RESUMO
Nephrotic syndrome (NS) associated with renal artery stenosis is not widely recognized or investigated as a cause of the NS. The mechanisms are incompletely understood, but have largely focused on hemodynamic factors resulting in hyperfiltration injury-induced focal and segmental glomerulosclerosis (FSGS) in the nonstenosed kidney with sparing of the stenotic kidney protected from hemodynamic stress. However, separation of hemodynamic from circulating factors (such as angiotensin II) as the cause of the nephrosis remains difficult. We report a patient presenting with NS who was incidentally discovered to have high-grade bilateral renal artery stenosis from fibromuscular dysplasia. Kidney biopsy revealed FSGS. Proteinuria in our patient did not initially respond to angiotensin-converting enzyme inhibition (ACEI) and correction of stenoses with angioplasties. There was prompt response to steroid treatment. A brief relapse several months later (without associated hypertension) responded to ACEI alone. This is the first reported case of an association between fibromuscular dysplasia and steroid-responsive nephrotic syndrome due to FSGS. This may shed insight into the nature of podocyte injury in patients with high angiotensin states and suggest a possible role for activated renin-angiotensin-aldosterone system (RAAS) triggering an immune-mediated injury, rather than hemodynamic insult. Furthermore the lack of initial response to angioplasty and ACEI suggests that RAAS-activated injury may in some cases require more aggressive immune modulatory therapy with steroids over and above angiotensin inhibition alone. This case also highlights the importance of being aware of possible occult renovascular disease contributing to idiopathic NS with FSGS even when hypertension is only modest.
RESUMO
INTRODUCTION: Acute antibody-mediated rejection (AMR) in renal-transplant recipients is generally less responsive to conventional antirejection therapy and has a worse prognosis than acute cellular rejection. AREAS COVERED: This review provides a broad understanding of the pathogenesis of AMR, recent advances in its therapy, and future directions. Conventional therapeutic approaches to AMR have minimal impact on mature plasma cells, the major source of antibody production. Emerging therapies include bortezomib, a proteasome inhibitor, and eculizumab, an anti-C5 antibody. In several reports, bortezomib therapy resulted in prompt reversal of rejection, decreased titers of donor-specific antibodies (DSA), and improved renal allograft function. Eculizumab also reversed AMR and prevented its development in patients with high post-transplantation DSA levels. EXPERT OPINION: Despite the small sample size and lack of controls, these studies are encouraging, and although larger studies and long-term follow-up are needed, bortezomib and eculizumab may play a major future role in AMR therapy.
Assuntos
Rejeição de Enxerto/imunologia , Isoanticorpos/imunologia , Transplante de Rim/imunologia , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Formação de Anticorpos/efeitos dos fármacos , Ácidos Borônicos/farmacologia , Ácidos Borônicos/uso terapêutico , Bortezomib , Rejeição de Enxerto/prevenção & controle , Humanos , Prognóstico , Inibidores de Proteases/farmacologia , Inibidores de Proteases/uso terapêutico , Pirazinas/farmacologia , Pirazinas/uso terapêuticoRESUMO
Collapsing glomerulopathy (CG) is a variant of focal segmental glomerulosclerosis (FSGS) characterized histologically by prominent glomerular capillary tuft collapse with hypertrophy and hyperplasia of podocytes and tubulointerstitial damage. Patients usually present with heavy proteinuria and rapidly progressive renal failure. We report a patient who developed de novo CG with severe clinical manifestations including worsening renal failure and nephrotic syndrome within six months of receiving deceased donor kidney transplant. Secondary work-up was negative, and despite therapy with high-dose steroids and plasmapheresis, allograft function rapidly deteriorated with the need for dialysis. Theories about the pathogenesis of this entity as well as treatment modalities are discussed.