Does this patient have drug-induced nephrotoxicity?

The initial diagnosis of drug-induced nephrotoxicity typically involves detection of abrupt changes in kidney function manifesting as acute increases in serum creatinine, blood urea nitrogen (BUN), or decreased urine output, which is temporally related to initiation or ongoing use of a potentially nephrotoxic drug. The mechanism and presentation of drug-induced nephrotoxicity may differ between various drugs or drug classes, and they are generally categorized based on the histological component of the kidney that is affected.

The most common drug-induced renal structural-functional alterations include acute tubular necrosis (ATN), hemodynamically mediated kidney injury, acute allergic interstitial nephritis (AIN), intratubular obstruction, and glomerular disease.

ATN is the most common presentation of DIN in acute-care settings. Drug-induced ATN may be caused by either direct toxic or ischemic effects of offending drugs. Damage is most often localized in the proximal and distal tubular epithelia, with cellular degeneration and sloughing from proximal and distal tubular basement membranes. The primary drugs implicated in ATN are aminoglycosides, radiographic contrast media, cisplatin, and amphotericin B.

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Aminoglycosides: Aminoglycoside-induced ATN is typically seen within 5 to 10 days after initiation of therapy. It manifests as a gradual progressive rise in serum creatinine (typically an increase of 0.5 mg/dL or more) and BUN, and a corresponding decrease in kidney function. Patients usually present with nonoliguria and sometimes have microscopic hematuria and proteinuria. Renal magnesium wasting can occur, but the risk of symptomatic hypomagnesemia is generally low.

The diagnosis of aminoglycoside-induced nephrotoxicity is often difficult, particularly in critically ill patients with multiple comorbidities, and is confounded by other factors that are associated with the development of acute kidney injury, including concurrent dehydration, sepsis, hypotension, ischemia, and use of other nephrotoxic drugs.

Radiographic contrast media: ATN induced by radiographic contrast media typically presents as nonoliguria. Kidney injury is apparent, manifesting as a rise in serum creatinine, within the first 24 to 48 hours after the administration of contrast. The serum creatinine concentration usually peaks between 3 and 5 days after exposure.

Cisplatin: Cisplatin nephrotoxicity occurs in as many as 20%-30% of patients and results in impaired tubular reabsorption and decreased urinary concentration ability, leading to increased excretion of salt and water within 24 hours of treatment. A decrease in kidney function evidenced by a rise in serum creatinine concentration may be seen within 72 to 96 hours after cisplatin exposure. Hypomagnesemia is a hallmark finding of cisplatin nephrotoxicity, and is often accompanied by hypocalcemia and hypokalemia. Serum creatinine peaks approximately 10 to 14 days after initiation of therapy.

Amphotericin B: Amphotericin B nephrotoxicity is typically observed after administration of cumulative doses of 2 to 3 g. The time to onset of kidney injury varies considerably, ranging from a few days to weeks. Tubular dysfunction usually manifests 1 to 2 weeks after treatment is begun, followed by a decrease in glomerular filtration rate and a rise in serum creatinine and blood urea nitrogen concentrations.

Hemodynamically mediated kidney injury may result from administration of drugs that affect the renin angiotensin system, and thus can cause an acute decrease in intraglomerular pressure by constricting glomerular afferent arterioles and/or dilating efferent arterioles. Angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), nonsteroidal antiinflammatory drugs (NSAIDs), and cyclooygenase-2 (COX-2) inhibitors and are most commonly implicated.

ACEIs/ARBs: ACEI and ARB therapy reduces the glomerular filtration rate (GFR), so a moderate rise in serum creatinine after initiation of therapy should normally be expected. A distinction must be made between a potentially detrimental reduction in GFR and a normal, predictable rise in serum creatinine. An increase in serum creatinine of up to 30% is commonly observed within 3 to 5 days of initiating therapy and is an indication that ACEIs and ARBs have begun to exert their desired pharmacologic effects. The increase in serum creatinine typically stabilizes within 1 to 2 weeks and is usually reversible upon stopping the drug. However, an increase in serum creatinine of more than 30% above baseline in the course of 1 to 2 weeks likely indicates hemodynamically mediated kidney injury.

