BACKGROUND One of the common late sequela in patients with end-stage renal disease(ESRD)is the calcium phosphate disorder leading to chronic hypercalcemia and hyperphosphatemia causing the precipitation of calcium sal...BACKGROUND One of the common late sequela in patients with end-stage renal disease(ESRD)is the calcium phosphate disorder leading to chronic hypercalcemia and hyperphosphatemia causing the precipitation of calcium salt in soft tissues.Tumoral calcinosis is an extremely rare clinical manifestation of cyst-like soft tissue deposits in different periarticular regions in patients with ESRD and is characterized by extensive calcium salt containing space-consuming painful lesions.The treatment of ESRD patients with tumoral calcinosis manifestation involves an increase in or switching of renal replacement therapy regimes and the adjustment of oral medication with the goal of improved hypercalcemia and hyperphosphatemia.CASE SUMMARY We describe a 40-year-old woman with ESRD secondary to IgA-nephritis and severe bilateral manifestation of tumoral calcinosis associated with hypercalcemia,hyperphosphatemia and tertiary hyperparathyroidism.The patient was on continuous ambulatory peritoneal dialysis and treatment with vitamin D analogues.After switching her to a daily hemodialysis schedule and adjusting the medical treatment,the patient experienced a significant dissolution of her soft tissue calcifications within a couple of weeks.Complete remission was achieved 11 mo after the initial diagnosis.CONCLUSION Reduced patient compliance and subsequent insufficiency of dialysis regime quality contribute to the aggravation of calcium phosphate disorder in a patient with ESRD leading to the manifestation of tumoral calcinosis.However,the improvement of the treatment strategy and reinforcement of patient compliance enabled complete remission of this rare disease entity.展开更多
Immune-mediated nephritis is a leading cause of acute kidney injury and chronic kidney disease.While the role of B cells and antibodies has been extensively investigated in the past,the advent of immune-checkpoint inh...Immune-mediated nephritis is a leading cause of acute kidney injury and chronic kidney disease.While the role of B cells and antibodies has been extensively investigated in the past,the advent of immune-checkpoint inhibitors has led to a reappraisal of the role of T cells in renal immunology.However,it remains elusive how T cells with specificity for renal autoantigens are activated and participate in immune-mediated nephritis.Here,we followed the fate and function of pathogen-activated autoreactive CD8 T cells that are specific for a renal autoantigen.We demonstrate that recently activated splenic CD8 T cells developed a hybrid phenotype in the context of renal autoantigen cross-presentation,combining hallmarks of activation and T cell dysfunction.While circulating memory T cells rapidly disappeared,tissue-resident memory T cells emerged and persisted within the kidney,orchestrating immune-mediated nephritis.Notably,T cells infiltrating kidneys of patients with interstitial nephritis also expressed key markers of tissue residency.This study unveils how a tissue-specific immune response can dissociate from its systemic counterpart driving a compartmentalized immune response in the kidneys of mice and man.Consequently,targeting tissue-resident memory T cells emerges as a promising strategy to control immune-mediated kidney disease.展开更多
文摘BACKGROUND One of the common late sequela in patients with end-stage renal disease(ESRD)is the calcium phosphate disorder leading to chronic hypercalcemia and hyperphosphatemia causing the precipitation of calcium salt in soft tissues.Tumoral calcinosis is an extremely rare clinical manifestation of cyst-like soft tissue deposits in different periarticular regions in patients with ESRD and is characterized by extensive calcium salt containing space-consuming painful lesions.The treatment of ESRD patients with tumoral calcinosis manifestation involves an increase in or switching of renal replacement therapy regimes and the adjustment of oral medication with the goal of improved hypercalcemia and hyperphosphatemia.CASE SUMMARY We describe a 40-year-old woman with ESRD secondary to IgA-nephritis and severe bilateral manifestation of tumoral calcinosis associated with hypercalcemia,hyperphosphatemia and tertiary hyperparathyroidism.The patient was on continuous ambulatory peritoneal dialysis and treatment with vitamin D analogues.After switching her to a daily hemodialysis schedule and adjusting the medical treatment,the patient experienced a significant dissolution of her soft tissue calcifications within a couple of weeks.Complete remission was achieved 11 mo after the initial diagnosis.CONCLUSION Reduced patient compliance and subsequent insufficiency of dialysis regime quality contribute to the aggravation of calcium phosphate disorder in a patient with ESRD leading to the manifestation of tumoral calcinosis.However,the improvement of the treatment strategy and reinforcement of patient compliance enabled complete remission of this rare disease entity.
基金supported by grants from the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation),Project-ID 431984000-CRC 1453 to FA,CS,and YT,Project-ID 256073931-CRC 1160 to S,CS,and YT,Project-IDs 491676693-TRR359,and 322977937-GRK 2344 to S,Project-IDs 241702976,438496892,501370692,and 386793560-CRU 329 to CS,the Else Kröner-Fresenius-Stiftung(2016_Kolleg.03),Bad Homburg,Germany to FA,the Berta-Ottenstein-Programme for Clinician Scientists,Faculty of Medicine,University of Freiburg,Germany to FA,the Research Commission of the Faculty of Medicine,University of Freiburg,Germany to FA,the MOTI-VATE Doctoral College,Faculty of Medicine,University of Freiburg,Germany to LK,the Wilhelm Sander-Stiftung(Wilhelm Sander Foundation)to CS.The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.Open Access funding enabled and organized by Projekt DEAL.
文摘Immune-mediated nephritis is a leading cause of acute kidney injury and chronic kidney disease.While the role of B cells and antibodies has been extensively investigated in the past,the advent of immune-checkpoint inhibitors has led to a reappraisal of the role of T cells in renal immunology.However,it remains elusive how T cells with specificity for renal autoantigens are activated and participate in immune-mediated nephritis.Here,we followed the fate and function of pathogen-activated autoreactive CD8 T cells that are specific for a renal autoantigen.We demonstrate that recently activated splenic CD8 T cells developed a hybrid phenotype in the context of renal autoantigen cross-presentation,combining hallmarks of activation and T cell dysfunction.While circulating memory T cells rapidly disappeared,tissue-resident memory T cells emerged and persisted within the kidney,orchestrating immune-mediated nephritis.Notably,T cells infiltrating kidneys of patients with interstitial nephritis also expressed key markers of tissue residency.This study unveils how a tissue-specific immune response can dissociate from its systemic counterpart driving a compartmentalized immune response in the kidneys of mice and man.Consequently,targeting tissue-resident memory T cells emerges as a promising strategy to control immune-mediated kidney disease.
