Progression Of Nephropathy In Patients Research Articles

Systematic Review of Genetic Modifiers Associated with the Development and/or Progression of Nephropathy in Patients with Sickle Cell Disease.

Sickle cell nephropathy (SCN) is a common complication of sickle cell disease (SCD) that significantly contributes to morbidity and mortality. In addition to clinical and life-style factors, genetic variants influence this risk. We performed a systematic review, searching five databases. Studies evaluating the effect of genetic modifiers on SCN were eligible. Twenty-eight studies (fair-to-good quality) were included: one genome-wide association study, twenty-six case-control studies, and one article combining both approaches. APOL1 was significantly associated with albuminuria and hyperfiltration in children and with worse glomerular filtration in adults. On the other hand, alpha-thalassemia protected patients against albuminuria and hyperfiltration, while BCL11A variants were protective against albuminuria alone. The HMOX1 long GT-tandem repeat polymorphism led to a lower glomerular filtration rate. No modifiers for the risk of hyposthenuria were identified. A genome-wide association approach identified three new loci for proteinuria (CRYL1, VWF, and ADAMTS7) and nine loci were linked with eGFR (PKD1L2, TOR2A, CUBN, AGGF1, CYP4B1, CD163, LRP1B, linc02288, and FPGT-TNNI3K/TNNI3K). In conclusion, this systematic review supports the role of genetic modifiers in influencing the risk and progression of SCN. Incorporating and expanding this knowledge is crucial to improving the management and clinical outcomes of patients at risk.

586-P: Light Physical Activity Prevents the Progression of Diabetic Nephropathy in Patients with Type 2 Diabetes

Background and aim: Diabetic nephropathy is one of the most important complications of diabetes mellitus. In recent years, aerobic exercise has been reported to be potentially effective in preventing nephropathy. However, the relationship with light physical activity (LPA), activities of daily living, is not clear. In this study, we researched the effect of LPA assessed by tri-axial acceleration sensors on the progression of nephropathy in patients with type 2 diabetes Materials and methods: We analyzed retrospectively the cohort study of type 2 diabetic patients (T2DM) with urinary albumin-to-creatinine ratio (UACR) under 300 mg/gCr who visited Ayabe City Hospital from April 2018 to March 2020 and were observed until May 2022. The progression of nephropathy was defined as an increase in the category of diabetic nephropathy. LPA time was measured using a tri-axial accelerometer ActiGraph GT3X-BT instructed to use the accelerometer for 7 days, except while bathing and sleeping. LPA was defined as 100-1,952 counts per min. Hazard ratio of LPA for the progression of nephropathy was calculated by Cox hazard model after adjusting by age, gender, BMI, hemoglobin A1c (HbA1c), smoking states, alcohol consumption, use of renin-angiotensin system inhibitor at baseline. Results: 167 patients (109 men) including 132 with stage1 and 35 with stage 2, mean age, body mass index, HbA1c, UACR, LPA and median observation period were 72.1 ± 12.3 years, 23.4 ± 3.4 kg/m2, 7.6 ± 0.9 %, 56.8 ± 137.4 mg/gCr, 305.6 ± 85.5 minutes/day and 1246 (406-1283) days. During follow-up, progression of nephropathy was observed in 39.5 % (66/167). The adjusted hazard ratio of LPA per 1 hour of progression of nephropathy was 0.81 (95% confidence interval 0.67-0.98, P = 0.031). Conclusion: Patients with T2DM with low LPA were shown to be at higher risk of developing diabetic nephropathy. This suggests that increasing activities of daily living in patients with T2DM is important in terms of preventing diabetic nephropathy. Disclosure T.Osaka: None. H.Okada: None. M.Fukui: None.