NSAIDs: NSAID- and COX-2 inhibitor-induced kidney injury can occur within days of initiating therapy, particularly with a short-acting agent such as ibuprofen, and usually coincides with concurrent illness leading to prerenal states. Patients typically present with complaints of decreased urine output, weight gain, and/or edema. Urine sodium concentrations (<20 mmol/L) and fractional excretion of sodium (<1%) are usually low, and BUN, serum creatinine, potassium, and blood pressure are typically elevated. The urine sediment is usually bland and unchanged from baseline, but may show occasional granular casts.

AIN has been described with the use of many drugs, and is classically associated with use of beta-lactam antibiotics. It usually manifests 2 weeks after drug exposure, but it may occur sooner if the patient was previously sensitized. AIN is an allergic hypersensitivity response characterized by a diffuse or focal interstitial infiltrate of lymphocytes, eosinophils, and occasional polymorphonuclear neutrophils.

Beta-lactams: Clinical signs of beta-lactam induced AIN present approximately 14 days after initiation of therapy and include fever, maculopapular rash, eosinophilia, arthralgia, and oliguria. Systemic hypersensitivity findings of the classic triad of fever, rash, and arthralgia, often along with eosinophilia and eosinophiluria, strongly suggest the diagnosis of AIN. However, this pattern of findings is not consistently reliable as one or more are frequently absent, so caution is warranted in basing diagnosis on hypersensitivity findings alone.

Intratubular obstruction and AKI may result from precipitation of drugs or their metabolites, which is due primarily to supersaturation of a low urine volume, or relative insolubility of the drug in either alkaline or acidic urine. Volume depletion is an important risk factor for the development of AKI. Urine pH decreases to approximately 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 in patients with volume depletion. Antiviral drugs, including acyclovir and indinavir, have been associated with intratubular precipitation and AKI.

Acyclovir is relatively insoluble at physiologic urine pH and is associated with intratubular precipitation in dehydrated oliguric patients. Indinavir has been associated with crystalluria, intratubular precipitation, dysuria, urinary frequency, back and flank pain, or nephrolithiasis in approximately 8% of treated patients.

Glomerular disease has been described with the use of a variety of drugs. Several different glomerular lesions may occur, including minimal change disease, focal segmental glomerulosclerosis (FSGS), and membranous nephropathy, mostly by immune mechanisms rather than direct cellular toxicity. The clinical presentation of each varies slightly, and typically involves abrupt onset of nephrotic range proteinuria, sometimes accompanied by hematuria and hypertension.

The bisphosphonates pamidronate and zoledronate are associated with the development of an aggressive form of FSGS called collapsing glomerulopathy. It presents with massive proteinuria (>8 g/day), and is typically characterized by rising serum creatinine at diagnosis and rapid progression to ESRD. Patients receiving intravenous formulations, high doses, or prolonged therapy are at highest risk.

What tests to perform?

Since the initial diagnosis of drug-induced nephrotoxicity typically involves detection of abrupt changes in kidney function, serum creatinine and BUN concentrations, surrogates of kidney function including urine output, and creatinine clearance or estimated GFR should be routinely assessed. Determination of other electrolytes such as sodium, potassium, magnesium, calcium and phosphorus in serum and urine is often useful for initial diagnosis and monitoring.

Urinalysis is instrumental for detecting early kidney abnormalities, and the urine sediment and level of proteinuria should also be evaluated to facilitate early diagnosis. The fractional excretion of sodium (FENa) should be performed to assess the functional integrity of the renal tubules.

