Acute kidney injury due to excessive and prolonged intramuscular injection of veterinary supplements containing vitamins A, D and E : a series of 16 cases

n e f r o l o g i a 2 0 1 7;37(1):61–67

w w w . r e v i s t a n e f r o l o g i a . c o m

RevistadelaSociedadEspañoladeNefrología

Original

article

Acute

kidney

injury

due

to

excessive

and

prolonged

intramuscular

injection

of

veterinary

supplements

containing

vitamins

A,

D

and

E:

A

series

of

16

cases

Elizabeth

De

Francesco

Daher

_,

_Lorena

_Vasconcelos

_Mesquita

_Martiniano

_,

Laio

Ladislau

Lopes

Lima

_,

_Newton

_Carlos

_Viana

_Leite

_Filho

_,

Louize

Emanuele

de

Oliveira

Souza

_,

_Paulo

_Henrique

_Palácio

_Duarte

_Fernandes

_,

Sonia

Leite

da

Silva

_,

_Geraldo

_Bezerra

_da

_Silva

_Junior

a_{DepartmentofInternalMedicine,SchoolofMedicine,MedicalSciencesGraduateProgram,FederalUniversityofCeará,Fortaleza,}

Ceará,Brazil

b_{SchoolofMedicine,PublicHealthGraduateProgram,UniversityofFortaleza,Fortaleza,Ceará,Brazil}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received23December2015 Accepted9May2016

Availableonline28August2016

Keywords:

Acutekidneyinjury

Vitaminsupplements

Hypercalcaemia

a

b

s

t

r

a

c

t

Background:Despitewell-documentedrisks,injectablesupplementscontaininghighdoses ofvitaminsarecommonlyused.

Objectives: Todescribeacutekidneyinjury(AKI)asacomplicationofvitaminintoxication. Methods:Ourseriesconsistedof16patientswithkidneycomplicationsresultingfromthe useofveterinaryintramuscularinjectionsupplementsofvitaminA,DandE.Thepatients wereadmittedtotworeferralhospitalsinFortaleza(Brazil)betweenJanuary2010and Jan-uary2015.

Results:Patients’mean agewas28.3±8.9years(19–53years),and11(68.7%)weremale. Mainsignsandsymptomsuponadmissionwerenausea(68.7%),vomiting(62.5%),weight loss(43.7%),epigastricpain(31.2%)andheadache(31.2%).Athospitaladmissionthemean laboratoryvalueswere:hemoglobin10±2.0g/dL(6.1–14.2),leukocytes10,542±4871/mm3 (4100–15,100),creatinine3.9±5.2mg/dL(0.7–22)andurea91±88mg/dL(22–306), respec-tively.Serumcalciumwas12±2.2mg/dL(8.8–15.5),24-hurinecalciumwas575±329mg (10.7–1058),serumPTHwas55±141pg/mL(2–406),andserumvitaminDconcentrationwas 135±75ng/mL(22–265).UsingKDIGOcriteria,AKIwasdiagnosedin13patients(81.2%), classifiedasstage1(n=3),stage2(n=3)orstage3(n=7).Nodeathsoccurredinthestudy period.

Conclusions: Excessiveuseofveterinaryvitaminsupplementscontaininghighdosesof vita-minA,DandEwasassociatedwithAKI.Hypercalcaemia,whichwasacommonfinding, appearstobeacontributingfactortothedevelopmentofthistypeofAKI.

©2016SociedadEspa ˜noladeNefrolog´ıa.PublishedbyElsevierEspa ˜na,S.L.U.Thisisan openaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/ by-nc-nd/4.0/).

∗

Correspondingauthor.

