Annual Loss Of eGFR Research Articles

Urinary Dickkopf-3 Reflects Disease Severity and Predicts Short-Term Kidney Function Decline in Renal Ciliopathies

BackgroundPhenotypic heterogeneity and unpredictability of individual disease progression present enormous challenges in ultrarare renal ciliopathies. The tubular-derived glycoprotein Dickkopf-related protein 3 (DKK3) is a promising biomarker for kidney fibrosis and prediction of kidney function decline. Here, we measured urinary (u)DKK3 levels in 195 pediatric renal ciliopathy patients to assess its potential as a discriminative and prediction marker. MethodsUDKK3 concentration was measured in 357 spot urine samples from 247 individuals including 52 healthy age-matched controls. Disease entities comprised nephronophthisis (NPH) (n=37), autosomal recessive polycystic kidney disease (ARPKD) (n=61), Bardet Biedl syndrome (BBS) (n=57) and hepatocyte nuclear factor 1 beta (HNF1B)-nephropathy (n=40). Results were correlated with chronic kidney disease (CKD) stage and annual estimated glomerular filtration rate (eGFR) decline. ResultsMedian uDKK3/creatinine ratios in all disease entities were significantly higher compared with healthy controls (11pg/mg uDKK3/crea, p<0.001): NPH 1.219pg/mg, HNF1B 731pg/mg, BBS 541pg/mg and ARPKD 437pg/mg. A significant correlation of CKD stage with uDKK3 levels was observed for all disease entities (p<0.0001) with no other clinical parameter having a relevant impact. In our cohort, uDKK3 values >4.700 pg/mg were associated with a significantly greater annual eGFR loss independently of diagnosis and eGFR (p=0.0029). While we observed a trend towards lower uDKK3 levels in glomerulopathies compared to renal ciliopathies, there was no discriminative difference between individual ciliopathy entities (p=0.2637). ConclusionIn renal ciliopathies uDKK3 is a marker to assess disease severity and estimate short-term kidney function decline.

123-OR: SGLT2 Inhibitors Are Associated with Kidney Benefits at All Degrees of Proteinuria—A Cohort Study

Background: The kidney benefits of sodium-glucose lowering co-transporter 2 inhibitors (SGLT2i) in adults with non-severe albuminuria, under-represented in SGLT2i trials, are not well established. Objective: We performed a retrospective cohort study to examine the effectiveness of SGLT2i compared to dipeptidyl peptidase-4 inhibitors (DPP4i), in Alberta, Canada. Methods: Using administrative data, we derived a cohort of SGLT2i new-users (2014-2018) with diabetes and eGFR ≥ 30 mL/min/1.73 m2. New SGLT2i users were matched 1:2 to DPP4i users by CKD stage, albuminuria, and diabetes therapy, and by time-conditional propensity-score (age, sex, A1c, etc.). Non-severe albuminuria was defined as a urine albumin to creatinine ratio ≤ 30 mg/mmol. Linear and Poisson regression models were used to determine the association of SGLT2i use with each outcome: eGFR decline (acute [≤ 60 days] and total), adverse kidney events, and all-cause mortality. An adverse kidney event was defined as sustained 40% loss of eGFR, initiation of kidney replacement therapy, or death from kidney causes. Results: SGLT2i users (n=19,238) had a mean age of 57.9 years (male 59.1%) and non-severe albuminuria in 94.4%. Mean eGFR was 91.7 mL/min/1.73m2, and 62.0% were dispensed ACE inhibitor or ARB. Median follow-up was 1.58 years (IQR 0.91-2.49). The acute change in eGFR was -2.79 (SGLT2i) vs -1.43 (DPP4i), for a difference of -1.36 (95% CI -1.74-[-0.98], p &amp;lt; 0.001). After day 60, SGLT2i use was associated with 0.83 (0.66-1.01, p &amp;lt; 0.001) less annual eGFR loss than in DPP4i users. SGLT2i use was associated with fewer adverse kidney events (IRR 0.58 [0.47-0.71], p &amp;lt; 0.001), driven mostly by less sustained loss of eGFR, but was not associated with all-cause mortality (IR 0.82 [0.66-1.01], p = 0.06). Similar findings were observed in those with non-severe albuminuria. Interpretation: SGLT2i may prevent eGFR decline and reduce the risk of adverse kidney events in adults with diabetes, regardless of baseline albuminuria status. Disclosure K.K.Fujita: None. F.Ye: None. D.Collister: None. S.Klarenbach: Research Support; Bayer Inc., Allergan, GlaxoSmithKline plc., CSL Behring, Lundbeck, University Hospital Foundation (University of Alberta), Purdue Canada. D.J.T.Campbell: None. D.Chew: None. A.E.Quinn: None. P.E.Ronksley: None. D.Lau: None.