Impact of oxidative stress on the activity of adenosine deaminase and its isoenzymes in nephropathy patients from Wasit-Iraq

Diabetes mellitus is a group of metabolic disorders that share with symptoms of hyperglycemia led to elevated free radical activity. Hyperglycemia is linked to a higher level of (ADA), which is one of the factors that cause oxidative stress by creating reactive oxygen species (ROS), that leads to insulin resistance. This study aimed to determine the relationship between serum total adenosine deaminase(TADA) and its isoenzyme (ADA1and ADA2) with the progression of nephropathy in patients with type 2 diabetes using a case-control study from Wasit-Iraq. In addition, we aimed to find if there is a link between oxidative stress with TADA and its isoenzyme. The One-way ANOVA was used to compare the mean values of fasting plasma sugar (FPS), total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde (MDA), microalbumin in urine, HbA1c, and TADA, ADA1, ADA2 between the three studied groups (Control(C), diabetic patients(DM), and diabetic nephropathy patient(DN). The results of our study revealed that there was a highly significant increase in TADA and its isoenzyme activities of DM and DN groups, as compared to the C group.

Association of glycosylated hemoglobin with urinary albuminuria for early detection and progression of renal damage in patients with type 2 diabetes mellitus

Background: Regular screening of levels of glycosylated hemoglobin and microalbuminuria (MA), diabetic nephropathy can be prevented.Recent studies found some of the sensitive and specific biomarker for early detection and progression of nephropathy in type 2 diabetes mellitus (T2DM) patients. Aim and Objectives: This study was carried out to correlation of glycosylated hemoglobin with urinary albuminuria for early detection and progression of nephropathy in patients with T2DM. Materials and Methods: This was a case–control study was conducted at tertiary care institute of India. A total 300 subjects included in the present study diagnosed with T2DM according to American diabetes association criteria and the cases are sub grouped based on albumin creatinine ration, the 100 patients T2DM with normoalbuminuria (NA) (ACR Ratio: <30 mg/dL) and 100 patients T2DM with MA (ACR Ratio: 30–299 mg/dL) along with that 100 healthy subjects were included in the study.FBS, PPBS, Urea, Creatinine, Uric acid, HbA1C, and Urinary Albumin was analyzed using laboratory standard methods. Results: The plasma fasting blood sugar, post-prandial blood sugar, serum urea, creatinine, uric acid, Glycosylated hemoglobin, and urinary albumin levels were increased in two groups of T2DM Patients when compared to healthy controls. Significantly elevated levels of plasma fasting blood sugar, post-prandial blood sugar, serum urea, creatinine, uric acid, Glycosylated hemoglobin, and urinary albumin are observed in all the parameters elevated in between patients T2DM with MA when compared to patients T2DM NA. Conclusion: Elevated levels of Glycated hemoglobin as well as urinary albumin were useful for detection and progression of different stages of nephropathy in patients with T2DM and also this study suggest that continuous monitoring of these investigations were useful for treatment of different stages of T2DM.

Management of Metabolic Acidosis in Chronic Kidney Disease: Past, Present, and Future Direction.

Chronic kidney disease(CKD) is a major global epidemic associated with increased morbidity and mortality. Despite the effectiveness of kidney protection strategies of hypertension, diabetes, and lipid control and use of newer hypoglycemic agents and anti-angiotensin II drugs, the nephropathy in CKD continues unabated toward irreversible kidney failure. Thus, interventions targeting modifiable risk factors in CKD such as metabolic acidosis (MA) are needed. Acid reduction with sodium-based alkali has been shown to be an effective kidney-protection strategy for patients with CKD and reduced glomerular filtration rate (GFR). Small-scale studies reveal diets emphasizing ingestion of plant-sourced over animal-sourced protein reduce dietary acid, improve MA, and slow further nephropathy progression in patients with CKD and reduced GFR. Additionally, veverimer, an investigational, nonabsorbed polymer that binds and removes gastrointestinal hydrochloric acid, is being developed as a novel treatment for MA. As further studies define how to best use these interventions for kidney protection, clinicians must become aware of their potential utility in the management of patients with CKD. The aim of the present review is to explore the various intervention strategies that increase or normalize serum [HCO3-] in patients with CKD-associated MA or low normal serum [HCO3-] that may further slow progression of CKD.

