Rate Of Decline In Renal Function Research Articles

Renal histology in diabetic nephropathy predicts progression to end-stage kidney disease but not the rate of renal function decline

BackgroundWhile histopathologic changes correlate with functional impairment in cross-sectional studies of diabetic nephropathy (DN), whether these findings predict future rate of kidney function loss remains uncertain. We thus sought to examine the relationship between kidney histopathology, incidence of end-stage kidney disease (ESKD), and rate of estimated glomerular filtration rate (eGFR) loss in DN.MethodsIn this longitudinal cohort study, we studied 50 adults diagnosed with biopsy-proven DN. We analyzed the histopathologic parameters of each patient’s kidney biopsy, as defined by the Renal Pathology Society classification system for DN, and tracked all available eGFR measurements post-biopsy. We additionally collected baseline clinical parameters (at the time of biopsy), including eGFR, albumin-to-creatinine ratio (ACR), and hemoglobin A1c. Multivariable linear regression was used to assess the relationship between histologic and clinical parameters at the time of the biopsy and eGFR slope. Kaplan-Meier curves and Cox regression were used to evaluate the association between histologic and clinical parameters and ESKD incidence.ResultsProgression to ESKD was associated with worsening interstitial fibrosis score (p = 0.05), lower baseline eGFR (p = 0.02), higher ACR (p = 0.001), and faster eGFR decline (p < 0.001). The rate of eGFR decline did not associate with any histologic parameter. Baseline ACR was the only studied variable correlating with eGFR slope (rho = − 0.41).ConclusionsRenal histology predicts ultimate progression to ESKD, but not the rate of progression. Future work is required to identify novel predictors of rapid functional decline in patients with diabetic nephropathy.

Treatment for IgA nephropathy with stage 3 or 4 chronic kidney disease: low-dose corticosteroids combined with oral cyclophosphamide.

The use of immunosuppressive therapy for IgA nephropathy patients with renal insufficiency and severe proteinuria is controversial. This was a monocentric retrospective study. We reviewed 132 consecutive IgA nephropathy (IgAN) patients with stage 3 or 4 chronic kidney disease and proteinuria ≥ 1.0g/d who received uncontrolled supportive care (n = 41), corticosteroids (CS) (n = 22) or low-dose CS combined with oral cyclophosphamide (CTX) (n = 69) between January 2008 and December 2016. The combined endpoint was defined as either a ≥ 50% reduction in eGFR or ESRD. All patients were followed for a medial of 33.2months, and 67 (50.8%) patients experienced the combined endpoint. The rate of renal function decline was - 4.5 (- 12.6, - 0.1) ml/min/1.73m2peryear. In multivariate Cox regression analyses, immunosuppressive therapy (HR = 0.349, 95% CI 0.194-0.629, P < 0.001) was associated with reduced risk of combined events after adjusting for age, sex, MAP, proteinuria, eGFR, mesangial hypercellularity score > 0.5 (M1), endocapillary hypercellularity present (E1), segmental glomerulosclerosis present (S1), tubular atrophy/interstitial fibrosis > 25% (T1-2), crescents present (C1-2), and RAAS blockers. Immunosuppressive therapy was also analyzed as a categorical variable, and multivariate Cox analyses showed that CS did not reduce the risk of combined events, whereas CS + CTX significantly reduced the risk of combined events. In the matched cohort, the CS + CTX group had a significantly lower reduction in TP-A [1.2 (0.6, 2.3) g/d verse 1.8 (1.2, 2.5), P = 0.023] and a better renal survival rate (39.4% verse 66.7%, P = 0.026) than the uncontrolled supportive care group. The number of hospitalizations required for infection was similar in the three study groups. Other adverse events did not differ significantly among the three groups. Low-dose CS combined with oral CTX treatment is possibly more effective than uncontrolled supportive care for IgAN patients with reduced renal function. The results need to be further confirmed by randomized controlled studies.

Detrimental effect of renin-angiotensin blockade on progression of chronic kidney disease at later stages: A matter of dosage adjustment?

