Niemann-Pick disease is a rare autosomal recessive lysosomal storage disorder caused by acid sphingomyelinase deficiency, leading to sphingomyelin accumulation in multiple organs. Type B is considered the less severe form and is typically characterized by visceral involvement, whereas renal manifestations are exceptionally reported. We describe the case of a 36-year-old White male patient with Niemann-Pick disease type B who developed end-stage renal disease secondary to uncommon renal involvement. Kidney biopsy demonstrated foamy podocytes and vacuolated tubular epithelial cells consistent with changes related to Niemann-Pick disease, associated with focal segmental glomerulosclerosis of the collapsing variant and severe vascular lesions compatible with thrombotic microangiopathy. The patient was treated with conventional hemodialysis and remained clinically stable after 7 years of follow-up. Given the absence of neurological impairment and well-controlled systemic involvement, a comprehensive pretransplant evaluation was performed. Despite the multiorgan nature of Niemann-Pick disease type B and potential cardiovascular risks, the patient was considered eligible for kidney transplant and was placed on the waiting list. This case highlights the rarity of renal involvement in Niemann-Pick disease type B and emphasizes the need for individualized assessment when considering kidney transplant in patients with lysosomal storage disorders.

Key words : Acid sphingomyelinase deficiency, Kidney biopsy, Lysosomal storage disorder

Introduction
Niemann-Pick disease (NPD) is a lysosomal storage disorder characterized by pathological lipid accumulation and infiltration of tissues by foam cells due to a primary deficiency of acid sphingomyelinase (ASM) activity. Affected individuals typically present with hepatosplenomegaly, pulmonary dysfunction, and depending on the disease subtype may also exhibit central nervous system involvement. Type B NPD is the less severe form of the disease. However, these patients exhibit broad phenotypic variability, with the onset of disease occurring anywhere from early childhood through adulthood.¹ Renal involvement in NPD is rare,² and unlike hepatic or pulmonary involvement where organ transplant has been described as a therapeutic option renal transplant has, to our knowledge, never been reported.^3,4 This observation therefore raises questions regarding the feasibility of renal transplant and clinical relevance in patients with advanced NPD-related renal impairment.

Case Report
A 36-year-old White male patient, with no relevant family history, was referred for chronic kidney failure at the age of 29 years. His history included unexplained cervical lymphadenopathy and splenomegaly. Upon admission, evaluation revealed hypertension, hepatosplenomegaly, and impaired left ventricular systolic function (ejection fraction ≈45%). Urinalysis showed mild proteinuria (2+) without hematuria. Laboratory test results showed elevated serum creatinine and marked hypertriglyceridemia, whereas liver function test results remained within reference limits (Table 1). Renal biopsy demonstrated complex lesions, that is, focal segmental sclerosis of the collapsing type with enlarged and some foamy podocytes; severe interstitial changes; foam cells in tubular epithelium and arterial walls; vacuolated tubular epithelial cells; and pronounced vascular damage characterized by features of thrombotic microangiopathy. Immunofluorescence revealed C3 deposits in 2 glomeruli. Suspicion of NPD type B was confirmed by measurement of residual ASM activity in peripheral blood leukocytes (0.16 U, reference range 0.42-0.92 U). The patient progressed to end-stage renal disease, which was managed with conventional hemodialysis. Over a follow-up of 7 years, he remained clinically stable. While being considered for renal transplant, a thoracic computed tomography scan was performed in response to radiography findings of interstitial lung abnormalities; the computed tomography scan showed nonspecific interstitial pneumonia. The patient was asymptomatic with unremarkable spirometry findings, and annual radiology and spirometry surveillance was recommended. Cardiovascular assessment showed a regular sinus rhythm on electrocardiography with evidence of left ventricular hypertrophy and no repolarization abnormalities. Transthoracic echocardiography demonstrated preserved left ventricular ejection fraction (60%) with left ventricular hypertrophy. According to the cardiology evaluation, there was no indication for coronary angiography. Neurological examination was unremarkable except for divergent strabismus, and brain magnetic resonance imaging showed no abnormalities. The remainder of the pretransplant evaluation did not show any additional significant findings (Table 2).

Discussion
This case illustrates that NPD, although primarily known for hepatic, splenic, pulmonary, or hematological involvement, can also lead to severe renal damage and end-stage kidney disease, a feature seldom described in the literature. The current literature on therapeutic interventions for NPD type B is limited, with no consensus on the treatment of ASM deficiency. Hematopoietic stem cell transplant has been demonstrated to reduce liver and spleen size, as well as treat pulmonary involvement; however, the complications associated with this method have been well documented.^5,6 Although some reports describe improvement in visceral manifestations, organ transplant remains a high-risk therapeutic intervention. In NPD, solid-organ transplant has predominantly involved liver or lung procedures, particularly in cases of ASM deficiency (type A and type B). Reported outcomes, however, are highly variable, with frequent complications such as early graft dysfunction, persistent metabolic abnormalities, and recurrent infections.^3,4 In our patient, assessment for kidney transplant eligibility was performed, taking into account his comorbidities and overall systemic disease profile. The absence of neurological deficits and presence of well-controlled systemic manifestations supported his candidacy to receive a kidney transplant. Nevertheless, the multisystem nature of NPD type B, including potential cardiovascular involvement, required a comprehensive pretransplant evaluation. Although renal transplant has not been systematically evaluated in NPD, the parallels with Fabry disease provide a useful framework for consideration. Both disorders are lysosomal storage diseases characterized by progressive intracellular lipid accumulation secondary to enzymatic deficiency, with potential multisystem involvement including the kidneys. Long-term studies in Fabry disease showed graft survival comparable with other etiologies of end-stage kidney disease and no significant recurrence within the allograft.⁷ Methodologically, these data support the feasibility of renal transplant in selected patients with NPD who meet standard clinical criteria. Transplant in our patient presented several challenges, including the risk of disease recurrence in the graft, as NPD is a systemic condition, and the need for tailored immunosuppression due to his underlying metabolic disorder. Notably, in a previously reported lung transplant case, the patient survived only 29 days after transplant, and the autopsy revealed NPD-like changes in the donor lungs, suggesting recurrence of the disease.³ Given the rarity of transplant in NPD and the absence of disease-specific transplant guidelines, an individualized approach was necessary. After evaluation by a multidisciplinary team, our patient was deemed eligible for kidney transplant and was placed on the wait list, with careful consideration of potential risks.

Conclusions
This case highlights the rare renal involvement in NPD type B and underscores the importance of individualized transplant evaluations, given the potential systemic risks related to multiorgan involvement, disease recurrence in the graft, and long-term cardiovascular and metabolic complications associated with lysosomal storage disorders.