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1.73 m2
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Pathogenesis:
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❑ An increase in blood flow, intraglomerular capillary filtration pressure
(PGC), and hyperfiltration (increased single-nephron effective GFR).
❑ Sustained increases in plasma flow and hydrostatic pressure lead to
hyperfiltration injury and glomerular sclerosis.
❑ ACEIs/ARBs prevent vasoconstriction of the efferent arteriole and
reduce the PGC. ---------------1st line.
Second Line:
❑ Calcium-channel blockers have been considered for
preventing progression of kidney disease owing to
their effects on renal hemodynamics and
cytoprotective and antiproliferative properties
(prevention of mesangial expansion and renal
scarring).
❑ Nondihydropyridine agents (e.g., diltiazem and
verapamil) have been beneficial in reducing
proteinuria when compared with dihydropyridines
(e.g., amlodipine), which have been found to worsen
proteinuria.
Albuminuria or Proteinuria
❑ Marker of kidney damage, progression factor, and
cardiovascular risk factor.
Diabetic Kidney Disease
Diagnosis
a. Long history of diabetes
b. Proteinuria
c. Retinopathy often coexists, suggestive of microvascular disease.
Monitoring
a. Type 1 diabetes: Begin annual monitoring for albuminuria 5 years
after diagnosis.
b. Type 2 diabetes: Begin annual monitoring for albuminuria
immediately (do not know how long patient has had diabetes
mellitus).
c. Monitor albuminuria twice annually if ACR is greater than 300 mg/g
and/or estimated eGFR is 30–60 mL/min/1.73 m2.
❖ Latest update KDIGO 2021 to BP Targets in
Diabetic Kidney Disease.
Management of DKD:
i. Either ACEIs or ARBs are preferred and should be used with any degree of
proteinuria, even if the patient is not hypertensive.
(a) Use moderate to high doses with proteinuria.
(b) Hold ACEI or ARB if serum potassium is greater than 5.6 mEq/L or if SCr
increases by more than 30% after initiation. Potassium binders can be
considered for chronic management of hyperkalemia.
(c) Increased risk of hyperkalemia if combined with direct renin inhibitor.
ii. Most patients will need diuretic in combination (thiazide with stages 1–3
and loop diuretics in stages 4 and 5).
Begin a two-drug regimen if blood pressure is greater than 20 mmHg above
goal.
iii. Calcium channel blockers (nondihydropyridine) are second line to ACEIs
and ARBs. Data are emerging for combined therapy.
iv. Dietary sodium consumption should be less than 2.4 g/day. Modify the
Dietary Approaches to Stop Hypertension (DASH) diet to limit K intake as
well.
❑ Intensive blood glucose control. Glycosylated
hemoglobin (A1C) less than 7%. Less aggressive with
more advanced CKD.
i. Consider the use of sodium-glucose co-transporter 2
inhibitors in adults with type 2 diabetes and estimated
GFR greater than 30 mL/min/1.73 m2 and ACR greater
than 300 mg/g.
❑ Protein restriction: Data are insufficient in adults with
diabetes, but 0.8 g/kg/day may slightly reduce
progression in stage 4 or 5 CKD and decrease the risk
of ESRD. Patients should avoid high-protein diets
(greater than 1.3 g/kg/day).
Nondiabetic Nephropathy
1. Management of hypertension
a. 2021 KDIGO Guidelines recommend a goal systolic blood
pressure less than 120 mmHg, regardless of severity of
albuminuria.
b. Initial treatment with ACEI or ARB, but not both.
• Blood pressure, serum potassium, and SCr should be
monitored within 2–4 weeks of initiation or dosage increase.
Other Guidelines to Slow Progression
1. Hyperlipidemia
2. Stop Smoking
Assessment of Kidney Function
1. Serum creatinine (SCr)
a. Avoid use as the sole assessment of kidney function.
b. Depends on age, sex, weight, and muscle mass
c. All laboratories now use “standardized” SCr.
