Normal Baseline Renal Function Research Articles

Age and estimated glomerular filtration rate in Chinese older adults: a cohort study from 2014 to 2020.

This study aimed to fill the data gap of the course of renal function decline in old age and explore changes in renal function across different health states with increasing age. This observational, retrospective, single-center cohort study included 5,112 Chinese older adults (3,321 men and 1,791 women, range 60-104 years). The individual rate of estimated glomerular filtration rate (eGFR) decline was analyzed using linear mixed-effects model to account for repeated measures over the years. The median age was 66 years, median BMI was 24.56 kg/m2, and median eGFR was 89.86 mL/min.1.73 m2. For every 1-year increase in age, women's eGFR decreased by 1.06 mL/min/1.73 m2 and men's by 0.91 mL/min/1.73 m2. We observed greater age-related eGFR decline in men and women with high systolic blood pressure (SBP). Men with high triglyceride (TG), high low-density lipoprotein cholesterol (LDL-C), and low high-density lipoprotein cholesterol (HDL-C), had greater age-related eGFR decline. In women, different BMI groups showed significant differences in age-related eGFR decline, with the highest decline in those with obesity. Additionally, participants with normal baseline eGFR had a faster age-related decline than those with low baseline eGFR. The eGFR declined linearly with age in Chinese older adults, with women exhibiting a slightly faster decline than men. Both men and women should be cautious of SBP. Older adults with normal baseline renal function experienced a faster eGFR decline. Men with high TG, LDL-C, and low HDL-C levels, as well as obese women, should be vigilant in monitoring renal function.

CT-guided ozone-mediated lumbar-renal sympathetic denervation for resistant hypertension treatment: A pilot single-arm clinical trial

BackgroundRenal sympathetic denervation (RDN) reduces blood pressure (BP). MethodsThis single-arm open-label study enrolled patients with resistant hypertension (RH) and treat them by CT-guided ozone mediated lumbar-renal sympathetic denervation (L-RDN). The primary endpoint was to assess the changes of BP over 24-h ambulatory BP monitoring (ABPM) and to evaluate the anti-hypertensive medication burden (AHMB) at 3-month follow-up. This study was registered in Chictr.org.cn (ChiCTR2300071375). Results17 patients (mean age 65.12 ± 10.77 years) with AHMB of 4.12 ± 1.11 were enrolled. After the procedure, 7 patients (46.7 %) matched the criteria for antihypertensive medication reduction. The AHMB decreased to 3.87 ± 0.96 for the whole objectives and from 3.87 ± 0.96 to 3.55 ± 0.78 for patients with normal baseline renal function. On top of the lessened AHMB, L-RDN further reduced morning systolic BP (SBP) by −8.6 ± 4.0 mmHg (p = 0.034) and diastolic BP (DBP) by −4.6 ± 2.1 mmHg (p = 0.032) for all participants and morning SBP by −13.2 ± 3.6 mmHg (p < 0.001), morning DBP by −6.2 ± 2.4 mmHg (p = 0.011) and daytime SBP by −4.1 ± 1.6 mmHg (p = 0.009) for those with normal baseline renal function at 3-month of follow-up. No adverse events were reported intra- and post operation. ConclusionsCT-guided ozone-mediated L-RDN might be an innovative approach of RDN for treating RH. Confirmatory studies are warranted.

Pharmacokinetics of recombinant human annexin A5 (SY-005) in patients with severe COVID-19.

Objective: Annexin A5 is a phosphatidylserine binding protein with anti-inflammatory, anticoagulant and anti-apoptotic properties. Preclinical studies have shown that annexin A5 inhibits pro-inflammatory responses and improves organ function and survival in rodent models of sepsis. This clinical trial aimed to evaluate the pharmacokinetic (PK) properties of the recombinant human annexin A5 (SY-005) in severe COVID-19. Methods: This was a pilot randomized, double-blind, placebo-controlled trial. Severe COVID-19 patients were randomly assigned to receive intravenous 50μg/kg (low dose, n = 3), 100μg/kg (high dose, n = 5) of SY-005 or placebo (n = 5) every 12h for 7 days. Plasma SY-005 levels were assessed using enzyme-linked immunosorbent assay (ELISA) and the PK parameters were determined using non-compartmental analysis. Results: All patients treated with SY-005 had a normal baseline estimated glomerular filtration rate (eGFR, 104-125mL/min/1.73m2). Both low and high doses of SY-005 were cleared within 6h after intravenous administration. Plasma maximum concentrations (Cmax), half-life, clearance and volume distribution of low and high doses of SY-005 were 402.4 and 848.9ng/mL, 0.92 and 0.96h, 7.52 and 15.19L/h, and 9.98 and 20.79 L, respectively. Daily pre-dose circulating annexin A5 levels were not significantly different when SY-005 was administered at the low or the high dose 12-h intervals. There was no significant effect on activated partial thromboplastin time (aPTT) or INR (international normalized ratio of prothrombin time) during 7days of SY-005 treatment. Conclusion: SY-005 doses of 50 and 100μg/kg were detectable and subsequently cleared from the plasma in severe COVID-19 patients with normal baseline renal function. There was no significant plasma SY-005 accumulation 6h after drug administration and coagulation was not altered during 7days of treatment. Clinical trials Registration: This study was registered with ClinicalTrials.gov (NCT04748757, first posted on 10 February 2021).

