Original Investigation

Acute Kidney Injury and Hair-Straightening Products: A

Case Series
Alon Bnaya, Nabil Abu-Amer, Pazit Beckerman, Alexander Volkov, Keren Cohen-Hagai, Meidad Greenberg,
Sydney Ben-chetrit, Kim Ben Tikva Kagan, Shira Goldman, Hadar Agmon Navarro, Marwan Abu Sneineh,
Benaya Rozen-Zvi, Yael Borovitz, Ana Tobar, Noa Berar Yanay, Ray Biton, Avital Angel-Korman,
Vladimir Rappoport, Adi Leiba, Younes Bathish, Evgeni Farber, Maital Kaidar-Ronat, Letizia Schreiber,
Moshe Shashar, Raisa Kazarski, Gil Chernin, Eyal Itzkowitz, Jawad Atrash, Nomy Levin Iaina, Shai Efrati,
Elad Nizri, Yael Lurie, Ofer Ben Itzhak, Suheir Assady, Yael Kenig-Kozlovsky, and Linda Shavit

Rationale & Objective: Keratin-based hair-
straightening treatment is a popular hair-styling
method. The majority of keratin-based hair-
straightening products in Israel contain glycolic
acid derivatives, which are considered safe
when used topically. Systemic absorption of
these products is possible, and anecdotal
reports have described kidney toxicity
associated with their use. We report a series of
cases of severe acute kidney injury (AKI)
following use of hair-straightening treatment in
Israel during the past several years.
Study Design: Case series.
Setting & Participants: We retrospectively
identified 26 patients from 14 medical centers in
Israel who experienced severe AKI and reported
prior treatment with hair-straightening products in
2019-2022.
Findings: The 26 patients described had a me-
dian age of 28.5 (range, 14-58) years and
experienced severe AKI following a hair-
straightening procedure. The most common
symptoms at presentation were nausea,
vomiting, and abdominal pain. Scalp rash was
noted in 10 (38%) patients. Two patients Complete author and article
experienced a recurrent episode of AKI information provided before
references.
following a repeat hair-straightening treatment.
Seven patients underwent kidney biopsies, Correspondence to
which demonstrated intratubular calcium oxalate A. Bnaya (alonb@szmc.org.il)
deposition in 6 and microcalcification in tubular Am J Kidney Dis. XX(XX):1-
cells in 1. In all biopsies, signs of acute tubular 10. Published online month
injury were present, and an interstitial infiltrate xx, xxxx.
was noted in 4 cases. Three patients required doi: 10.1053/
temporary dialysis. j.ajkd.2022.11.016
© 2023 by the National
Limitations: Retrospective uncontrolled study,
Kidney Foundation, Inc.
small number of kidney biopsies.
Conclusions: This series describes cases of AKI
with prior exposure to hair-straightening
treatments. Acute oxalate nephropathy was the
dominant finding on kidney biopsies, which may
be related to absorption of glycolic acid
derivatives and their metabolism to oxalate. This
case series suggests a potential
underrecognized cause of AKI in the young
healthy population. Further studies are needed
to confirm this association and to assess the
extent of this phenomenon as well as its
pathogenesis.

N ephrotoxic acute kidney injury (AKI) is a well-

recognized and relatively common cause of decreased
kidney function. Although various medications, herbal
products, and diagnostic agents have been reported to be
associated with kidney damage, other potential environ-
mental and chemical toxic agents may be underrecognized
by medical practitioners.1-3 Hair straightening using
chemical agents is a popular hair-styling technique globally.
This technique produces a smooth and shiny appearance to
the hair that lasts as long as several months. During the past
2 decades, keratin-based treatment (also called Brazilian
keratin treatment) has become a popular hair-straightening
method because it enhances hair color and shine and may
be applied on all types of hair.4 Originally, the Brazilian
keratin treatment formulation contained formaldehyde or
formaldehyde releasers in addition to synthetic hydrolyzed
liquid keratin. However, formaldehyde is a carcinogenic
and teratogenic agent, and acute exposure may result in skin
lesions, headaches, eye irritation, and injury to the respi-
ratory tract.5 Thus, it has been banned in Brazil, Canada, and
the European Union as an active ingredient in straightening
products. This led to an increase in the use of glycolic acid
derivatives in hair-straightening products.4,6 Although these
agents are widely approved for cosmetic purposes in many
countries and are marketed as “formaldehyde-free,” several
studies suggest that glycolic acid derivatives may also release
formaldehyde when exposed to high temperatures.6,7 In
Israel, most hair-straightening products contain glycolic acid
derivatives (glyoxalic acid, glyoxyloyl carbocysteine, and
glyoxyloyl keratin amino acids).
In recent years, anecdotal cases of AKI following hair-
straightening treatment were reported in Israel and
Egypt.8-10 In this study, we describe additional cases of AKI
associated with hair-straightening products in Israel during
a recent 4-year period, detailing the clinical presentation,
course of illness, histopathologic findings, and outcomes
of these patients.
Methods
We contacted all nephrology departments/institutions in
Israel to identify cases of AKI following hair straightening.