E-mailaddress:ef.daher@uol.com.br(E.DeFrancescoDaher).

http://dx.doi.org/10.1016/j.nefro.2016.05.017

Da ˜no

renal

agudo

debido

a

inyección

intramuscular

excesiva

y

prolongada

de

suplementos

veterinarios

con

vitaminas

A,

D

y

E:

serie

de

16

casos

Palabrasclave: Da ˜norenalagudo Suplementosvitamínicos Hipercalcemia

r

e

s

u

m

e

n

Antecedentes:Suplementosinyectablesquecontienenaltasdosisdevitaminassonutilizados confrecuencia,apesardelosriesgosbiendocumentados.

Objetivo:Describirlaocurrenciadeda ˜norenalagudo(IRA)comocomplicaciónde intoxi-caciónporsuplementosvitamínicos.

Métodos:Estaesunaseriede16pacientesconcomplicacionesrenalesresultantesdela utilizacióndeinyecciónintramusculardesuplementosveterinariosconvitaminasA,Dy E.Lospacientesfueroningresadosen2hospitalesdereferenciaenFortaleza(Brasil),entre enerode2010yenerode2015.

Resultados:Laedadmediadelospacientesfuede28,3±8,9a ˜nos(19–53a ˜nos)y11(68,7%)eran varones.Signosysíntomasprincipalesalingresofueronnáuseas(68,7%),vómitos(62,5%), pérdidadepeso(43,7%),dolorepigástrico(31,2%)ycefalea(31,2%).Alingresoenelhospital losvaloresmediosdelaboratoriofueron:hemoglobina10±2,0g/dL(6,1–14,2),leucocitos 10.542±4.871/mm3_{(4.100–15.100),creatinina3,9±5,2mg/dL(0,7–22)yurea91±88mg/dL} (22–306),respectivamente.Elniveldecalcioséricofuede12±2,2mg/dL(8,8–15,5),elde calcioenorinade24hfuede575±329mg(10,7–1.058),eldePTHséricofuede55±141pg/mL (2–406)yelniveldevitaminaDséricafuede135±75ng/mL(22–265).Utilizandocriterios KDIGO,sediagnosticóIRAen13pacientes(81,2%);fueronclasificadascomoclase1(n=3), clase2(n=3)yclase3(n=7).Nohubomuertesenelperíododeestudio.

Conclusiones:Elusoexcesivodesuplementosvitamínicosveterinariosquecontienenaltas dosisdevitaminaA,DyEseasocióconIRA.Lahipercalcemia,unhallazgocomún,parece serunfactorquecontribuyealdesarrollodeestetipodeIRA.

©2016SociedadEspa ˜noladeNefrolog´ıa.PublicadoporElsevierEspa ˜na,S.L.U.Esteesun art´ıculoOpenAccessbajolalicenciaCCBY-NC-ND(http://creativecommons.org/licenses/ by-nc-nd/4.0/).

Introduction

Bodysculptingisanincreasinglycommonpracticeinmodern society.1_{Someenthusiastsresorttosubstanceabusetoboost}

results,despitetheserioushealthrisksinvolved.Anumber ofcommerciallyavailablesubstances,fromanabolicsteroids (hormonespromotingmuscleanabolism)tooilycompounds (increasingmusclevolumebywayofretention,without con-tributingtoanabolism),areknowntocauseseveredamageto theorganism.2

Onesuchsubstanceisthecompound“ADE”,aveterinary productcontainingliposolublevitaminA,DandE,indicated forthetreatmentofvitamindeficiencyandinfectionincattle andhorses.Accordingtothemanufacturers,animalsshould notbeinjectedwithmorethan5mLper120-dayperiodof fattening.However,muchhigherdoses areusedbyhuman bodysculptors.2_{TheinjectionofADEproducesalocal}

gran-ulomatousreactionandencapsulation.Ifencapsulationfails, orifthesubstanceentersthebloodstream,embolismmay occur,insomecasesfollowedbydeath.2_{InBrazil,humanADE}

usewasfirstdescribedinthelate1980s,butmayhavestarted earlier.3

Thepurposeofthepresentstudywastoevaluatethe occur-renceofacutekidneyinjury(AKI)orchronickidneydisease (CKD)inaseriesofpatientsadmittedtotwoBrazilianreferral hospitalsduetocomplicationsfromexcessiveandprolonged intramuscularinjectionofADEvitamins.