#3235 ELECTROLYTE DISORDERS IN COMMUNITY-ACQUIRED ACUTE KIDNEY INJURY

Abstract Background and Aims The kidney plays a decisive role in regulating the homeostasis of the internal environment. Acute kidney injury (AKI) compromises the kidney's ability to maintain this regulation intact, and the appearance of various electrolyte disorders is to be expected in this situation. There are few data in the literature that describe these alterations in patients with community-acquired AKI (CA-AKI). The purpose of this study is to analyze the incidence of electrolyte disorders in a cohort of patients with CA-AKI admitted to the nephrology service of a tertiary level hospital. Method This is a single-center, observational, longitudinal, and retrospective study based on a cohort of patients with CA-AKI admitted to the Nephology Service of a third level hospital from January 2010 to December 2018. We analyzed the incidence of changes in sodium, potassium, chloride, bicarbonate, calcium, and phosphorus in these patients and their clinical consequences during admission and follow-up after hospital discharge. Results A total of 639 patients were included in the final analyses. The mean age was 72,93±13,38 years. 61,7% were men. Charlson comorbidity index was 5,87 ±2,4 points. The length of stay was 11,63±10,14 days. In view of the Etiology of AKI, 72,1% had prerenal AKI and 27,9% non-prerenal. 436 patients had a history of previous chronic kidney disease (CKD) (68.23%). AKI KDIGO stages were: stage I, 105 cases (16.4%); stage II, 67 cases (10.5%); stage III 467 cases (63.1%). Hemodialysis (HD) was required in 114 patients (17.8 %). 62 patients (9.7 %) died during hospital stay. The percentage of patients with alterations in the different ions was: chlorine 54%, potassium 60.1%, sodium 45.23%, bicarbonate 85.67%, calcium 52.68%, phosphorus 54.49%. The most frequent ionic alterations at a global level were low bicarbonate (78.3%), hyperkalemia (53.05%), hypocalcemia (49.6%) and hyponatremia (41.5%). No significant differences were observed in these percentages when comparing patients with previous CKD with respect to carriers of normal baseline renal function (glomerular filtration rate &amp;gt; 60 ml/min). When analyzing whether electrolyte alterations occurred simultaneously: 2.2% of cases did not present any, 6.3% only one, 18.2% two, 26.4% three, 26.1% four, 14.9% five and 5.9% six simultaneous alterations. In the univariate analysis, patients with hypernatremia (Chi square 22.7; p &amp;lt; 0.001), hyperkalemia (Chi square 9.7; p = 0.008) and hyperphosphatemia (Chi square 18.5; p &amp;lt; 0.001) had higher mortality during admission. In the multivariate analysis using logistic regression, the variables that were independently associated with mortality during hospitalization were phosphorus (OR 1.425; 95% CI 1.212 - 1.676) and chlorine (OR 1.045; 95% CI 1.002 - 1.089). In the follow-up after hospital discharge, the Kaplan-Meier curves in the univariate analysis showed higher mortality in patients who presented hyperkalemia (log rank test: Chi square 15.5; p &amp;lt; 0.0001), hypernatremia (log rank test: Chi square 47.7; p &amp;lt; 0.0001), hypocalcemia (log rank test: Chi square 6.73; p &amp;lt; 0.034) and hyperphosphatemia (log rank test: Chi square 10.24; p &amp;lt; 0.006). In the multivariate analysis using Cox regression, the variables that were independently associated with mortality after hospital discharge were sodium (Exp(B) 1.001; 95% CI 1.002 - 1.048; p = 0.048), potassium (Exp(B) 1.140; 95% CI 1.055 - 1.233; p = 0.001) and phosphorus (Exp(B) 1.087; 95% CI 1.023 - 1.048; p = 0.154). Conclusion In our series of patients with CA-AKI, we detected a high prevalence of electrolyte disorders, without a history of previous CKD having any influence on it. The most frequent was the finding of three or four simultaneous alterations. Phosphorus and chlorine independently influenced mortality during admission. In the follow-up after hospital discharge, sodium, potassium, and phosphorus were independent predictors of mortality. The clinician who treats cases of CA-AKI must expect the appearance of frequent electrolyte disorders and must be prepared for their correct management.