IntroductionThe renoprotective effect of renin-angiotensin (RAS) blockers (angiotensin converting enzyme inhibitors and angiotensin receptor blockers) has been questioned in patients with advanced chronic kidney disease (CKD). Moreover, combination therapy (dual RAS blockade) can further accelerate renal function decline in some populations at risk. However, it is unknown whether this adverse outcome is due to a dose-dependent effect or if it can be attributed more specifically to a drug interaction. AimThis study aims to investigate if the rate of renal function decline in advanced CKD patients is associated to the doses of RAS blockers, and if dual RAS blockade worsens renal function independently of major confounding factors. Material and methodsRetrospective, observational study in an incident cohort of adult patients with CKD stage 4 or 5 not on dialysis, treated with RAS blockers for at least 6 months prior to the study inclusion. Inclusion criteria were: having at least three consecutive measurements of estimated glomerular filtration rate (eGFR) in a follow-up period >3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. Equipotent doses of RAS blockers were normalised for a body weight of 70 kg or a body surface area of 1.73 m2 (END-RASI). Associations of END-RASI or dual RAS blockade with the rate of renal function decline were analysed by uni- or multivariate linear regression models, accounting for major confounding variables. ResultsThe study group consisted of 813 patients (mean age 64 ± 14 years, 430 males) with a mean eGFR 14.9 ± 4.2 ml/min/1.73 m2. 729 patients were on RAS blockade monotherapy and 84 on dual RAS blockade. Median END-RASI in the whole group was 0.91 (I.Q. ranges 0.69–1.20). Patients on dual RAS blockade had significantly higher END-RASI than the rest of study patients (1.52 ± 0.49 vs. 0.93 ± 0.44; p < 0.0001). In univariate linear regression, END-RASI were significantly correlated with eGFR decline (R = −0.149; p < 0.0001). Patients on dual RAS blockade showed a significantly faster decline of renal function than the rest of the study patients (−6.19 ± 5.57 vs. −3.04 ± 5.37 ml/min/1.73 m2/year, p < 0.0001). By multivariate linear regression, while dual RAS blockade remained independent and significantly associated with faster renal function decline (beta = −0.094; p = 0.005), END-RASI (normalised either for body weight or surface area) did not reach statistical significance. ConclusionEND-RASI are significantly associated with the rate of renal function decline in advanced CKD patients. However, the detrimental effect of dual RAS blockade on CKD progression seems to be independent of END-RASI and other major confounding factors.

MON-299 KIDNEY OUTCOMES ASSOCIATED WITH INITIATION OF SODIUM GLUCOSE CO-TRANSPORTER 2 INHIBITION VERSUS OTHER GLUCOSE LOWERING DRUGS - AN ANALYSIS FROM THE CVD-REAL STUDY

Recent cardiovascular outcome trials have shown that sodium glucose co-transporter 2 inhibitors (SGLT-2i) slow progression of chronic kidney disease in patients with type 2 diabetes at high cardiovascular risk. Whether these benefits extend to patients with type 2 diabetes treated in clinical practice is unknown. The purpose of this study was to determine kidney outcomes and estimated glomerular filtration rate (eGFR) decline in patients initiating SGLT-2i versus other glucose lowering drugs (oGLDs) in a real world setting. New users of SGLT-2i and oGLDs were identified via claims, medical records, and national registries in Japan and Israel. Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching. Propensity score included amongst others baseline eGFR and eGFR slope prior to SGLT-2i or oGLDs initiation (index date). After propensity score matching more than 25000 individuals were included. The primary outcome measure was the total eGFR slope after the index date calculated with a linear mixed regression model. Differences in eGFR slope between SGLT-2is and oGLDs were calculated by country and pooled using weighted meta-analyses. Additional outcomes were a composite endpoint of 50% eGFR decline or end-stage kidney disease (ESKD) and their individual components. Hazard ratios (HRs) for these outcomes, calculated with Cox proportional hazard models, were assessed by country and pooled using weighted meta-analysis. After propensity matching, there were 14120 episodes of treatment initiation in each group. Dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, luseogliflozin and tofogliflozin accounted for 30.1%, 62.8%, 1.6%, 3.3%, 0.9%, and 1.3% of SGLT2i initiation, respectively. At the index date, mean age was 61.5 years, eGFR was 91.5 ml/min/1.73m2, HbA1c was 8.4%, and 40.4% were female. Annual eGFR change prior to oGLDs or SGLT2i initiation was −0.75 and −0.71 ml/min/1.73m2/year, respectively. The annual rate of eGFR change during oGLDs was −1.0 (95%CI −1.1 to −0.9) ml/min/1.73m2/year and during SGLT2i treatment 0.0 ml/min/1.73m2/year (95%CI −0.1 to 0.1; p vs. oGLDs <0.001). During a mean follow-up of 18 months, 52 (0.37%) patients reached the primary renal endpoint in the SGLT2i group and 104 (0.74%) in the oGLDs group (hazard ratio 0.51 [95%CI 0.36 to 0.71]). Use of SGLT2i versus oGLD was associated with a lower risk of the individual components of the endpoint: ESKD (HR 0.32 [95%CI 0.15 to 0.71); 50% eGFR decline (HR 0.53 [95%CI 0.38 to 0.76]). These effects were consistent across countries. In this large international real world clinical practice database of patients with type 2 diabetes, SGLT2i use was associated with a slower rate of renal function decline and lower risk of clinically meaningful renal events compared to oGLDs. These data indicate that the beneficial effects of SGLT2i on kidney function as observed in clinical trials translate to daily clinical practice.

