Effectiveness of immunosuppressive therapy for nephrotic syndrome in a patient with late-onset Fabry disease: a case report and literature review

Fujisawa, Hironobu; Nakayama, Yosuke; Nakao, Shoichiro; Yamamoto, Ryo; Kurokawa, Yuka; Nakamura, Nao; Nagata, Akihisa; Tsukimura, Takahiro; Togawa, Tadayasu; Sakuraba, Hitoshi; Fukami, Kei

doi:10.1186/s12882-019-1657-7

Cited by 11 publications

(13 citation statements)

References 20 publications

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“…Patient 3 did not show any typical symptoms of FD. Patient 4 exhibited nephrotic syndrome, with completely diminished proteinuria due to prednisolone administration, as recently reported [ 19 ]. FD prevalence in male patients with CKD Stages 1–5 [0.48% (2/419)] was much higher than in those with CKD Stage 5D [0.06% (1/1703)].…”

Section: Resultssupporting

confidence: 64%

Screening of Fabry disease in patients with chronic kidney disease in Japan

Nagata

Nasu

Kaida

et al. 2021

Nephrology Dialysis Transplantation

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Background Fabry disease (FD), an X-linked lysosomal storage disorder caused by a deficiency in alfa-galactosidase A (α-Gal A) activity due to mutations in the GLA gene, has a prevalence of 0–1.69% in patients undergoing haemodialysis; however, its prevalence in patients with chronic kidney disease (CKD) Stages 1–5 is unknown. Methods Serum α-Gal A activity analysis and direct sequencing of GLA were used to screen for FD in 2122 male patients with CKD, including 1703 patients with CKD Stage 5D and 419 with CKD Stages 1–5. The correlation between serum α-Gal A activity and confounding factors in patients with CKD Stages 1–5 was evaluated. Results FD prevalence rates in patients with CKD Stage 5D and CKD Stages 1–5 were 0.06% (1/1703) and 0.48% (2/419), respectively. A patient with CKD Stage 5D exhibited a novel GLA mutation, p.Met208Arg, whereas two patients with CKD Stages 1–5 had c.370delG and p.Met296Ile. p. Met208Arg caused moderate structural changes in the molecular surface region near the substituted amino acid residue but did not affect the catalytic residues Asp170 and Asp231 in α-Gal A. Serum α-Gal A activity in patients with CKD Stages 1–5 was inversely correlated with age (P < 0.0001) but directly correlated with estimated glomerular filtration rate (P < 0.0001). Conclusions FD prevalence was much higher in male patients with CKD Stages 1–5 than in those with CKD Stage 5D. FD screening in patients with CKD Stages 1–5 may improve patient survival, decreasing the number of patients with CKD Stage 5D.

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Section: Resultssupporting

confidence: 64%

Screening of Fabry disease in patients with chronic kidney disease in Japan

Nagata

Nasu

Kaida

et al. 2021

Nephrology Dialysis Transplantation

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“…Another reported therapy targeting sphingolipids is enzyme replacement therapy (ERT), which currently represents a standard of therapy for Fabry disease, or lipid storage disease. In a recent case report of a Japanese man with FSGS and low activity of alpha-galactosidase (with mutation in M296I), ERT in association with immunotherapy with steroids and cyclosporine A [ 111 ] improved proteinuria levels, while in another case report of an obese male with histologically proven FSGS and low activity of alpha-galactosidase (with missense mutation in R310Q) no improvement in renal function despite ERT was described [ 112 ]. Thus, while ERT may be a very promising therapy for the treatment of lipid storage disease, its therapeutic potential in the treatment of patients with FSGS warrants further investigation.…”

Section: Targeting Sphingolipids In Dkd and Fsgsmentioning

confidence: 99%

Role of Sphingolipid Signaling in Glomerular Diseases: Focus on DKD and FSGS

Mitrofanova

Drexler

Merscher

et al. 2020

Journal of Cellular Signaling

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Sphingolipids are well-recognized as major players in the pathogenesis of many human diseases, including chronic kidney disease. The kidney is a very sensitive organ to alterations in sphingolipid metabolism. The critical issues to be addressed in this review relate to the role of sphingolipids and enzymes involved in sphingolipid metabolism in the pathogenesis of glomerular diseases with a special focus on podocytes, a key cellular component of the glomerular filtration barrier. Among several sphingolipids, we will highlight the role of ceramide, sphingosine, sphingosine-1-phosphate and ceramide-1-phosphate. Additionally, we will summarize the current knowledge with regard to the use of sphingolipids as therapeutic agents for the treatment of podocyte injury in kidney disease.

