Predictors Of ESRD Research Articles

P0386OUTCOMES OF PAUCI-IMMUNE CRESCENTIC GLOMERULONEPHRITIS BASED ON THE INTERNATIONAL HISTOPATHOLOGICAL CLASSIFICATION AND RECENTLY PROPOSED RENAL RISK SCORE IN ADULTS: A SINGLE CENTER STUDY

Abstract Background and Aims Pauci-immune crescentic glomerulonephritis is rare form of glomerulonephritis that frequently presents as rapidly progressive renal failure. The histopathological classification proposed by Berden a decade earlier described difference in the outcomes of patients in the focal, crescentic, mixed and sclerotic category with best prognosis for focal and worst for sclerotic group. The newly proposed renal risk score (Brix SR at al.) takes into account both the histopathological parameters (% of normal glomeruli, tubular atrophy and interstitial fibrosis) and clinical parameter (eGFR) which influence outcome in these patients. Present study was undertaken to determine outcomes of pauci-immune crescentic glomerulonephritis based on both of these prognostic systems and also to determine effect of individual risk factors on renal outcome. Method 64 patients diagnosed as pauci-immune crescentic glomerulonephritis from January 2013 to December 2018 were retrospectively analyzed. There histopathological slides were reviewed for percentage normal glomeruli, extent of interstitial fibrosis and tubular atrophy and biopsies were also grouped according to histopathological classification into focal, crescentic, mixed and sclerotic categories. The clinical parameters including serum creatinine, eGFR at time of biopsy and follow-up, and status of ANCA positivity were obtained from electronic records. Renal biopsies were scored based on renal risk score depending on the % of normal glomeruli (>25%,10-25% and <10%), percentage of tubular atrophy and interstitial fibrosis(≤25%,>25%) and eGFR(>15ml/min,≤15ml/min) into 3 risk categories. Results There were 61 adult patients and 3 pediatric patients. Two patient with insufficient glomeruli (<7) on biopsy and 8 patients without follow-up were excluded. A total of 51 adult patients were included of which 28 were male and 23 females. The mean age was 51.2±15.7 years. The mean serum creatinine at the time of biopsy was 7.05±4.57 mg/dl and the mean eGFR was 13.6±12.16 ml/min/1.73m2. There were 33 ANCA positive and 18 ANCA negative(35%) cases. Distribution of patients according to Berden’s histopathological classification was focal(4), crescentic(29), mixed(12) and sclerotic(6). The distribution of patients into risk categories based on renal risk score was low(8),medium(23) and high(20). Univariate Cox regression analysis showed that eGFR at biopsy (p 0.024), % IFTA (p 0.001) and % normal glomeruli in biopsy (p 0.023) are predictors of ESRD. Multivariate Cox regression analysis including age, eGFR, % IFTA and % normal glomeruli in biopsy also confirmed IFTA (p<0.001) and % normal glomeruli in biopsy (p 0.018) as significant predictors of ESRD. When % normal glomeruli was replaced by Berden’s histopathological classed it didn’t reach statistical significance to predict ESRD. Kaplan-Meier survival analysis for histological categories showed best renal survival in focal group and worst in sclerotic group (Log-Rank p=0.046). Kaplan-Meier analysis for the renal risk categories showed best survival in low risk group followed by medium and high risk groups respectively (Log-Rank p=0.002). Kaplan-Meier survival analysis was also done for percentage of normal glomeruli, IFTA and renal function. Conclusion In our study of Pauci-immune crescentic glomerulonpehritis ANCA was negative in 35% cases. Percentage of normal glomeruli, IFTA and eGFR at time of biopsy were important histopathological and clinical risk factors influencing renal survival in these patients. Results of our study validate that recently proposed renal risk score is a better predictor of survival (p=0.002) as compared to histological classification proposed by Berden (p=0.046).