Patients

and

methods

Studydesign

Thisisadescriptive studybasedonacaseseries. Wehave

evaluatedaseriesof16patientswithkidneycomplications

resulting from theuse ofveterinary intramuscularvitamin

supplementscontaininghighdosesofvitaminA,DandE.The patientswereadmittedtotworeferralhospitalsinFortaleza (NortheasternBrazil)betweenJanuary2010andJanuary2015. Patientswithahistoryofrenalfailure,hypertension,diabetes mellitus,nephrolithiasis,nephrotoxicdruguse,orany comor-biditypotentiallydetrimentaltorenalfunction,wereexcluded fromtheanalysis.

Vitaminsupplementsused

All studied patients have used vitamin supplements

con-taining vitaminsA, D and E. In each 100mLthe following

compositionwasobserved:vitaminA20,000,000IU,vitaminD 35,000,000IUandvitaminE6000IU,whichrepresentsavery

high dose, higher than the recommended daily intake for

humans.

Studyparameters

Informationwas collectedondemographics, lengthof

n e f r o l o g i a 2017;37(1):61–67

63

for dialysis, treatment and mortality. Clinical information included all clinical signs and symptoms registered upon admissionand duringhospitalization. The laboratorytests included complete blood count, serum urea, creatinine, sodium,potassium,calcium,aspartateaminotransferase, ala-nineaminotransferase,parathyroidhormone(PTH),vitaminD andurinalysis.Twenty-four-hoururinarycalciumlevelswere alsoregistered.

Definitions

AKI and CKD were diagnosed and classified according to KDIGOcriteria.4_{Duetolackofinformationonserum}

creat-ininelevelspriortoadmission,allpatientswereassumedto haveabaselineglomerularfiltrationrateof100mL/min/m2_.

The patients were classified as the highest KDIGO stage observed duringhospitalization. Oliguria was defined as a urineoutput<0.5mL/kg/h.Dialysiswasindicatedforpatients whoremained oliguricaftereffectivehydration foratleast 24h, for refractory hypervolemia, severe metabolic acido-sisor uremia. Highblood pressure was defined assystolic blood pressure ≥140mmHgand/or diastolicblood pressure

≥90mmHg.

Ethicalaspects

The study protocol was reviewed and approved by the ResearchEthics CommitteesoftheGeneralHospitalof For-talezaandtheWalterCantídioUniversityHospital.

Results

Patients’ mean age was 28.3±8.9 years (19–53 years), and

11(68.7%)weremale.Meanlengthofhospitalstaywas15±13

days (1–52 days). Upon admission, all patients reported a

history of intramuscular injection of vitamin supplements

containing vitamins A, D and E for estheticpurposes. Six

patients reported concurrent use of anabolic steroids. All

werebodybuildingpractitionersandattendedgymsregularly.

Themedian time between the last injection and

hospital-izationwas 10 months (range: 1–48 months). The median

timebetweenthefirstuseandhospitalizationwas28months (range:4–60months).Table1summarizes patients’clinical andlaboratorycharacteristics.

Mainsigns andsymptomsuponadmissionwerenausea (68.7%),vomiting(62.5%),weightloss(43.7%),epigastricpain (31.2%)andheadache(31.2%),fever(25%),paresthesiainthe upperandlowerlimbs(25%),polyuria(18.7%),syncope(18.7%) andanorexia (18.7%).Patients alsoreportedlow backpain, edema,nocturiaandpallor(12.5%each),andgynecomastia andlymphadenopathy(6.2%each).