413-P: Intensive Insulin Therapy Delays the “Breakpoint” to Progressive Kidney Function Decline—New Findings and Implications of eGFR Trajectory Analysis in DCCT/EDIC Data

Patterns of kidney function decline vary among those with T1D. End-stage kidney disease (ESKD) develops after progressive kidney function decline that begins when kidney function is normal, regardless of albuminuria. We aimed to determine if these findings were observed in the DCCT/EDIC cohort, which enrolled 1,441 individuals and randomly assigned them to intensive insulin therapy (n=711) or conventional insulin therapy (n=730). Baseline mean eGFR and AER were 125 ml/min/1.73m2 and 12 mg/24 hours, respectively. During 27 years of follow-up 129 individuals reached reduced eGFR &amp;lt;60ml/min/1.73m2 or ESKD. For these individuals we applied latent class trajectory analysis minimizing sum of squares of linear spline models with varying knot placement to identify patterns of eGFR decline. We identified two patterns: i) slow decline without eGFR breakpoint (n=56) and ii) fast decline with clear breakpoint (n=73). Slow decliners reached reduced eGFR but rarely ESKD (2%), while many fast decliners progressed to ESKD (35%) within 5-15 years after the breakpoint. Fast decline was less frequent in intensive compared to conventional insulin therapy [26 (3.7%) vs 47 (6.4%), respectively, p=0.022] and had longer median time from enrollment to breakpoint (18 vs 13 years, respectively, p=0.0004). However, the slope of annual loss of eGFR after breakpoint did not differ. In conclusion, we identified a unique phenotype - the “breakpoint” to fast decline in eGFR - as the main predictor of ESKD in T1D. This breakpoint started while eGFR was normal, subsequent decline was linear, and the onset of the breakpoint was substantially delayed by intensive insulin therapy rather than the slope of decline itself. Research on biomarkers that predict the onset of the eGFR ‘breakpoint’ is needed. Disclosure K.Ihara: None. J.K.Skupien: None. E.Satake: None. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO). A.Krolewski: None.

Effectiveness of Mycophenolate Mofetil Among Patients With Progressive IgA Nephropathy

The role of mycophenolate mofetil (MMF) in management of immunoglobulin A nephropathy (IgAN) remains highly controversial. To evaluate the efficacy and safety of MMF in patients with IgAN at high risk of kidney function loss. This randomized clinical trial with open-label, blinded end-point design was conducted among adults with IgAN, proteinuria greater than 1.0 g/d, and estimated glomerular filtration rate (eGFR) greater than 30 and less than 60 mL/min/1.73m2 or with persistent hypertension from September 2013 to December 2015. During a 3-month run-in period, 238 patients received optimized supportive care (SC), including losartan. Patients with a urinary protein excretion rate of 0.75 g/d or greater despite of 3 months optimized SC were enrolled into the trial for 3 years. Survivors of the trial who did not receive dialysis or transplant were followed up after the trial for a median (IQR) of 60 (47-76) months. Data were analyzed from March through June 2022. A total of 170 participants were randomized in a 1:1 ratio to receive MMF (initially, 1.5 g/d for 12 months, maintained at 0.75-1.0 g for at least 6 months) plus SC or SC alone. The primary outcomes were (1) a composite of doubling of serum creatinine, end-stage kidney disease (dialysis, transplant, or kidney failure without receiving kidney replacement therapy), or death due to kidney or cardiovascular cause and (2) progression of chronic kidney disease. Among 170 randomized patients (mean [SD] age 36.6 [9.4] years; 94 [55.3%] male patients), 85 patients received MMF with SC and 85 patients received SC alone. The mean (SD) eGFR was 50.1 (17.9) mL/min/1.73m2 and mean (SD) proteinuria level was 1.9 (1.7) g/d; 168 patients (98.8%) completed the trial, and 157 participants (92.4%) survived and did not receive dialysis or transplant. Primary composite outcome events occurred in 6 patients (7.1%) in the MMF group and 18 patients (21.2%) in the SC group (adjusted hazard ratio [aHR], 0.23; 95% CI, 0.09-0.63). Progression of chronic kidney disease occurred in 7 participants (8.2%) in the MMF group and 23 participants (27.1%) in the SC group (aHR, 0.23; 95% CI, 0.10-0.57). The effect of MMF treatment on primary outcomes was consistent across prespecified subgroups, with no significant interaction per subgroup. During posttrial follow-up, annual loss of eGFR accelerated after discontinuation of MMF; mean (SD) annual eGFR loss during the study period was 2.9 (1.0) mL/min/1.73m2 in the MMF group and 6.1 (1.2) mL/min/1.73m2 among 66 patients in the MMF group who discontinued MMF after the trial. Serious adverse events were not more frequent with MMF vs SC alone. This study found that addition of MMF to SC compared with SC alone significantly reduced risk of disease progression among patients with progressive IgAN. ClinicalTrials.gov Identifier: NCT01854814.