Aspartate aminotransferase to alanine aminotransferase ratio and the risk of diabetic nephropathy progression in patients with type 2 diabetes mellitus: A biopsy-based study

PurposeTo study the relationship between baseline serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR) in both clinicopathological features and renal outcome among type 2 diabetes mellitus (T2DM) patients with biopsy-confirmed diabetic nephropathy (DN). MethodsAs a retrospective cohort study, we included 253 patients with T2DM and biopsy-confirmed DN. For receiver operating characteristic (ROC) curve showed that the optimal cut-off for AAR to predict end stage renal disease (ESRD) was 1.22. So, patients were divided into two groups according to their AAR at the time of renal biopsy: high AAR Group (those with AAR > 1.22); low AAR Group (those with AAR ≤1.22). Association between AAR and clinicopathological features as well as renal outcome were analyzed. ResultsPatients with higher AAR presented elder, more hypertensive, more insulin use, higher serum cholesterol, more proteinuria and lower estimated glomerular filtration rate (eGFR). Compared with low AAR group, patients with high AAR had more severe glomerular pathological lesions and interstitial fibrosis and tubular atrophy. For prognostic analysis, high AAR Group was associated with a higher risk of progression to ESRD in univariate analysis. No matter treated with continuous or categorical variate, higher AAR remained an independent predictor for ESRD after adjusted for various confounding factors: gender, age, the duration of diabetes, serum glucose level, hypertension, serum lipid level, smoking, insulin use, eGFR and proteinuria. ConclusionHigh AAR was associated with more severe renal pathologic lesions and worse renal function in patients with T2DM and DN, which might be a novel noninvasive predictor for ESRD. Clinical relevanceTo our knowledge, there was no biopsy-based cohort study. In our study, high AAR was associated with more severe renal pathologic lesions and worse renal function in patients with T2DM and DN, which might be a novel noninvasive predictor of ESRD for patients with DN.

Prescribing pattern of Antihypertensive, Anti-Diabetic, Hypolipidaemic and Anti-Obesity Drugs in Diabetic Nephropathy

Objective: The Purpose of this study is to evaluate prescribing pattern of drugs to prevent progression of nephropathy in patients of diabetes in a tertiary care hospital. Materials and Methods: It was conducted in a tertiary care hospital, written informed consent was taken from those patients, who fulfilled study criteria and study sample included type 2 diabetic nephropathy outdoor patients who aged more than 40 years who were in stage of micro albuminuria (stage 3 diabetic nephropathy), details like sex, duration of illness, on-going treatment concurrent medicines were recorded in predesigned and pretested case record forms, these data were subjected to analysis using descriptive methods, Microsoft excel was used for data entry and descriptive analysis. A total of 100 patients were included in the study. A written permission has been obtained from Institutional Ethics Committee for the conduct of the study. Results: In the present study there were 100 patients, of whom 63 were males and 37 were females, majority of patients have diabetes for more than 20 years, all patients received anti-hypertensive, anti-diabetic and hypolipidaemic drugs. Among antihypertensive drugs, ACE inhibitors are prescribed most followed by diuretics and calcium channel blockers, among ACE inhibitors; Enalapril and Ramipril were prescribed most. Insulin was prescribed in 50% of patients and Glimepiride was the most common sulfonylurea prescribed. Statins were prescribed most among hypolipidaemic drugs; orlistat was prescribed only for 5% of patients. Majority of the patients were advised by physician regarding regular exercise, protein restricted diet, salt restriction, avoidance of cigarette smoking and weight reduction. Conclusion: Our study concluded that prescribing pattern of drugs in diabetic nephropathy was as per current practices and recommendations of guidelines. The pattern of drug use was to achieve better control of all the risk factors which are involved in progression of nephropathy. Further large scale and more detailed study, which includes sample from government setup and private clinics, is recommended to confirm our findings

IDF21-0125 Correlation between Urinary Copper and Microalbuminuria in Algerian Patients with Type 2 Diabetics

