Drop In eGFR Research Articles

Using chronic kidney disease trigger tools for safety and learning: a qualitative evaluation in East London primary care.

An innovative programme to improve identification and management of chronic kidney disease (CKD) in primary care was implemented across three clinical commissioning groups (CCGs) in 2016. This included a falling estimated glomerular filtration rate (eGFR) trigger tool built from data in the electronic health record (EHR). This tool notifies GP practices of falling eGFR values. By alerting clinicians to patients with possible CKD progression the tool invites clinical review, a referral option, and written reflection on management. To identify practitioner perceptions of trigger tool use from interviews, and compare these with reflections on clinical management recorded within the tools. A qualitative analysis set in 136 practices across East London during 2016-2018. Eight semi-structured interviews with GPs and practice staff were recorded, and thematic analysis was undertaken using framework analysis. The reflective comments recorded in the trigger tools of 1921 cases were categorised by age group, referral status, and by the drop in eGFR (>15 or >25 ml/min). Three themes emerged from the interviews: getting started, patient safety, and trigger tools for learning. Well-organised practices found the tool was readily embedded into workflow and expressed greater motivation for using it. The tool was seen to support patient safety, and was used for learning about CKD management, both individually and as a practice. Reflective comments from 1921 trigger tools were reviewed. These supported the theme of patient safety. The free-text data, stratified by age, challenged the expectation that younger cases, at higher risk of progressive CKD, would have higher referral rates. Building electronic trigger tools from the EHR can identify patients with a falling eGFR, prompting review of the eGFR trajectory and management plan. Interview and reflective data illustrated that practice use of the tool supports the patient safety agenda and encourages learning about CKD management.

243-OR: ADA Presidents' Select Abstract: Dapagliflozin Reduces Measured GFR by Reducing Renal Efferent Arteriolar Resistance in Type 2 Diabetes

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) improve hard renal outcomes in type 2 diabetes (T2D) patients. An acute and reversible drop in eGFR that stabilizes over time, as with RAS inhibitors, suggests involvement of a beneficial renal hemodynamic mechanism. In hyperfiltering T1D patients, SGLT2i lowered GFR by increasing afferent arteriolar resistance, possibly by activating tubuloglomerular feedback. We studied the renal hemodynamic effects of SGLT2i dapagliflozin in T2D patients like those included in recent outcome trials. Methods: Forty-four T2D patients on metformin monotherapy, (62.9±7.0 years, HbA1c 7.38±0.63%, GFR 113±19 mL/min) were randomized to 12 weeks dapagliflozin 10mg (DAPA, n=24) or gliclazide 30mg (GLIC, n=20) QD to achieve glycemic equipoise. At baseline and week 12, GFR and renal plasma flow (RPF) were measured by gold-standard inulin and para-aminohippurate clearances. The measurements were performed 1) in the fasting state, 2) during clamped euglycemia (90 mg/dL) and 3) hyperglycemia (270 mg/dL). Renal vascular resistance (RVR) and filtration fraction (FF) were calculated using GFR, RPF, Ht and MAP. Afferent and efferent arteriolar resistances were estimated by Gomez’ equations. Results: HbA1C decreased similarly (0.47% with DAPA and 0.65% with GLIC; p=ns), while only DAPA significantly reduced MAP by approximately 6 mmHg. DAPA reduced GFR during all three conditions by 8.9 (p<0.01), 9.0 (p=0.01) and 13.4 mL/min (p<0.001), respectively, without altering RPF, thus also reducing FF. Importantly, DAPA lowered RVR and efferent arteriolar resistance. GLIC did not alter any renal hemodynamic variables. Conclusion: We confirm that SGLT2i induces beneficial renal hemodynamic changes in T2D beyond glycemic control that are characterized by reduced GFR and FF. However, in contrast to standing opinion, this is mediated by efferent arteriolar dilation rather than afferent arteriolar constriction. Disclosure E.J. van Bommel: None. M.A. Muskiet: Consultant; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. M.J. van Baar: None. M.H. Kramer: None. M. Nieuwdorp: Advisory Panel; Self; Caelus health. J.A. Joles: None. D.H. van Raalte: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Sanofi. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Sanofi. Funding AstraZeneca Nederland BV

Impact of Chronic Kidney Disease on Outcomes in Cirrhosis.

