A 52-year-old black man with type 2 insulin-dependent diabetes mellitus presents to hospital suffering from significant weakness and nausea; he says he has had no appetite for the past week, but has not been vomiting. He reports seeing blood in his urine, and that his urinary output has decreased.
He looks very ill but shows no signs of distress – he is mentally alert and aware of his surroundings. He does not use over-the-counter medications or herbal remedies, nor does he smoke, drink alcohol, or use any illicit drugs.
His medical history reveals that 3 weeks previously, he had visited the hospital for treatment of a diabetic foot ulcer. He explains that he was hospitalized at that time for treatment of his foot ulcer as well as for chronic osteomyelitis.
Ultimately, treatment involved amputation of his left fourth and fifth metatarsal, cuboid, and lateral cuneiform bone. The patient’s recovery from the operation was uneventful, and he was sent home with instructions to take oral clindamycin 600 mg every 8 hours. He was also on insulin glargine.
He explained that 5 days previously, he had consulted his family doctor for loss of appetite and nausea, and for significant generalized weakness. His physician explained that these symptoms are likely related to clindamycin’s gastrointestinal adverse effects. The patient is sent home with instructions to take his antibiotic with food and to drink lots of water. No investigative blood tests were performed at that time.
At home, the patient follows his family physician’s instructions and takes his medication with meals and ensures that he drinks lots of water. However, his symptoms continue to worsen and the appearance of blood in his urine prompts him to go to the hospital, where he is assessed and then admitted. He tells the admitting physician that his symptoms to date have not included fever, chills, headache, confusion, or vomiting; nor has he been short of breath or had palpitations, diarrhea, or abdominal pain. Examination for skin rashes and edema were negative, and the patients’s vital signs on admission were normal.
Investigations continue, and the patient has no clinical evidence of dehydration. His heart sounds are normal with no pericardial rub. Notably, he does not take an angiotensin-converting enzyme (ACE) inhibitor. Auscultation reveals that both lungs are clear; the abdomen is soft, and an examination fails to note any tenderness.
Results of laboratory tests at this time are as follows:
- Creatinine: 0.9 mg/dL
- Glomerular filtration rate: 115 mL/min/1.73 m2
- Proteinuria: 30 mg/dL
- Sodium: 125 mEq/L
- Potassium: 6.7 mEq/L
- Chloride: 90 mEq/L
- Bicarbonate: 17.1 mEq/L
- Blood urea nitrogen: 89 mg/dL
- Creatinine: 12.6 mg/dL
- Glucose: 263 mg/dL
- Phosphate: 7.8 mg/dL
Complete blood cell count and differential are normal, with no evidence of eosinophilia. Urine analyses showed specific gravity of £1.005, a large amount of blood, protein level 100 mg/dL, small leukocyte esterase, urine white blood cell count of 7-20 high power field (hpf), red blood cell count of 7-20 hpf, and few bacteria.
Urine cultures did not show any growth, and toxicology was negative. Urine sediment (which is spun at this point), showed muddy brown casts, but was negative for eosinophils. The urine protein-to-creatinine ratio was 2,914.1 mg/g. The patient’s serum protein electrophoresis, urine protein electrophoresis, and complement levels were all normal.
As well, negative results were found for tests of glomerular basement membrane IgG antibodies (<0.2 units), antimyeloperoxidase antibodies (<5.0 units), and proteinase-3 antibodies (<5.0 units).
Chest x-ray on admission was normal, with no infiltrates, effusion, or pulmonary vascular congestion. Electrocardiography revealed an old right bundle branch block but no ischemic changes; PR interval was normal and there were no peaked T waves.
An indwelling urinary catheter yielded no urine output. Ultrasounds of bladder and kidneys showed an empty urinary bladder with the tip of the catheter in the bladder, and normal kidneys without hydronephrosis.
Diagnosis and Treatment
The diagnosis of oliguric acute kidney injury (AKI) was made. The patient was admitted to critical care, where he received intravenous (IV) normal saline, insulin, albuterol, bicarbonate, and kayexalate for his hyperkalemia. Clindamycin was discontinued.
The patient refused renal biopsy due to concerns about potential complications. His urine output remained less than 50 mL of urine output for the next 24 hours. He continued to be oliguric after an IV fluid challenge, with worsening metabolic acidosis and persistent hyperkalemia that eventually required temporary renal-replacement therapy.
Clinicians continued intermittent hemodialysis throughout his 4-week stay in the hospital. When his renal function returned to baseline, dialysis was discontinued. Ongoing ceftriaxone treatment for osteomyelitis was completed with no adverse effects or complications. Based on the resolution of the symptoms following discontinuation of clindamycin and the failure to identify any other causes for his AKI, clinicians concluded that the patient did have clindamycin-induced AKI.