Efecto negativo del bloqueo del sistema renina-angiotensina sobre la progresión de la enfermedad renal crónica avanzada: ¿una cuestión de ajuste de dosis?

IntroductionThe renoprotective effect of renin-angiotensin (RAS) blockers (angiotensin converting enzyme inhibitors and angiotensin receptor blockers) has been questioned in patients with advanced chronic kidney disease (CKD). Moreover, combination therapy (dual RAS blockade) can further accelerate renal function decline in some populations at risk. However, it is unknown whether this adverse outcome is due to a dose-dependent effect or if it can be attributed more specifically to a drug interaction.Aim This study aims to investigate if the rate of renal function decline in advanced CKD patients is associated to the doses of RAS blockers, and if dual RAS blockade worsens renal function independently of major confounding factors. Material and methodsRetrospective, observational study in an incident cohort of adult patients with CKD stage 4 or 5 not on dialysis, treated with RAS blockers for at least 3 months prior to the study inclusion. Inclusion criteria were: having at least three consecutive measurements of estimated glomerular filtration rate (eGFR) in a follow-up period >3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. Equipotent doses of RAS blockers were normalised for a body weight of 70kg or a body surface area of 1.73m2 (END-RASI). Associations of END-RASI or dual RAS blockade with the rate of renal function decline were analysed by uni- or multivariate linear regression models, accounting for major confounding variables. ResultsThe study group consisted of 813 patients (mean age 64±14 years, 430 males) with a mean eGFR 14.9±4.2ml/min/1.73m2; 729 patients were on RAS blockade monotherapy and 84 on dual RAS blockade. Median END-RASI in the whole group was 0.91 (I.Q. ranges: 0.69-1.20). Patients on dual RAS blockade had significantly higher END-RASI than the rest of study patients (1.52±0.49 vs. 0.93±0.44; p<0.0001). In univariate linear regression, END-RASI were significantly correlated with eGFR decline (R=−0.149; p<0.0001). Patients on dual RAS blockade showed a significantly faster decline of renal function than the rest of the study patients (−6.19±5.57 vs. −3.04±5.37ml/min/1.73m2/year, p<0.0001). By multivariate linear regression, while dual RAS blockade remained independent and significantly associated with faster renal function decline (beta=−0.094; p=0.005), END-RASI (normalised either for body weight or surface area) did not reach statistical significance. ConclusionEND-RASI are significantly associated with the rate of renal function decline in advanced CKD patients. However, the detrimental effect of dual RAS blockade on CKD progression seems to be independent of END-RASI and other major confounding factors.

Renal Function Decline in Latinos With Type 2 Diabetes

IntroductionDiabetic nephropathy remains a highly prevalent microvascular complication in individuals with type 2 diabetes mellitus (T2DM). Hispanic individuals are at increased risk of metabolic and cardiovascular complications compared with non-Hispanic white individuals. We described the long-term kidney outcomes using a culturally based approach to diabetes management in Hispanic patients implemented by the Joslin Diabetes Center’s Latino Diabetes Initiative.MethodsOur retrospective study included 594 Hispanic patients evaluated at the Joslin Diabetes Center from July 2002 to July 2015. Demographic and clinical data were collected from the outpatient visits.ResultsUncontrolled high blood pressure (hazard ratio [HR]: 1.72; 95% confidence interval [CI]:1.18–2.51; P = 0.005), overweight (HR: 2.68; 95% CI: 1.13–6.38; P = 0.026), and longstanding T2DM duration (HR: 1.11; 95% CI: 1.08–1.14; P < 0.0001) at baseline were significantly associated with increased risk of chronic kidney disease (CKD). Although poor glycemic control (HR: 1.18; 95% CI: 1.099–1.258; P < 0.0001), systolic blood pressure (SBP) >140 (HR: 1.01; 95% CI: 1.006–1.02; P = 0.0002), and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use (HR: 1.53; 95% CI: 1.03–2.29; P = 0.04) were significantly associated with increased CKD incidence during follow-up. Interestingly, statin use was associated with lower CKD incidence during the follow-up (HR: 0.52; 95% CI: 0.42–0.65; P < 0.0001). The annual rate of renal function decline in our cohort was estimated to be –1.39 ml/min per 1.73 m2.ConclusionRenal function decline in Latinos is associated with expected but modifiable variables, such as uncontrolled diabetes, uncontrolled hypertension, and being overweight. However, the annual rate of renal function decline in our cohort was estimated to be comparatively higher than previous reports in Hispanic individuals without T2DM, and the general US population with T2DM, but lower than expected for this high-risk group. We highlight the importance of a culturally based patient-centered therapeutic approach to improve long-term outcomes in Hispanic patients at high risk of CKD.

