Renal Flare as a Predictor of Incident and Progressive CKD in Patients with Lupus Nephritis

Abstract

SummaryBackground and objectives Renal flares are common in lupus nephritis. The impact of flares on the development of CKD in lupus nephritis was examined.Design, setting, participants, & measurements A retrospective analysis of prospectively collected data from the Ohio Systemic Lupus Erythematosus (SLE) Study was conducted to determine if renal flares predispose to new CKD or progression of preexisting CKD. Patients in the Ohio SLE Study were followed from 2001 to 2009, with a median follow-up of 6 years. For this analysis, patients with biopsy-proven lupus nephritis and at least 3 years of follow-up were included (n=56). Frequency and duration of renal flares were compared between patients who never developed CKD (n=29) and patients who developed new CKD (n=12) and between patients with preexisting but stable CKD (n=7) and patients who progressed (n=8). Groups were also combined into good (no CKD and stable CKD) or poor (new CKD and progressive CKD) for analysis.Results The new CKD group had more renal flares per year compared with the no CKD group (median=0.56 flares/yr [range=0-2] versus median=0 flares/yr [range=0-1.4]; P,0.001). Additionally, the poor outcome group had more renal flares per year compared with the good outcome group (median=0.50 flares/yr [range=0-2] versus median=0 flares/yr [range=0-1.4]; P,0.001). New or progressive CKD was not preferentially associated with nephritic compared with proteinuric renal flares. Logistic regression showed that spending more than 30% of time in renal flare (odds ratio, 20; 95% confidence interval, 4.6 to 91.3; P,0.001) and age.35 years (odds ratio, 69; 95% confidence interval, 6.3 to 753.6; P,0.001) were independent predictors of the combined end point of developing new or progressive CKD. All four subjects over 35 years of age that spent over 30% of time in renal flare had a poor outcome. ConclusionIn patients with lupus nephritis, the relative duration of renal flare is an independent predictor of incident and progressive CKD.

Long‐term renal outcomes in multi‐ethnic Southeast Asians with lupus nephritis: a retrospective cohort study

“…Renal flares increase cumulative injury to the renal parenchyma, thus increasing the likelihood of chronic damage. The Ohio SLE study found that renal flare for more than 30% of the follow‐up duration was independently associated with developing new or progressive CKD (odds ratio 20, 95% confidence interval 4.6–91.3) . It is thus important to minimise occurrence and duration of flares with adequate immunosuppressive therapy, balanced against the risk of immunosuppressant‐related complications such as infections …”

Update on Lupus Nephritis

“…For example, kidney biopsies after induction therapy with high-dose corticosteroids and cyclophosphamide or MMF generally show an increase in chronic damage, even in those patients who achieved a complete clinical remission to induction alone (57). LN flare is also an important risk factor for CKD and CKD progression (76) and flares may occur in 25% of patients (77,78). These outcome statistics suggest there is considerable room for improvement in the treatment of LN.…”

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“…Proteinuria induces structural and functional changes in different kidney cells; with more protein traffic to the proximal/distal collecting ducts and subsequent inflammation and fibrosis, and progressive loss of kidney function [45]. Proteinuria produces active glomerular inflammation and can be considered a manifestation of an Acute Kidney Injury (AKI), which is a recognized risk factor for CKD [46]. Touma et al, demonstrated that proteinuria is a marker for the long term prognosis of kidney function [47].…”

“…In SLE, nephritic and proteinuric flares (with increase in 24H-P>1.0 g/day) of LN contribute equally to poor kidney outcomes [46], with heavy proteinuria resulting in a higher risk for CKD and end stage CKD with requirement for dialysis [57]. Fiehn et al, compared the renal prognosis of patients with LN in 2 groups: from 1980-1989 (group 1) and 1990-2000 (group 2), showing less histological signs of chronicity and proteinuria for group 2.…”

“…During an active phase of the disease, there is a diffuse vascular damage secondary to endothelial dysfunction and apoptosis, been present in the kidney and in other systems as well [44], with the secondary development of abnormalities in the glomerular slit diaphragm and a pro-inflammatory vascular state that stimulates atherosclerosis [65]. Persistent proteinuria can accelerate the decline of the GFR and is a manifestation and a risk factor for Chronic Kidney Disease (CKD) [46]. Proteinuria and CKD are known risk factors for Cardiovascular Disease (CVD), as shown by different cohorts followed for more than 15 years [66].…”