2. Measurement of GFR: Inulin, iothalamate, and others
are very rarely used in clinical practice.
3. Measurement of CrCl through urine collection.
Case
Discussion
Case 1
A 55-year-old man has a history of hypertension. His estimated
glomerular filtration rate (eGFR) is 48 mL/minute/1.73 m2. His
albumin/creatinine ratio (ACR) is 28 mg/g. Which best
represents what this patient’s goal blood pressure should be
less than (in mm Hg), according to the latest Kidney Disease:
Improving Global Outcomes (KDIGO) guidelines?
A. 130/80.
B. 140/90. Answer
Answer: E 2021 KDIGO Guidelines recommend a goal systolic
C. 140/80. blood pressure less than 120 mmHg, regardless of severity of
albuminuria.
D. 130/90
E. SBP < 120.
Answer
Answer: E
2021 KDIGO Guidelines recommend a goal systolic blood
pressure less than 120 mmHg, regardless of severity of
albuminuria.
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Case 2
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Case 3
A 25 yr old Hispanic female reports for follow up after
being hospitalized last week for newly diagnosed type
1 diabetes mellitus. You are considering all of the
additional work up which needs to be performed in this
patient including diabetic nephropathy screening. When
should this patient be screened for diabetic nephropathy?
1. Immediately today
2. Within six months after diagnosis
3. Within one year after diagnosis
4. Within five years after diagnosis
Answer
Answer: D
Within five years after diagnosis
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Case 4
A 55-year-old man has a history of hypertension and newly
diagnosed type 2 diabetes. He denies alcohol use but does
smoke cigarettes (1 pack/day). His medications include atenolol
50 mg/day and a multivitamin. At your pharmacy, his blood
pressure is 149/92 mm Hg. His ACR is 400 mg/g.
A recent SCr is 1.9 mg/dL, which is consistent with a value
measured 3 months earlier. His eGFR is 50 mL/minute/1.73 m2.
1) Which category best reflects his kidney disease, according
to the KDIGO criteria?
A. G2.
B. G3a.
C. G3b.
D. G4.
Answer
Answer: B
The patient’s CKD should be classified as KDIGO category 3a
(GFR 45–59 mL/minute/1.73 m2) (Answer B is correct), which
can be calculated by the MDRD formula or Cockcroft-Gault. The
five categories range from mild kidney damage (G1) to kidney
failure (G5). A patient’s CKD would be classified as category G2 if
the GFR were 60–89 mL/minute/1.73 m2 (Answer A is incorrect),
category G3b if the GFR were 30–44 mL/minute/1.73 m2
(Answer C is incorrect), or category G4 if the GFR were 15–29
mL/minute/1.73 m2 (Answer D is incorrect).
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2) Using the KDIGO categorization, which best assesses this
patient’s albuminuria?
A. Category A1.
B. Category A2.
C. Category A3.
D. Nephrotic-range proteinuria.
Answer
Answer: C
The KDIGO guideline also provides guidance on categorizing
albuminuria according to the urinary ACR. This patient has
category A3, or severely increased albuminuria, given the
patient’s ACR greater than 300 mg/g (Answer C is correct).
Category A2 is moderately increased albuminuria with an ACR
of 30–300 mg/g (Answer B is incorrect). Category A1 is an
ACR less than 30 mg/g (Answer A is incorrect). Nephrotic-
range proteinuria requires protein excretion exceeding 3 g/day
(Answer D is incorrect).
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3) Assuming that non-pharmacologic approaches have been
optimized, which is best to limit the progression of his kidney
disease?
