Chronic Kidney Disease, CKD, Nephrology, Specialty rounds, Internal Medicine, Uremia, CDUH, Evardone

1. Jose Socrates “Dee” Matuod Evardone
Year Level 2
Nephrology 2
Chronic Kidney
Disease
• NEPHROLOGY ROUNDS

2. PRE TEST

3. PRETEST
1) Urine albumin per gram of creatinine
content that signifies Chronic Renal
Damage:
A.17mg in males, 25mg in females
B.25mg in males, 17mg in females
C. 25mg in both sexes
D. None of the above

4. PRETEST
2) In CKD with Uremia, these compounds with
a molecular mass between 500 and 1500 Da,
are also retained and contribute to morbidity
and mortality
A.Guanidino compounds
B. products of nucleic acid metabolism
C.Polyamines
D.middle molecules

5. PRETEST
3) Diuretics used in combination of loop
diuretics, which inhibits the sodium chloride
co-transporter in the distal convoluted
tubule, can help effect renal salt excretion:
A. Ethacrynic acid
B. Metolazone
C. Acetazolamide
D. Eplerenone

6. PRETEST
4) The combination of ACE inhibitor and
ARB is associated with a greater
reduction in proteinuria compared to
either agent alone.
True or False

7. PRETEST
5) Testing for microalbumin is
recommended in all diabetic patients at
least:
A. Every 6 months
B. Every 3 months
C.Every 12 months
D. Every clinic visit

8. PRETEST
6) CKD is defined by the presence of
kidney damage or decreased kidney
function, irrespective of the cause, for at
least:
A.2 months
B.3 months
C.6 months
D. 12 months

9. PRETEST
7) In CKD dietary recommendation, at least
how much of the protein intake should be of
high biologic value:
A.50%
B. 40%
C.60%
D. 30%

10. PRETEST
8) In CKD, NO dose adjustment is needed for
agents/drugs that are excreted by a nonrenal
route by more than:
A.50%
B. 60%
C.70%
D. 80%

11. PRETEST
9) In CKD, educational programs should be
commenced no later than stage __ CKD so that the
patient has sufficient time and cognitive function to
learn the important concepts, to make informed
choices, and implement preparatory measures for
renal replacement therapy.
A.Stage 2
B. Stage 3
C.Stage 4
D. Stage 5

12. PRETEST
10) Parathyroid hormone(PTH) itself is
considered a uremic toxin.
True or False

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. CASE
E.R.
63M
HTN>10yrs, poor med compliance
nonDM
previously smoker(stopped 15ys ago)
alcoholic beverage drinker(2beer/week)
CC: DYSPNEA

20. CASE
HPI:
1 month ago: exertional dyspnea
plus, 2 pillow orthopnea, loss of appetite,
body malaise, nausea and vomiting
admitted at CVGH, creatinine was
20mg/dl, px was advised for hemodialysis (did
not consent)

21. CASE
HPI:
1 week PTA:
Bilateral LE swelling
weight loss
Oliguria
Dyspnea at rest

22. Awake, in respiratory
distress
Anicteric sclerae, Pale
palpebral conjunctivae
C/L: Equal chest expansion,
bibasal rales, decrease
breath soundson the left
lower lobe
CVS: Distinct heart sounds,
normal rate, regular rhythm
ABD: Normoactive bowel
sounds, soft, non tender, no
organomegaly
NEURO: Unremarkable
BP: 190/100mmHg
PR: 98 bpm
RR: 35 cpm
Temp: 36.2°C
P.E.
SKIN: cold,clammy
EXT: Bipedal edema grade 3

24. ECG

25. LABS RENAL PANEL C
CBC Adm
Hgb 5.4
Hct 16.8
WBC
Seg
Bas
Eos
Lymph
Mono
11.3
95
0
0
2
3
RBC 2.56
Platelet 121
MCV
MCH
MCHC
65.6
21.1
32.2
ABG
pH 6.99
pCO2 17
pO2 300
HCO3 4.2
fiO2 60%
SO2 100%
pF
ratio
500
Temp 36.2

26. LABS
RENAL PANEL C
Glucose 107 mg/dl
BUN 197 mg/dl
Creatinine 37.8 mg/dl
Uric Acid 8.7 mg/dl
Calcium 5.6 mg/dl
Phosphorus 17.6 mg/dl
Sodium 127 mmol/L
Potassium 6.8 mmol/L
Chloride 89 mmol/L
Enz. CO2 8.0 mmol/L
Total Chole 99 mg/dl
Triglycerides 103 mg/dl
Total Protein 5.4 g/dL
Albumin 2.9 g/dL
Globulin 2.5 g/dL
A/G Ratio 0.7
SGPT/ALT 38 U/L
Allk Phos 70 U/

27. IMPRESSION
1. ESRD with Uremia sec. to Hypertensive Nephrosclerosis
2. Pulmonary Congestion sec . to Fluid Overload sec. to #1
3. Metabolic acidosis, part. Compensated sec. to #1
4. Electrolyte Imbalance sec to #1
5. Essential Hypertension
6. CAP-High Risk
7. Microcytic, Hypochromic Anemia sec to #1

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

29. 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.