We hypothesize that the prevalence of chronic kidney disease (CKD) among patients with cirrhosis has increased due to the increased prevalence of CKD-associated comorbidities, such as diabetes. We aimed to assess the characteristics of hospitalized patients with cirrhosis with CKD and its impact on renal and patient outcomes. The North American Consortium for the Study of End-Stage Liver Disease (NACSELD) prospectively enrolled nonelectively admitted patients with cirrhosis and collected data on demographics, laboratory results, in-hospital clinical course, and postdischarge 3-month outcomes. CKD positive (CKD+) patients, defined as having an estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease-4 variable formula) of ≤60 mL/minute for >3 months, were compared with chronic kidney disease negative (CKD-) patients for development of organ failures, hospital course, and survival. There were 1099 CKD+ patients (46.8% of 2346 enrolled patients) who had significantly higher serum creatinine (2.21±1.33 versus 0.83±0.21 mg/dL in the CKD- group) on admission, higher prevalence of nonalcoholic steatohepatitis cirrhosis etiology, diabetes, refractory ascites, and hospital admissions in the previous 6 months compared with the CKD- group (all P<0.001). Propensity matching (n=922 in each group) by Child-Pugh scores (9.78±2.05 versus 9.74±2.04, P=0.70) showed that CKD+ patients had significantly higher rates of superimposed acute kidney injury (AKI; 68% versus 21%; P<0.001) and eventual need for dialysis (11% versus 2%; P<0.001) than CKD- patients. CKD+ patients also had more cases of acute-on-chronic liver failure as defined by the NACSELD group, which was associated with reduced 30- and 90-day overall survival (P<0.001 for both). A 10 mL/minute drop in eGFR was associated with a 13.1% increase in the risk of 30-day mortality. In conclusion, patients with CKD should be treated as a high-risk group among hospitalized patients with cirrhosis due to their poor survival, and they should be monitored carefully for the development of superimposed AKI.

Role of anemia and proteinuria in the development of subsequent renal function deterioration in a general population with preserved glomerular filtration rate: a community-based cohort study.

Risk factors for renal function deterioration in the general population are not fully understood. We aimed to clarify the determinants of estimated glomerular filtration rate (eGFR) decline using a community-based cohort. Among 3217 subjects who underwent repeated health check-ups, we excluded 478 subjects with eGFR ≤ 60mL/min/1.73m2 and examined 2739 subjects. EGFR decline rate was calculated from the difference in eGFR between the first and last visits. EGFR decline, which was defined as a drop in GFR accompanied by a 25% or greater drop in eGFR from baseline and/or a sustained decline of more than 5mL/min/1.73m2/year, was observed in 209 subjects (7.6%). Anemia according to the WHO definition (16.7% vs. 11.7%, p = 0.03), and proteinuria (3.3% vs. 0.8%, p < 0.001) at baseline were more commonly observed in subjects with eGFR decline. Multivariable logistic regression analysis showed that anemia and proteinuria were independently associated with eGFR decline. Anemia and proteinuria were closely related to eGFR decline, which suggests that we should consider these parameters as risk factors of the development of renal function deterioration even in the general population.

Contribution of Genetic Background and Data Collection on Adverse Events of Anti–human Immunodeficiency Virus (HIV) Drugs (D:A:D) Clinical Risk Score to Chronic Kidney Disease in Swiss HIV-infected Persons With Normal Baseline Estimated Glomerular Filtration Rate

In human immunodeficiency virus (HIV), the relative contribution of genetic background, clinical risk factors, and antiretrovirals to chronic kidney disease (CKD) is unknown. We applied a case-control design and performed genome-wide genotyping in white Swiss HIV Cohort participants with normal baseline estimated glomerular filtration rate (eGFR >90 mL/minute/1.73 m2). Univariable and multivariable CKD odds ratios (ORs) were calculated based on the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) score, which summarizes clinical CKD risk factors, and a polygenic risk score that summarizes genetic information from 86 613 single-nucleotide polymorphisms. We included 743 cases with confirmed eGFR drop to <60 mL/minute/1.73 m2 (n = 144) or ≥25% eGFR drop to <90 mL/minute/1.73 m2 (n = 599), and 322 controls (eGFR drop <15%). Polygenic risk score and D:A:D score contributed to CKD. In multivariable analysis, CKD ORs were 2.13 (95% confidence interval [CI], 1.55-2.97) in participants in the fourth (most unfavorable) vs first (most favorable) genetic score quartile; 1.94 (95% CI, 1.37-2.65) in the fourth vs first D:A:D score quartile; and 2.98 (95% CI, 2.02-4.66), 1.70 (95% CI, 1.29-2.29), and 1.83 (95% CI, 1.45-2.40), per 5 years of exposure to atazanavir/ritonavir, lopinavir/ritonavir, and tenofovir disoproxil fumarate, respectively. Participants in the first genetic score quartile had no increased CKD risk, even if they were in the fourth D:A:D score quartile. Genetic score increased CKD risk similar to clinical D:A:D score and potentially nephrotoxic antiretrovirals. Irrespective of D:A:D score, individuals with the most favorable genetic background may be protected against CKD.