Abstract 13248: The Association of Serial Measures of Plasma Trimethylamine N-Oxide With Incident Chronic Kidney Disease and Renal Function Decline Among Older Adults: The Cardiovascular Health Study

Introduction: Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite of dietary phosphatidylcholine and carnitine. Experimentally, TMAO causes renal tubulointerstitial fibrosis and kidney injury. Yet, little is known about prospective associations between TMAO and renal outcomes. Hypothesis: Higher plasma TMAO levels are prospectively associated with higher risk of incident chronic kidney disease (CKD) and greater renal function decline. Methods: We included 4,131 US adults from the Cardiovascular Health Study, a community-based cohort, with normal baseline renal function (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73m 2 ). TMAO was measured using liquid chromatography-mass spectrometry at baseline and year 7. Creatinine and Cystatin C were measured 4 times during serial follow-up and used to compute eGFR. Incident CKD was defined by eGFR (decline ≥ 30% plus eGFR&lt;60 at a follow-up visit) or presence of CKD hospitalization ICD codes. Time-varying Cox models assessed how serial TMAO measures related to incident CKD, adjusting for sociodemographic, lifestyle, diet, and CVD risk factors. Linear regression models assessed how baseline TMAO related to annualized eGFR change in 3,997 participants with at least one follow-up eGFR measure. Results: During a median follow-up of 14 years, 1,136 participants developed CKD. There was a non-linear dose-response relationship of TMAO with CKD incidence: higher TMAO levels were associated with higher risk of incident CKD with a plateauing of risk above the ~75 th percentile of TMAO levels (top Figure ). Higher baseline TMAO levels were also associated with greater annualized eGFR decline (P-linearity=0.004. bottom Figure ) after adjusting for baseline eGFR and other covariates. Conclusions: In this community-based cohort of older US adults, higher serial measures of plasma TMAO were associated with a higher risk of incident CKD and a greater rate of annualized renal function decline.

S1818 Rare Sequelae of Obstructive Jaundice: Hyperferritinemia and Bile Cast Nephropathy

