SGLT2 inhibitors show weight benefits and stable potassium in kidney transplant recipients, but a lab quirk inflates albuminuria readings

Sodium-glucose cotransporter-2 inhibitors, better known as SGLT2 inhibitors, have become one of the most celebrated drug stories in modern nephrology. Originally designed to lower blood sugar, they now carry proven protection for kidneys and the cardiovascular system in chronic kidney disease. Yet one large group of patients has remained largely on the sidelines of this success: people living with a transplanted kidney. Kidney transplant recipients were excluded from the landmark trials that established these drugs, leaving clinicians without solid evidence on whether the benefits and safety record seen in chronic kidney disease translate to the transplant setting. A new retrospective study from University Hospital Münster, published in Frontiers in Transplantation, offers one of the most detailed real-world pictures to date, and its findings carry practical messages for both patients and the laboratories that monitor them.

The research team, led by Lino Henkel and Stefan Reuter, matched 100 kidney transplant recipients taking an SGLT2 inhibitor with 100 comparable recipients who were not taking the drugs. The matching used a mathematical procedure, the Hungarian algorithm, that paired patients based on age at transplantation, time since transplantation, and sex. The investigators then tracked body mass index, HbA1c, urine albumin-to-creatinine ratio, estimated glomerular filtration rate, serum potassium, blood pressure, and a battery of safety outcomes at six and twelve months. Roughly two-thirds of the treated group had diabetes, reflecting how these drugs are prescribed in routine care, where they are typically offered first to patients with the most pressing metabolic problems.

The clearest signal to emerge concerned body weight. Body mass index fell in the treated group, from 27.6 to 27.2 kilograms per square meter over a year, while it rose slightly in the control group, from 26.1 to 26.3. The adjusted between-group difference across follow-up remained statistically significant, meaning the weight trajectory diverged in a way that could not be explained by baseline differences alone. HbA1c, the standard marker of long-term blood sugar control, also appeared to improve in the treated group, dropping from 6.9 percent to around 6.5 to 6.7 percent, but this apparent benefit dissolved once the researchers applied multivariable adjustment. The authors are careful on this point: because the treated patients started with higher body weight and worse glycemic control, some of the observed change may reflect regression to the mean rather than a true drug effect.

Blood pressure, often cited as a secondary benefit of SGLT2 inhibition in chronic kidney disease, stayed essentially flat in both groups throughout the study. This mirrors what a recent placebo-controlled trial in transplant recipients found, and it suggests that the metabolic changes observed here are not simply a byproduct of lowered blood pressure. The authors also note that they cannot distinguish between weight loss driven by fluid and volume changes and weight loss driven by genuine metabolic effects, a distinction that would require body composition measurements their retrospective design could not capture.

On the question that matters most to transplant physicians, graft function, the results are more nuanced. Estimated glomerular filtration rate, calculated with the CKD-EPI formula, dipped in the treated group during the first six months, from about 49.8 to 47.7 milliliters per minute per 1.73 square meters, while remaining stable in controls. This early decline is a well-known hemodynamic signature of SGLT2 inhibition, caused by the drug restoring tubuloglomerular feedback and reducing pressure inside the kidney’s filtering units. By twelve months, the gap had narrowed and was no longer statistically significant. Urine albumin-to-creatinine ratio, a key marker of kidney damage, showed no meaningful difference between groups at either time point. The authors emphasize that their data neither confirm nor rule out a renoprotective effect; they simply show that one year is too short and the cohort too small to detect one if it exists.

Potassium, a persistent worry in transplant medicine, emerged as a relative bright spot. Serum potassium remained stable over the follow-up period, and hyperkalemia, defined as a level above 5.0 millimoles per liter, was associated with lower graft function but not with SGLT2 inhibitor treatment. The group-by-time interaction for hyperkalemia was far from significant, and patient-level analysis confirmed that each unit increase in estimated glomerular filtration rate was associated with lower odds of hyperkalemia. Notably, more patients in the treated group started a renin-angiotensin-aldosterone system inhibitor during follow-up, but the authors interpret this as confounding by indication rather than a drug effect, since these patients had more cardiovascular risk factors to begin with. Persistence with existing RAAS blockade did not differ between groups.

