Persistent proteinuria and dyslipidemia increase the risk of progressive chronic kidney disease in lupus erythematosus

Abstract

Advances in immunotherapy have improved survival of patients with systemic lupus erythematosus who now face an increasing burden of chronic diseases including that of the kidney. As systemic inflammation is also thought to contribute directly to the progression of chronic kidney disease (CKD), we assessed this risk in patients with lupus, with and without a diagnosis of nephritis, and also identified modifiable risk factors. Accordingly, we enrolled 631 patients (predominantly Caucasian), of whom 504 were diagnosed with lupus within the first year and followed them an average of 11 years. Despite the presence of a chronic inflammatory disease, the rate of decline in renal function of 238 patients without nephritis was similar to that described for non-lupus patient cohorts. Progressive loss of kidney function developed exclusively in patients with lupus nephritis who had persistent proteinuria and dyslipidemia, although only six required dialysis or transplantation. The mortality rate was 16% with half of the deaths attributable to sepsis or cancer. Thus, despite the presence of a systemic inflammatory disease, the risk of progressive CKD in this lupus cohort was relatively low in the absence of nephritis. Hence, as in idiopathic glomerular disease, persistent proteinuria and dyslipidemia (modifiable risks) are the major factors for CKD progression in lupus patients with renal involvement.

Efficacy and toxicity of treatments for nephritis in a series of consecutive lupus patients

“…The role of sustained proteinuria as a prognostic marker in SLE nephritis has been recently proposed [57,58]: our results suggest that this parameter independently predicts the risk of late or non-remission in populations of patients receiving heterogeneous treatments.…”

Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis

“…Partial renal response, defined as ≥50% reduction in proteinuria to subnephrotic levels and normal or near-normal GFR, should be achieved preferably by 6 months and no later than 12 months following treatment initiation 9 33–35. Improvement includes any reduction in proteinuria and normalisation or stabilisation of GFR.…”

“…Such outcomes, however, are not frequent and may occur late in the course of LN. Intermediate outcome measures, such as renal response and flares, occurring in the majority of patients within the first 2 years after treatment initiation, correlate with hard outcomes in studies with long-term follow-up and are commonly used as endpoints in trials 9 33–35 37–39 44. Correlation does not guarantee surrogacy of these outcomes for all patients, some of whom may still have hard outcomes diverging from their intermediate outcomes.…”

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“…The addition of as Cr ≤ 1.0 mg/dl to the 24H-P<0.8 g/day target increased the specificity (87%) but lowered the sensitivity (78%) for the prediction of good renal prognosis at 12 months, suggesting that the degree of proteinuria is of utmost importance for the development of CKD. Reich et al, showed that the time-averaged proteinuria was the predictor of the rate of progression of renal function decline [59], with higher decline for higher proteinuria: subjects with 24H-P 0-1 g/day losing 1.15 ± 5.37 ml/min per 1.73 mt 2 per year of GFR vs subjects with 24H-P > 2.0 g/day losing 6.68 ± 14.6ml/min per 1. highlighted the importance of persistent proteinuria and indicated that in the short term, proteinuria is a predictor of doubling creatinine and developing CKD. Recently, Touma et al, showed that the development of long-term renal outcomes (e.g.…”