Clinical and Histopathologic Characteristics Associated with Renal Outcomes in Lupus Nephritis.
ABSTRACT: The prognostic significance of histopathologic (sub)classes in the current classification of lupus nephritis (LN) is controversial. We analyzed clinical and histopathologic predictors of renal outcome in LN outside the framework of the classification.Variables (50 histopathologic and ten clinical) were tested in mixed, linear, and Cox regression models for their association with renal flare, ESRD, and eGFR during follow-up (1, 5, and 10 years) in 105 patients with LN who underwent biopsy from 1987 to 2011. The Cockcroft-Gault (normalized to a body surface area of 1.73 m2) and Schwartz formulas were used to calculate eGFR for adults and children, respectively.During median follow-up of 9.9 years (25th-75th percentile, 5.9-13.8), 47 patients experienced a renal flare and 21 progressed to ESRD. Renal flare was predicted by fibrinoid necrosis (hazard ratio [HR], 1.04 per %; 95% confidence interval [95% CI], 1.00 to 1.07) and nonwhite race (HR, 2.23; 95% CI, 1.23 to 4.04). ESRD was predicted by fibrinoid necrosis (HR, 1.08 per %; 95% CI, 1.02 to 1.13), fibrous crescents (HR, 1.09 per %; 95% CI, 1.02 to 1.17), interstitial fibrosis/tubular atrophy (IF/TA) ?25% (HR, 3.89; 95% CI, 1.25 to 12.14), eGFR at baseline (HR, 0.98 per ml/min per 1.73 m2; 95% CI, 0.97 to 1.00), and nonwhite race (HR, 7.16; 95% CI, 2.34 to 21.91). A higher mean eGFR during follow-up was associated with normal glomeruli (+0.2 ml/min per 1.73 m2 per %; 95% CI, 0.1 to 0.4). Like ESRD, a lower eGFR during follow-up was associated with fibrous crescents, IF/TA?25%, and nonwhite race, as well as with cellular/fibrocellular crescents (-0.4 ml/min per 1.73 m2 per %; 95% CI, -0.6 to -0.2) and age (-0.8 ml/min per 1.73 m2 per year; 95% CI, -1.2 to -0.4).The LN classification should include an index of evidence-based prognosticators. Awaiting validation of a formal index, we suggest that at least fibrinoid necrosis, fibrous crescents, and IF/TA warrant explicit independent scoring to assess the risk of progressive renal dysfunction in conjunction with clinical findings.
Project description:BACKGROUND:A working group on the Oxford classification of IgA nephropathy (IgAN) recently reported that crescents detected in kidney tissue predicted a worse renal outcome. However, this finding must be validated in independent cohorts before it can be widely applied to clinical practice. METHODS:Biopsy-proven IgAN patients were continuously recruited from two large renal centers in China from 1989 to 2014. All patients were followed for more than 1 year unless end stage renal disease (ESRD) occurred within 12 months. Crescents were defined as focal cellular or fibrocellular crescent formations. IgAN patients without detectable crescents were recruited to the C0 group. Patients with crescents in less than or more than 1/4 of all glomeruli were recruited to the C1 or C2 group, respectively. Primary outcome was defined as the time to ESRD, and the secondary outcome was defined as the time to an estimated glomerular filtration rate (eGFR) decline equal to or greater than 50% or to ESRD. RESULTS:In total, 1152 IgAN patients were recruited in this study. Among all patients, 53.7% were in the C0 group, 38.8% were in the C1 group, and 7.5% were in the C2 group. Compared to patients in the C0 group, patients in the C1 or C2 group were younger, had more urinary protein excretion and lower eGFR, and presented with more severe mesangial hypercellularity, endocapillary proliferation or tubular atrophy/interstitial fibrosis. After 45 months of follow-up, ESRD had occurred in 80 (12.9%), 46 (10.3%) and 18 (20.9%) of patients in the C0, C1 and C2 groups, respectively. By multivariable Cox regression analysis, inclusion in the C1 (HR?=?1.07, 95% CI 0.71-1.63), C2 (HR?=?0.84, 95% CI 0.41-1.73), or C1 or C2 group (HR?=?1.02, 95% CI 0.68-1.52) was not associated with a higher rate of ESRD than inclusion in the C0 group after adjusting for age, gender, eGFR, mean arterial pressure (MAP), MEST scores, and immunosuppressive treatment. However, in patients with nephrotic-range proteinuria, patients in either the C1 or C2 group had a higher rate of the primary outcome, ESRD (HR?=?2.54, 95% CI 1.14-5.66) after adjusting for age, gender, eGFR, MAP, MEST scores, and immunosuppressive treatment. Similar results were found when we evaluated the association between crescents and the secondary outcome. CONCLUSIONS:IgAN patients with crescents had more severe clinical and pathological manifestations than those without crescents. However, we failed to replicate the association between crescents and renal function progression in Chinese IgAN patients followed for more than 1 year.