Background: The relationship between certain trace mineral elements and type 2 diabetes remains complex, and an alteration in the metabolism of these trace elements has been reported by some studies to be the cause of the development of diabetes or its complications. Aim: In order to study the role that copper could play in type 2 diabetes and more particularly in diabetic nephropathy, we evaluated the link between the status of urinary copper and microalbuminuria (biomarker of renal damage) in Algerian patients with type 2 diabetes. Method: The study involved a total of 46 unbalanced T2DM subjects with HbA1c> 7 (G1) and 50 well balanced T2DM subjects (G2) as well as 40 controls (G3). The respective mean age is estimated at 65.42 ± 4.07 years for G1 and 56.15 ± 6.66 years for G2 and 44.33 ± 3.47 years for G3. All study subjects were normotensive. A 24-hour urine copper assay on the thermo Fisher ICE 3300 atomic absorption spectrometer was performed for all patients, as well as a microalbuminuria assay on the Siemens DCA Vantage. Results: In this study, G1 had the highest urinary copper levels (p <0.001). A strong positive and significant correlation was found between urinary copper levels and microalbuminuria in G1 (r = 0.67) (p <0.01). The same is true for G2 where a weaker correlation was observed (r = 0.38), it nevertheless remains significant (p <0.01). Discussion: This study shows significantly higher urinary copper levels in diabetic patients with microalbuminuria than in patients without it. This high urinary Cu excretion may be due to the excretion of its transporter proteins. Urinary copper excretion may also be due to dissociations of the copper-albumin and ceruloplasmin-copper complexes, which are filtered by the damaged glomerulus and which may play a role in the progression of nephropathy in patients with nephropathy advanced.

The role of vitamin D deficiency and elevated inflammatory biomarkers as risk factors for the progression of diabetic nephropathy in patients with type 2 diabetes mellitus

Abstract Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Albuminuria is the most sensitive marker for the early recognition of DN. Therefore, we aimed to study the risk factors of albuminuria as a marker of DN among diabetic patients. The study included 41 patients with type 2 diabetes mellitus (T2DM), 50 type 2 diabetic nephropathy (T2DN) patients with macroalbuminuria, 43 T2DN patients with microalbuminuria and 38 healthy controls. Logistic regression was used to detect the most significant risk factors for albuminuria. A high statistically significant difference was found between the groups regarding age, sex, body mass index (BMI), diabetes mellitus (DM) duration, glucose, glycated haemoglobin (HbA1c), creatinine, glomerular filtration rate (GFR), lipid profile, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), the albumin–creatinine ratio (ACR), vitamin D, total parathyroid hormone (PTH), urea, total calcium and chemerin (p &lt; 0.001). It was found that the duration of DM, BMI, glucose, GFR, total cholesterol (TC), low-density lipoprotein (LDL), TNF-α, IL-6, CRP, ACR, vitamin D, PTH and chemerin are significant albuminuria risk factors in DN. Vitamin D deficiency and associated inflammatory mediators such as chemerin, TNF-α, IL-6 and CRP are the most essential risk factors for albuminuria in T2DM patients.

Діагностика діабетичної нефропатії у хворих на цукровий діабет 2-го типу в поєднанні з неалкогольною жировою хворобою печінки (Огляд літератури та власні дані)

У статті досліджено показники ниркових проб у хворих на цукровий діабет (ЦД) 2-го типу в поєднанні з неалкогольною жировою хворобою печінки (НАЖХП). Встановлено, що НАЖХП у хворих на ЦД 2-го типу потенціює розвиток діабетичної нефропатії. У хворих на ЦД 2-го типу з НАЖХП констатується підсилення канальцевої реабсорбції, що виникає внаслідок порушення співвідношення «вазоконстрикція/вазодилатація». Креатинін сечі можна вважати стабільним показником серед параметрів печінкових проб і раннім маркером прогресування діабетичної нефропатії у хворих на ЦД 2-го типу з НАЖХП.

