P0904EFFECT OF EMPAGLIFLOZIN ON SERUM MARKERS OF OSTEOCYTE AND OSTEOBLAST FUNCTION AND ALBUMINURIA IN DIABETIC AND NON-DIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Sodium-glucose co-transporter 2 (SGLT2) inhibitors are new class of oral antidiabetic drugs that show potent cardio- and nephroprotective actions. Despite having a favorable safety profile the treatment with SGLT2 inhibitors has been associated with several side-effects including increased risk of fractures. Although the pathomechanism of this complication has not been elucidated these drugs may inhibit tubular reabsorption of phosphate which may stimulate a secretion of fibroblast growth factor 23 (FGF23). The study was designed to assess the effect of SGLT2 inhibitor on markers of calcium-phosphate metabolism, bone turnover and early glomerular injury in diabetic and non-diabetic patients with stage 3 chronic kidney disease (CKD). Method 41 patients with chronic kidney disease including 23 without diabetes (13 M, 11F, age 52.9±0.7 years, estimated glomerular filtration rate (eGFR) 38.6±10.8 ml/min/1.73 m2) and 18 with type 2 diabetes (12 M, 6F, age 58.8±1.4 years, eGFR 38.8±7.7 ml/min/1.73 m2) were recruited. Main inclusion criteria were CKD stage 3 and urine albumin secretion >100 mg/g creatinine. All subjects received oral empagliflozin 10 mg once daily for 7 days. Serum calcium, phosphorus, parathormone (PTH), calcitriol, bone alkaline phosphatase (BAP), FGF23 and urine calcium, phosphate and albumin were measured at baseline and after 7 days of empagliflozin treatment. Results Plasma calcitriol, serum and urine calcium, phosphorus and BAP did not change significantly during the administration of empagliflozin. Urine phosphate/creatinine ratio was similar in both subgroups at baseline and did not change during empagliflozin administration. Plasma PTH was higher in non-diabetics than in diabetics both at baseline and after empagliflozin. The increase of PTH after empagliflozin tended to be higher in diabetic patients (p=0.07). There was only a trend towards an increase of serum FGF23 in both non-diabetic and diabetic subgroup (by 4.2±0.2 vs. 9.3±1.1 pg/mL, ns). BAP was significantly higher at baseline in diabetic patients but did not significantly change after empagliflozin in the subgroups. Albumin/creatinine ratio decrease after empagliflozin administration was significant only in non-diabetic patients (-62±17 vs. -2±8 mg/g in diabetic patients, p=0.03 for difference). Conclusion Our study showed no effect of short-time administration of empagliflozin on calcium-phosphate and bone metabolism markers in patients with both diabetic and non-diabetic CKD. Empagliflozin decreased albuminuria significantly only in non-diabetic CKD that may suggest a potentially greater nephroprotective effect of this SGLT2 inhibitor in non-diabetic than in diabetic nephropathy.

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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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Different Effects of Empagliflozin on Markers of Mineral-Bone Metabolism in Diabetic and Non-Diabetic Patients with Stage 3 Chronic Kidney Disease

Medicina ◽

10.3390/medicina57121352 ◽

2021 ◽

Vol 57 (12) ◽

pp. 1352

Author(s):

Anna Masajtis-Zagajewska ◽

Tomasz Hołub ◽

Katarzyna Pęczek ◽

Agnieszka Makówka ◽

Michał Nowicki

Keyword(s):