Introduction: Obstructive jaundice occurs due to a physical blockage in the biliary outflow tract or external compression. While jaundice and scleral icterus are common symptoms initially, long term sequelae include severe systemic manifestations from the buildup of various compounds normally excreted in bile such as bilirubin. Case Description/Methods: A 67-year-old male smoker presented with 3 weeks of pruritus, acholic stools, dark urine, nausea, vomiting, and 20-pound weight loss. Physical exam was notable for jaundice and scleral icterus, LUQ and epigastric tenderness to palpation, but lacked hepatosplenomegaly, ascites or other stigmata of cirrhosis. Liver function tests showed AST 486 IU/L, Alk Phos 1419 IU/L, Alt 600 IU/L, and total bilirubin >30.0 mg/dL with direct bilirubin >10.0 mg/dL. Ferritin was >7500 ng/mL with decreased transferrin of 159 mcg/dL. Hepatitis panel and malignancy/autoimmune markers were negative. CMP showed BUN 74 mg/dL, and creatinine 5.1 mg/dL with 2+bilirubin on urinalysis and microscopic analysis showing pigmented renal tubular cells, bilirubin crystals, and waxy casts suggestive of ATN due to bilirubin damage and possible CKD given waxy casts (Table). CT abdomen reported severe intra and extra hepatic biliary duct dilation with CBD of 17 mm and abrupt tapering with pancreatic head fullness confirmed with MRCP. On day 2, ERCP showed a tight 15mm distal biliary stricture. A small sphincterotomy followed by balloon dilation allowed for placement of a CBD stent with excellent drainage of dark green bile. Following ERCP, patient had a drop of liver function tests and ferritin levels, gradual improvement in BUN and creatinine, and was discharged in stable condition on hospital day 6. On day 16, EUS revealed a hypoechoic area within the periampullary area with atypical cells in brushings collected during repeat ERCP (Figure). Discussion: Iron and iron binding proteins have been shown to be excreted in bile, primarily in iron excess. Our patient showed a large increase in ferritin signifying the potential role of biliary excretion of excess ferritin, with unknown ramifications. Additionally, severe biliary tree obstruction led to markedly elevated bilirubin, overwhelming renal clearance leading to severe tubular damage. With alleviation of obstruction, there was a steady decrease in ferritin and return to normal baseline renal function. Further research is needed to clarify both the consequences of excess ferritin in biliary obstruction and the significance of excess bilirubin in renal injury.Figure 1.: a) Ampulla prior to ERCP on day 2 shows no periampullary abnormality. b) Day 16 - Endoscopic Ultrasound showing narrowing of distal common bile duct with hypoechoic intraductal area. c) Bile casts and bilirubin crystals seen on microscopy. Table 1. - Patient’s Laboratory test results on and post admission Laboratory Values Reference Range Day 1 Day 5 (3 days post-ERCP) Day 21 AST 13 – 39 IU/L 486 187 18 ALT 7 – 52 IU/L 600 315 27 Alkaline Phosphatase 34 – 104 IU/L 1419 886 160 Total Bilirubin 0.3 - 1.2 mg/dL >30.0 13.0 4.4 Albumin 3.5 - 5.2 g/ 3.0 2.9 3.4 BUN 7 – 25 mg/dL 74 64 18 Creatinine 0.5 - 1.2 mg/dL 5.1 2.90 1.01 WBC 4 – 11 K/cmm 13.8 17.7 10.1 Hgb 13.7 - 17.5 g/dL 11.9 9.4 8.5 Ferritin 24 – 336 >7500 4677 976 Transferrin 300 to 360 mcg/dL 159 233 Iron 50 - 182 ug/dL 126 61 Iron Saturation 57% 19% TIBC 250 – 450 ug/dl 233 326 Urine Bilirubin Negative 2+ Negative Urobilinogen 0.0 - 2.0 EU/dL 4.0 < 2.0 PT 9.1 - 13.2 sec 26.6 12.8 PTT 23.3 - 36.6 SEC 42.0 33.0 INR 0.8 - 1.2 2.3 1.1 Alpha-1-Antitrypsin (ATT) 83 – 199 mg/dL 256 Ceruloplasmin 18– 36 mg/dL 51 Carcinoembryonic Antigen (CEA) 0.0 - 3.0 ng/mL 3.9

Effects of high-activity radioactive iodine treatment on renal function in patients with differentiated thyroid carcinoma - retrospective study.

It is not clear whether high-activity radioactive iodine (¹³¹I) treatment will affect renal function. This study aimed to investigate the effects of high-activity ¹³¹I treatment on the clinical metrics of renal function in patients with differentiated thyroid carcinoma (DTC). 262 DTC patients with abnormal baseline renal function (group A) and 262 DTC patients with normal baseline renal function (group B) who received 131I therapy were analysed. Each group was further divided into three subgroups based on the cumulative activity of 131I: subgroup 1 if the cumulative activity was less than 11.1 GBq; subgroup 2 if the cumulative activity was between 11.1 GBq and 18.5 GBq; and subgroup 3 if the cumulative activity was more than 18.5 GBq. The clinical metrics of renal function including serum creatinine (SCr), blood urea nitrogen (BUN) and estimated glomerular filtration rate (eGFR) were measured and compared before initial 131I treatment and 5 years later. There was no significant difference of the demographics between the two groups. In group A, SCr and BUN levels were elevated in 186 and 113 patients, respectively, and eGFR was decreased in 108 patients before the initial ¹³¹I therapy. SCr and BUN levels were found to be increased in all subgroups 5 years after the initial ¹³¹I therapy; furthermore, eGFR was found to be decreased in all subgroups after ¹³¹I therapy, and the difference was statistically significant (p < 0.05). A gender bias was not observed in the changing trends of SCr and BUN levels and eGFR. In group B, no significant difference in the mean levels of SCr, BUN, and eGFR was observed in the 3 subgroups (p > 0.05), regardless of gender, before the initial ¹³¹I therapy and 5 years later. A total of 5, 2, and 2 patients presented with abnormal renal function after ¹³¹I treatment in subgroups 1, 2, and 3, respectively. No statistically significant difference was observed in the incidence of renal dysfunction among the 3 subgroups (p = 0.423). Our findings suggest that the nephrotoxicity of high-activity ¹³¹I therapy, regardless of gender, is very low in patients with DTC with normal renal function; however, high-activity ¹³¹I therapy may exacerbate the loss of renal function in those with renal dysfunction.

