EFFICACY AND SAFETY OF DAPAGLIFLOZIN IN PRESERVING RESIDUAL URESIS IN PATIENTS STARTING PERITONEAL DIALYSIS AT THE HOSPITAL REGIONAL ISSSTE PUEBLA

The treatment of end-stage chronic kidney disease represents a significant clinical and economic challenge in Mexico. Patients starting renal support therapy, such as peritoneal dialysis (PD), face high morbidity and mortality, primarily from cardiovascular causes. In this context, residual uresis, defined as a urine volume greater than 200 ml per 24 hours that a patient produces independently despite being on dialysis, emerges as a crucial prognostic factor. Residual uresis contributes to the elimination of uremic toxins, improves fluid and electrolyte balance, fluid control, lowers blood pressure, and reduces the required dialysis dose, resulting in improved quality of life and survival.

Historically, dialysis patients have been excluded from clinical trials with new drugs, limiting their therapeutic options. This is the case with sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin. Although these drugs have demonstrated substantial cardiorenal benefits in patients with less advanced CKD, their use in patients starting dialysis is limited and under-researched.

The primary objective of this study was to determine whether dapagliflozin is safe and confers a benefit in preserving residual uresis in patients starting peritoneal dialysis, comparing them with a control group that did not receive the drug, during a three-month follow-up period in the Nephrology Department of the HRP ISSSTE Puebla. The underlying hypothesis was that dapagliflozin, through its mechanisms of glucosuria and natriuresis, could help maintain and even increase urine production, thus mitigating the complications associated with the loss of residual kidney function.

Study Design: A quasi-experimental, prospective, longitudinal, comparative, randomized, open-label study was conducted.

Study Population: A cohort of 32 patients starting peritoneal dialysis was recruited at the ISSSTE Puebla HRP. Patients were randomly assigned to two homogeneous groups:

• Intervention Group (Cases, n=16): They received dapagliflozin 10 mg orally every 24 hours for three months, in addition to their standard PD treatment.

• Control Group (n=16): They received only standard PD treatment without dapagliflozin.

Inclusion and Exclusion Criteria: Patients over 18 years of age with end-stage renal disease starting peritoneal dialysis, who agreed to enter the study and signed informed consent, were included. Patients with active infections, decompensated liver disease, history of hemodialysis, allergy to dapagliflozin or previous use of the drug, pregnancy, and/or breastfeeding were excluded.

Variables and Measurement: The primary variable was the volume of residual uresis (in ml/24 hours), measured at five time points: before the start of dialysis, during hospitalization, and at the first, second, and third months of follow-up. Secondary variables included estimated glomerular filtration rate (eGFR), hemoglobin levels, erythropoietin dose used, and the incidence of adverse effects (peritonitis and infections).

Statistical Analysis: Chi-square tests were used for categorical variables, and independent samples t tests and Mann-Whitney U tests were used to compare the means and medians of residual uresis and other continuous variables between groups

Baseline Population Characteristics:

Both groups were comparable at baseline in terms of demographic and clinical characteristics. The mean age was 57 years, males predominated (59.4%), and type 2 diabetes was the primary etiology of CKD in 81.3% of patients. There were no significant differences in baseline erythropoietin use between the groups.

Primary Outcome: 

Significant Increase in Residual Uresis

The analysis revealed a statistically significant difference in residual uresis favoring the dapagliflozin group at all measurement points.

• During Hospitalization: The dapagliflozin group had a mean uresis of 715.38 ± 356.5 ml, compared to 377.56 ± 367.20 ml in the control group. This represents a mean difference of +337.81 ml (p=0.003) in favor of the intervention group from the early stages.

• At Month 1: The gap widened. Mean uresis in the case group was 947.50 ± 588.98 ml, while in the control group it was 409.63 ± 428.74 ml, with a mean difference of +537.88 ml (p=0.003).

• At Month 2: The difference peaked. The dapagliflozin group averaged 1038.13 ± 547.63 ml, versus 357.00 ± 465.08 ml in the control group, representing a mean difference of +681.13 ml (p=0.001).

• At Month 3 (End of Follow-up): Superiority was maintained. The intervention group had a uresis of 1015.63 ± 657.31 ml, compared to 465.44 ± 540.07 ml in the control group, with a mean difference of +550.19 ml (p=0.007).

Nonparametric analysis confirmed these findings, reporting a median between-group difference of +585 ml (95% CI: 190–880 ml) in favor of the dapagliflozin group at month 3. These results strongly demonstrate that dapagliflozin not only preserves but significantly increases residual uresis in patients starting peritoneal dialysis.

Secondary Outcomes:

Glomerular Filtration Rate 

A modest and statistically significant improvement was observed only in the first month in the dapagliflozin group (+2.45 ml/min/1.73 m², p=0.013). This difference lost statistical significance in the second and third months, suggesting that the main effect was not on stable eGFR, but on urinary flow.

Hemoglobin and Erythropoietin Use: A trend toward increased hemoglobin was identified in the intervention group at month three (12.03 g/dL vs. 10.58 g/dL), with a difference of +1.45 g/dL, although this difference did not reach statistical significance (p=0.096). There were no significant differences in the dose of erythropoietin used.

Safety and Tolerance: The safety profile of dapagliflozin was excellent. Only one case of peritonitis was recorded in the intervention group (6.25% vs. 0% in the control group, p=1.000), with no significant association. No urinary tract or respiratory infections, episodes of severe hypoglycemia, or ketoacidosis were reported. Drug tolerance was 100%, with no discontinuations due to adverse effects.

This study demonstrates that the administration of dapagliflozin 10 mg daily is an effective and safe intervention for preserving and significantly increasing residual uresis in patients with end-stage chronic kidney disease starting peritoneal dialysis. The primary endpoint was clearly and strongly met, with a sustained benefit observed over the three months of follow-up without an increase in adverse effects, particularly infections with adequate tolerability.