Peritoneal Ultrafiltration in the Long-Term Treatment of Chronic Heart Failure Refractory to Pharmacological Therapy.

IntroductionDespite continuous improvement in the treatment, heart failure (HF) is a growing health problem and a major cause of mortality and morbidity in the world. There is some positive experience with the removal of the fluid excess via peritoneum in those patients, regardless of their renal function. The aim of this single center pilot study was to assess the efficacy of peritoneal ultra filtration (PUF) with a nightly 12-h exchange in the long-term treatment of refractory HF.MethodsThe study included patients with chronic HF resistant to updated HF therapy (pharmacological and devices if applicable), who had experienced at least three hospitalizations due to HF during the preceding year and were disqualified from heart transplantation. All of them were treated with nightly 12-h 7.5% icodextrin exchange.ResultsThere were 15 patients (13 men), aged 72 ± 9 years, with charlson comorbidity index (CCI) 9 ± 1.2, NYHA class IV (11 patients) or III (4 patients), and eGFR 32 ± 11 ml/min/1.73m2. They were followed up for 24 ± 8 months (range 12–43, median 26 months). During the 1st year, all patients improved their NYHA functional class from 3.7 ± 0.5 to 2.6 ± 0.5; P = 0.0005, with stable (34.3 ± 12.4, and 35.6 ± 16.5%, respectively) left ventricular ejection fraction (LVEF), and inferior vena cava (IVC) diameter decreased from 27.8 ± 2.7 to 24.4 ± 3.4 mm; P = 0.09. Daily diuresis increased from 867 ± 413 to 1221 ± 680 ml; P = 0.25, while the dose of furosemide could be reduced from 620 ± 256 to 360 ± 110 mg/d; P = 0.0005, however, the kidney function deteriorated, with eGFR drop from 32 ± 11 to 25.6 ± 13 ml/min/1.73m2; P = 0.01). HF-related hospitalizations decreased from 8.9 ± 2.8 days/month to 1.5 ± 1.2 days/month (P = 0.003). Mechanical peritoneal dialysis complications occurred in five patients and infectious complications in four (peritonitis rate 1 per 72 patient-month). Patient survival was 93% at 1 year and 73% at 2 year. Technique survival was 100%.ConclusionIn patients with refractory HF, PUF with one overnight icodextrin exchange appears to be a promising therapeutic option as an adjunct to pharmacological management of those who are not transplant candidates. It should be emphasized that the treatment can have a great impact on the quality of life and the total costs of treating these patients.

Renal function and risk factors for renal disease for patients receiving HIV pre-exposure prophylaxis at an inner metropolitan health service.

BackgroundPre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) significantly reduces the risk of HIV acquisition. TDF is a known nephrotoxin however, renal dysfunction from TDF is mostly reversible following discontinuation.AimsTo describe the renal function, risk factors for renal disease and associated clinical testing practices in a cohort of PrEP patients.MethodsA retrospective review was conducted of all PrEP patients commenced on TDF/FTC at an inner metropolitan sexual health clinic in Sydney, Australia between April 2016 and July 2017, with follow-up data obtained at 3-monthly intervals until 18 months.Results525 patients met inclusion criteria. Patients were almost exclusively male and median age was 34 years (IQR: 28 to 42). At baseline, 1.5% had an estimated glomerular filtration rate (eGFR) <70 mL/min/1.73m2. A small significant drop in eGFR of -2.5 mL/min/1.73m2 (p<0.05) occurred between PrEP commencement and the first follow-up period, followed by a progressive decline in eGFR of -0.38 mL/min/1.73m2 per month (95%CI: -0.57 to -0.20; p<0.001). Renal impairment (eGFR <70 mL/min/1.73m2) occurred in 6.5% of patients and persisted across consecutive follow-up periods in five (1.0%) patients. Patients aged ≥40 years had a greater risk of renal impairment than younger patients (HR 3.9, 95%CI: 1.8 to 8.4; p<0.001), despite similar rates of eGFR decline (p = 0.19). PrEP was discontinued in two patients (0.4%) due to renal function concerns.ConclusionPrEP use led to an initial drop in eGFR and a more gradual progressive decline subsequently, but significant renal impairment remained uncommon up to 18 months of follow-up.

