This document provides an overview of pharmacotherapy for renal disorders. It begins by outlining various renal disorders including acute renal failure, chronic renal failure, drug-induced renal disease, glomerulonephritis, nephrotic/nephritic syndromes, acid-base disorders, and disorders of fluid and electrolyte homeostasis. It then focuses on acute kidney injury (AKI), discussing definition, staging, risk factors, pathophysiology, clinical presentation, investigations, and management. Prevention and treatment of specific causes of AKI like contrast-induced nephropathy and nephrolithiasis are also covered.

1. Pharmacotherapy of Renal Disorders
By Arega Gashaw
B.pharm, MSc in pharmacy practice
gemechu2002@gmail.com
1

2. Pharmacotherapy of renal disorders
 Acute Renal failure
 Chronic Renal Failure
 Drug induced Renal Disease
 Glomerulonephritis
 Nephrotic/nephritic syndromes
 Acid-base disorders
 Disorders of fluid and electrolyte
homeostasis
 Hemodialysis and peritoneal dialysis
 Case studies on Renal Disorders 2

3. Acute Renal Failure
3

4. • What do you know about ARF?
• What do you want to know about ARF?
4

5. I have following ……..
AS the Learning objectives
• Understand basic renal physiology and
the role of the kidney
• Identify patients at high risk of developing
acute kidney injury ARF
• Describe the pathophysiology and the
most common causes of prerenal,
intrinsic, and postrenal ARF
• Describe the prevention, management of
5

6. Introduction
–An organ attached to the posterior
wall of abdominal cavity bilaterally
–Is only 0.4% of body weight but
receives ~25% of CO
–Filters ~180L plasma/day
–Contains ~1 million nephrons each
6

7. – Glomerulus
– Bowman’s capsule
– Proximal tubule
– Loop of Henle
– Distal tubule
– Collecting duct
• Basic processes
– Filtration
– Reabsorption
– Secretion
7

8. What is the functions of kidney?
1. Regulation of Water & Electrolyte Balance
2. Excretion of Metabolic Waste Products
3. Excretion of Foreign Chemicals & Drugs
4. Regulation of Arterial Blood Pressure
5. Regulation of Erythropoiesis
6. Regulation of Vitamin D
7. Gluconeogenesis and metabolism of
endogenous compounds
8

9. Acute Kidney Injury (AKI)
• Sudden loss of kidney function resulting in retention of
nitrogenous waste as well as electrolyte and volume
homeostasis abnormalities with or without oliguria (urine
output <500 mL/d)
• It is a common and serious problem in clinical medicine.
• AKI is diagnosed when one of the following criteria is
met
– SrCr rises by ≥ 0.3mg/dl within 48 hours
– SrCr rises ≥ 1.5 fold from the baseline, which is
known or presumed to have occurred within one week
or
– urine output is < 0.5ml/kg/hr for >6 consecutive hours
No single serum creatinine value is a
threshold for ARF.(Ethiopian STG 2013
9

10. Staging classification of AKI
Stage Increase in serum Creatinine Urine out put
1 > 0.3 mg/dl increase or 1.5 to 2-fold
from baseline
< 0.5 ml/kg/hour for >
6 hours
2 >2- to 3-fold increase from baseline < 0.5 ml/kg / hour
for 12 hours
3 >3-fold from baseline or serum
creatinine > 4.0 mg/dl with an acute
increase of at least 0.5 mg/dl
< 0.3 ml/kg/ hour for
24 hours or
Anuria for 12 hours
10

11. 11

12. Measurement of the kidney function
1. The glomerular filtration rate (GFR) is the single best
indicator of kidney function
• GFR- Volume of plasma filtered across the glomerulus
per unit time
• The normal values for GFR are 127 ± 20 mL/min/1.73
m2
2. Exogenous and endogenous compounds for measurement
of GFR
3. Urine output measured over a specified period of time (4–
24 hours) allows for short-term assessment of kidney
function
• Equations to estimate creatinine clearance or GFR
12

13. 13

14. Laboratory Procedures to Detect the
Presence of Kidney problem
• Urine Analysis
–Urine pH, Glucose, Ketones, Nitrite, Heme,
Protein or Albumin, Specific Gravity, Blood
Urea Nitrogen, Serum Creatinine etc.
–Formed elements in the urine include
erythrocytes and leukocytes, casts, and
crystals
14

