Worse Renal Outcome Research Articles

Urinary renal tubular epithelial cells and casts as predictors of renal outcomes in patients with biopsy-proven diabetic nephropathy.

Urine sediment examination is a time-tested and non-invasive diagnostic tool. Thisstudy investigated the characteristics of urine sediment and its association with severity and renal outcomes in diabetic nephropathy (DN) patients. A total of 201 biopsy-proven diabetic nephropathy patients (according to the pathological classification of diabetic nephropathyproposed by the Renal Pathology Society in 2010)who underwent manual urine sediment microscopic examination were included. We compared the clinicopathologicalcharacteristics of diabetic nephropathy patients with and without urinary renal tubular epithelial cells (RTECs) or renal tubular epithelial cell casts. The predictive value of urinary renal tubular epithelial cells or renal tubular epithelial cell casts for renal outcomes in diabetic nephropathy was analyzed. Fifty of 201 (24.9%) diabetic nephropathy patients had renal tubular epithelial cells or renal tubular epithelial cell casts in urine sediment. Diabetic nephropathy patients with renal tubular epithelial cells or renal tubular epithelial cell casts in urine sediment had a significantly higher level of proteinuria [6.0 (3.1, 9.7)vs.3.6 (1.8, 6.8) g/24h, p = 0.001], higher serum creatinine [227.9 (151.6, 338.1)vs.177.0 (104.4, 288.4) μmol/L, p = 0.016] and lower estimated glomerular filtration rate (eGFR) [25.8 (15.8, 44.8)vs.35.7 (19.9, 65.0) mL/min/1.73m2, p = 0.025] than those without.Cox regression analysis demonstrated that the presence of urinaryrenal tubular epithelial cells or renal tubular epithelial cell casts was independently associated with the development of end-stage kidney disease (ESKD) in diabetic nephropathy patients [HR 1.670, 95% CI (1.042, 2.676), p = 0.033]. Adding the presence of urinary renal tubular epithelial cells or renal tubular epithelial cell casts to the predictive model could improve the effectiveness of the model for predicting the risk of ESKD within one year after renal biopsy. The presence of urinary renal tubular epithelial cells or renal tubular epithelial cell casts was associated with more severe kidney injury and worse renal outcomes in patients with diabetic nephropathy, thus perhaps providing a noninvasive biomarker for predicting diabetic nephropathy.

#1774 ANCA vasculitis with renal involvement: age as a prognostic factor

Abstract Background and Aims Older patients with antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) commonly experience renal impairment and poor prognosis. The European Vasculitis Study Group trials showed that approximately 16.7% and 22.5% of older patients with AAV suffered from end-stage renal disease (ESRD) in 5- and 10-year durations. The aim of this study was to analyze differences in course and outcome of patients with AAV with respect to age. Method This retrospective observational study included patients with diagnosis of AAV and biopsy proven renal involvement between 2000-2021. Patients were divided into two groups according to age: ≥65 or <65 years old. We recorded baseline characteristics and clinical data during follow-up. Response was defined as a BVAS reduction of at least 50% or BVAS of 0, while receiving prednisone dose higher than 4 mg; and remission as BVAS of 0 while receiving prednisone dose of 4 mg or less. Results We included 42 patients with AAV diagnosis, 47.6% of which were 65 years-old or older. Mean age of the older age group was 77 ± 8 years. No differences were found between older and younger patients at baseline (BVAS, FFS extra-renal symptoms, serum creatinine at diagnosis, hematuria), Patients > 65 years were significantly more likely to present p-ANCA positive MPA, as shown in Table 1. There was no difference in initial or maintenance immunosuppressive therapy between the two groups. No differences were found between older and younger patients with regard to treatment response. Although we found no statistical differences, older patients had worse renal outcomes. The older adult group had a higher mortality rate, p 0.01. The average time to death was 27 months for patients over 65 years and 34.5 in those who were younger (p 0.71). Conclusion No differences were found between older and younger patients with regard to treatment response. However, mortality was higher during follow-up in the group of older patients. Our results suggest that more attention should be paid to older patients with severe renal impairment.

Kidney Measurement and Glomerular Filtration Rate Evolution in Children with Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron, and over time the cystic dilatation leads to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts leads to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and hematuria. However, the presentation of ADPKD varies in children, from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by a mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end-stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra-normal kidney function, we explored the glomerular filtration rates dynamics and the renal ultrasound-adjusted percentiles. In total, 14 out of 16 patients had kidney percentiles over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 mL/min/1.73 m2 when compared to Schwartz eGFR 126.28 ± 33.07 mL/min/1.73 m2, p = 0.14). Also, when the quadratic equation was employed, not even a single patient reached the glomerular hyperfiltration threshold. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1 year of follow-up (quadratic ΔeGFR = -0.32 ± 5.78 mL/min/1.73 m2), as opposed to the Schwartz formula that can falsely classify children in a hyperfiltration state (ΔeGFR = 7.51 ± 19.46 mL/min/1.73 m2), p = 0.019.

