| PartⅠ The association between serum cystatin C and residual renal function in peritoneal dialysis patientsBackground:Serum cystatin C is a kind of endogenous marker which can be used to reflect the kidney function.However,it is unknown whether the serum cystatin C can be used to reflect the residual renal function(RRF)of peritoneal dialysis(PD)patients.Objective:This study aims to probe the association between serum cystatin C and RRF in peritoneal dialysis PD patients.Methods:This was a retrospective research and we recruited PD patients who received PD treatment with a good condition from October 2019 to March 2020 in PD center of our Hospital.We collected demographic data of PD patients.PD patient’s laboratory parameters were also collected.We used particle-enhanced turbidimetric immunoassay method to test cystatin C level.We used Baxter Adequest 2.0 software to calculate dialysis adequacy indexes including urea clearance index(Kt/V)and creatinine clearance rate(Ccr).The average of 24h urea nitrogen and creatinine clearance rate was seen as RRF of PD patients.The correlations of serum cystatin C and various indexes were analyzed by Pearson or Spearman correlation analysis.RRF<2 ml/min/1.73m2 was taken as a significant RRF loss.We used receiver operating characteristic(ROC)curve to analyze the diagnostic value of creatinine,cystatin C and urea nitrogen.Areas under the curve(AUC)were also compared by DeLong test.The sensitivity and specificity at the cut-off value were compared.All the PD patients were divided into three groups according to the RRF level,group A:RRF=0ml/min/1.73m2,group B:0ml/min/1.73m2<RRF<2ml/min/1.73m2,group C:RRF≥2ml/min/1.73m2.Serum cystatin C,creatinine and urea levels were compared among the three groups.We used the multivariate linear regression analysis to analyze influencing factor of serum cystatin C.We also calculate the average of PD fluid/serum cystatin C and the clearance of cystatin C by PD.Results:A total of 141 PD patients were enrolled,71 males(50.35%)and 70 females(49.65%),with an average serum cystatin C level(7.86±1.40)mg/L.RRF level was 1.16(0.00,2.57)ml/min/1.73m2.Correlation analysis showed that serum cystatin C was not related with gender,age,height,weight or body surface area(BSA)(P>0.05).Serum creatinine was negatively related with age and gender(male 1,female 2),and positively associated with height and BSA(P<0.05).Serum urea nitrogen was negatively related with gender(male 1,female 2),and positively associated with height,weight and BSA(P<0.05).Serum creatinine and cystatin C were negatively correlated with RRF,RRF Kt/V and RRF Ccr(P<0.05),while serum urea was not correlated with RRF,RRF Kt/V or RRF Ccr(P>0.05).The correlation coefficient between serum cystatin C and RRF was-0.785.The correlation coefficient between serum creatinine and RRF was-0.457.Serum cystatin C was more relevant to RRF.ROC curve showed that both serum creatinine and cystatin C could judge the RRF status(P<0.05),serum urea could not judge the RRF status(P>0.05).The AUC of serum cystatin C was larger(0.893 vs 0.757,P<0.001).The sensitivity and specificity of serum cystatin C at the cut-off value were higher than those of serum creatinine(P<0.05).All the PD patients were divided into three groups based on the RRF value.The levels of serum cystatin C and creatinine were different(P<0.05),and the level of serum urea was not different among the three groups(P=0.927).Further pairwise comparison was taken by least significant difference(LSD)-t test.Creatinine:The level of A group was not different from B group(P=0.058)and other pairwise comparisons were different(P<0.001).Cystatin C:All pairwise comparisons were different(P<0.001).Multiple linear regression analysis showed that RRF Kt/V or RRF Ccr was independent factor affecting serum cystatin C(P<0.001),while PD Ccr or PD Kt/V had no significant effect on serum cystatin C(P>0.05).The concentration of cystatin C in the PD fluid was one-tenth of that in the serum cystatin C.The clearance