The latest analysis results of the CRENDENCE trial: Canagliflozin can reduce adverse renal events

I believe everyone is familiar with the CRENDENCE test, right? In general, the CRENDENCE trial is to study the effect of canagliflozin, a sodium-glucose cotransporter 2 (SGLT-2) inhibitor, on patients with type 2 diabetes and chronic kidney disease (CKD)
.

The test result is that canagliflozin can significantly reduce the risk of end-stage renal disease, creatinine doubling, kidney or cardiovascular death in patients with type 2 diabetes and chronic kidney disease (CKD)
.

On May 21, 2021, CRENDENCE researchers brought us the latest subgroup analysis
.

This analysis found that canagliflozin can reduce adverse renal events in patients with type 2 diabetes and CKD
.

Study Design This study is a post-mortem analysis of the CREDENCE trial, which is a randomized double-blind controlled multi-center international clinical trial
.

The main analysis results of the study are as follows: ➤The effect of canagliflozin on kidney-related adverse events; ➤The effect of canagliflozin on kidney-related serious adverse events and acute kidney injury (AKI); ➤Participants' baseline characteristics and kidney-related adverse events The relevance of events and AKI; ➤AKI incidence and outcome
.

CREDENCE participants meet the following conditions: ≥30 years old, diagnosed type 2 diabetes, glycosylated hemoglobin between 6.
5% and 12.
0%, estimated glomerular filtration rate (eGFR) between 30 and 90mL/min/1.
73㎡, Urine protein-creatinine ratio (UACR) is between 300-5000mg/g (33.
9-565.
6mg/mmol)
.

 All participants received the maximum dose or tolerable dose of angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) for more than four weeks before randomization
.

Participants had no history of non-diabetic nephropathy, type 1 diabetes, previous immunosuppressive nephropathy treatment or renal replacement therapy
.

Study Results 01 Canagliflozin and kidney-related adverse events There were 2200 cases in the canagliflozin group and 2197 cases in the placebo group
.

During an average follow-up of 2.
1 years (standard deviation: 0.
9), a total of 678 participants reported kidney-related adverse events
.

The specific risk ratio (HR) is shown in Table 1.
However, the effect of canagliflozin on renal-related adverse events is not constant during the follow-up period.
In the first few months after the intervention, the canagliflozin group is more likely to develop kidney Related adverse events, including eGFR reduction and creatinine increase, but after 12 months, the probability of renal-related adverse events in the canagliflozin group was much lower than that in the placebo group
.

 At the same time, researchers found that canagliflozin can increase the incidence of kidney-related adverse events in subgroups with higher UACR
.

 02 Canagliflozin and severe renal adverse events and a total of 82 (3.
7%) participants in the AKI placebo group had severe renal adverse events, while a total of 61 cases (2.
8%) in the canagliflozin group
.

In terms of AKI, there were 98 cases (4.
5%) in the placebo group and 86 cases (3.
9%) in the canagliflozin group.
The specific risk ratios are shown in Table 1
.

Canagliflozin group is more likely to have serious renal adverse events and AKI in the early stage, which is consistent with a decrease in eGFR and an increase in creatinine
.

 In addition, there were 50 cases (2.
3%) of severe renal adverse events related to AKI in the placebo group and 41 cases (1.
9%) in the canagliflozin group.
The specific risk ratios are shown in Table 1
.

 The HRs of the two groups are shown in the following table.
03 Baseline characteristics and adverse renal events.
In general, renal-related adverse reactions in the canagliflozin group and placebo group are related to the following baseline characteristics, which are young, black, and persistent diabetes Long time, low eGFR; high systolic blood pressure, UACR, triglyceride and total cholesterol levels; and use of insulin or diuretics
.

At the same time, serious adverse events of AKI and kidney are also related to the above-mentioned baseline characteristics
.

The incidence and prognosis of 04AKI First of all, some patients have experienced multiple AKI events
.

184 patients recorded 212 AKI events, of which 90 patients in the placebo group had 114 AKIs, while 86 patients in the canagliflozin group had 98 AKIs
.

A total of about 19 patients have experienced multiple AKIs, the main causes of which are dehydration, blood drip volume, and septic shock
.

Half of the patients choose to continue taking the drug after an AKI event
.

 In terms of AKI recovery, 53.
1% of patients in the canagliflozin group who had AKI recovered completely, 28.
6% partially recovered, and 18.
4% did not recover; while in the placebo group, 35.
4% completely recovered, 29.
2% partially recovered, 35.
4% did not recover
.

 Thirty days after the onset of AKI, 10.
5% of the patients in the canagliflozin group who developed AKI had dialysis, 2.
3% had chronic dialysis, and 7.
0% had died; while in the placebo group, 16.
3% had dialysis, 4.
1 % Of patients were chronically dialysis, 10.
2% of patients died
.

  In summary, canagliflozin can reduce the incidence of renal-related adverse events, which further confirms that canagliflozin is very safe for patients with type 2 diabetes and CKD on the kidneys, and canagliflozin is effective against AKI.
The prognosis after the occurrence is also helpful
.

References 1.
Heerspink HJL, Oshima M, Zhang H, et al.
Canagliflozin Reduces Kidney-Related Adverse Events in Type 2 Diabetes and CKD: Findings From the Randomized CREDENCE Trial.
Am J Kidney Dis.
2021 May 21.