15. Classifications based on…….Urine output
– Anureic: < 50mL/24 hr (worse outcome)
– Oliguric: 50-500 mL/24 hrs
– Nonoliguric: >500 mL/24 hrs….better outcome
• Other classifications
– Community-acquired AKI
– Hospital acquired AKI
– ICU acquired AKI
15

16. Risk factors
• Volume depletion
– sepsis, hemorrhage, vomiting, diarrhea, poor fluid intake/
dehydration, diuretic use
– Poor renal perfusion
• Pre-existing CKD
• Nephrotic drugs:
– AG, Contrast Dye, NSAID, ACEI, ARBS, Cyclosporine and
Cimetidine, TMP: inhibit kidney tubular secretion of SCr
• Co-morbidities (e.g., liver failure, heart failure, diabetes)
• Advanced age
• Benign prostatic hypertrophy (BPH)
• Malignancy
16

17. Pathophysiology and Classification of AKI
Can be divided into 3 categories:
17

18. Pathophysiology of AKI
• Prerenal: Pathology secondary to decreased renal
perfusion leading to a decrease in glomerular filtration
rate (GFR);
– reversible if factors decreasing perfusion are corrected;
– otherwise, it can progress to an intrarenal pathology known
as ischemic ATN.
• Intrarenal: Pathology secondary to pathology within
the kidney;
– Acute tubular necrosis (ATN) is the most common cause via
ischemic or nephrotoxic injury to the kidney;
– 75% of ATN is a complication of prerenal etiology.
• Postrenal: Pathology secondary to extrinsic or
intrinsic obstruction of the urinary collection system18

19. Etiology
• Prerenal (~55%):
– Hypotension, volume contraction, severe heart failure, or liver failure
• Intrarenal (~40%):
– ATN (from prolonged prerenal failure, radiographic contrast material,
aminoglycosides, or nephrotoxic substances),
– Glomerulonephritis, acute interstitial nephritis (drug-induced), arteriolar
insults, vasculitis, accelerated hypertension, cholesterol embolization
(common after arterial procedures),
– Intrarenal deposition or sludging (seen in increased uric acid and
multiple myeloma—bence-jones proteins)
• Postrenal (~5%):
– Extrinsic compression (prostatic hypertrophy, carcinoma),
– Intrinsic obstruction (calculus, tumor, clot, stricture, sloughed papilli),
– Decreased function (neurogenic bladder)
19

20. Commonly Associated Conditions
 Hyperphosphatemia, hypercalcemia, hyperuricemia,
 Hydronephrosis, BPH, nephrolithiasis,
 Congestive heart failure (CHF), pericarditis,
cirrhosis, chronic renal insufficiency, malignant
hypertension, vasculitis,
 Drug reactions, sepsis, severe trauma, burns,
transfusion reactions, recent chemotherapy, muscle
injury, internal bleeding
20

21. Clinical Presentation of AKI
Dependent on the underlying etiology
– Oliguria/Anuria
– Urine discoloration (cola-colored urine is a blood in urine i.e.
commonly associated with acute glomerulonephritis)
– Fatigue, sudden weight gain, or severe abdominal or flank pain
– Peripheral edema, pulmonary edema, pleural effusion or ascites
– Pericardial effusion
– Decreased appetite, nausea and vomiting
– Hiccups
– Mucocutaneous bleeding
– Change in mental status/flapping tremor/seizure
21

22. Clinical presentation…
Physical Exam
• Prerenal signs: Tachycardia, orthostatic
hypotension, dry mucous membranes, decreased skin
turgor; look for stigmata of associated comorbidities
such as liver and heart failure, as well as sepsis.
• Intrinsic renal signs: Pruritic rash, livedo
reticularis, subcutaneous nodules, ischemic digits
despite good pulses
• Postrenal signs: Suprapubic distension, flank pain,
and enlarged prostate
22

23. Investigations
• Urinalysis: Dipstick for blood & protein; microscopy for
cells, casts, and crystals
• BUN and creatinine
• Serum electrolytes
• ECG – to look for evidence of hyperkalemia
• Imaging
– Renal ultrasound: r/o urinary tract obstruction (postrenal causes
if negative) and assess kidney size or identifies presence of
kidneys, hydronephrosis, and nephrolithiasis
– Doppler-flow kidney US: r/o renal artery stenosis/thrombosis
– Abdominal x-ray: Rules out renal calculi
• Pathological Findings
– Kidney biopsy:
23