Correlation of glycosylated hemoglobin with urinary albuminuria for early detection and progression of nephropathy in patients with type 2 diabetes millitus

diabetic nephropathy is a one of the most leading disorder in patients with type 2 diabetes mellitus. Urinary albuminuria used for detection of nephropathy in type 2 diabetes mellitus but its not an a sensitive and specific biomarker for DN. Recent studies found some of the sensitive and specific biomarker for early detection and progression of nephropathy in type 2 diabetes mellitus patients.A total 150 subjects included in the present study in that 100 patients diagnosed with type 2 diabetes mellitus and 50 healthy controls. All the subjects included after informed consent and blood, urine samples were collected from the all the subjects. FBS, PPBS, Urea, Creatinine, Uric acid, HbA1C and Urinary Albumin was analysed by using laboratory standard methods.statistically elevated levels of plasma FBS, PPBS, HbA1C in both the groups of type 2 diabetes mellitus when compared to healthy controls. Serum Urea, Creatinine and Uric Acid levels elevated in type 2 diabetes mellitus with microalbuminuria when compared to other two groups of study subjects. The Glycosylated hemoglobin positively correlated with urinary microalbuminuria in patients with two groups of type 2 diabetes mellitus.This study suggest that the poor glycemic control leads to increased further complications in patients with type 2 diabetes mellitus. Continuous monitoring of HbA1C and Urinary Albumin Levels were useful for progression and treatment of patients with type 2 diabetes mellitus.

Динаміка метаболічних параметрів та вмісту VEGF в сироватці крові хворих на діабетичну хворобу нирок під впливом комплексної нефропротекторної терапії

The goal of many studies around the world is to find preventive agents that may slow the progression of diabetic nephropathy in patients with type 2 diabetes mellitus at different stages of the disease, accordingly to preventing the progression of chronic kidney disease. The purpose of the work was to study the effect of complex nephroprotective therapy with the use of an inhibitor of the sodium glucose co-transporter 2 and spathogenetic therapy on metabolic parameters and the level of vasculoendothelial growth factor in blood serum of diabetic nephropathy patients at different stages of the disease. Materials and methods. 78 patients with type 2 diabetes mellitus were examined. Depending on the presence of albuminuria and glomerular filtration rate level, patients with diabetes mellitus were divided into the following groups: group I – patients with type 2 diabetes mellitus with normal glomerular filtration rate and albuminuria (n=62), group II – patients with type 2 diabetes mellitus with decreased glomerular filtration rate and albuminuria (n=16). The concentration of the vasculoendothelial growth factor was determined by enzyme-linked immunosorbent assay before and after 12 months of pathogenetic therapy. The glomerular filtration rate was calculated using the CKD EPI formula (KDIGO 2012). Patients of the first cohort received basic therapy, which included: blockers of the renin-angiotensin-aldosterone system, a coenzyme A reductase inhibitor and metformin, patients of the second cohort additionally received a sodium glucose co-transporter 2 inhibitor. Results and discussion. A decrease in vasculoendothelial growth factor levels in blood serum was found in all groups of examined patients, both under the influence of standard nephroprotective therapy, and with the use of complex treatment with an additional prescription of the sodium glucose co-transporter 2 inhibitor dapagliflozin. The highest level of response to treatment was observed in the group with the early stages of nephropathy. The therapy led to a significant improvement in the lipid spectrum of blood serum (increase of high-density lipoprotein cholesterol, decrease of total cholesterol, triglycerides and low-density lipoproteins) in all study groups. Conclusion. A decrease in serum vasculoendothelial growth factor levels against the background of an improvement in the basic clinical and laboratory parameters indicates not only an improvement kidneys function, but also a decrease in cardiovascular risk in this category of patients. The results of investigation indicate the feasibility of practical use of study vasculoendothelial growth factor serum level of diabetic nephropathy patients as an early diagnostic marker of cardiac disorders, prognosis assessment and improvement of the cardionephroprotective strategy

Short- and long-term treatment with angiotensin-converting enzyme inhibitors or calcium channel blockers for the prevention of diabetic nephropathy progression: A meta-analysis.