Skin autofluorescence is associated with rapid renal function decline in subjects at increased risk of coronary artery disease

Skin autofluorescence (AF) has been validated as a tool for estimating tissue advanced glycation end products (AGEs) accumulation and predicting long-term cardiovascular outcomes. However, whether measurements of skin AF could predict renal function decline remains controversial. From April, 2014 to April, 2015, we enrolled 245 subjects with at least two conventional risk factors for coronary artery disease (CAD). All were measured for body height and weight, blood pressure, plasma creatinine level, and skin AF at the start of the study. Baseline demographics and laboratory tests data were obtained by chart reviews and patient interviews. Serial plasma creatinine levels were followed regularly every 6–12 months for 2 years. In a stepwise multivariate linear regression analysis, skin AF, was an independent factor for predicting the relative renal function decline rate after adjustment of multiple covariates (ß = -0.036±0.016; p = 0.03). Subgroups analysis revealed that skin AF was a significant factor for relative renal function decline rate in subgroups of age < 65 years (ß = -0.068±0.024; p = 0.02), male sex (ß = -0.053±0.016; p< 0.01), body mass index≧25 Kg/m2(ß = -0.042±0.021; p = 0.04), and estimated glomerular filtration rate ≥ 60 ml/min/1.73m2(ß = -0.043±0.020; p = 0.04). However, only an interaction between skin AF and age attained significance (p for interaction = 0.04). Skin AF is a useful predictor for renal function decline in patients at increased risk of CAD.

The Primary-Secondary Care Partnership to Improve Outcomes in Chronic Kidney Disease (PSP-CKD) Study: A Cluster Randomized Trial in Primary Care.

Most patients with CKD are managed in the community. Whether nurse-led CKD management programs improve outcomes in patients with CKD in primary care is unclear. To assess the effect of such a program on the rate of renal function decline in patients with CKD (stages 3-5) in primary care in the United Kingdom, we conducted a cluster randomized trial, the Primary-Secondary Care Partnership to Improve Outcomes in Chronic Kidney Disease study. A software program designed for the study created a data file of patients with CKD in participating practices. In 23 intervention practices (11,651 patients), a CKD nurse practitioner worked with nominated practice leads to interpret the data file and implement guideline-based patient-level CKD management interventions. The 23 control practices (11,706 patients) received a data file but otherwise, continued usual CKD care. The primary outcome was defined at the cluster (practice) level as the change from baseline of the mean eGFR of the patients with CKD at 6-month intervals up to 42 months. Secondary outcomes included numbers of patients coded for CKD, mean BP, numbers of patients achieving National Institute for Health and Care Excellence BP targets for CKD, and proteinuria measurement. After 42 months, eGFR did not differ significantly between control and intervention groups. CKD- and proteinuria-related coding improved significantly along with the number of patients achieving BP targets in the intervention group versus usual care. CKD management programs in primary care may not slow progression of CKD, but they may significantly improve processes of care and potentially decrease the cardiovascular disease burden in CKD and related costs.

Modelling the long-term benefits of tolvaptan therapy on renal function decline in autosomal dominant polycystic kidney disease: an exploratory analysis using the ADPKD outcomes model

BackgroundThe short-term efficacy of tolvaptan in patients with autosomal dominant polycystic kidney disease (ADPKD) has been demonstrated across several phase 3 trials, while the ADPKD Outcomes Model (ADPKD-OM) represents a validated approach to predict natural disease progression over a lifetime horizon. This study describes the implementation of a tolvaptan treatment effect within the ADPKD-OM and explores the potential long-term benefits of tolvaptan therapy in ADPKD.MethodsThe effect of tolvaptan on ADPKD progression was modelled by applying a constant treatment effect to the rate of renal function decline, consistent with that observed in the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes trial (TEMPO 3:4; ClinicalTrials.gov identifier NCT00428948). Predictions generated by the ADPKD-OM were compared against aggregated data from a subsequent extension trial (TEMPO 4:4; ClinicalTrials.gov identifier NCT01214421) and the Replicating Evidence of Preserved Renal Function an Investigation of Tolvaptan Safety Efficacy in ADPKD trial (REPRISE; ClinicalTrials.gov identifier NCT02160145). Following validation, an application of the ADPKD-OM sought to estimate the benefit of tolvaptan therapy on time to end-stage renal disease (ESRD), in a range of ADPKD populations.ResultsModel validation against TEMPO 4:4 and REPRISE demonstrated the accuracy and generalisability of the tolvaptan treatment effect applied within the ADPKD-OM. In simulated patients matched to the overall TEMPO 3:4 trial population at baseline, tolvaptan therapy was predicted to delay the mean age of ESRD onset by five years, compared to natural disease progression (57 years versus 52 years, respectively). In subgroup and sensitivity analyses, the estimated delay to ESRD was greatest among patients with CKD stage 1 at baseline (6.6 years), compared to CKD 2 and 3 subgroups (4.7 and 2.7 years, respectively); and ADPKD patients in Mayo subclasses 1C–1E.ConclusionsThis study demonstrated the potential for tolvaptan therapy to delay time to ESRD, particularly among patients with early-stage CKD and evidence of rapidly progressing disease. Data arising from this study highlight the value to be gained by early intervention and long-term treatment with tolvaptan, which may alleviate the economic and societal costs of providing care to patients who progress to ESRD.

