Pharmacy

1. Drug-induced Kidney Disease
By: Aster Wakjira
(B.Pharm ,MSc,clinical Pharmacist)
Email:asterwakjira@gmail.com

2. Introduction to DIKD
 Drug-Induced Kidney Disease (DIKD ) or nephrotoxicity is
adverse functional or structural change in the kidney caused by
diagnostic or therapeutic agents when systemically absorbed.
 It is a relatively common complication with variable
presentations depending on the drug and clinical setting,
inpatient or outpatient.
2

3. Epidemiology
 Studies show that incidence of …..
🞑 community-acquired DIKD is up to 20% of hospital admissions due
to AKI
🞑 up to 30% of critically ill patients experience AKI during their
hospitalization,
 1 in 4 cases is associated with nephrotoxic medications
🞑 drugs …… 26% of all cases of in-hospitalAKI
🞑 radiographiccontrast media, NSAIDs,ACEIs
3

4. Manifestations
 A decline in the GFR ……. the most common
…… ’’
 Rise in Scr and BUN
 acid–base abnormalities
 electrolyte imbalances
 urine sediment abnormalities
 proteinuria
 pyuria
 hematuria
4

5. Signs/symptoms
 Malaise, anorexia, vomiting, shortness of breath, or edema
 ↓d urine output …. progress to volume overload & HTN
 Proximal tubular injury:
🞑 metabolic acidosis with bicarbonaturia
🞑 glycosuriain the absence of hyperglycemia
🞑 reductionsin serum PO4, uric acid, K, Mg due to ↑d urinarylosses
 Distal tubularinjury:
🞑 Polyuriafrom failure to maximally concentrateurine
🞑 metabolic acidosis from impaired urinary acidification
🞑 hyperkalemia from impaired potassium excretion
5

6. Lab tests
 Abrupt reduction in kidney function (within 48hrs)
🞑 defined as an absolute increase in Scr of ≥0.3 mg/dL
🞑 a percentage increase in Scr of ≥50% (1.5-fold from baseline) within 7
days,or
🞑 oliguriaof <0.5 mL/kg/ hr for more than 6 hrs
6

7. Lab tests ….
 Changes in Scr or urine output consistent with the diagnostic criteria
for AKI, when correlated temporally with the initiation ofdrug
therapy, are a common threshold for the identification of DIKD.
 Nephrotoxicity may also be evidenced by primary alterations in renal
tubular function without a corresponding loss of glomerular
filtration.
🞑 Under this condition, urinary enzymes and low-molecular-weight
proteins may be used as more specific biomarkers of nephrotoxicity
compared with Scr and BUN.
7

8. Prevention of DIKD
 Interventions used to reduce the development of nephrotoxicity
…..
🞑 Avoid the use of nephrotoxic agents for patients at increased
risk for toxicity
🞑Adjust medication dosage regimens based on estimates of renal
function
🞑 Adequate hydration to establish high urine flow rates
8

9. ATN
 Drugs cause renal tubular epithelial cell damage through direct
cellular toxicity or ischemia.
 Damage that is localized in the proximal and distal tubular epithelia
is termed acute tubular necrosis (ATN).
 ATN …..
🞑 the most common presentation of DIKD in inpatients
🞑 manifests as cellular debris-filled, muddy-brown, granular casts in the
urinary sediment
9

10. ATN…..
 Specific indicators of proximal tubular injury include …
🞑 metabolic acidosis,glycosuria,
🞑 reductionsin serum phosphate,uric acid, potassium, magnesium as a
result of increased urinarylosses.
 Indicators of distal tubular injury include:
🞑 polyuria, metabolic acidosis, hyperkalemia
 ATN is common with AGs, radiocontrast media, cisplatin,
amphotericin B, osmotically active agents (e.g, Igs, dextrans,
mannitol)
10

11. Aminoglycoside nephrotoxicity
 Incidence: 10 - 25% of pts receiving the therapeutic course
 Critically ill patients have higher risk …..58%
 Clinical evidence of AG-associated nephrotoxicity is typically seen
within 5 to 7 days after initiation of therapy;
🞑 manifests as a gradual progressive rise in Scr and BUN and decrease in
creatinine clearance
 Present with nonoliguria, sometimes hematuria and proteinuria.
 Full recovery is common if AG is discontinued immediately.
 Renal replacement therapy ….if severe AKI
11