At hospital admission the mean laboratory values were: hemoglobin 10±2.0g/dL (range 6.1–14.2), leukocytes 10,542±4871/mm3 _{(4100–15100), creatinine 3.9±5.2mg/dL}

(0.7–22)andurea91±88mg/dL(22–306),respectively.Serum calcium level was 12±2.2mg/dL (8.8–15.5), 24-h urine cal-ciumlevel was 575±329mg (10.7–1058),median PTH level was 55±141pg/mL (2–406), and serum vitamin D concen-tration was 135±75ng/mL (22–265). During hospital stay

Table1–Clinicalandlaboratorycharacteristics of16patientswithacutekidneyinjuryduetovitamin supplementsabuse.

n %

Age(years) 28.3±8.9 –

Gender

Male 11(68.7%) 68.7

Female 5(31.3%) 31.3

Lengthofhospitalstay (days)

15±13 –

Mediantimebetween firstuseand admission(months)

28 –

Signsandsymptomsatadmission

Nausea 11 68.7

Vomiting 10 62.5

Weightloss 7 43.7

Epigastricpain 5 31.2

Headache 5 31.2

Fever 4 25

Paresthesia(limbs) 4 25

Polyuria 3 18.7

Syncope 3 18.7

Anorexia 3 18.7

Lowbackpain 2 12.5

Edema 2 12.5

Nocturia 2 12.5

Pallor 2 12.5

Gynecomastia 1 6.2

Lymphadenopathy 1 6.2

AKI 13 81.2

Laboratorytests

Hbadm(g/dL) 10±2.0 –

Leukocytesadm (1×/mm3₎

10,542±4871 –

Cradm(mg/dL) 3.9–5.2mg –

Crmax(mg/dL) 4.3±5.2 –

Crdis(mg/dL) 1.6±1.8 –

Uradm(mg/dL) 91±88 –

Urmax(mg/dL) 102±86 –

Urdis(mg/dL) 45±28 –

Caadm(mg/dL) 12–2.2 –

Camax(mg/dL) 13±2.2 –

24h-Ca(mg/dL) 575±329 –

PTH(pg/mL) 55±141 –

VitaminD(ng/mL) 135±75 –

Mean±SDand%.

Hb,hemoglobina(g/dL);Ur,urea(mg/dL);Cr,creatinine(mg/dL);Ca, calcium(mg/dL);24h-Ca,24hcalciuria(mg/dL);adm,atadmission; max,maximumathospitalstay;dis,athospitaldischarge.

maximum creatinine ranged from 0.8 to 8.6mg/dL (mean

4.3±5.2mg/dL)and serumcalcium from 10.2to16.8mg/dL

(mean13±2.2mg/dL).Laboratoryfindingsforeachpatientare summarizedinTable2.

Three patients had imaging findings compatible with nephrocalcinosisandsevenhadnephrolithiasis.UsingKDIGO criteria,AKIwasdiagnosedin13cases(81.2%)andclassifiedas stage1(23%),stage2(23%)orstage3(54%).Nodeathsoccurred inthestudyperiod.

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Table2–Laboratorytestsduringhospitalstayof16patientswithkidneyinjuryduetovitaminsupplementsabuse. # Age Gender Ht

adm Hb adm

WBC adm

Platelets adm

Ur adm

Ur max

Ur dis

Cr adm

Cr max

Crdis AST/ALT adm

AST/ALT max

AST/ALT dis

Na adm

Kadm Ca adm

Ca max

Cadis VitD 24h calciuria

PTH

1 22 F 27.5 9.2 7584 397,709 30 45 33 1.6 1.6 1.1 21/14 – – 140 3.5 11.9 12.4 11.1 >150 – – 2 29 M 30 10.1 8214 463,100 62 73 66 1.6 2.4 1.7 19/35 25/52 20/52 139 4.4 11.7 14.6 10 >150 499.8 3.4 3 34 F 26.5 8.9 12,530 288,800 46 80 78 2.5 2.5 1.4 24/14 47/26 – 146 3.5 15.5 16.8 10.1 – 422.8 7