Longitudinal progression trajectory of random urine creatinine as a novel predictor of ESRD among patients with CKD

BackgroundThe clinical importance of random urine creatinine concentration in CKD population remains undetermined. Earlier studies found that lower 24-h urine creatinine excretion was associated with the risk of ESRD and all-cause mortality among CKD patients. MethodsWe modeled the longitudinal trajectories of serial random urine creatinine among 4689 CKD patients enrolled in a national registry-based pre-ESRD program between 2003 and 2015 at a tertiary medical center. Other biochemical parameters including kidney function and serum albumin were regularly evaluated. Primary study outcomes were ESRD requiring maintenance dialysis and all-cause mortality. ResultsBy group-based trajectory modeling, the urine creatinine trajectories were characterized into three patterns: (1) stable low; (2) medium; and (3) high-declining. The adjusted hazard ratio of incident ESRD and all-cause mortality increased by 6% (95% CI: 1–12%) and 9% (95% CI: 2–17%), respectively, for each 20 mg/dL reduction in baseline random urine creatinine concentration. Consistently, there was a significant inverse linear dose-response relationship between baseline random urine creatinine and incident ESRD, but not all-cause mortality. Compared to patients with “medium” and “high-declining” urine creatinine trajectories combined, the adjusted hazard ratio for incidental ESRD among patients with a “stable-low” trajectory who had serial random urine creatinine concentrations stably below 100 mg/dL was 1.46 (95% CI: 1.00–2.12) after considering the competing risk of death. ConclusionsRandom urine creatinine not only serves as a common urinary concentration corrector but has its own clinical significance in risk stratification and outcome prediction in patients with advanced CKD.

Predicting Outcome in Patients with Anti-GBM Glomerulonephritis.

Large studies on long-term kidney outcome in patients with anti-glomerular basement membrane (anti-GBM) GN are lacking. This study aimed to identify clinical and histopathologic parameters that predict kidney outcome in these patients. This retrospective analysis included a total of 123 patients with anti-GBM GN between 1986 and 2015 from six centers worldwide. Their kidney biopsy samples were classified according to the histopathologic classification for ANCA-associated GN. Clinical data such as details of treatment were retrieved from clinical records. The primary outcome parameter was the occurrence of ESRD. Kidney survival was analyzed using the log-rank test and Cox regression analyses. The 5-year kidney survival rate was 34%, with an improved rate observed among patients diagnosed after 2007 (P=0.01). In patients with anti-GBM GN, histopathologic class and kidney survival were associated (P<0.001). Only one of 15 patients with a focal class biopsy sample (≥50% normal glomeruli) developed ESRD. Patients with a sclerotic class biopsy sample (≥50% globally sclerotic glomeruli) and patients with 100% cellular crescents did not recover from dialysis dependency at presentation. In multivariable analysis, dialysis dependency at presentation (hazard ratio [HR], 3.17; 95% confidence interval [95% CI], 1.59 to 6.32), percentage of normal glomeruli (HR, 0.97; 95% CI, 0.95 to 0.99), and extent of interstitial infiltrate (HR, 2.02; 95% CI, 1.17 to 3.50) were predictors of ESRD during follow-up. Dialysis dependency, low percentage of normal glomeruli, and large extent of interstitial infiltrate are associated with poor kidney outcome in anti-GBM GN. Kidney outcome has improved during recent years; the success rate doubled after 2007. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_11_21_CJASNPodcast_18_1_v.mp3.

Epidemiology of low-proteinuric chronic kidney disease in renal clinics.

CKD patients with low-grade proteinuria (LP) are common in nephrology clinics. However, prevalence, characteristics, and the competing risks of ESRD and death as the specific determinants, are still unknown. We analyzed epidemiological features of LP status in a prospective cohort of 2,340 patients with CKD stage III-V referred from ≥6 months in 40 nephrology clinics in Italy. LP status was defined as proteinuria <0.5 g/24h according to current KDIGO guidelines. Patients with higher proteinuria constituted the control group (CON). LP patients were 54.5% of the whole cohort. As compared to CON, LP were older (70.0±12.1 vs 65.4±14.1 y), and less likely to be male (55.8 vs 62.0%) and diabetic (27.6 vs 34.1%), and had hypertension as the most common cause of CKD (39.8%). They had higher eGFR (34.8±13.5 vs 26.8±13.2 mL/min/1.73m2) and hemoglobin (12.7±1.7 vs 12.3±1.7 g/dL), while systolic blood pressure (137±18 vs 140±18 mmHg) and serum phosphorus (3.7±0.8 vs 3.9±0.8 mg/dL) were lower [P<0.001 for all comparisons]. Over a median follow-up of 48 months, an inverse relative risk of ESRD and death was observed in LP (death>>ESRD; P = 0.002) versus CON (ESRD>>death; P<0.0001). Modifiable risk factors were also different in LP, with smoking, lower hemoglobin, and proteinuria being associated with higher mortality risk while lower BMI and higher phosphorus predicting ESRD at multivariable Cox analyses [P<0.05 for all]. Therefore, in nephrology clinics, LP patients are the majority and show distinctive basal features. More important, they are more exposed to death than ESRD and do present specific modifiable determinants of either outcome; indeed, in LP, while smoking plays a role for mortality, lower BMI and higher phosphorus levels -even if in the normal range- are predictors of ESRD. These data support the need to further study the low proteinuric CKD population to guide management.