Clinical Value of Complement Activation Biomarkers in Overt Diabetic Nephropathy

BackgroundExperimental studies support a role of complement activation in diabetic nephropathy (DN), yet few clinical correlates exist. We evaluated urinary levels of sC5b-9 membrane attack complex (MAC) in patients with overt DN, and examined its association with the glomerular filtration rate (GFR) decline, proteinuria, and inflammatory biomarkers. We explored different complement pathways and compared our findings to autoimmune glomerulonephritis.MethodsWe prospectively followed 83 patients with DN and obtained repeated measurements of proteinuria, complement fragments (sC5b-9, C4a, C1q, mannose-binding lectin–associated serine protease [MASP]-1, and factor Bb), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor (TGF)-β1. We assessed independence and interactions using general linear models and repeated measures analyses and compared levels with subjects with active focal and segmental glomerulosclerosis, ANCA-associated vasculitis, and membranous and IgA nephropathies (n = 63).ResultsThe diabetic cohort had an initial GFR of 25 ± 9 ml/min per 1.73 m2 and a renal function decline of 2.9 ± 3.0 ml/min per 1.73 m2 per year. All complement biomarkers were strongly intercorrelated and associated with biomarker inflammation and fibrosis, proteinuria, and the rate of renal function decline. There was a significant interaction (P = 0.03) between the level of proteinuria and urinary sC5b-9: in individuals with higher levels of urinary MAC, the relationship between proteinuria and the rate of renal function decline was more pronounced than in those with low urinary MAC. Finally, patients with DN had levels of urinary sC5b-9 comparable to autoimmune glomerulonephritis, when stratified by the level of proteinuria.ConclusionUrinary MAC is present in patients with overt DN at levels comparable to autoimmune glomerulonephritis and correlates with the GFR decline, supporting that complement activation and its measurement are clinically relevant in DN.

Long-Term Effects of Intensive Low-Salt Diet Education on Deterioration of Glomerular Filtration Rate among Non-Diabetic Hypertensive Patients with Chronic Kidney Disease

Background: Diet modification, especially a decrease in salt intake, might be an important non-pharmacological strategy to improve chronic kidney disease (CKD) prognosis. Objectives: We conducted a prospective cohort study to investigate whether an intensive low-salt diet education program effectively attenuated the rate of renal function decline in hypertensive patients with CKD. Methods: This cohort study recruited 171 participants from a previous open-labelled, case-controlled, randomized clinical trial that originally consisted of 245 hypertensive CKD patients who were assigned to two groups, intensive low-salt diet or conventional education. We evaluated the renal outcomes, which included the rate of change in estimated glomerular filtration rate (eGFR) per year, the increase in serum creatinine ≥50%, the decrease in eGFR ≥30%, and the percent change in albuminuria throughout the entire study period. Results: The baseline characteristics of the cohort participants between the two groups were similar at the time of trial phase randomization. During the whole study period, the rate of renal function decline was significantly faster in the conventional group (0.11 ± 4.63 vs. –1.53 ± 3.04 mL/min/1.73 m2/year, p = 0.01). The percent of incremental change in serum creatinine ≥50% was 1.1% in the intensive group and 8.2% in the conventional group (p = 0.025), and the percent of decremental change in eGFR ≥30% was 3.3% in the intensive group and 11.1% in the conventional group (p= 0.048). With logistic regression analysis adjusted for related factors, we found that the conventional group showed a higher risk for deterioration in serum creatinine and eGFR during the entire study period. Especially, we found that the intensive education program preserved eGFR in participants with one, several, or all of the following characteristics at the time of randomization: older age, female, obese, had higher protein intake, higher amounts of albuminuria, higher salt intake. Conclusion: This cohort study demonstrated that an intensive low-salt diet education program attenuated the rate of renal function decline in hypertensive CKD patients independent of its effect on lowering salt intake or albuminuria during the 36 months of follow-up.