Off-clamp vs on-clamp robotic partial nephrectomy: Perioperative, functional and oncological outcomes from a propensity-score matching between two high-volume centers

IntroductionAim of the study was to compare perioperative, functional and oncological outcomes after off-clamp vs on-clamp robotic partial nephrectomy (RPN). Materials and methodsPatients who underwent off-clamp or on-clamp (warm ischemia) RPN were extracted from 2 institutional prospectively-maintained databases. 123 patients who underwent off-clamp RPN at one institution were excluded, so that each institution contributed with unselected patients (institution 1:on-clamp RPN vs institution 2:off-clamp). 2:1 propensity-score matching (age, sex, smoking, diabetes, hypertension, ASA score, solitary kidney, preoperative eGFR, tumor size and R.E.N.A.L.score). Perioperative outcomes were compared. A linear mixed model was fitted to eGFR as the outcome regressed on fixed effects for 1) management of clamping (on-clamp/off-clamp), 2) time (at baseline, at discharge, at 12 and 24 months postoperatively), and 3) clamp/time interaction. Survival events were compared between groups. Results1983 patients were pooled. After matching, 400 on-clamp vs 200 off-clamp patients were analyzed. No significant differences were found in key perioperative outcomes. The effect of on-clamp on eGFR changed over time. At discharge, groups had similar drop in eGFR. The difference between groups was greatest at 12-months postoperatively, with on-clamp patients showing a deficit of 5 ml/min. At 24-months follow-up, this gap shrunk to 2 ml/min. There were no significant differences in overall survival (p = 0.1), recurrence (χ2 = 0.008, p = 0.9), or metastasis free survival (χ2 = 0.962 p = 0.3). Only one cancer-specific death occurred in off-clamp group. ConclusionWe confirm no significant differences in the perioperative and oncological outcomes between off-clamp and on-clamp RPN. Avoided ischemia benefits renal function within 1-year follow-up after surgery. At longer follow-up, difference with on-clamp is softened.

Effectiveness, treatment completion and safety of sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir + dasabuvir in patients with chronic kidney disease: an ERCHIVES study.

Chronic kidney disease (CKD) was a relative contraindication to hepatitis C virus (HCV) treatment in the interferon/ribavirin era. To determine the efficacy, tolerability and safety of sofosbuvir/ledipasvir (SOF/LDV) and paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens in persons with CKD. We identified persons initiated on a SOF/LDV or PrOD regimen from October 30, 2014 to April 30, 2016. We excluded those with missing HCV genotype or eGFR values. We determined treatment completion and sustained virologic response (SVR) rates, and proportion developing worsening renal function or grade 3/4 haematologic toxicity. Among 13663 persons on SOF/LDV±ribavirin, 14% and 1% persons had CKD Stage 3 and 4-5 respectively, 67.8% completed treatment, 98.2% achieved SVR. Treatment completion or SVR rates did not decline with advanced CKD or ribavirin administration. Among 3961 persons on PrOD±ribavirin, 9% and 3% persons had CKD Stage 3 and 4-5, respectively, 74.0% completed treatment and 98.2% achieved SVR. A decrease in treatment completion rates was seen in CKD stage 4-5 and those on ribavirin, but this did not impact SVR rates. A >10mL/min/1.73m2 drop in eGFR from baseline was observed in 30%-38% of persons with baseline eGFR ≥60mL/min/1.73m2 , but in only 0%-6% with CKD4-5. Grade 3/4 anaemia was more frequent in persons with CKD4-5, but ribavirin co-administration did not appear to affect this. SOF/LDV and PrOD achieved high SVR rates in CKD population. Treatment completion rates were lower than expected. A decline in eGFR and development of anaemia were observed in a substantial proportion of persons, but the clinical implications remain unclear.

Impact of the off-clamp endoscopic robot-assisted simple enucleation (ERASE) of clinical T1 renal tumors on the postoperative renal function: Results from a matched-pair comparison

PurposeTo evaluate the surgical and functional outcomes of a matched-paired series of on-clamp vs off-clamp endoscopic robot-assisted simple enucleation (ERASE) and standardized renorraphy in a tertiary referral institution, to search for predictors of functional drop after surgery and to investigate the influence of off-clamp technique in patients presenting these characteristics. Materials and methodsA matched-pair comparison of 120 on-clamp vs 120 off-clamp over 491 patients treated with ERASE was performed. Perioperative and functional outcomes were compared between groups. ResultsPatients treated with on-clamp and off-clamp technique had comparable complication and positive surgical margin rate. The off-clamp group had a significantly lower eGFR drop compared to the on-clamp group at 3rd postoperative day (POD) (1% vs 7%, p = 0.0001) and at 30th POD (2.5% vs 9%, p = 0.01) from baseline. This difference lost its statistical significance at 6th month and at last follow-up (median 40 months). At multivariable analysis the Charlson comorbidity index (OR 2.06, p < 0.0001), uncontrolled type 2 diabetes mellitus (OR 4.13, p < 0.001) were independent predictive factors of a >15% eGFR drop from baseline to last follow-up. In a subanalysis over 64 comorbid patients, those patients who underwent off-clamp ERASE had a significantly lower eGFR drop compared to the comorbid counterpart during the whole follow-up. ConclusionsThe off-clamp ERASE is a safe surgical technique with a significantly lower renal function drop compared to on-clamp ERASE in the early perioperative time. Patients with comorbidity might represent a subgroup of patients having a functional benefit after off-clamp RAPN even in the long-term period.

