Paradoxical Dapagliflozin Effect on Proteinuria in a Female Patient with Classic Fabry Disease First Literatura Report

Case Report

Austin J Nephrol Hypertens. 2023; 10(1): 1105.

Paradoxical Dapagliflozin Effect on Proteinuria in a Female Patient with Classic Fabry Disease First Literatura Report

Sebastián Jaurretche1,2*; Facundo Daminato3

¹Biophysics and Human Physiology, Medicine School, Instituto Universitario Italiano de Rosario, Santa Fe, Argentina

²Renal and páncreas transplant, Sanatorio Parque de Rosario, Santa Fe, Argentina

³Nephrology, Dialysis and Kidney Transplantation, Hospital Privado de Rosario, Santa Fe, Argentina

*Corresponding author: Jaurretche SInstituto Universitario Italiano de Rosario, Corrientes 2001, P.C: 2000. Rosario, Santa Fe, Argentina. Tel: 54-341-372841 Email: sebastianjaurretche@hotmail.com

Received: June 26, 2023 Accepted: July 31, 2023 Published: August 07, 2023

Abstract

A 75-year-old female patient, with “classic” Fabry disease (DEL 3&4 EXON, GLA gene) and severe multi-organic compromise (cardiac, brain, renal and peripheral nervous system) is presented. Patient presented treatment initiation criteria, and was a “classic” Fabry phenotype, for this reason, agalsidase-β was indicated. In addition, enalapril, were indicated. After the treatment start and to date, the patient presented: i) LVH stabilization; ii) brain damage stabilization; iii) stable eGFR and sustained improvement in proteinuria and; iv) pain improvement. In September 2022, due to the results of DAPA-CKD study, it was decided to start treatment with dapagliflozin to extend the renal protective effect; patient presented good tolerance to drug and no adverse effects were recorded. A slight decrease in eGFR was observed, but suspension was decided after 8 weeks due to increased proteinuria. Kidney disease is a major Fabry disease complication; it is more severe in the “classic” phenotype and males, although the “non-classic” Fabry phenotype and affected females may also present severe renal disease. Patients with Fabry disease and chronic kidney disease have a high risk of cardiovascular events, SGLT-2 inhibitor drugs have shown favorable effects on cardiovascular events in chronic kidney disease patients, both DBT and non-DBT. Multiple pathophysiological mechanisms have been described in Fabry nephropathy, none of them could explain, the reason why SGLT-2 blockade produced an increase in proteinuria in presented case.

Study limitation: short follow-up period of an isolated case.

Conclusion: SGLT-2 blockade effect should be analyzed in prospective studies, to define benefit or not in Fabry nephropathy.

Keywords: Fabry disease; Renal disease; Proteinuria; Dapagliflozin

Abbreviations: a-gal-A: a-Galactosidase A; CKD: Chronic Kidney Disease; DBT: Diabetes; ESRD: End-Stage Renal Disease; (DAPA) Dapagliflozin; eGFR: Estimated Glomefrular Filtration Rate; ERT: Enzyme Replacement Therapy; FD: Fabry Disease; LVH: Left Ventricular Hypertrophy; MNR: Magnetic Nuclear Resonance; PNS: Peripheral Nervous System; QST: Quantitative Sensory Testing; RAAS: Renin-Angiotensin-Aldosterone System; SGLT-2: Sodium-Glucose Co-Transporter 2; TGFP: Túbulo-Glomerular Feedback Pathway

Case Presentation

A 75-year-old female patient, with a history of heat and exercise intolerance, hypo-hidrosis, and recurrent febrile seizures accompanied by neuropathic pain in the extremities since childhood. FD was diagnosed by family screening, due to other affected patients in the family. The genetic test showed a pathogenic variant (DEL 3&4 EXON, GLA gene) causing the “classic” phenotype of Fabry disease (FD, OMIM #301500).

Complementary tests revealed severe organic involvement due to FD: i) cardiac: Left Ventricular Hypertrophy (LVH) on echocardiography and cardiac Magnetic Nuclear Resonance (MNR); ii) brain: brain MRN white matter lesions typical of FD; iii) renal: serum creatinine 0.8 mg/dl, estimated Glomefrular Filtration Rate (eGFR): 76.3 ml/min/m2, proteinuria: 800 mg/24 h and; iv) Peripheral Nervous System (PNS): Quantitative Sensory Testing (QST) with severe involvement of peripheral small fibers thin, also typical of FD. Cardiac, renal, brain, and PNS damage were attributed to DF after other causes had been ruled out. The GFR was estimated by the CKD-EPI equation and all determinations of urinary protein excretion were confirmed with a second sample. Since the moment of FD diagnosis, patient presented normal blood pressure, glycemia, and uric acid values during follow-up.

Patient presented treatment initiation criteria [10], and was a "classic" FD phenotype, for this reason, Enzyme Replacement Therapy (ERT) with agalsidase-β was indicated [1]. In addition, enalapril (at maximum tolerable doses), carbamazepine, acetylsalicylic acid, statins, and a cardio/nephro-protective diet were indicated.

After the treatment start and to date, the patient presented: i) LVH stabilization observed by echocardiography and cardiac MRN; ii) stabilization of brain damage: no new white matter lesions were observed in brain MRN; iii) stable eGFR (Figure 1) and sustained improvement in proteinuria (Figure 2) and; iv) pain improvement as evidenced by the SF-36 questionnaire.

Citation: Jaurretche S, Daminato F. Paradoxical Dapagliflozin Effect on Proteinuria in a Female Patient with Classic Fabry Disease First Literatura Report. Austin J Nephrol Hypertens. 2023; 10(1): 1105.