24. • Generally, the first noticeable signs of AKI are
elevations of BUN, SCr, & possibly ∆s in urine output
• Cases of isolated ↑ in BUN or SCr not resulting from a
decreased GFR are termed "pseudorenal failure.“
• Although both parameters may increase in any type of
AKI, BUN/SCr ratio increases >15 in prerenal AKI
–kidney absorbs high urea (not creatinine) with
water by passive diffusion in the proximal
tubule to compensate for hypoxia or poor
perfusion
24

25. • AKI in CKD may develop when an abrupt rise in the
patient’s Scr occurs (increase by > 1mg/dl from baseline)
• In hospitalized patients, changes in urine output may be
helpful in characterizing the cause of the patient’s AKI
– Acute anuria is typically caused by either complete
urinary obstruction or a catastrophic event (e.g., shock
or acute cortical necrosis).
– Oliguria, which often develops over several days,
suggests prerenal azotemia, whereas nonoliguric renal
failure usually results from acute intrinsic renal failure
or incomplete urinary obstruction.
25

26. Fractional excretion of Na
• Evaluating the urine sodium concentration and percent
excreted (FeNa) is particularly helpful in differentiating
between a pre-renal AKI and ATN.
• In pre-renal, kidneys should excrete very little Na as a
compensatory mechanism to increase water reabsorption.
• Under normal conditions, the kidneys excrete
approximately 1 to 2% of the total sodium intake (normal
FeNa value).
• * FE Na= [(UNa × SCr)/(SNa × UCr)] × 100
Where U= urine and S=serum
* < 1 prerenal,
>1 renal
26

27. • Urinary Na < 20
• Urine Osms > 500
• Highly concentrated urine (>500 mOsm/kg [>500
mmol/kg]) suggests stimulation of antidiuretic and intact
tubular function.
• These findings are consistent with prerenal
azotemia.
• Common lab abnormalities in ARF:
– Increased: K+, phosphate, Mg, uric acid
– Decreased: Hematocrit (Hct), Na, Ca
27

28. Creatinine Clearance
• The first diagnostic tool…………
• (Very!) Rough estimate …….. 100/Cr
• GC (Cockroft-Gault)- To Calculate Creatine
Clearance
 (140 - age) x weight in kg (x 0.85 for women)
72 x serum creatinine
• Creatinine clearance of
– < 50 adjust medications
– < 25 refer to nephrology for pre-dialysis
– < 10 most people need dialysis
28

29. Prerenal
/Functional
Intrinsic Postrenal
History/
Presentation
Volume
depletion
Renal artery
stenosis
Hypercalcemia
NSAID/ACEI use
Cyclosporine
Ischemic failure
Nephrotoxic
Vascultitis
Glomerulenephritis
Kidney stones
BPH
Cancers
Physical
examination
Hypotension
Dehydration
Ascites
Edema
Hypersensitivity
Rash, Fever, edema
Distended
bladder
Enlarged
prostate
Serum
BUN/SCr ratio
> 20:1 15:1 15:1
29

30. Prerenal
/Functional
Intrinsic Postrenal
Urine
Concentrate
d?
Yes
Low urine Na
(<20 mEq/L)
Low FENa (<1)
High Uosm
No
Urine Na >40 mEq/L
FENa >2
Low Uosm
No
Urine Na>40
mEq/L
FENa >2
Low Uosm
Urine
Sediment
Normal
(Transparent
hyaline casts)
pigmented granular
/muddy brown casts—
ATN
Variable, may
be normal
Urinary WBC Negative 2-4+ casts (acute
interstitial nephritis)
Variable
Urinary RBC Negative 2-4+ casts
(glomerulonephritis)
1+
Proteinuria Negative Positive Negative 30

31. Management
• Desired outcome
–The primary goal of therapy is to prevent
ARF
–If ARF develops, the goals are
• To provide supportive measures until
kidney function returns
• To maintenance of blood pressure, fluid,
and electrolyte homeostasis
• To avoid or minimize further renal insults
that would delay recovery 31

32. How????
• Manage the underlying state appropriately like
– Acute infection
– Acute blood loss in trauma
– Dehydration
– Chronic kidney disease (CKD).
– Cardiovascular disease
• Avoid nephrotoxin administration (e.g.,
radiocontrast dye)
• Strict glycemic control with insulin in diabetics
has also reduced the development of ARF.
32