Octogenarians with chronic kidney disease in the nephrology clinic: Progressors vs. non-progressors.

The current definition of chronic kidney disease applied to patients over the age of 80 has increased the number of referrals to Nephrology. However not all of these patients may benefit from its assessment. This study aims to analyze the evolution of ≥80 years old patients referred to Nephrology. Single-center study including patients ≥80 years old with eGFR <60 mL/min/1,73m2 who were referred to Nephrology consultation for the first time. Clinical and analytical parameters were collected retrospectively 12 months before the visit, and prospectively at baseline, and 12 and 24 months after the initial visit. We divided patients into two groups based on annual eGFR loss: progressors (>5 mL/min/1.73m2) and non-progressors (≤5 mL/min/1,73m2). A total of 318 patients were included, mean age was 84,9 ± 4 (80-97) years. Baseline serum creatinine was 1,65 ± 0,62 mg/dL, eGRF 35 (28-42) mL/min/1,73, and albumin/creatinine ratio 36 (7-229) mg/g. 55,7% of the patients met the definition of progressor at baseline (initial-progressors), 26,3% were progressors after a 12-month follow-up and 13,4% after 24 months. 21,2% and 11,4% of initial-progressors met this definition at 12 and 24 month follow up. The main risk factor for progression was albuminuria. No relationship was found between the nephrologist intervention and the evolution of renal function among initial non-progressors. Elderly patients who have stable renal function at the time of referral will continue to have stable renal function over the subsequent 24 months and thus may not need to be referred to a nephrologist.

MO430: Octogenarians Referred to the Nephrologist: Evolution and Progression Risk Factors

Abstract BACKGROUND AND AIMS The actual definition of chronic kidney disease (CKD) applied to patients ˃80 years has generated an increase in the number of referrals to Nephrology for consultation. Nowadays there is a debate about the evolution of kidney function in elderly patients, from physiological evolution of kidney function to identifying which factors are associated with a real progression of CKD. The aim of this study is to analyse the evolution of kidney function in patients ˃80 years referred to Nephrology for consultation for the first time. METHOD A single-centre retrospective study in which we included patients ˃80 years with an estimated glomerular filtration rate (eGFR) &amp;lt;60 mL/min/1,73m2 who were referred to Nephrology consultation from 2015 to 2018. We collected clinical and analytical parameters at the following points in time: 12 months before the visit, baseline and 12 months after the initial visit. We divided patients into two groups based on annual eGFR loss: Group 1 progressors (&amp;gt;5 mL/min/1.73m2) and group 2 non-progressors (≤5 mL/min/1.73m2). RESULTS A total of 348 patients were included in the study, 55.2% were women and the mean age was 84 years (80–97). At the time of first medical visit, the mean creatinine value was 1.6 ± 0.6 mg/dL, median eGRF was 38 mL/min/1.73m2 (29–44) and median albumin/creatinine ratio was 55 mg/g (6–419), with 12% of the patients, presenting albuminuria over 1000 mg/g. The most frequent referral criteria were worsening of renal function (85.6%). Comorbidities were very common, and hypertension, dyslipidaemia and diabetes mellitus were present in 89.4%, 42.8% and 42.2% respectively. A total of 51% of the patients met the definition of progressor at baseline (initial-progressors) and 29.4% were progressors after a 12-month follow-up. Interestingly, only 21.6% of initial-progressors kept meeting this definition 12 months after (Figure 1). The main risk factors for progression were a higher baseline eGFR (P &amp;lt; 0.001) and albuminuria (P &amp;lt; 0.002). No association with comorbidities was found in the multivariate analysis. CONCLUSION The majority of patients ˃80 years evaluated by a Nephrologist were non-progressors at 12 months according to our definition (70.6%). It is more important to estimate the progression of CKD patients and request albuminuria and/or proteinuria than an isolated GFR value. It is likely that non-progressors do not need to be followed by a Nephrologist and may remain under primary care control.

