scholarly journals Nephroprotection by SGLT2i in CKD Patients: May It Be Modulated by Low-Protein Plant-Based Diets?

2020 ◽  
Vol 7 ◽  
Author(s):  
Adamasco Cupisti ◽  
Domenico Giannese ◽  
Diego Moriconi ◽  
Claudia D'Alessandro ◽  
Massimo Torreggiani ◽  
...  

Sodium-glucose-transporter 2 inhibitors (SGLT2i) are a new class of anti-diabetic drugs that in large trials such as CREDENCE have shown also a reduction of glomerular hyperfiltration and albuminuria in type 2 diabetic patients. Hence, the interest toward SGLT2i is focused toward this potential nephroprotective effect, in order to reduce the progression to overt nephropathy, and it seems to be confirmed in the most recent DAPA-CKD trial. This is the reason why the indication for SGLT2i treatment has been extended to chronic kidney disease (CKD) patients with eGFR up to 30 ml/min, namely with CKD stage 1–3. In patients with CKD stage 3 to 5, the most recent KDIGO guidelines recommend low-protein diet and plant-based regimens to delay end-stage kidney disease (ESKD) and improve quality of life. Similarly to SGLT2i, low-protein diets exert renal-protective effects by reducing single nephron hyperfiltration and urinary protein excretion. Beyond the glomerular hemodynamic effects, both protein restriction and SGLT2i are able to restore autophagy and, through these mechanisms, they may exert protective effects on diabetic kidney disease. In this perspective, it is likely that diet may modulate the effect of SGLT2i in CKD patients. Unfortunately, no data are available on the outcomes of the association of SGLT2i and low-protein and/or vegan diets. It is therefore reasonable to investigate whether CKD patients receiving SGLT2i may have further advantages in terms of nephroprotection from the implementation of a low-protein and/or plant-based diet or whether this association does not result in an additive effect, especially in vascular nephropathies.

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Liliana Garneata ◽  
Carmen-Antonia Mocanu ◽  
Tudor Petrisor Simionescu ◽  
Andreea Elena Mocanu ◽  
Gabriel Mircescu

Abstract Background and Aims Dietary protein restriction is rediscussed as mainstay approach in advanced Chronic Kidney Disease (CKD), both in diabetics and non-diabetics to defer renal replacement therapy (RRT), mainly by better metabolic control; improvements in mineral bone disorders (MBD) were also suggested, but less studied in Diabetic Kidney Disease (DKD). An unicentric prospective interventional trial aimed to assess the effects of ketoanalogue-supplemented low protein diet (sLPD) on proteinuria and CKD progression (data already presented). The parameters of MBD were also evaluated. Method Adult diabetic patients (452) with stable CKD stage 4+, proteinuria>3g/g creatininuria and SGA A were enrolled in a run-in phase (3 mo), with LPD (0.6g/kg dry ideal bw). Those who proved adherent (92, 64% males, median age 55.7 yrs, 65% on insulin) received sLPD (Ketosteril®, 1 tablet/10kg) for 12mo. Monitoring and treatment followed the Best Practice Guidelines. The primary endpoint was proteinuria during intervention as compared to pre-enrolment. Serum levels of calcium, phosphates and iPTH were considered to assess MBD. Nutrition, inflammation (SGA, BMI, serum albumin, CRP) and compliance were safety parameters. Results In patients with advanced DKD and severe proteinuria, sLPD was associated with a 69 (63; 82) % reduction in proteinuria (data presented). Significant amelioration in MBD was noted: serum levels of calcium and phosphates were significantly ameliorated at the end of the study as compared to enrolment - 4.3 (4.2-4.9) vs 3.2 (3.1-3.5) mg/dL and 5.4 (4.9-6.1) vs 8.2 (7.8-8.9) mg/dL, respectively. Serum iPTH significantly decreased: 185 (168-212) vs 375 (354-585) pg/mL. The need for calcium supplementation decreased: 6.5 (6.0-6.7) vs 7.0 (6.8-7.3) g/day. Vitamin D was required by only 35% vs 65% of patients. Nutritional status was preserved and dietary compliance was very good throughout the study. Conclusion In patients with advanced DKD ketoanalogue supplemented low protein diet seems to be effective and safe as part of MBD management.