Project description:Previous studies reported the risk of ESRD after kidney donation, but not the renal outcomes that precede ESRD. Here, we estimated the risk of proteinuria, reduced GFR, and ESRD in 3956 white kidney donors, assessed the contribution of postdonation hypertension and diabetes to these outcomes, and developed a risk calculator. After a mean±SD follow-up of 16.6±11.9 years, 215 (6.1%) donors developed proteinuria. Men had a higher risk of proteinuria (hazard ratio [HR], 1.56; 95% confidence interval [95% CI], 1.18 to 2.05; P<0.001) as did those with higher body mass index (HR, 1.10; 95% CI, 1.06 to 1.13; P<0.001). In all, 1410 (36%) donors reached an eGFR<60 ml/min per 1.73 m(2), and 112 (2.8%) donors had either an eGFR<30 ml/min per 1.73 m(2) or ESRD (28 donors developed ESRD). An eGFR<30 ml/min per 1.73 m(2) or ESRD associated with older age (HR, 1.07; 95% CI, 1.05 to 1.09; P<0.001), higher body mass index (HR, 1.08; 95% CI, 1.04 to 1.13; P<0.001), and higher systolic BP (HR, 1.02; 95% CI, 1.00 to 1.04; P=0.01) at donation. Postdonation diabetes and hypertension associated with a fourfold higher risk of proteinuria and a >2-fold higher risk of ESRD. Models predicting proteinuria and reduced eGFR performed well (C-index 0.77-1.00). In conclusion, severe reduction in GFR and ESRD after kidney donation were uncommon and were highly associated with postdonation diabetes and hypertension. Furthermore, information available before donation may predict long-term renal outcomes in white living kidney donors.
Project description:Elevated levels of fine particulate matter <2.5 µm in aerodynamic diameter (PM2.5) are associated with increased risk of cardiovascular outcomes and death, but their association with risk of CKD and ESRD is unknown. We linked the Environmental Protection Agency and the Department of Veterans Affairs databases to build an observational cohort of 2,482,737 United States veterans, and used survival models to evaluate the association of PM2.5 concentrations and risk of incident eGFR <60 ml/min per 1.73 m2, incident CKD, eGFR decline ?30%, and ESRD over a median follow-up of 8.52 years. County-level exposure was defined at baseline as the annual average PM2.5 concentrations in 2004, and separately as time-varying where it was updated annually and as cohort participants moved. In analyses of baseline exposure (median, 11.8 [interquartile range, 10.1-13.7] µg/m3), a 10-µg/m3 increase in PM2.5 concentration was associated with increased risk of eGFR<60 ml/min per 1.73 m2 (hazard ratio [HR], 1.21; 95% confidence interval [95% CI], 1.14 to 1.29), CKD (HR, 1.27; 95% CI, 1.17 to 1.38), eGFR decline ?30% (HR, 1.28; 95% CI, 1.18 to 1.39), and ESRD (HR, 1.26; 95% CI, 1.17 to 1.35). In time-varying analyses, a 10-µg/m3 increase in PM2.5 concentration was associated with similarly increased risk of eGFR<60 ml/min per 1.73 m2, CKD, eGFR decline ?30%, and ESRD. Spline analyses showed a linear relationship between PM2.5 concentrations and risk of kidney outcomes. Exposure estimates derived from National Aeronautics and Space Administration satellite data yielded consistent results. Our findings demonstrate a significant association between exposure to PM2.5 and risk of incident CKD, eGFR decline, and ESRD.