30. 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.

31. 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

32. 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

33. 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

34. 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

35. 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

36. 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

37. 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

38. 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

39. 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

40. 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

41. 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)

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

43. 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

44. 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

45. CKD

50. 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

51. 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

52. 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

53. 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

54. 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

55. 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’

56. 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

57. 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

58. 3 Spheres of dysfunction of Uremic Syndrome
Toxins
Homeostasis
Progressive
systemic
inflammation
UREM

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

60. 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.

61. 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.

62. 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

63. 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

64. 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

65. 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

66. 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

67. 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

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

69. 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

70. 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

71. RenalPotassiumHandling

72. 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

73. 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

74. 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

75. RenalHandlingofAcid
Excretion

76. • 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

77. 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

78. 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

79. 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

80. 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

81. 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

82. 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

83. 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.

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

85. 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

86. 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

87. 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

88. 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.

89. 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

90. 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

91. 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

92. 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.

93. 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

94. 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)

95. DERMATOLOGIC ABNORMALITIES
Pruritus
nephrogenic
fibrosing dermopathy

96. 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

97. 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

98. 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

99. 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

100. 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

101. TREATMENT

102. 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

103. 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

104. 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

105. 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

106. 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

108. 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

109. 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

110. 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

111. TREATMENT
MANAGING OTHER COMPLICATIONS OF CHRONIC
KIDNEY DISEASE
1. Medication Dose Adjustment
2. Preparation for Renal Replacement Therapy
3. Patient Education
Kidney transplantation - offers the best potential for
complete rehabilitation

112. THANK YOU

113. PRETEST
1) Urine albumin per gram of creatinine
content that signifies Chronic Renal
Damage:
A.17mg in males, 25mg in females
B.25mg in males, 17mg in females
C. 25mg in both sexes
D. None of the above

114. PRETEST
2) In CKD with Uremia, these compounds with
a molecular mass between 500 and 1500 Da,
are also retained and contribute to morbidity
and mortality
A.Guanidino compounds
B. products of nucleic acid metabolism
C.Polyamines
D.middle molecules

115. PRETEST
3) Diuretics used in combination of loop
diuretics, which inhibits the sodium chloride
co-transporter in the distal convoluted
tubule, can help effect renal salt excretion:
A. Ethacrynic acid
B. Metolazone
C. Acetazolamide
D. Eplerenone

116. PRETEST
4) The combination of ACE inhibitor and
ARB is associated with a greater
reduction in proteinuria compared to
either agent alone.
True or False

117. PRETEST
5) Testing for microalbumin is
recommended in all diabetic patients at
least:
A. Every 6 months
B. Every 3 months
C.Every 12 months
D. Every clinic visit

118. PRETEST
6) CKD is defined by the presence of
kidney damage or decreased kidney
function, irrespective of the cause, for at
least:
A.2 months
B.3 months
C.6 months
D. 12 months

119. PRETEST
7) In CKD dietary recommendation, at least
how much of the protein intake should be of
high biologic value:
A.50%
B. 40%
C.60%
D. 30%

120. PRETEST
8) In CKD, NO dose adjustment is needed for
agents/drugs that are excreted by a nonrenal
route by more than:
A.50%
B. 60%
C.70%
D. 80%

121. PRETEST
9) In CKD, educational programs should be
commenced no later than stage __ CKD so that the
patient has sufficient time and cognitive function to
learn the important concepts, to make informed
choices, and implement preparatory measures for
renal replacement therapy.
A.Stage 2
B. Stage 3
C.Stage 4
D. Stage 5

122. PRETEST
10) Parathyroid hormone(PTH) itself is
considered a uremic toxin.
True or False

123. RenalPotassiumHandling

128. RenalCalciumandPhosphate
Handling

129. Chronic Kidney Disease

130. Leading Categories of Etiologies
of CKD∗

131. Chronic Kidney
Disease
NEPHROLOGY ROUNDS
Jose Socrates M. Evardone
Year Level 2
Nephrology 2

132. RenalPotassiumHandling

133. Normal Lab Values