Cryoglobulinemic vasculitis and glomerulonephritis: concerns in clinical practice

Objective:Cryoglobulinemia often causes systemic vasculitis,thereby damaging to skin and internal organs including kidneys,even life-threatening.This review aimed to introduce the advances in understanding,detection,and treatment of this disease in recent years,with a particular concern to clinical practice.Data sources:All the data in this review were from the English or Chinese literature in the PubMed and China National Knowledge Infrastructure databases as of March 2019.Study selection:This review selected important original articles,meaningful reviews,and some reports on cryoglobulinemia published in recent years and in history,as well as the guidelines for treatment of underlying diseases which lead to cryoglobulinemia.Results:Diagnosis of cryoglobulinemia relies on serum cryoglobulin test,in which to ensure that the blood sample temperature is not less than 37℃ in the entire pre-analysis phase is the key to avoid false negative results.Cryoglobulinemic vasculitis (Cryo Vas),including cryoglobulinemic glomerulonephritis (Cryo GN),usually occurs in types Ⅱ and Ⅲ mixed cryoglobulinemia,and can also be seen in type Ⅰ cryoglobulinemia caused by monoclonal IgG3 or IgG1.Skin purpura,positive serum rheumatoid factor,and decreased serum levels of C4 and C3 are important clues for prompting types Ⅱ and Ⅲ Cryo Vas.Renal biopsy is an important means for diagnosis of Cryo GN,while membranous proliferative GN is the most common pathological type of Cryo GN.In recent years,great advances have been made in the treatment of Cryo Vas and its underlying diseases,and this review has briefly introduced these advances.Conclusions:Laboratory examinations of serum cryoglobulins urgently need standardization.The recent advances in the diagnosis and treatment of Cryo Vas and GN need to be popularized among the clinicians in related disciplines.

Purinergic 2X7Receptor is Involved in the Podocyte Damage of Obesity-Related Glomerulopathy via Activating Nucleotide-Binding and Oligomerization Domain-Like Receptor Protein 3 Inflammasome

Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R).This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation ofNLRP3 inflammasome.Methods:A mouse model of ORG was established by high-fat diet feeding.The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079).The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3,ASC,and caspase-1,as well as the podocyte-associated molecules including nephrin,podocin,and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Westem blot analysis,respectively.Results:The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo,which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules.Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression ofpodocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro,and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.Conclusions:P2X7R could trigger the activation ofNLRP3 inflammasome,and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.

Renal Parenchymal Malakoplakia Presenting as Acute Renal Failure in a Young Woman

To the Editor： A 26-year-old woman was admitted to the hospital because of a 4-day history of fever （39.3℃）, accompanied by red urine, urinary frequency, odynuria, urgency, bilateral flank pain, and 2 days of anuria. The patient had no medical history and never received medical examinations. In the recent 1 month,