Impact of Uric Acid Levels on Kidney Disease Progression

Background: Hyperuricemia is associated with the progression of chronic kidney disease (CKD), but it is not known whether the relationship is causal. We examined the association of hyperuricemia and uric acid lowering therapy (UALT) with progression of CKD in patients with CKD 3 and 4 in the Cleveland Clinic CKD registry. Methods: We included 1,676 patients with CKD stages 3 and 4 from Ohio, who had measured their uric acid (UA) levels a year prior to the recording of the second eGFR <60 mL/min/1.73 m2, and follow-up eGFR, between 2005 and 2009. Our primary composite outcome included a 50% drop in eGFR or progression to ESRD. Secondary outcomes included the rate of decline in eGFR, all-cause mortality, progression to ESRD, and a composite measure of progression to ESRD or death. We assessed the association between UA, UALT, and outcomes using Cox models and competing risks regression models. Results: In multivariable models, higher UA was associated with the composite endpoint, but it reached statistical significance only in the 4th quartile (≥8.9 mg/dL). Receipt of UALT was significantly associated with increased risk of the composite outcome. Neither UA nor UALT (considered a time-dependent covariate) was significantly associated with mortality. The inference was similar for UA as high vs. low, quartiles, or continuous. Similarly, neither high UA nor UALT were significantly associated with ESRD, the composite of ESRD and mortality, or eGFR decline. Conclusions: Hyperuricemia is associated with increased risk of progression to ESRD in patients with CKD stages 3 and 4, but UALT does not ameliorate the risk, suggesting that the relationship is not causal.

Outcomes After Cryoablation Versus Partial Nephrectomy for Sporadic Renal Tumors in a Solitary Kidney: A Propensity Score Analysis

BackgroundWhile partial nephrectomy (PN) is considered the standard approach for a tumor in a solitary kidney, percutaneous cryoablation (PCA) is emerging as an alternative nephron-sparing option. ObjectiveTo compare outcomes between PCA and PN for tumors in a solitary kidney. Design, setting, and participantsPatients who underwent PCA or PN between 2005 and 2015 for a single primary renal tumor in a solitary kidney were identified using Mayo Clinic Registries. Exclusion criteria were inherited tumor syndromes and salvage procedures. InterventionPCA and PN. Outcome measurements and statistical analysisTo achieve balance in baseline characteristics, we used inverse probability of treatment weighting (IPTW) based on propensity to receive treatment. The risk of having a post-treatment complication and percent drop in estimated glomerular filtration rate (eGFR), as well as the risks of local/ipsilateral recurrence, distant metastasis, and cancer-specific mortality, were compared between groups using logistic, linear, and Fine-and-Gray competing risk regression models. Results and limitationsThe cohort included 118 patients (PCA: 54; PN: 64) with a median follow-up of 47 mo (interquartile range 18, 74). In unadjusted analyses, PCA was associated with a lower risk of complications (15% vs 31%; odds ratio [OR]=0.38; 95% confidence interval [CI] 0.15, 0.96; p=0.04). However, upon accounting for baseline differences with IPTW adjustment, there was no longer a significant difference in the risk of complications (28% vs 29%; OR=0.95; 95% CI 0.53, 1.69; p=0.9). There were no significant differences between PCA and PN in percentage drop in eGFR at discharge (mean: 11% vs 16%; β=–5%; 95% CI –13, 3; p=0.2) or at 3 mo (12% vs 9%; β=3%; 95% CI –3, 10; p=0.3). Likewise, no significant differences were noted in local recurrence (HR=0.87; 95% CI 0.38, 1.98; p=0.7), distant metastases (HR=0.60; 95% CI 0.30, 1.20; p=0.2), or cancer-specific mortality (HR=1.13; 95% CI 0.32, 3.98; p=0.8). Limitations include the sample size, given the relative rarity of renal masses in solitary kidneys. ConclusionsOur study found no significant difference in complications, renal function outcomes, and oncologic outcomes between PN and PCA for patients with a tumor in a solitary kidney. Validation in a larger multi-institutional analysis may be warranted. Patient summaryPartial nephrectomy (surgery) and percutaneous cryoablation are both options for treating a kidney tumor while preserving the normal portion of the kidney. In patients with a tumor in their only kidney, we found no difference in the risk of complications, kidney function outcomes, or cancer control outcomes between these two approaches.

