Study of the Cardio Renal Effects of SGLT2 Inhibitors Among Diabetic and Non-diabetic Lupus Nephritis Patients
Phase: PHASE4
Conditions: SLE, Lupus Nephritis, SGLT2 Inhibitors
Sponsor: Mansoura University

Study Protocol 
Official Title: 
Study of the Cardio Renal Effects of SGLT2 Inhibitors Among Diabetic and Non-diabetic 
Lupus Nephritis Patients 
ClinicalTrials.gov Identifier (NCT Number): 
NCT05748925 
Date of Document: 
May 11, 2024 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Internal Medicine Department 
Faculty of Medicine – Mansoura University 
 
 
Study of the cardio renal effects of SGLT2 inhibitors among 
diabetic and non-diabetic lupus nephritis patients. 
 
 
 
Thesis submitted as partial fulfillment of M.D in Nephrology 
By 
Nour Elsabah Mohamed Elbialy 
(Nour M. Elbialy) 
M.B.B.ch, MSC 
Specialist of Nephrology, 
Urology and Nephrology center- Mansoura University 
 
Under supervision of 
Prof. Dr. Mohamed Abdel-Kader Sobh 
(Mohamed A. Sobh) 
Professor of internal medicine (Nephrology), 
Urology & Nephrology Center, 
Faculty of Medicine- Mansoura University,Egypt. 
 
 
 
Prof. Dr. Ayman Fathi Refaie 
(Ayman F. Refaie) 
Consultant of internal medicine (Nephrology), 
Urology & Nephrology Center 
Faculty of Medicine –Mansoura University, Egypt. 
 
 
Dr. Kareem Nagaty Zayed 
 
 
1

 
(Kareem N. Zayed) 
lecturer of internal medicine (Nephrology), 
Faculty of Medicine- Mansoura University, Egypt. 
 
 
 
2021 
 
 
 
 
 
 
Introduction 
 
Sodium-glucose cotransporter 2 inhibitors have been the recent 
 
focus in a large number of diseases, not only type 2 diabetes but also 
congestive heart failure and chronic kidney disease. (1) 
 
Latest studies show that sodium-glucose cotransporter 2 inhibitors 
originally approved for glycemic control in patients with type 2 diabetes 
(2). 
 
 
SGLT2i also exert protective renal effects independently from their 
effects on blood glucose level (2). 
 
Recently it is obvious that SGLT2i treatment can be effective in 
 
patients with non-diabetic chronic kidney disease, including primary and 
secondary glomerular diseases. (3) 
 
Glomerular diseases can result from either immune or nonimmune 
mediated damage, it appears that SGLT2i would not target the mechanism 
of immune-mediated glomerular diseases; it may improve the source of 
injury from the original glomerular damages. (4) 
 
 
It is still not obvious at what point of the mechanism of specific 
glomerular diseases (either immune or nonimmune mediated) SGLT2i can 
be beneficial. So, more studies targeting nondiabetic primary and 
 
2

 
secondary glomerular diseases are ensured to assess the efficacy and safety 
of SGLT2i in patients with glomerular diseases. (4) 
 
SLE is a chronic inflammatory disease that has renal effect in about 
 
half of patients. Lupus nephritis is a major risk factor for morbidity and 
mortality in patients with SLE, and in spite of strong anti-inflammatory 
and immunosuppressive therapies still ends in CKD or ESRD. (5) 
 
Based on this observation, we aim to determine the effect of SGLT2i 
 
treatment in patients with glomerulonephritis secondary to SLE who either 
is diabetic or non-diabetic. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aim of the work 
 
 
This study aims to assess SGT2i role in regression of ongoing kidney and 
cardiac diseases among lupus nephritis patient either diabetic or non-
diabetic under different immunosuppressive therapy. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patients and methods 
 
 
Technical design: 
 
 
Study sitting: .1 
 
 
Nephrology and renal transplant unit at urology and nephrology center 
in Mansoura University. 
 
It will include 100 patients with lupus nephritis, Diagnosis of 
glomerulonephritis was performed by renal biopsy, and all of the renal 
biopsies were carried out at urology and nephrology center. 
 
Patients with an estimated glomerular filtration rate (eGFR) >30 
ml/min/1.73m2 will be randomized into two groups 
 
Study group will receive SGLT2i inhibitor as add on drug or replace ● 
another drug according to patient clinical situation, Dapagliflozin 10 
mg and 25 mg will be used once daily with or without food. 
 
 
Control group will be maintained on placebo. ● 
 
The primary endpoint will be sustained decline in eGFR ≥50%, ESKD, 
or kidney or cardiovascular death 
 
We will follow up all patients for 12 months and compare their results. 
 
 
 
 
 
 
 
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2. Inclusion criteria: 
 
Patients aged more than 16 year. .1 
 
 
Willing to sign informed consent. .2 
 
 
Diagnosis of SLE according to EULAR/ACR classification .3 
criteria. 
 
Renal biopsy showed lupus nephritis. .4 
 
 
Patient with eGFR > 30 ml/min/1.73m2 by cockcroft-gault .5 
equation. 
 
3. Exclusion criteria: 
 
Patients with eGFR <30 ml/min per 1.73 m2. .1 
 
 
Current pregnancy or lactation. .2 
 
 
Medical history of chronic disease (CLD, cancer, severe .3 
respiratory distress, gastrointestinal tract lesions). 
 
Patients refusing to participate in the study or lost follow up. .4 
 
 
Evidence of urinary obstruction of difficulty in voiding at .5 
screening. 
 