33. Non-pharmacologic Approaches
• Appropriate fluid replacement should be initiated.
• In outpatient, educate patient on preventive measures
– optimal daily fluid intake (~2 L/day) to avoid dehydration,
especially if they are to receive nephrotoxic medication
• In inpatient
– adequate hydration, standardized hemodynamic support in
critically ill, & avoidance of nephrotoxic medications
– Sometimes , the potential insult to the kidneys cannot be avoided but
may be preventable with aggressive hydration and removal of any
additional insults.
33

34. Recommended therapies for prevention of AKI
• Normal saline infusion
• Sodium bicarbonate infusion: 154 mEq/L (154 mmol/L)
infused at 3 mL/kg/h for 1 hr before the procedure & at 1
mL/kg/h for 6 hrs after the procedure
• Ascorbic acid … antioxidant that alleviate oxidative
stress caused by CIN-associated ischemia reperfusion
injury
– 3 g orally before the procedure and 2 g orally BID for
two doses after the procedure
• N-acetylcysteine (NAC) … antioxidant for CIN only
34

35. • Medications associated with diminished renal
blood flow should be stopped.
• Maintenance of adequate cardiac output and
blood pressure to optimize tissue perfusion
• Renal replacement therapy (RRT), such as
hemodialysis and peritoneal dialysis
35

36. Electrolyte management
• Hyperkalemia is the most common and serious
electrolyte abnormality in ARF.
• Typically, potassium must be restricted to less than 3
g/day and monitored daily.
• Hypernatremia and fluid retention commonly occur,
necessitating restricting daily sodium intake to no more
than 3 g.
• All sources of sodium, including antibiotics, need to be
considered when calculating daily sodium intake.
• Phosphorus and magnesium should be monitored;
neither is efficiently removed by dialysis.
36

37. 1. Contrast-Induced Nephropathy (CIN)
• Common cause of ATN in inpatients (>0.5 mg/dl ↑ Scr)
• Onset …an ↑in Scr or Oliguria develops w/in 24 hrs
• Prevention:
– N-acetylcystine 600 mg po bid for four doses, with the
first two doses administered prior to contrast exposure
and then the last 2 doses after
– 600 mg PO b.i.d. on day prior to and day of contrast [A]
and
– isotonic NaHCO3 3 mL/kg/h × 1 h before administration
of contrast material and 1 mL/kg/h × 6 h after contrast
material [B].
37

38. – Give 0.45% NS IV …1 ml/kg/h for 12 hrs before &
after the procedure
• Hydration--dilutes the contrast media, prevents renal
vasoconstriction that contributes to hypoxia & ischemia,
and minimize tubular obstruction
…….CIN
38

39. 2. Nephrolithiasis
• Kidney stones…….incidence……5-10%
• Strong genetic association
• Male : female ratio………..3:1
• Usually contains....Ca+ salts (account 70-80%)
• Drug-induced…..insoluble drugs in urine …..
– form crystals in distal tubules
– E.g acyclover, sufla, triamterene, MTX, indinavir
• Hydration is a key……………may add anti-pain
39

40. 3. Diabetic Nephropathy
• Incidence………Type I (up to 50%) vs. Type II (few)
• The first sign………Proteinuria
• Recommended Test
– Microalbuminuria test…………..30-300 mg/day
• Type I…………have test yearly at 5 years from
diagnosis
• Type II ……….begin test at diagnosis
• Prevention:
– ACE inhibitors
– Control of hypertension
– Low protein diet………reduce excessive BUN
40

41. 4. Penicillin-Induced AIN
• Acute interstitial necrosis
– Occurs 6-10 days
– Associated w/fever, rash, malaise…..?????
– Usually non-oligouric
– Treatment………..stop Penicillin & give supportive
therapy
– Prednisone 1 mg/kg for 7 days and then gradually
taper the dose over the next several weeks (total
therapy of can be up to 8-14 weeks)
– How??????????????
41

42. Treatment of AKI
• Current treatment is focused on primary prevention,
treating the underlying cause, and treating
associated complications.
• Diuretics if edema occurs……IV furosemide
• Prerenal azotemia: Correct primary hemodynamic
– Normal saline if volume depleted
– Pressure management if needed (↓BP)
– Blood products if needed (↓Hgb)
• Postrenal azotemia – relieve obstruction
– Consult Urology….BPH, Prostate Cancer
• The ultimate goal is to have the patient’s renal
function restored to pre-AKI baseline 42