4 23 M 34.7 11.6 4100 200,000 61 61 48 2.5 2.5 1.4 117/73 117/73 – 139 4 – 12.8 9.1 – – –

5 29 F 33.3 11.5 10,800 313,000 32 32 30 1.4 1.5 1.2 58/75 58/75 – 136 2.9 11.8 12.8 11.7 182.4 484.16 8.41

6 28 M 29.6 9.16 6060 286,000 32 – 29 1.1 – 0.9 – – – 139 3.8 9.5 – 8.8 154.4 – –

7 19 M 34.8 11.8 23,900 594,000 54 35 30 3.5 3.5 0.8 – – – 137 4.2 13.3 13.3 7.9 – 1058 –

8 45 F 34.4 11.5 10,540 250,000 32 57 15 1.5 1.5 0.8 – 15/22 15/22 139 3.8 11 11.3 9.8 >160 428.4 –

9 26 M – – 5500 – 55 77 15 2.7 3.7 0.6 – – – 135 3 10.6 16.8 8 116.7 1039.5 –

10 53 M 27.7 9.44 15,100 320,000 68 68 42 3.2 3.2 1.3 40/32 50/25 35/22 139 4.8 14 14 9.6 160 536.3 5.15 11 24 M 30.6 10.9 8350 60,000 200 200 56 8.6 8.6 1.8 30/22 – – 141 3.4 13.8 14.2 – 53.9 330.2 6.32 12 21 M 43.9 14.2 13,000 247,000 22 28 16 0.7 1 0.7 33/44 33/44 22/30 140 4.6 9.2 10.2 10 – – –

13 25 F 25.3 8.02 7480 457,000 – – – 0.79 0.8 0.8 – – – – – 10.01 10.73 10.73 129.1 – 2

14 25 M 19.8 6.1 12,540 31,200 247 247 56 5.8 5.8 1.3 31/29 39/48 – 148 4.9 15 15 12 – – –

15 24 M 20.4 6.8 12,440 114,600 306 306 124 22 22 8.5 – – – 120 4.6 8.8 9 8.6 22.5 10.73 406 16 27 M 33 10.8 – – 122 122 37 4.1 4.1 1.3 43/45 43/111 36/111 136 5.3 14.9 14.9 9.3 265.25 1012 4.1

n e f r o l o g i a 2017;37(1):61–67

65

hypercalcemia(18.7%)andlocalinfections(18.7%)resulting fromintramuscularinjectionsofvitaminsupplements with-out sterilization. Hypercalcemia was treatedwith vigorous hydration,steroidsandloopdiuretics.DuetosevereAKI,two patientsrequired dialysis.One(#11) received 5 hemodialy-sissessionsduringhospitalization.Theother(#15)developed chronickidneydiseaseandwasstartedonregular hemodial-ysis three times a week. Six previously non-hypertensive patients presented hypertensive peaks upon admission. Hypertensionpersistedin four caseswho were discharged withprescriptionsforanti-hypertensivedrugs.

Discussion

Aconsiderablenumberofpatientswithseverekidney compli-cations(includingchronickidneyfailure)fromexcessiveuse

ofvitaminsupplements aredescribed inthis study.Kidney

injury due to vitamin abuse is seldom reported in

litera-ture and it seems to be a frequent complication, atleast

amongpatientstakingveryhighdosesofvitamins(veterinary doses).5_{Thepossiblemechanismsinvolvedinthe}

pathophy-siologyofkidney injuryassociatedwithhypercalcemiaand injectablevitaminsA,DandEsupplementsisschematizedin

Fig.1.