EFFECT OF COMBINING LOSARTAN AND PERINDOPRIL IN DIABETIC PATIENTS WITH PROTEINURIA

Objective: This retrospective study compared the efficacy and safety of losartan monotherapy versus losartan and perindopril combination therapy in diabetic patients with hypertension and albuminuria. Factors affecting the change in albuminuria were identified.Methods: Through quota sampling, the study recruited patients from a tertiary care hospital. Outcome parameters included urinary albumin creatinine ratio (UACR), blood pressure (BP), serum creatinine, and estimated glomerular filtration rate (eGFR). Both pre- and post-treatment measurements were traced from patient’s medical records.Results: No significant differences (p=0.615) were detected in the pre- and post-treatment change in UACR between the monotherapy group (−38.3 mg/g, interquartile range [IQR]:−618.8-0) and combination therapy group (−88.4 mg/g, IQR: −729.3-+375.7). There was a considerably higher percentage of patients attaining the target BP of &lt;125/75 mmHg in the combination group (66.7%; p&lt;0.001). In terms of safety, combined losartan and perindopril caused more hypotension (p=0.003), higher rise in serum creatinine (p=0.481), and greater drop in eGFR (p=0.861). Body mass index was shown to have significant negative correlation with UACR reduction (r=−0.449; p=0.036).Conclusion: The main finding of this study was that losartan alone was as equally efficacious as combined losartan and perindopril in lowering UACR and BP among diabetic patients.

1 Sacubitril/valsartan in chronic symptomatic heart failure with reduced ejection fraction: first clinical experience from a large uk tertiary centre

Introduction Sacubitril/valsartan (SV) is a new drug that has recently been approved by the National Institute for Health and Care Excellence (NICE) to be used as an alternative to ACE-inhibitors/Angiotensin Receptor Blockers in patients with symptomatic chronic heart failure with reduced ejection fraction (HFrEF). We report an early clinical experience of SV use in HF patients at a large tertiary cardiac centre in the UK. Methods Patients with HFrEF (NYHA class II-IV and Left Ventricular Ejection Fraction Results A total of 44 patients were commenced on SV and in 25 patients (57%) up-titration to the target dose was achieved. In 12 patients (27%) an improvement of NYHA class was seen. Nine patients (20%) had symptomatic systolic blood pressure drop of >10 mmHg at follow-up with 3 patients having hyperkalaemia (7%), preventing target dose up-titration. A total of 4 hospital admissions occurred: 2 due to decompensated heart failure (5%), 1 for hyperkalaemia and 1 non-cardiovascular (CV) related. Out of those hospital admissions, 2 patients died (see table). Four patients (9%) had a worsening of the eGFR>10 (without progressive renal failure preventing up-titration) and in 2 patients (5%) the drug was stopped to due intolerability (reported postural dizziness and abdominal pain). Conclusion The clinical use of SV in our centre has a high rate of tolerability with significant improvement in NYHA class (27%). However, in a large proportion of patients the target dose was not achieved (43%), mainly due to symptomatic hypotension and secondly due to hyperkalaemia (7%). A significant number of patients had a drop in eGFR, but this did not prevent up-titration. Our results confirm that HFrEF patients commencing sacubitril/valsartan require close monitoring of symptoms, renal function and dose titration by a ?specialist heart failure team.

Association of estimated glomerular filtration rate and urine albumin-to-creatinine ratio with incidence of cardiovascular diseases and mortality in chinese patients with type 2 diabetes mellitus \u2013 a population-based retrospective cohort study

BackgroundEstimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) are renal markers associated with risks of cardiovascular diseases (CVD) and all-cause mortality in diabetic patients. This study aims to quantify such risks in Chinese diabetic patients based on eGFR and UACR.MethodsThis was a territory-wide retrospective cohort study on primary care diabetic patients with documented eGFR and UACR but without baseline CVD in 2008/2009. They were followed up till 2013 on CVD events and mortality. Associations between eGFR/UACR and incidence of CVD/mortality were evaluated by multivariable Cox proportional models adjusted with socio-demographic and clinical characteristics.ResultsThe data of 66,311 patients who had valid baseline eGFR and UACR values were analysed. The risks of CVD events and mortality increased exponentially with the decrease in eGFR, with a hazard ratio (HR) increasing from 1.63 to 4.55 for CVD, and from 1.70 to 9.49 for mortality, associated with Stage 3 to 5 CKD, compared to Stage 1 CKD. UACR showed a positive linear association with CVD events and mortality. Microalbuminuria was associated with a HR of 1.58 and 2.08 for CVD and mortality in male (1.48 and 1.79 for female), respectively, compared to no microalbuminuria. Male patients with UACR 1–1.4 mg/mmol and eGFR ≥90 ml/min/1.73 m2 (60–89 ml/min/1.73 m2) had a HR of 1.25 (1.43) for CVD. Female patients with UACR 2.5–3.4 mg/ml and eGFR ≥90 ml/min/1.73 m2 (60–89 ml/min/1.73 m2) had a HR of 1.45 (1.65) for CVD.ConclusionsRisks of CVD events and mortality increased exponentially with eGFR drop, while UACR showed positive predictive linear relationships, and the risks started even in high-normal albuminuria. UACR-based HR was further modified according to eGFR level, with risk progressed with CKD stage. Combining eGFR and UACR level was more accurate in predicting risk of CVD/mortality. The findings call for more aggressive screening and intervention of microalbuminuria in diabetic patients.