AJKD Vol XX | Iss XX | Month 2023 1


PLAIN-LANGUAGE SUMMARY
Exposure to environmental toxins may lead to acute
kidney injury (AKI). Nevertheless, chemical products
associated with kidney impairment are occasionally
overlooked and underreported by clinicians. During a
recent 4-year period, episodes of severe AKI following
hair straightening have been described in healthy young
women in Israel. Clinical symptoms, including
abdominal pain, nausea, vomiting, and scalp irritation,
appeared during or immediately after the procedure. In
30% of cases, a kidney biopsy was performed,
demonstrating deposition of calcium oxalate crystals in
the tubules and acute tubular injury. Kidney function
recovered spontaneously in most patients. This case
series suggest a possible association between hair
straightening and AKI, which may in turn result from
acute oxalate nephropathy.
AKI was defined according to Acute Kidney Injury
Network criteria, and AKI severity was graded using
KDIGO criteria.11
AKI was considered to be related to hair-straightening
treatment if it met the following criteria: AKI developed
during the 48-72 hours following hair-straightening
product exposure; other etiologies for AKI were excluded
after extensive clinical, laboratory, and imaging evaluation
by the primary treating physicians and the nephrology
consultants; and the patient experienced systemic signs
(such as abdominal pain, vomiting, and scalp eruption/
irritation) within 24 hours of hair-straightening product
exposure.
To assess the causality between exposure to hair-
straightening agents and the development of AKI, we
used the Adverse Drug Reaction Probability Scale (i.e.,
Naranjo Scale).12 For each patient, a score between −4 and
13 was calculated. The relationship between exposure to
hair-straightening agents and AKI was considered defini-
tive if the score was 9 or higher, probable if 5-8, possible
if 1-4, and doubtful if 0 or lower.
For each case, demographic, clinical, and laboratory
data were retrieved. Imaging studies including ultrasound
or computed tomography were also reviewed.
The clinical course of the patients, including need for
kidney replacement therapy, specific therapy (eg, steroid
treatment), and kidney function at the time of hospital
discharge as well as after discharge were assessed. Baseline
serum creatinine level was defined as the closest mea-
surement obtained before the index admission. The esti-
mated glomerular filtration rate was calculated using the
2009 CKD-EPI creatinine equation.13
Interpretation of kidney biopsies (when available) was
based on local hospital pathology reports. In cases with
calcium oxalate crystals deposition, the ratio of crystals to
glomeruli was calculated. A cutoff ratio of at least 0.25 was
2 AJKD Vol XX | Iss XX | Month 2023
Bnaya et al
chosen to distinguish oxalate nephropathy from other
kidney pathologic processes.14
Descriptive statistics were calculated for all study vari-
ables. Quantitative variables were expressed as mean and
SD or median and IQR as appropriate, and binary variables
were expressed as frequencies and percentages. The study
was approved by the institutional review board, which,
because of the retrospective nature of the study and the use
of unidentified data, waived the need for informed consent
to this study.
Results
Demographic and Clinical Characteristics
Between January 2019 and August 2022, 26 cases of AKI
following hair-straightening treatment were identified in
14 medical centers in Israel. Baseline demographic and
clinical features are presented in Table 1. All patients were
female and 5 (19%) were younger than 20 years (median
age, 28.5 [range, 14-58] years). The majority of patients
were healthy, and all patients denied any long-term
exposure to medications (including renin-angiotensin-
aldosterone inhibitors or diuretic agents), herbal adulter-
ants, or over-the-counter supplements before admission.
Three patients had a history of nephrolithiasis and 3 had a
skin disorder (2 had psoriasis and 1 had atopic dermatitis).
There was no family history of kidney disease. Three pa-
tients reported consumption of 1-3 tablets of nonsteroidal
anti-inflammatory drugs for abdominal and flank pain that
occurred after the hair-straightening treatment. One patient
received an antibiotic (cefalexin), and 1 patient took 2
tablets of omeprazole for heartburn 3 days before
admission.
At presentation, all patients were in hemodynamically
stable condition (mean systolic and diastolic blood pres-
sures, 126 ± 13 and 78 ± 10 mm Hg, respectively). The
most common symptoms were nausea or vomiting (25
[96%]) and abdominal pain (12 [46%]), which occurred
during or immediately following the hair-straightening
procedure. Flank pain was reported in 9 (35%) cases. In
10 patients (38%), scalp erosion and/or rash were noted.
Laboratory studies are described in Table 2. The mean
peak serum creatinine concentration during admission was
5.3 ± 2.4 mg/dL, and all patients were classified as having
stage 3 AKI. At admission, mild leukocytosis without
eosinophilia was observed in 11 (42%) patients. Liver
function and creatinine phosphokinase were in the refer-
ence range in all patients. Mild metabolic acidosis was
noted in 14 of 21 (67%) patients, with high anion gap in 7
of 15 (47%). Immune serology tests were unrevealing.
Urinalysis demonstrated mild proteinuria in 9 (35%) pa-
tients. Urine sediment examination revealed granular casts
in 2 patients. No crystals were noted.
Eleven (42%) patients had been exposed to keratin-
based products containing glycolic acid derivatives. These
agents were labeled as “formaldehyde-free” products. In
the other 15 patients, the specific hair-straightening
Bnaya et al

Table 1. Clinical Characteristics and Hair-Straightening Products

Time From Scr, mg/dL
Comorbidities Exposure Hair
Age, and Medical Clinical Symptoms to AKI Kidney Follow- Straightening
Pt No. y History and Signsa Diagnosis, d Biopsy Peak Discharge up Method
1 24 Healthy Abdominal pain, nausea 2 No 5.82 2.36 0.59 Unknown
2 22 Healthy Abdominal pain, nausea 1 No 2.76 0.72 NA Keratin-based
and vomiting, scalp rash treatmentc
3 30 Nephrolithiasis Nausea and vomiting, 4 No 4.81 3.26 0.8 Keratin-based
flank pain, scalp rash treatmentc
4 29 Healthy Nausea and vomiting, 3 No 2.09 1.51 0.57 Unknown
scalp rash
5 21 Epilepsy Abdominal pain, vomiting, 4 Yes 11.83 2.64 0.77 Unknown
headache, scalp rash
6 58 Healthy Nausea, flank pain, 1 Yes 7.54 1.39 NA Keratin-based
syncope treatment
7 14 Healthy Nausea, flank pain, 2 No 3.8 1.27 NA Unknown
headache
8 31 Healthy, smoking Abdominal pain, vomiting 3 No 8.14b 1.53 NA Unknown
diarrhea
9 29 Nephrolithiasis Vomiting, scalp rash 1 No 6.8 2.53 NA Unknown
10 52 Psoriasis, Abdominal and flank 2 No 3.4 2.1 NA Unknown
nephrolithiasis pain, nausea and
vomiting
11 24 Healthy Abdominal pain, nausea, 3 No 2.17 1.13 0.5 Keratin-based
fever treatmentc
12 33 Healthy Nausea and vomiting, 3 No 6 3 1.1 Keratin-based
chills treatmentc
13 13 Healthy Abdominal pain, nausea 1 Yes 3.56b 1.3 0.5 Unknown
and vomiting
14 17 Psoriasis Abdominal pain, nausea 1 Yes 7.1b 1.1 0.7 Keratin-based
and vomiting treatmentc
15 17.5 Healthy Abdominal pain, nausea 1 No 2.9 1.26 0.8 Keratin-based
and vomiting, fever, scalp treatmentc
rash
16 24 Healthy Abdominal pain, nausea 5 No 4.2 1.4 0.8 Unknown
and vomiting, scalp rash
17 36 Healthy Nausea and vomiting, 1 No 6 4.4 0.9 Unknown
scalp rash
18 21 Healthy Abdominal pain, nausea 1 No 3.2 1.8 NA Unknown
and vomiting
19 41 Hypothyroidism, Nausea and vomiting 3 Yes 3.46 0.98 NA Keratin-based
sleeve treatmentc
gastrectomy
20 19 Healthy Nausea, flank pain, 2 Yes 5.09 2.1 0.9 Unknown
headache
21 44 Hypercoagulability Vomiting, flank pain 2 No 7.8 2 0.87 Unknown
state (prothrombin
variant)
22 50 Healthy Nausea and vomiting 5 No 7.3 5.6 1.23 Unknown
23 21 Healthy Nausea and vomiting, 5 No 3.68 1.41 0.99 Keratin-based
flank pain, scalp rash treatmentc
24 28 Atopic dermatitis, Nausea and vomiting, 2 No 2.83 1.06 0.71 Keratin-based
gastroesophageal flank pain, scalp rash treatmentc
reflux disease
25 32 Healthy Abdominal pain, nausea 4 Yes 9.03 2.75 0.65 Keratin-based
and vomiting treatmentc
26 30 Healthy Flank pain 7 No 7.36 3.32 0.85 Unknown
All patients were female. Abbreviations: AKI, acute kidney injury; NA, not available; pt, patient; Scr, serum creatinine.
a
In all patients, clinical symptoms started during or 1-3 hours after hair-straightening treatment.
b
Required temporary hemodialysis.
c
Known to contain glycolic acid derivatives.