In rare instances, ie, when noninvasive tests demonstrate poor sensitivity and specificity, and the patient is an acceptable candidate for the procedure without excessive risk, a renal biopsy may be valuable in establishing a diagnosis. Histological examination of the kidney tissue may also provide prognostic information and thus impact subsequent therapeutic decisions.

Aminoglycoside-induced nephrotoxicity: Presence of proteinuria, granular casts or tubular epithelial cells in urine sediment, and FENa >1% support diagnosis of aminoglycoside-induced ATN.

Radiographic contrast-induced nephropathy: Urinalysis typically reveals tubular enzymuria with hyaline and granular casts, but may also be completely void of casts. Unlike the presentation of typical ATN in which the FENa is usually >1%, the FENa observed with contrast-induced nephropathy is usually <1%.

Cisplatin nephrotoxicity: Urinalysis typically reveals leukocytes, renal tubular epithelial cells, and granular casts. Glucosuria and urinary magnesium wasting are common.

Amphotericin B nephrotoxicity: Nonoliguria, renal tubular potassium, sodium, and magnesium wasting, impaired urinary concentrating ability, and distal renal tubular acidosis are usually observed.

NSAID hemodynamically mediated kidney injury: Urine sodium concentrations and FENa are usually low (<20 mmol/L and <1%, respectively), and BUN, serum creatinine, potassium, and blood pressure are typically elevated. The urine sediment is usually bland and unchanged from baseline, but may show occasional granular casts.

AIN: Eosinophilia and eosinophiluria are frequently present. Tubular dysfunction is usually seen in drug-induced AIN, manifested by acidosis, hyperkalemia, salt wasting, and concentrating defects. The urine sediment usually reveals white cells, red cells, white cell casts, and granular casts; there is also usually normal or only mildly increased protein excretion (less than 1 g/day). The FENa is usually >1%. Kidney biopsy may be needed to confirm the diagnosis.

Intratubular obstruction: Intratubular obstruction resulting from deposition of drug crystals typically manifests in urine as red and white blood cells, granular casts, and characteristic crystals of the corresponding drug.

Glomerular disease: Proteinuria, particularly nephrotic range proteinuria with or without a decline in the GFR is a hallmark sign of drug-induced glomerular injury. Kidney function indices and blood pressure should be aggressively monitored. Kidney biopsy may be needed to confirm the diagnosis.

How should patients with drug-induced nephrotoxicity be managed?

The offending drug should be identified and, whenever possible, discontinued. When discontinuation is not an option, then dose adjustment based on accurate estimates of kidney function should be made, and standard supportive treatment focused on maintaining fluid and electrolyte balance should be employed.

Aminoglycoside-induced ATN: Aminoglycoside use should be discontinued if a decline in kidney function is evident, i.e., there is a serum creatinine increase of 0.5 mg/dL or more that is not attributable to another cause. Other nephrotoxic drugs should be discontinued if possible, and the patient should be maintained adequately hydrated and hemodynamically stable. Hypomagnesemia should be corrected with intravenous magnesium supplementation as needed.

Radiographic contrast-induced nephropathy: There is no specific therapy for established contrast-induced nephropathy. Treatment is supportive in nature, focused on maintaining fluid and electrolyte balance. Renal replacement therapy should be used as indicated.

Cisplatin nephrotoxicity: Cisplatin nephrotoxicity is usually partially reversible with time and supportive care, including real replacement therapy. Kidney function indices should be closely followed, with serum creatinine and BUN concentrations checked daily. Serum magnesium, potassium, and calcium concentrations should be monitored daily and corrected as needed.

Amphotericin B nephrotoxicity: Kidney function indices should be closely followed, with serum creatinine and BUN concentrations checked daily, and serum magnesium, potassium, and calcium concentrations monitored every other day and corrected as needed.

NSAID hemodynamically mediated kidney injury: NSAID-induced AKI is treated by discontinuation of therapy and supportive care.