Chronic Kidney Disease ◽

Calcium Phosphate ◽

Kidney Disease ◽

Bone Metabolism ◽

Bone Fractures ◽

Sglt2 Inhibitor ◽

Diabetic Patients ◽

Mineral Density ◽

Increased Risk ◽

Fgf 23

Background and objectives: Treatment with sodium–glucose co-transporter 2 (SGLT2) inhibitors decrease tubular reabsorption of phosphate, which may explain the reduction of bone mineral density and an excess of bone fractures observed in some studies with this class of drugs. Since an increased risk of bone fractures may also be a result of diabetes itself, our study aimed to compare the effect of empagliflozin on the markers of mineral-bone metabolism between diabetic (DKD) and non-diabetic (ND-CKD) patients with stage 3 chronic kidney disease (CKD). Materials and Methods: Forty-two patients with stage 3 CKD and A2 albuminuria, including 18 with DKD and 24 ND-CKD, were investigated. All subjects received 10 mg empagliflozin for 7 days. Serum calcium, phosphate, parathormone (PTH), calcitriol, bone alkaline phosphatase (BAP), FGF-23 and urine calcium, phosphate, albumin and the renal tubular maximum reabsorption rate of phosphate to the glomerular filtration rate (TmP-GFR) were measured before and after empagliflozin administration. Differences in biomarkers response to empagliflozin between DKD and ND-CKD were the main measures of outcome. Results: There was a significant increase of PTH, FGF-23 and phosphate in DKD but not in ND-CKD whereas BAP and TmP/GFR did not change in either group. The reduction of albuminuria was only significant in ND-CKD. Conclusions: The effect of SGLT2 inhibitor on serum mineral and bone markers and on albuminuria in patients with CKD may be differently modified by the presence of diabetes mellitus.

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Pleiotropic Effects of Sodium-Glucose Cotransporter-2 Inhibitors: Renoprotective Mechanisms beyond Glycemic Control

International Journal of Molecular Sciences ◽

10.3390/ijms22094374 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4374

Author(s):

Tomoaki Takata ◽

Hajime Isomoto

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Glycemic Control ◽

Kidney Injury ◽

Sglt2 Inhibitors ◽

Pleiotropic Effects ◽

Future Research ◽

Diabetic Patients ◽

Sodium Glucose Cotransporter ◽

Stage Renal Disease

Diabetes mellitus is a major cause of chronic kidney disease and end-stage renal disease. However, the management of chronic kidney disease, particularly diabetes, requires vast improvements. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for the treatment of diabetes, have been shown to protect against kidney injury via glycemic control, as well as various other mechanisms, including blood pressure and hemodynamic regulation, protection from lipotoxicity, and uric acid control. As such, regulation of these mechanisms is recommended as an effective multidisciplinary approach for the treatment of diabetic patients with kidney disease. Thus, SGLT2 inhibitors are expected to become key drugs for treating diabetic kidney disease. This review summarizes the recent clinical evidence pertaining to SGLT2 inhibitors as well as the mechanisms underlying their renoprotective effects. Hence, the information contained herein will advance the current understanding regarding the pleiotropic effects of SGLT2 inhibitors, while promoting future research in the field.

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Study of metformin in diabetes mellitus with stage 3 and 4 chronic kidney disease

Journal of Diabetes and Endocrine Association of Nepal ◽

10.3126/jdean.v4i1.30073 ◽

2020 ◽

Vol 4 (1) ◽

pp. 21-28

Author(s):