2017 ◽  
Vol 86 (3-4) ◽  
Author(s):  
Miodrag Janić ◽  
Špela Volčanšek ◽  
Mojca Lunder ◽  
Andrej Janež

Metformin represents the first line of treatment and is the most widely prescribed antihypergycemic drug in type 2 diabetic patients. It can be used as monotherapy or in combination with other oral antihyperglycemic drugs or insulin. Additionally, it is also prescribed in type 1 diabetic patients, it proved to be effective in prediabetes and also provided beneficial effects in other insulin resistant states, for example in polycystic ovary syndrome. Nevertheless, the exact molecular mechanism of its action remains unknown. It was shown that it inhibits liver gluconeogenesis, facilitates glucose uptake into peripheral tissues, such as striated muscle; it also acts in the gut. Besides antihyperglycemic effects, metformin was also shown to possess several beneficial, protective effects, so-called pleiotropic effects: particularly on the cardiovascular system and in cancer patients. Metformin has only few side effects, the most serious being metformin-associated lactic acidosis. The latter appears in rare clinical cases with pre-existing chronic kidney disease or advanced heart failure with tissue hypoperfusion, which consequently represent relative contraindications for metformin use. In the past, metformin treatment was usually discontinued when performing iodine contrast imaging, however recently there is evidence of its safety even in patients with higher stages of chronic kidney disease. All in all, metformin is a drug with a long tradition and a promising future.


2021 ◽  
pp. 1-9
Author(s):  
Ching-Fang Wu ◽  
Hung-Hsiang Liou ◽  
Chin-Chi Kuo ◽  
Ming-Hsien Tsai ◽  
Min-Yu Chang ◽  
...  

<b><i>Introduction:</i></b> Sclerostin could enhance renal excretion of calcium (Ca) and phosphate (P). The association between sclerostin and magnesium (Mg) has not yet discovered. In patients with type 2 diabetes mellitus (T2DM) or chronic kidney disease (CKD), higher serum sclerostin and altered renal excretion of Ca, P, and Mg were detected. Therefore, we tried to evaluate if there was any association between sclerostin and fractional excretion of Ca, P, and Mg (FeCa, FeP, and FeMg) in T2DM with CKD. <b><i>Methods:</i></b> In this prospective cohort study, 43 T2DM patients without CKD or with CKD stage 1–5 were enrolled. Values of parameters, including serum and urine sclerostin, were collected at baseline and 6 months later. For baseline data, the Mann-Whitney U test, χ<sup>2</sup> test, or Spearman’s correlation were used. For multivariate repeated measurement analysis, generalized estimating equation (GEE) model was utilized. <b><i>Results:</i></b> Patients with lower estimated glomerular filtration rate had higher serum sclerostin, FeP, FeMg, and lower FeCa. By correlation analysis, serum sclerostin was negatively associated with FeCa (<i>p</i> = 0.02) and positively associated with FeP (<i>p</i> = 0.002). The urine sclerostin to creatinine ratio (Uscl/Ucre) was positively correlated with FeP (<i>p</i> = 0.007) and FeMg (<i>p</i> = 0.005). After multivariate analyses by GEE model, serum sclerostin was still inversely associated with FeCa, while Uscl/Ucre was significantly associated with FeMg. On the other hand, FeP lost its associations with serum sclerostin or Uscl/Ucre. <b><i>Conclusion:</i></b> In our study population of T2DM patients with or without CKD, the inverse correlation between serum sclerostin and FeCa could not be explained by the calciuric effect of sclerostin. In addition, a newly discovered positive association between urinary sclerostin and FeMg indicated a possible role of urinary sclerostin in regulating renal Mg handling especially over distal convoluted tubules.


Diabetology ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 51-64
Author(s):  
Satoru Yamada

Low-protein diets have been recommended as diet therapy for the management of chronic kidney disease; however, its effect on chronic kidney disease has not been scientifically proven. Although several studies have reported significantly more favorable results with low-protein diet than with normal-protein diet, the renal protective effects of low-protein diets are still unclear in diabetic patients with chronic kidney disease. Moreover, some studies have reported that extremely low-protein diets may increase the risk of mortality. Thus, this paper describes the effectiveness and safety of low-protein diets for patients with diabetic kidney disease by reviewing the historical background of different low-protein diets that were critically examined in several studies.