AJKD Vol XX | Iss XX | Month 2023 3

 Bnaya et al

Table 2. Laboratory and Radiologic Characteristics (N = 26) poor corticomedullary differentiation in 6. No stones or
Characteristic Value signs of nephrocalcinosis were reported. In 2 patients with
enlarged and hyperechoic kidneys during admission,
Laboratory findings
Hemoglobin, g/dL 12.6 ± 1
repeat ultrasound findings several weeks later were
White blood cell count, ×109/L 10.8 ± 4.6 normal.
Platelet count, ×109/L 268 ± 60 In the remaining 9 (35%) cases, computed tomography
Sodium, mEq/L 137 ± 3.8 was performed and demonstrated nonobstructive neph-
Potassium, mEq/L 4.2 ± 0.5 rolithiasis in 3 patients. There were no signs of neph-
Calcium, mg/dL 9 ± 0.6 rocalcinosis or extrarenal calcifications.
Phosphorus, mg/dLa 4.5 ± 1.2
Magnesium, mg/dLb 2.4 ± 0.4 Kidney Biopsy Findings
Chloride, mg/dLb 105 ± 5.9 Seven patients underwent kidney biopsy during hospital-
Bicarbonate, mmol/Lc 20.7 ± 3.3 ization (Fig 1; Table 3). In 5, multiple crystal depositions
Baseline creatinine, mg/dLc 0.73 ± 0.1
in renal tubules were identified and exhibited bright
Admission serum urea nitrogen, mg/dL 37 ± 18.9
birefringence when viewed under polarized light,
Admission creatinine, mg/dL 4.2 ± 2.4
compatible with a diagnosis of acute oxalate nephropathy
Peak creatinine, mg/dL 5.3 ± 2.4
(patients 6, 14, 19, 20, and 25). One biopsy showed
Discharge creatinine, mg/dL 2 ± 1.1
Follow-up creatinine, mg/dLd 0.79 ± 0.2
microcalcifications incorporated within the tubular
Creatinine phosphokinase, IU/L 68.6 ± 35.8
epithelium (patient 13), and, in another biopsy, a few
Uric acid, mg/dL 7 ± 1.5 calcium oxalate crystals were seen (patient 5). The mean
C-reactive protein, mg/dL 6.1 ± 6.3 ratio of calcium oxalate crystals to glomeruli was 3.3 ± 2.8.
Urinalysis Signs of acute tubular damage were noted in all 7 biopsies,
Hematuria 13 (50%) and interstitial inflammatory infiltrates were noted in 4.
Leukocyturia 14 (54%) The glomeruli appeared normal in all biopsies. Immuno-
Proteinuria 9 (35%) fluorescence staining was positive for mesangial immu-
Urinary protein-creatinine ratio, mg/g 493 ± 345 noglobulin A in 1 biopsy.
Adverse Drug Reaction Probability score 7.3 ± 0.5
Values for continuous variables given as mean ± SD; categorical variables as count Clinical Course and Outcome
(percentage).
a
b
n = 23. The median duration of hospital stay was 6 (IQR, 5-7.8)
n = 15.
c
n = 21. days. During hospitalization, one patient experienced se-
d
n = 18. vere dyspnea with bilateral lung infiltrates (considered to
be related to toxic agent exposure), which resolved within
several days. Duration of stay was longer among patients
products were unknown; however, in Israel, the vast who had a biopsy than among those who did not (medians
majority of these products contain glycolic acid. Two pa- of 12 [IQR, 3.5-19] vs 5 [IQR, 4-7] days). Otherwise, the
tients reported another previous AKI episode following clinical presentation and outcome were similar among
hair-straightening treatment. patients who underwent kidney biopsy and those who did
According to the Adverse Drug Reaction Probability not. The mean creatinine concentration at admission was
Scale (Naranjo Scale), all cases of AKI were defined as 4.2 ± 2.4 mg/dL (5 ± 3.8 mg/dL in patients who under-
probably related to prior exposure to hair-straightening went kidney biopsy and 3.9 ± 1.7 mg/dL in those who did
agents. not). Four of 7 patients (57%) who had biopsies per-
formed (vs 1 [5%] who did not) were treated with steroids
Chemical Analyses because of biopsy evidence of interstitial infiltration. Two
According to information obtained from the Israeli Min- patients in the kidney biopsy group and 1 in the no-biopsy
istry of Health, analyses of hair-straightening products group required hemodialysis; all 3 were successfully
marketed in Israel revealed varying concentrations of weaned from dialysis.
glyoxylic acid (range, 0.56%-17.9%), with pH below 1 in Kidney function gradually improved in all patients.
some of the products. Ethylene glycol and diethylene Mean creatinine concentration at discharge was
glycol were not detected. The concentration of formalde- 2 ± 1.1 mg/dL (1.7 ± 0.7 mg/dL in patients who un-
hyde was <200 ppm in most tested products, but the derwent kidney biopsy and 2.2 ± 1.2 mg/dL in those
concentration was relatively high in one (504 ppm). who did not). Postdischarge follow-up was available in
18 of 26 patients for a median period of 1.3 (IQR, 0.53-
Imaging Findings 19) months. Kidney function returned to normal in all
As part of AKI evaluation, abdominal ultrasound was patients.
performed in 17 (65%) patients. The kidneys were Serum from 2 patients was assayed for glycolic acid and
hyperechoic in 6 patients and symmetrically enlarged with formic acid, which were not detected. In one of these