rate of cystatin C by PD was about 0.26 mg/h.Conclusion:Serum cystatin C was closely associated with RRF in PD patients.It could judge the RRF status and was more sensitive and specific than serum creatinine.Serum cystatin C level was mainly determined by RRF,not by PD.Serum cystatin C may be an endogenous biomarker that can be used to measure RRF in PD patients.Part Ⅱ Comparison of cystatin-C-based formulas for evaluation of residual renal function in peritoneal dialysis patientsBackground:RRF is critical important for PD patients and it is necessary to test RRF periodically in clinical practice.Serum cystatin C is a kind of endogenous marker which can be used to reflect the kidney function.Some scholars have developed the calculation formulas of RRF based on cystatin C,but the applicability of each equation in PD patients is not clear.Objective:The present study aims to compare three cystatin-C-based formulas which were used to evaluate RRF in PD patients.Methods:We recruited patients who were undergoing PD treatment at our PD Center between June and December 2018.All patients’ 24h urine volume>100 ml.Demographic data and biochemical data were collected.The particle-enhanced turbidimetric immunoassay method was applied to determine cystatin C level.The average clearance of 24h urea and creatinine was taken as the gold standard,which was called measured RRF(mRRF).RRF was also estimated by the chronic kidney disease epidemiology collaboration(CKD-EPI),Hoek and Yang formulas.Absolute deviation was defined as the differences between mRRF and estimated RRF(eRRF)calculated by the three formulas.The relative deviation was calculated by absolute deviation/mRRF.We used the Bland-Altman plot to assess the bias and degree of agreement between eRRF and mRRF graphically.The percentage of eRRF within 30%or 50%of mRRF was used to express the accuracy.mRRF<2.0 ml/min/1.73m2 was taken as a significant RRF loss.We used ROC curve to analyze the diagnostic value of eRRF calculated by the three formulas.The sensitivity and specificity at the cut-off value were compared.Results:We enrolled 94 patients(47 male and 47 female).The serum level of cystatin C was(7.12±1.45)mg/L.The mRRF was(2.54±1.79)ml/min/1.73m2.eRRF was(6.41±1.95)ml/min/1.73 m2 for the CKD-EPI formula,(2.82±0.84)ml/min/1.73 m2 for the Hoek formula and(1.68±1.11)ml/min/1.73 m2 for the Yang formula.The mean bias and limit of agreement were-3.9(-0.7 to-7.1)ml/min/1.73 m2 for the CKD-EPI formula,-0.3(2.6 to-3.2)ml/min/1.73 m2 for the Hoek formula and 0.9(3.6 to-1.9)ml/min/1.73 m2 for the Yang formula.The mean bias in eRRF was highest for the CKD-EPI formula and lowest for the Hoek formula.The Yang formula underestimated RRF,while the CKD-EPI and Hoek formulas overestimated RRF.Relative deviations among the three groups were different(Z=85.04,P<0.001).The relative deviation of the Yang formula was the smallest and that of the CKD-EPI formula was the largest.The accuracy within 30%/50%was 6.3 8%/10.64%for the CKD-EPI formula,34.04%/56.38%for the Hoek formula and 35.11%/61.7%for the Yang formula.The accuracy within 30%and 50%for the CKD-EPI formula was worse than that for the Hoek formula and Yang formula(P<0.001).There was no significant difference in accuracy within 30%and 50%between the Hoek and Yang formulas(P>0.05).mRRF<2.0 ml/min/1.73 m2 was taken as a significant RRF loss.For the CKD-EPI formula,AUC was 0.808,specificity was 0.784 and sensitivity was 0.702.The corresponding values for the Hoek formula were 0.805,0.703 and0.807.The corresponding values for the Yang formula were 0.813,0.811 and 0.737.There was no difference in AUC,specificity and sensitivity of the three formulas(P>0.05).Conclusion:The CKD-EPI formula showed the largest bias and the lowest accuracy.The Hoek formula showed the smallest mean bias and the Yang formula had the smallest relative differences.There was no difference between the Yang and Hoek formulas for accuracy within 30%and 50%.It may be inappropriate to use the CKD-EPI formula to