Properdin has an ascendancy over factor H regulation in complement-mediated renal tubular damage

BACKGROUND: Urinary (U)-complement components have been detected in patients with proteinuric renal diseases, and complement activation via the alternative pathway (AP) is believed to play a role in renal tubular damage. The present study aimed to examine the regulation of complement AP activation in patients with renal tubular damage by focusing on the balance between properdin (P) and factor H (fH). METHODS: In the in vivo studies, U concentrations of P, fH and membrane attack complex (MAC) were measured in patients with renal diseases using an enzyme-linked immunosorbent assay (ELISA), and their relationships with the clinical data were evaluated. In the in vitro studies, human proximal tubular epithelial cells (PTECs) were incubated with normal human serum (NHS), P-depleted serum (PDS), purified P and/or fH. Changes in cell morphology and phenotype were assessed by microscopy, real-time polymerase chain reaction (PCR), immunostaining and a cell viability assay. RESULTS: The U-P, fH and MAC concentrations were significantly higher in patients with renal disease than in normal controls and correlated with the U-protein and tubular damage markers. Furthermore, multivariate analysis revealed a relationship between P levels and tubular damage markers. There were no significant changes in morphology and mRNA expression in the AP components (P, fH, fB, C3, C5 and C9) after the addition of up to 25% NHS. Dose-dependent depositions of P or fH were observed after the addition of P or fH on PTECs. Depositions of P were not inhibited by fH in a mixture of a fixed concentration of P and a variable concentration of fH, and vice versa. Preincubation with the fixed concentration of P before the addition of NHS or PDS increased the depositions of P, C3 and MAC compared with incubation with intact NHS or intact PDS only; the depositions of C3 and MAC showed a serum-dependent trend. Preincubation with P before NHS addition significantly suppressed cell viability without causing morphological changes. CONCLUSIONS: In the pathogenesis of renal tubular damage, P can directly bind to PTECs and may accelerate AP activation by surpassing fH regulation

Importance of AST-120 (Kremezin®) Adherence in a Chronic Kidney Disease Patient with Diabetes

We report herein an adult case of chronic kidney disease (CKD) associated with diabetes. The patient had been treated with insulin injection for diabetes 10 years ago. At the time of his first visit to our division for further examinations, we diagnosed him as CKD: cause (C) diabetes; glomerular filtration rate (GFR) (G) G5 (estimated [e] GFR, 10.2 mL/min/1.73 m2; serum creatinine of 4.90 mg/dL); and albuminuria (A) A3 (2.62 g/gCr) by the Japanese Society of Nephrology (JSN) CGA classification. Because he had complained of severe constipation and kidney function, i.e., eGFR was not improved by previous medications, we added on a minimal dosage (2 g/day) of AST-120 (Kremezin®; ordinary dose 6 g/day). After 3 months of AST-120 therapy, eGFR was increased to 17.8 mL/min/1.73 m2 (serum creatinine of 2.90–2.72 mg/dL). Although the patient used some laxative products, he could not continue to take Kremezin and completely stopped 8 months after starting this drug. Kidney function then abruptly declined and progressed to end-stage kidney disease (ESKD). In June 2017, he was introduced to hemodialysis. It appears that the adherence of Kremezin is very important for inhibiting the progression to ESKD for patients with CKD with diabetes

Clinical and Laboratory Characteristics That Differentiate Hereditary Angioedema in 72 Patients with Angioedema

Background: Hereditary angioedema (HAE) is a rare but life-threatening condition that results from mutations in C1-inhibitor (C1-INH). Since distinguishing HAE from other causes of angioedema (AE) is a critical problem in emergencies, the objective of the present study was to clarify the differences between HAE and other forms of AE. Methods: Seventy-two patients with AE were enrolled in this study. The medical history and laboratory data of patients with HAE at the first visit were compared to those with other types of AE. Results: Subjects included 23 patients with HAE, 33 with mast cell-mediated AE, 5 with drug-induced AE and 11 with idiopathic AE. The average age of HAE onset (19.5±8.0 years old) was significantly lower than in other groups. A family history of AE was noted in 82.6% of HAE patients, which was significantly higher than other groups. Swelling affecting the extremities and gastrointestinal (GI) tract was observed in the majority (60 to 80%) of HAE patients. Life threatening laryngeal edema was observed in 30.4% of HAE patients. In 95.6% of HAE patients serum levels of C4 were less than the lower limit of the normal range. In our subjects, the sensitivity and specificity of low C4 for HAE were 95.6% and 93.8%, respectively. Conclusions: Early onset of AE, positive family history, recurrent AE in the extremities and GI tract, and suffocation are distinctive characteristics of HAE. A low serum level of C4 is a useful marker for making a differential diagnosis of HAE