12. Pathogenesis
 AG-associated ATN is primarilydue to …..
🞑 Accumulation of high drug concentrations within proximal tubular
epithelial cells, and subsequent generation of reactive oxygen species
that produce mitochondrialinjury
, leading to cellular apoptosis and
necrosis.
 The degree of nephrotoxicity is related to cationic charge of AGs
and directly proportional to the number of cationic groups on the
drug molecule.
🞑 E.g. higher rates of toxicity with neomycinvs. other AGs.
🞑 neomycin>gentamycin>tobramicin>amikacin>streptomycin
12

13. Risk factors
 Large total cumulative dose
 Prolonged therapy
 Combination drug therapy (synergistic nephrotoxicity)
🞑 cyclosporine, amphotericin B,vancomycin, diuretics, iodinated
radiographic contrast agents, cisplatin, NSAIDs
 Preexisting clinical conditions of the patient
🞑kidney disease, DM, increased age, dehydration, etc.
13

14. Prevention
 Use alternative antibiotics,
🞑 FQs(such as ciprofloxacinor levofloxacin)
🞑 3rd or 4th-generationcephalosporins(ceftazidime, cefepime)
 When AGs are necessary, gentamicin, tobramycin, and amikacin
are most commonly used
 Avoid volume depletion
 Avoid concomitant therapy with other nephrotoxic drugs
 Limit the total AG dose administered
 Once daily dosing
14

15. Management
15
 Discontinue AG or revise the dosage regimen if AKI is evident
 Discontinue other nephrotoxic drugs, if possible
 Maintain adequate hydration

16. Contrast-induced nephrotoxicity (CIN)
 It is the third leading cause of hospital-acquiredAKI;
🞑 accountingfor 10% to 13% of cases
 Present commonly as nonoliguria with kidney injury apparent
within the first 24 - 48 hours following adm’n of contrast.
 Irreversible oliguric AKI requiring dialysis may occur in high-risk
patients.
 Urinalysis …….. tubular enzymuria with/without hyaline and
granular casts
16

17. Pathogenesis of nephrotoxicity
 Mechanism of toxicity: renal ischemia and direct cellular toxicity
 Disruption of PG synthesis and release of adenosine, endothelin
and other renal vasoconstrictors …. results in systemic
hypotension and renal VC leading to renal ischemia
 Contrast may reduce renal blood flow leading to ↑d conc of
contrast in the renal tubules that exacerbates the direct
cytotoxicity &ATN
 High osmolar contrast agents are hyperosmolar to plasma…
🞑 causes….osmotic diuresis, dehydration, renal ischemia, and increased
blood viscosity caused by red blood cell aggregation
17

18. Risk factors
 Preexisting kidney disease [GFR <60mL/min/1.73 m2]
 Conditions associated with decreased renal blood flow
🞑 CHF, dehydration/volume depletion, hypotension
 Patients with atherosclerosis
 Diabetes, due to coexisting kidney disease (diabetic nephropathy)
 Larger volumes or doses of contrast
 Use of high osmolar contrast agents
 Concurrent use of nephrotoxins, NSAIDs and ACEIs
 Risk factors are additive
18

19. Prevention
 Use alternative imaging procedures (e.g., ultrasound,) in high-risk
pts.
 Minimize contrast volume/ dose, if it must be used
 Use iso-osmolar contrast agents (e.g., iodixanol)
 Avoid concurrent use of nephrotoxic drugs, e.g., NSAIDs, AGs
 Hydration with isotonic saline for CIN prevention
🞑 infuse at 1mL/kg/h adjusting post-exposure as needed to maintain
urine flow rate of ≥150 mL/h
 N-acetylcysteine for patients with preexisting kidney disease
🞑 600 mg po bid for 2 days, the first dose prior to contrast
19

20. Management
 Currently no specific therapy available
 Supportive care
 Close monitoring ….
🞑 Scr
🞑 urine output
🞑 electrolytes(e.g., Na, K)
🞑 volume status
 Renal replacement therapy, when indicated
20

