Sex Differences in Biopsy-Confirmed Diabetic Kidney Disease

Wang, Yiting; Zhang, Jue; Zhang, Junlin; Wu, Yucheng; Zhang, Rui; Ren, Honghong; Cooper, Mark E.; Liu, Fang

doi:10.3389/fendo.2021.670674

Cited by 5 publications

(2 citation statements)

References 39 publications

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“…Sex may play a role in the risk of progression to these dreaded complications. For example, women with diabetes have higher mortality rates and higher prevalence of diabetic kidney disease [ 37 , 38 , 39 , 40 ]. In contrast, a recent review by Giandalia et al noted that the risk of developing and worsening diabetic kidney disease is higher in men with DM, while women are at higher risk of glomerular damage.…”

Section: Discussionmentioning

confidence: 99%

Increased Renal Medullary NOX-4 in Female but Not Male Mice during the Early Phase of Type 1 Diabetes: Potential Role of ROS in Upregulation of TGF-β1 and Fibronectin in Collecting Duct Cells

et al. 2023

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Chronic diabetes mellitus (DM) can lead to kidney damage associated with increased reactive oxygen species (ROS), proteinuria, and tubular damage. Altered protein expression levels of transforming growth factor-beta 1 (TGF-β1), fibronectin, and renal NADPH oxidase (NOX-4) are associated with the profibrotic phenotype in renal tubular cells. NOX-4 is one of the primary sources of ROS in the diabetic kidney and responsible for the induction of profibrotic factors in collecting duct (CD) cells. The renal medulla is predominantly composed of CDs; in DM, these CD cells are exposed to high glucose (HG) load. Currently there is no published literature describing the expression of these markers in the renal medulla in male and female mice during the early phase of DM, or the role of NOX-4-induced ROS. Our aim was to evaluate changes in transcripts and protein abundances of TGF-β1, fibronectin, and NOX-4 along with ROS levels in renal medullary tissues from male and female mice during a short period of streptozotocin (STZ)-induced type 1 DM and the effect of HG in cultured CD cells. CF-1 mice were injected with or without a single dose of STZ (200 mg/kg) and euthanized at day 6. STZ females showed higher expression of fibronectin and TGF-β1 when compared to control mice of either gender. Interestingly, STZ female mice showed a >30-fold increase on mRNA levels and a 3-fold increase in protein levels of kidney medullary NOX-4. Both male and female STZ mice showed increased intrarenal ROS. In primary cultures of inner medullary CD cells exposed to HG over 48 h, the expression of TGF-β1, fibronectin, and NOX-4 were augmented. M-1 CD cells exposed to HG showed increased ROS, fibronectin, and TGF-β1; this effect was prevented by NOX-4 inhibition. Our data suggest that at as early as 6 days of STZ-induced DM, the expression of profibrotic markers TGF-β1 and fibronectin increases in renal medullary CD cells. Antioxidants mechanisms in male and female in renal medullary tissues seems to be differentially regulated by the actions of NOX-4.

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Section: Discussionmentioning

confidence: 99%

Increased Renal Medullary NOX-4 in Female but Not Male Mice during the Early Phase of Type 1 Diabetes: Potential Role of ROS in Upregulation of TGF-β1 and Fibronectin in Collecting Duct Cells

et al. 2023

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“…The highest incidence rate of ESRD was observed in male SLE–DM patients, but the multivariable‐adjusted HRs were nearly equivalent in women and men. Although male sex in some studies has been associated with poor renal outcome in SLE (33,34), this is not a general finding (35) and in diabetic nephropathy, the risk of ESRD does not appear to be sex dependent (36).…”

Section: Discussionmentioning

confidence: 99%

Risk of End‐Stage Renal Disease in Patients With Systemic Lupus Erythematosus and Diabetes Mellitus: A Danish Nationwide Cohort Study