43. Treatment
• Intrinsic: no universal therapy
– Avoid insult
– Consider fluid bolus…..perfusion/urine production
– Loop diuretics for oliguric/euvolemic or hypevolemic
• Furosemide ………..40-80 mg IV every 6-8 hrs or
• Furosemide infusion 40-80 mg IV bolus; then, 10-20 mg/hr iv
• Furosemide is a commonly used intervention.
N.B Studies show that it is ineffective in preventing and treating
ARF [A].
– Dopamine therapy …………1-2 mcg/kg/min….
• Not recommended anymore
– Natriuretic peptides, insulin-like growth factor, and
thyroxine also have no benefit in the treatment of ARF
– Acidosis……………. restrict dietary protein
• HCO3 to maintain arterial pH > 7.35
– Dialysis if needed
43

44. Additional Treatment
• General Measures
– Identify and correct all prerenal and postrenal causes.
– Review drug list: Stop nephrotoxic drugs and renally
adjust others.
– Always record ins and outs and daily weights.
– Watch for complications, including hyperkalemia,
pulmonary edema, and acidosis—all potential reasons
to start dialysis.
– Ensure good cardiac output and subsequent renal
blood flow.
– Follow nutrition suggestions and be aware of
infections; treat aggressively if they occur.
– Start patients on H2 inhibitors or proton pump
inhibitors, and avoid aspirin to avoid bleeding
44

45. • One of your family child was admitted to ACS
hospital. You are going to visit him. What are the
most likely and best thing you are planning?
A. Asking him with a 1 litter mango juice
B. Asking him with a kilo of banana
C. Asking him with a pack of biscuit
D. Asking with a bottled water
45

46. Diet for AKI patients
• Total caloric intake should be 35–50 kcal/kg/d to
avoid catabolism.
• Sodium should be restricted to 2 g/d [A].
• Potassium intake should be restricted to 40
mEq/d.
• Phosphorus should be restricted to 800 mg/d. If it
becomes high, treat with calcium carbonate or
other phosphate binder [A].
• Magnesium compounds should be avoided.
46

47. Patient Education
• Keep well hydrated.
• Avoid nephrotoxic drugs such as NSAIDs, ACE
inhibitors, and aminoglycosides.
47

48. Treatment of AKI complication
Hypertension
Hyperkalimia
Hypocalcemia
hyperphosphatemia
Acidocis
Anemia
48

49. 1. Hypertension
• Cause:
– Volume overload; Intrinsic renal disease
• Volume overload: direct vasodilators
–calcium channel blockers, clonidine,
nicardipine drip, nitropruside, etc.
• Intrinsic renal disease:
–ACE Inhibitors
–Goal is to prevent stroke, CHF
49

50. 2. Hyperkalemia
• Other risk factors:
–infection, hemolysis, acidosis
• How can you tell if it is “real”?
• It’s real. What’s the first thing to do?
• What’s next?
50

51. Hyperkalemia…
• Role of the following agents:
– insulin (+ glucose to prevent hypoglycemia)
– bicarbonate infusion
– albuterol (SQ/aerosol)
• What happens to ionized calcium level as you
correct the acidosis?
• What’s the third step?
51

52. 3. Calcium and Phosphate
• Metastatic calcification: Ca+2 x PO4 > 60-70
• Often are reciprocal: PO4 Ca+
• Symptoms of hypocalcemia:
– irritability, tetany, Symptoms
• If hypoalbuminemic:
– check ionized Ca or
– correct (0.8 increase of Ca for each 1.0 of albumin
below 4)
52

53. Hypocalcemia and hyperphosphatemia…
• Reduce PO4 with calcium acetate if can
swallow pills, calcium carbonate if needs
liquid
• Diet restriction
• Avoid exogenous PO4: Fleet's, carafate, TPN
53

54. 4. Acidosis
• Correct if bicarbonate is < 15
• Acidosis makes feel terrible
• Restict dietary protein (<0.5 g/kg/day)
• Sodium bicarbonate (arterial pH >7.2)
• Dialysis
• BUT...
– watch sodium and fluid overload
– watch lowering ionized calcium levels (by
increasing binding of calcium to albumin) 54