Asinothergranulomatousconditions,suchas tuberculo-sis,sarcoidosisandfungalinfections,vitaminDisconverted extra-renalintoitsactiveformbygranulomacells(especially macrophages).Thisincreasestheintestinalabsorptionof vita-minD-dependentcalciumandraisesserumcalciumlevels.6

Hypercalcemiaandhighlevelof1.25(OH)2D3concentrations

haveanegativeimpactontheparathyroidglands,reducing

PTHproductionandserumlevels.7_{Thispatternwasobserved}

inmostofourpatientsandinmostpatientsreportedinthe literature.5,8–10

Ontheotherhand,somebelievehypervitaminosisisthe resultoftheabsorptionofinjectedvitaminD.Furtherstudies arenecessarytoclarifythemechanismsinvolved,butthefact thatasimilarreactionoccurswhenothersubstances(suchas paraffin)areinjectingintothemuscle,alongwiththeobserved lateonset ofhypercalcemia(monthslater), pointto granu-lomaformationandextra-renalconversionasthemostlikely explanation.3_{IftheabsorptionofinjectedvitaminDwerethe}

culprit,theonsetofhypercalcemiawouldbeacute.11–13

Theeffects ofhypervitaminosis Aand Ein humansare lessstudiedthanhipervitaminosisD.Itisknownthatafter consumptionofhighdosesofvitaminAtheconcentrations ofretinoids andmetabolites areelevated inplasma. Toxic-ity following high consumptionof vitaminA canbe acute (intake>660,000IU)orchronic,whenintakelastsformonths oryears(adose>100,000IUformorethan6monthsis con-sidered toxic),14,15 _{and our patientsconsumed a dose very}

higherthanthelevelsconsideredtoxic.Themaineffectsof hypervitaminosisAarerelatedtobonemetabolism.Thereis association between highvitamin Aintake and osteoporo-sisandpathologicalfractures.14_{Other signsandsymptoms}

of vitamin A toxicity includes include dry skin, nausea, headache,fatigue,irritability,anorexia,liverdisease,hairloss and alopecia, hyperostosis, high cholesterol and increased cerebrospinalfluidpressure.15_{HypervitaminosisEisrare,but}

itispossibletobemorefrequentonceconsumptionofthis vitaminisincreasingduetoits potentiallyantioxidant and antiatherogenic effects.Toxic effectsofhypervitaminosis E includesprolongationofprothrombintimeandhemorrhage

Immune

Reabsorption _{Hipercalcemia}

Granuloma Response

25(OH)D3

1,25(OH)₂D₃

PTH

Reabsorption

Direct renal

Vasoconstriction

Acute kidney injury Chronic

kidney disease

Glomerular filtration rate Dehydration

Nephrogenic

diabetes

insipidus Nephrocalcinosis

nephrolithiasis

Nausea Vomiting

Urinary Ca2+

1α(OH)ase

(dueto antagonist effects ofvitaminE againstvitamin K), hypertension, angina and stroke.16 _{Our patients had}

nau-sea,vomitingandheadache,whichcouldbeattributableto hypervitaminosisAandE,butthesesymptomscouldalsobe consequenceofAKI-associateduremia.

Inthepresentcaseseries,kidneyinjuryrangedfrom rel-atively mild and reversible acute injury to severe disease progressingtoend-stagechronickidneyfailure(asobserved in patient #15). Persistent hypercalcemia with serum cal-ciumlevels >11mg/dL may inup to20% ofcases develop into nephrogenic diabetes insipidus, which usually reverts withtheresolutionofthehypercalcemiccondition.Though notyetfullyunderstood,themechanismofnephrogenic dia-betesinsipiduspossiblyinvolvestheinhibitionofreabsorption ofsodiumchlorideinthethick ascendinglimbofthe loop ofHenle (in detrimentto countercurrent exchange)and of vasopressin-mediatedwaterpermeabilityintheterminal col-lectingduct.17

Hypercalcemiahasbeenshowntodownregulate aquapor-ine 2protein expressioninrat kidney medulla,interfering withthe abilityto concentrateurine.18 _{Calcium deposition}

inthe medulla(acauseoftubulointerstitialinjury)appears toplayanimportantroleinthisprocess.19_{Theactivationof}

calcium-sensingreceptorcanaffecttheurinary-concentrating mechanismbyactinginboththeloopofHenleandthe col-lectingtubules.20