Project description:Overproduction of oxalate in patients with primary hyperoxaluria (PH) leads to calcium oxalate deposition in the kidney and ESRD in a substantial number of cases. However, the key determinants for renal outcome remain unclear. Thus, we performed a retrospective analysis to identify predictors for renal outcome among patients with PH participating in the Rare Kidney Stone Consortium (RKSC) PH Registry.We characterized clinical and laboratory features of patients enrolled in the RKSC PH Registry. We assessed correlation between urinary measures and eGFR at diagnosis by Spearman rank correlation and estimated renal survival using the Kaplan-Meier method. We determined factors associated with renal survival by Cox proportional hazard models.Of 409 patients enrolled in the RKSC Registry as of March 2014, we excluded 112 patients who had ESRD at PH diagnosis from analysis. Among the remaining 297 patients, 65% had PH type 1, 12% had type 2, 13% had type 3, and 11% had unclassified PH. Median (25th, 75th percentile) age at PH diagnosis was 8.1 (4.0, 18.2) years with an eGFR of 73.0 (56.4, 97.5) ml/min per 1.73 m(2) and urinary oxalate excretion rate of 1.64 (1.11, 2.44) mmol/1.73 m(2) per 24 hours. During a median follow-up of 3.9 (1.0, 12.8) years, 59 (20%) patients developed ESRD. Urinary oxalate excretion at diagnosis stratified by quartile was strongly associated with incident ESRD (hazard ratio [HR], 3.4; 95% confidence interval [95% CI], 1.4 to 7.9). During follow-up there was a significant association between urinary oxalate quartile (Q) and incident ESRD (Q4 versus Q1: HR, 3.3; 95% CI, 1.2 to 9.3). This association remained even when adjusted for sex, age, and baseline eGFR (HR, 4.2; 95% CI, 1.6 to 10.8).Among patients with PH, higher urinary oxalate excretion is predictive of poor renal outcome.
Project description:To investigate the association of estimated glomerular filtration rate (eGFR) slopes before dialysis initiation with cause-specific mortality after dialysis initiation.In this retrospective cohort study of 18,874 US veterans who had transitioned to dialysis from October 1, 2007, through September 30, 2011, we examined the association of pre-end-stage renal disease (ESRD) eGFR slopes with all-cause, cardiovascular, and infection-related mortality during the post-ESRD period over a median follow-up of 2.0 years (interquartile range, 1.1-3.2 years). Associations were examined using Cox models with adjustment for potential confounders.Before the 18,874 patients transitioned to dialysis, 4485 (23.8%), 5633 (29.8%), and 7942 (42.1%) experienced fast, moderate, and slow eGFR decline, respectively, and 814 (4.3%) had increasing eGFR (defined as eGFR slopes of less than -10, -10 to less than -5, -5 to <0, and ?0 mL/min per 1.73 m(2) per year). During the study period, a total of 9744 all-cause, 2702 cardiovascular, and 604 infection-related deaths were observed. Compared with patients with slow eGFR decline, those with moderate and fast eGFR decline had a higher risk of all-cause mortality (adjusted hazard ratio [HR], 1.06; 95% CI, 1.00-1.11; and HR, 1.11; 95% CI, 1.04-1.18, respectively) and cardiovascular mortality (HR, 1.11; 95% CI, 1.01-1.23 and HR, 1.13; 95% CI, 1.00-1.27, respectively). In contrast, increasing eGFR was only associated with higher infection-related mortality (HR, 1.49; 95% CI, 1.03-2.17).Rapid eGFR decline is associated with higher all-cause and cardiovascular mortality, and increasing eGFR is associated with higher infection-related mortality among incident dialysis cases.