Chronic Kidney Disease Severity Is Associated With Selective Expansion of a Distinctive Intermediate Monocyte Subpopulation

Chronic kidney disease (CKD) affects 11–13% of the world's population and greatly increases risk of atherosclerotic cardiovascular disease (ASCVD) and death. It is characterized by systemic inflammation and disturbances in the blood leukocytes that remain incompletely understood. In particular, abnormalities in the numbers and relative proportions of the three major monocyte subsets—classical, intermediate, and non-classical—are described in CKD and end-stage renal disease. In this study, we characterized absolute numbers of blood leukocyte subtypes in adults with renal function varying from normal to advanced CKD. The primary aim was to identify monocyte subpopulations that associated most closely with current estimated glomerular filtration rate (eGFR) and subsequent rate of eGFR decline. Leucocyte and monocyte populations were enumerated by multi-color flow cytometry of whole blood and peripheral blood mononuclear cell (PBMC) samples from adults with CKD stage 1–5 (n = 154) and healthy adults (n = 33). Multiple-linear regression analyses were performed to identify associations between numbers of leucocyte and monocyte populations and clinical characteristics including eGFR and rate of eGFR decline with adjustment for age and gender. In whole blood, total monocyte and neutrophil, but not lymphocyte, numbers were higher in adults with CKD 1-5 compared to no CKD and were significantly associated with current eGFR even following correction for age. In PBMC, classical and intermediate monocyte numbers were higher in CKD 1-5 but only intermediate monocyte numbers were significantly associated with current eGFR in an age-corrected analysis. When intermediate monocytes were further sub-divided into those with mid- and high-level expression of class II MHC (HLA-DRmid and HLA-DRhi intermediate monocytes) it was found that only DRhi intermediate monocytes were increased in number in CKD 1-5 compared to no CKD and were significantly associated with eGFR independently of age among the total (No CKD + CKD 1-5) study cohort as well as those with established CKD (CKD 1-5 only). Furthermore, blood number of DRhi intermediate monocytes alone proved to be significantly associated with subsequent rate of renal functional decline. Together, our data confirm neutrophil and monocyte subset dysregulation in CKD and identify a distinct subpopulation of intermediate monocytes that is associated with higher rate of loss of kidney function.

Urinary mitochondrial DNA level as a biomarker of tissue injury in non-diabetic chronic kidney diseases

BackgroundUrinary mitochondrial DNA (mtDNA) fragment level has been proposed as a biomarker of chronic kidney disease (CKD). In this study, we determine the relation between urinary mtDNA level and rate of renal function deterioration in non-diabetic CKD.MethodsWe recruited 102 non-diabetic CKD patients (43 with kidney biopsy that showed non-specific nephrosclerosis). Urinary mtDNA level was measured and compared to baseline clinical and pathological parameters. The patients were followed 48.3 ± 31.8 months for renal events (need of dialysis or over 30% reduction in estimated glomerular filtration rate [eGFR]).ResultsThe median urinary mtDNA level was 1519.42 (inter-quartile range 511.81–3073.03) million copy/mmol creatinine. There were significant correlations between urinary mtDNA level and baseline eGFR (r = 0.429, p < 0.001), proteinuria (r = 0.368, p < 0.001), severity of glomerulosclerosis (r = − 0.537, p < 0.001), and tubulointerstitial fibrosis (r = − 0.374, p = 0.014). The overall rate of eGFR decline was − 2.18 ± 5.94 ml/min/1.73m2 per year. There was no significant correlation between the rate of eGFR decline and urinary mtDNA level. By univariate analysis, urinary mtDNA level predicts dialysis-free survival, but the result became insignificant after adjusting for clinical and histological confounding factors.ConclusionUrinary mtDNA levels have no significant association with the rate of renal function decline in non-diabetic CKD, although the levels correlate with baseline renal function, proteinuria, and the severity of histological damage. Urinary mtDNA level may be a surrogate marker of permanent renal damage in non-diabetic CKD.

