Emergence of T cell immunosenescence in diabetic chronic kidney disease

Abstract Background Type 2 diabetes is an important challenge given the worldwide epidemic and is the most important cause of end-stage renal disease (ESRD) in developed countries. It is known that patients with ESRD and advanced renal failure suffer from immunosenescence and premature T cell aging, but whether such changes develop in patients with less severe chronic kidney disease (CKD) is unclear. Method 523 adult patients with type 2 diabetes were recruited for this study. Demographic data and clinical information were obtained from medical chart review. Immunosenescence, or aging of the immune system was assessed by staining freshly-obtained peripheral blood with immunophenotyping panels and analyzing cells using multicolor flow cytometry. Result Consistent with previously observed in the general population, both T and monocyte immunosenescence in diabetic patients positively correlate with age. When compared to diabetic patients with preserved renal function (estimated glomerular filtration rate > 60 ml/min), patients with impaired renal function exhibit a significant decrease of total CD3+ and CD4+ T cells, but not CD8+ T cell and monocyte numbers. Immunosenescence was observed in patients with CKD stage 3 and in patients with more severe renal failure, especially of CD8+ T cells. However, immunosenescence was not associated with level of proteinuria level or glucose control. In age, sex and glucose level-adjusted regression models, stage 3 CKD patients exhibited significantly elevated percentages of CD28−, CD127−, and CD57+ cells among CD8+ T cells when compared to patients with preserved renal function. In contrast, no change was detected in monocyte subpopulations as renal function declined. In addition, higher body mass index (BMI) is associated with enhanced immunosenescence irrespective of CKD status. Conclusion The extent of immunosenescence is not significantly associated with proteinuria or glucose control in type 2 diabetic patients. T cells, especially the CD8+ subsets, exhibit aggravated characteristics of immunosenescence during renal function decline as early as stage 3 CKD. In addition, inflammation increases since stage 3 CKD and higher BMI drives the accumulation of CD8+CD57+ T cells. Our study indicates that therapeutic approaches such as weight loss may be used to prevent the emergence of immunosenescence in diabetes before stage 3 CKD.

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The Effect of Renal Dysfunction on Circulating Sclerostin Level in Patients with Type 2 Diabetes

International Journal of Endocrinology ◽

10.1155/2014/715908 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 4

Author(s):

Se Hwa Kim ◽

Soo Young Yoon ◽

Sung-Kil Lim ◽

Yumie Rhee

Keyword(s):

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

Renal Dysfunction ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Cross Sectional ◽

Sclerostin Level

Objective. Sclerostin is a Wnt inhibitor produced specifically by osteocytes. However, it is not currently clear whether renal dysfunction has an effect on circulating sclerostin level in patients with type 2 diabetes. The aim of the study was to evaluate this relationship. Design and Patients. We conducted a cross-sectional observational study of 302 type 2 diabetic patients with or without chronic kidney disease. Serum sclerostin level was analyzed by ELISA, and renal function was assessed by estimated glomerular filtration rate (eGFR) using chronic kidney disease epidemiology collaboration (CKD-EPI) equation. Results. There was a strong correlation between sclerostin level with renal function presented as serum creatinine (r=0.745, P<0.001) and eGFR (r=-0.590, P<0.001). Serum sclerostin level was significantly higher in patients with CKD-G3 stage than those with CKD-G1/2 stages after adjusting for age, sex, and BMI (P=0.011). Patients with CKD-G4/5 stages had dramatically increased level of circulating sclerostin. Multiple regression analyses found that age, sex, and eGFR were independent determining factors for circulating sclerostin level. Conclusion. Our data showed that serum sclerostin levels start to increase in diabetic patients with CKD-G3 stage. Further studies are needed to establish the potential role of elevated sclerostin in diabetic patients with CKD.

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Guidelines adherence in the prevention and management of chronic kidney disease in patients with diabetes mellitus on the background of recent European recommendations – a registry-based analysis

BMC Nephrology ◽

10.1186/s12882-021-02394-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Peter Bramlage ◽

Stefanie Lanzinger ◽

Sascha R. Tittel ◽

Eva Hess ◽

Simon Fahrner ◽

...

Keyword(s):