Filtration Markers as Predictors of ESRD and Mortality: Individual Participant Data Meta-Analysis.

Serum β-trace protein (BTP) and β-2 microglobulin (B2M) are associated with risk of ESRD and death in the general population and in populations at high risk for these outcomes (GP/HR) and those with CKD, but results differ among studies. We performed an individual patient-level meta-analysis including three GP/HR studies (n=17,903 participants) and three CKD studies (n=5415). We compared associations, risk prediction, and improvement in reclassification of eGFR using BTP (eGFRBTP) and B2M (eGFRB2M) alone and the average (eGFRavg) of eGFRBTP, eGFRB2M, creatinine (eGFRcr), and cystatin C (eGFRcys), to eGFRcr, eGFRcys, and their combination (eGFRcr-cys) for ESRD (2075 events) and death (7275 events). Mean (SD) follow up times for ESRD and mortality for GP/HR and CKD studies were 13 (4), 6.2 (3.2), 14 (5), and 7.5 (3.9) years, respectively. Compared with eGFRcr, eGFRBTP and eGFRB2M improved risk associations and modestly improved prediction for ESRD and death even after adjustment for established risk factors. eGFRavg provided the most consistent improvement in associations and prediction across both outcomes and populations. Assessment of heterogeneity did not yield clinically relevant differences. For ESRD, addition of albuminuria substantially attenuated the improvement in risk prediction and risk classification with novel filtration markers. For mortality, addition of albuminuria did not affect the improvement in risk prediction with the use of novel markers, but lessened improvement in risk classification, especially for the CKD cohort. These markers do not provide substantial additional prognostic information to eGFRcr and albuminuria, but may be appropriate in circumstances where eGFRcr is not accurate or albuminuria is not available. Educational efforts to increase measurement of albuminuria in clinical practice may be more cost-effective than measurement of BTP and B2M for improving prognostic information.

Adolescent Predictors of ESRD in Middle-Aged Men

Adolescent Predictors of ESRD in Middle-Aged Men

Serum beta-2 microglobulin concentration predicts cardiovascular and all-cause mortality

Beta-2 microglobulin (B2M) is the light chain in the major histocompatibility complex (MHC) Class 1 molecule [ [1] Saper M.A. Bjorkman P.J. Wiley D.C. Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution. J Mol Biol. 1991; 219: 277-319 Crossref PubMed Scopus (965) Google Scholar ], which is present in all nucleated cells. It has been suggested as an initiator of inflammation [ [2] Xie J. Yi Q. Beta2-microglobulin as a potential initiator of inflammatory responses. Trends Immunol. 2003; 24 ([author reply 229–230]): 228-229 Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar ], and is an early marker of diseases related to inflammation such as cardiovascular and renal disease [ 3 Winchester J.F. Novel changes in beta2-microglobulin in dialysis patients. Clin Chem. 2005; 51: 1089-1090 Crossref PubMed Scopus (4) Google Scholar , 4 Liabeuf S. Lenglet A. Desjardins L. et al. Plasma beta-2 microglobulin is associated with cardiovascular disease in uremic patients. Kidney Int. 2012; 82: 1297-1303 Crossref PubMed Scopus (104) Google Scholar ]. B2M is renally excreted and so the serum level increases in renal dysfunction. We and others have reported that serum B2M level predicts mortality in certain patient populations [ 4 Liabeuf S. Lenglet A. Desjardins L. et al. Plasma beta-2 microglobulin is associated with cardiovascular disease in uremic patients. Kidney Int. 2012; 82: 1297-1303 Crossref PubMed Scopus (104) Google Scholar , 5 Astor B.C. Shafi T. Hoogeveen R.C. et al. Novel markers of kidney function as predictors of ESRD, cardiovascular disease, and mortality in the general population. Am J Kidney Dis. 2012; 59: 653-662 Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar , 6 Cheung A.K. Greene T. Leypoldt J.K. et al. Association between serum 2-microglobulin level and infectious mortality in hemodialysis patients. Clin J Am Soc Nephrol. 2008; 3: 69-77 Crossref PubMed Scopus (80) Google Scholar , 7 Cheung A.K. Rocco M.V. Yan G. et al. Serum beta-2 microglobulin levels predict mortality in dialysis patients: results of the HEMO study. J Am Soc Nephrol. 2006; 17: 546-555 Crossref PubMed Scopus (354) Google Scholar , 8 Shinkai S. Chaves P.H. Fujiwara Y. et al. Beta2-microglobulin for risk stratification of total mortality in the elderly population: comparison with cystatin C and C-reactive protein. Arch Intern Med. 2008; 168: 200-206 Crossref PubMed Scopus (84) Google Scholar , 9 Cheung C.L. Lam K.S. Cheung B.M. Serum beta-2 microglobulin predicts mortality in people with diabetes. Eur J Endocrinol. 2013; 169: 1-7 Crossref PubMed Scopus (23) Google Scholar ]. We therefore examined whether serum B2M level predicted cardiovascular and all-cause mortality in a large nationally representative cohort.