D. Peeyush ◽

M. Lamsal ◽

R. Maskey ◽

S.K. Sharma

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Lactic Acidosis ◽

Blood Sugar ◽

Case Reports ◽

Glycosylated Hemoglobin ◽

Diabetic Patients ◽

Insulin Group ◽

Metformin Group ◽

Ckd Stage

Background: Chronic Kidney Disease is one of the major complications of Diabetic patients. Cardiovascular mortality increases in patient with diabetes and more so with diabetic CKD. Clinician treating diabetic CKD finds option limited as metformin is considered contraindicated when serum creatinine is greater than 1.5 mg/dl in males and greater than 1.4 mg/dl in females. The primary aim of the study is to evaluate the efficacy of metformin in terms of glycemic control in patient with diabetic stage 3 and 4 CKD. Methods: This is Randomised open labelled clinical trial done in the Department of Internal Medicine, B. P. Koirala Institute of Health Sciences, Dharan, Nepal. Primary end point were glycemic status at 6 months as defined by with fasting, post prandial blood sugar, glycosylated hemoglobin in comparison to baseline. Results: Altogether 73 diabetic patients with diabetic CKD stage 3 and 4 were included in the study. 41 patients were included in insulin group and 32 patients in metformin group. In metformin group, the fasting and past prandial blood sugar declined progressively compared to insulin group, where fasting and post prandial blood sugar declined more rapidly. Conclusions: Metformin is found to be efficacious in diabetic CKD as it had already proved to be effective in diabetes without CKD. In this study metformin was not associated with lactic acidosis and the level of lactate with metformin treatment was similar to that of treatment with insulin. The vast majority of case reports relating metformin to lactic acidosis report at least one other disease/illness that could result in lactic acidosis. Despite increasing disregard of contraindications to metformin by physicians, the incidence of lactic acidosis has not increased, as does the result of this study. So metformin may be safe even in patients with diabetic CKD stage 3 and 4.

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Effects of the SGLT2 inhibitor dapagliflozin on proteinuria in non-diabetic patients with chronic kidney disease (DIAMOND): a randomised, double-blind, crossover trial

The Lancet Diabetes & Endocrinology ◽

10.1016/s2213-8587(20)30162-5 ◽

2020 ◽

Vol 8 (7) ◽

pp. 582-593 ◽

Cited By ~ 17

Author(s):

David Z I Cherney ◽

Claire C J Dekkers ◽

Sean J Barbour ◽

Daniel Cattran ◽

Abdul Halim Abdul Gafor ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Crossover Trial ◽

Sglt2 Inhibitor ◽

Diabetic Patients ◽

Double Blind

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Effects of the SGLT2 Inhibitor Dapagliflozin on Proteinuria in Non-Diabetic Patients with Chronic Kidney Disease (DIAMOND): A Randomised Double Blind Cross-Over Trial

SSRN Electronic Journal ◽

10.2139/ssrn.3532536 ◽

2020 ◽

Author(s):

David Cherney ◽

Claire C. J. Dekkers ◽

Sean J. Barbour ◽

Daniel Cattran ◽

Abdul Halim Abdul Gafor ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Sglt2 Inhibitor ◽

Diabetic Patients ◽

Double Blind

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Investigation on Urinary and Serum Alpha Klotho in Dogs with Chronic Kidney Disease

10.21203/rs.3.rs-16759/v1 ◽

2020 ◽

Author(s):

Hong jae Yi ◽

Jong bok Lee ◽

Kyu pil Lee ◽

Kun ho Song ◽

Kyoung won Seo

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Fibroblast Growth Factor 23 ◽

Stepwise Multiple Regression ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Phosphorus Concentration ◽