Histological reappraisal of IgA nephropathy: the role of glomerular pattern of injury and mesangial complement deposition

BackgroundThere is a clear need to refine the histological assessment in IgA Nephropathy (IgAN). We sought to investigate the clinical significance of the light microscopy (LM) pattern of glomerular injury and of the intensity of mesangial C3 staining in IgAN.MethodsWe conducted a retrospective, observational study that included all patients with biopsy-proven primary IgAN that had at least 12 months of follow-up. The LM pattern of glomerular injury was reevaluated based on a modified HAAS classification. Mesangial C3 deposition by immunofluorescence (IF) staining was scored semi-quantitatively. The study primary composite endpoint was defined as doubling of serum creatinine or ESRD (dialysis, renal transplant or eGFR < 15 ml/min). The secondary study endpoint was eGFR decline per year.ResultsThis cohort included 214 patients with IgAN (mean age, 41.4 ± 12.6 years), with a mean eGFR and median 24-h proteinuria of 55.2 ± 31.5 ml/min/1.73m2 and 1.5 g/day (IQR:0.8–3.25), respectively. The most frequent LM pattern was the mesangioproliferative (37.4%), followed by the sclerotic (22.5%) and proliferative/necrotizing patterns (21.4%). Regarding the IF findings, mild-moderate and intense mesangial C3 staining was present in 30.6% and 61.1% of patients, respectively. Those with sclerosing and crescentic patterns had the worst renal survival (5-year renal survival of 48.8% and 42.9%) and the highest rate of eGFR change/year (-2.32 ml/min/y and − 2.16 ml/min/y, respectively) compared to those with other glomerular patterns of injury. In addition, those with intense C3 staining reached the composite endpoint more frequently compared to those without intense C3 staining (35.5% vs. 21.4%, p = 0.04). After multivariate adjustment, patients with crescentic and sclerosing patterns had a 3.6-fold and 2.1-fold higher risk for the composite endpoint compared to those with mesangioproliferative pattern, while an intense mesangial C3 deposition being also associated with a worse renal outcome (HR, 3.33; 95%CI, 1.21–9.2).ConclusionsWe have shown that the LM pattern of glomerular injury and the intensity of mesangial C3 deposition might stratify more accurately the renal outcome in patients with IgAN.

Fluid balance, biomarkers of renal function and mortality in critically ill patients withAKI diagnosed before, or within 24h of intensive care unit admission: a prospective study.

To evaluate fluid balance, biomarkers of renal function and its relation to mortality in patients with acute kidney injury (AKI)diagnosed before, or within 24h of intensive care unit admission. A prospective cohort study considered773 critically ill patients observedover six years. Pre-intensive care unit-onset AKI was defined as AKI diagnosed before, or within 24h of intensive care unit admission. Body weight-adjusted fluid balance and fluid balance-adjusted biomarkers of renal function were measured daily for the first three days of intensive care unit admission. Primary outcome was mortality in theintensive care unit. Prevalence of pre-intensive care unit-onset AKI was 55.1%, of which 55.6% of cases were hospital-acquired and 44.4% were community-acquired. Fluid balance was higher in AKI patients than in non-AKI patients (p < 0.001) and had a negative correlation with urine output (p < 0.01). Positive fluid balance and biomarkers of renal function were independently related to mortality. Multivariate analysis identified the followingAKI-related variables associated with increased mortality: (1) In AKI patients: type 1 cardiorenal syndrome (OR 2.00), intra-abdominal hypertension (OR 1.71), AKI stage 3 (OR 2.15) and increase in AKI stage (OR 4.99); 2) In patients with community-acquiredAKI: type 1 cardiorenal syndrome (OR 5.16), AKI stage 2 (OR 2.72), AKI stage 3 (OR 4.95) and renal replacement therapy (OR 3.05); and 3) In patients with hospital-acquiredAKI: intra-abdominal hypertension (OR 2.31) and increase in AKI stage (OR 4.51). In patients with pre-intensive care unit-onset AKI, positive fluid balance is associated with worse renal outcomes. Positive fluid balance and decline in biomarkers of renal function are related to increased mortality, thus in this subpopulation of critically ill patients, positive fluid balance is not recommended and renal function must be closely monitored.

Cardiovascular outcomes of emergent vs elective transcatheter aortic valve replacement in severe aortic stenosis: regression matched meta-analysis.