Thrombocytopenia Associated With Teicoplanin Use: A Retrospective Observational Study.

Contradictory studies reporting vast heterogeneity in the teicoplanin-induced thrombocytopenia (TIT) incidence exist. To identify the incidence of TIT associated with teicoplanin dosing range (6-12 mg/kg/dose) and the risk factors of TIT. This retrospective observational study included adult patients who received teicoplanin for ≥3 consecutive days over a period of 3.5 years. Thrombocytopenia was defined as a platelet count of <100 × 103/µL coupled with at least a 25% drop from the baseline count. The TIT incidence was assessed using the adverse drug reaction probability scale (Naranjo scale). Data from 482 patients who received teicoplanin and met the predefined inclusion criteria were included in the analyses. The cohort presented a mean age of 53.5 ± 19 years, where 72.4% were male, and 49.2% exhibited normal baseline renal function. Teicoplanin was most commonly used for bacteremia (n = 134), and the most common isolated pathogen being Staphylococcus aureus (n = 221). The TIT incidence was 4.6% (the possible and probable category using the Naranjo scale; 22/482). The median time to first platelet count dropped to <100 × 103/µL after teicoplanin initiation was 5 (interquartile range [IQR], 3-10) days and 8 (IQR, 5-14) days till the maximum platelet count dropped. None of the tested patient variables were found to be independently associated with an increased risk of thrombocytopenia. The overall TIT incidence was low across our study cohort, including critically ill patients. Our study results may aid in the optimal monitoring of such serious teicoplanin-induced adverse effects.

High Intakes of Bioavailable Phosphate May Promote Systemic Oxidative Stress and Vascular Calcification by Boosting Mitochondrial Membrane Potential-Is Good Magnesium Status an Antidote?

Chronic kidney disease is characterized by markedly increased risk for cardiovascular mortality, vascular calcification, and ventricular hypertrophy, and is associated with increased systemic oxidative stress. Hyperphosphatemia, reflecting diminished glomerular phosphate (Pi) clearance, coupled with a compensatory increase in fibroblast growth factor 23 (FGF23) secretion are thought to be key mediators of this risk. Elevated serum and dietary Pi and elevated plasma FGF23 are associated with increased cardiovascular and total mortality in people with normal baseline renal function. FGF23 may mediate some of this risk by promoting cardiac hypertrophy via activation of fibroblast growth factor receptor 4 on cardiomyocytes. Elevated serum Pi can also cause a profound increase in systemic oxidative stress, and this may reflect the ability of Pi to act directly on mitochondria to boost membrane potential and thereby increase respiratory chain superoxide production. Moreover, elevated FGF23 likewise induces oxidative stress in vascular endothelium via activation of NADPH oxidase complexes. In vitro exposure of vascular smooth muscle cells to elevated Pi provokes an osteoblastic phenotypic transition that is mediated by increased mitochondrial oxidant production; this is offset dose-dependently by increased exposure to magnesium (Mg). In vivo, dietary Mg is protective in rodent models of vascular calcification. It is proposed that increased intracellular Mg opposes Pi’s ability to increase mitochondrial membrane potential; this model could explain its utility for prevention of vascular calcification and predicts that Mg may have a more global protective impact with regard to the direct pathogenic effects of hyperphosphatemia.

Vitamin C in the Prevention of Contrast-induced Nephropathy among High-risk Patients Undergoing Coronary Angiogram: A Meta-analysis