21. Cisplatin nephrotoxicity
 Nephrotoxicity is the dose-limiting toxicity of platin-containing
compounds.
 The damage is dose related and cumulative with subsequent cycles
of therapy.
 Cisplatin causes impaired tubular reabsorption and decreased
urinary concentration ability
🞑 ↑d excretion of salt & water (polyuria)within 24hrs
🞑 ↓GFR (↑Scr) within 72 to 96 hrs of adm’n.
 Carboplatin is the preferred agent in high-risk patients.
🞑 lower incidence of nephrotoxicity than cisplatin
21

22. Cisplatin nephrotoxicity….
 Hypomagnesemia is hallmark finding of cisplatin nephrotoxicity
🞑 due to ↓Mg reabsorption, ↑ urinary Mg losses
🞑 Hypomagnesemia is often accompanied by hypocalcemia and
hypokalemia
 may be severe, leading to seizures, neuromuscular irritability
 Urinalysis: leukocytes, tubular epithelial cells, granular casts
 Renal biopsy: reveals necrosis of proximal, distal tubules or
collecting ducts
 Risk factors: large cumulative doses, increased age, dehydration,
concurrent use of nephrotoxic drugs, alcohol abuse
22

23. Prevention
 Dose reduction
🞑 use of platin cpds in combination with other chemo
 Avoid concurrent use of other nephrotoxic drugs, and diuretics such
as furosemide & mannitol
 Hydration with isotonic saline
🞑 initiate 24hrs prior to & continue for 2-3days after cisplatin adm’n
 Pretreatment with amifostine for patients at high risk
🞑 dose: 910 mg/m2 IV over 15min, start 30min prior to cisplatin
🞑 Amifostine…. chelates cisplatin in normal cells
 a cytoprotective agent
23

24. Management
 Cisplatin inducedAKI …usually reversible with time
 Supportive care,
🞑 such as chronicdialysis if irreversiblenephrotoxicityoccurs
 Monitor Scr and BUN daily
 Monitor serum Ma, K, and Ca daily & correct as needed.
 Hypocalcemia and hypokalemia may be difficult to reverse until
hypomagnesemia is corrected.
24

25. Amphotericin B nephrotoxicity
 Its incidence is associated with cumulative dose
🞑 30% …..at median cumulative doses of 240mg
🞑 >80% …..when cumulative doses approach 5g
 Tubular dysfunction ….manifests 1 to 2 weeks after therapy
🞑 ↓in GFR, ↑in Scr and BUN
🞑 Nonoliguria,
🞑 renaltubular K, Na, and Ma wasting
🞑 impaired urinaryconcentratingability
🞑 distal renal tubular acidosis
25

26. Amphotericin B nephrotoxicity….
 Pathogenesis ….
🞑direct tubular epithelial cell toxicity
 lead to ↑ tubular cell membrane permeability, lipid peroxidation,
and eventual necrosisof proximal tubular cells.
🞑afferent arteriolar vasoconstriction
 lead to ↓renal blood flow and GFR, and ischemictubular injury
 Nephrotoxicity is lower in liposomal formulations than
conventional amphotericin B.
26

27. Amphotericin B nephrotoxicity….
 Risk factors
🞑 Preexistingkidneydisease
🞑 Large individual and cumulative doses
🞑 Short infusion times
🞑 V
olume depletion
🞑 Hypokalemia
🞑 Increased age
🞑 Concomitant adm’n of diuretics & other nephrotoxins (e.g,
vancomycin, cyclosporine)
27

28. Prevention
 Switch to a liposomal formulation of amphotericin B
🞑 for high-risk patients
 Limit the cumulative dose & increase the infusion time
 Hydration
🞑 a single IV infusion of NS 10 - 15 mL/kg prior to adm’n of each
dose of amphotericin B
 Avoid concomitant adm’n of other nephrotoxins
 Use alternatives drugs such as itraconazole, voriconazole
28

29. Management
 Discontinue amphotericin B and substitute with an alternative
antifungal therapy
 Monitor Scr and BUN daily
 Monitor dailyserum Ma, K, Ca & correct as needed
29