Nephrotic-range proteinuria in type 2 diabetes: Effects of empagliflozin on kidney disease progression and clinical outcomes.

SummaryBackgroundDiabetic kidney disease with nephrotic-range proteinuria (NRP) is commonly associated with rapid kidney function loss, increased cardiovascular risk, and premature mortality. We explored the effect of empagliflozin in patients with type 2 diabetes and cardiovascular disease, complicated by presence of this major risk factor for progressive kidney disease, in a post-hoc analysis of data from the EMPA-REG OUTCOME trial (NCT01131676).MethodsCox proportional hazards models were used to investigate the risk of cardiovascular and kidney outcomes in participants with and without NRP, defined by urine albumin-to-creatinine ratio (UACR) ≥2200 mg/g at baseline. Annual loss of eGFR during chronic treatment (eGFR slopes) and hypothetical time to projected end-stage kidney disease (ESKD), conditioning upon linearity of eGFR change over time if a patient did not decease before projected ESKD, were calculated using a random-intercept random-coefficient model. Safety was described based on investigator-reported adverse events.Findings112 participants (pooled empagliflozin, n = 70; placebo, n = 42; median on-treatment follow-up of 1·9 years on placebo compared with 2·3 years on empagliflozin) presented with NRP at baseline; eGFR and UACR were balanced between treatments. Empagliflozin benefits on cardiovascular death, hospitalisation for heart failure, or kidney outcomes, were consistent in participants with and without NRP (pinteraction >0·1). Treatment effects of empagliflozin on adjusted annual mean eGFR slope were more pronounced in participants with NRP versus those without (pinteraction 0·005). Empagliflozin was estimated to double the median hypothetical time to projected ESKD in participants with NRP. The overall safety profile of empagliflozin was comparable between participants with and without NRP at baseline.InterpretationOur data suggests that empagliflozin might slow kidney function loss and delay the estimated onset of projected ESKD in patients with type 2 diabetes and cardiovascular disease complicated by NRP.

Pre-dialysis chronic kidney disease progression over 4 years in the context of the Public Health System in Brazil: is ethnicity a factor?

Introduction: The prevalence of chronic kidney disease (CKD) significantly increased, and populations with high social vulnerability tend to have worse CKD progression. Objective: To evaluate the impact of ethnicity on the control of pre-dialytic CKD in a Brazilian Unified Health System interdisciplinary outpatient clinic. Material and Methods: Data of 1,992 CKD patients were retrospectively collected from August/2010 to December/2014. Patients referred by primary health care, &gt;18 years, ≥ two consultations were included. Sociodemographic data were collected upon admission; clinical and laboratory data were obtained at each consultation. Patients were divided into groups according to skin colour (self-identified). A descriptive analysis was performed; variables were compared using ANOVA, chi-square or Mann-Whitney U tests. Variables associated with the delta of the estimated glomerular filtration rate (eGFR) were evaluated using linear regression, adjusting for confounding variables. Results: 25.1% were black, 34.4% brown, and 40.5% white. Approximately 51.2% had income ≤ two minimum wages, 84.8% had low level education, 14.0% were illiterate. Black patients were younger and had lower education level; they had higher systolic blood pressure, total cholesterol, high-density lipoproteins, intact parathyroid hormone; their haemoglobin and vitamin D were lower. The median annual eGFR loss was 0 (P25 −6.70, P75 +8.76), 36.5% had rapid eGFR loss (&gt;5 ml/min/year). Only use of angiotensin-converting enzyme inhibitors and low proteinuria were determined as significant for the outcome (RR: 0.92, CI: 0.010–0.684, p=0.02; RR: 0.8, CI: 0.998-0.999, p=0.001). Conclusion: Ethnicity did not impact CKD progression, even though black patients presented clinical and sociodemographic characteristics associated with worse disease progression.