A. Add nifedipine.
B. Add diltiazem.
C. Add enalapril.
D. Increase atenolol.
Answer
Answer: C
Given the diagnosis of diabetes mellitus and the presence of severe albuminuria, this patient
probably has diabetic nephropathy. Progression will be accelerated by smoking, poor diabetes
control, and poor blood pressure control. In patients with diabetes, a target A1C of less than 7%
is associated with a decrease in the rate of disease progression. Blood pressure control of less
than 130/80 mm Hg in patients also decreases the progression of kidney disease. The standard
of care in patients with diabetic nephropathy is ACEIs (evidence for reduced mortality and
reduced progression of CKD) or ARBs (evidence for reduced progression but no mortality data),
so enalapril (Answer C) is the best choice. A nondihydropyridine (Answer B) might be initiated in
patients who cannot tolerate ACEI or ARB therapy, but this would not be a choice yet.
Dihydropyridine therapy (Answer A) is not recommended in diabetic nephropathy because of
conflicting literature on its efficacy. An increase in atenolol (Answer D) might control blood
pressure, but inhibition of the renin-angiotensin system is still the best answer. In addition, a
meta-analysis evaluating atenolol in patients with hypertension and diabetes mellitus found
either no difference or worse outcomes.
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4) Enalapril is added to this patient’s regimen. Two weeks
later, he returns for a follow-up. His blood pressure is
139/89 mm Hg. A repeat SCr is 2.3 mg/dL, and serum
potassium is 5.2 mEq/L. Which is the best
recommendation for this patient?
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Complications
of CKD
Secondary Complications of
CKD:
Anemia:
The primary cause of anemia of CKD is a decrease in production of
erythropoietin, by interstitial fibroblasts in the renal cortex of the kidney
where approximately 90% of production occurs.
Iron deficiency anemia is common in individuals with advanced kidney
disease (ie, CKD 4 and 5) due to:
• Decreased gastrointestinal (GI) absorption of iron
• Inflammation and frequent blood testing
• Blood loss from hemodialysis (HD)
• Increased iron demands from erythropoiesis stimulating agent (ESA)
therapy. (resistance to ESAs )
Anemia workup: Initiate evaluation when CrCl is less than 60
mL/minute/1.73 m2 or when Hgb is
less than 13 g/dL (men) or less than 12 g/dL (women).
• Mean corpuscular volume
• Reticulocyte count
• Iron studies
(a) TSAT (serum iron/total iron-binding capacity × 100): Assesses available
iron
(b) Ferritin: Measures stored iron
• Serum vitamin B12 and folate concentrations
• Stool guaiac
Management of anemia of CKD according
to KDIGO and KDOQI guidelines.
ESAs
i. Initiation
(a) Patients with CKD (non-dialysis): Not to be initiated if Hgb is greater than 10 g/dL
unless symptomatic. If Hgb is less than 10 g/dL, consider the rate of decline in Hgb
and the need to reduce the likelihood of transfusion (particularly in patients who may
receive a renal transplant).
(b) Patients with CKD (dialysis): Initiate therapy for Hgb less than 10 g/dL (KDIGO
guidelines recommend avoiding an Hgb decrease below 9 g/dL) (Start between 9 –
10 )
(c) Use with caution, if at all, in patients with a history of stroke or cancer (evidence
for increased risk of stroke is stronger in patients with nondialysis-dependent CKD
compared with the risk in patients on dialysis).
(d) Iron stores should be replaced before initiating ESAs.
(e) Additional contraindications include uncontrolled hypertension and
hypersensitivity reactions.
Therapy goals
i. Use the lowest possible dose of ESA to prevent blood transfusion.
ii. In non-dialysis patients with CKD, hold or reduce the dose when Hgb is greater
than 10 g/dL.
iii. In dialysis patients, hold or reduce the dose when Hgb is greater than 11 g/dL
(KDIGO suggests an upper limit of 11.5 g/dL).
iv. Do not exceed an Hgb greater than 13 g/dL.