Treatments with angiotensin-converting enzyme (ACE) inhibitors or calcium channel blockers (CCBs) may delay the development of albuminuria in patients with early diabetic nephropathy. However, evidence in the literature has not been consistent. The present meta-analysis aimed to compare the short- and long-term therapeutic effects of ACE inhibitors and CCBs (when used separately) for preventing the progression of nephropathy in patients with diabetes mellitus. A comprehensive search of various databases was performed from inception until March 2015 for studies in the Chinese and English languages. Randomized controlled trials (RCTs) comparing the efficacy of ACE inhibitors with that of CCBs in patients with early diabetic nephropathy were considered. A total of 12 RCTs were included with a total of 947 patients. ACE inhibitors were indicated to be more effective in reducing the albumin excretion rate than CCBs after short-term treatments (<6 months) [mean difference (MD), 32.35; 95% confidence interval (CI), 31.62-33.07; P<0.00001]. There was no difference in serum creatinine values after treatment with either drug (MD, 8.7; 95% CI, -21.5-38.91; P=0.57). Data from six studies were used to compare long-term treatment effects (≥1 year). In terms of progression to normoalbuminuria, a marginal difference was obtained between the two drugs with better outcomes with ACE inhibitors [odds ratio (OR), 0.70; 95% CI, 0.49-1.00; P=0.05]. There was no statistically significant difference between ACE inhibitors and CCBs regarding the progression from microalbuminuria to macroalbuminuria (OR, 1.78; 95% CI, 0.82-3.87; P=0.15). In conclusion, the present study indicated that the antiproteinuric efficacy of CCBs may be less than that of ACE inhibitors after short-term treatment in patients with DN. However, both types of drugs are equally effective in reducing the progression of microalbuminuria to macroalbuminuria in the long term.

The Evaluation of SCUBE-1 and sCD40L Levels in Diabetic Nephropathy

Aim: There is a close link between diabetic nephropathy and atherosclerotic heart disease. We aimed to evaluate the changes of SCUBE-1 and sCD40L, which play role in the course of atherosclerosis, with the progression of nephropathy in patients with type 2 diabetes.Material and Methods: Thirty healthy subjects (group 1) and 74 patients with type 2 diabetes (divided into 3 groups as normal albuminuria group (group 2, n=33), moderately increased albuminuria group (group 3, n=22) and severely increased albuminuria group (group 4, n=19)) were enrolled in the study. Plasma SCUBE-1 and sCD40L levels were measured using the enzyme-linked immunosorbent assay technique.Results: Mean SCUBE-1 levels were significantly higher in group 4 compared to group 1 and group 2 (p=0.005 and p=0.014, respectively) and in group 3 compared to group 1 and group 2 (p=0.011 and p=0.028, respectively). Mean sCD40L levels were significantly higher in group 4 than in other three groups (all p&amp;lt;0.001), and in group 3 than in group 1 and group 2 (p=0.001 and p=0.016, respectively). Furthermore, SCUBE-1 level was positively correlated with total cholesterol level (r=0.212, p=0.031) and triglyceride (r=0.194, p=0.049). Likewise, sCD40L level was positively correlated with only creatinine level (r=0.297, p=0.002).Conclusion: SCUBE-1 and sCD40L levels increased with the progression of nephropathy in type 2 diabetes. This increment suggested that SCUBE-1 and sCD40L may play key role in the course of atherosclerosis due to diabetic nephropathy and, diabetic nephropathy may affect the levels of these parameters.