Fasting in Ramadan is not associated with deterioration of chronic kidney disease: A prospective observational study.

Although not mandatory for patients, many Muslims fast in Ramadan. We aimed to investigate the effects of long hours (17.5) fasting on renal functions in patients with chronic kidney disease (CKD). Stage 3-5 CKD patients with stable renal function were recruited to this prospective observational study three months ahead of Ramadan in 2015. All patients were instructed regarding possible deleterious effects of dehydration caused by fasting. Forty-five patients (mean age 66.8 ± 10.3 years, 68.8% male) chose to fast and 49 (mean, age: 64.1 ± 12.6 years, 51% male) chose not to fast. Clinical and laboratory data were recorded before and after Ramadan. Baseline clinical and laboratory parameters were similar in the two groups, except for higher serum creatinine and lower estimated glomerular filtration rate (eGFR) in the nonfasting group (2.22 ± 0.99 vs. 1.64 ± 0.41 mg/dL, P <0.001 and 3 1.9 ± 12.4 vs. 42.6 ± 9.8 mL/min, P <0.001, respectively). More than 30% elevation in serum creatinine after Ramadan occurred in 8.8% and 8.1% of fasting and nonfasting patients, respectively (P = 0.9). More than 25% drop eGFR after Ramadan was noted in seven (15.5%) and six (12.2%) fasting and nonfasting patients, respectively (P = 0.642). Patients with ≥ 25% drop in eGFR (13 vs. 81) were older (72.3 ± 8.3 years vs. 64.3 ± 11.7 years, P = 0.020) and more frequently using diuretics (69.2% vs. 35.8%, P = 0.023). In multiple linear regression analysis, only advanced age was found to be associated with ≥25% drop in eGFR after Ramadan in the fasting group. Fasting during Ramadan was not associated with increased risk of declining in renal functions in patients with Stage 3-5 CKD. However, elderly patients may still be under a higher risk.

Risk of Chronic Kidney Disease among Patients Developing Mild Renal Impairment during Tenofovir-Containing Antiretroviral Treatment.

BackgroundTenofovir (TDF) can cause kidney injury through tubular dysfunction, with or without drop of estimated glomerular filtration rate (eGFR). Whether mild eGFR reductions during treatment should be considered a reason for prompt TDF discontinuation, however, remains unclear.MethodsPatients with normal pre-TDF eGFR levels, who had developed mild renal impairment (i.e., two consecutive eGFR results between 89–60 ml/min) on TDF, were observed until onset of chronic kidney disease (CKD), defined as two eGFR<60 ml/min 3 to 6 months apart. Multivariable Poisson regression analysis was used to investigate whether outcome was associated with current and cumulative use of TDF (modeled as time-varying covariates).Results2023 (29%) out of 6984 patients developed mild renal impairment on TDF. Among them, 191 progressed to CKD. The incidence of CKD did not significantly differ during TDF treatment (2.6 per 100 PYFU; 95%CI 2.2–3.2) or after its discontinuation (2.2 per 100 PYFU; 95%CI 1.8–2.6). However, the rate of CKD was significantly higher among patients continuing with TDF treatment compared to those who had discontinued it within 6 months of occurrence of mild renal impairment (aIRR 4, 95%CI 2.4–6.8). In contrast, among patients who had maintained TDF >6 months despite mild renal impairment, current TDF use was not associated with a significantly higher rate of CKD. Other significant predictors of CKD were older age, intravenous drug use, diabetes, hypertension, lower pre-TDF eGFR, higher eGFR drop since TDF introduction and longer exposure to TDF.ConclusionsPrompt discontinuation of TDF among patients developing mild renal impairment may prevent further progression of renal damage.

