Complement C3 and incident hospitalization due to chronic kidney disease: a population-based cohort study

Abstract

Background Circulating C3 has been associated with diabetes and hypertension, which are the leading causes of chronic kidney disease (CKD). C3 activation is considered to contribute to several renal diseases. Here we examined whether elevated C3 concentration is associated with hospitalization due to CKD in the general population, and whether this relationship is mediated by factors such as diabetes and hypertension. Methods Baseline plasma C3 was quantified in 4552 participants, without previous hospital admission due to CKD, from the Malmö Diet and Cancer cohort study. Incidence of first hospitalization due to CKD (main diagnosis) was investigated in relation to C3 levels using Cox proportional hazards regression models after a mean follow-up of 19.2 ± 4.16 years. Traditional risk factors of CKD including diabetes, blood pressure, C-reactive protein and baseline renal function were considered in adjustments and sensitivity analyses. Results During the follow-up period, 94 subjects were admitted to hospital due to CKD. After multivariate adjustment, the hazard ratios (95% confidence interval) for hospitalization from CKD across quartiles of C3 were 1.00 (reference), 1.68 (0.69, 4.13), 2.71 (1.15, 6.39), and 3.16 (1.36, 7.34) ( p for trend = 0.003). Results were generally consistent across different sensitivity analyses. Conclusions These findings indicate that C3 is associated with incidence of first hospitalization due to CKD in the general population. The observed relationship cannot be entirely attributed to hyperglycemia and hypertension.

Predicting COVID-19—Comorbidity Pathway Crosstalk-Based Targets and Drugs: Towards Personalized COVID-19 Management

“…Therefore, IFN-α treatment for COVID-19 patients with CKDs needs further evaluation. Our second pathway-based identified target, C3, is upregulated in various CKDs [100,101] and COVID-19 [102]. Decreased C3 levels in serum are associated with poor prognosis for COVID-19 patients [103].…”

Gut Mycobiome in Patients With Chronic Kidney Disease Was Altered and Associated With Immunological Profiles

“…Kidneys contribute to immune homeostasis, and the components of the immune system mediate renal disease and play a central role in the progression of CKD ( 9 ). For instance, serum complement 3 (C3), as partially originated from the kidney, was not only increased in CKD patients but also associated with a decreased estimated glomerular filtration rate (eGFR) ( 10 ). Additionally, an elevated serum C-reactive protein (CRP) level has been linked to CKD ( 11 – 13 ).…”

Complement in Renal Disease as a Potential Contributor to Arterial Hypertension

“…Additionally, patients with therapy-resistant arterial hypertension had significantly higher C3 plasma levels compared to patients with controlled hypertension [11]. In contrast, in a population-based cohort study elevated plasma C3 was associated with increased incidence of first hospitalization due to CKD but independent of BP [12]. However, the latter study was restricted to the investigation of C3 plasma levels, whilst local expression of complement factors and complement activation were not investigated.…”

“…The majority of patients with CKD present with elevated blood pressure (BP) [9], but the exact pathogenesis of hypertension is unknown. Several studies are available describing an association of plasma C3 and hypertension [10,11], while another study could not confirm these observations [12]. In the rat DOCAsalt hypertension model, glomerular C3 deposition was increased in DOCA-salt rats and decreased by antihypertensive therapy, that is, spironolactone and triple therapy with hydrochlorothiazide, reserpine, and hydralazine [13].…”