Nintedanib is a small-molecule tyrosine kinase inhibitor (TKI) approved for idiopathic pulmonary fibrosis (IPF) and systemic sclerosis–associated interstitial lung disease. Although nephrotoxicity from nintedanib is uncommon, case reports have linked it to nephrotic syndrome (NS), acute kidney injury (AKI), thrombotic microangiopathy (TMA) and, less frequently, anti–glomerular basement membrane nephritis. Optimal management of nintedanib-associated glomerular disease has not been established.
This report describes a patient who developed significant glomerular disease after prolonged nintedanib exposure and the clinical course after drug withdrawal and supportive therapies, including the later introduction of a sodium–glucose cotransporter 2 inhibitor (SGLT2i).
A 69-year-old man with a clinical history of IPF, hypertension, diabetes and underlying chronic kidney disease developed persistent nephrotic syndrome and progressive renal dysfunction 16 months after starting nintedanib. The abstract reports that proteinuria remained in the nephrotic range despite discontinuation of nintedanib and intensification of renin–angiotensin system inhibition together with mineralocorticoid receptor blockade. Exact laboratory values, proteinuria quantification, eGFR numbers and additional timeline details were not provided in the abstract.
Subsequently, dapagliflozin, an SGLT2 inhibitor, was started. The authors report a temporal association between initiation of the SGLT2i and a gradual, sustained reduction in proteinuria, culminating in partial remission while the patient’s estimated glomerular filtration rate was preserved.
Renal biopsy demonstrated features of glomerular endothelial injury with microangiopathic characteristics. In addition, there was secondary collapsing focal segmental glomerulosclerosis (collapsing FSGS) alongside background changes consistent with diabetic kidney disease. These combined histologic findings support an endothelial injury process with subsequent podocyte/segmental sclerosis changes rather than a primary podocytopathy alone.
The biopsy findings align with prior case reports documenting nintedanib-associated glomerular microangiopathy and other TKI-related glomerular lesions.
After the diagnosis, nintedanib was discontinued. Supportive care measures included intensification of renin–angiotensin system blockade and addition or intensification of mineralocorticoid receptor blockade. Despite these measures, nephrotic-range proteinuria persisted.
Dapagliflozin was then initiated. The abstract states that initiation of the SGLT2 inhibitor was temporally associated with a gradual and sustained decline in proteinuria and achievement of partial remission, while eGFR was preserved. The authors frame this outcome as an association; causality cannot be inferred from the single case and the abstract does not provide numerical trends, exact durations, or other adjunctive interventions that could have influenced the course.
TKIs such as nintedanib can produce nephrotoxic effects through mechanisms that include endothelial injury, microangiopathy and direct effects on glomerular cells. The combination of microangiopathic endothelial injury with secondary collapsing FSGS in this case suggests an initial endothelial insult with subsequent podocyte and segmental sclerosis changes.
Therapeutic options for TKI-associated glomerular disease are limited beyond drug cessation and supportive measures (blood pressure control, RAS inhibition, mineralocorticoid receptor antagonism). The authors report that SGLT2 inhibition in this patient coincided with meaningful and sustained proteinuria reduction and preserved renal function. They propose that SGLT2 inhibitors may have a role as an adjunctive therapy in selected patients with TKI-associated glomerular injury and underlying chronic kidney disease, but emphasize that this observation requires systematic evaluation.
It is important to note the limitations inherent to a single case report: temporal association does not prove therapeutic effect, the abstract does not report baseline and follow-up quantitative data, and potential confounders or coincident interventions were not detailed in the abstract. The authors reference prior reports of nintedanib-induced renal TMA and other glomerular complications to situate this case within emerging clinical experience.
This case report describes nintedanib-associated glomerular endothelial injury with secondary collapsing FSGS in a patient with IPF, hypertension, diabetes and chronic kidney disease. After stopping nintedanib and instituting guideline-based supportive therapy, persistent nephrotic-range proteinuria remained. Subsequent initiation of the SGLT2 inhibitor dapagliflozin was temporally associated with a gradual, sustained reduction in proteinuria and partial remission while preserving eGFR. The authors identify this as the first reported instance of such an association and suggest that SGLT2 inhibition may be a potential adjunctive therapeutic option that merits further systematic study. Detailed quantitative outcomes and longer-term follow-up were not reported in the abstract.
References cited in the full report include earlier case reports of nintedanib-associated renal microangiopathy and related glomerular lesions; the abstract lists additional references but full text review is required for comprehensive data extraction.