World Health Organization

Gender: definitions.

de Boer IH Caramori ML Chan JCN et al.

Executive summary of the 2020 KDIGO Diabetes Management in CKD Guideline: evidence-based advances in monitoring and treatment.

Kidney Int. 98: 839-848https://doi.org/10.1016/j.kint.2020.06.024Hyde JS Bigler RS Joel D Tate CC van Anders SM

The future of sex and gender in psychology: five challenges to the gender binary.

Am Psychol. 74: 171-193https://doi.org/10.1037/amp0000307Piani F Melena I Tommerdahl KL et al.

Sex-related differences in diabetic kidney disease: a review on the mechanisms and potential therapeutic implications.

J Diabetes Complications. 35107841https://doi.org/10.1016/j.jdiacomp.2020.107841

Twenty years and still counting: including women as participants and studying sex and gender in biomedical research.

BMC Womens Health. 15: 94https://doi.org/10.1186/s12905-015-0251-9Laprise C Cole K Sridhar VS et al.

Sex and gender considerations in transplant research: a scoping review.

Transplantation. 103: e239-e247https://doi.org/10.1097/TP.0000000000002828

Reutens AT. Epidemiology of diabetic kidney disease. 2022. (1557-9859 Electronic)

Li H Lu W Wang A Jiang H Lyu J.

Changing epidemiology of chronic kidney disease as a result of type 2 diabetes mellitus from 1990 to 2017: estimates from Global Burden of Disease 2017.

J Diabetes Investig. 12: 346-356https://doi.org/10.1111/jdi.13355Piani F Melena I Tommerdahl KL et al.

Sex-related differences in diabetic kidney disease: a review on the mechanisms and potential therapeutic implications.

J Diabetes Complications. 35107841https://doi.org/10.1016/j.jdiacomp.2020.107841

Neugarten J, Acharya A, Silbiger SR. Effect of gender on the progression of nondiabetic renal disease: a meta-analysis. (1046-6673 print). 2022

Cobo G Hecking M Port Friedrich K et al.

Sex and gender differences in chronic kidney disease: progression to end-stage renal disease and haemodialysis.

Clin Sci. 130: 1147-1163https://doi.org/10.1042/CS20160047Neugarten J Golestaneh L Kolhe NV.

Sex differences in acute kidney injury requiring dialysis.

BMC Nephrol. 19: 131-131https://doi.org/10.1186/s12882-018-0937-yJafar TH Schmid CH Stark PC et al.

The rate of progression of renal disease may not be slower in women compared with men: a patient-level meta-analysis.

Nephrol Dial Transplant. 18: 2047-2053https://doi.org/10.1093/ndt/gfg317

Menopause and chronic kidney disease.

Semin Nephrol. 37: 404-411https://doi.org/10.1016/j.semnephrol.2017.05.013

De Cosmo S, Viazzi F, Pacilli A, et al. Predictors of chronic kidney disease in type 2 diabetes: a longitudinal study from the AMD Annals initiative. (1536-5964 (Electronic)). 2022

Harjutsalo V, Maric C, Forsblom C, et al. Sex-related differences in the long-term risk of microvascular complications by age at onset of type 1 diabetes. (1432-0428 (Electronic)). 2022

Möllsten A, Svensson M, Waernbaum I, et al. Cumulative risk, age at onset, and sex-specific differences for developing end-stage renal disease in young patients with type 1 diabetes: a nationwide population-based cohort study. (1939-327X (Electronic)). 2022

Schultz CJ Konopelska-Bahu T Dalton RN et al.

Microalbuminuria prevalence varies with age, sex, and puberty in children with type 1 diabetes followed from diagnosis in a longitudinal study.

Oxford Regional Prospective Study Group. (0149-5992 (Print)),

Renal hyperfiltration in adolescents with type 2 diabetes: physiology, sex differences, and implications for diabetic kidney disease.

Curr Diabetes Rep. 18: 22https://doi.org/10.1007/s11892-018-0996-2Bjornstad P Cherney DZ Snell-Bergeon JK et al.

Rapid GFR decline is associated with renal hyperfiltration and impaired GFR in adults with type 1 diabetes.