AIN: The offending drug should be discontinued immediately. If kidney function does not begin to recover within one week, then corticosteroid therapy may be beneficial, and should be initiated immediately or soon after diagnosis of AIN. Oral prednisone 1 mg/kg/day (60 mg maximum) for 8 to 12 weeks with a stepwise taper has been used successfully. Kidney function indices and signs and symptoms of AIN should be monitored closely for improvement.

Intratubular obstruction: Treatment typically consists of vigorous hydration in order to achieve and maintain volume repletion, a high urine output, along with urinary alkalinization to enhance solubility of drug crystals.

Glomerular disease: Management of drug-induced glomerular disease varies based on the glomerular lesion, and mirrors treatment of non-drug causes of glomerular disease, typically requiring short to long courses of immunosuppressive therapy.

What happens to patients with drug-induced nephrotoxicity?

Aminoglycoside-induced ATN: Full recovery of kidney function is common if aminoglycoside therapy is discontinued immediately upon discovering signs of toxicity. The serum creatinine concentration usually returns to baseline within 21 days of discontinuing therapy. However, severe ATN and acute kidney injury may develop occasionally, particularly in patients with pre-existing CKD, and for these individuals renal replacement therapy may be required.

Contrast-induced nephropathy: This is usually mild and transient in nature, with recovery after 7 to 10 days after exposure. However, irreversible oliguric (urine volume <500 mL/day) kidney injury requiring renal replacement therapy has been reported in high-risk patients, including patients with pre-existing CKD and diabetes.

Cisplatin nephrotoxicity: Up to 25% of patients may have reversible elevations in serum creatinine and BUN for 2 weeks after cisplatin treatment. Kidney function usually recovers within 21 days. However, kidney damage is dose related and cumulative with subsequent cycles of therapy, so the serum creatinine concentration may continue to rise, and irreversible kidney injury may result.

Amphotericin B nephrotoxicity: Kidney damage is usually reversible with discontinuation of therapy, improving gradually in most patients. However, recurrent kidney injury may be observed if treatment is reinstituted.

NSAID hemodynamically mediated kidney injury: Kidney injury is rarely severe and recovery is usually rapid. Occasionally, the hemodynamic insult is sufficiently severe to cause ATN, which can prolong injury.

AIN: Early recognition of and prompt discontinuation of the offending drug typically leads to full recovery of kidney function. The extent of recovery depends on the duration of kidney injury prior to discontinuation of the offending drug, with poorer recovery observed when this period exceeds 2 weeks. Up to one third of these patients may develop chronic kidney disease.

Intratubular obstruction: Kidney injury is usually reversible with initiation of discontinuation of the offending drug and initiation of adequate hydration.

Glomerular disease: Kidney damage is usually reversible, improving over weeks to months in most patients with discontinuation of the offending drug and initiation of immunosuppressive therapy.

How to utilize team care?

Clinical pharmacists should be consulted to provide individualized pharmacokinetic dosing and monitoring of drugs whenever possible, particularly for aminoglycosides, vancomycin, and other measureable and potentially nephrotoxic drugs.

Other considerations


The primary principle for prevention of nephrotoxicity is to avoid the use of nephrotoxic drugs in patients at increased risk for toxicity. Therefore, an awareness of potentially nephrotoxic drugs and knowledge of risk factors that increase kidney vulnerability is essential. Exposure to these drugs often cannot be avoided, so several interventions should be used to reduce the potential for the development of nephrotoxicity.

Aminoglycoside-induced ATN may be prevented by avoiding use in high-risk patients (i.e., pre-existing CKD, diabetes, increased age, hypovolemia, hypotension), use of alternative antibiotics whenever possible and as soon as microbial sensitivities are known, limiting the total aminoglycoside dose administered, and avoiding concomitant therapy with other nephrotoxic drugs. Prospective, individualized pharmacokinetic dosing and monitoring should be used.