Transcatheter aortic valve replacement (TAVR) has been highly increased as the recommended option for patients with a high surgical risk. This study aims to commit a systematic review and meta-analysis to assess the outcomes in severe aortic stenosis patients following emergency transcatheter aortic valve replacement (emergent TAVR) compared to elective TAVR or eBAV followed by elective TAVR. We conducted a systematic literature search of PubMed, Embase, Cochrane CENTRAL, CINAHL, Science Direct, and Google Scholar. We included nine studies in the latest analysis that reported the desired outcomes. Outcomes were classified into primary outcomes: 30-day all-cause mortality and 30-day readmission rate, and secondary outcomes, which were further divided into (a) peri-procedural outcomes, (b) vascular outcomes, and (c) renal outcomes. Statistical analysis was performed using Stata v.17 (College State, TX) software. A total of 44,731 patients with severe aortic stenosis were included (emergent TAVR n = 4502; control n = 40045). 30-day mortality was significantly higher in the emergent TAVR group (OR: 2.62; 95% CI = 1.76-3.92; P < 0.01). Regarding post-procedural outcomes, the length of stay was significantly higher in the emergent TAVR group (Hedges's g: +4.73 days; 95% CI = +3.35 to +6.11; P < 0.01). With respect to vascular outcomes, they were similar in both groups. Regarding renal outcomes, both acute kidney injury (OR: 2.52; 95% CI = 1.59-4.00; P < 0.01) and use of renal replacement therapy (OR: 2.33; 95% CI = 1.87-2.91; P < 0.01) were significantly higher in emergent TAVR group as compared to the control group. Our study demonstrated that despite increased 30-day mortality and worse renal outcomes, the post-procedural outcomes were similar in emergent and elective TAVR groups. The increased mortality and worse renal outcomes are likely due to hemodynamic instability in the emergent group. The similarity of post-procedural outcomes is evidence of the safety of TAVR even in emergent settings.

Evaluation of the impact of hemotransfusion on hospitalization length and complications in patients with non-variceal upper gastrointestinal bleeding

Background: Upper gastrointestinal bleeding (UGB) is a common emergency associated with high morbidity and mortality. It can be caused by various factors, including peptic ulcers and vascular lesions. The decision to perform blood transfusion in stable UGB patients is still controversial, with more restrictive strategies showing better outcomes. Methods: A retrospective cohort study reviewed 1433 medical records of non-variceal UGB patients in a Brazilian tertiary care setting. Patients were divided into groups based on whether they received blood transfusion or not. Patient characteristics, laboratory values, procedures, and outcomes were analyzed. Logistic and linear regression models were used to assess the association of blood transfusion with complications and hospital stay. Results: Blood transfusion was associated with increased hospitalization length (p&lt;0.001), higher rebleeding rates (p&lt;0.001), and greater clinical severity. However, no association with worse renal outcomes was observed (p=0.203). Adjusting for clinical severity (Glasgow-Blatchford score) reduced the significance of the association with hospitalization length. Conclusion: Blood transfusion in stable UGB patients may serve as a marker of severity, associated with longer hospital stay and increased rebleeding rates. It does not appear to have a direct causal relationship with worse renal outcomes. The study suggests that clinical severity may play a pivotal role in outcomes, as indicated by the association with Glasgow-Blatchford score.

Impact of red blood cell distribution width–albumin ratio on prognosis of patients with CKD

The red blood cell distribution width–albumin ratio (RAR) is a prognostic factor for adverse outcomes in various populations. However, whether RAR is associated with renal outcomes remains unclear. Therefore, we aimed to investigate the impact of RAR on the prognosis in patients with chronic kidney disease (CKD). We conducted a retrospective cohort study using 997 CKD patients who were enrolled in the Fukushima Cohort Study. Patients were categorized into tertiles (T1-3) according to the baseline RAR. The associations of RAR with end-stage kidney disease (ESKD) were assessed using Kaplan–Meier curves and multivariable cox regression analyses. Receiver operating characteristic (ROC) curves were performed to test whether significant differences were present between red cell distribution width (RDW) and RAR. The median age was 66, 57% were men, the median eGFR was 47.8 ml/min/1.73 m2, and the median value of RAR was 3.5. The higher RAR group showed an increased risk for ESKD in the Kaplan–Meier curve analysis. Compared to the lowest RAR group, higher RAR groups had a higher risk of ESKD (hazard ratio [HR] 1.37, 95% CI 0.68–2.78 and 2.92, 95% CI 1.44–5.94) for T2 and T3 groups, respectively. ROC curve analysis proved that the discriminating ability of RAR for ESKD was superior to RDW. A higher RAR value was associated with worse renal outcomes in patients with CKD. RAR could be a convenient and useful prognostic marker for renal prognosis.

Sex as a biological variable in acute kidney injury.

The purpose of this review is to provide an overview of the preclinical and clinical studies investigating sex as a biological variable, as well as the impact of gender, on the development of and progression of acute kidney injury (AKI). Despite a matched degree of ischemia-reperfusion AKI based on measured glomerular filtration rates, male and female mice demonstrated important sex biases in cardiorenal outcomes (1). Although the 2012 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for AKI reported that female sex is associated with increased rates of hospital acquired AKI, subsequent meta-analyses do not show increased risk of AKI in women. Recent large scale, multicenter epidemiologic studies suggest males have higher rates of hospital acquired AKI. However, women have been consistently shown to have worse renal outcomes after AKI. There may be also be gender-based differences in presentation to care and management. Sex is an important biological variable in animal models of acute kidney injury. The impact of sex on AKI likely varies based on the etiology of AKI. Preclinical studies demonstrate the nuances of sex chromosomes, sex hormones and epigenetic factors on AKI, however these have not been well studied in humans. Gender may also impact processes of care, treatment and clinical outcomes related to AKI. The scientific rigor and reproducibility of translational studies benefit from the consideration of sex and gender.