Nephrol Dial Transplant. 30: 1706-1711https://doi.org/10.1093/ndt/gfv121Lovshin JA Skrtic M Bjornstad P et al.

Hyperfiltration, urinary albumin excretion, and ambulatory blood pressure in adolescents with type 1 diabetes mellitus.

Am J Physiol Renal Physiol. 314: F667-F674https://doi.org/10.1152/ajprenal.00400.2017

Cystatin C is ready for clinical use.

Curr Opin Nephrol Hypertens. 29: 591-598Inker LA Eneanya ND Coresh J et al.

New creatinine- and cystatin C–based equations to estimate GFR without race.

N Engl J Med. 385: 1737-1749https://doi.org/10.1056/NEJMoa2102953Delgado C Baweja M Crews DC et al.

A unifying approach for GFR estimation: recommendations of the NKF-ASN Task Force on reassessing the inclusion of race in diagnosing kidney disease.

Am J Kidney Dis. 79: 268-288https://doi.org/10.1053/j.ajkd.2021.08.003Huebschmann AG Huxley RR Kohrt WM Zeitler P Regensteiner JG Reusch JEB.

Sex differences in the burden of type 2 diabetes and cardiovascular risk across the life course.

Diabetologia. 62: 1761-1772https://doi.org/10.1007/s00125-019-4939-5

Cherney DZ, Montanari A. Gender, clamped hyperglycemia and arterial stiffness in patients with uncomplicated type 1 diabetes mellitus. (1525-6006 (Electronic)). 2022

The effect of sex on endothelial function responses to clamped hyperglycemia in type 1 diabetes.

Hypertens Res. 37: 220-224https://doi.org/10.1038/hr.2013.136Russo G Pintaudi B Giorda C et al.

Age- and gender-related differences in LDL-cholesterol management in outpatients with type 2 diabetes mellitus.

Int J Endocrinol. 2015957105https://doi.org/10.1155/2015/957105Ferrara A Mangione CM Kim C et al.

Sex disparities in control and treatment of modifiable cardiovascular disease risk factors among patients with diabetes.

Diabetes Care. 31: 69https://doi.org/10.2337/dc07-1244Plows JF Stanley JL Baker PN Reynolds CM Vickers MH.

The pathophysiology of gestational diabetes mellitus.

Int J Mol Sci. 19: 3342https://doi.org/10.3390/ijms19113342McIntyre HD Catalano P Zhang C Desoye G Mathiesen ER Damm P.

Gestational diabetes mellitus.

Nat Rev Dis Primers. 5: 47https://doi.org/10.1038/s41572-019-0098-8Bomback AS Rekhtman Y Whaley-Connell AT et al.

Gestational diabetes mellitus alone in the absence of subsequent diabetes is associated with microalbuminuria.

Diabetes Care. 33: 2586https://doi.org/10.2337/dc10-1095Shah BR Feig DS Herer E et al.

Increased risk for microvascular complications among women with gestational diabetes in the third trimester.

Diabetes Res Clin Pract. 180109068https://doi.org/10.1016/j.diabres.2021.109068Beharier O Shoham-Vardi I Pariente G et al.

Gestational diabetes mellitus is a significant risk factor for long-term maternal renal disease.

J Clin Endocrinol Metab. 100: 1412-1416https://doi.org/10.1210/jc.2014-4474Landon MB Spong CY Thom E et al.

A multicenter, randomized trial of treatment for mild gestational diabetes.

N Engl J Med. 361: 1339-1348https://doi.org/10.1056/nejmoa0902430Khalil R Kim NR Jardi F et al .

Sex steroids and the kidney: role in renal calcium and phosphate handling.

Mol Cell Endocrinol. 465: 61-72https://doi.org/10.1016/j.mce.2017.11.011Yanes LL Sartori-Valinotti JC Reckelhoff JF.

Sex steroids and renal disease: lessons from animal studies.

Hypertension. 51: 976-981https://doi.org/10.1161/hypertensionaha.107.105767Irsik DL Romero-Aleshire MJ Chavez EM et al.

Renoprotective impact of estrogen receptor-alpha and its splice variants in female mice with type 1 diabetes.