POTENTIALS TO PREDICT THE DEVELOPMENT OF DIABETES 1 TYPE COMPLICATIONS BY GLUCOSE CONTROL INDICATORS

Diabetes mellitus is recognized as a new non-infectious «epidemic of the XXI century» due to its steady increase in morbidity and a number of medical and social problems. These problems are associated with disability and mortality of patients resulted from the development of chronic complications of the disease. Hyperglycemia plays a major role in the development of diabetic complications. Diabetic microangiopathies predetermine the course and prognosis of the disease. HbA1c level and glucose variability are the complementary characteristics of glucose control. The aim of the study was to develop a mathematical model for predicting the development of diabetic microangiopathy in patients with diabetes type 1 by using continuous glucose monitoring system (CGMS). 62 patients (aged 18–45 years) with type 1 diabetes mellitus were examined. Clinical laboratory examination included: assessment of the of HbA1c level, C-peptide level, levels of blood creatinine and albuminuria. Patients were divided into groups: group 1 had HbA1c≤7.0% (n = 18), group 2 had HbA1c&gt; 7.0% (n = 44). Long-term monitoring of blood glucose levels was conducted with using the CGMS system during 6 days. Maximum blood glucose level, minimum blood glucose level and the difference of maximum and minimum blood glucose levels were accounted. The mathematical equation was obtained by using the simple linear regression analysis. This mathematical equation shows relationship between the level of albuminuria and the difference between maximum and minimum blood glucose levels. It can be used to predict the progression of diabetic nephropathy in patients with type 1 diabetes. We suggested the method for prognosticating the development and progression of diabetic microangiopathy (on an example of diabetic nephropathy) in patients with diabetes mellitus type 1 that does not require special software. This calculation may be performed using self-monitoring of blood glucose in clinical practice.

Combining SGLT2 Inhibition With a Thiazolidinedione Additively Attenuate the Very Early Phase of Diabetic Nephropathy Progression in Type 2 Diabetes Mellitus.

Although both sodium glucose co-transporter 2 inhibition by dapagliflozin and thiazolidinedione, pioglitazone have glucose-lowering and anti-inflammatory effects, the therapeutic efficacy of their combination on diabetic nephropathy has not been investigated. 9-week-old male db/db mice were randomly assigned to 4 groups and administrated with (1) vehicle, (2) dapagliflozin, (3) pioglitazone, or (4) dapagliflozin and pioglitazone combination. Human proximal tubule (HK-2) cells were treated with glucose or palmitate acid in the presence of medium, dapagliflozin, pioglitazone, or both. Glomerular tuft area and mesangial expansion of the kidney more reduced in the combination group compared to control and single therapy groups. Podocyte foot process width and glomerular basement membrane thickness decreased regardless of treatment, while the combination group showed the slowest renal hypertrophy progression (P < 0.05). The combination treatment decreased MCP-1, type I and IV collagen expression in the renal cortex. Only the combination treatment decreased the expression of angiotensinogen, IL-6, and TGF-β while it enhanced HK-2 cell survival (all P < 0.05). In conclusion, dapagliflozin and pioglitazone preserved renal function, and combination therapy showed the greatest benefit. These findings suggest that the combination therapy of dapagliflozin with pioglitazone is more effective than the single therapy for preventing the progression of nephropathy in patients with type 2 diabetes.

Dietary Protein Intake Is Not Associated with Progression of Diabetic Nephropathy in Patients without Macroalbuminuria

Background/Aims: Diabetic nephropathy is an important problem in patients with diabetes. However, little is known about the effect of dietary protein intake on albuminuria in patients with diabetes. Thus, the aim of this study was to clarify the association between dietary protein intake and change in urinary albumin excretion (UAE) or estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes. Methods: In this retrospective cohort study, we included 143 patients (71 men, average 64.0 (10.5) years, and median 14.5 (6.7-38.5) mg/gCr) without macroalbuminuria (UAE over 300 mg/gCr). Change in UAE or eGFR was defined as increase of UAE or GFR/follow-up duration (year). Habitual protein intake was estimated by a self-administered diet history questionnaire. Results: Median follow-up duration was 5 years. Logistic regression analyses showed that baseline UAE was associated with change in UAE (β = 0.217, p = 0.012), but the protein intake was not (β = -0.064, p = 0.454) (Table). In addition, baseline Cr was associated with change in eGFR (β = 0.344, p = 0.001), but the protein intake was not (β = 0.001, p = 0.988). Conclusions: Dietary protein intake was not associated with change in UAE or eGFR. This result suggests that protein restriction is not necessary in patients without macroalbuminuria. Multiple regression analysis on δUAE or δeGFRδUAEstandardized regression coefficientp valueδeGFRstandardized regression coefficientp valueLog (UAE+1)0.2170.012Log (UAE+1)0.0490.560Protein intake (g/kg/day)-0.0640.454Protein intake (g/kg/day)-0.0330.698Usage of RAS inhibitor0.1140.193Usage of RAS inhibitor-0.2020.021Creatinine0.0470.646Creatinine0.398&amp;lt;0.001Age-0.0030.977Age0.0610.490BMI0.1190.184BMI-0.0420.634Men-0.1430.163Men0.1210.237 Disclosure A. Kaji: None. Y. Hashimoto: Research Support; Self; Asahi Kasei Corporation, Fuji Foundation for Protein Research, Japan Society for the Promotion of Science, MSD K.K.. R. Sakai: None. T. Okamura: None. M. Yamazaki: None. M. Fukui: Research Support; Self; Grant-in-Aid for Scientific Research (C), Ono Pharmaceutical Co., Ltd., AstraZeneca, Astellas Pharma US, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kyowa Hakko Kirin Co., Ltd., Kissei Pharmaceutical Co., Ltd., MSD K.K., Novo Nordisk Foundation.