Hypercalciuriasecondary tohypercalcemiaalsoleadsto thedepositionofcalciumintherenalparenchyma, eventu-ally causing nephrocalcinosis and irreversible damageand predisposingtowardthedevelopmentofchronic nephropa-thy.Whentheconcentrationofcalcium phosphateexceeds solubility, Randall’s plaques are formed in the basement membranes of the thin limbsof the loop of Henle in the innermedullaryinterstitium.21–23 _{Thesecalciumphosphate}

plaques can extend into the surrounding interstitial tis-sue, producingmedullar nephrocalcinosis,orpenetrate the urothelium where they are believed to provide a nidus forintratubularstone formation,leadingtonephrolithiasis, obstructiveuropathyandkidneyinjury.24

Thus,nephropathyinducedbyvitaminsupplementabuse canindeedleadtochronickidneydisease.Thisshedslighton thefindingsandoutcomeofpatient#15inourseries.Unlike theotherpatients,#15hadlowcalciumandvitaminDlevels andhighPTHlevels.Combinedwithanemiaandtheneedfor persistentdialysis,thesefindingsareanindicationof termi-nalchronickidneyinjury.Intheabsenceofotheroffending factors,itmaybeinferredthattheconditionofthis25-year oldpatientwasspecificallytheresultofvitaminsupplement abuse.

Most of our patients experienced acute kidney injury, but did not develop chronic kidney disease (nephrocalci-nosis or hydronephrosis).The observed kidney injury may haveinvolvedothermechanisms.Thus,serumcalcium lev-elsinexcessof12–15mg/dLcanacutelyinduceareversible decreaseinglomerularfiltrationbydirectrenal vasoconstric-tionofthearteriolesanddecreasedextracellularfluidvolume duetoanorexia,vomitingandinabilitytoconcentrateurine (nephrogenicdiabetesinsipidus).25_{Vomitingwasacommon}

symptominourpatients,mostlikelyduetohypercalcemia. Insuchcases,kidneyfunctionisoftenfullyrestoredbyearly

treatment. Onthe other hand,non-renalfunctionrecovery or partialrecovery in patients withchronic hypercalcemia withtubulardegeneration,fibrosisandnephrocalcinosisare observed.26

High blood pressure observed in these patients is due mainly to hypercalcemia or kidney injury. Hypercalcemia affects thevascularsmoothmuscledirectlyincreasing vas-cular resistance, and indirectly increasing catecholamines levels. However,theimpactismuchstrongeronrenal vas-cular resistance than on peripheral vascular resistance.27

There are also reports associating vitamin A intoxication with hypercalcemia.28,29 _{Itsmechanism isstill poor}

under-stoodandmayincludeup-regulationofosteoclastsbyretinol metabolites.29

Inconclusion,excessiveuseofveterinaryvitamin supple-ments thatcontaininghigh dosesofvitaminA,D andEis associatedwithAKIandprolongedusewithCKD. Hypercal-cemia,acommonfinding,appearstobeacontributingfactor forthisoutcome.Theimportanceofthisreportistoalertthe medicalcommunitytotheongoinganddangerouspracticeof vitaminandsupplementabusebyyoungindividuals.

Study

limitations

Asthisisadescriptivestudy,therearesomelimitations.We

havedescribed asmallnumberofpatients,but thisis

rep-resentativeofararecomplication(AKI-associatedtovitamin supplementsabuse),whichisstillnotwelldescribedin liter-ature.Somelaboratorytests,suchascreatinekinase(CK),to ruleoutrhabdomyolysis,andserumvitaminDwerenot avail-ableforallpatientsduetotechnicalandeconomicproblems.It wasnotpossibletoperformapowerfulstatisticalanalysis,so itwasnotpossibletodrawstatisticallysignificantassociations betweenpossiblecausalfactorsforAKI.

Conflict

of

interest

Theauthorshavenoconflictsofinteresttodisclose.

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