Am J Physiol Renal Physiol. 315: F512-F520https://doi.org/10.1152/ajprenal.00231.2017

17beta-Estradiol attenuates diabetic kidney disease by regulating extracellular matrix and transforming growth factor-beta protein expression and signaling.

Am J Physiol Renal Physiol. 293: F1678-F1690https://doi.org/10.1152/ajprenal.00079.2007Catanuto P Doublier S Lupia E et al.

17 beta-estradiol and tamoxifen upregulate estrogen receptor beta expression and control podocyte signaling pathways in a model of type 2 diabetes.

Kidney Int. 75: 1194-1201https://doi.org/10.1038/ki.2009.69Wells CC Riazi S Mankhey RW Bhatti F Ecelbarger C Maric C.

Diabetic nephropathy is associated with decreasedcirculating estradiol levels and imbalance in the expression of renal estrogen receptors.

Gend Med. 2: 227-237https://doi.org/10.1016/s1550-8579(05)80052-xSzekacs B Vajo Z Varbiro S et al.

Postmenopausal hormone replacement improves proteinuria and impaired creatinine clearance in type 2 diabetes mellitus and hypertension.

BJOG. 107: 1017-1021https://doi.org/10.1111/j.1471-0528.2000.tb10406.xAgarwal M Selvan V Freedman BI Liu Y Wagenknecht LE.

The relationship between albuminuria and hormone therapy in postmenopausal women.

Am J Kidney Dis. 45: 1019-1025https://doi.org/10.1053/j.ajkd.2005.02.025Hadjadj S Gourdy P Zaoui P et al.

Effect of raloxifene – a selective oestrogen receptor modulator – on kidney function in post-menopausal women with type 2 diabetes: results from a randomized, placebo-controlled pilot trial.

Diabet Med. 24: 906-910https://doi.org/10.1111/j.1464-5491.2007.02165.xQuinkler M Meyer B Bumke-Vogt C et al.

Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor.

Eur J Endocrinol. 146: 789-799https://doi.org/10.1530/eje.0.1460789Maric C Forsblom C Thorn L Waden J Groop PH

FinnDiane Study Group. Association between testosterone, estradiol and sex hormone binding globulin levels in men with type 1 diabetes with nephropathy.

Steroids. 75: 772-778https://doi.org/10.1016/j.steroids.2010.01.011Nishad R Mukhi D Tahaseen SV Mungamuri SK Pasupulati AK.

Growth hormone induces Notch1 signaling in podocytes and contributes to proteinuria in diabetic nephropathy.

J Biol Chem. 294: 16109-16122https://doi.org/10.1074/jbc.RA119.008966Birzniece V McLean M Reddy N Ho KKY.

Disparate effect of aromatization on the central regulation of GH secretion by estrogens in men and postmenopausal women.

J Clin Endocrinol Metab. 104: 2978-2984https://doi.org/10.1210/jc.2019-00265Salonia A Lanzi R Scavini M et al.

Sexual function and endocrine profile in fertile women with type 1 diabetes.

Diabetes Care. 29: 312-316https://doi.org/10.2337/diacare.29.02.06.dc05-1067

Sex and gender differences in cardiovascular-renal physiology and pathophysiology.

Steroids. 75: 745-746https://doi.org/10.1016/j.steroids.2010.05.020

Gender differences in insulin resistance, body composition, and energy balance.

Gend Med. 6: 60-75https://doi.org/10.1016/j.genm.2009.02.002Millstein RJ Pyle LL Bergman BC et al.

Sex-specific differences in insulin resistance in type 1 diabetes: the CACTI cohort.

J Diabetes Complications. 32: 418-423https://doi.org/10.1016/j.jdiacomp.2018.01.002Yeung EH Zhang C Mumford SL et al.

Longitudinal study of insulin resistance and sex hormones over the menstrual cycle: the BioCycle Study.

J Clin Endocrinol Metab. 95: 5435-5442https://doi.org/10.1210/jc.2010-0702

Sex hormones, insulin sensitivity, and diabetes mellitus.

ILAR J. 45: 160-169https://doi.org/10.1093/ilar.45.2.160Hesp AC Schaub JA Prasad PV et al.

The role of renal hypoxia in the pathogenesis of diabetic kidney disease: a promising target for newer renoprotective agents including SGLT2 inhibitors?.

