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

Cobo, Gabriela; Hecking, Manfred; Port, Friedrich K.; Exner, Isabella; Lindholm, Bengt; Stenvinkel, Peter; Carrero, Juan Jesús

doi:10.1042/cs20160047

Cited by 194 publications

(177 citation statements)

References 214 publications

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“…The effect of gender on CKD progression remains a topic of debate; the majority of evidence points toward better outcomes in female patients [20,21]. This has been further confirmed in a recent meta-analysis, where male sex and substantial proteinuria were found to be significant perpetuating factors for the progression from latestage CKD to ESRD [22].…”

Section: Discussionmentioning

confidence: 53%

Clinical Management of Chronic Kidney Disease Patients in Italy: Results from the IRIDE Study

Cozzolino

Bolasco

Ronco

et al. 2018

Nephron

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Background: Lack of adequate management of chronic kidney disease (CKD) often results in delayed diagnosis and inadequate treatment. This study assessed the clinical management and outcome of stages 1–5 CKD patients. Methods: Patients were prospectively followed for 3 years in 25 nephrology centers across Italy. Clinical characteristics were measured at baseline and every 6 months. Outcome measures included CKD staging, presence of comorbidities, treatment, mineral bone disorder (MBD) parameters, and patient outcomes. Results: Of 884 enrolled patients (59.7% males, aged 66.2 ± 14.6 years), 587 (66.4%) completed the study. The majority of patients were referred by a general practitioner (44.7%) and had stage 3 or 4 CKD (40.9 and 23.8% respectively). Data reveal that 91.3% of patients had at least 1 concomitant disease, most frequently hypertension (80.1%) and dyslipidemia (42.5%); 94.6% of patients were receiving cardiovascular medication and 52.6% were receiving lipid-lowering medication. Approximately 40% of patients had proteinuria and intact parathyroid hormone levels outside the normal range. As expected, stages 4 and 5 CKD patients had a higher prevalence of proteinuria (68 and 74%), MBD (59 and 88%) and anemia (28 and 73%), as well as a higher risk of hospitalization (34.3 and 51.9%) and need for dialysis (69.5 and 70%). The overall probability of survival over 36 months was 90.6%. Conclusions: This is the first Italian prospective study performed with a large cohort of CKD patients over a 3-year period. Considering the multifactorial burden of diseases associated with CKD patients, the need for greater attention to CKD and related disorders is paramount.

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Section: Discussionmentioning

confidence: 53%

Clinical Management of Chronic Kidney Disease Patients in Italy: Results from the IRIDE Study

Cozzolino

Bolasco

Ronco

et al. 2018

Nephron

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“…Recent studies have demonstrated sex differences in renal damage among healthy and diabetic individuals [16]. In non-diabetic individuals with chronic kidney disease, male sex has been identified as a risk factor for rapid decline in renal function as opposed to pre-menopausal women [17]. In diabetic individuals conflicting reports exist in different populations; a recent study among Japanese subjects with type 2 diabetes identified a higher risk in women [18], whereas a report regarding European individuals indicated an increased risk for renal decline in men [19].…”

Section: Introductionmentioning

confidence: 99%

Sex difference in the risk for exercise-induced albuminuria correlates with hemoglobin A1C and abnormal exercise ECG test findings