Treatment switch in Fabry disease- a matter of dose?

BackgroundPatients with Fabry disease (FD) on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in chronic kidney disease epidemiology collaboration-based estimated glomerular filtration rate (eGFR) and...

Medullary Blood Oxygen Level-Dependent MRI Index (R2*) is Associated with Annual Loss of Kidney Function in Moderate CKD

Background: The estimated glomerular filtration rate (eGFR) is frequently used to monitor progression of kidney disease. Multiple values have to be obtained, sometimes over years to determine the rate of decline in kidney function. Recent data suggest that functional MRI (fMRI) methods may be able to predict loss of eGFR. In a prior study, baseline data with multi-parametric MRI in individuals with diabetes and moderate CKD was reported. This report extends our prior observations in order to evaluate the temporal variability of the fMRI measurements over 36 months and their association with annual change in eGFR. Methods: Twenty-four subjects with moderate CKD completed 3 sets of MRI scans over a 36-month period. Blood oxygenation level-dependent (BOLD), arterial spin labeling perfusion, and diffusion MRI images were acquired using a 3 T scanner. Coefficients of variation was used to evaluate variability between subjects at each time point and temporal variability within each subject. We have conducted mixed effects models to examine the trajectory change in GFR over time using time and MRI variables as fixed effects and baseline intercept as random effect. Associations of MRI image markers with annual change in eGFR were evaluated. Results: Multi-parametric functional renal MRI techniques in individuals with moderate CKD showed higher temporal variability in R2* of medulla compared to healthy individuals. This was consistent with the significant lower R2* in medulla observed at 36 months compared to baseline values. The results of linear mixed model showing that R2*_Medulla was the only predictor associated with change in eGFR over time. Furthermore, a significant association of medullary R2* with annual loss of eGFR was observed at all the 3 time points. Conclusions: The lower R2* values and the higher temporal variability in the renal medulla over time suggest the ability to monitor progressive CKD. These were confirmed by the fact that reduced medullary R2* was associated with higher annual loss in eGFR. These data collectively emphasize the need for inclusion of medulla in the analysis of renal BOLD MRI studies.

Cellular Senescence Is Associated with Faster Progression of Focal Segmental Glomerulosclerosis

Background: A current, albeit unproven, hypothesis is that an acceleration of cellular senescence is involved in impaired renal repair and progression of glomerular diseases. Focal segmental glomerulosclerosis (FSGS) is a glomerular disease with a substantial risk for progression to ESRD. However, if and to what extent cell senescence predicts a negative outcome in FSGS is still unknown. Methods: The hypothesis that cell senescence represents a proximate mechanism by which the kidney is damaged in FSGS (NOS phenotype) was investigated in 26 consecutive kidney biopsies from adult FSGS cases (eGFR 72 ± 4 mL/min, proteinuria 2.3 ± 0.6 g/day) who were incident for 2 years in a Northern Italian nephrology center and had a 6-year clinical follow-up. Results: Cell senescence (p16^INK4A, SA-β-galactosidase [SA-β-Gal]) was upregulated by ∼3- to 4-fold in both glomerular and tubular cells in kidney biopsies of FSGS as compared to age-matched controls (p < 0.05–0.01). Tubular SA-β-Gal correlated with proteinuria and glomerulosclerosis, while only as a trend, tubular p16^INK4A was directly associated with interstitial fibrosis. At univariate analysis, basal eGFR, proteinuria, and tubular expression of SA-β-Gal and p16^INK4A were significantly directly related to the annual loss of eGFR. No correlation was observed between glomerular p16^INK4A and eGFR loss. However, at multivariate analysis, eGFR, proteinuria, and tubular p16^INK4A, but not SA-β-Gal, contributed significantly to the prediction of eGFR loss. Conclusions: The results indicate that an elevated cell senescence rate, expressed by an upregulation of p16^INK4A in tubules at the time of initial biopsy, represents an independent predictor of progression to ESRD in adult patients with FSGS.