30. Osmotic nephrosis
 Renal lesions observed in patients with severe AKI after parenteral
adm’n of hyperosmolar agents is referred to as osmotic nephrosis.
 IV immunoglobulin solutions containing hyperosmolar sucrose may
cause osmotic nephrosis and AKI.
🞑 sucrose nephrosis
🞑 reversibleshortly after discontinuingtherapy
 It occurs due to an osmotic gradient between the tubular lumen and
epithelial cells.
 Characterized by severe swelling and vacuolization of the proximal
tubular epithelial cells.
30

31. Osmotic nephrosis ….
 Mechanism of kidneyinjury
🞑 Uptake of the offending agent by pinocytosis into proximal
tubular epithelial cells
🞑 Formation of vacuoles and accumulation of lysosomes
🞑Oncotic gradient
🞑Cellular swelling, tubular luminal occlusion
31

32. Osmotic nephrosis ….
 Factors associated with osmotic nephrosis:
🞑 drugs (such as mannitol, LMW dextran, hydroxyethylstarch)
🞑 drug vehicles (e.g., sucrose,maltose, propyleneglycol)
🞑 radiographiccontrast media
 Urinalysis: proteinura or vacuolated tubular cells in patients with
AKI
 Definitive diagnosis of osmotic nephrosis…..kidney biopsy
32

33. Osmotic nephrosis ….risk factors
 Excessive doses of offendingagents
 Preexisting kidney disease
 Ischemia
 Older age (>65 years)
 Concomitant use of other nephrotoxins, esp. cyclosporine
33

34. Prevention
 Limit dose and reduce rate of infusion
 Avoid dehydration
 Avoid concomitant nephrotoxins
 Renal replacement therapy
 Usually reversible upon withdrawal of the offending drug
34

35. Hemodynamicallymediated kidneyinjury
 It refers to any cause of AKI resulting from ….
🞑 acute ↓ intraglomerular pressure
🞑 ↓ renalblood flow (e.g., hypovolemia,CHF)
🞑 medicationsthat affect RAS
 The kidneys receive ~25% of CO
🞑 rendersthe kidneys susceptible to alterations in renal blood flow
🞑 enhances the exposure of kidneys to circulating drugs
35

36. Hemodynamicallymediated ….
 Within each nephron,
🞑 blood flow and pressure are regulated by glomerular afferent and
efferent arterioles
 to maintain intraglomerular capillary hydrostatic pressure, glomerular
filtration, and urine output.
 Afferent & efferent arteriolar VCs…primarily mediated by AT-II
 Afferent vasodilation …..primarily mediated by PG E2
 Together these processes maintain GFR and urine output.
36

37. Hemodynamicallymediated ….
 Normally, the kidney attempts to maintain GFR by dilating the
afferent arteriole and constricting the efferent arteriole in response to
a decrease in renal blood flow.
🞑 ↓d blood flow ….. ↑reninsecretion …..↑AT-II
 Drug-induced causes of hemodynamic kidney injury results from…
🞑 constriction of glomerular afferent arterioles,and/ or
🞑 dilation of glomerular efferent arterioles
 Drugs most commonly involved …..
🞑 ACEIs,ARBs, NSAIDs
37

38. ACEIs/ARBs-induced kidney injury
 Incidence is most likely in patients with …..
🞑 renalarterystenosis
🞑 volume depletion
🞑 CHF
🞑 preexisting kidney disease, including diabetic nephropathy
 ↓GFR
 ↑Scr ….up to 30% within 3 to 5 days
🞑 reversibleupon stopping the offending drug
38

39. Cont’d
 ACEIs (e.g., enalapril, ramipril)
🞑 ↓synthesisof AT-II, then it preferentiallydilate efferent arteriole
🞑 ↓ outflow resistance from the glomerulus
🞑 ↓ hydrostaticpressure in the glomerular capillaries
 ↓ GFR leading to nephrotoxicity
39

40. Risk factors
 Patients with ↓d arterial blood volume (prerenal states)
🞑 CHF
🞑 volume depletion from excess diuresis or GI fluid loss
🞑 hepatic cirrhosiswith ascites
🞑 nephroticsyndrome
 Preexisting kidney disease; renal artery stenosis
 Concurrent nephrotoxic drugs
40