estimate RRF of PD patients.We can use Yang formula or Hoek formula to estimate RRF of PD patients.Part Ⅲ The estimation of peritoneal dialysis volume based on serum cystatin CBackground:RRF is crucial important for PD patients.The prescription of appropriate peritoneal dialysis volume(PDV)can not only make full use of PD patients’ RRF,but also ensure the adequacy of PD patients.Professor Yu proposed a formula for calculating PDV based on the RRF level of PD patients.Serum cystatin C can be used to reflect the RRF level of PD patients,but it is not clear whether serum cystatin C can be used to estimate PDV of PD patients.Objective:To explore the formula for calculating PDV based on serum cystatin C and validate it.Methods:In the first part,we recruited 198 PD patients who were regularly treated with PD in our PD center from January 2017 to June 2019.This was modeling group.In the second part,63 PD patients with stable condition and 24h urine volume≥100ml from January 2020 to May 2020 were enrolled to validate the formula established from the modeling group.Demographic data and biochemical data were collected.The serum cystatin C levels in serum and peritoneal fluid were measured by particle-enhanced turbidimetric immunoassay method.We used Baxter Adequest 2.0 software to calculate Kt/V,Ccr and normalized protein catabolic rate(NPCR).The average clearance rate of 24h urea nitrogen and creatinine was taken as RRF.In the first part it was divided into Kt/V≥1.7 group and Kt/V<1.7 group.The differences of related indexes between the two groups were compared.It was also divided into three groups according to the RRF level to analyze the influence of RRF on dialysis adequacy,group A:RRF=0ml/min/1.73m2,group B:0ml/min/1.73m2<RRF<2ml/min/1.73m2,group C:RRF>2ml/min/1.73m2.The differences of PDV/BSA,total Kt/V,total Ccr,NPCR and albumin among the three groups were compared.Pearson correlation was used to analyze the correlation between serum cystatin C and PDV/BSA.We used linear regression analysis to obtain PDV/BSA formula based on cystatin C.Finally,we validated the formula in the 63 PD patients of the second part.Results:In the first part of 198 PD patients,there were 109 males(55.05%)and 89 females(44.95%).In the second part of 63 PD patients,there were 31 males(49.21%)and 32 females(50.79%).The average age was(54.35±10.17)years and the serum cystatin C was(7.37±1.27)mg/L.In the modeling group,a total of 1358 comprehensive evaluations were performed on 198 patients,of which Kt/V≥1.7 was 906(66.72%)and Kt/V<1.7 was 452(33.28%).Serum cystatin C,creatinine,urea,and ultrafiltration were lower while serum albumin,urine volume,RRF,NPCR,PDV/BSA,RRF Kt/V,PD Kt/V,total Kt/V,RRF Ccr,PD Ccr and total Ccr were higher in the Kt/V≥1.7 group compared to the Kt/V<1.7 group(P<0.05).We divided the first part into three groups according to the RRF level.There were statistical differences in PDV/BSA,total Kt/V,total Ccr,NPCR and albumin among the three groups.Further comparison showed that group C with the highest RRF level had the lowest PDV/BSA,the highest total Kt/V,total Ccr,NPCR and albumin(P<0.001).In the modeling group,392 evaluations with stable dialysis status,24h urine volume≥100ml and total Kt/V between 1.7 and 2.0 were selected.The Pearson correlation analysis showed that there was a positive correlation between serum cystatin C and PDV/BSA(r=0.501,P<0.001).Serum cystatin C was taken as independent variable and PDV/BSA was taken as dependent variable,formula was obtained by linear regression analysis:PDV/BSA=2.377+0.277×serum cystatin C,PDV(L/d)=(2.377+0.277×serum cystatin C)×BSA.Finally,we validated the formula in the 63 PD patients of the second part.The 63 PD patients adopted the PDV estimated from the formula and Kt/V was test 1 month later.Kt/V was 1.97±0.35.Kt/V<1.7 was 12(19.05%),1.7-2.0 was 36(57.14%)and>2.0 was 15(23.81%).A total of 51(80.95%)PD patients achieved dialysis adequacy.Conclusion:RRF plays an important role in the dialysis adequacy of PD