Switching from Allopurinol to Febuxostat: A Comparison of The Rate of Renal Functional Decline in Patients With Moderate and Severe Chronic Kidney Disease

Switching from Allopurinol to Febuxostat: A Comparison of The Rate of Renal Functional Decline in Patients With Moderate and Severe Chronic Kidney Disease

Elevated Baseline Glomerular Filtration Rate Is Associated with a More Rapid Decline in Chinese Patients with Type 2 Diabetes with Normoalbuminuria

Aims: To investigate the association between estimated baseline glomerular filtration rate (GFR) and renal function decline in Chinese patients with type 2 diabetes with normoalbuminuria. Main Methods: A longitudinal study was performed on 368 Chinese patients with type 2 diabetes whose estimated GFR (eGFR) was determined at baseline with a 3.12-year follow-up. The patients were divided into three groups according to baseline eGFR (mL/min/1.73 m2): G1 (eGFR ≥ 120), G2 (90 ≤ eGFR &amp;lt; 120), G3 (60 ≤ eGFR &amp;lt; 90). The association between baseline eGFR and the renal function decline rate was assessed using binary logistic regression. Decliners were defined as a negative change ≥ −3.3% per year. Key Findings: Among G1 patients, the decliners were younger, had a higher baseline eGFR, shorter duration of diabetes, and lower diastolic blood pressure, compared with non-decliners. The G1 eGFR decline slope (% per year) was significantly higher than that in G2 and G3 patients. The percentage of decliners among G1 patients was significantly higher than that among G2 and G3 patients. Baseline eGFR group, HbA1c, hypertension history, and diastolic blood pressure were independent risk factors for progressive renal decline. Patients in the decliners group were more likely to progress to microalbuminuria and macroalbuminuria compared with those in the non-decliners group; however, the albuminruria progression percentage was not significantly different among G1, G2, and G3 decliners. Significance: Patients with baseline eGFR ≥ 120 mL/min/1.73 m2 had a higher risk for more rapid eGFR decline among Chinese patients with type 2 diabetes with nomalbuminuria. Disclosure J. Wan: None. H. Chen: None.

Urinary mitochondrial DNA level in non-diabetic chronic kidney diseases

BackgroundMitochondrial dysfunction plays an important role in the pathogenesis and progression of chronic kidney disease (CKD). We study the relation between urinary mitochondrial DNA (mtDNA) levels and renal dysfunction in non-diabetic CKD. MethodsWe recruited 32 CKD patients (20 had hypertensive nephrosclerosis, 12 had IgA nephropathy). Urinary supernatant mtDNA level was measured and compared to baseline clinical and pathological parameters. The patients were followed 57.8 ± 30.5 months for renal function decline. ResultsThe average urinary supernatant mtDNA level was 222.0 ± 210.3 copy/μL. There was a modest but significant correlation between urinary mtDNA level and proteinuria (Spearman's r = 0.387, p = 0.035), but not any other baseline clinical or pathological parameter. Urinary mtDNA level had a significant inverse correlation with the slope of GFR decline (r = −0.402, p = 0.023). Urinary mtDNA level is a predictor of renal survival even after adjusting for baseline proteinuria with multivariate Cox analysis. In this model, every increase in urinary mtDNA by 100 copy/μL confers a 25.0% increase in risk of doubling of serum creatinine or need of dialysis (95%CI, 0.7% to 55.1%). ConclusionMitochondrial DNA is readily detectable in the urinary supernatant of non-diabetic CKD, and its level correlates with the rate of renal function decline and predicts the risk of doubling of serum creatinine or need of dialysis. Further studies are needed to determine the value of urinary supernatant mtDNA level as a prognostic indicator of non-diabetic CKD

Vitamin K antagonist use and renal function in pre-dialysis patients.

PurposeA post hoc analysis of a recent trial on direct oral anticoagulants versus vitamin K antagonists showed that amongst patients with mildly decreased kidney function, use of vitamin K antagonists was associated with a greater decline in renal function than use of direct oral anticoagulants. Whether these vitamin K antagonist effects are the same in pre-dialysis patients is unknown. Therefore, the aim of this study was to investigate the association between vitamin K antagonist use and the rate of renal function decline and time until start of dialysis in incident pre-dialysis patients.MethodsData from 984 patients from the PREdialysis PAtient REcord study, a multicenter follow-up study of patients with chronic kidney disease who started pre-dialysis care in the Netherlands (1999–2011), were analyzed. Of these patients, 101 used a vitamin K antagonist. Linear mixed models were used to compare renal function decline between vitamin K antagonist users and non-users. Cox proportional hazards models were used to estimate the HR with 95% CI for starting dialysis.ResultsVitamin K antagonist use was associated with an extra change in renal function of −0.09 (95% CI −1.32 to 1.13) mL/min/1.73 m2 per year after adjustment for confounding. The adjusted HR for the start of dialysis was 1.20 (95% CI 0.85 to 1.69) in vitamin K antagonist users, compared to non-users.ConclusionIn incident pre-dialysis patients, the use of vitamin K antagonists was not associated with an accelerated kidney function decline or an earlier start of dialysis compared to non-use. The lack of knowledge on the indication for vitamin K antagonist use could lead to confounding by indication.