Background: Contrast-Induced nephropathy (CIN) is one of the leading causes of acute kidney injury. The most common procedures associated with CIN are coronary angiography and contrast enhanced computed tomography (CT) [1]. The most common definition in use is an increase in serum creatinine (SCr) of &gt;25% of the baseline values occurring following the intravascular administration of contrast media without an alternative explanation [2]. Generation of reactive oxygen species is thought to play a role in the pathogenesis of CIN, hence researches have been conducted into the potential role of antioxidants in the prevention of contrast-induced nephropathy [3]. Vitamin C, a potent antioxidant in humans has the ability to oxidize free radicals, and has been studied in different trials to measure its ability to prevent CIN among patients undergoing coronary angiogram.&#x0D; Objective: To determine if vitamin C prevents CIN among High-risk patients (Creatinine Clearance &lt;60 ml/min/m2, Diabetics, and on administration of high-volume contrast media).&#x0D; Methodology: All studies, limited to randomized clinical trials were sought for this analysis through PubMed, the Cochrane Library, ClinicalTrials.gov. Database was searched using the terms “vitamin C”, “Prevention”, “acute kidney injury” and “contrast-induced nephropathy”. Adult patients (40-90 years old) with Creatinine Clearance of &lt;60 ml/min/m2 or baseline creatinine &gt;1.2 mg/dl, Diabetes Mellitus Type II, and were administered with high-volume contrast media (&gt;100ml) undergoing coronary angiogram were included in the study. Exclusion Criteria were patients with normal baseline renal function, without risk factors for CIN, with EGFR &lt; 30 ml/min/m2, with regular intake of Vitamin C and were on dialysis. Statistical data were obtained using Review Manager (RevMan) Version 5.3 freeware program. P Value was obtained using the Cochran–Mantel–Haenszel test (CMH). Included patients were given Vitamin C at doses of 1 gram to 3 grams, taken orally or administered intravenously pre-and post coronary angiogram.&#x0D; Results: Seven hundred and one (N=701) patients were included in this meta-analysis. CIN occurred in 3.5% of patients (N=25) in the ascorbic acid group and in 6% of patients (N= 42) in the placebo group (p value of 0.03).&#x0D; Conclusion: Vitamin C given at doses 1 gram to 3 grams in combination with hydration prior to coronary angiogram may have a significant effect in the prevention of CIN in high-risk patients.

Renal function in patients receiving streptozocin for locally advanced or metastatic digestive neuroendocrine tumours: results of the Streptotox-FFCD 0906 study

IntroductionStreptozocin can impair renal function. The purpose of this study was to evaluate the evolution of renal function in patients receiving this anti-mitotic for the treatment of locally advanced/metastatic digestive well differentiated neuroendocrine tumours. MethodsA prospective and a retrospective cohort of patients with normal baseline renal function were analysed. The primary endpoint was the incidence of a decrease in the estimated glomerular filtration rate ≥ 25% during treatment. Secondary endpoints were the evaluation of glomerular filtration rate changes, the impact of combined nephrotoxic treatments, other toxicities, compliance, and the objective response rate. ResultsAfter screening 142 patients, 27 were included in the prospective and 84 in the retrospective cohort. A decrease in estimated glomerular filtration rate ≥ 25% was observed in 32 patients (30%): respectively four (15.4%) and 28 patients (34.1%) among respectively 26 and 82 patients with numerous measures (P = 0.0097). Altogether, 39 patients (35%) experienced grade 1–2 renal toxicity, while no grade 3−4 occurred in the prospective and 1 occurred in the retrospective cohort. Renal toxicity was more frequent in the retrospective cohort with a less careful follow up. As best responses, objective response was achieved in 27% of patients with pancreatic primary tumours, disease control in 78.9% of patients with pancreatic primary tumours, in 87% of those with small bowel tumours and in 72.7% of patients with other primary locations. ConclusionsStrongly recommended for pancreatic NET, streptozocin is associated with frequent mild renal toxicity but low occurrence of renal impairment in patients with baseline normal renal function and under adequate hydration.

Longitudinal Measures of Trimethylamine N-oxide and Incident Atherosclerotic Cardiovascular Disease Events in Older Adults: The Cardiovascular Health Study

Abstract Objectives Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite of dietary choline, L-carnitine and phosphatidylcholine-rich animal foods. Based on experimental studies and cohorts with prevalent disease, elevated TMAO may increase risk of atherosclerotic cardiovascular disease (ASCVD). TMAO is also renally cleared and may interact with and causally contribute to renal dysfunction and elevated cystatin-C. Yet, the associations of serial TMAO levels with incident ASCVD in a community-based prospective cohort, and the potential mediating and modifying role of renal function, are not established. Methods We investigated the associations of serial measures of plasma TMAO, assessed at baseline and 7 years post baseline, with incident ASCVD among 4144 older adults in the Cardiovascular Health Study (CHS). TMAO was measured using stable isotope dilution LC/MS/MS (lab CV &amp;lt;6%). Incident ASCVD (myocardial infarction, fatal coronary heart disease, stroke, sudden cardiac death, or other atherosclerotic death) was centrally adjudicated using medical records. Risk was assessed by multivariable Cox proportional hazards regression including time-varying demographics, lifestyle factors, medical history, and laboratory and dietary variables. We assessed potential mediating effects and interaction by renal function estimated by cystatin-C. Results During a median 15 years follow-up, 1757 ASCVD events occurred. After multivariable adjustment, TMAO was associated with a higher risk of ASCVD, with an extreme quintile HR (95% CI) of 1.22 (1.04, 1.44), P-trend = 0.01. This relationship appeared further mediated or confounded by estimated glomerular filtration rate (eGFR): adjusting for cystatin-C-based eGFR, the HR (95% CI) was 1.06 (0.98–1.25). Significant interaction was also observed by renal function (P-interaction &amp;lt; 0.001), with TMAO associated with higher risk of ASCVD among individuals with impaired renal function (eGFR ≤ 60) [1.63 (1.03–2.59)], but not normal baseline renal function (eGFR &amp;gt; 60) [1.15 (0.96–1.37)], even with further adjustment for continuous eGFR. Conclusions In this large community-based cohort of older US adults, higher serial measures of TMAO were associated with an elevated risk of ASCVD, in particular among those with impaired renal function. Funding Sources NIH, NHLBI.