Creatinine Ratio ◽

Ckd Stage ◽

Clinical Consequences

Abstract Background: As a co-receptor for fibroblast growth factor 23, klotho plays a pivotal role in phos-phate metabolism. The kidney is known to be not only the main source of soluble alpha-klotho but also functions as the principal regulator maintaining its concentration. Previous studies in human par-ticipants showed that the concentration of soluble alpha-klotho in serum and urine decreased in chronic kidney disease (CKD) patients. However, no previous study has assessed soluble alpha-klotho levels in dogs. This study aimed to measure serum and urinary alpha-klotho levels in CKD dogs and identify their associations with International Renal Interest Society (IRIS) CKD stages and other parameters known to be associated with CKD.Methods: Serum and urinary alpha klotho concentrations were measured by a commercially avail-able canine-specific sandwich enzyme-linked immunosorbent assay kit and compared between groups by a nonparametric Kruskal–Wallis test. Spearman’s correlation coefficient was used to eval-uate the relationships between variables. A stepwise multiple regression analysis was performed to estimate the effects of independent predictors on klotho concentrations.Results: The urine klotho-to-creatinine ratio (UrKl/Cr) was significantly lower in stage 3 dogs than the control group and was significantly lower in dogs with stage 3 and 4 CKD than in those with stage 1 and 2 disease. UrKl/Cr was negatively correlated with serum symmetric dimethylarginine (sSDMA), blood urea nitrogen (BUN), creatinine, and phosphorus concentration. Serum alpha-klotho concentration in dogs with stages 2 and 3 CKD were significantly lower than those in the control group. There was no significant correlation between serum alpha-klotho and BUN, creatinine, and phosphorus concentrations. No statistically significant differences were observed in UrKl/Cr and se-rum alpha-klotho concentration between groups based on sex, age, urine protein-to-creatinine ratio (UPC), or blood pressure.Conclusions: UrKl/Cr decreased in dogs with advanced CKD, and it was negatively correlated with sSDMA, BUN, creatinine, and phosphorus concentrations. Thus, klotho may play a role in the path-ogenesis of CKD and its clinical consequences, including CKD-mineral bone disorder, in dogs. Alt-hough serum klotho concentration was negatively correlated with sSDMA levels, it was not appar-ently related to IRIS CKD stage or other parameters known to be associated with CKD.

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Serum Intact Parathyroid Hormone Level is Inversely Correlated with Glycated Haemoglobin in Diabetic Chronic Kidney Disease Stages 3-5 Predialysis Patients

BIRDEM Medical Journal ◽

10.3329/birdem.v7i2.32447 ◽

2017 ◽

Vol 7 (2) ◽

pp. 110-113

Author(s):

Wasim Md Mohosin Ul Haque ◽

Muhammad Abdur Rahim ◽

Palash Mitra ◽

Tabassum Samad ◽

Samira Humaira Habib ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Parathyroid Hormone ◽

Kidney Disease ◽

Negative Correlation ◽

Glycated Haemoglobin ◽

Diabetic Patients ◽

Intact Parathyroid Hormone ◽

Ipth Level ◽

Ckd Stage ◽

The Relationship

Introduction: Diabetes mellitus (DM) is one of the leading causes of chronic kidney disease (CKD). Management of chronic kidney disease-mineral and bone disorder (CKD-MBD) is an integral component of CKD management; serum intact parathyroid hormone (iPTH) level is the key target. This study was designed to evaluate the relationship between glycated haemoglobin (HbAlc) and iPTH in diabetic CKD stages 3-5 patients not yet on dialysis.Methods: This cross-sectional study was conducted in BIRDEM General Hospital, Dhaka, Bangladesh from January 2013 to December 2014. Diabetic patients suffering from CKD stages 3-5, who were not on dialysis, were consecutively and purposively included in this study. Along with base-line characteristics, clinical and laboratory data including HbAlc and iPTH levels were recorded for all patients. Data were analyzed by using SPSS version 20.0 and Pearsons correlation test was applied to evaluate the relationship between HbAlc and iPTH.Results: Total patients were 306, including 166 (54.2%) males. Mean age was 56.5±11.3 years. Mean duration of DM and CKD were 12.8±7.6 and 2.9±1.7 years respectively. Among the study population, 49 (16.0%) were in CKD stage 3, 90 (29.4%) in CKD stage 4 and rest 167 (54.6%) in CKD stage 5. Mean HbAlc (%), serum creatinine (mg/dl), urea (mg/dl), calcium (mg/dl), phosphate (mg/dl), alkaline phosphatase (U/L) and iPTH (pg/ml) were 7.77±2.14, 6.8±3.0, 141.1±75.7, 8.1±1.2, 5.2±1.9,164.1±135.3 and 229.7±151.2 respectively. Mean HbAlc (%) and iPTH (pg/ml) in CKD stages 3, 4 and 5 were 8.36±1.59 and 171.7±127.9, 7.99±1.92 and 179.5±131.4, and 7.77±2.14 and 273.8±119.2 respectively. On correlation analysis, HbAlc had a significant negative correlation with iPTH (r=-0.002).Conclusion: The results of current study showed that most diabetic CKD stages 3-5 predialysis patients had poor glycaemic control and HbAlc had negative correlation with iPTH. As iPTH level is influenced by presence and control of DM, the targets of iPTH in CKD stages 3-5 in general, as recommended in existing guidelines, may not be appropriate in diabetic CKD patients and this issue merits further investigation.Birdem Med J 2017; 7(2): 110-113