41. Prevention
 Initiate therapy with very low doses short-acting ACEI (e.g.,
captopril 6.25 mg to 12.5 mg),
🞑 gradually titrate the dose upward & convert to a longer-acting
 Monitor renal function indices & serum K daily
 Avoid concurrent use of hypotensive agents and other drugs
that affect renal hemodynamics (e.g., NSAIDs, diuretics)
 Avoid dehydration
41

42. Management
 Renal function usually improves over several days after
ACEI/ ARBis discontinued
 Manage severe hyperkalemia
 ACEI/ ARBtherapy may be reinitiated,
🞑 for patients with CHF, after intravascular volume depletion has been
correctedor diureticdoses reduced.
42

43. NSAIDs and selective COX-2 inhibitors
 NSAID and COX-2-induced AKI can occur within days of initiating
therapy, particularly with a short-acting agent such as ibuprofen.
 Pathogenesis: disruption of normal intraglomerular autoregulation.
 NSAIDs inhibit COX-catalyzed synthesis of vasodilatory PGs (PG
I2, PG E2)
 Typical complaints: diminished urine output, weight gain, edema
 Elevated BUN, Scr, K, BP.
43

44. Cont’d
 Effects of the PGs are primarily local and result in net afferent
arteriolar vasodilation, and serve a vital autoregulatory role in the
protection against renal ischemia & hypoxia by antagonizing renal
arteriolar VC.
🞑 Renal arteriolar vasoconstrictors  AT-II, norepinephrin,
endothelin,and vasopressin
 NSAIDs inhibit PG activity and alter the normal autoregulatory
balance in favor of renal vasoconstrictors, thereby promoting renal
ischemia and a reduction in glomerular filtration.
44

45. Risk factors
 Age > 60yrs
 Preexisting kidney disease
 Hepatic disease with ascites
 CHF
 Intravascular volume depletion/dehydration
 Concurrent diuretic therapy
 Combined use of NSAIDs or COX-2 inhibitors
 Concurrent use of nephrotoxic drugs
45

46. Prevention
 Avoid potent drugs (e.g., indomethacin)
 Use analgesics with less PG inhibition (acetaminophen, aspirin)
 Use minimal dose for shortest duration...if NSAID is essential
 Avoid concurrent use of ACEIs, ARBs, diuretics
 Avoid dehydration
 Selective COX-2 inhibitors (meloxicam, celecoxib, valdecoxib) may
be beneficial in high-risk patients.
 Management of NSAID-induced AKI
🞑 Discontinue the therapy; Supportive care
46

47. Cyclosporine,tacrolimus
 Cyclosporine & tacrolimus (immunosuppressives).
 Acute hemodynamically mediated kidney injury may occur within
days of initiating therapy
🞑 ↑Scr , ↓creatinine clearance
 Renal biopsy ….
🞑 thickening of arterioles
🞑 proximal tubular epithelial cell vacuolization and atrophy
🞑 interstitial fibrosis
 May also cause delayed chronic interstitial nephritis
47

48. Cont’d
 Cyclosporine and tacrolimus therapy
🞑 ↑ potent VCs (thromboxane A2, endothelin)
🞑↓ vasodilators (nitric oxide, PG E2)
🞑Net effect is an imbalance in afferent & efferent tone
 afferent VC and ↓GFR
 Acute nephrotoxicity is dose related
48

49. Risk factors
 Age over 65
 Higher dose
 Diuretic use
 Concomitant therapy with nephrotoxic drugs (e.g., NSAIDS)
 Older kidneyallograft age
49

50. Prevention
 Pharmacokinetic and pharmacodynamic monitoring
🞑 b/ c kidneyinjuryis concentrationrelated
 CCBs ….may antagonize the vasoconstrictor effect of
cyclosporine by dilating glomerular afferent arterioles and
preventing acute decreases in renal blood flow and glomerular
filtration
50

51. Management
 Discontinuation of interacting drugs
 Dose reduction
 Treatment of contributing illness
 Monitor Scr and BUN closely
51