SAT-030 CONTRAST INDUCED NEPHROPATHY IN HIGH RISK PATIENTS – MYTH OR REALITY

Contrast induced nephropathy (CIN) is a potential complication of administration of contrast media. CIN is defined as an elevation of serum creatinine (Scr) of more than 25% or ≥0.5 mg/dl (44 μmol/l) from baseline within 48-72 hours in the absence of alternate causes of acute kidney injury (AKI). Incidence of contrast induced acute kidney injury (CI-AKI) in patients undergoing coronary angiography with normal baseline renal function was reported to be < 2%7. However, the incidence of CI-AKI was found to be as high as 50% in chronic kidney disease (CKD) patients undergoing Coronary Angiography. This high incidence reported by studies is mainly due to differences in definition, background renal failure, types and dose of contrast medium used and frequency of other co-existing potential cause of AKI. Recent studies have been published showing that risk of CIN is an ‘overestimated entity” in the literature. The objective of this study is to determine the frequency of CIN in CKD patients with creatinine clearance (CrCl) less than 60ml/min undergoing contrast exposure. We conducted prospective, controlled single center trial in 44 patients with CrCl than 60ml/min who were risk stratified according to Mehran scoring system and underwent coronary angiography or contrast enhanced CT scan and specific protocol for prevention of CIN i.e. IV Hydration with 0.9% Normal Saline was given before procedure and were followed up to 72 hours post procedure. Thirty-three patients out of Forty-Four patients (75%) got adequate hydration as per protocol however eleven patients underwent procedure without hydration as preexisting condition did not allow so. Out of forty-four patients, risk stratification according to Mehran protocol revealed that fifteen out of forty-four patients (34%) were in very high-risk group, sixteen (36%) were in High risk group and thirteen (29%) were in intermediate risk group. Our experience revealed that five Patients out of total Forty-Four patients (11.3%) suffered from Contrast induced Nephropathy and none of them needed hemodialysis. Our study has raised a serious question regarding the incidence of Contrast induced Nephropathy in High risk patients as reported previously. However, more studies are needed on this issue. Till that time, we might consider CIN “a myth rather than a reality”.

A nomogram for predicting the renal dysfunction in a Chinese population with reduction in cadmium exposure based on an 8 years follow up study.

Cadmium exposure is associated with renal dysfunction. However, the outcome of renal function in subjects who have had a reduction in cadmium exposure for years has not been completely clarified, particularly for individuals with normal baseline renal function. In this study, we used a nomogram model to predict renal dysfunction after a reduction in cadmium exposure in subjects with normal baseline renal function. In 1998, a survey was performed in 790 subjects living in control and cadmium-polluted areas. A total of 497 subjects was followed up in 2006. 404 subjects with normal baseline urinary β2-microglobulin (UBMG), 373 subjects with normal baseline urinary N-acetyl-β-d-glucosaminidase (UNAG) and 407 subjects with normal baseline urinary albumin (UALB) were included in this analysis. Cadmium in the blood (BCd) and urine (UCd) was detected using graphite-furnace atomic absorption spectrometry. A logistic regression model was used to identify potential predicting factors of renal function at follow-up. Nomograms were developed based on those predictive factors. Bootstrap self-sampling, calibration curves and receiver operating characteristic (ROC) curves were performed to quantify our modeling strategy. Adjusted and unadjusted logistic regression models both showed that age, BCd and UBMG or UNAG at baseline were independent risk factors for renal tubular dysfunction. Baseline age, sex, BCd and UNAG or UBMG or UALB were used to construct the nomogam. The internal validation showed that the C-index was 0.70-0.74 for predicting renal dysfunction. The area under the curve of the nomogram was 0.70-0.74. Decision curve analysis verified the predictive value of the nomogram. A nomogram may be a useful risk assessment tool for predicting the progress of renal function in a cadmium-exposed population with normal baseline kidney function.