Renal and Cardiac Implications of Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors: The State of the Science.

To review the role of the sodium-glucose cotransporter-2 (SGLT2) inhibitors in the management of type 2 diabetes (T2DM), including the effects on renal and cardiovascular (CV) outcomes. A literature search of MEDLINE databases (1964 through May 2018) was conducted utilizing key words sodium-glucose co-transporter-2 inhibitors, SGLT2 inhibitors, and diabetes; additional limits for drug names were added. Available English-language data from reviews, abstracts, presentations, and clinical trials of use of SGLT2 therapy specifically detailing outcomes on CV and renal disease in humans were reviewed. This review will explore the role of the SGLT2 inhibitors on CV and renal outcomes in patients with T2DM. Relevance to Patient Care and Clinical Practice: A paradigm shift regarding the regulation of medications for the treatment of T2DM has resulted in the need for CV outcomes data as part of the drug approval process. Reduction of major CV events and progression of nephropathy in patients with T2DM represent major outcomes of clinical significance. Few medications have been able to establish a reduction in these end points; data for the use of SGLT2 inhibitors are favorable in this regard. The SGLT2 inhibitors represents a class of medications that reduce glucose levels via a novel and complementary mechanism. Emerging evidence suggests a plausible explanation for the observed reduction in adverse renal and CV outcomes in recent clinical trials. Questions remain whether these agents reduce renal disease risk greater than achievement of the same glycemic goals as other antidiabetics and whether CV and renal benefits are reproducible in high-risk patients with chronic kidney disease.

Wnt6: another player in the yin and yang of renal Wnt signaling

diabetic nephropathy (DN) remains the single most common cause of end-stage kidney disease, necessitating dialysis or transplantation, in the Western world. Hence, novel therapies beyond tight blood pressure and glycemic control are required to slow or reverse progression of nephropathy in patients

Effects of Omega-3 Fatty Acid Supplementation on Diabetic Nephropathy Progression in Patients with Diabetes and Hypertriglyceridemia.

Beneficial effects of omega-3 fatty acid (O3FA) supplementation in a wide range of disease condition have been well studied. However, there is limited information regarding the effects of O3FAs on chronic kidney disease (CKD), especially in diabetic nephropathy (DN) with hypertriglyceridemia. We investigate whether O3FA supplementation could help maintain renal function in patients with diabetes and hypertriglyceridemia. Total 344 type 2 diabetic patients with a history of O3FA supplementation for managing hypertriglyceridemia were included. Reduction in urine albumin to creatinine ratio (ACR) and glomerular filtrate rate (GFR) were examined. Subgroup analyses were stratified according to the daily O3FA doses. Serum total cholesterol, triglyceride, and urine ACR significantly reduced after O3FA supplementation. Overall, 172 (50.0%) patients did not experience renal function loss, and 125 (36.3%) patients had a GFR with a positive slope. The patients treated with O3FAs at 4g/day showed greater maintenance in renal function than those treated with lower dosages (p < 0.001). This dose dependent effect remains significant after adjustment for multiple variables. O3FA supplementation in diabetic patients with hypertriglyceridemia shows benefits of reducing albuminuria and maintaining renal function. The effects are dependent on the dose of daily O3FA supplementation.