Generalized atherosclerosis sparing the transplanted kidney in Schimke disease

Abstract

Schimke-immuno-osseous dysplasia (SIOD) is a multisystem disorder caused by a mutation of the chromatin remodeling protein. The main clinical findings are spondyloepiphyseal dysplasia with disproportional growth deficiency, nephrotic syndrome with focal and segmental glomerulosclerosis, and defective cellular immunity. Transitory ischemic attacks due to vaso-occlusive processes are still an untreatable and life-limiting complication in patients with SIOD. The underlying pathophysiology of vaso-occlusive processes in SIOD is unclear. We report the clinical and pathological findings of the eldest published patient with the severe form of SIOD, who died at the age of 23 years due to pulmonary hypertension with subsequent right heart failure. The autopsy revealed a severe generalized atherosclerosis including the brain, heart, and pulmonary arteries. However, the kidney that was transplanted at the age of 5 years showed a good graft function without glomerular sclerosis and with only minimal nephrosclerosis on histology. Thus, the absence of severe vaso-occlusive processes in the transplanted organ and in the severely atherosclerotic host may indicate that the vaso-occlusive processes in SIOD are not caused by post-transplant cardiovascular morbidity such as arterial hypertension and hyperlipidemia. Instead, vascular factors of the host such as endothelial dysfunction may explain the pathophysiology of atherosclerosis in SIOD.

Schimke immuno-osseous dysplasia: a clinicopathological correlation

“…Glomerular disease did not recur in the renal allograft of SD600 or SD840, supporting a cell-autonomous mechanism. Also, Lücke et al 24 recently showed that atherosclerosis did not recur within the renal allograft during 18 years after transplantation.…”

Schimke‐immuno‐osseous dysplasia: New mutation with weak genotype–phenotype correlation in siblings

“…In contrast to these earlier generalizations, we recently presented a patient with all the symptoms of severe SIOD who reached the age of 23 years [Lü cke et al, 2004]. In addition, Lou et al [2002], published a 20-year-old woman with the molecular and clinical criteria for the severe form of SIOD.…”

Şiddetli seyirli Schimke immün-kemik displazili olgu sunumu

“…Our patient had all her ischemic attacks in August and September, but she had no heath intolerance. It has been reported that diffuse and progressive atherosclerosis is the basic cause of cerebrovascular events in patients with Schimke immuno-osseous dysplasia (7,10). Although hypertension, hyperlipidemia, proteinuria and ESRD which were also found in our patient are significant risk factors for atherosclerosis, symptoms of cerebrovascular ischemia have been observed in patients with SIOD even before renal disease started (13).…”

“…High blood pressure in our patient was controlled with enalapril and amlodipine. Interestingly, it was reported that glomerulosclerosis did not recur after renal transplantation in this patient (9,10).…”