After ten years of follow-up, no difference between supportive care plus immunosuppression and supportive care alone in IgA nephropathy

The randomized, controlled STOP-IgAN trial in patients with IgA nephropathy (IgAN) and substantial proteinuria showed no benefit of immunosuppression added on top of supportive care on renal function over three years. As a follow-up we evaluated renal outcomes in patients over a follow-up of up to ten years in terms of serum creatinine, proteinuria, end-stage kidney disease (ESKD), and death. The adapted primary endpoint was the time to first occurrence of a composite of death, ESKD, or a decline of over 40% in the estimated glomerular filtration rate (eGFR) compared to baseline at randomization into STOP-IgAN. Data were analyzed by Cox-regression models. Follow-up data were available for 149 participants, representing 92% of the patients originally randomized. Median follow-up was 7.4 years (inter quartile range 5.7 to 8.3 years). The primary endpoint was reached in 36 of 72 patients randomized to supportive care and 35 of 77 patients randomized to additional immunosuppression (hazard ratio 1.20; 95% confidence interval 0.75 to 1.92). ESKD occurred in 17 of the patients with supportive care and in 20 of the patients with additional immunosuppression. Additionally, the rates of eGFR loss over 40% and annual eGFR loss did not differ between groups. Two patients died with supportive care and three with additional immunosuppression. Thus, within the limitations of a retrospective study, over a follow-up of up to ten years, and using an adapted primary endpoint, we failed to detect differences in key clinical outcomes in IgAN patients randomized to receive added immunosuppression on top of supportive care versus supportive care alone.

Renal outcomes of STOP-IgAN trial patients in relation to baseline histology (MEST-C scores)

BackgroundThe Oxford classification of IgA nephropathy (IgAN) defines histologic criteria (MEST-C) that provide prognostic information based on the kidney biopsy. There are few data on the predictive impact of this classification in randomized clinical trial settings.MethodsWe performed an exploratory analysis of MEST-C scores in 70 available renal biopsies from 162 randomized STOP-IgAN trial participants and correlated the results with clinical outcomes. Analyses were performed by researchers blinded to the clinical outcome of the patients. Biopsies had been obtained 6.5 to 95 (median 9.4) months prior to randomization.ResultsMesangial hypercellularity (M1) associated with higher annual eGFR-loss during the 3-year trial (M1: − 5.06 ± 5.17 ml/min/1.73 m2, M0: − 0.79 ± 4.50 ml/min/1.73 m2, p = 0.002). An M0-score additionally showed a weak association with full clinical remission, whereas the percentage of patients losing ≥15 ml/min/1.73 m2 over the 3-year trial phase was higher among those scored as M1. Among patients with additional immunosuppression, ESRD occurred more frequently in patients when tubulointerstitial fibrosis (T1/2) was present (T1/2 = 33%, T0 = 0%, p = 0.008). In patients receiving supportive care only, ESRD frequencies were similar (T1/2 = 18%, T0 = 7%, p = 0.603). At randomization, eGFR was significantly lower when tubulointerstitial fibrosis was present (T1/2: 45.2 ± 15.7 ml/min/1.73 m2, T0: 74.6 ± 28.2 ml/min/1.73 m2, p < 0.0001). Endocapillary hypercellularity (E), and glomerular segmental sclerosis (S) were not associated with any clinical outcome parameter. In the analyzed cohort, patients with glomerular crescents (C1/2 scores) in their biopsies were more likely to develop ESRD during the 3-year trial phase, but this trend was only significant in patients under supportive care.ConclusionsThis secondary analysis of STOP-IgAN biopsies indicates that M1, T1/2 and C1/2 scores associate with worse renal outcomes.