 
 
6

 
Patients who are receiving high dose diuretics or combined .6 
ACEI, ARBS. 
 
Patients who have frequent hypotensive episode or SBP .7 
<100 mmHg. 
 
 
 
 
 
 
 
Operational design: 
 
 
Study Protocol: 
 
 
Patients included in the study will treated with dapaglifilozin ● 
initiated at a total daily dosage of 10 mg/kg per day. 
 
Study design: 
 
 
Type of the study: randomized controlled study. 
 
 
The following data will be gathered and evaluated for all  
 
patients: 
 
 
I-before intervention: 
 
Serum creatinine, Creatinine clearance. .1 
 
24 hour urine protein, urine protein/creatinine ratio. .2 
 
Urine analysis. .3 
 
HBA1c. .4 
 
HGB. .5 
 
Uric acid and lipid profile. .6 
 
Lupus serology. .7 
 
 
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II-after intervention: All patients will be evaluated monthly regarding: 
 
Serum creatinine, creatinine clearance. .1 
 
24 hour proteinuria, protein/creatinine ratio. .2 
 
Fasting, random and postprandial glucose levels. .3 
 
CNI trough level if used. .4 
 
Urine analysis. .5 
 
HGB level. .6 
 
Uric acid, lipid profile. .7 
 
Lupus serology. .8 
 
Cardiovascular assessment: .9 
 
ECCHO. 
 
Atherosclerosis and vascular calcification incidence (NCCT model). 
 
Regular measurement of blood pressure each visit. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Outcomes: 
 
Effect of dapagliflozin compared to placebo on eGFR. .1 
 
Effect of dapagliflozin compared to placebo on systolic/diastolic blood .2 
pressure. 
 
Effect of dapagliflozin compared to placebo on body weight. .3 
 
Safety of dapagliflozin vs. placebo - the number of hypoglycemia .4 
episodes between groups and serious adverse events. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Statistical Analysis: 
 
 
Qualitative data were displayed in cross tabulations, and 
quantitative data were described in terms of arithmetic mean ± SD. 
Bivariate techniques were used for initial evaluation of contrasts. Thus, 
the chi-square and Fisher's exact tests were used for comparisons of 
frequencies of qualitative variables; the Mann-Whitney test and the 
unpaired t-test were used for comparisons of means of two quantitative 
variables. A p-value <0.05 was considered significant. Graft and patient 
survival rates were assessed using the Kaplan-Meier method. All 
analyses were carried out using the computer package SPSS for 
windows, release 16 SPSS Inc. Chicago, III, USA. 
 
 
 
 
 
Administrative design ● 
 
Informed consent will be obtained from all subjects and the approval will 
be obtained from institutional review board (IRB) in Faculty of Medicine, 
Mansoura University. There is no funding. 
 
 
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Research question 
 
 
The main research question is: Does use of SGLT2i will show 
 
superiority over conventional lines of treatment of lupus nephritis patient as 
regard efficacy and safety. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rationale and justification 
 
 
The rational of this study is that SGLT2i are now one of the common 
 
lines in regression of chronic kidney disease either is diabetic or not. 
 
 
Large trials on this issue exclude patient with glomerulonephritis, so 
 
we will study its renal efficacy in patient with secondary glomerulonephritis 
to SLE to prove their efficacy and safety in this group of patients. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Objectives 
 
 
The main objective of this study is to: 
 
 
 
To compare use of SGLT2i versus standard care in regression of ● 
chronic kidney disease in patient with LN. 
 
To study the safety and efficacy of this drug group with use of ● 
immunosuppression and possible interaction. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Hypothesis 
 
 
SLE is the one of the leading causes of secondary 
 
glomerulonephritis. 
Despite 
the 
use 
immunosuppressive 
and 
 
antiproteinuric drugs, a number of patients are at risk of progressing to 
end-stage kidney disease. Additional therapies to slow kidney function 
decline are highly desired. The DAPA-CKD trial demonstrated that the 
sodium glucose co-transporter 2 inhibitor dapagliflozin significantly 
reduced the risk of kidney failure and prolonged survival in participants 
with chronic kidney disease with and without type 2 diabetes. The 
DAPA-CKD population excluded patients with lupus nephritis, so we 
determined the long-term efficacy and safety of dapagliflozin on major 
kidney and cardiovascular outcomes in these patients. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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References 
 
 
James Matera, DO. SGLT2 Inhibitors and CKD in 
-1 
2021. Consultant360. Published online May 25, 2021. 
 
Dan Xu, Owain Chandler, Cleo Wee, et al. Sodium- 
-2 
 
Glucose Cotransporter-2 Inhibitor (SGLT2i) as a Primary 
Preventative Agent in the Healthy Individual: A Need of 
August 2021 
 
Hiddo J.L. Heerspink, Ph.D., Bergur V. Stefánsson, et 
-3 
al. Dapagliflozin in Patients with Chronic Kidney Disease. 
N Engl J Med 2020; 383:1436-1446. 
 
 
Kana N. Miyataa, Shao-Ling Zhanga John S.D. Chana 
-4 
. The Rationale and Evidence for SGLT2 Inhibitors as a 
Treatment 
for 
Nondiabetic 
Glomerular 
Disease. 
CJASN May 2017, 12 (5) 825-835. 
 
 
Salem 
Almaani, Alexa 
Meara and Brad 
H. 
-5 
Rovin. Update 
on           Lupus 
Nephritis           Clin 
PharmacolTher 2007;81:228-34. 
10.1038/sj.clpt.6100039. 
 
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