Contrast-induced nephropathy may often be anticipated, and several preventative measures are warranted in patients at high-risk for developing contrast nephropathy, particularly those with pre-existing CKD, diabetes, volume depletion, or hypotension. Consider alternative imaging procedures (eg, ultrasound, non-contrast magnetic resonance imaging, and nuclear medicine scans).

If contrast media must be used, then the smallest adequate volume/dose should be administered, and repetitive studies (within 48 to 72 hours) should be avoided; noniodinated, low- or iso-osmolar contrast agents should be used. Concurrent use of potentially nephrotoxic drugs, such as NSAIDs and aminoglycosides, should be avoided beginning the day prior to and held for 2–4 days following contrast exposure.

Intravenous isotonic sodium chloride or sodium bicarbonate should be administered prior to and following the administration of contrast. Infuse at 1-1.5 mL/kg/hr beginning 12 hours prior to contrast exposure and continue 12-24 hours post-exposure. In urgent cases, initiate the infusion at 3 mL/kg/hr, beginning 1-hour prior to contrast exposure, then continue at 1 mL/kg/hr for 6 hours post-exposure.

Administer N-acetylcysteine 600 mg to 1,200 mg PO every 12 hours x4 doses beginning prior to contrast exposure, ie, one dose prior to exposure and three doses post-exposure.

Cisplatin nephrotoxicity: Vigorous hydration with isotonic saline should be used in all patients with a goal of maintaining at least 100-150 mL/h of urine output during and after cisplatin treatment. Hydration should be initiated 12 to 24 hours prior to, and continued for 2 to 3 days after cisplatin administration at rates of 100 to 250 mL/h, as tolerated, to maintain a urine flow of 3 to 4 L/day.

Pretreatment with amifostine may be considered in patients who are at high risk for kidney injury, particularly patients who are elderly, volume depleted, have CKD, or are receiving other nephrotoxic drugs concurrently. The current recommended dose of amifostine is 910 mg/m2 administered intravenously over 15 minutes, beginning 30 minutes prior to cisplatin administration.

Amphotericin B nephrotoxicity: A low threshold for stopping amphotericin B or switching to a liposomal formulation should be employed. Several liposomal amphotericin B formulations are now available and should be used in most high-risk patients.

Nephrotoxicity can also be minimized by limiting the cumulative dose, increasing the infusion time, ensuring the patient is well hydrated, and avoiding concomitant administration of other nephrotoxins. Administration of 1 L intravenous 0.9% sodium chloride daily during the course of therapy may reduce toxicity, and a single infusion of saline 10 to 15 mL/kg prior to administration of each dose of amphotericin B is generally recommended.

NSAID hemodynamically mediated kidney injury:

NSAID-induced hemodynamically mediated kidney injury can be prevented by maintaining adequate intravascular volume, avoiding potent compounds such as indomethacin, and using analgesics with less prostaglandin inhibition, such as acetaminophen, nonacetylated salicylates, aspirin, and possibly nabumetone. Nonnarcotic analgesics may also be useful.

When NSAID therapy is essential for high-risk patients, the minimal effective dose should be used for the shortest duration possible, and NSAIDs with short half-lives should be considered (e.g., sulindac) along with optimal management of predisposing medical problems and frequent kidney function monitoring. Moreover, use of concurrent hypotensive agents and other drugs that affect renal hemodynamics should be avoided.

Intratubular obstruction: Kidney injury caused by intratubular precipitation of drugs can be prevented by administering the drug after vigorously prehydrating the patient, maintaining a high urine output, and urinary alkalinization.

Intratubular indinavir crystal precipitation can be prevented in nearly 75% of treated patients if one assures that the patient consumes at least 2 to 3 L of fluid per day.

What is the evidence?

Aminoglycoside-induced nephrotoxicity

Drusano, GL, Ambrose, PG, Bhavnani, SM. “Back to the future: using aminoglycosides again and how to dose them optimally”. Clin Infect Dis. vol. 45. 2007. pp. 753-760.