ESA dose adjustment is based on Hgb response.
i. Adjustment parameters are similar for epoetin alfa and darbepoetin alfa.
ii. Maximal increase in Hgb is about 1 g/dL every 2–4 weeks.
iii. Dosages should not be titrated more often than every 4 weeks.
iv. In general, dose adjustments are made in 25% increments (i.e., dosages titrated
or tapered by 25% according to current dose).
The most common causes of ESA resistance are
⮚ Iron deficiency
⮚ Acute illness
⮚ Inflammation
⮚ Infection
⮚ Chronic bleeding and hemolysis
⮚ Aluminum toxicity
⮚ Malnutrition
⮚ Hyperparathyroidism
⮚ Cancer and chemotherapy
⮚ Deficiencies in folate and vitamin B12
⮚ Vitamin C deficiency
⮚ Use of ACEIs and ARBs
ESA monitoring
i. Hgb every 2–4 weeks during initiation phase. In maintenance phase
of therapy, monitor Hgb at least monthly in dialysis patients and at
least every 3 months in non-dialysis patients with CKD.
ii. Monitor blood pressure because it may rise (treat as necessary).
iii. Iron stores
• Epoetin alfa (Epogen, Procrit)
(a) Same molecular structure as human erythropoietin
(recombinant DNA technology)
(b) Binds to and activates erythropoietin receptor
(c) Administered subcutaneously or intravenously
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Case 2:
A 67 years old man weighs 60kg with a history of type II Diabetis mellitus, HTN,
hypercholesterolemia, and stage 4 CKD on dialysis presents to his nephrologist for routine
follow up : Na (140), HB (10.1), Calcium (8.5), iron (80), Potassium (4.0) Phosphorus (4.1) ,
Transferrin saturation (19%) Albumin(2.8) , Ferritin (90) Cr(1.9) . 6 month ago Cr(1.7) ,
Urinanalysis -ve protienuria
Which pharmacological treatment is the best to be initiate for this patient at this time?
A. Calcitriol 0.25mcg orally once daily plis sevelamer 800mg orally three times daily
B. Darbapoitin 40mcg Sc once weekly plus ferrous sulfate 325mg orally three times per day
C. Initiate IV iron immediately.
D. Calcium carbonate 500mg orally three times per day plus sevelamer 800mg orally three
times per day
Answer:
Answer: C
According to Guidelines this patient meets Anemia for a chronic
disease with iron deficiency so this patient need to take iron
because his tranferrin and ferritin is low , the best form of iron is
IV form so Answer B is incorrect and answer C is correct. Although
Calcium seems low but after correction with albumin it will be
within normal range and phosphate within normal range
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Case 3:
A 60-year-old patient on HD has had ESRD for 10 years. His HD access is a left arteriovenous
fistula. He has a history of hypertension, coronary artery disease, mild CHF, type 2 diabetes,
and a seizure disorder.
Medications are as follows: epoetin alfa 14,000 units intravenously three times/week at dialysis,
a renal multivitamin once daily, atorvastatin 20 mg/day, insulin, calcium acetate 2 tablets three
times/day with meals, phenytoin 300 mg/day, and intravenous iron 100 mg/month.
Laboratory values are as follows: hemoglobin 10.2 g/dL, immunoassay for parathyroid hormone
(PTH) 800 pg/mL, Na 140 mEq/L, K 4.9 mEq/L, Cr 7.0 mg/dL, calcium 9.5 mg/dL, albumin 2.5
g/dL, and phosphorus 7.8 mg/dL. Serum ferritin is 550 ng/mL, and transferrin saturation (TSAT)
is 32%. The red blood cell count indices are normal. His WBC is normal, and he is afebrile.
1) Which is most likely to be contributing to relative epoetin resistance in this patient?
A. Iron deficiency.
B. Hyperparathyroidism.
C. Phenytoin therapy.
D. Infection.
Answer
Answer: B
Hyperparathyroidism is associated with epoetin resistance in patients on HD (Answer
B).