Noninvasive Central Systolic Blood Pressure Is More Strongly Related to Kidney Function Decline Than Peripheral Systolic Blood Pressure in a Chinese Community–Based Population

This study aimed to investigate the association of noninvasive central aortic blood pressure with kidney function decline in a Chinese community-based population with normal kidney function at baseline. A total of 3153 Chinese participants from an atherosclerosis cohort were included in our analysis. The primary outcome was renal function decline defined as a drop in estimated glomerular filtration rate (eGFR) category accompanied by a ≥25% drop in eGFR from baseline; or a sustained decline in eGFR of >5 mL/min per 1.73 m(2)/y. The secondary outcomes were rapid eGFR decline (a decline in eGFR of >3 mL/min per 1.73 m(2)/y) and new incidence of chronic kidney disease. Participants were 56.6±8.5 years old, 36.0% were males, and 48.8% had hypertension. Mean (SD) baseline eGFR was 101.2±10.6 mL/min per 1.73 m(2) After a mean 2.35-year follow-up, the incidence of renal function decline, rapid eGFR decline and chronic kidney disease were 7.3%, 19.7%, and 0.7%, respectively. In multivariate logistic-regression analyses, central and peripheral systolic blood pressure (SBP) were both independently associated with all outcomes after adjustment for various confounders. When peripheral SBP was forced into the model with central SBP simultaneously, its significant association with the 3 outcomes all disappeared; however, central SBP was still significantly related with all outcomes even after further adjusting peripheral SBP. In conclusion, central SBP is a stronger predictor compared with peripheral SBP for early kidney function decline in a Chinese community-based population with normal kidney function at baseline.

Circadian blood pressure profile in patients with chronic kidney disease stage 1-3

Background The population of patients with chronic kidney disease (CKD) is prone to high cardiovascular morbidity and mortality. Aberrant circadian pattern of blood pressure is associated with increase cardiovascular risk. The study investigated circadian blood pressure profile in patients with early stages of CKD. Material and methods The study included 90 patients with CKD stage 1–3, aged 34–79 years and 30 healthy volunteers as control group. All patients underwent ambulatory blood pressure monitoring (ABPM). Patient was classified as “dipper” if relative decreases in SBP and DBP at night was at least 10%. If the drop the SBP or DBP was less than 10% patient was classified as “non-dipper”. Results Hypertension was present in 78.9% of patients with CKD stage 1–3. “Non-dipper” profile was found in 59 (66%) of the surveyed patients with CKD, namely in 16 (53%) in CKD stage 1, 23 (70%) in CKD stage 2, and 20 (74%) in CKD stage 3. “Non-dipper” profile was observed in 9 (30%) of control patients. In the whole study population (n = 120) significant positive correlation was found between % drop in SBP and eGFR (r = 0.25; p < 0.01). There was no significant correlation between % drop in SBP and eGFR (r = 0.12; p = 0.26) in 90 CKD patients. There was statistically significant negative correlation between % drop in SBP and age (r = –0.25; p < 0.05) and BMI (r = –0.24; p < 0.05). Conclusions “Non-dipper” profile is a common finding among patients with early stages of CKD and may be associated with a higher cardiovascular risk. ABPM should be a standard procedure in patients with CKD, even in early stages of the disease.

Impact of Fenestrated Endovascular Abdominal Aortic Aneurysm Repair on Renal Function

Purpose: To investigate the impact of fenestrated endovascular aneurysm repair (fEVAR) on renal function perioperatively and at midterm. Methods: A case-controlled study was performed involving 58 patients (mean age 75±7 years; 51 men) who underwent elective fEVAR for a juxtarenal or short-necked abdominal aortic aneurysm (AAA) matched on age, sex, smoking, diabetes, and baseline estimated glomerular filtration rate (eGFR) with a contemporaneous group undergoing open aneurysm repair (OAR) for the same indications. Perioperative incidence of acute kidney injury (AKI) and levels of eGFR at 30 days and 1 year were compared. A systematic literature review was performed to identify studies that had used eGFR as renal outcome after fEVAR; the pooled data were meta-analyzed using an eGFR drop >30% at 1 month and the latest follow-up as endpoints. Results are reported as the pooled proportion and 95% confidence interval (CI). Results: The incidence of AKI after fEVAR was 28% compared to 10% after OAR (p=0.03). Following fEVAR, the mean eGFR dropped from 78±8 to 74±9 mL/min/1.73 m2 at 30 days compared to a change from 79±8 to 80±16 mL/min/1.73 m2 after OAR (p<0.01). However, the absolute drop in eGFR between fEVAR and OAR at 1 year was similar (7 mL/min/1.73 m2; p=0.53); 7% of the fEVAR patients had an eGFR drop >30% at that point compared with none for OAR (p=0.12). The systematic literature review identified eGFR outcomes for 193 fEVAR patients. Combining these patients with the 58 from our cohort study, the pooled proportions of eGFR drop >30% were 20% (95% CI 9% to 39%) at 30 days and 8% (95% CI 0.5% to 13%) at the end of follow-up. Conclusion: fEVAR has a significant perioperative impact on renal function, but 1-year results are similar to OAR. fEVAR patients may benefit from targeted AKI prevention strategies that need to be assessed in relevant studies.