Validation of a renal risk score in a cohort of children with ANCA-associated glomerulonephritis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is extremely rare in children. Renal involvement is a common and severe complication of AAV as it can cause end stage kidney disease (ESKD). ANCA renal risk score (ARRS) is helpful in predicting long-term ESKD in patients with ANCA-associated glomerulonephritis (AAGN). This retrospective study included 61 consecutive patients with kidney biopsy specimen-proven AAGN from Clinical Center for Children's Kidney Disease in China. Each patient was assessed by eGFR, normal glomeruli, and tubular atrophy/interstitial fibrosis, and the renal outcome was evaluated using the ARRS. Based on the ARRS, 27 (44.26%), 21 (34.43%), and 13 (21.31%) patients were divided into the low-risk, medium-risk, and high-risk groups, respectively. The median follow-up period was 46.36 (14.58-95.62) months. The high-risk group had worse renal outcomes than the low-risk group (p< 0.05) and the medium-risk group (p < 0.05). COX multivariate regression analysis showed that eGFR ≤ 15 ml/min/1.73 m2 (p = 0.015, Hazard Ratio (HR) = 9.574, 95% CI 4.205-25.187) and ARRS (p = 0.012, HR = 2.115, 95% CI 1.206-4.174) were independent risk factors for ESKD.The area under the curve for ESKD prediction of ARRS was 0.880, and the best cutoff value was 5.50. Delong test result showed that ARRS exhibited better predictive value for ESKD than the Berden classification (p < 0.001) and rapidly progressive glomerulonephritis (p < 0.001). This is the first study to investigate the value of the ARRS for predicting renal prognosis among Chinese children. The ARRS is a preferred index that can predict ESKD in Chinese children with AAGN.

#6849 CLINICOPATHOLOGIC CHARACTERISTICS IN RENAL THROMBOTIC MICROANGIOPATHY

Abstract Background and Aims Thrombotic microangiopathy (TMA) is a life-threatening condition that can be caused on the background of various mechanisms, converging to a severe endotheliopathy that often affects the kidneys. Morphologic features of TMA on kidney biopsy have not been systematically studied. We studied the diagnostic and prognostic role of a kidney biopsy in patients with TMA, either linked to a coexisting condition (i.e., secondary TMA) or not (i.e., complement-mediated [C-]TMA). Method Patients with TMA on kidney biopsy and an enzymatic activity of ADAMTS13 &amp;gt;10% were recruited from the Limburg Renal Registry. C-TMA was defined as massive ex vivo C5b9 formation on the endothelium and/or rare variants in complement genes [1]; secondary TMA was defined as the presence of a coexisting condition and normal complement regulation. Kidney tissue sections were studied for activity and chronicity; also, C3d staining was performed. Results C-TMA and secondary TMA was diagnosed in 35 and 39 patients, respectively. The diagnosis TMA was based on a kidney biopsy in 52 (70%) out of 74 patients as systemic hemolysis, that is, microangiopathic hemolytic anemia (MAHA) and thrombocytopenia, was lacking. Morphologic activity, such as, glomerular thrombosis and mesangiolysis, was not associated with MAHA (p = 0.116) and/or thrombocytopenia (p = 0.380). Morphologic activity, however, was associated with C-TMA, as was lower age and higher serum creatinine. C3d staining did not differentiate C-TMA from secondary TMA. A Mayo Clinic Chronicity Score (MCCS) of ≥4 was associated with an increased partial- (p = 0.023) and complete renal remission rate (p = 0.030), and decreased end-stage kidney disease (p = 0.050). Conclusions Only a small proportion of patients with TMA on kidney biopsy initially present with systemic hemolysis, suggesting an essential role of histologic examination to prevent underdiagnosing. Glomerular thrombosis and mesangiolysis were associated with C-TMA, however there is no role for staining of C3d in differentiating C-TMA from secondary TMA. An increased MCCS indicates worse renal outcome in patients with TMA.