Hansen

Falasinnu

Faurschou

et al. 2023

Arthritis Care & Research

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ObjectiveThe risk of end‐stage renal disease (ESRD) is increased in patients with systemic lupus erythematosus (SLE). This study was undertaken to determine whether diabetes mellitus (DM) increases ESRD risk in a large inception cohort of SLE patients.MethodsBy means of the Danish National Patient Registry, we identified 3,178 adult patients diagnosed as having SLE between January 1, 1996, and July 31, 2018. DM was defined as the date of first hospital contact for DM or date of a first prescription of an antidiabetic drug. ESRD was defined as first registration of dialysis, renal transplant, or terminal renal insufficiency in the Danish National Patient Registry. ESRD incidence was compared between SLE patients with DM (SLE–DM) and those without DM (SLE–non‐DM). Hazard ratios (HRs), adjusted for sex, age, educational level, and occupational status at baseline were calculated for sex, age, educational level, and hypertension (at baseline or during follow‐up) strata. The overall hazard ratio (HR) was also adjusted for hypertension.ResultsThe SLE–DM group included 290 patients, of whom 77% were female, compared with 85% of the 2,859 patients in the SLE–non‐DM group. SLE–DM patients had a 3 times higher risk of ESRD compared with SLE–non‐DM patients (multivariable‐adjusted HR 3.3 [95% confidence interval 1.8–6.1]). In stratified multivariable‐adjusted analyses, DM increased the rate of ESRD in women and men, patients ≥50 years old at baseline, those with low educational level at baseline, and those with concomitant hypertension.ConclusionOur findings indicate that SLE patients with DM have a markedly higher risk of developing ESRD compared with SLE patients without DM.

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Sex Differences in Kidney Health and Disease

Harvey,

Alvarez de la Rosa

2024

Nephron

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Background: Sex differences exist in kidney physiology and disease which are underpinned by the biological actions of the sex hormones estrogen, progesterone and testosterone. In this review, we present an up-to-date discussion of the hormonal and molecular signalling pathways implicated in sex differences in kidney health and disease. Summary: Estrogen and progesterone have protective effects on renal blood flow, glomerular filtration rate and nephron ion and water reabsorptive processes, whereas testosterone tends to compromise these functions. The biological effects of estrogen appear to be the most important in reinforcing kidney function and protecting against kidney diseases in females. The actions of estrogen are myriad but all tend to bolster kidney physiology to maintain a steady-state and adaptable extracellular fluid volume (ECFV) and blood pressure. Estrogen safeguards ECFV homeostasis by stimulating renal epithelial sodium channel (ENaC) and water channel (AQP2) expression and transport function. Renal maintenance of ECFV within narrow physiological limits is a first-line of defense against hypertension and lowers the risk of cardiovascular disease in women. The estrogenic and XX chromosome basis for a female advantage are evident in a wide range of kidney diseases including acute kidney injury, chronic kidney disease, end-stage kidney disease, diabetic kidney disease, and polycystic kidney disease. The molecular mechanisms involve estrogen regulation of nephron ion and water transport, genetic immunogenic responses, activation of the protective arm of the renin angiotensin-aldosterone system and XX chromosome reinforcement of immune responses. Kidney disease can also predispose patients to cancer and women are protected in renal cancer with lower incidence, morbidity, and mortality than age-matched men with the disease. Key Messages: This review underscores the importance of incorporating sex-specific considerations into clinical practice and basic research to bridge the gap in understanding and addressing biological sex disparities in kidney disease and renal cancer.

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Sex Differences in Biopsy-Confirmed Diabetic Kidney Disease

Cited by 5 publications

References 39 publications

Increased Renal Medullary NOX-4 in Female but Not Male Mice during the Early Phase of Type 1 Diabetes: Potential Role of ROS in Upregulation of TGF-β1 and Fibronectin in Collecting Duct Cells

Increased Renal Medullary NOX-4 in Female but Not Male Mice during the Early Phase of Type 1 Diabetes: Potential Role of ROS in Upregulation of TGF-β1 and Fibronectin in Collecting Duct Cells

Risk of End‐Stage Renal Disease in Patients With Systemic Lupus Erythematosus and Diabetes Mellitus: A Danish Nationwide Cohort Study

Sex Differences in Kidney Health and Disease

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