD without evidence of acute ischemia.

63. CARDIOVASCULAR ABNORMALITIES
2) Heart failure
“bat wing” distribution - form of “low-
pressure” pulmonary edema

64. CARDIOVASCULAR ABNORMALITIES
3) Hypertension and left ventricular
hypertrophy
• anemia and the placement of an
arteriovenous fistula
• low blood pressure actually carries a worse
prognosis than does high blood pressure
• erythropoiesis-stimulating agents

65. MANAGEMENT OF HYPERTENSION
• Blood pressure should be reduced to
125/75
• Salt restriction should be the first line of
therapy
MANAGEMENT OF CARDIOVASCULAR
DISEASE
• Lifestyle changes, including regular
exercise
• Manage dyslipidemia

66. Pericardial disease
Chest pain with respiratory accentuation, accompanied
by a friction rub, is diagnostic of pericarditis.
Classic electrocardiographic abnormalities include PR-
interval depression and diffuse ST-segment elevation
Initiation of dialysis
No heparin

67. HEMATOLOGIC ABNORMALITIES
Anemia
A normocytic, normochromic anemia is
observed as early as stage 3 CKD and is almost
universal by stage 4.
The primary cause in patients with CKD is
insufficient production of erythropoietin (EPO) by the
diseased kidneys.

68. Causes of Anemia in CKD
1. Relative deficiency of erythropoietin
2. Diminished red blood cell survival
3. Bleeding diathesis
4. Iron deficiency
5. Hyperparathyroidism/bone marrow fibrosis
6. “Chronic inflammation”
7. Folate or vitamin B12 deficiency
8. Hemoglobinopathy
9. Comorbid conditions: hypo/hyperthyroidism, pregnancy,
HIV-associated disease, autoimmune disease,
immunosuppressive drugs

69. recombinant human EPO and modified EPO
Products
Use of EPO in CKD may be associated with an:
1. increased risk of stroke in those with type 2 diabetes,
2. an increase in thromboembolic events,
3. and perhaps a faster progression to the need for
dialysis
target a hemoglobin concentration of 100–115 g/L

70. HEMATOLOGIC ABNORMALITIES
Abnormal hemostasis
1. prolonged bleeding time,
2. decreased activity of platelet factor III,
3. abnormal platelet aggregation and adhesiveness,
4. and impaired prothrombin consumption.
Clinical manifestations include
1. an increased tendency to bleeding and bruising,
2. prolonged bleeding from surgical incisions,
3. menorrhagia,
4. and spontaneous GI bleeding

71. Abnormal bleeding time and coagulopathy in patients
with renal failure may be reversed temporarily with
• desmopressin(DDAVP),
• cryoprecipitate,
• IV conjugated estrogens,
• blood transfusions, and
• EPO therapy.
Optimal dialysis will usually correct a prolonged
bleeding time.

72. NEUROMUSCULAR ABNORMALITIES
Central nervous system (CNS), peripheral, and
autonomic neuropathy
mild disturbances in memory and concentration and
sleep disturbance.
Neuromuscular irritability, including hiccups, cramps,
and fasciculations or twitching of muscles, becomes
evident at later stages.
In advanced untreated kidney failure, asterixis,
myoclonus,
seizures, and coma can be seen

73. GASTROINTESTINAL AND NUTRITIONAL
ABNORMALITIES
Uremic fetor , a urine-like odor on the breath, derives
from the breakdown of urea to ammonia in saliva and is
often associated with an unpleasant metallic taste
(dysgeusia)

74. DERMATOLOGIC ABNORMALITIES
Pruritus
nephrogenic
fibrosing dermopathy

75. EVALUATION AND MANAGEMENT OF PATIENTS WITH
CKD
Laboratory investigation
Serial measurements of renal function
Serum concentrations of calcium, phosphorus, vitamin
D, and PTH should be measured to evaluate
metabolic bone disease.
Hemoglobin concentration, iron, B 12 , and
Folate
A 24-h urine collection

76. EVALUATION AND MANAGEMENT OF PATIENTS WITH
CKD
Imaging studies
most useful imaging study is a renal ultrasound
CKD with normal sized kidneys
DM nephropathy
amyloidosis
HIV nephropathy
voiding cystogram
judicious administration of sodium bicarbonate-
containing solutions and N -acetyl-cysteine