#2533 PROGNOSTIC SIGNIFICANCE OF ARTERIOLAR C4D POSITIVITY AS A MARKER OF MICROANGIOPATHY IN ANCA-ASSOCIATED VASCULITIS

Abstract Background and Aims ANCA-associated vasculitis (AAV) represent a group of systemic autoimmune diseases characterized by necrotizing inflammation of small to medium-size blood vessels frequently associated with anti-neutrophil cytoplasmic antibody (ANCA) positivity. Another term they are commonly referred with is “paucimmune vasculitis”, reflecting the lack of immune complex deposition on histological samples, in contrast with other small vessel vasculitis, e.g. cryoglobulinemic vasculitis. The absence or the paucity of deposition of immunoglobulins and complement components was interpreted in the past as a lack of complement cascade involvement in the pathogenesis of AAV. Only in relatively recent times the possible role of complement in AAV was investigated. A few studies proved the relationship between C3 hypocomplementemia and worse renal outcome[1]. Moreover, the overactivation of the alternative complement pathway (ACP) in AAV could be responsible for thrombotic microangiopathy (TMA). A strong association between low serum C3 and histologic signs of thrombotic microangiopathy on renal biopsy was shown in patients with AAV, with a worse renal prognosis. Currently, there are no clear early histological markers of endothelial damage that allow to identify high-risk patients, other than the seldom not identified or misidentified presence of TMA. The association between renal arteriolar C4d deposition (as a vicariate of TMA) has been already described in several glomerulonephritis, including IgA nephropathy [2], but its prognostic meaning has not yet been explored [3]. Our study aims to explore the predictive role of arteriolar C4d in ANCA-associated GN. Method All patients with ANCA-associated GN who underwent a kidney biopsy between January 1990 and June 2021 at the Renal Unit of Parma University Hospital, Parma, Italy with at least 6 months follow-up data were included. All histology slides were retrieved and reviewed by experienced nephropathologists. Percent IFTA, percent global glomerulosclerosis, Brix score, the presence or absence of TMA, the positivity or negativity of C4d (immunohistochemical staining on paraffin-embedded formalin-fixed slides) were taken note of. C4d positivity was correlated with the presence of TMA and patients outcome (Fig. 1). Results We identified 58 patients who met our criteria. 14 patients were excluded because biopsy specimens were not available for histologic review. Clinical and laboratory baseline and follow-up data for the remaining 44 patients were thus collected. Conclusion C4d and TMA were independently associated (p = 0.003). A tendency towards association between C4d and death-censored ESRD was observed (Fig. 2), although not statistically significant (p = 0.434), likely due to the limited sample size. In order to test our hypothesis, validation on a larger cohort is currently underway.

#4951 NON-ADHERENCE TO CARDIOMETABOLIC DRUGS AS ASSESSED BY LS-MS/MS IN URINE AND ITS ASSOCIATION WITH RENAL AND CARDIOVASCULAR OUTCOMES IN T2DM

Abstract Background and Aims Cardiovascular and renal complications have a detrimental impact on the prognosis and quality of life of patients with type 2 diabetes mellitus (T2DM). Guidelines recommend combination drug therapy to prevent or delay these complications[1]. However, non-adherence to medication is common and a barrier to successful disease management[2]. Most previous studies on adherence and outcome used indirect methods to assess adherence[3]. In this study we used liquid chromatography-tandem mass spectrometry (LC-MS/MS), a direct and objective adherence measure, to asses adherence to cardiometabolic drugs in a large real-world cohort of individuals with T2DM and analyzed non-adherence in the context of cardiovascular and renal outcomes. Method 1125 eligible PROVALID participants were included. PROVALID is a prospective observational cohort study of patients with T2DM followed annually at the primary health care level. Urine samples from the PROVALID biobank were screened for 79 cardiometabolic drugs and metabolites thereof by LC-MS/MS. An individual was classified as fully adherent when markers for all prescribed drugs were detected, partially non-adherent when at least a marker for one drug was detected and totally non-adherent when no marker for any prescribed drug was detectable. In order to assess outcome by adherence we defined a cardiovascular (myocardial infarction, stroke, and cardiovascular death) and a renal (ESKD, renal death, sustained 40% reduction in eGFR to &amp;lt; 60 ml/min per 1.73 m², sustained progression of albuminuria) composite endpoint. Results The mean age was 64.2 (±8.9) years and 46.1% were female. The mean duration of T2DM was 11.4 (±7.9) years. The mean HbA1c was 7.1 (±1.1)%, the mean eGFR was 77.6 (±23.6) ml/min/1.73 m2 and mean albuminuria 67.3 (±287.9) mg/g creatinine. Participants were prescribed 5.4 (±2.0) cardiometabolic drugs on average. Based on the results of LC-MS/MS measurements, 56.3% were totally adherent, 42.0% were partially adherent, and 1.7% were totally non-adherent to screened cardiometabolic drugs. Adherence was highest to antiplatelet and glucose lowering drugs and lowest to lipid lowering drugs (totally adherent individuals 90.1%, 89.2% and 70.7%, respectively). Non-adherent patients had a longer history of T2DM (12.3 ± 8.5 vs. 10.7 ± 7.5, p = 0.003) and a higher number of prescribed drugs (5.8 ± 2.1 vs. 5.1 ± 1.9, p &amp;lt; 0.001). Age per se had no influence on adherence, however the number of prescribed medications had more impact on adherence in younger patients (Fig. 1). Ex-smokers were more likely to be adherent than current or never-smokers (odds ratio 1.4, p-value = 0.014). Patients who were adherent to lipid lowering drugs had significantly lower LDL (82.4 ± 29.8 vs. 111.4 ± 39.7 mg/dl, p &amp;lt; 0.001). A trend for lower HbA1c with adherence to glucose-lowering drugs and lower systolic blood pressure with adherence to antihypertensive drugs could be observed, however these differences were not statistically significant. In the longitudinal analysis, worse cardiovascular prognosis was especially seen with non-adherence to antiplatelet drugs and worse renal outcome especially with non-adherence to antihypertensive drugs (Fig. 2). Conclusion Our analysis confirms that non-adherence, especially partial non-adherence, to cardiometabolic drugs is common in T2DM. A higher incidence of cardiovascular events was observed with non-adherence to antiplatelet drugs, whereas non-adherence to antihypertensive drugs was associated with a higher renal event rate.