4 AJKD Vol XX | Iss XX | Month 2023

Bnaya et al
patients, this test was performed only 7 days after hair
straightening.
Discussion
In this case series, we present 26 female adolescents and
young adults with AKI following a hair-straightening
procedure. The clinical constellation of abdominal
pain, nausea, vomiting, scalp rash, and severe AKI that
appears shortly after exposure suggests intoxication, and
kidney biopsy findings confirmed acute oxalate neph-
rotoxicity as the main cause of AKI. As further evidence
supporting an association between hair-straightening
treatment and AKI, all cases for which the product
was known involved a keratin-based treatment, and
these products contained derivatives of glycolic acid that
are metabolized to oxalate. Also, AKI reappeared after
repeat exposure to the product in 2 patients. Moreover,
the timing of the onset and the absence of other plau-
sible causes of severe AKI in these healthy young in-
dividuals further reinforces our hypothesis.
The association between hair-straightening treatment
and AKI was originally described in 2019 by Ahmed et al.8
In that report, severe AKI occurred in 2 female adolescents
less than 48 hours after use of hair-straightening products.
Similar to our cases, the clinical presentation included
vomiting and scalp rash. In their cases, kidney biopsies
demonstrated acute tubulointerstitial nephritis. The au-
thors suggested that the likely toxic agent was formalde-
hyde. However, in our case series, the prominent biopsy
findings were calcium oxalate crystal deposition in the
renal tubules, compatible with a diagnosis of acute oxalate
nephropathy.
Oxalate nephropathy, defined as calcium oxalate crystal
deposition in kidney tissue, can present as an acute or
chronic decrease in kidney function. Well-recognized
causes of chronic oxalate nephropathy include enteric
and primary hyperoxaluria. However, acute oxalate ne-
phropathy is extremely rare and has been described pri-
marily in cases of extreme oxalate load (such as toxic
ingestion of ethylene glycol and consumption of high
doses of vitamin C and starfruit).15,16
The extent of renal impairment related to oxalate ne-
phropathy may be underestimated. In 2 large studies
examining kidney biopsies, the rates of oxalate nephrop-
athy ranged from 1% to 4%. The cause of oxalate ne-
phropathy was undetermined in >40% of cases.14,17
Notably, in these 2 cohorts, other common pathologic
findings were acute tubular necrosis and interstitial
nephritis, similar to the kidney biopsy findings in the
present study.
At the time of writing, glycolic acid and its de-
rivatives are widely used in the cosmetic industry,
including in hair-smoothing products. Although glycolic
acid is usually considered relatively safe and without
local or systemic toxicity, when it is used topically, high
doses of glycolic acid may be absorbed through the skin
AJKD Vol XX | Iss XX | Month 2023
and cause skin and eye irritation.6,18 The absorption of
glycolic acid by the skin is dependent on the pH of the
product, its concentration, the duration of exposure on
the skin, and the lipophilic properties of the product.18-21
In the United States, the Cosmetic Ingredient Review
Expert Panel suggested that these agents are safe for
short-term use at a concentration <30% and at final
formulation pH higher than 3 when used by a trained
professional.18 In Israel, the recommended pH for
cosmetic products is higher than 2.
Glycolic acid is metabolized to glyoxylic acid by gly-
colate oxidase in human liver cells. Glyoxylic acid is con-
verted further into glycine by alanine-glyoxylate
aminotransferase 1 or into oxalate by cytoplasmatic lactate
dehydrogenase or peroxisomal glycolate oxidase22-24 (Fig 2).
Early studies in rats fed with glycolic acid resulted in
abnormally increased oxalate secretion in the kidney, an in-
crease in kidney weight, and nephrotoxicity due to deposi-
tion of calcium oxalate crystals in the tubules.25-30 However,
systemic absorption of glycolic acid through the skin in
humans is poorly described. In 1996, Slavin et al described a
kidney transplant recipient in whom AKI developed after 5
glycolic acid facial peels. Kidney biopsy demonstrated tubular
vacuolization and intraluminal oxalate crystals.31 In our cases,
enhanced absorption of glycolic acid derivatives may be
related at least in part to the impairment of skin integrity (as
evidenced by scalp rash and erosion in 38% of patients).
Another interesting observation in our study was the
presence of kidney stones in 3 patients. This may be an
undercount because, even though most of our patients had
an ultrasound examination as part of the AKI evaluation,
small kidney stones may be overlooked. Because many
women perform hair straightening uneventfully, a possible
predisposing genetic factor in oxalate metabolism and
excretion may play a role in the clinical presentation in our
cases. Previous studies have tried to elucidate a genetic
basis for kidney stone formation, with some reporting a
high prevalence of a HOGA1 variant in patients with
hyperoxaluria of unknown etiology32-34 and others char-
acterizing a series of gene variations (such as affecting
SLC26A1 and SLC26A6) that are involved in renal tubular
function related to kidney stone formation, including
oxalate.35-38
An additional concern regarding the use of products
containing high concentrations of glycolic acid relates to
the potential release of formaldehyde when these agents
are subjected to high temperature.6,7 In Israel, the use of
heating with these products is forbidden. In the past,
formaldehyde was commonly used in hair-straightening
products because of its ability to promote cross-linking
of hydrolyzed keratin solution to the hair fiber keratin.
However, because of its toxic effects, the use of formal-
dehyde was banned by several countries, and others
limited the maximum permitted concentration in cosmetic
products.39-42 Formaldehyde exposure has been previously
shown to cause acute tubular injury in rats.43,44 In
humans, intravesicular formaldehyde administration as a
5
 Bnaya et al

Figure 1. Pathologic features associated with hair-straightening procedure. (A) Injured tubular cell with loss of brush borders and
epithelial cell vacuolization (patient 5). (B) Microcalcifications incorporated within the tubular epithelium (arrow; patient 13). (C)
Tubular simplification, calcium oxalate crystals in the tubular lumen, and mild lymphocyte infiltration (patient 6). (D-H) Intratubular cal-
cium oxalate crystal deposition (arrows in E-H; patients 6, 14, 20, and 25). Images in D, F, G, and H were obtained under polarized
light microscopy. Calcium oxalate crystals are seen in the right lower quadrants (all images show hematoxylin and eosin staining).
Original magnifications, ×20 (B, D, and G) and ×40 (A, C, E, F, and H).