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“…in chronic kidney disease patients who were not on dialysis was found to be 0.2% by Yeniçerio glu (0.4% in male, 0.0% in female) [19]. Although FD can coexist with several renal diseases, including IgA nephropathy, lupus nephritis, membranous GN, and crescentic nephritis, nephrotic syndrome as the first clinical clue of Fabry-related kidney damage remains rare, with only nine cases reported (shown in Table 2), of which five were male and four were female [20][21][22][23][24][25][26][27]. Zarate et al reported a 16-year-old male patient with minimal change nephrotic syndrome and underlying FD in 2010, who was responded well to steroid and ERT treatment, eventually his proteinuria became undetectable [26].…”

Section: Discussionmentioning

confidence: 99%

“…Research by Linthorst reported that among patients who underwent renal replacement therapy, 0.33% of male patients and 0.10% of females had FD [ 18 ]; and the prevalence of FD in chronic kidney disease patients who were not on dialysis was found to be 0.2% by Yeniçerioğlu (0.4% in male, 0.0% in female) [ 19 ]. Although FD can coexist with several renal diseases, including IgA nephropathy, lupus nephritis, membranous GN, and crescentic nephritis, nephrotic syndrome as the first clinical clue of Fabry-related kidney damage remains rare, with only nine cases reported (shown in Table 2 ), of which five were male and four were female [ 20–27 ]. Zarate et al.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, Fujisawa et al. reported a 67-year-old male patient with late onset FD who also suffered from nephrotic syndrome probably due to FSGS or MCD, he finally achieved complete remission after immunosuppressive (steroids and cyclosporine A) therapy and ERT [ 20 ]. Although it is not fully understood why FD patients are prone to secondary nephrotic syndrome, there is convincing evidence that FD may contribute in some way to cause progressive podocyte damage with foot process effacement and podocyte loss, that ultimately leads to proteinuria and even glomerulosclerosis, which may be related to the persistent accumulation of toxic glycosphingolipid in the podocytes, specific or unspecific signal pathway (e.g.…”

Section: Discussionmentioning

confidence: 99%

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Sudden onset of nephrotic syndrome in an asymptomatic Fabry patient: a case report

et al. 2020

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Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the mutation of the GLA gene, encoding the a-galactosidase, which is responsible for the catabolism of neutral glycosphingolipids. Microalbuminuria or low-grade proteinuria, and continuously progressive renal failure are common manifestations in FD males. However, sudden onset of nephrotic syndrome in FD, is rarely reported. Case report: A 32-year-old Chinese man was admitted to our hospital because of sudden onset of generalized edema due to nephrotic syndrome. He denied hypohidrosis, nocturia, and any history of episodic hand or foot pain. A few scattered angiokeratoma can be found on the low back skin on examination. Except for the similar locating pattern of angiokeratoma, no evident abnormality was found in the laboratory work up and physical examination of his younger brother. The patient was diagnosed with FD companying with minimal change disease by renal biopsy. Genetic analysis on our patient and his sibling revealed a nonsense GLA gene variant (c.707G > A, p.Trp236 Ã), which has been previously reported in FD. Immunotherapy alone (steroids and tacrolimus), but without enzyme replacement therapy, much improved the massive proteinuria. Follow up to date, his 24-h urine protein is stable at about 0.5 g, and renal function keeps normal. Conclusion: Sudden onset of nephrotic syndrome, although rare, may occur in FD, even as the primary renal manifestation, but this usually suggests additional renal disease. Immunosuppressive treatment should be considered in such FD patient companying with nephrotic syndrome.

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Effectiveness of immunosuppressive therapy for nephrotic syndrome in a patient with late-onset Fabry disease: a case report and literature review

Cited by 11 publications

References 20 publications

Screening of Fabry disease in patients with chronic kidney disease in Japan

Screening of Fabry disease in patients with chronic kidney disease in Japan

Role of Sphingolipid Signaling in Glomerular Diseases: Focus on DKD and FSGS

Sudden onset of nephrotic syndrome in an asymptomatic Fabry patient: a case report

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