#6399 ROLE OF THERAPEUTIC PLASMAPHERESIS IN PAUCI-IMMUNE VASCULITIS – A SINGLE CENTRE EXPERIENCE

Abstract Background and Aims The indication for plasmapheresis (PLF) in pauci-immune vasculitis (PIV) is controversial. This study aimed to characterize the population and renal outcome of patients with PIV undergoing PLF in a hospital in the north of Portugal. Method We conduct a retrospective cohort study of patients followed by a multidisciplinary team, from diagnosis to death or May/22. Two groups were defined: patients undergoing PLF (group A, GA) and not undergoing PLF (group B, GB). Demographic variables, comorbidities, serological subtype, clinical presentation, histological classification and therapeutic were evaluated. Recorded outcomes were death and ESRD (end-stage renal disease) (eGFR,15 ml/min per 1.73 m2, dialysis, or transplantation). Renal survival was estimated using the Kaplan-Meier analysis and differences between curves were evaluated using the log-rank test. Results A total of 72 patients, 26 (36.1%) in group A and 46 (63.9%) in group B were included. In both groups the most frequent serotype was myeloperoxidase ((MPO) (n = 23, GA; n = 38, GB)). In both groups, most patients were male (61.5% in GA and 56.5% in GB), with a mean age at admission of 64 (SD±11.5) and 66.5 years (SD±12.2) in GA and GB, respectively (p = 0.362). Most GA patients had pulmonary and renal involvement on admission (80.7%, n = 21), versus GB (36.9%, n = 17), p&amp;lt;0.05. Mean serum creatinine was superior in GA (6.74 mg/dl, SD ± 2.75) versus GB (3.82 mg/dl, SD±2.95), p&amp;lt;0.05. Twenty patients from GA (76.9%) and 7 from GB (15.2%) required dialysis upon admission, p&amp;lt;0.05. In both groups, almost all patients underwent induction immunosuppression with cyclophosphamide (mean cumulative dose of 4.4 grams (SD ± 2.6) and 5.9 grams (SD ± 2.7), in GA and GB, respectively) and azathioprine in the maintenance phase, with a rapid corticosteroid weaning scheme in both phases. Median follow-up time (months) of GA and GB was 11 (IQR [4.8-37.5]) and 58.5 (IQR [14.5-92]) months. Regarding renal prognosis, 9 of 20 patients in GA and 3 of 7 patients in GB who needed dialysis on admission, partial recover of renal function (p = 1.00). About 37% (n = 17) of patients of GB and 73% (n = 19) of patients of GA reached the composite renal outcome, with a median time of 0 (IQR 0 - 21.8) and 38.5 months (IQR 5.3-92), respectively. GA showed worse renal survival, with a mean of 30.9 months vs. 116.5 months in GB, p = 0.01. Renal survival at 2 years was 68.7% in GB and 24% at GA. Patients in both groups with admission serum creatinine ≥ 5.7 mg/dl had similar renal survival (GA 39.9 and GB 32 months, p = 0.714). Regarding the histological classification, 91.7% and 38.9% in GA and GB belonged to the crescentic class, (p = 0.009). Renal survival in the subgroup of patients with crescentic class was worse in GA (16.6±10.2 vs 83.3±16.1, p = 0.015). The analysis of the Renal Risk Score showed no statistically significant difference between the groups, and between patients with crescentic class in both groups, p = 0.274. Mortality and hospitalization rate due to infection were similar in both groups (p&amp;gt;0.05). Conclusion Patients undergoing PLF had a worse renal outcome, consistent with the higher proportion of patients with severe azotemia and requiring dialysis at admission, in a sample that was mostly ANCA MPO. As described in the literature, the experience of our centre did not demonstrate benefit in the addition of PLF, despite the limitations inherent to an observational, retrospective study and the modest sample size. A better knowledge of etiopathogenesis is essential for the optimization of the therapeutic strategy, together with the promotion of measures that allow timely referral, an early diagnosis and consequent improvement of renal prognosis.

Disease modification achievement in patients with lupus nephritis in a real-life setting: mission impossible?

ObjectiveA preliminary definition of disease modification (DM) in lupus nephritis (LN) was recently developed focusing on long-term remission and damage prevention, with minimal treatment-associated toxicity. We aimed to further specify...