Although iron deficiency is the most common cause of epoetin deficiency, the
laboratory results in this patient do not indicate iron deficiency (Answer A) because
TSAT is greater than 30% and serum ferritin is greater than 500 ng/mL.
Phenytoin therapy (Answer C) has been associated with anemia in other patient
populations but not in patients on HD.
Infection (Answer D) and inflammation are very common causes of epoetin
deficiency in patients on HD, but nothing in this patient’s presentation suggests an
infectious or inflammatory process.
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2) In addition to diet modification and emphasizing
adherence, which is best for managing this patient’s
hyperparathyroidism?
A. Increase calcium acetate.
B. Change calcium acetate to sevelamer and add cinacalcet.
C. Hold calcium acetate and add intravenous vitamin D
analog.
D. Add intravenous vitamin D analog.
Answer
Answer: B
This patient needs treatment for his elevated PTH (800pg/mL), which places him at high risk of renal
osteodystrophy and vascular calcification. He has high serum phosphorus, and although the measured
serum calcium concentration is normal, his corrected calcium concentration is elevated, given the
presence of hypoalbuminemia (corrected calcium is 10.7 mg/dL). Current phosphate binder therapy is
contributing to calcium exposure; therefore, calcium acetate should be discontinued and sevelamer
initiated; also, cinacalcet should be added, which will lower PTH and, potentially, serum calcium
(Answer B is correct). Answer A is incorrect because increasing the calcium acetate may worsen the
hypercalcemia. Answer C is incorrect for two reasons. First, the patient needs some type of phosphate
binder; second, intravenous vitamin D analogs can worsen hypercalcemia and are not very effective at
reducing elevated PTH in the presence of hyperphosphatemia. Answer D is incorrect because
intravenous vitamin D analogs can worsen hypercalcemia and are not very effective at reducing
elevated PTH in the presence of hyperphosphatemia. Because this patient also has a seizure disorder,
close monitoring of serum calcium concentrations is recommended with the introduction of cinacalcet
and discontinuation of calcium acetate. Significant reductions in serum calcium can lower the seizure
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threshold and potentially worsen seizures.
Case 4:
-Which of the following is a typical dose of IV iron
recommended in the hemodialysis population with absolute
iron deficiency?
A) 100 mg per week for 8 weeks
B) 250 mg administered over 1 hour
C) 500 mg administered in divided doses
D) 1000 mg administered in divided doses
—
Answer
Answer: D
1000 mg administered in divided doses
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Case 5:
-Which of the following preparations needs a
test dose it may cause anaphylactic reactions?
A) Iron dextran
B) Sodium ferric gluconate
C) Iron sucrose
D) Ferumoxytol
Answer
Answer: A
Iron dextran
PRESENTATION TITLE 73
Case 6:
A 59-year-old patient who has had CKD category G5D for 10 years has
hypertension, coronary artery disease, mild heart failure with reduced
ejection fraction (HFrEF), and type 2 diabetes.
Medications are as follows: epoetin 10,000 units intravenously three
times/week at dialysis, renal multivitamin once daily, atorvastatin 20
mg/day, insulin, and calcium acetate 1334 mg three times daily with
meals. Laboratory values are as follows: hemoglobin (Hgb) 9.2 g/dL,
parathyroid hormone (PTH) 300 pg/mL, Na 140 mEq/L, K 4.9 mEq/L, SCr
7.0 mg/dL, calcium 9 mg/dL, albumin 3.5 g/dL, and phosphorus 4.8 mg/dL.
His serum ferritin concentration is 80 ng/mL and transferrin saturation
(TSAT) is 14%. Mean corpuscular volume, mean corpuscular hemoglobin
concentration, and white blood cell count (WBC) are all normal. He is
afebrile.
Which is best for managing this patient’s anemia?