6 AJKD Vol XX | Iss XX | Month 2023

Bnaya et al

Table 3. Histopathologic Findings of Kidney Biopsies

Pt No. Light Microscopy Immunofluorescence Additional Staining
5 8 normal glomeruli; blood vessels normal; small Mesangial IgA: 1-2+; C3, C1q, EM: no deposits
mononuclear interstitial infiltrate with spare IgM: negative (1 glomerulus)
eosinophils; ATI pattern; 3 calcium oxalate
crystals in the tubules
6 20 glomeruli: 19 normal, 1 sclerotic; mild ATI; No glomeruli Masson trichrome:
small mononuclear interstitial infiltrate; multiple 10% fibrosis
tubules containing oxalate crystals (2.9 crystals
per glomerulus); small-medium artery with
intimal thickening
13 12 normal glomeruli; ATI, mainly involving the Negative Masson trichrome: no fibrosis;
proximal tubules; microcalcifications silver stain: intact membranes
incorporated within the tubular epithelium
14 10 normal glomeruli; blood vessels normal; Negative –
small tubulointerstitial lymphoid aggregates in
the tubulointerstitium; ATI pattern; multiple
calcium oxalate crystals in the tubules (8.1
crystals per glomerulus)
19 16 glomeruli: 14 normal, 2 globally sclerotic; C3: 1+ (in wall of blood Masson trichrome: 7%-10%
multifocal mixed inflammatory infiltrates with vessels); IgM: trace; IgG, IgA, fibrosis; EM: normal structure of
multiple eosinophils and foci of tubulitis (1 with C4, C1q, κ- and λ-light chain, the glomerulus; no deposits
epithelioid granuloma formation); tubules with albumin, fibrinogen: negative found
signs of diffuse tubular injury; multiple tubules
containing oxalate crystals (1.3 crystals per
glomerulus)
20 17 normocellular glomeruli; tubules with diffuse Negative –
ATI; multiple tubules filled with calcium oxalate
crystals; few small calcium oxalate crystals
present in the urinary space of glomerulus (1.18
crystals per glomerulus); interstitium with mild
edema and sparse eosinophils
25 6 normocellular glomeruli; ATI; tubules filled IgG, IgA, IgM, C3, κ- and –
with calcium oxalate crystals (2.2 crystals per λ-light chain: trace
glomerulus)
Abbreviations: ATI, acute tubular injury; EM, electron microscopy; Ig, immunoglobulin; pt, patient.

treatment for refractory hemorrhagic cystitis may result in
edematous urinary obstruction and acute tubular injury.45-47
Previous studies found a high level of formaldehyde that
exceeded occupational exposure limits in hair-straightening
products, even when labeled as formaldehyde-free.7,48,49
Although we cannot exclude formaldehyde as a potential
nephrotoxic component contributing to AKI in our patients,
the consistent finding of calcium oxalate deposition in kidney
biopsies suggests the metabolism of glycolic acid derivatives
to oxalate as the main mechanism of nephrotoxicity in our
cases.
The proposed mechanism for AKI following hair-
straightening treatment is summarized in Fig 2. Although
the presented case series implies an association between
hair straightening and AKI, other potential explanations
cannot be completely excluded. In this regard, the main
differential diagnosis considered by the treating physicians
during hospitalization included decreased kidney perfu-
sion (consistent with a history of vomiting and low
intake), acute interstitial nephritis (due to antibiotic and
proton pump inhibitor exposure), and acute tubular ne-
crosis (due to nonsteroidal anti-inflammatory drugs).
However, vomiting and abdominal pain appeared shortly
after hair straightening, and most patients had no clinical
signs of decreased kidney perfusion at presentation
(including normal blood pressure and a ratio of serum
urea nitrogen to creatinine <1:20). Moreover, the use of
nonsteroidal anti-inflammatory drugs, a proton pump in-
hibitor, and an antibiotic agent was in response to
abdominal pain, and the doses and durations of exposure
were minimal, making these drugs unlikely to be the cause
of AKI in these young, healthy patients. Although hyper-
acute allergic reaction to medications can induce acute
interstitial nephritis, the clinical presentation in such cases
frequently includes acute urticaria, peripheral eosinophilia,
and leukocyturia with eosinophiluria, which were absent
in our patients. Of the 5 patients who had a history of drug
exposure before admission, a kidney biopsy was per-
formed in one case, demonstrating acute oxalate ne-
phropathy. It is important to emphasize that our patients
had no history of other unusual nutritional, herbal, or
medicine exposure known to cause acute oxalate ne-
phropathy. AKI due to urinary obstruction was excluded
by kidney imaging in all patients, and the presence of
bland urine sediment, minimal proteinuria, and normal
blood pressure was not suggestive of glomerular diseases.
The present report is, to our knowledge, the first to
attribute a series of AKI cases associated with hair-