Project description:Few data has been available on the effect of serum HDL-C levels on the prognosis of lupus nephritis (LN) patients. The present study therefore aimed to explore the effect of serum HDL-C levels on LN patients.We included 775 patients with follow-up information registered in an LN database between 1 January 2006 and 31 December 2011. The patients were divided into groups with low, intermediate and high HDL-C, according to NCEP ATPIII criteria. Cox regression analyses were used to explore the effects of HDL-C levels on end-stage renal disease (ESRD), all-cause mortality and cardiovascular disease (CVD) mortality.During a median follow-up of 56 months (3-206 months), 71 (9.2%) had ESRD. 84 (10.8%) deaths occurred, 17 (20.2%) of which were due to CVD. There was no statistically significant association of HDL-C category or continuous HDL-C levels with ESRD in the total cohort, but in subgroup analyses by eGFR, with each 0.1 mmol/L increase in HDL-C level, adjusted HRs for ESRD were 0.92 (95% CI: 0.83-1.04, P = 0.173) for eGFR ≥60 ml/min/1.73m2 and 1.11 (95% CI: 1.01-1.23, P = 0.036) for eGFR <60 ml/min/1.73m2. The effect of the interaction between eGFR category and serum HDL-C level on ESRD was statistically significant (β = -1.738, P = 0.005). Low HDL-C was associated with all-cause mortality (HR = 2.16, 95% CI: 1.06-4.40, P = 0.033) with intermediate HDL-C as reference category after adjusting for several variables.Our results demonstrate that high HDL-C levels were associated with increased risk of ESRD in LN patients with advanced renal dysfunction. While low HDL-C levels were associated with increased risk of all-cause mortality in LN patients.ClinicalTrials.gov Identifier: NCT03001973 , 22 December 2016 retrospectively registered.
Project description:OBJECTIVE:We examined the association of urine complement proteins with progression to end-stage renal disease (ESRD) or death in people with type 2 diabetes and proteinuric diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS:Using targeted mass spectrometry, we quantified urinary abundance of 12 complement proteins in a predominantly Mexican American cohort with type 2 diabetes and proteinuric DKD (n = 141). The association of urine complement proteins with progression to ESRD or death was evaluated using time-to-event analyses. RESULTS:At baseline, median estimated glomerular filtration rate (eGFR) was 54 mL/min/1.73 m2 and urine protein-to-creatinine ratio 2.6 g/g. Sixty-seven participants developed ESRD or died, of whom 39 progressed to ESRD over a median of 3.1 years and 40 died over a median 3.6 years. Higher urine CD59, an inhibitor of terminal complement complex formation, was associated with a lower risk of ESRD (hazard ratio [HR] [95% CI per doubling] 0.50 [0.29-0.87]) and death (HR [95% CI] 0.56 [0.34-0.93]), after adjustment for demographic and clinical covariates, including baseline eGFR and proteinuria. Higher urine complement components 4 and 8 were associated with lower risk of death (HR [95% CI] 0.57 [0.41-0.79] and 0.66 [0.44-0.97], respectively); higher urine factor H-related protein 2, a positive regulator of the alternative complement pathway, was associated with greater risk of death (HR [95% CI] 1.61 [1.05-2.48]) in fully adjusted models. CONCLUSIONS:In a largely Mexican American cohort with type 2 diabetes and proteinuric DKD, urine abundance of several complement and complement regulatory proteins was strongly associated with progression to ESRD and death.