Analysis of heterogeneity in kidney function decline in the aged population

Objective To study the rate of kidney function decline and the influencing factors in the aged population. Methods This was a prospective population-based study of 468 participants aged 65 years and older.All participants’ general health information and serum creatinine levels were collected as the baseline.After a 3-year follow-up, the serum creatinine level of each participant was measured again.Kidney function was assessed with estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation.Outcomes of interest were mean eGFR decline and rapid decline in eGFR (annual eGFR loss≥3 ml·min-1·1.73 m-2). Risk factors were analyzed with Logistic regression. Results At baseline, the mean age of participants was(78.4±8.7)years and the mean eGFR was(74.8 ± 14.5)ml·min-1·1.73 m-2.Annual eGFR decline was 1.5 ml·min-1·1.73 m-2, with rapid declines in 149 (32%) participants and stable kidney function in 319 (68%) individuals.The rate of kidney function loss slowed down as the age increased.Baseline eGFR was an independent predictor for rapid kidney function decline.The incidence of rapid kidney function decline in individuals with eGFR≥60 ml·min-1·1.73 m-2 was 2.40 times (95%CI: 1.16-4.98) higher than that of participants with eGFR<60 ml·min-1·1.73 m-2 after adjustment for confounders. Conclusions Kidney function changes in the community-dwelling elderly in China are heterogeneous.Most elderly individuals do not show appreciable kidney function decline over a 3-year period. Key words: Glomerular filtration rate; Kidney function decline

Fabry disease under enzyme replacement therapy-new insights in efficacy of different dosages.

Fabry patients on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in estimated glomerular filtration rate (eGFR) and an increase of the Mainz Severity Score Index. In this prospective observational study, we assessed end-organ damage and clinical symptoms in 112 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, who were (i) non-randomly assigned to continue this treatment regime (regular-dose group, n = 37); (ii) received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n = 38); or (iii) were re-switched to agalsidase-beta after receiving agalsidase-alfa for at least 12 months (re-switch group, n = 37) with a median follow-up of 53 (38-57) months. eGFR of patients in the regular-dose group remained stable. Patients in the switch group showed an annual eGFR loss of - 4.6 ± 9.1 mL/min/1.73 m2 (P < 0.05). Patients in the re-switch group also had an eGFR loss of - 2.2 ± 4.4 mL/min/1.73 m2 after re-switch to agalsidase-beta, but to a lower degree compared with the switch group (P < 0.05). Patients in the re-switch group suffered less frequently from diarrhoea (relative risk 0.42; 95% confidence interval 0.19-0.93; P = 0.02). Lyso-Gb3 remained stable in the switch (P = 0.97) and the regular-dose (P = 0.48) groups, but decreased in the re-switch group after change of the therapy regimen (P < 0.05). After switch to agalsidase-alfa, Fabry patients experienced a continuous decline in eGFR, while this decline was attenuated in patients who were re-switched to agalsidase-beta. Decreasing lyso-Gb3 levels may indicate a better treatment response in the latter group.

N-Glycan Profile and Kidney Disease in Type 1 Diabetes.

Poorer glycemic control in type 1 diabetes may alter N-glycosylation patterns on circulating glycoproteins, and these alterations may be linked with diabetic kidney disease (DKD). We investigated associations between N-glycans and glycemic control and renal function in type 1 diabetes. Using serum samples from 818 adults who were considered to have extreme annual loss in estimated glomerular filtration rate (eGFR; i.e., slope) based on retrospective clinical records, from among 6,127 adults in the Scottish Diabetes Research Network Type 1 Bioresource Study, we measured total and IgG-specific N-glycan profiles. This yielded a relative abundance of 39 total (GP) and 24 IgG (IGP) N-glycans. Linear regression models were used to investigate associations between N-glycan structures and HbA1c, albumin-to-creatinine ratio (ACR), and eGFR slope. Models were adjusted for age, sex, duration of type 1 diabetes, and total serum IgG. Higher HbA1c was associated with a lower relative abundance of simple biantennary N-glycans and a higher relative abundance of more complex structures with more branching, galactosylation, and sialylation (GP12, 26, 31, 32, and 34, and IGP19 and 23; all P < 3.79 × 10-4). Similar patterns were seen for ACR and greater mean annual loss of eGFR, which were also associated with fewer of the simpler N-glycans (all P < 3.79 × 10-4). Higher HbA1c in type 1 diabetes is associated with changes in the serum N-glycome that have elsewhere been shown to regulate the epidermal growth factor receptor and transforming growth factor-β pathways that are implicated in DKD. Furthermore, N-glycans are associated with ACR and eGFR slope. These data suggest that the role of altered N-glycans in DKD warrants further investigation.