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Calcium - Phosphate Index: Considerable Indicator in Different Stages of Chronic Kidney Disease

Journal of Medical Science & Research ◽

10.47648/jmsr.2012.v1902.01 ◽

2012 ◽

Vol 19 (Number 2) ◽

pp. 3-6

Author(s):

N Y Mili ◽

Md. E Hoque ◽

S Akhter ◽

N S Lovely

Keyword(s):

Chronic Kidney Disease ◽

Calcium Phosphate ◽

Kidney Disease ◽

Serum Calcium ◽

Phosphate Level ◽

Ckd Stage ◽

P Index ◽

Group A ◽

Group B ◽

Serum Inorganic Phosphate

Since the early 1970s. calcium phosphate (Ca-P) index has been regarded as a risk factor for extra skeletal calcification. tumoral calcinosis and increased cardiovascular event and death. The general consensus was not to exceed 70 ing2h1Lt (5.6 unno1/1,2) in chronic kidney disease. The present study was done to find out the Ca - P index in different stages of (CKB) patients to assess the risks of the patients which can be understood and be negotiated. In this study 100 of previously diagnosed chronic kidney disease patients of different stages as CKD stage Ill. IV and stage V were included. Subjects were divided into three groups according to staging of chronic kidney disease : group A (stage 111) were 34 patients, group 8 (Stage IV) were 36 and group C (Stage V) were 30 patients. Mean serum inorganic phosphate level was in group A .5.41 + 2.49. group 8 8.17 + 3.63 and in group C 10.50 + 3.06. Mean serum Calcium level in three groups were in group-A 8.36± 0.74. group- B 8.10± 0.75 and in group- C was 7.43± 1.27 ). Ca - P index was calculated by multiplying the serum calcium and phosphate level. Mean Ca-P index was in group-A 49.39+ 22.95. group B-67.93+ 31.2 and in group-C 90.76+ 24.82. Statistical analysis was done betWeen these groups and it was signifimuly higher in group B than group A ( p< 0.06. group A is group 8). in group C than group A ( p< 0.00. group A vs group C) and in ,group C than group ft ( p< .002. group B vs group C). It was found that as the renal function deteriorates gradually the Ca P index increases and it is highly significantly higher in CKD — V patient than other stages.

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Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database

10.2337/figshare.16434609 ◽

2021 ◽

Author(s):

Hajime Nagasu ◽

Yuichiro Yano ◽

Hiroshi Kanegae ◽

Hiddo J.L. Heerspink ◽

Masaomi Nangaku ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Clinical Practice ◽

Kidney Disease ◽

Kidney Function ◽

Sglt2 Inhibitor ◽

Sglt2 Inhibitors ◽

Glucose Lowering ◽

Glucose Transporter 2 ◽

Egfr Decline

Objective: Randomized controlled trials have shown kidney protective effects of sodium glucose transporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitors initiation modifies treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients is unknown. Research Design and Methods: Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease. Results: At baseline, mean age at initiation of the SGLT2 inhibitor (n=1,033) or other glucose-lowering drug (n=1,033) was 64.4 years; mean eGFR was 68.1 mL/min per 1.73 m²; and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs other drugs 0.75 mL/min/1.73 m² per year (0.51 to 1.00). During a mean follow-up of 24 months, 103 c<a>omposite kidney outcomes </a>occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26 to 0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiating SGLT2 inhibitors (pheterogeneity ≥0.35). Conclusions: The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.

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