Drug-induced kidney disease (DIKD) can have various presentations depending on the drug and clinical setting. Studies show that 20-30% of hospital-acquired acute kidney injury (AKI) cases are associated with nephrotoxic medications such as aminoglycosides, iodinated contrast media, and NSAIDs. DIKD most commonly manifests as acute tubular necrosis, characterized by rises in serum creatinine and BUN, along with urinary abnormalities. Prevention focuses on avoiding unnecessary nephrotoxic drugs, proper dosing based on kidney function, and adequate hydration. Management involves discontinuing causative agents and providing supportive care.

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
72