Novel Markers of Kidney Function as Predictors of ESRD, Cardiovascular Disease, and Mortality in the General Population

Cystatin C level predicts mortality more strongly than serum creatinine level. It is unknown whether this advantage extends to other outcomes, such as kidney failure, or whether other novel renal filtration markers share this advantage in predicting outcomes. Observational cohort study. 9,988 participants in the Atherosclerosis Risk in Communities (ARIC) Study, a population-based study in 4 US communities, followed for approximately 10 years. Serum creatinine-based estimated glomerular filtration rate calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (eGFR(CKD-EPI)) and cystatin C, β-trace protein (BTP), and β(2)-microglobulin (B2M) levels. Mortality, coronary heart disease, heart failure, and kidney failure. Higher cystatin C and B2M concentrations were associated more strongly with mortality (n = 1,425) than BTP level and all were associated more strongly than eGFR(CKD-EPI) (adjusted HR for the upper 6.7 percentile compared with the lowest quintile: 1.6 [95% CI, 1.3-1.9] for eGFR(CKD-EPI), 2.9 [95% CI, 2.3-3.6] for cystatin C level, 1.9 [95% CI, 1.5-2.4] for BTP level, and 3.0 [95% CI, 2.4-3.8] for B2M level). Similar patterns were observed for coronary heart disease (n = 1,279), heart failure (n = 803), and kidney failure (n = 130). The addition of cystatin C, BTP, and B2M levels to models including eGFR(CKD-EPI) and all covariates, including urinary albumin-creatinine ratio, significantly improved risk prediction for all outcomes (P < 0.001). No direct measurement of GFR. B2M and, to a lesser extent, BTP levels share cystatin C's advantage over eGFR(CKD-EPI) in predicting outcomes, including kidney failure. These additional markers may be helpful in improving estimation of risk associated with decreased kidney function beyond current estimates based on eGFR(CKD-EPI).

Novel Markers of Kidney Function as Predictors of ESRD, Cardiovascular Disease, and Mortality in the General Population

Novel Markers of Kidney Function as Predictors of ESRD, Cardiovascular Disease, and Mortality in the General Population

Albuminuria and Estimated Glomerular Filtration Rate as Predictors of Diabetic End-Stage Renal Disease and Death

We investigated predictive value of albuminuria and estimated GFR (eGFR) for ESRD in Pima Indians with type 2 diabetes. Beginning in 1982, 2420 diabetic Pima Indians ≥18 years old were followed until they developed ESRD or died or until December 31, 2005. Individuals were classified at baseline by urinary albumin-to-creatinine ratio (ACR) and by eGFR, calculated by the Chronic Kidney Disease Epidemiology Collaboration equation. Predictors of ESRD and mortality were examined by proportional hazards regression. During a mean follow-up of 10.2 years, 287 individuals developed ESRD. Incidence of ESRD among individuals with macroalbuminuria (ACR ≥ 300 mg/g) was 9.3 times that of those with normoalbuminuria (ACR < 30 mg/g), controlled for age, gender, and duration of diabetes. Incidence among individuals with eGFR 15 to 29 ml/min per 1.73 m(2) was 81.9 times that of those with eGFR 90 to 119 ml/min per 1.73 m(2). Models that combined albuminuria and eGFR added significant predictive information about risk of ESRD or death compared with models containing eGFR or albuminuria alone. The hazard ratio for ESRD associated with a 10-ml/min per 1.73 m(2) lower eGFR was 1.36, whereas that associated with an increase in albuminuria category was 2.69; corresponding hazard ratios for death were 1.15 and 1.37. These results suggest that incorporation of quantitative information about albuminuria into staging systems based on eGFR adds significant prognostic information about risk for diabetic ESRD and death.

