The quantifying relationship between the remission duration and the cardiovascular and kidney outcomes in the patients with primary nephrotic syndrome

Abstract Background Patients with persistent nephrotic-range proteinuria have a high risk of kidney dysfunction and cardiovascular events. Recently, the maintenance of proteinuria remission has been demonstrated to reduce the risk of kidney endpoint. However, the effect of remission duration on cardiovascular outcomes remains unclear. Methods This study enrolled 982 patients with primary nephrotic syndrome who had achieved clinical remission. Remission duration was defined as the maintenance time (months) of the first remission. Arteriosclerotic cardiovascular disease (ASCVD) and kidney dysfunction (ESKD or eGFR reduction >50%) were the endpoints. Survival curves, Cox regression models, restricted cubic spline analysis were used and the cutoff time points were determined. Results During the 38.3 months of follow-up, 161 (16.4%) patients developed ASCVD (51.3 per 1000 patient-years) and 52 (5.3%) patients developed kidney dysfunction (15.3 per 1000 patient-years). Multivariate analysis showed that remission duration was an independently protective factor to ASCVD, in which each one-year extension associated with a 15% reduction of the risk (HR, 0.854; 95% CI, 0.776 ∼ 0.940, p = .001). The initial time point was seven months for remission to present the protective effect to ASCVD and the maximum time point was 36 months. Remission duration was also an independently protective factor to kidney dysfunction. This effect was shown from the beginning of remission and reached the maximum at 26 months. Conclusions The maintenance of proteinuria remission was crucial for the improvement of cardiovascular and kidney outcomes in nephrotic syndrome patients.

[1]  B. Rovin,et al.  KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. , 2021, Kidney international.

[2]  A. Go,et al.  Primary Nephrotic Syndrome and Risks of ESKD, Cardiovascular Events, and Death: The Kaiser Permanente Nephrotic Syndrome Study , 2021, Journal of the American Society of Nephrology : JASN.

[3]  Yusuke Suzuki,et al.  Quantifying Duration of Proteinuria Remission and Association with Clinical Outcome in IgA Nephropathy. , 2020, Journal of the American Society of Nephrology : JASN.

[4]  Sue-Kyung Park,et al.  Mediation of the relationship between proteinuria and serum phosphate: Insight from the KNOW-CKD study , 2020, PloS one.

[5]  Daniel E Forman,et al.  2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. , 2019, Journal of the American College of Cardiology.

[6]  E. Petridou,et al.  Albuminuria and Cerebral Small Vessel Disease: A Systematic Review and Meta‐Analysis , 2018, Journal of the American Geriatrics Society.

[7]  D. Cattran,et al.  Membranous Nephropathy: Quantifying Remission Duration on Outcome. , 2017, Journal of the American Society of Nephrology : JASN.

[8]  Eva Dizin,et al.  Proteinuria Increases Plasma Phosphate by Altering Its Tubular Handling. , 2015, Journal of the American Society of Nephrology : JASN.

[9]  M. Woodward,et al.  Kidney measures beyond traditional risk factors for cardiovascular prediction: A collaborative meta-analysis , 2015, The lancet. Diabetes & endocrinology.

[10]  G. Bakris,et al.  Cardiovascular disease in CKD in 2014: New insights into cardiovascular risk factors and outcomes , 2015, Nature Reviews Nephrology.

[11]  M. Cushman,et al.  Association between urinary albumin excretion and coronary heart disease in black vs white adults. , 2013, JAMA.

[12]  S. Yusuf,et al.  Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. , 2011, Kidney international.

[13]  U. Dafni Landmark Analysis at the 25-Year Landmark Point , 2011, Circulation. Cardiovascular quality and outcomes.

[14]  C. Schmid,et al.  Evaluation of the Chronic Kidney Disease Epidemiology Collaboration equation for estimating the glomerular filtration rate in multiple ethnicities. , 2011, Kidney international.

[15]  G. Moneta,et al.  Major Lipids, Apolipoproteins, and Risk of Vascular Disease , 2010 .

[16]  J. Danesh,et al.  Major lipids, apolipoproteins, and risk of vascular disease. , 2009, JAMA.

[17]  D. Goldsmith,et al.  Nephrotic syndrome in adults , 2008, BMJ : British Medical Journal.

[18]  G. Navis,et al.  High Absolute Risks and Predictors of Venous and Arterial Thromboembolic Events in Patients With Nephrotic Syndrome: Results From a Large Retrospective Cohort Study , 2008, Circulation.

[19]  M. Weir Microalbuminuria and cardiovascular disease. , 2007, Clinical journal of the American Society of Nephrology : CJASN.

[20]  K. Borch-Johnsen,et al.  Albuminuria reflects widespread vascular damage , 1989, Diabetologia.

[21]  F. Locatelli,et al.  A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy. , 1995, Kidney international.

[22]  R. Hiatt,et al.  The increased risk of coronary heart disease associated with nephrotic syndrome. , 1993, Kidney international.

[23]  F. Locatelli,et al.  Remissions and relapses in idiopathic membranous nephropathy. , 1992, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[24]  C. Ponticelli,et al.  Long-term outcome of patients with membranous nephropathy after complete remission of proteinuria. , 1989, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.