2020 ◽  
Vol 51 (5) ◽  
pp. 411-420
Author(s):  
Maria Schoina ◽  
Charalampos Loutradis ◽  
Ioanna Minopoulou ◽  
Marieta Theodorakopoulou ◽  
Nikolaos Pyrgidis ◽  
...  

Background: Diabetic kidney disease is the leading cause of end-stage renal disease worldwide. Whether diabetes mellitus (DM) is an additional factor leading to elevated blood pressure (BP) levels and BP variability (BPV) in patients with chronic kidney disease (CKD) is unknown. This study aimed to compare ambulatory BP levels, BP trends and BPV in diabetic and non-diabetic patients with CKD. Methods: This study included 48 diabetic and 48 non-diabetic adult patients (>18 years) with CKD (estimated glomerular filtration rate [eGFR] <90 and ≥15 mL/min/1.73 m2), matched in a 1:1 ratio for age, sex and eGFR within each CKD stage (2, 3a, 3b and 4). All patients underwent 24-h ambulatory BP measurement with the Mobil-O-graph device. To evaluate the effect of DM and time on the trajectories of 24-h BP levels, we performed two-way mixed ANOVA analysis for repeated measurements using hourly means. BPV was calculated with validated formulas. Results: In total, patients with DM had significantly higher 24-h systolic BP (SBP; 132.13 ± 10.71 vs. 124.16 ± 11.45; p = 0.001) and pulse pressure (PP; 57.1 ± 9.6 vs. 49.5 ± 10.9; p < 0.001), but similar 24-h diastolic BP (DBP; 75.00 ± 8.43 vs. 74.62 ± 6.86 mm Hg; p = 0.809) compared to patients without DM. A similar trend was evident across all CKD stages. The effect of DM on BP trajectories during the recording period was significant for SBP (F = 18.766, p < 0.001, partial η2 = 0.261) and marginally significant for DBP (F = 3.782, p = 0.057, partial η2 = 0.067). Twenty-four hour SBP SD, weighted SD (wSD) and average real variability (ARV; 10.94 ± 2.75 vs. 9.46 ± 2.10; p = 0.004), as well as 24 h DBP SD, wSD, coefficient of variation (CV) and ARV (8.23 ± 2.10 vs. 7.10 ± 1.33; p = 0.002) were significantly higher in diabetic compared to non-diabetic CKD patients. Conclusions: Ambulatory SBP and PP levels are higher and SBP-profile is different in patients with diabetic compared to those with non-diabetic CKD. Systolic and diastolic BPV are also higher in diabetics. These findings may signify a higher cardiovascular risk for patients with both DM and CKD compared to patients with CKD alone, through higher BP levels and BPV.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 539-P
Author(s):  
YOSHINORI KAKUTANI ◽  
MASANORI EMOTO ◽  
KATSUHITO MORI ◽  
YUKO YAMAZAKI ◽  
AKINOBU OCHI ◽  
...  

2019 ◽  
Vol 15 (5) ◽  
pp. 349-356 ◽  
Author(s):  
Angus Gill ◽  
Stephen P. Gray ◽  
Karin A. Jandeleit-Dahm ◽  
Anna M.D. Watson

Background: The sodium glucose co-transporter 2 (SGLT2) is primarily located within S1 of the renal proximal tubule being responsible for approximately 90% of glucose re-uptake in the kidney. Inhibition of SGLT2 is an exciting new pharmacological approach for the reduction of blood glucose in type 2 diabetic patients via inhibition of tubular glucose reabsorption. In addition to lowering glucose, this group of drugs has shown significant cardiovascular and renal protective effects. Conclusion: This review aims to outline the current state of preclinical research and clinical trials for different SGLT2 inhibitors and outline some of the proposed mechanisms of action, including possible effects on sympathetic nerve activity, which may contribute to the unexpected beneficial cardiovascular and reno-protective effects of this class of compounds.


2021 ◽  
Vol 6 (4) ◽  
pp. S158
Author(s):  
R.K. YADAV ◽  
S. Sangha ◽  
A. S Kumar ◽  
S. Bagchi ◽  
S. Mahajan ◽  
...  

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