Oliveira, JF, Silva, CA, Barbieri, CD. “Prevalence and risk factors for aminoglycoside nephrotoxicity in intensive care units”. Antimicrob Agents Chemother. vol. 53. 2009. pp. 2887-2891.

Radiographic contrast-induced nephropathy

Barrett, BJ, Parfrey, PS. “Clinical practice. Preventing nephropathy induced by contrast medium”. N Engl J Med. vol. 354. 2006. pp. 379-386.

Briguori, C, Airoldi, F, D’Andrea, D, Bonizzoni, E, Morici, N, Focaccio, A, Michev, I, Montorfano, M, Carlino, M, Cosgrave, J, Ricciardelli, B, Colombo, A. “Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL): a randomized comparison of 3 preventive strategies”. Circulation. vol. 115. 2007. pp. 1211-1217.

Kelly, AM, Dwamena, B, Cronin, P. “Meta-analysis: effectiveness of drugs for preventing contrast-induced nephropathy”. Ann Intern Med. vol. 148. 2008. pp. 284-294.

McCullough, PA. “Contrast-induced acute kidney injury”. J Am Coll Cardiol. vol. 51. 2008. pp. 1419-28. (A comprehensive review of the epidemiology, prognostic implications, pathophysiology, and strategies for the prevention of contrast-induced acute kidney injury. Based largely on data from the Contrast-Induced Nephropathy (CIN) Consensus Working Panel, it provides series of consensus statements and a proposed algorithm for the risk stratification and management of contrast-induced acute kidney injury.)

Schweiger, MJ, Chambers, CE, Davidson, CJ, Zhang, S, Blankenship, J, Bhalla, NP, Block, PC, Dervan, JP, Gasperetti, C, Gerber, L, Kleiman, NS, Krone, RJ, Phillips, WJ, Siegel, RM, Uretsky, BF, Laskey, WK. “Prevention of contrast induced nephropathy: Recommendations for the high risk patient undergoing cardiovascular procedures”. Catheter Cardiovasc Interv. vol. 69. 2006. pp. 135-140.

Solomon, R, Dauerman, HL. “Contrast-induced acute kidney injury”. Circulation. vol. 122. 2010. pp. 2451-2455.

Weisbord, SD, Palevsky, PM. “Strategies for the prevention of contrast-induced acute kidney injury”. Curr Opin Nephrol Hypertens. vol. 19. 2010. pp. 539-549. (The authors examined the risk factors for and recent evidence related to interventions for the prevention of contrast-induced acute kidney injury.)

Cisplatin nephrotoxicity

Hensley, ML, Hagerty, KL, Kewalramani, T. “American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants”. J Clin Oncol. vol. 27. 2009. pp. 127-145.

Launay-Vacher, V, Rey, JB, Isnard-Bagnis, C. “Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care”. Cancer Chemother Pharmacol. vol. 61. 2008. pp. 903-909. (The authors provide detailed recommendations and supporting evidence for specific strategies to prevent cisplatin nephrotoxicity.)

Pabla, N, Dong, Z. “Cisplatin nephrotoxicity: mechanisms and renoprotective strategies”. Kidney Int. vol. 73. 2008. pp. 994-1007. (An excellent review of recent data pertaining to the mechanisms of cisplatin nephrotoxicity.)

Yao, X, Panichpisal, K, Kurtzman, N, Nugent, K. “Cisplatin nephrotoxicity: a review”. Am J Med Sci. vol. 334. 2007. pp. 115-124.

Amphotericin B nephrotoxicity

Deray, G. “Amphotericin B nephrotoxicity”. J Antimicrob Chemother. vol. 49. 2002. pp. 37-41.

Saliba, F. “Antifungals and renal safety–getting the balance right”. Int J Antimicrob Agents. vol. 27. 2006. pp. 21-24.