52. Crystal nephropathy
 Crystal nephropathy is caused by precipitation of drug crystals in
distal tubular lumens, which commonly leads to…
🞑intratubular obstruction
🞑interstitial nephritis
🞑Acute tubular necrosis
 Numerous medications have been associated with development of
crystal nephropathy.
52

53. Intratubular obstruction
 Caused by drugs through….
🞑 direct precipitation of the drug itself
🞑 promoting the release and precipitation of tissue-degradation
products(indirect)
 Antineoplastic drugs
🞑 Cause tubular obstruction byinducing….
 tumor lysis syndrome
 hyperuricemia
 intratubular uric acid crystals
🞑 Cause acute oliguric or anuric kidney injury
🞑 Diagnosis:urine uric acid-to-creatinineratio >1.
53

54. Intratubular obstruction ….
 Uric acid precipitation can be prevented by
🞑 Vigorous hydration with NS, beginning at least 48 hrs prior to
chemo, to maintain urine output 100 mL/hr in adults
🞑 Allopurinol 100 mg/m2 tid (300 to 600 mg daily; max. 800
mg/day) started 2 to 3 days prior to chemo
🞑 Urinary alkalinization to pH 7.0
54

55. Intratubular obstruction ….
 Intratubular precipitation of drugs can directly cause AKI.
 Precipitation of drug crystals is due primarilyto….
🞑 supersaturation of a low urine volume with the offending drug, or
🞑 relative insolubility of the drug in either alkaline or acidic urine
55

56. Intratubular obstruction ….
 Urine pH decreases to ~4.5 during maximal stimulation of renal
tubular hydrogen ion secretion.
 Certain solutes can precipitate and obstruct the tubular lumen at
this acid pH, particularly when urine is concentrated, such as for
patients with volume depletion.
 Several antiviral drugs …. intratubular precipitation &AKI
🞑 Eg., Acyclovir is associated with intratubular precipitation in
dehydratedoliguricpatients.
56

57. Intratubular obstruction ….
 Foscarnet forms complex with ionized calcium ….
🞑 calcium-foscarnet salt crystals in renal glomeruli …. crystalline
glomerulonephritis
 Indinavir (PI) may cause ….
🞑 crystalluria,crystal nephropathy, nephrolithiasis
🞑 dysuria,urinary frequency, back and flank pain
🞑 prevented by use of 2 to 3 L of fluid per day
 Sulfadiazine at high dose and methotrexate may precipitate in
acidic urine
57

58. Intratubular obstruction ….
 Prevention ….
🞑Vigorous hydration prior to the drug adm’n
🞑Maintain a high urine volume
🞑Urinary alkalinization
58

59. Nephrolithiasis
 It is a type of crystal nephropathy
🞑 formation of renal calculi or kidney stones
🞑 GFR is usually not decreased
 Drug-induced nephrolithiasis
🞑 abnormal crystal precipitationin the renal collecting system
🞑 cause pain, hematuria, infection, or urinary tract obstruction with
kidneyinjury
 Overall prevalence of drug-induced nephrolithiasis is 1%, i.e.,
rare.
59

60. Cont’d
 Triamterene…..kidney stone formation
 Sulfadiazine is a poorly soluble sulfonamide
🞑 cause symptomatic acetylsulfadiazine crystalluria with stone formation
and flank or back pain, hematuria, or kidney injury
 Other drugs that cause nephrolithiasis
🞑 Indinavir, foscarnet,ciprofloxacin
 A high urine volume and urinary alkalinization to pH >7.15 may be
protective.
60

61. Tubulointerstitial nephritis
 Tubulointerstitial nephritis refers to diseases in which the
predominant changes occur in the renal interstitium rather than the
tubules.
 Presentation may be ….
🞑 acute and reversible with interstitial edema, rapid loss of renal
function, or
🞑 chronic and irreversible,with interstitial fibrosis
61