Predictive abilities of cardiovascular biomarkers to rapid decline of renal function in Chinese community-dwelling population: a 5-year prospective analysis

BackgroundPredictive abilities of cardiovascular biomarkers to renal function decline are more significant in Chinese community-dwelling population without glomerular filtration rate (GFR) below 60 ml/min/1.73m2, and long-term prospective study is an optimal choice to explore this problem. Aim of this analysis was to observe this problem during the follow-up of 5 years.MethodsIn a large medical check-up program in Beijing, there were 948 participants with renal function evaluated at baseline and follow-up of 5 years. Physical examinations were performed by well-trained physicians. Blood samples were analyzed by qualified technicians in central laboratory.ResultsMedian rate of renal function decline was 1.46 (0.42–2.91) mL/min/1.73m2/year. Rapid decline of renal function had a prevalence of 23.5% (223 participants). Multivariate linear and Logistic regression analyses confirmed that age, sex, baseline GFR, homocysteine and N-terminal pro B-type natriuretic peptide (NT-proBNP) had independently predictive abilities to renal function decline rate and rapid decline of renal function (p < 0.05 for all). High-sensitivity cardiac troponin T (hs-cTnT), carotid femoral pulse wave velocity and central augmentation index had no statistically independent association with renal function decline rate and rapid decline of renal function (p > 0.05 for all).ConclusionsHomocysteine and NT-proBNP rather than hs-cTnT had independently predictive abilities to rapid decline of renal function in Chinese community-dwelling population without GFR below 60 ml/min/1.73m2. Baseline GFR was an independent factor predicting the rapid decline of renal function. Arterial stiffness and compliance had no independent effect on rapid decline of renal function. This analysis has a significant implication for public health, and changing the homocysteine and NT-proBNP levels might slow the rapid decline of renal function.

Retinopathy and left ventricular hypertrophy in patients with chronic kidney disease: Interrelationship and impact on clinical outcomes

BackgroundRetinopathy and left ventricular hypertrophy (LVH) are representative markers of microvascular and cardiac dysfunction in patients with chronic kidney disease (CKD). However, their relationship and their combined effects on clinical outcomes are unknown. MethodsWe included 401 patients with nondialysis-dependent CKD stage 3–5 who had been examined with fundus photography for diabetic or hypertensive retinopathy. The presence of LVH was identified by echocardiography. The clinical significance of retinopathy and LVH was evaluated in terms of the rate of renal function decline and for any cardiovascular event (CVE)/death. ResultsCKD patients with retinopathy had a higher prevalence of LVH than those without retinopathy (38.9% vs. 27.6%, P=0.017). The presence of retinopathy was independently associated with LVH (odds ratio 1.69, 95% confidence interval [CI] 1.02, 2.80). Compared with subjects without either retinopathy or LVH, the coexistence of retinopathy and LVH was independently associated with rapid renal function decline (β=−3.28; 95% CI −6.52, −0.04), whereas retinopathy or LVH alone were not. Patients with both retinopathy and LVH had a higher risk of CVE/death (adjusted hazard ratio 2.75; 95% CI 1.44, 5.26) than patients with either factor alone. A significant synergistic interaction was observed between retinopathy and LVH to predict CVE/death (P for interaction=0.049). ConclusionsRetinopathy was independently associated with LVH. The coexistence of retinopathy and LVH was associated with higher risks of CKD progression and CVE/death than was either factor alone, and their combined effects synergized to predict the risk of CVE/death.

Baseline and Time-Averaged Values Predicting Residual Renal Function Decline Rate in Japanese Peritoneal Dialysis Patients.

Residual renal function (RRF) is a strong prognostic factor of morbidity and mortality in patients undergoing peritoneal dialysis (PD). We determined predictors of the RRF rate of decline using both baseline values and time-averaged ones. We retrospectively analyzed 94 patients being treated with PD at the Japanese Red Cross Medical Center. The decline rate of RRF was calculated by a diminution in the weekly renal Kt/V between the first and last follow up divided by follow-up years. The mean follow-up period was 2.28 years, and the mean decline rate of weekly renal Kt/V was 0.25 per year. A multivariate analysis using baseline parameters identified dialysis-to-plasma ratios of creatinine at 4 h (P = 0.02), urinary protein (P = 0.02), and mean blood pressure (MBP) (P < 0.01) as being positively associated with the RRF rate of decline, while the use of angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) had a negative correlation (P = 0.03). When using time-averaged values as independent variables, a lower weekly total renal Kt/V (P < 0.0001), higher urinary protein (P < 0.0001), and higher MBP (P = 0.04) independently predicted a faster RRF rate of decline. We demonstrated that PD patients with a lower MBP and lower urinary protein both at baseline and throughout their PD duration had a slower RRF rate of decline. We recommend strict control of blood pressure and anti-proteinuric therapy for PD patients.