77. ESTABLISHING THE DIAGNOSIS AND ETIOLOGY OF CKD
Renal biopsy
Contraindications:
• bilaterally small kidneys
• uncontrolled hypertension,
• active urinary tract infection,
• bleeding diathesis (including ongoing
anticoagulation),
• and severe obesity

78. EVALUATION AND MANAGEMENT OF PATIENTS WITH
CKD
The most important initial diagnostic step in the
evaluation of a patient presenting with elevated serum
creatinine is to distinguish newly diagnosed CKD from
acute or subacute renal failure
SUGGESTS CHRONICITY
1. hyperphosphatemia,
2. hypocalcemia,
3. elevated PTH and bone alkaline Phosphatase
4. Normochromic, normocytic anemia
5. bilaterally reduced kidney size <8.5 cm

79. Topic Outline
IV TREATMENT
A.SLOWING THE PROGRESSION OF CKD
1. Reducing Intraglomerular Hypertension and Proteinuria
B.SLOWING PROGRESSION OF DIABETIC RENAL DISEASE
1. Control of Blood Glucose
2. Control of Blood Pressure and Proteinuria
3. Protein Restriction
C.MANAGING OTHER COMPLICATIONS OF CHRONIC KIDNEY
DISEASE
1. Medication Dose Adjustment
2. Preparation for Renal Replacement Therapy
3. Patient Education

80. TREATMENT

81. TREATMENT
Any acceleration in the rate of decline should prompt a
search for superimposed acute or subacute processes
that may be reversible
1. ECFV depletion,
2. uncontrolled hypertension,
3. urinary tract infection,
4. new obstructive uropathy,
5. exposure to nephrotoxic agents
6. and reactivation or flare of the original
7. disease, such as lupus or vasculitis

82. TREATMENT
SLOWING THE PROGRESSION OF CKD:
Reducing Intraglomerular Hypertension and
Proteinuria
renoprotective effect of antihypertensive medications -
↓proteinuria
125/75 mmHg as the target blood pressure
ACE inhibitors and ARBs
Adverse effects from these agents include cough and
angioedema with ACE inhibitors, anaphylaxis, and hyperkalemia
with either class
2nd line - diltiazem and verapamil

83. TREATMENT
SLOWING PROGRESSION OF DIABETIC RENAL
DISEASE
Control of Blood Glucose
preprandial glucose be kept in the 5.0–7.2 mmol/L, (90–
130 mg/dL)
hemoglobin A 1C should be < 7%
use and dose of oral hypoglycemic needs to be reevaluated
Chlorpropramide
Metformin
Thiazolidinediones

84. TREATMENT
SLOWING PROGRESSION OF DIABETIC RENAL
DISEASE
Control of Blood Pressure and Proteinuria
albuminuria
a strong predictor of cardiovascular events
and nephropathy
Microalbumin testing
At least ANNUALLY

85. TREATMENT
SLOWING PROGRESSION OF DIABETIC RENAL
DISEASE
Protein Restriction
CKD – 0.60 and 0.75 g/kg per day
at least 50% of the protein intake be of high
biologic value
Stage 5 CKD - 0.9g/kg/day
Caloric requirement – 35cal/kg/day

87. TREATMENT
MANAGING OTHER COMPLICATIONS OF CHRONIC
KIDNEY DISEASE
1. Medication Dose Adjustment
loading dose – no dose adjustment
>70% excretion is by a nonrenal route
– no adjustment
NSAIDs should be avoided
Nephrotoxic medical imaging radiocontrast agents
and gadolinium should be avoided
http://www.globalrph.com/renaldosing2.htm

88. TREATMENT
MANAGING OTHER COMPLICATIONS OF CHRONIC
KIDNEY DISEASE
1. Medication Dose Adjustment
2. Preparation for Renal Replacement Therapy
symptoms and signs of impending uremia, such as
anorexia, nausea, vomiting, lassitude – RX with
Protein restriction
optimal time for initiation of renal replacement
therapy have been established – KDOQI
Delaying – worse prognosis

89. HEMODIALYSIS
ABSOLUTE INDICATIONS:
●Uremic pericarditis or pleuritis
●Uremic encephalopathy
Common indications:
1. Declining nutritional status
2. Persistent or difficult to treat volume overload
3. Fatigue and malaise
4. Mild cognitive impairment
5. Refractory acidosis, hyperkalemia, and
hyperphosphatemia

90. Chronic Kidney Disease

91. Leading Categories of Etiologies
of CKD∗

92. RenalPotassiumHandling

93. Normal Lab Values