The Association Of Serum Phosphorus With Chronic Kidney Disease Progression

Chronic kidney disease(CKD)has become a major worldwide public health issue due to its increasing prevalence,poor outcomes,and high cost of treatment for kidney failure.Early diagnosis and proper management of CKD and its risk factors are crucial for slowing the progression of the disease.Despite a large and convincing body of evidence suggesting a robust association of CKD progression with hypertension and proteinuria,a growing body of evidence has suggested a link between serum phosphorous levels and the progression of CKD.Hyperphosphatemia is associated with an increased rate of hyperparathyroidism,mineral and bone disorder(MBD),vascular calcifications,cardiovascular events,and mortality,and it has been demonstrated to be an independent risk factor for the progression of CKD.However,some studies have failed to reveal such a relationship between serum phosphorous levels and the progression of CKD.Notably,most of the existing data concerning the relationship between serum phosphorus concentrations and the prognosis of CKD did not include a sufficiently long follow-up period,and comparisons between different underlying kidney diseases have remained unclear.The association of serum phosphorus with the progression of kidney disease in specific CKD patient subgroups remains to be elucidated.Some studies have shown differences in phosphorus metabolism in patients with diabetic nephropathy versus non-diabetic nephropathy;however,the relationship between serum phosphorus and CKD progression is unclear.We utilized CKD-MBD(chronc kidney disease mineral and bone disorder)cohort patients with stage 2-4 CKD were treated at our division from December 2013 to July 2015 to investigated the incidence,risk factors of hyperphosphatemia,the relationship between serum phosphorus and change of eGFR in patients with chronic kidney disease.We utilized another cohort from January 2003 that were treated at our center,including patients with biopsy-positive IgA nephropathy,membranous nephropathy and diabetic nephropathy with stage 1-4 CKD.We clerify the relationship between serum phosphorus and CKD progression,adding more evidence for early intervention of mineral and bone disorder to slow the progression of CKD.Part 1.The incidence and risk factors of hyperphosphatemia in patients with chronic kidney diseaseObjective:To investigated the incidence,risk factors of hyperphosphatemia in patients with CKDMethods:A total of 1014 patients with stage 2-5 CKD from December 2013 to July 2015 were retrospectively reviewed.We investigated the incidence of hyperphosphatemia and use univariate and multivariate regression to analysis risk factors of hyperphosphatemia.Results:A total of 1014 patients were were recruited,653(64.4%)were male and 361(35.6%)were female,with an average age of 45.7±12.4years.Common cause of CKD in this study was IgA nephropathy,diabetic nephropathy and lupus nephritis.Serum phosphorus was negatively correlated with eGFR,age,BMI,serum albumin and was positively correlated with uric acid,iPTH.The incidence of hyperphosphatemia in stage 2 CKD,stage 3a CKD,stage 3b CKD,stage 4 CKD,stage 5 CKD was:5.0%,9.8%,14.3%,22.5%,53.7%respectively.univariate analyses indicated that male,young patients,diabetes,eGFR decline,uric acid,iPTH,lower 1,25(OH)2D3,urinary protein and lower total carbon dioxide is the risk factor hyperphosphatemia;the risk of the hyperphosphatemia was 2.89-fold(95%CI,1.97,4.25)higher in patients with diabetic nephropathy compared with the risk of those with chronic glomerulonephritis.Multivariate analyses indicated that:young patients,diabetes,eGFR decline,uric acid is the risk factor hyperphosphatemia;the risk of the hyperphosphatemia was 2.94 times(95%CI,1.50,5.78)higher in patients with diabetic nephropathy than patients with non-diabetic nephropathy.eGFR thresholds for detecting hyperphosphatemia with 90%sensitivity were 54.9,40.2ml/min per 1.73 m2 for diabetic nephropathy and chronic glomerulonephritis respectively..Conclusions:Diabetes,eGFR decline,young patients,uric acid is the risk factor hyperphosphatemia;earlier onset and greater severity of hyperphosphatemia are found in patients with diabetic nephropathy.Part 2.The association of serum phosphorus with short-term change of renal function in patients with chronic kidney diseaseObjective:Whether higher serum phosphorus is associated with the progression of CKD is not well established.The aim of this study was to determine the effect of serum phosphorus level on kidney function decline in patients with CKD.Methods:The change of eGFR and the relationship between serum phosphorus and change of eGFR in patients with stage 2-4 CKD were retrospectively investigated,using spearman correlation analysis to evaluate the relationship between serum phosphorus and the rate of decline in eGFR.The patients were classified into four groups based on the quartile of serum phosphorus,included as a categorical variable in the multivariate cox regression to evaluate the effects of serum phosphorus level on the prognosis of CKD.Results:The average annual decline value and decline rate of eGFR were 2.2 ml/min per 1.73 m2 and 7.2%.While patients with diabetic nephropathy showed higher value and more rapid decline rate of eGFR,reaching up to 9.8 ml/min per 1.73 m2 and 19.1%,respectively.Serum phosphorus levels was positively correlated with the decline of eGFR(r=0.163,P<0.001),especially in diabetic nephropathy patients(r=0.253,P<0.001).Univariate cox regression indicated that the risk of end point was2.47(P<0.001)times higher in the highest quartile of phosphorus(?1.33mmol/l)than the lowest quartile(<1.05mmol/l).Multivariate cox regression analysis indicated that participants in the highest quartile of serum phosphorus had a 2.08-fold higher risk of kidney function decline of CKD compared with those in the lowest quartile.Conclusions:Serum phosphorus level is related to the decline of eGFR.Higher serum phosphorus levels is an independent risk factor for the decline of eGFR in patients with chronic kidney disease.Part 3.The association of serum phosphorus with progression of chronic kidney diseaseObjective:Whether higher serum phosphorus is associated with the progression of CKD is not well elucidated.To analyze the effect of serum phosphorus level on the prognosis of diabetic nephropathy and non-diabetic nephropathy.Methods:The clinical and laboratory data of diabetic nephropathy,IgA nephropathy,and membranous nephropathy with stage 1-4 CKD were retrospectively investigated,the four cohorts were classified into four groups based on the quartile of serum phosphorus,included as a categorical variable in the multivariate cox regression to evaluate the effects of serum phosphorus level on the prognosis of CKD.Results:In all patients,univariate and multivariate Cox regression indicated that the risk of end point was 5.29(P<0.001)and2.59(P<0.001)times higher in the highest quartile of phosphorus than the lowest quartile.In diabetic nephropathy patients,univariate and multivariate Cox regression revealed that the risk of end point was 5.99(P<0.001)and 2.88(P=0.024)times higher in the highest quartile of phosphorus.While in non-diabetic nephropathy,multivariate Cox regression showed no relation between phosphorus level and progression of CKD.Conclusions:Hyperphosphatemia is an independent risk factor for progression of disease in diabetic nephropathy.Analysising of serum phosphorus level on the prognosis of patients with CKD should consider the effect of the underlying disease.