Proteinuria In Non-diabetic Patients Research Articles

The Effectiveness of SGLT2 Inhibitors in CKD Patients

Sodium-glucose cotransporter-2 inhibitors, often known as SGLT2Is, are a class of medications used largely for anti-diabetic activity in oral dose form that lowers blood glucose levels. In recent years, numerous trials have documented the use of medications for conditions including renal and cardiovascular illness that go beyond only decreasing blood sugar. Other benefits of SGLT2Is' glucose-lowering activities include slowing or halting the progression of chronic kidney disease, lowering estimated glomerular filtration rate, lowering albuminuria, improving renal and cardiovascular health, and reducing estimated glomerular filtration rate. Published clinical trials reported all of these SGLT2I effects. The studies that we reviewed for this article are the Canagliflozin CardioVascular Assessment Study (CANVAS), Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA - CKD) trial, Effects of SGLT2I dapagliflozin on Proteinuria in Non-Diabetic Patients with The clinical studies, SGPLT2I class of medications, and their impact on cardiovascular and renal illnesses in diabetic and non-diabetic individuals are adequately covered in this review study.
 Keywords: SGLT2Is, Chronic kidney disease, dapagliflozin, Canagliflozin

MO157: Evaluating the Effect of SGLT2 Inhibitors on Proteinuria and Glomerular Filtration Rate in Non-Diabetic Patients with Proteinuria

Abstract BACKGROUND AND AIMS Proteinuria is strongly associated with the risk of CKD progression in non-diabetic and diabetic patients. SGLT2 inhibitors, as a promising new class, may provide protective effects for the kidney. Even though various studies have been conducted in this area, especially in diabetic patients, little information is available about how SGLT2 inhibitors affect proteinuria, kidney function or blood pressure in non-diabetic patients. Due to the lack of adequate information in previous studies, in this study, we investigated the effect of SGLT2 inhibitors on protein excretion and glomerular filtration rate (GFR) in patients with proteinuria. METHOD The present study was conducted as a single-group clinical trial (before and after). Thirty patients with proteinuria were enrolled. In addition to conventional treatment, empagliflozin 10 mg daily was administered. Height, weight, body mass index (BMI), GFR content, systolic and diastolic blood pressure, proteinuria and side effects in patients at the study's beginning and end were evaluated and recorded. In the end, the data were collected and analysed statistically. RESULTS In the present study, 30 patients with proteinuria were followed for 13.26 ± 5.90 weeks. The mean proteinuria of patients decreased significantly during the follow-up period (from an average of 1007.9 mg at the beginning of the study to 672.33 mg at the end (P < .05)). There was no significant difference in serum creatinine levels and glomerular filtration levels (P > .05). However, there was a significant decrease in blood pressure (systolic and diastolic) (P < .05). BMI and patients' weight were decreased compared to the beginning of the study, but this difference was not statistically significant (P > .05). Hypoglycaemia or hypokalemia did not occur in any of the patients. In 10% of patients, temporary dysuria was seen. Also, urinary tract infection was recorded in one patient (3.3%). In 3.3% of patients, the drug was discontinued due to intolerance. CONCLUSION The results of this study demonstrated that administration of empagliflozin significantly decreases proteinuria in non-diabetic patients with chronic kidney disease. However, further studies are recommended in this area.

Efficacy and Safety of Dapagliflozin in Children With Inherited Proteinuric Kidney Disease: A Pilot Study

Efficacy and Safety of Dapagliflozin in Children With Inherited Proteinuric Kidney Disease: A Pilot Study

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

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

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

SGLT2 inhibition decreases albuminuria and reduces the risk of kidney disease progression in patients with type 2 diabetes. These benefits are unlikely to be mediated by improvements in glycaemic control alone. Therefore, we aimed to examine the kidney effects of the SGLT2 inhibitor dapagliflozin in patients with proteinuric kidney disease without diabetes. DIAMOND was a randomised, double-blind, placebo-controlled crossover trial done at six hospitals in Canada, Malaysia, and the Netherlands. Eligible participants were adult patients (aged 18-75 years) with chronic kidney disease, without a diagnosis of diabetes, with a 24-h urinary protein excretion greater than 500 mg and less than or equal to 3500 mg and an estimated glomerular filtration rate (eGFR) of at least 25 mL/min per 1·73 m2, and who were on stable renin-angiotensin system blockade. Participants were randomly assigned (1:1) to receive placebo and then dapagliflozin 10 mg per day or vice versa. Each treatment period lasted 6 weeks with a 6-week washout period in between. Participants, investigators, and study personnel were masked to assignment throughout the trial and analysis. The primary outcome was percentage change from baseline in 24-h proteinuria during dapagliflozin treatment relative to placebo. Secondary outcomes were changes in measured GFR (mGFR; via iohexol clearance), bodyweight, blood pressure, and concentrations of neurohormonal biomarkers. Analyses were done in accordance with the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT03190694. Between Nov 22, 2017, and April 5, 2019, 58 patients were screened, of whom 53 (mean age 51 years [SD 13]; 32% women) were randomly assigned (27 received dapagliflozin then placebo and 26 received placebo then dapagliflozin). One patient discontinued during the first treatment period. All patients were included in the analysis. Mean baseline mGFR was 58·3 mL/min per 1·73 m2 (SD 23), median proteinuria was 1110 mg per 24 h (IQR 730-1560), and mean HbA1c was 5·6% (SD 0·4). The difference in mean proteinuria change from baseline between dapagliflozin and placebo was 0·9% (95% CI -16·6 to 22·1; p=0·93). Compared with placebo, mGFR was changed with dapagliflozin treatment by -6·6 mL/min per 1·73 m2 (-9·0 to -4·2; p<0·0001) at week 6. This reduction was fully reversible within 6 weeks after dapagliflozin discontinuation. Compared with placebo, bodyweight was reduced by 1·5 kg (0·03-3·0; p=0·046) with dapagliflozin; changes in systolic and diastolic blood pressure and concentrations of neurohormonal biomarkers did not differ significantly between dapagliflozin and placebo treatment. The numbers of patients who had one or more adverse events during dapagliflozin treatment (17 [32%] of 53) and during placebo treatment (13 [25%] of 52) were similar. No hypoglycaemic events were reported and no deaths occurred. 6-week treatment with dapagliflozin did not affect proteinuria in patients with chronic kidney disease without diabetes, but did induce an acute and reversible decline in mGFR and a reduction in bodyweight. Long-term clinical trials are underway to determine whether SGLT2 inhibitors can safely reduce the rate of major clinical kidney outcomes in patients with chronic kidney disease with and without diabetes. AstraZeneca.