Safety outcomes were reassuring across the board. There were no statistically detectable differences in urinary tract infections, hospital admissions, cardiovascular events, or marked declines in graft function. Only one case of genital mycosis occurred in the treated group. Two graft losses happened in the treated arm, but both were attributed to pneumonia with septic shock and antibody-mediated rejection rather than to the drug itself. Twelve patients stopped the SGLT2 inhibitor during the year, mostly because of mild urinary infections, a pattern the authors describe as cautious real-world prescribing in a population where long-term experience remains limited. No deaths occurred in either group during the observation window.

Perhaps the most practically useful finding is a laboratory quirk with real clinical consequences. SGLT2 inhibitors cause glucosuria, the spilling of glucose into the urine, and glucose interferes with the Jaffé method, the older colorimetric assay for urinary creatinine that reacts with alkaline picrate. The researchers collected 128 urine samples from treated patients, all with glucosuria above 55 millimoles per liter, and measured creatinine in parallel using both the Jaffé method and a more specific enzymatic assay. The Jaffé readings came out consistently lower, inflating the calculated albumin-to-creatinine ratio by roughly 8.5 percent. In four of the 128 samples, this analytical artifact pushed the result into a higher albuminuria stage, three moving from A1 to A2 and one from A2 to A3. While the effect is statistically robust, its clinical impact was limited, but the authors argue that enzymatic assays should be preferred where available, and that the assay type should always be reported alongside the ratio to avoid misinterpretation in transplant follow-up, where small changes in albuminuria can influence decisions about RAAS blockade or the need for further graft assessment.

The study has clear limitations. It is retrospective, single-center, and modest in size, and the treated patients carried a heavier metabolic burden at baseline, with more diabetes, higher HbA1c, higher body mass index, and more frequent RAAS inhibitor use. The matching algorithm did not account for these differences, leaving residual confounding by indication that the authors acknowledge candidly. They also note that potassium was only measured at three time points, so transient episodes between visits may have been missed. Patients with chronic antibody-mediated rejection were excluded from the principal albuminuria analysis because that condition can dramatically distort the ratio, though a sensitivity analysis including them produced materially unchanged results.

Taken together, the findings support cautious use of SGLT2 inhibitors in selected stable kidney transplant recipients, particularly those with metabolic indications, while tempering expectations about rapid renal benefit. The consistent weight reduction and stable potassium profile are encouraging, and the absence of new safety signals in a real-world cohort is meaningful given how different transplant physiology is from native kidney disease. What remains unresolved is the longer-term question of whether these drugs can slow graft decline the way they slow decline in chronic kidney disease, a question that will require larger prospective trials with extended follow-up. For now, the study adds a carefully documented chapter to a rapidly evolving story, and it sends a practical reminder that the tools used to measure kidney health can themselves be quietly reshaped by the treatments being tested.

Subject of Research: Effects and safety of SGLT2 inhibitor therapy in kidney transplant recipients, including metabolic changes, potassium-related outcomes, and assay interference in albuminuria measurement

Article Title: SGLT2 inhibitors in kidney transplant recipients: metabolic changes, potassium-related safety and implications for albuminuria assessment

Article References: Henkel, L., Ingmanns, L., Westphal, F., Menke, A. F., Pavenstädt, H., Jehn, U., Boeckel, G. R., & Reuter, S. (2026). SGLT2 inhibitors in kidney transplant recipients: metabolic changes, potassium-related safety and implications for albuminuria assessment. Frontiers in Transplantation, 5, Article 1927374. https://doi.org/10.3389/frtra.2026.1927374

Image Credits: AI Generated

DOI: 10.3389/frtra.2026.1927374

Keywords: SGLT2 inhibitors, kidney transplant recipients, albuminuria, glomerular filtration rate, hyperkalemia, body mass index, HbA1c, RAAS inhibitors, urinary creatinine, Jaffé method, transplant safety, chronic kidney disease