AJKD Vol XX | Iss XX | Month 2023 7


Figure 2. Suggested mechanism of acute kidney injury following hair-straightening treatment. AGT, alanine-glyoxylate aminotrans-
ferase; GO, glycolate oxidase; HOGA, 4-hydroxy-2-oxoglutarate aldolase; LDH5, lactate dehydrogenase 5.
straightening products to acute oxalate nephropathy. As
noted above, in Israel, most hair-straightening products
contain glycolic acid derivatives. However, in the United
States and Europe, hair-straightening products containing
cysteine, acetic acid, ammonium thioglycolate, and thio-
glycolic acid are commonly used. Although this may partly
explain the absence of reported cases of AKI following hair
straightening in those countries, a lack of awareness by
treating physicians of a possible relationship between
exposure to keratin-based products and AKI may lead to
underreporting.
Our case series has several limitations. Its retrospective
design has inherent biases. The relatively small number of
kidney biopsies limits the generalizability of our findings.
However, because kidney function improved spontane-
ously and rapidly in many of the patients, repeat biopsy
was not clinically indicated or justified. Nevertheless,
consistent findings were observed in most biopsies,
including crystal deposition and acute tubular injury.
Importantly, because we were not aware of the possibility
of oxalate nephropathy as the main cause of AKI in these
patients until all data were collected and analyzed, there
was no 24-hour urine collection for oxalate testing, nor
blood testing for glycolic acid and formic acid. Further-
more, information regarding the specific components of
the hair-treatment products, including concentration of
glycolic acid derivatives and the pH of the products, the
use of heating during hair treatment (which may be
associated with the release of formaldehyde), and exposure
time of these agents on the scalp during treatment was
unavailable in most cases. It should also be noted that,
because there is no clear information regarding the total
number of people undergoing hair straightening in Israel,
clear incidence cannot be established. Finally, because the
8 AJKD Vol XX | Iss XX | Month 2023
Bnaya et al
follow-up period was relatively short and the number of
patients was limited, we could not identify patient char-
acteristics or clinical features associated with more severe
presentation, slower recovery, or need for dialysis.
In summary, this case series suggests an association
between keratin-based hair-straightening products and
AKI, possibly mediated by the toxic effects of glycolic acid
derivative absorption and acute oxalate nephropathy. In
addition, potential exposure to formaldehyde may also
contribute to the clinical presentation.
Our findings may reflect only the “tip of the iceberg”;
potentially, subclinical kidney injury after hair-
straightening procedures may occur as well. Alterna-
tively, these cases may represent dire ramifications of the
use of unsupervised products with high levels of glycolic
acid derivatives, low pH, or poor technique (ie, heating).
As of the time of writing, the Israeli Ministry of Health is
conducting a formal investigation of AKI events associated
with hair treatments and monitoring adherence to
regulations.
Article Information
Authors’ Full Names and Academic Degrees: Alon Bnaya, MD,
Nabil Abu-Amer, MD, Pazit Beckerman, MD, Alexander Volkov, MD,
Keren Cohen-Hagai, MD, Meidad Greenberg, MD, Sydney Ben-
chetrit, MD, Kim Ben Tikva Kagan, MD, Shira Goldman, MD, Hadar
Agmon Navarro, MD, Marwan Abu Sneineh, MD, Benaya Rozen-
Zvi, MD, Yael Borovitz, MD, Ana Tobar, MD, Noa Berar Yanay, MD,
Ray Biton, MD, Avital Angel-Korman, MD, Vladimir Rappoport, MD,
Adi Leiba, MD, Younes Bathish, MD, Evgeni Farber, MD, Maital
Kaidar-Ronat, MD, Letizia Schreiber, MD, Moshe Shashar, MD,
Raisa Kazarski, MD, Gil Chernin, MD, Eyal Itzkowitz, MD, Jawad
Atrash, MD, Nomy Levin Iaina, MD, Shai Efrati, MD, Elad Nizri, MD,
Yael Lurie, MD, Ofer Ben Itzhak, MD, Suheir Assady, MD, Yael
Kenig-Kozlovsky, MD, and Linda Shavit, MD.
Bnaya et al
Authors’ Affiliations: Institute of Nephrology, Shaare Zedek Medical
Center (AB, EI, JA, LS), Hebrew University of Jerusalem (RK, GC),
Jerusalem; Institute of Nephrology and Hypertension (NA-A, PB)
and Department of Pathology (AV), Sheba Medical Center,
Sackler Faculty of Medicine (NA-A, PB, KC-H, MG, SB-c, KB-T,
SG, HAN, MAS, BR-Z, YB, AT, MK-R, SE, EN), Tel Aviv University,
and Department of Nephrology, Hillel Yaffe Hospital (NBY), Tel
Aviv; Department of Nephrology and Hypertension, Meir Medical
Center, Kfar Saba (KC-H, MG, SB-c); Departments of Nephrology
and Hypertension (KB-T, SG, HAN, MAS, BR-Z) and Pathology
(AT), Rabin Medical Center, Petah Tikva; Nephrology Institute,
Schneider Children's Medical Center, Petah Tikva, Israel (YB);
Nephrology and Hypertension Institute, Samson Assuta Ashdod
University Hospital, Ashdod (RB, AA-K, VR, AL); Faculty of Health
Sciences, Ben Gurion University of the Negev, Beersheba (AA-K,
VR, AL, NLI); Nephrology Unit, Ziv Medical Centre, Safed (YB);
Nephrology Unit, Baruch Padeh Medical Center, Tiberias (EF);
Edith Wolfson Medical Center Ringgold Standard Institution (MK-
R) and Department of Pathology, Edith Wolfson Medical Center
(LS), Holon; Department of Nephrology and Hypertension, Laniado
Hospital, Netanya (MS); Nephrology Institute, Kaplan Medical
Center, Rehovot (RK, GC); Department of Nephrology and
Hypertension, Barzilai Medical Center, Ashkelon (NLI); Department