Intensive compared with less intensive blood pressure control to prevent adverse cardiac remodelling in children with chronic kidney disease (HOT-KID): a parallel-group, open-label, multicentre, randomised, controlled trial

Optimal target blood pressure to reduce adverse cardiac remodelling in children with chronic kidney disease is uncertain. We hypothesised that lower blood pressure would reduce adverse cardiac remodelling. HOT-KID, a parallel-group, open-label, multicentre, randomised, controlled trial, was done in 14 clinical centres across England and Scotland. We included children aged 2-15 years with stage 1-4 chronic kidney disease-ie, an estimated glomerular filtration rate (eGFR) higher than 15 mL/min per 1·73 m2-and who could be followed up for 2 years. Children on antihypertensive medication were eligible as long as it could be changed to angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) if they were not already receiving these therapies. Participants were randomly assigned (1:1) to standard treatment (auscultatory office systolic blood pressure target between the 50th and 75th percentiles) or intensive treatment (systolic target <40th percentile) by the chief investigator using a rapid, secure, web-based randomisation system. ACE inhibitors or ARBs were used as first-line agents, with the dose titrated every 2-4 weeks to achieve the target blood pressure levels. The primary outcome was mean annual difference in left ventricular mass index (LVMI) by echocardiography measured by a masked observer and was assessed in the intention-to-treat population, defined as all the children who underwent randomisation irrespective of the blood pressure reached. Secondary and safety outcomes were the differences between groups in mean left ventricular relative wall thickness, renal function, and adverse effects and were also assessed in the intention-to-treat population. This trial is registered with ISRCTN, ISRCTN25006406. Between Oct 30, 2012, and Jan 5, 2017, 64 participants were randomly assigned to the intensive treatment group and 60 to the standard treatment group (median age of participants was 10·0 years [IQR 6·8-12·6], 69 [56%] were male and 107 [86%] were of white ethnicity). Median follow-up was 38·7 months (IQR 28·1-52·2). Blood pressure was lower in the intensive treatment group compared with standard treatment group (mean systolic pressure lower by 4 mm Hg, p=0·0012) but in both groups was close to the 50th percentile. The mean annual reduction in LVMI was similar for intensive and standard treatments (-1·9 g/m2·7 [95% CI -2·4 to -1·3] vs -1·2 g/m2·7 [-1·5 to 0·8], with a treatment effect of -0·7 g/m2·7 [95% CI -1·9 to 2·6] per year; p=0·76) and mean value in both groups at the end of follow-up within the normal range. At baseline, elevated relative wall thickness was more marked than increased LVMI and a reduction in relative wall thickness was greater for the intensive treatment group than for the standard treatment group (-0·010 [95% CI 0·015 to -0·006] vs -0·004 [-0·008 to 0·001], treatment effect -0·020 [95% CI -0·039 to -0·009] per year, p=0·0019). Six (5%) participants reached end-stage kidney disease (ie, an eGFR of <15 mL/min per 1·73 m2; three in each group) during the course of the study. The risk difference between treatment groups was 0·02 (95% CI -0·15 to 0·19, p=0·82) for overall adverse events and 0·07 (-0·05 to 0·19, p=0·25) for serious adverse events. Intensive treatment was not associated with worse renal outcomes or greater adverse effects than standard treatment. These results suggest that cardiac remodelling in children with chronic kidney disease is related to blood pressure control and that a target office systolic blood pressure at the 50th percentile is close to the optimal target for preventing increased left ventricular mass. British Heart Foundation.

Abstract 13779: Metabolic Profiles Identify Distinct Cardiorenal Risk Factors in People With Diabetes Mellitus: Insights From the EXSCEL Trial

Introduction: Impaired fatty acid oxidation is common to both kidney and CV complications of diabetes mellitus (DM). We compared metabolic profiles of different cardiorenal trajectories to identify common pathways and unique signatures which may inform disease mechanisms. Methods The EXSCEL trial randomized patients with type 2 DM to exenatide vs placebo. For this study, we performed targeted metabolomics of 60 metabolites (45 acylcarnitines [ACs], 15 amino acids, ketone bodies, and nonesterified fatty acids) in 978 EXSCEL participants. Principal components analysis (PCA) was used for dimensionality reduction and multivariable logistic regression to examine the association of each PCA factor with four cardiorenal outcomes: CV (CV death, MI, or stroke), renal (≥30% eGFR decline, ESKD, or renal death), cardiorenal (both outcomes), or neither. We also evaluated the factors associations with hospitalization for heart failure (HHF) and new-onset albuminuria, adjusting for baseline CKD, medication, and treatment allocation. Results PCA metabolite factors and cardiorenal outcome associations are listed in Table 1. Considering the directionality of factor loadings, baseline levels of small-chain dicarboxylated ACs and medium-chain ACs were associated with worse cardiorenal outcomes. Long-chain ACs were associated with worse renal outcomes. In contrast, 12-month change in medium-chain saturated ACs and long-chain unsaturated ACs were associated with better CV and renal outcomes, respectively. No factors associated with albuminuria. Baseline nonesterified fatty acids (OR 0.64, 95% CI 0.42-0.99) and 12-month change in medium-chain ACs (OR 1.57, 95% CI 1.04-2.37) associated with HHF. Conclusions Baseline associations between ACs and adverse cardiorenal outcomes further link mitochondrial dysfunction with both disorders. However, the association between changes in some ACs with improved outcomes may suggest an adaptive role for these metabolites.

Predictive Value of HbA1c and Metabolic Syndrome for Renal Outcome in Non-Diabetic CKD Stage 1-4 Patients.