Systems Biology-Derived Biomarkers to Predict Progression of Renal Function Decline in Type 2 Diabetes.

Chronic kidney disease (CKD) in diabetes has a complex molecular and likely multifaceted pathophysiology. We aimed to validate a panel of biomarkers identified using a systems biology approach to predict the individual decline of estimated glomerular filtration rate (eGFR) in a large group of patients with type 2 diabetes and CKD at various stages. We used publicly available "omics" data to develop a molecular process model of CKD in diabetes and identified a representative parsimonious set of nine molecular biomarkers: chitinase 3-like protein 1, growth hormone 1, hepatocyte growth factor, matrix metalloproteinase (MMP) 2, MMP7, MMP8, MMP13, tyrosine kinase, and tumor necrosis factor receptor-1. These biomarkers were measured in baseline serum samples from 1,765 patients recruited into two large clinical trials. eGFR decline was predicted based on molecular markers, clinical risk factors (including baseline eGFR and albuminuria), and both combined, and these predictions were evaluated using mixed linear regression models for longitudinal data. The variability of annual eGFR loss explained by the biomarkers, indicated by the adjusted R2 value, was 15% and 34% for patients with eGFR ≥60 and <60 mL/min/1.73 m2, respectively; variability explained by clinical predictors was 20% and 31%, respectively. A combination of molecular and clinical predictors increased the adjusted R2 to 35% and 64%, respectively. Calibration analysis of marker models showed significant (all P < 0.0001) but largely irrelevant deviations from optimal calibration (calibration-in-the-large: -1.125 and 0.95; calibration slopes: 1.07 and 1.13 in the two groups, respectively). A small set of serum protein biomarkers identified using a systems biology approach, combined with clinical variables, enhances the prediction of renal function loss over a wide range of baseline eGFR values in patients with type 2 diabetes and CKD.

Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy

Background: Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits. Methods: The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy. Results: Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR. Conclusion: In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline.

Functional Status and Mortality in Chronic Kidney Disease: Results from a Prospective Observational Study

Background/Aims: Measures of functional status are used in the general population to aid prognostication but their use has not been explored in pre-dialysis chronic kidney disease (CKD). This analysis considers the association between the Karnofsky performance score (KPS) and all-cause mortality in a CKD stage 3-5 cohort. Methods: Patients were selected from the Chronic Renal Insufficiency Standards Implementation Study (CRISIS), a prospective observational study of outcome in CKD. Risk for death was assessed using multivariate Cox regression, and differences in progression of biochemical parameters were considered in a mixed-effects model. Results: A total of 1,515 patients with a median follow-up time of 2.9 (1.5-4.8) years were considered. Baseline age was 60 ± 11 years and eGFR was 30 ± 12 ml/min/1.73 m². Patients with a reduced KPS had an increased risk for death. The hazard ratio (HR) for death was: KPS 90 group, HR 1.2 (95% CI 0.9-1.5), p = 0.1; KPS ≤80 group, HR 1.8 (95% CI 1.4-2.4), p < 0.001. In the mixed-effects model, the average annual loss of eGFR was greater in patients with a KPS ≤80 versus patients with a KPS >80 (5 vs. 3%, p = 0.008). Conclusion: A reduced KPS is independently associated with risk for mortality in patients with CKD stages 3-5. This may relate to a more rapid loss of eGFR.

Chronic kidney disease in patients with the Philadelphia-negative chronic myeloproliferative neoplasms

The progression of kidney function and frequency of chronic kidney disease (CKD) in patients with the Philadelphia-negative myeloproliferative neoplasms (MPN) is unknown, although CKD is linked to increased mortality. This longitudinal retrospective study evaluates the estimated glomerular filtration rate (eGFR) in 143 MPN patients over a period of 9 years. 29% of patients had CKD stage 3 or 4 at time of diagnosis. 20% of patients had a rapid annual loss of eGFR (>3mL/min/1.73m(2)) and eGFR was negatively correlated to monocyte and neutrophil counts. Kidney impairment might contribute to the increased mortality observed in MPN patients.