Kidney Int. 98: 579-589https://doi.org/10.1016/j.kint.2020.02.041Bjornstad P Maahs DM Cherney DZ et al.

Insulin sensitivity is an important determinant of renal health in adolescents with type 2 diabetes.

Diabetes Care. 37: 3033-3039https://doi.org/10.2337/dc14-1331White MC Fleeman R Arnold AC.

Sex differences in the metabolic effects of the renin-angiotensin system.

Biol Sex Differ. 10: 31https://doi.org/10.1186/s13293-019-0247-5Miller JA Cherney DZ Duncan JA et al.

Gender differences in the renal response to renin-angiotensin system blockade.

J Am Soc Nephrol. 17: 2554-2560https://doi.org/10.1681/asn.2005101095Komukai K Mochizuki S Yoshimura M.

Gender and the renin-angiotensin-aldosterone system.

Fundam Clin Pharmacol. 24: 687-698https://doi.org/10.1111/j.1472-8206.2010.00854.xAgrawal M Spencer HJ Faas FH.

Method of LDL cholesterol measurement influences classification of LDL cholesterol treatment goals.

J Investig Med. 58: 945-949https://doi.org/10.2310/JIM.0b013e3181fb7ca7Liu H Sridhar VS Boulet J et al.

Cardiorenal protection with SGLT2 inhibitors in patients with diabetes mellitus: from biomarkers to clinical outcomes in heart failure and diabetic kidney disease.

Metabolism. 126154918https://doi.org/10.1016/j.metabol.2021.154918Kafami M Hosseini M Niazmand S Farrokhi E Hajzadeh MA Nazemi S.

The effects of estradiol and testosterone on renal tissues oxidative after central injection of angiotensin II in female doca - salt treated rats.

Horm Mol Biol Clin Investig. 37https://doi.org/10.1515/hmbci-2018-0044Tonneijck L Muskiet MH Smits MM et al.

Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment.

J Am Soc Nephrol. 28: 1023-1039https://doi.org/10.1681/ASN.2016060666Bjornstad P Nehus E El Ghormli L et al.

Insulin sensitivity and diabetic kidney disease in children and adolescents with type 2 diabetes: an observational analysis of data from the TODAY clinical trial.

Am J Kidney Dis. 71: 65-74https://doi.org/10.1053/j.ajkd.2017.07.015Cherney DZ Sochett EB Miller JA.

Gender differences in renal responses to hyperglycemia and angiotensin-converting enzyme inhibition in diabetes.

Kidney Int. 68: 1722-1728https://doi.org/10.1111/j.1523-1755.2005.00588.xSkrtic M Lytvyn Y Bjornstad P et al.

Influence of sex on hyperfiltration in patients with uncomplicated type 1 diabetes.

Am J Physiol Renal Physiol. 312: F599-F606https://doi.org/10.1152/ajprenal.00357.2016Slyvka Y Malgor R Inman SR Ding J Heh V Nowak FV.

Antioxidant diet and sex interact to regulate NOS isoform expression and glomerular mesangium proliferation in Zucker diabetic rat kidney.

Acta Histochem. 118: 183-193https://doi.org/10.1016/j.acthis.2015.12.011Cherney DZ Scholey JW Sochett EB.

Sex differences in renal responses to hyperglycemia, L-arginine, and L-NMMA in humans with uncomplicated type 1 diabetes.

Diabetes Care. 36: 1290-1296https://doi.org/10.2337/dc12-1305Nair AV Yanhong W Paunescu TG Bouley R Brown D.

Sex-dependent differences in water homeostasis in wild-type and V-ATPase B1-subunit deficient mice.

PLoS One. 14e0219940https://doi.org/10.1371/journal.pone.0219940Veiras LC Girardi ACC Curry J et al.

Sexual dimorphic pattern of renal transporters and electrolyte homeostasis.

J Am Soc Nephrol. 28: 3504-3517https://doi.org/10.1681/ASN.2017030295Sabolic I Vrhovac I Eror DB et al.

Expression of Na+-D-glucose cotransporter SGLT2 in rodents is kidney-specific and exhibits sex and species differences.