Project description:Few studies have compared different blood pressure (BP) indexes for end-stage renal disease (ESRD) risk among individuals with chronic kidney disease.We examined the relationship between systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and mean arterial pressure (MAP) and ESRD risk among 2,772 participants with an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) calculated using the Chronic Kidney Disease Epidemiology Collaboration equation in the REasons for the Geographic And Racial Differences in Stroke (REGARDS) study. BP was measured during a baseline study visit between January 2003 and October 2007 with ESRD incidence through August 2009 ascertained via linkage with the United States Renal Data System (n = 138 ESRD cases).The mean age was 72.1(standard deviation: 8.7) years. After multivariable adjustment for socio-demographic and clinical risk factors including antihypertensive medication use, the hazard ratio (HR) for ESRD associated with one standard deviation higher SBP (18 mm Hg) was 1.67, (95% confidence intervals (CI) 1.43-1.96), DBP (11 mm Hg) was 1.38, (95% CI 1.16-1.63), PP (15 mm Hg) was 1.50, (95% CI 1.27-1.78) and MAP (11 mm Hg) was 1.54, (95% CI 1.32-1.79). Higher levels of SBP remained associated with an increased HR for ESRD after additional adjustment for DBP (1.65, 95% CI: 1.35-2.01), PP (1.73, 95% CI: 1.32-2.26), and MAP (1.61, 95% CI: 1.16-2.23). After adjustment for SBP, the other BP indexes were not significantly associated with incident ESRD.These data suggest that of several blood pressure indexes including DBP, PP and MAP, SBP may have the strongest association with ESRD incidence among individuals with reduced eGFR.
Project description:Living kidney donation represents the optimal renal replacement therapy, but recent data suggest an increased long-term renal risk for the donor. Here, we evaluated the risk for reduced estimated glomerular filtration rate (eGFR), death, and major cardiovascular events such as nonfatal myocardial infarction or cerebrovascular event including TIA (transient ischemic attack) and stroke in 225 donors, who underwent pre-donation examinations and live donor nephrectomy between 1985 and 2014 at our center. The median follow-up time was 8.7 years (1.0-29.1). In multivariate analysis, age and arterial hypertension at baseline were significantly associated with a higher risk of adverse renal outcomes, such as (1) eGFR <60 mL/min/1.73 m2 (age per year: HR (hazard ratio) 1.05, 95% confidence interval (CI) 1.03-1.08, hypertension: HR 2.25, 95% CI 1.22-3.98), (2) eGFR <60 mL/min/1.73 m2 and a decrease of ?40% from baseline (age: HR 1.08, 95% CI 1.03-1.13, hypertension: HR 4.22, 95% CI 1.72-10.36), and (3) eGFR <45 mL/min/1.73 m2 (age: HR 1.12, 95% CI 1.05-1.20, hypertension: HR 5.06, 95% CI 1.49-17.22). In addition, eGFR at time of donation (per mL/min/1.73 m2) was associated with a lower risk of (1) eGFR <60 mL/min/1.73 m2 (HR 0.98, 95% CI 0.97-1.00) and (2) eGFR <45 mL/min/1.73 m2 (HR 0.95, 95% CI 0.90-1.00). Age was the only significant predictor for death or major cardiovascular event (HR 1.08, 95% CI 1.01-1.16). In conclusion, arterial hypertension, lower eGFR, and age at the time of donation are strong predictors for adverse renal outcomes in living kidney donors.
Project description:eGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past trajectory (slope) beyond that of the current eGFR is unclear. We examined 22 cohorts to determine the association of past slopes and current eGFR level with subsequent ESRD. We modeled hazard ratios as a spline function of slopes, adjusting for demographic variables, eGFR, and comorbidities. We used random effects meta-analyses to combine results across studies stratified by cohort type. We calculated the absolute risk of ESRD at 5 years after the last eGFR using the weighted average baseline risk. Overall, 1,080,223 participants experienced 5163 ESRD events during a mean follow-up of 2.0 years. In CKD cohorts, a slope of -6 versus 0 ml/min per 1.73 m(2) per year over the previous 3 years (a decline of 18 ml/min per 1.73 m(2) versus no decline) associated with an adjusted hazard ratio of ESRD of 2.28 (95% confidence interval, 1.88 to 2.76). In contrast, a current eGFR of 30 versus 50 ml/min per 1.73 m(2) (a difference of 20 ml/min per 1.73 m(2)) associated with an adjusted hazard ratio of 19.9 (95% confidence interval, 13.6 to 29.1). Past decline contributed more to the absolute risk of ESRD at lower than higher levels of current eGFR. In conclusion, during a follow-up of 2 years, current eGFR associates more strongly with future ESRD risk than the magnitude of past eGFR decline, but both contribute substantially to the risk of ESRD, especially at eGFR<30 ml/min per 1.73 m(2).