of Nephrology, Shamir (Assaf Harofeh) Medical Center, Zerifin
(SE, EN); Clinical Pharmacology and Toxicology Section, Israel
Poison Information Center (YL), and Departments of Pathology
(OBI) and Nephrology and Hypertension (SA, YK-K), Rambam
Medical Center; and B. Rappaport Faculty of Medicine, Technion
(YL, OBI, SA, YK-K), Haifa, Israel.
Address for Correspondence: Alon Bnaya, MD, Nephrology Unit,
Shaare Zedek Medical Center, PO Box 3235, Jerusalem 91031,
Israel. Email: alonb@szmc.org.il
Authors’ Contributions: Research idea and study design: AB, LS;
data acquisition: all authors; data analysis and interpretation: AB,
LS; supervision or mentorship: LS. Each author contributed
important intellectual content during manuscript drafting or revision
and agrees to be personally accountable for the individual’s own
contributions and to ensure that questions pertaining to the
accuracy or integrity of any portion of the work, even one in which
the author was not directly involved, are appropriately investigated
and resolved, including with documentation in the literature if
appropriate.
Support: None.
Financial Disclosure: The authors declare that they have no
relevant financial interests.
Peer Review: Received July 7, 2022. Evaluated by 2 external peer
reviewers, with direct editorial input from the Pathology Editor, an
Associate Editor, and the Editor-in-Chief. Accepted in revised form
November 27, 2022.
References
1. Uber AM, Sutherland SM. Nephrotoxins and nephrotoxic acute
kidney injury. Pediatr Nephrol. 2020;35(10):1825-1833. doi:
10.1007/s00467-019-04397-2
2. Soderland P, Lovekar S, Weiner DE, Brooks DR, Kaufman JS.
Chronic kidney disease associated with environmental toxins
and exposures. Adv Chronic Kidney Dis. 2010;17(3):254-264.
doi:10.1053/j.ackd.2010.03.011
3. Perazella MA. Toxic nephropathies: core curriculum 2010. Am J
Kidney Dis. 2010;55(2):399-409. doi:10.1053/j.ajkd.2009.10.046
4. Barreto T, Weffort F, Frattini S, Pinto G, Damasco P, Melo D.
Straight to the point: what do we know so far on hair
straightening? Skin Appendage Disord. 2021;7(4):265-271.
doi:10.1159/000514367
AJKD Vol XX | Iss XX | Month 2023
5. Committee to Review the Formaldehyde Assessment in the
National Toxicology Program 12th Report on Carcinogens;
Board on Environmental Studies and Toxicology; Division on
Earth and Life Sciences; National Research Council. Review of
the Formaldehyde Assessment in the National Toxicology
Program 12th Report on Carcinogens. Washington, DC, Na-
tional Academies Press, 2014.
6. Boga C, Taddei P, Micheletti G, et al. Formaldehyde replace-
ment with glyoxylic acid in semipermanent hair straightening: a
new and multidisciplinary investigation. Int J Cosmet Sci.
2014;36(5):459-470. doi:10.1111/ics.12148
7. Aglan MA, Mansour GN. Hair straightening products and the
risk of occupational formaldehyde exposure in hairstylists. Drug
Chem Toxicol. 2020;43(5):488-495. doi:10.1080/01480545.
2018.1508215
8. Ahmed HM, Rashad SH, Ismail W. Acute kidney injury following
usage of formaldehyde-free hair straightening products. Iran J
Kidney Dis. 2019;13(2):129-131.
9. Mitler A, Houri S, Shriber L, Dalal I, Kaidar-Ronat M. Recent use
of formaldehyde-’free’ hair straightening product and severe
acute kidney injury. Clin Kidney J. 2021;14(5):1469-1471. doi:
10.1093/ckj/sfaa272
10. Kaidar M, Mitler A, Greenberg M, Cohen-Adam D, Abu-Ata M,
Borovitz Y. Hair straightening – not straightforward. Harefuah.
2021;160(12):810-813.
11. Mehta RL, Kellum JA, Shah SV, et al; Acute Kidney Injury
Network. Acute Kidney Injury Network: report of an initiative to
improve outcomes in acute kidney injury. Crit Care.
2007;11(2):R31. doi:10.1186/cc5713
12. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating
the probability of adverse drug reactions. Clin Pharmacol Ther.
1981;30(2):239-245. doi:10.1038/clpt.1981.154
13. Levey AS, Stevens LA, Schmid CH, et al; CKD-EPI (Chronic
Kidney Disease Epidemiology Collaboration). A new equation
to estimate glomerular filtration rate [published erratum ap-
pears in Ann Intern Med. 2011;155(6):408]. Ann Intern Med.
2009;150(9):604-612. doi:10.7326/0003-4819-150-9-200905
050-00006
14. Buysschaert B, Aydin S, Morelle J, Gillion V, Jadoul M,
Demoulin N. Etiologies, clinical features, and outcome of oxa-
late nephropathy. Kidney Int Rep. 2020;5(9):1503-1509. doi:
10.1016/j.ekir.2020.06.021
15. Rosenstock JL, Joab TMJ, DeVita MV, Yang Y, Sharma PD,
Bijol V. Oxalate nephropathy: a review. Clin Kidney J.
2021;15(2):194-204. doi:10.1093/ckj/sfab145
16. Demoulin N, Aydin S, Gillion V, Morelle J, Jadoul M. Patho-
physiology and management of hyperoxaluria and oxalate ne-
phropathy: a review. Am J Kidney Dis. 2022;79(5):717-727.
doi:10.1053/j.ajkd.2021.07.018
17. Yang Y, Sharma PD, Nair V, et al. Kidney oxalate crystal
deposition in adult patients: A relatively common finding. Clin
Nephrol. 2020;93(5):243-250. doi:10.5414/CN109980
18. Andersen FA. Final report on the safety assessment of glycolic
acid, ammonium, calcium, potassium, and sodium glycolates,
methyl, ethyl, propyl, and butyl glycolates, and lactic acid,
ammonium, calcium, potassium, sodium, and tea-lactates,
methyl, ethyl, isopropyl, and butyl lactates, and lauryl, myristyl,
and cetyl lactates. Int J Toxicol. 1998;17(suppl 1):1-241.
https://doi.org/10.1177/109158189801700101
19. Jiang M, Qureshi SA. Assessment of in vitro percutaneous
absorption of glycolic acid through human skin sections
using a flow-through diffusion cell system. J Dermatol
Sci. 1998;18(3):181-188. doi:10.1016/s0923-1811(98)
00039-5
9