Glycated hemoglobin (HbA1c) levels are commonly used to indicate long-term glycemic control. An HbA1c level of 6.5–5.7% is defined as pre-diabetes and is proposed as a criterion for diagnosing metabolic syndrome (MetS). However, HbA1c levels can be affected by chronic kidney disease (CKD). Whether HbA1c is associated with clinical outcomes in nondiabetic CKD patients with or without MetS is still unknown. This study included 1270 nondiabetic CKD stage 1–4 Asian patients, divided by HbA1c and MetS. Through linear regression, HbA1c was positively associated with age, waist circumference, hemoglobin levels, and C-reactive protein and was negatively associated with malnutrition–inflammation. HbA1c levels were 5.5% (0.6%) and 5.7% (0.6%) in non-MetS and MetS, respectively (p < 0.001). In Cox regression, higher-level HbA1c was associated with worse composite renal outcome in MetS patients, but with better renal outcome in non-MetS patients: Hazard ratio (HR) (95% confidence interval [CI]) of HbA1c ≥5.7%, compared with HbA1c <5%, was 2.00 (1.06–3.78) in MetS and 0.25 (0.14–0.45) in non-MetS. An association between HbA1c and all-cause mortality was not found. In conclusion, higher HbA1c levels are associated with worse renal outcomes in nondiabetic CKD stage 1–4 patients modified by the presence of MetS.

Hyperuricemia, a Non-Independent Component of Metabolic Syndrome, Only Predicts Renal Outcome in Chronic Kidney Disease Patients without Metabolic Syndrome or Diabetes.

Uric acid (UA) is elevated in metabolic syndrome (MS) and diabetes (DM). UA is associated with central obesity and blood glucose and is proposed as a criterion of MS. Previous reports showed that UA could predict renal outcome in CKD. However, recent clinical trials did not demonstrate the benefits of urate-lowering agents (ULA) for renal outcome. Whether the prognostic value of UA for renal outcome is independent of MS or secondary to MS in CKD patients is unknown. Our study included 2500 CKD stage 1–4 Asian patients divided by UA tertiles and MS/DM. In linear regression, UA was associated with obesity, C-reactive protein, and renal function. In Cox regression, high UA was associated with worse renal outcome in non-MS/DM, but not in MS/DM: hazard ratio (95% confidence interval) of UA tertile 3 was 3.86 (1.87–7.97) in non-MS/DM and 1.00 (0.77–1.30) in MS/DM (p for interaction < 0.05). MS was associated with worse renal outcome, but redefined MS (including hyperuricemia as the 6th criteria) was not. In conclusion, hyperuricemia is associated with worse renal outcome in non-MS/DM and is not an independent component of MS in CKD stage 1–4 patients. Hyperuricemia secondary to MS could not predict renal outcome.

Natural course and determinants of short-term kidney function decline in hereditary transthyretin amyloidosis: a French observational study

Data regarding renal involvement in patients with hereditary transthyretin (ATTRv) amyloidosis are scarce and the natural course of chronic kidney disease (CKD) in this population remains unclear. This observational study, including adult patients diagnosed with ATTRv amyloidosis at the French Reference Centre for Cardiac Amyloidosis, investigated renal function outcome and its determinants. Multivariable logistic regression models identified factors associated with CKD at baseline. Determinants of the change in estimated glomerular filtration rate (eGFR) over 24 months of follow-up were assessed with a multivariable linear mixed-effects model. In total, 232 patients (78 women [34%], mean age: 64 years) with ATTRv amyloidosis were classified on the basis of their TTR variants: ATTRV122I (37%), ATTRV30M (29%), and other variants (34%). Median baseline eGFR was 78 ml/min/1.73 m2. Seventy-two patients (31%) had an eGFR below 60 ml/min/1.73m2 and 27/137 patients (20%) had significant proteinuria (urine protein/creatinine ratio ≥30 mg/mmol). Renal biopsy, performed in four cases, found typical Congo red-positive and TTR-labelled amyloid deposits in all cases. Older age (OR 1.07, p < .001) and a prior history of hypertension (OR 2.09, p = .04) were associated with a higher prevalence of CKD at baseline, whereas higher left ventricular global longitudinal strain (LVGLS) (OR 0.83, p < .001) was associated with a lower prevalence. The estimated change in eGFR was −7.12 [−9.61, −4.63] and −8.21 [−10.81, −5.60] ml/min/1.73 m2 after 12 and 24 months of follow-up, respectively. eGFR decline was independently associated with older age ((67–74], coefficient= −14.35 mL/min/1.73 m2, p < .01, >74, coefficient = −22.93 mL/min/1.73 m2, p < .001, versus <56), ATTRV122I (coefficient = −17.17 mL/min/1.73m2, p < .01, versus ATTRV30M) and LVGLS (coefficient = 1.22, p < .01). These data suggest that CKD is a common finding in patients with ATTRv amyloidosis, and that eGFR decline is rapid during the first year of evaluation. Older age, lower LVGLS and ATTRV122I were associated with a worse renal outcome. Further studies are now needed to evaluate effects of new targeted therapies on long term renal function.