Brzezinski

Etz-Hadar

Grupper

et al. 2017

Cardiovasc Diabetol

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BackgroundAlbuminuria is an established marker for endothelial dysfunction and cardiovascular risk in diabetes and prediabetes. Exercise induced albuminuria (EiA) appears earlier and may be a more sensitive biomarker for renal endothelial damage. We sought to examine the association between EiA, parameters of the metabolic syndrome, A1C levels, exercise ECG test results and sex related differences in a large cohort of healthy, pre-diabetic and diabetic subjects.MethodsA total of 3029 participants from the Tel-Aviv Medical Center Inflammation Survey cohort (mean age 46 years, 73% men) were analyzed. Multiple physiologic and metabolic parameters including A1C were collected and albuminuria was measured in all subjects before and immediately after completing an exercise ECG test.ResultsExercise increased urinary albumin to creatinine ratio (ΔEiA) by 2.8 (0–13.6) mg/g for median (IQR) compared to rest albuminuria (p < 0.001). An increase in ΔEiA was observed with accumulating parameters of the metabolic syndrome. ΔEiA showed significant interaction with sex and A1C levels; i.e. women with A1C > 6.5% had an increased risk of higher ΔEiA (p < 0.001). Using a cutoff of ΔEiA > 13 mg/g (top quartile) we found that women with ΔEiA > 13 mg/g were at greater risk for abnormal exercise ECG findings, (OR = 2.7, p = 0.001).ConclusionExercise promotes excessive urinary albumin excretion in dysmetabolic patients. In women, a significant correlation exists between ΔEiA and A1C levels. A cutoff of ΔEiA > 13 mg/g in women may be used to identify populations at risk for abnormal exercise ECG test findings and perhaps increased cardiovascular risk. Future studies will be needed to further validate the usefulness of ΔEiA as a biomarker for cardiovascular risk in women with and without diabetes.

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“…Sex has an impact on the development and progression of vascular and renal disease [12–14]. A number of experimental studies in Apoe -deficient mice detected sex differences in the development and progression of vascular and renal disease [15].…”

Section: Introductionmentioning

confidence: 99%

Sex differences in the development of vascular and renal lesions in mice with a simultaneous deficiency of Apoe and the integrin chain Itga8

et al. 2017

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Background Apoe-deficient (Apoe −/−) mice develop progressive atherosclerotic lesions with age but no severe renal pathology in the absence of additional challenges. We recently described accelerated atherosclerosis as well as marked renal injury in Apoe −/− mice deficient in the mesenchymal integrin chain Itga8 (Itga8 −/−). Here, we used this Apoe −/−, Itga8 −/− mouse model to investigate the sex differences in the development of atherosclerosis and concomitant renal injury. We hypothesized that aging female mice are protected from vascular and renal damage in this mouse model.Methods Apoe −/− mice were backcrossed with Itga8 −/− mice. Mice were kept on a normal diet. At the age of 12 months, the aortae and kidneys of male and female Apoe −/− Itga8 +/+ mice or Apoe −/− Itga8 −/− mice were studied. En face preparations of the aorta were stained with Sudan IV (lipid deposition) or von Kossa (calcification). In kidney tissue, immunostaining for collagen IV, CD3, F4/80, and PCNA and real-time PCR analyses for Il6, Vegfa, Col1a1 (collagen I), and Ssp1 (secreted phosphoprotein 1, synonym osteopontin) as well as ER stress markers were performed.ResultsWhen compared to male mice, Apoe −/− Itga8 +/+ female mice had a lower body weight, equal serum cholesterol levels, and lower triglyceride levels. However, female mice had increased aortic lipid deposition and more aortic calcifications than males. Male Apoe −/− mice with the additional deficiency of Itga8 developed increased serum urea, glomerulosclerosis, renal immune cell infiltration, and reduced glomerular cell proliferation. In females of the same genotype, these renal changes were less pronounced and were accompanied by lower expression of interleukin-6 and collagen I, while osteopontin expression was higher and markers of ER stress were not different.ConclusionsIn this model of atherosclerosis, the female sex is a risk factor to develop more severe atherosclerotic lesions, even though serum fat levels are higher in males. In contrast, female mice are protected from renal damage, which is accompanied by attenuated inflammation and matrix deposition. Thus, sex affects vascular and renal injury in a differential manner.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-017-0141-y) contains supplementary material, which is available to authorized users.

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

Cited by 194 publications

References 214 publications

Clinical Management of Chronic Kidney Disease Patients in Italy: Results from the IRIDE Study

Clinical Management of Chronic Kidney Disease Patients in Italy: Results from the IRIDE Study

Sex difference in the risk for exercise-induced albuminuria correlates with hemoglobin A1C and abnormal exercise ECG test findings

Sex differences in the development of vascular and renal lesions in mice with a simultaneous deficiency of Apoe and the integrin chain Itga8

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