New Study Shows SGLT-2i Safely Reduces Proteinuria Levels And Protects Kidney Function in Kidney Transplant Patients

Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) have been shown to attenuate the decline in renal function and reduce proteinuria in patients with chronic kidney disease (CKD). At present, for kidney transplant patients, there are few related studies on SGLT-2i, and it is related to the safety of kidney transplant recipients. For example, does the use of SGLT-2i increase the risk of genital and urinary tract infections (UTIs) after surgery in kidney transplant recipients? Also, does the hemodynamic effect of SGLT-2i reduce renal function in patients?

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Recently, International Urology and Nephrology published a study on the use of SGLT-2i in kidney transplant recipients. The study found that SGLT-2i can reduce proteinuria levels in kidney transplant patients with good safety.

Research design

This is a two-center randomized controlled study with 1-year follow-up to evaluate the efficacy and safety of SGLT-2i in kidney transplant recipients with diabetes. The inclusion criteria of the study were kidney transplant recipients (successful kidney transplantation), patients with diabetes mellitus (new-onset diabetes before or after transplantation), and patients with complete data. The exclusion criteria were blood sugar returned to normal after kidney transplantation and death immediately after kidney transplantation (such as infection with a new crown, or sudden cardiac death).

The study was divided into two groups: the control group, which did not receive SGLT-2i treatment; the SGLT-2i group, which received SGLT-2i treatment. Among them, the SGLT-2i group was divided into a and b subgroups. Patients in subgroup a started SGLT-2i treatment immediately within 3 months after kidney transplantation, while subgroup b started SGLT-2i treatment after 3 months. 2i treatment.

Of note, the definition of diabetes in this study was based on random blood glucose, not glycated hemoglobin (HbA1c) or fasting blood glucose.

The study endpoints were the incidence of UTI; changes in HbA1c, estimated glomerular filtration rate (eGFR), and tacrolimus dosage; the risk of acute rejection; proteinuria levels.

Research result

A total of 57 patients were enrolled, including 21 patients in the control group. SGLT-2i

There were 11 cases in subgroup a and 11 cases in subgroup SGLT-2i b. 45.6% of the patients had been diagnosed with diabetes before kidney transplantation, and the rest were new-onset diabetes patients after kidney transplantation. Notably, 3 patients (2 in group 2a and 1 in group 2b) who received SGLT-2i for 6 months had their blood glucose returned to normoglycemia and no longer needed hypoglycemic drugs. Therefore, the aforementioned patients were also excluded from the final analysis. Furthermore, ketoacidosis was not observed throughout the study.

UTI occurred in 21.1% of all patients, with female patients at higher risk (75% vs 25%; P = 0.002). There were no significant differences between the control group and the SGLT-2i group in terms of UTI incidence and hospitalization rates. Not surprisingly, HbA1c levels were significantly lower in the SGLT-2i group compared with the control group.

In terms of renal function, there was no significant difference in eGFR between the control group and the SGLT-2i group at 3, 6, and 12 months. However, the eGFR of patients in the SGLT-2i group decreased first and then increased, from the baseline of 71.94±18.17ml/min/1.73㎡ to 68.36±19.98ml/min/1.73㎡, and then rose to 72.96±16.62 ml/min/1.73㎡ ; while the control group has been showing a downward trend, from 73.20±19.72 ml/min/1.73㎡ to 65.36 ml/min/1.73㎡.

During the 12-month follow-up period, the levels of tacrolimus or tacrolimus plasma concentrations used in the control group and the SGLT-2i group were also relatively similar, with no significant difference. On this basis, the risk of acute rejection in the SGLT-2i group was lower than that in the control group (P = 0.040). Moreover, in the control group, the occurrence of acute rejection significantly decreased the patients' eGFR (P = 0.003), but not in the SGLT-2i group (P = 0.129).

Finally, in terms of proteinuria, the SGLT-2i group showed a significant decrease from 321 (45~2565) mg/d at baseline to 195 (51~1905) mg/d (P = 0.008), while the control group did not. significant change (P = 0.210). In addition, SGLT-2i was able to significantly reduce proteinuria levels in patients regardless of whether patients received SGLT-2i treatment immediately.

research discussion

Cardiorenal benefits of SGLT-2i have been demonstrated, but only in patients with autologous kidneys. For kidney transplant recipients, there are few related studies, only 9 related studies. A meta-analysis showed that SGLT-2i may slightly reduce blood pressure and stabilize renal function in kidney transplant recipients. There have also been studies showing that SGLT-2i appears to reduce body weight in kidney transplant recipients. A Korean study showed that SGLT-2i reduced the risk of all-cause mortality in kidney transplant recipients.

All of the above studies found a higher risk of urinary tract infection (UTI) among kidney transplant recipients treated with SGLT-2i. However, it should be noted that the risk of UTI is closely related to the kidney transplant itself. Studies have shown that the risk of UTI in kidney transplant recipients ranges from 6% to 86%, and previous studies mainly focused on the risk of UTI within 3 months after kidney transplantation but lacked regular assessment of UTI risk. In addition, researchers should also consider the relationship between the patient's medical history and the risk of UTI. In this study, some patients had a previous history of UTI and recurred UTI after kidney transplantation leading to urosepsis. Therefore, in terms of the risk and progress of UTIs, more research may be needed, and a stricter exclusion mechanism should be established.

In addition, studies of kidney transplant recipients are fraught with uncertainties, such as the optimal setting of baseline criteria, whether the efficacy and safety endpoints are consistent with autologous kidney patients, and whether the etiology of kidney disease affects the prognosis of transplanted kidneys. Therefore, the researchers believe that more similar studies are necessary to improve the prognosis of kidney transplant recipients.

Overall, SGLT-2i can safely and effectively reduce proteinuria levels in kidney transplant recipients, control blood sugar in patients, or be beneficial to the final prognosis of patients.

references:

1. Demir ME, Özler TE, Merhametsiz Ö, et al. The results of SGLT-2 inhibitors use in kidney transplantation: 1-year experiences from two centers. Int Urol Nephrol. 2023 Jun 8:1–11.