20. Kraeling MEK, Bronaugh RL. In vitro percutaneous absorption
of alpha hydroxy acids in human skin. J Soc Cosmet Chem.
1997;48:187-197.
21. Copoví A, Díez-Sales O, Herr! aez-Domínguez JV, Herr! aez-
Domínguez M. Enhancing effect of alpha-hydroxyacids on
“in vitro” permeation across the human skin of compounds with
different lipophilicity. Int J Pharm. 2006;314(1):31-36. doi:10.
1016/j.ijpharm.2006.01.033
22. Schnedler N, Burckhardt G, Burckhardt BC. Glyoxylate is a
substrate of the sulfate-oxalate exchanger, sat-1, and increases
its expression in HepG2 cells. J Hepatol. 2011;54(3):513-520.
doi:10.1016/j.jhep.2010.07.036
23. Garrelfs S, van Harskamp D, Peters-Sengers H, et al. Endog-
enous oxalate production in primary hyperoxaluria type 1 pa-
tients. J Am Soc Nephrol. 2021;32(12):3175-3186. doi:10.
1681/ASN.2021060729
24. Knight J, Jiang J, Assimos DG, Holmes RP. Hydroxyproline
ingestion and urinary oxalate and glycolate excretion. Kidney
Int. 2006;70(11):1929-1934. doi:10.1038/sj.ki.5001906
25. Silbergeld S, Carter HE. Toxicity of glycolic acid in male and
female rats. Arch Biochem Biophys. 1959;84:183-187. doi:10.
1016/0003-9861(59)90568-5
26. Ogawa Y, Morozumi M, Tanaka T, Yamaguchi K. A comparison
between effects of pyruvate and herb medicines in preventing
experimental oxalate urolithiasis in rats. Hinyokika Kiyo.
1986;32(8):1127-1133.
27. Richardson KE. Endogenous oxalate synthesis in male and
female rats. Toxicol Appl Pharmacol. 1965;7:507-515. doi:10.
1016/0041-008x(65)90035-9
28. Harris KS, Richardson KE. Glycolate in the diet and its conver-
sion to urinary oxalate in the rat. Invest Urol. 1980;18:106-109.
29. Chow FC, Dysart MI, Hamar DW, Udall RH. Control of oxalate
urolithiasis by DL-alanine. Invest Urol. 1975;13:113-116.
30. Chow FH, Hamar DW, Boulay JP, Lewis LD. Prevention of
oxalate urolithiasis by various compounds. Invest Urol.
1978;15:493-495.
31. Slavin JW, Ritota PC, Elfenbein IB. Renal failure after glycolic
acid skin treatments. Aesthetic Surg J. 1996:1675-1676. doi:
10.1016/S1090-820X(96)70018-3
32. Monico CG, Rossetti S, Belostotsky R, et al. Primary hyperoxaluria
type III gene HOGA1 (formerly DHDPSL) as a possible risk factor
for idiopathic calcium oxalate urolithiasis. Clin J Am Soc Nephrol.
2011;6(9):2289-2295. doi:10.2215/CJN.02760311
33. Beck BB, Baasner A, Buescher A, et al. Novel findings in pa-
tients with primary hyperoxaluria type III and implications for
advanced molecular testing strategies. Eur J Hum Genet.
2013;21:162-172. doi:10.1038/ejhg.2012.139
34. Williams EL, Bockenhauer D, van’t Hoff WG, et al. The enzyme
4-hydroxy-2-oxoglutarate aldolase is deficient in primary
hyperoxaluria type 3. Nephrol Dial Transplant. 2012;27:3191-
3195. doi:10.1093/ndt/gfs039
35. Gee HY, Jun I, Braun DA, et al. Mutations in SLC26A1 cause
nephrolithiasis. Am J Hum Genet. 2016;98:1228-1234. doi:
10.1016/j.ajhg.2016.03.026
10
Bnaya et al
36. Dawson PA, Sim P, Mudge DW, Cowley D. Human SLC26A1
gene variants: a pilot study. ScientificWorldJournal.
2013;2013:541710. doi:10.1155/2013/541710
37. Shimshilashvili L, Aharon S, Moe OW, Ohana E. Novel hu-
man polymorphisms define a key role for the SLC26A6-
STAS domain in protection from Ca2+-oxalate lithogenesis.
Front Pharmacol. 2020;11:405. doi:10.3389/fphar.2020.
00405
38. Jiang H, Pokhrel G, Chen Y, et al. High expression of SLC26A6
in the kidney may contribute to renal calcification via an
SLC26A6-dependent mechanism. PeerJ. 2018;6:e5192. doi:
10.7717/peerj.5192
39. Boyer IJ, Heldreth B, Bergfeld WF, et al. Amended safety
assessment of formaldehyde and methylene glycol as used in
cosmetics. Int J Toxicol. 2013;32(suppl):5S-32S. doi:10.1177/
1091581813511831
40. European Economic Community. Council Directive of 27 July
1976 on the approximation of the laws of the member states
relating to cosmetic products. 1976. Accessed April 23, 2013.
http://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=CONSLEG:
1976L0768:20100301:en:PDF
41. Australian Department of Health and Ageing. Formaldehyde.
Priority existing chemical assessment report no. 28; 2006.
Accessed July 5, 2011. https://www.industrialchemicals.gov.
au/sites/default/files/PEC28-Formaldehyde.pdf
42. Health Canada. Cosmetic ingredient hotlist (list of prohibited
and restricted cosmetic ingredients). Accessed July 5, 2011.
http://www.hc-sc.gc.ca/cps-spc/cosmet-person/indust/hot-list-
critique/hotlist-liste_dl-eng.php
43. Boj JR, Marco I, Cort! es O, Canalda C. The acute nephrotoxicity
of systemically administered formaldehyde in rats. Eur J Pae-
diatr Dent. 2003;4:16-20.
44. Ramos CO, Nardeli CR, Campos KKD, et al. The exposure to
formaldehyde causes renal dysfunction, inflammation and redox
imbalance in rats. Exp Toxicol Pathol. 2017;69(6):367-372. doi:
10.1016/j.etp.2017.02.008
45. Sarnak MJ, Long J, King AJ. Intravesicular formaldehyde instil-
lation and renal complications. Clin Nephrol. 1999;51(2):122-
125.
46. Merimsky E, Jossiphov J. Toxic effects on the kidney by endo-
vesical installations of formol. Hematogenic diffusion or reflux.
J Urol (Paris). 1980;86:527-529.
47. _Inci M, Zararsız _I, Davarcı M, G€orür S. Toxic effects of formal-
dehyde on the urinary system. Turk J Urol. 2013;39:48-52. doi:
10.5152/tud.2013.010
48. Pierce JS, Abelmann A, Spicer LJ, et al. Characterization
of formaldehyde exposure resulting from the use of four
professional hair straightening products. J Occup Environ
Hyg. 2011;8(11):686-699. doi:10.1080/15459624.2011.
626259
49. Monakhova YB, Kuballa T, Mildau G, et al. Formaldehyde in hair
straightening products: rapid 1H NMR determination and risk
assessment. Int J Cosmet Sci. 2013;35:201-206. doi:10.
1111/ics.12027
AJKD Vol XX | Iss XX | Month 2023