62. Acute allergic interstitial nephritis (AIN)
 It is the underlying cause for up to 3% of all cases of AKI.
 Associated with allergic hypersensitivity response (idiosyncratic)
 Clinical signs present 2 weeks after exposure to a drug but may
occur sooner if the patient was previously sensitized.
 Drugs responsible ….
🞑 β-lactam antibiotics (including cephalosporins)
🞑 NSAIDs
🞑 Ciprofloxacin, PPIs, loop duiretics
62

63. Cont’d
 Management …..
🞑Discontinue the offending drug
🞑 Corticosteroid therapy soon after diagnosis of AIN.
 Oral prednisone 1 mg/kg/day for 8 to 14wks with a stepwise taper.
🞑Close monitoring of Scr, BUN and signs & symptoms of AIN
63

64. Chronic Interstitial Nephritis
 The lesion is usually progressive and irreversible.
 Drugs involved:
🞑 Lithium-nephrotoxicity…. prevalence…..1.2%
🞑 Cyclosporine
🞑 Tacrolimus
64

65. Cont’d
 Lithium-nephrotoxicity …..
🞑 usually recognized by↑BUN or Scr
🞑 Polydipsia (excessive thirst) and polyuria (excessive urination; >3L/d)
are observed in patients with nephrogenicDI
🞑 Biopsy:interstitial fibrosis,tubular atrophy
, and glomerular sclerosis.
🞑 Risk factor …..
 Long-term lithium therapy
 ↑d age
65

66. Prevention
 Maintain low lithium concentrations
 Avoid dehydration
 Monitor renal function
 Amiloride …. for prevention and treatment of lithium-induced
nephrogenic diabetes insipidus
🞑 Amiloride blocks epithelial Li+ transport into the collecting duct in
the distal nephron.
66

67. Management
 Discontinue lithium therapy
 Amiloride 5 to 10mg daily during continued lithium therapy
 ↑amiloride dose to 20 mg daily─If polyuria does not resolve within
7 to 10 days of therapy.
 Adequate hydration
 Avoidance of other nephrotoxic agents
 Monitor Li serum concentrations and renal function indices (urine
output, BUN, and Scr, )
67

68. Analgesic nephropathy
 X/d by chronic tubulointerstitial nephritis with papillary necrosis.
 Chronic excessive consumption of combination analgesics,
particularly those containing phenacetin; aspirin, actaminophen,
and NSAIDs, alone or in combination
68

69. Analgesic nephropathy….
 Clinical presentation
🞑 Often asymptomatic
🞑 Early manifestations: headache and upper GI symptoms but are
nonspecific
🞑 Later manifestations: impaired urinary concentrating ability
, dysuria,
sterile pyuria, microscopic hematuria, mild proteinuria (<1.5 g/day),
and lower back pain.
🞑 As disease progresses, hypertension, atherosclerotic CV disease, renal
calculi, & bladder stones are common
🞑 Pyelonephritisis a classic finding in advanced analgesicnephropathy.
69

70. Analgesic nephropathy….
 The most sensitive and specific diagnostic criteria include
🞑 a history of chronic daily habitual analgesic ingestion (daily use for at
least 3 to 5 yrs)
🞑 ↑Scr …. up to 4 mg/dL
🞑 Papillarycalcifications
 Risk Factors
🞑 Cumulative consumption of combination analgesics
🞑 Chronic use of therapeuticdoses of NSAIDs alone
🞑 High-doseacetaminophen use
70

71. Prevention and Management
 Prevention
🞑 Limit the total dose
🞑 Avoid combined use of two or more analgesics
🞑 Maintain good hydration
🞑 Use acetaminophen for patients with renal insufficiency
 Management
🞑 Cessation of analgesic consumption
🞑 Renal function indices, including urine output, BUN, and Scr, should
be monitored everyseveral months.
71

72. Renal vascular disease
 Drug-induced renal vascular disease commonly presents as ….
🞑 vasculitis, thrombosis …… associated with hydralazine,
propylthiouracil,allopurinol
🞑 cholesterolemboli …..drugs associated are warfarin, thrombolytic
agents
 Present with hematuria, proteinuria, oliguria, & red cell casts, along
with fever, malaise, myalgias, & arthralgias.
 Treatment ….
🞑 withdraw the offending drug
🞑 Adm’n of corticosteroids/other immunosuppressive therapy
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