Severe Lupus Nephritis

This study assessed whether certain clinicopathologic variables could explain the impact of race on outcome in 86 patients who had severe lupus nephritis and were available for long-term follow-up after participating in a prospective, controlled, clinical trial. Fifty-four (63%) patients were white, 21 (24%) were black, and 11 (13%) were categorized as other. The proportion of patients with anti-Ro, anti-nRNP, and anti-Sm was significantly greater among black patients. Biopsies with segmental active proliferative and necrotizing lesions that involved >or=50% of glomeruli +/- membranous glomerulonephritis (class III >or=50%+/-V) were significantly more common (white 44%, black 76%, other 36%; P < 0.05) and diffuse proliferative glomerulonephritis +/- membranous glomerulonephritis (class IV+/-V) was less common (white 54%, black 24%, other 64%) among black patients. Attainment of a remission was greatest among white patients (white 52%, black 29%, other 27%; P = 0.09). Features that were predictive of a remission were white race, baseline serum creatinine, and class IV+/-V lesions. Patient survival at 10 yr (white 81%, black 59%, other 73%; P = 0.029) and renal survival at 10 yr (white 68%, black 38%, other 61%; P = 0.015) were significantly poorer in black patients. Predictors of ESRD were serum creatinine, the presence of anti-Ro antibodies, class III >or=50%+/-V lesions, and failure to achieve a remission. In conclusion, racial differences were observed in the serologic and histologic features at presentation, response to treatment, and outcome of patients with severe lupus nephritis. In a population of patients with severe lupus nephritis, black patients were significantly more likely to have a serologic profile and renal lesions that were associated with more aggressive renal disease and resulted in worse outcomes than white patients.

Association of Single Measurements of Dipstick Proteinuria, Estimated Glomerular Filtration Rate, and Hematocrit with 25-Year Incidence of End-Stage Renal Disease in the Multiple Risk Factor Intervention Trial

The incidence of ESRD is increasing rapidly. Limited information exists regarding early markers for the development of ESRD. This study aimed to determine over 25 yr the risk for ESRD associated with proteinuria, estimated GFR (eGFR), and hematocrit in men who did not have identified kidney disease and were randomly assigned into the Multiple Risk Factor Intervention Study (MRFIT). A total of 12,866 men who were at high risk for heart disease were enrolled (1973 to 1975) and followed through 1999. Renal replacement therapy was ascertained by matching identifiers with the United States Renal Data System's data; vital status was from the National Death Index. Men who initiated renal replacement therapy or died as a result of kidney disease were deemed to have developed ESRD. Dipstick urine for proteinuria, eGFR, and hematocrit were related to development of ESRD. During 25 yr, 213 (1.7%) men developed ESRD. Predictors of ESRD were dipstick proteinuria of 1+ or > or =2+ (hazard ratio [HR] 3.1 [95% confidence interval (CI) 1.8 to 5.4] and 15.7 [95% CI 10.3 to 23.9] respectively) and an eGFR of <60 ml/min per 1.73 m(2) (HR 2.4; 95% CI 1.5 to 3.8). Correlation between eGFR and serum creatinine was 0.9; the risk for ESRD with a 1-SD difference of each was identical (HR 1.21). Bivariate analysis demonstrated a 41-fold increase in ESRD risk in those with an eGFR <60 ml/min per 1.73 m(2) and > or =2+ proteinuria (95% CI 15.2 to 71.1). There was no association between hematocrit and ESRD. Other baseline measures that independently predicted ESRD included age, cigarette smoking, BP, low HDL cholesterol, and fasting glucose. Among middle-aged men who were at high risk for cardiovascular disease but had no clinical evidence of cardiovascular disease or significant kidney disease, dipstick proteinuria and an eGFR value <60 ml/min per 1.73 m(2) were strong predictors of long-term development of ESRD. It remains unknown whether intervention for proteinuria or early identification of those with chronic kidney disease reduces the risk for ESRD.