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

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

Proteinuria in Nondiabetic Patients: Clinical Significance

Proteinuria in Nondiabetic Patients: Clinical Significance

Hyperphosphatemia is associated with overt proteinuria in non-diabetic patients with late-stage chronic kidney disease: a cross-sectional study

Proteinuria plays an important role in the progression of chronic kidney disease (CKD), as well as a powerful predictor of cardiovascular morbidity and mortality. The aim of our study was to investigate the potential determinants associated with overt proteinuria in non-diabetic patients with late-stage CKD. Between January 2006 and September 2011, a total of 418 non-diabetic patients with CKD stage 3-5 were enrolled from the outpatient department of nephrology. Urinary protein-to-creatinine ratio and serum phosphorus were determined. Other laboratory parameters, associated comorbidities, medication use, body mass index, and blood pressure were also assessed. The mean age of the patients was 66.7 ± 14.0 years. In multiple logistic regression analysis and adjusting for established risk factors, the odds ratios for overt proteinuria were 3.96 (95 % confidence interval, 1.80-8.76; p = 0.001) for higher serum phosphorus level (≥4.3 mg/dl) and 3.56 (95 % confidence interval, 1.47-8.63; p = 0.005) for hypercholesterolemia (≥217 mg/dl), compared to subjects with serum phosphorus <3.3 mg/dl and cholesterol level 158-184 mg/dl. The similar significant findings remained robust in individuals not receiving phosphate binder. Hyperphosphatemia and high serum cholesterol are associated with overt proteinuria in non-diabetic patients with late-stage CKD. Further studies should clarify whether this relation is causal and whether serum phosphorus level should be a new therapeutic target for proteinuria reduction.

Effect of pentoxifylline on proteinuria, markers of tubular injury and oxidative stress in non-diabetic patients with chronic kidney disease - placebo controlled, randomized, cross-over study.

Inhibition of the renin-angiotensin-aldosterone system (RAAS) with angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II subtype 1 receptor antagonists (ARB) is a common strategy used in the management of patients with chronic kidney disease (CKD). However, there is no universal therapy that can stop progression of CKD. Pentoxifylline (PTE) is a non-specific phosphodiesterase inhibitor with anti-inflammatory properties. It has been reported to have promising effects in CKD treatment. In a placebo-controlled, randomized, cross-over study we evaluated the influence of PTE (1200 mg/day) added to RAAS blockade on proteinuria, surrogate markers of tubular injury and oxidative stress-dependent products in 22 non-diabetic patients with proteinuria (0.4-4.3 g per 24 h) with normal or declined kidney function [eGFR 37-178 mL/min]. In an eight-week run-in period, therapy using ACEI and/or ARB was adjusted to achieve a blood pressure below 130/80 mm Hg. Next, patients were randomly assigned to one of two treatment sequences: PTE/washout/placebo or placebo/washout/PTE. Clinical evaluation and laboratory tests were performed at the randomization point and after each period of the study. The PTE therapy reduced proteinuria (by 26%) as compared to placebo. There were no differences in alpha(1)-microglobulin, urine excretion of N-acetyl-beta-d-glucosaminidase (NAG), hsCRP, the urinary excretion of 15-F(2)t-isoprostane, blood pressure (BP), eGFR and serum creatinine between the PTE and placebo groups. Pentoxifylline may decrease proteinuria in non-diabetic patients with CKD.

Optimal antiproteinuric dose of losartan in nondiabetic patients with nephrotic range proteinuria

Although the antiproteinuric response to antihypertensive treatment is the main predictor of renoprotective efficacy in long-term renal disease, to date, dose-finding studies of antihypertensives have been based only on blood pressure. We aimed to find the optimal antiproteinuric dose of the angiotensin II antagonist losartan. An open-label, dose-response study using subsequent 6-week treatment periods was performed in 10 nondiabetic patients with proteinuria of 5.8 ± 0.8 g/d and a mean arterial pressure of 103 ± 3.7 mm Hg without antihypertensive medication. All patients had normal to moderately impaired renal function. After the baseline period, five periods followed with a daily losartan dose of 50 mg, 100 mg, 150 mg, and 50 mg and a recovery without losartan. At the end of each period, proteinuria and mean arterial pressure were measured. The consecutive doses of losartan had a similar antihypertensive response (−11.3 ± 2.8% by the 100-mg dose). The optimal antiproteinuric response was reached at 100 mg of losartan (−30 ± 8%). The 50-mg dose (−13 ± 7%) was less effective, and the 150-mg dose (−28 ± 8%) was not more effective. A 100-mg dose of losartan is optimal for reduction of proteinuria in nondiabetic patients with nephrotic range proteinuria. © 2001 by the National Kidney Foundation, Inc.