Clinicians reporting this case1 — Igor Dumic, MD, of Icahn School of Medicine at Mount Sinai in New York City, and colleagues — noted that medication-induced AKI occurs frequently, with an incidence of up to 60%; older patients and individuals with chronic diseases, particularly chronic kidney disease and diabetes mellitus, are at greatest risk.2,3
Additional factors associated with increased susceptibility for nonspecific AKI including dehydration, female gender, black race, various chronic diseases, and various exposures are described in the Kidney Disease: Improving Global Outcomes (KDIGO) ATI practice guideline summary.4 AKI criteria have also been proposed by RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease)5 and AKIN (Acute Kidney Injury Network), among others.6
Dumic, et al. also explained that in contrast with the situation for other antibiotics frequently linked with AKI, such as beta lactams, acyclovir, aminoglycosides, and amphotericin, clindamycin-related AKI rarely occurs.
This is the first reported case of AKI affecting an African American, the authors noted. In two retrospective studies from China of 507 and 24 patients8 with biopsy-proven ATI, all the patients were Asian. The median age of those affected was approximately 42.
The mechanism of AKI varies depending on the medication, the authors noted. For antibiotics, causes of AKI include the following:
- Glomerular injury
- Acute interstitial nephritis due to clindamycin
- Acute tubular necrosis
- Tubular damage secondary to crystallization of the drug within the tubules
- Hemodynamic protuberances
Other medication classes such as ACE inhibitors and non-steroidal anti-inflammatory drugs are known to alter intra-glomerular hemodynamics.9,10 Clindamycin has been associated primarily with gastrointestinal effects such as abdominal discomfort, diarrhea, nausea, and vomiting; however, it has also been associated with rash, clostridium difficile colitis, and allergic reactions.3
Clindamycin is a lincosamide antibiotic that works primarily by binding to the 50s ribosomal subunit of bacteria. The medication reaches 90% bioavailability when taken orally, and while it has good penetration into abscesses and bone, it does not achieve significant levels in cerebrospinal fluid and so is not effective for treating central nervous system infections.11
Clindamycin is frequently used to treat a range of infections due to its broad spectrum of activity against anaerobes, staphylococci (including methicillin-resistant Staphylococcus aureus), viridans group streptococci, Streptococcus pyogenes, and Streptococcus pneumoniae, making it an excellent choice for treatment of various infections.11
Clindamycin is metabolized in the liver and excreted in urine; its half-life is approximately 2 hours in patients with normal renal function. This increases to 6 hours in patients who have chronic kidney disease. It is not cleared through either hemodialysis or peritoneal dialysis.11
AKI caused by clindamycin generally occurs within 1 to 4 days of beginning treatment. It is marked most frequently by proteinuria (62%) and hematuria (42-62%), as was observed by clinicians reporting this patient’s case.7,8
In fact, Dumic and co-authors noted, this patient’s proteinuria worsened significantly from 30 mg/dL on discharge to 100 mg/dL on re-admission.
The KDIGO AKI Guideline Work Group reported that any one of the following criteria identify AKI4:
- Increase in serum creatinine by ≥0.3 mg/dl (≥26.5 μmol/l) within 48 hours
- Increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days
- Urine volume <0.5 ml/kg/hour for 6 hours
To avoid delays in diagnosis, Dumic, et al. emphasized the importance of maintaining clinical suspicion when presented with these symptoms. AKI due to clindamycin is frequently associated with gross hematuria, and initial presentation can be quite severe and require temporary renal-replacement therapy. Despite the dramatic presentation and severity, all reported cases of clindamycin-induced AKI were improved and were successfully weaned off renal-replacement therapy, the authors concluded.
1. Subedi P, et al “Clindamycin: An Unusual Cause of Acute Kidney Injury” Am J Case Rep 2019; 20: 248-251.
2. Shahrbaf FG, Assadi F “Drug-induced renal disorders” J Renal Inj Prev 2015; 4(3): 57–60.
3. Naughton CA “Drug-induced nephrotoxicity” Am Fam Physician 2008; 78(6): 743-750.
4. Kellum JA, et al “KDIGO AKI Guideline Work Group. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)” Crit Care 2013; 17(1): 204.
5. Bellomo R, et al “Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: The Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group” Crit Care 2004; 8: R204-R212.
6. Mehta RL, et al “Acute Kidney Injury Network: Report of an initiative to improve outcomes in acute kidney injury” Crit Care 2007; 11: R31.
7. Wan H, et al “Clindamycin-induced kidney diseases: A retrospective analysis of 50 patients” Intern Med 2016; 55(11): 1433-1437.
8. Xie H, et al “Clindamycin-induced acute kidney injury: Large biopsy case series” Am J Nephrol 2013; 38(3): 179-183.
9. Naughton CA “Drug-induced nephrotoxicity” Am Fam Physician 2008; 78(6): 743-750.
10. Zager RA “Pathogenetic mechanisms in nephrotoxic acute renal failure” Semin Nephrol 1997; 17(1): 3-14.
11. Cimino JE, Tierno PM Jr: “Hemodialysis properties of clindamycin (7-chloro-7-deoxylincomycin)” Appl Microbiol 1969; 17(3): 446-448.
None of the authors reported having any conflicts of interest.