Nephrotic syndrome: pathophysiology and consequences.

In patients with kidney disease, nephrotic syndrome can lead to several complications including progressive kidney dysfunction. Proteinuria may lead to the formation of cellular or fibrous crescents with reciprocal development of rapidly progressive glomerulonephritis or focal glomerulosclerosis. Proteinuria may also cause overload and dysfunction of tubular epithelial cells, eventually resulting in tubular atrophy and interstitial fibrosis. Hypoalbuminemia is usually associated with increased risk of mortality and kidney dysfunction. Dyslipidemia may increase the risk of atherosclerotic complications, cause podocyte dysfunction and contribute to vascular thrombosis. Urinary loss of anticoagulants and overproduction of coagulation factors may facilitate a hypercoagulable state. Edema, hypogammaglobulinemia, loss of complement factors, and immunosuppressive therapy can favor infection. Treatment of these complications may reduce their impact on the severity of NS. Nephrotic syndrome is a kidney disorder that can worsen the quality of life and increase the risk of kidney disease progression.

Primary membranous nephropathy: an endless story.

Primary membranous nephropathy (PMN) is an autoimmune disease caused by the attack of autoantibodies against podocyte antigens leading to the in situ production of immune complexes. However, the etiology is unknown and the pathogenesis is still far from being completely elucidated. MN is prevalently idiopathic or primary, but in about 20-30% of cases it is secondary to chronic infections, systemic diseases, exposure to drugs, or malignancy. The differentiation between primary and secondary MN may be difficult, particularly when MN precedes signs and symptoms of the original disease, as in some cases of cancer or systemic lupus erythematosus. The natural course of PMN is variable, but in the long term 40-60% of patients with nephrotic syndrome progress to end-stage renal disease (ESRD) or die from thrombotic or cardiovascular events. PMN is a treatable disease. Patients with asymptomatic proteinuria should receive supportive care. Immunosuppressive treatments should be given to patients with nephrotic syndrome or risk of progression. The most frequently adopted treatments rely on cyclical therapy alternating steroids with a cytotoxic agent every other month, i.e., rituximab at different doses, or calcineurin inhibitors plus low-dose steroids. A good rate of response may be obtained but relapses can occur. Randomized controlled trials, with adequate size, long-term follow-up, and fair definition of endpoints are needed to identify treatment with the best therapeutic index.

Improvement of Erdheim-Chester disease-related renal failure after treatment with anakinra

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by infiltrates of lipid-laden CD68+/CD1- histiocytes, affecting heart, lungs, central nervous system, and bones. Kidney and adjacent structures can also be affected, leading to renal failure in about 30% of cases. The diagnosis is challenging, and treatment is generally based on administration of interferon-alpha (IFNalpha), but preliminary results also showed the therapeutic efficacy of anakinra, an antagonist of the receptor of interleukin-1 (IL-1). We report the case of an elderly patient with ECD and severe involvement of the heart and kidneys who was successfully treated with anakinra.