A. Increase epoetin.
B. Add oral iron.
C. Add intravenous iron.
D. Maintain current regimen; patient is at goal.
Answer
Answer: C
This patient’s Hgb is not at goal (greater than 10 g/dL), so maintaining
the current regimen would not be appropriate (Answer D is
incorrect). Iron studies show the patient is iron deficient, with TSAT
less than 30% and ferritin less than 500 ng/mL (Answer A is
incorrect). Increasing the epoetin dose would not increase red
blood cell production in the absence of adequate iron. Although a
trial of oral iron might be indicated in non– dialysis patients with
CKD, patients on HD should be given intravenous iron as first line
(Answer B is incorrect; Answer C is correct).
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Case 7:
A 55-year-old white male with a past medical history of chronic kidney disease
on hemodialysis, hypertension, hyperlipidemia, s/p CABG x3 vessels, type 2
diabetes mellitus, gastroparesis and GERD has been consulted to you. His
current medications include aspirin 81 mg qd, lisinopril 20 mg bid, amlodipine 10
mg qd, metoprolol 50 mg twice daily, 70/30 insulin 42 units in the am and 30
units in the pm, atorvastatin 40 mg qhs, calcium acetate 1334 mg with each
meal, omeprazole 20 mg qd, and multivitamin. The most recent set of fasting
labs reveal K+ = 4.5, Cr = 2.8 mg/dL, glucose = 154 mg/dL, Ca++ = 10.1, PO4 =
6.1, HgbA1c = 7.7%, AST/ALT = 25/32, total cholesterol = 192 mg/dL;
triglycerides = 223 mg/dL, HDL-c = 32 mg/dL, LDL-c = 117 mg. Vital signs:
temperature = 98.9, respirations = 16, pulse = 61, B/P = 137/74 mmHg. The
nephrologist has consulted you for your recommendations on further secondary
prevention for cardiovascular disease.
Which of the following interventions would be the best do
first in this patient that would positively impact several of his
comorbidities?
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Case 8:
A 68-year-old patient has diabetes, hypertension, and an eGFR of
40 mL/minute/1.73 m2. Medications include a renal multivitamin
once daily, simvastatin, lisinopril, and hydrochlorothiazide.
Laboratory values are as follows: Hgb 11.2 g/dL, immunoassay
for PTH 200 pg/mL, Na 138 mEq/L, K 4.9 mEq/L, calcium 8.6
mg/dL, albumin 3.5 g/dL, phosphorus 5.8 mg/dL, and 25-
hydroxyvitamin D 45 ng/mL.
Which is best to prevent CKD–mineral and bone disorder (MBD)
in this patient?
A. Ergocalciferol.
B. Calcium acetate.
C. Calcitriol.
Answer
Answer: B
Many factors can contribute to the development of CKD-MBD, including
hyperphosphatemia, hypocalcemia, decreased vitamin D and decreased production of
active 1,25-dihydroxyvitamin D, and hyperparathyroidism. Although this patient’s PTH
concentration is elevated, it may be related to hyperphosphatemia. Therefore, the first
approach would be to administer a phosphate binder such as calcium acetate to
decrease his serum phosphate concentrations. A calcium-containing phosphate binder
such as calcium acetate is acceptable with a corrected serum calcium concentration is
the low-normal range [measured Ca + (0.8)(4 – serum albumin) = 8.6 mg/dL + (0.8)(3.5 –
3.0) = 8.6 + 0.4 = 9.0 mg/ dL] (Answer B is correct). Ergocalciferol is not necessary in this
patient because the 25-hydroxyvitamin D concentration is greater than 30 ng/mL,
indicating adequate intake (Answer A is incorrect). The 2017 KDIGO CKD-MBD guidelines
suggest that calcitriol should not be routinely used in G3–G5 CKD, but in G4–G5 CKD for
patients with severe and progressive hyperparathyroidism (Answer C is incorrect).
Cinacalcet is reserved for patients with hyperparathyroidism despite normalization of
phosphate when hypercalcemia is present (Answer D is incorrect).
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Thank you