Am J Physiol Cell Physiol. 302: C1174-C1188https://doi.org/10.1152/ajpcell.00450.2011

Pharmacology of angiotensin II receptors in the kidney.

Kidney Int. 46: 1486-1491https://doi.org/10.1038/ki.1994.426

Sex-specific contributions of endothelin to hypertension.

Curr Hypertens Rep. 20: 58https://doi.org/10.1007/s11906-018-0856-0Matsumoto T Kakami M Kobayashi T Kamata K.

Gender differences in vascular reactivity to endothelin-1 (1-31) in mesenteric arteries from diabetic mice.

Peptides. 29: 1338-1346https://doi.org/10.1016/j.peptides.2008.04.001

Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction.

Int J Mol Sci. 18: 1321https://doi.org/10.3390/ijms18061321Looker HC Krakoff J Funahashi T et al.

Adiponectin concentrations are influenced by renal function and diabetes duration in Pima Indians with type 2 diabetes.

J Clin Endocrinol Metab. 89: 4010-4017https://doi.org/10.1210/jc.2003-031916Lindsay RS Funahashi T Hanson RL et al.

Adiponectin and development of type 2 diabetes in the Pima Indian population.

Lancet. 360: 57-58https://doi.org/10.1016/s0140-6736(02)09335-2Laughlin GA Barrett-Connor E May S

Sex-specific determinants of serum adiponectin in older adults: the role of endogenous sex hormones.

Int J Obes (Lond). 31: 457-465https://doi.org/10.1038/sj.ijo.0803427

Mechanisms of adiponectin action: implication of adiponectin receptor agonism in diabetic kidney disease.

Int J Mol Sci. 20: 1782https://doi.org/10.3390/ijms20071782O'Donoghue ML Kato ET Mosenzon O et al.

The efficacy and safety of dapagliflozin in women and men with type 2 diabetes mellitus.

Diabetologia. 64: 1226-1234https://doi.org/10.1007/s00125-021-05399-2Rådholm K Zhou Z Clemens K Neal B Woodward M.

Effects of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes in women versus men.

Diabetes Obes Metab. 22: 263-266https://doi.org/10.1111/dom.13876Segerer H, Wurm M Grimsmann JM et al.

Diabetic ketoacidosis at manifestation of type 1 diabetes in childhood and adolescence—incidence and risk factors.

Dtsch Arztebl Int. 118: 367-372https://doi.org/10.3238/arztebl.m2021.0133Hampp C Swain RS Horgan C et al.

Use of sodium–glucose cotransporter 2 inhibitors in patients with type 1 diabetes and rates of diabetic ketoacidosis.

Diabetes Care. 43: 90https://doi.org/10.2337/dc19-1481Lega IC Bronskill SE Campitelli MA et al.

Sodium glucose cotransporter 2 inhibitors and risk of genital mycotic and urinary tract infection: a population-based study of older women and men with diabetes.

Diabetes Obes Metab. 21: 2394-2404https://doi.org/10.1111/dom.13820Bihan H Ng WL Magliano DJ Shaw JE.

Predictors of efficacy of GLP-1 agonists and DPP-4 inhibitors: a systematic review.

Diabetes Res Clin Pract. 121: 27-34https://doi.org/10.1016/j.diabres.2016.08.011

Gender difference in cardiovascular outcomes with SGLT-2 inhibitors and GLP-1 receptor agonist in type 2 diabetes: a systematic review and meta-analysis of cardio-vascular outcome trials.

Diabetes Metab Syndr. 14: 181-187https://doi.org/10.1016/j.dsx.2020.02.012Lachaux M Barrera-Chimal J Nicol L et al.

Short- and long-term administration of the non-steroidal mineralocorticoid receptor antagonist finerenone opposes metabolic syndrome-related cardio-renal dysfunction.

Diabetes Obes Metab. 20: 2399-2407https://doi.org/10.1111/dom.13393Pitt B Filippatos G Agarwal R et al.

Cardiovascular events with finerenone in kidney disease and type 2 diabetes.

N Engl J Med. 385: 2252-2263https://doi.org/10.1056/nejmoa2110956Bakris GL Agarwal R Anker SD et al.

Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes.