patients.Calculating the PDV based on serum cystatin C and BSA can exert the RRF and the majority of PD patients can reach the state of adequacy.Part Ⅳ Relationship between serum cystatin C and prognosis of nondiabetic peritoneal dialysis patientsBackground:RRF is closely related to prognosis of PD patients.Serum cystatin C can be used to reflect RRF of PD patients.However,it is unclear whether serum cystatin C is associated with prognosis of PD patients.Objective:To explore the relationship between serum cystatin C and prognosis of newonset PD patients without diabetes mellitus.Methods:We included all non-diabetic patients who began PD at our H ospital between January 2010 and January 2019.Demographic data and biochemical data were collected.Serum cystatin C was determined by particle-enhanced turbidimetric immunoassay method.Baseline RRF was estimated by Modification of the Diet in Renal Disease(MDRD)equation.Adequacy of dialysis was determined by urea clearance index(Kt/V)calculated by PD Adequest 2.0 software.Adequacy and 4h dialysate to 2h plasma creatinine ratio(D/PCr)were recorded at 1 month after PD.Episodes of peritonitis in the first year of PD were also recorded.All patients were followed up until death or study termination on July 1,2019.End-point events we observed included withdrawal from PD and death.The patients were divided into low serum cystatin C group and high serum cystatin C group according to the threshold value calculated by X-tile software developed by Yale University.Survival was analyzed by Kaplan-Meier method and survival difference between the groups was compared by the log-rank test.Risk factors for end-point events were analyzed by Cox regression model.Covariates with P<0.1 in univariate models were selected for multivariate Cox regression models.The Nomogram was used to predict 1,3 and 5 years technical survival rates of PD patients by meaningful indicators.The calibration curve and Harrell concordance index(C-index)were used to verify the accuracy of the Nomogram in predicting the technical survival rates of PD patients.Results:We enrolled 163 patients,including 90 men(55.21%)and 73 women(44.79%),with an average age of(48.75± 13.23)years.The serum cystatin C was(5.56±1.08)mg/L.Up to July 1,2019,66 patients withdrew from PD,including 42(63.64%)who transferred to HD and 24(36.36%)who died.When withdrawal from PD was taken as the end point,the threshold value of serum cystatin C calculated by X-tile software was 4.8mg/L.The technical survival of the low cystatin C group was better than that of the high cystatin C group(χ2=7.232,P=0.007).When death was taken as the end point,the threshold value of serum cystatin C calculated by X-tile software was 4.0mg/L.There was no significant difference in overall survival between the low cystatin C group and the high cystatin C group(χ2=0.470,P=0.493).Univariate Cox regression showed that higher serum cystatin C,male gender,peritonitis episodes in the first year,and higher D/PCr were risk factors for PD failure,while higher serum albumin,RRF Kt/V and total Kt/V were protective factors for PD technical survival.Serum cystatin C was not associated with overall survival of PD patients.Advanced age and presence of cardiovascular complications were risk factors for mortality in PD patients.After incorporating the covariates with P<0.1 into a multivariate Cox regression,serum cystatin C was an independent risk factor for PD failure(HR=1.29,95%CI 1.03-1.60,P=0.025).The C-index of Nomogram predicting the technical survival rate of PD patients was 0.71(95%CI 0.65-0.77).The calibration curve also showed a good consistency between the prognostic Nomogram model and the actual observed values.Conclusion:We found that patients with higher RRF had a higher technical survival rate.Serum cystatin C which is a marker for RRF of PD patients could predict PD failure,but was not associated with overall survival.Increased monitoring is needed for PD patients with high serum cystatin C level. |
PDF Full Text Request