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Clinical Practice ◽

Kidney Disease ◽

Analysis Data ◽

Disease Diagnosis ◽

Diabetic Patients ◽

European Society Of Cardiology

Abstract Background Recent European Society of Cardiology (ESC)/European Association for the Study of Diabetes (EASD) guidelines provide recommendations for detecting and treating chronic kidney disease (CKD) in diabetic patients. We compared clinical practice with guidelines to determine areas for improvement. Methods German database analysis of 675,628 patients with type 1 or type 2 diabetes, with 134,395 included in this analysis. Data were compared with ESC/EASD recommendations. Results This analysis included 17,649 and 116,747 patients with type 1 and type 2 diabetes, respectively. The analysis showed that 44.1 and 49.1 % patients with type 1 and type 2 diabetes, respectively, were annually screened for CKD. Despite anti-diabetic treatment, only 27.2 % patients with type 1 and 43.5 % patients with type 2 achieved a target HbA1c of < 7.0 %. Use of sodium-glucose transport protein 2 inhibitors (1.5 % type 1/8.7 % type 2 diabetes) and glucagon-like peptide-1 receptor agonists (0.6 % type 1/5.2 % type 2 diabetes) was limited. Hypertension was controlled according to guidelines in 41.1 and 67.7 % patients aged 18–65 years with type 1 and 2 diabetes, respectively, (62.4 vs. 68.4 % in patients > 65 years). Renin angiotensin aldosterone inhibitors were used in 24.0 and 40.9 % patients with type 1 diabetes (micro- vs. macroalbuminuria) and 39.9 and 47.7 %, respectively, in type 2 diabetes. Conclusions Data indicate there is room for improvement in caring for diabetic patients with respect to renal disease diagnosis and treatment. While specific and potentially clinically justified reasons for non-compliance exist, the data may serve well for a critical appraisal of clinical practice decisions.

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Impact of sodium–glucose cotransporter 2 inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease with normoalbuminuria

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-020-0516-9 ◽

2020 ◽

Vol 12 (1) ◽

Cited By ~ 4

Author(s):

Akinobu Nakamura ◽

Hideaki Miyoshi ◽

Hiraku Kameda ◽

Kumiko Yamashita ◽

Yoshio Kurihara

Keyword(s):

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

Sglt2 Inhibitor ◽

Sglt2 Inhibitors ◽

Creatinine Ratio ◽

Sodium Glucose Cotransporter ◽

Clinical Records

Abstract Background We compared the effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease (CKD) classified by degree of albuminuria. Methods A retrospective review of the clinical records of Japanese participants with type 2 diabetes (age > 20 years; SGLT2 inhibitor treatment > 2 years; estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) was conducted. Based on the urinary albumin-to-creatinine ratio (UACR) or urinary protein-to-creatinine ratio (UPCR) at the start of SGLT2 inhibitor administration, participants were categorized into three groups: normoalbuminuria (A1; UACR < 30 mg/g Cr or UPCR < 0.15 g/g Cr), microalbuminuria (A2; UACR 30 to < 300 mg/g Cr or UPCR 0.15 to < 0.50 g/g Cr), and macroalbuminuria (A3; UACR ≥ 300 mg/g Cr or UPCR ≥ 0.50 g/g Cr). The study outcome was a comparison of the rates of change in renal function evaluated by eGFR at 2 years after starting SGLT2 inhibitor among the three groups. Results A total of 87 participants (40 females, 47 males) were categorized into three groups: A1 (n = 46), A2 (n = 25), and A3 (n = 16). eGFR was similarly decreased at 2 years before starting SGLT2 inhibitor in all three groups. However, the decline in eGFR was ameliorated at 2 years after starting SGLT2 inhibitor, and eGFR was rather increased in the A1 and A2 groups. Interestingly, the rate of change in eGFR at 2 years after starting SGLT2 inhibitor in the A1 group was significantly higher than that in the A3 group. Conclusions These results demonstrate that more favorable effects of SGLT2 inhibitors on renal function were observed in participants with type 2 diabetes and CKD with normoalbuminuria compared with those with macroalbuminuria. Trial registration UMIN-CTR: UMIN000035263. Registered 15 December 2018

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MO235EFFECT OF OMEGA-3 POLYUNSATURATED FATTY ACID SUPPLEMENTATION ON GLYSEMIC CONTROL AND RENAL FUNCTION IN TYPE 2 DIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab092.00113 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Mehmet Usta ◽

Alpaslan Ersoy ◽

Canan Ersoy ◽

Yavuz Ayar ◽

Gultekin Goksel ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

Diabetic Patients ◽

Omega 3 ◽

Short Term ◽

Type 2 Diabetic Patients ◽

Pufa Supplementation ◽

Type 2 Diabetic

Abstract Background and Aims The aim of this study was to evaluate the short-term effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) supplementation on glycemic control and renal function in type 2 diabetic patients with chronic kidney disease. Method Twenty-five diabetic patients received medication containing 2 g/day n-3 PUFA orally in addition to standard treatments. Their estimated glomerular filtration rates (eGFR) were <80 mL/min/1.73 m2. Biochemical values were evaluated before and 3 months after treatment. Results After three months of supplementation, the changes in serum creatinine, uric acid, eGFR and urinary albumin excretion levels did not reach statistical significance. There was no difference between serum glucose, HbA1C and lipid profile values before and after the n-3 PUFA supplementation in patients. Only serum albumin significantly increased from 4.10±0.26 to 4.28±0.31 g/dL (p=0.016), and systolic blood pressure decreased from 121.4±14.5 to 116.6±14.9 mmHg (p=0.001). Conclusion Short-term n-3 PUFA supplementation did not affect renal function and glycemic control in patients with type 2 diabetes with chronic kidney disease.

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