N Engl J Med. 383: 2219-2229https://doi.org/10.1056/NEJMoa2025845Heerspink HJL Parving H-H Andress DL et al.

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial.

Lancet. 393: 1937-1947https://doi.org/10.1016/s0140-6736(19)30772-xde Vries ST Denig P Ekhart C Mol PGM van Puijenbroek EP.

Sex differences in adverse drug reactions of metformin: a longitudinal survey study.

Drug Safety. 43: 489-495https://doi.org/10.1007/s40264-020-00913-8

Gender and the prevalence and progression of renal disease.

Adv Chronic Kidney Dis. 20: 390-395

White MC, Fleeman R, Arnold AA-O. Sex differences in the metabolic effects of the renin-angiotensin system. Biol Sex Differ. 2019;10(1):31.

Szekacs B Vajo Z, Varbiro S et al.

Postmenopausal hormone replacement improves proteinuria and impaired creatinine clearance in type 2 diabetes mellitus and hypertension.

BJOG. 107: 1017-1021Agarwal M Selvan V Freedman BI et al

The relationship between albuminuria and hormone therapy in postmenopausal women.

Am J Kidney Dis. 45: 1019-1025

Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors: a state-of-the-art review.

JACC Basic Transl Sci. 5: 632-644https://doi.org/10.1016/j.jacbts.2020.02.004

The tubular hypothesis of nephron filtration and diabetic kidney disease.

Nat Rev Nephrol. 16: 317-336https://doi.org/10.1038/s41581-020-0256-yNeal B Perkovic V Mahaffey KW et al.

Canagliflozin and cardiovascular and renal events in type 2 diabetes.

N Engl J Med. 377: 644-657https://doi.org/10.1056/nejmoa1611925Perkovic V Jardine MJ Neal B et al.

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy.

N Engl J Med. 380: 2295-2306https://doi.org/10.1056/nejmoa1811744Zinman B Wanner C Lachin JM et al.

Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.

N Engl J Med. 373: 2117-2128https://doi.org/10.1056/nejmoa1504720Wiviott SD Raz I Bonaca MP et al.

Dapagliflozin and cardiovascular outcomes in type 2 diabetes.

N Engl J Med. 380: 347-357https://doi.org/10.1056/nejmoa1812389Hammersen J Tittel SR Warncke K et al.

Previous diabetic ketoacidosis as a risk factor for recurrence in a large prospective contemporary pediatric cohort: results from the DPV initiative.

Pediatr Diabetes. 22: 455-462Ehrmann D Kulzer B Roos T Haak T Al-Khatib M Hermanns N.

Risk factors and prevention strategies for diabetic ketoacidosis in people with established type 1 diabetes.

Lancet Diabetes Endocrinol. 8: 436-446https://doi.org/10.1016/S2213-8587(20)30042-5Eberly LA Yang L Eneanya ND et al.

Association of race/ethnicity, gender, and socioeconomic status with sodium-glucose cotransporter 2 inhibitor use among patients with diabetes in the US.

JAMA Network Open. 4: e216139https://doi.org/10.1001/jamanetworkopen.2021.6139Quinn A Campbell D Au F et al.

Describing the uptake and patterns of SGLT2 inhibitor use among adults with type 2 diabetes in Alberta, Canada.

Can J Diabetes. 45https://doi.org/10.1016/j.jcjd.2021.09.049Agarwal R Joseph A Anker S et al.

Hyperkalemia risk with finerenone: results from the FIDELIO-DKD trial.

J Am Soc Nephrol. 33: 225-223https://doi.org/10.1681/ASN.2021070942Mauvais-Jarvis F Berthold HK Campesi I et al.

Sex- and gender-based pharmacological response to drugs.

Pharmacol Rev. 73: 730https://doi.org/10.1124/pharmrev.120.000206Maric-Bilkan C Manigrasso MB.

Sex differences in hypertension: contribution of the renin–angiotensin system.

Gender Med. 9: 287-291https://doi.org/10.1016/j.genm.2012.06.005

Sex and the renin angiotensin system: implications for gender differences in the progression of kidney disease.

Adv Ren Replace Ther. 10: 15-23https://doi.org/10.1053/jarr.2003.50006