Slavin, MA, Szer, J, Grigg, AP. “Guidelines for the use of antifungal agents in the treatment of invasive Candida and mould infections”. Intern Med J. vol. 34. 2004. pp. 192-200.

Ullmann, AJ. “Nephrotoxicity in the setting of invasive fungal diseases”. Mycoses. vol. 51. 2008. pp. 25-30.

NSAID hemodynamically mediated kidney injury

Cheng, HF, Harris, RC. “Renal effects of non-steroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors”. Curr Pharm Des. vol. 11. 2005. pp. 1795-1804.

House, AA, Silva Oliveira, S, Ronco, C. “Anti-inflammatory drugs and the kidney”. Int J Artif Organs. vol. 30. 2007. pp. 1042-1046.

Whelton, A. “Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications”. Am J Med. vol. 106. 1999. pp. 13S-24S.


Clarkson, MR, Giblin, L, O’Connell, FP. “Acute interstitial nephritis: clinical features and response to corticosteroid therapy”. Nephrol Dial Transplant. vol. 19. 2004. pp. 2778-2783.

Gonzalez, E, Gutierrez, E, Galeano, C. “Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis”. Kidney Int. vol. 73. 2008. pp. 940-946. (The authors performed a multicenter retrospective evaluation of the influence of steroids in 61 patients with biopsy-proven drug-induced acute interstitial nephritis. Patients that did not receive steroids had poorer outcomes, with significantly higher final serum creatinine concentrations and a higher proportion of patients requiring chronic dialysis therapy.)

Markowitz, GS, Perazella, MA. “Drug-induced renal failure: a focus on tubulointerstitial disease”. Clin Chim Acta. vol. 351. 2005. pp. 31-47.

Perazella, MA, Markowitz, GS. “Drug-induced acute interstitial nephritis”. Nat Rev Nephrol. vol. 6. 2010. pp. 461-70. (The authors provide a comprehensive review of the clinical presentation, pathogenesis, diagnosis, and treatment of drug-induced acute interstitial nephritis. Clinical presentation is reviewed within the context of individual drug classes commonly associated with AIN.)

Intratubular obstruction

Daudon, M, Jungers, P. “Drug-induced renal calculi: epidemiology, prevention and management”. Drugs. vol. 64. 2004. pp. 245-275.

Yarlagadda, SG, Perazella, MA. “Drug-induced crystal nephropathy: an update”. Expert Opin Drug Saf. vol. 7. 2008. pp. 147-58.

Glomerular disease

Albaqumi, M, Soos, TJ, Barisoni, L, Nelson, PJ. “Collapsing glomerulopathy”. J Am Soc Nephrol. vol. 17. 2006. pp. 2854-2863.

Izzedine, H, Launay-Vacher, V, Bourry, E. “Drug-induced glomerulopathies”. Expert Opin Drug Saf. vol. 5. 2006. pp. 95-106.

Perazella, MA, Markowitz, GS. “Bisphosphonate nephrotoxicity”. Kidney Int. vol. 74. 2008. pp. 1385-1393.


Choudhury, D, Ahmed, Z. “Drug-associated renal dysfunction and injury”. Nat Clin Pract Nephrol. vol. 2. 2006. pp. 80-91.

John, R, Herzenberg, AM. “Renal toxicity of therapeutic drugs”. J Clin Pathol. vol. 62. 2009. pp. 505-15.

Nolin, TD, Himmelfarb, J. “Mechanisms of Drug-Induced Nephrotoxicity”. Handb Exp Pharmacol. vol. 196. 2010. pp. 111-130.

Perazella, MA. “Renal vulnerability to drug toxicity”. Clin J Am Soc Nephrol. vol. 4. 2009. pp. 1275-1283. (An overview of patient-specific, kidney-related, and drug-related risk factors associated with increased vulnerability to drug-indiced kidney disease is presented.)