Use of Pamidronate for Hypercalcemia of Malignancy in Renal Dysfunction

Background: Few studies have been conducted investigating the use of bisphosphonates in hypercalcemia of malignancy (HCM) in the setting of renal dysfunction. Objective: The primary objective was to compare the incidence of acute kidney injury (AKI) within 7 days of receiving pamidronate for the treatment of HCM with pre-existing renal dysfunction versus normal renal function at the time of pamidronate administration. The secondary objectives explored the effects of pamidronate doses and infusion rates on the safety and efficacy in those with pre-existing renal dysfunction for the treatment of HCM. Methods: A retrospective chart review was conducted on patients who received pamidronate for the treatment of HCM at a community teaching hospital in Indianapolis, Indiana, from January 1, 2013, to May 31, 2017. Results: A total of 141 pamidronate administrations were included (116 patients had normal baseline renal function, and 25 patients had pre-existing renal dysfunction before pamidronate administration for the treatment of HCM). Two (8%) patients developed AKI in the pre-existing renal dysfunction group, compared with 4 (3.4%) patients in those without pre-existing renal dysfunction (P = .288). For those with pre-existing renal dysfunction, the incidence of AKI did not differ based on the dosage of pamidronate given (P = .762) or infusion rates (P = .373). Conclusion: Pamidronate appears to have limited impact on renal function at doses up to 90 mg in the setting of pre-existing renal dysfunction for the treatment of HCM.

2292. Incidence of Acute Kidney Injury Associated with Duration of Vancomycin and Piperacillin/tazobactam Combination Therapy

BackgroundEmpiric antibiotic therapy for serious and healthcare-acquired infections often requires coverage for resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. These regimens commonly consist of vancomycin plus an antipseudomonal β-lactam. Recent studies have reported increased acute kidney injury (AKI) risk associated with concomitant vancomycin and piperacillin/tazobactam therapy compared with each agent alone. The objective of this study was to determine whether vancomycin with piperacillin/tazobactam had an increased AKI incidence compared with vancomycin plus cefepime or meropenem. Furthermore, data were analyzed to determine whether a specific duration was associated with an increased AKI incidence.MethodsA retrospective cohort study was conducted analyzing patients who received vancomycin in combination with piperacillin/tazobactam (V+PT), cefepime (V+C), or meropenem (V+M) between January 1, 2018 through June 30, 2018. Adult patients with normal baseline renal function and receipt of at least 48 hours of combination therapy, with the two antibiotics initiated within 24 hours of one another, were included. AKI events, evaluated using the Acute Kidney Injury Network (AKIN) criteria, during antibiotic therapy and up to 72 hours after antibiotic discontinuation were recorded. This data were used to calculate the AKI incidence with each regimen and AKI incidence associated with each day of therapy.ResultsA total of 181 patients were included in the study. The incidence of AKI in the V+PT group was 22.8% vs. 5.6% and 16.7% in the V+C and V+M groups, respectively (P = 0.237). Median duration of therapy when AKI occurred was 3 days for V+PT, 4 days for V+C, and 2 days for V+M (P = 0.015). Patients in the V+M group received more nephrotoxic agents compared with V+PT and V+C (P = 0.004). Statistical analysis did not find a specific day of V+PT therapy predictive of AKI. However, a time to event analysis demonstrated a steady increase in AKI risk with V+PT from day 2 through 6.ConclusionAlthough not statistically significant, V+PT therapy was associated with a higher incidence of AKI compared with V+C or V+M. Future studies are needed to further assess the impact of duration of therapy on AKI incidence.Disclosures All authors: No reported disclosures.

A Nomogram for Predicting the Renal Dysfunction Based on an 8 Years Follow Up Study in a Chinese Population Reducing Exposed to Cadmium

Objective: Cadmium exposure is associated with renal dysfunction. However, the outcome of renal function in subjects with reduction in cadmium exposure for years has not completely clarified, in particular for individuals with normal baseline renal function. In this study, we used nomogram model to predict the renal dysfunction after reduction of cadmium exposure in those subjects with normal baseline renal function. Methods: In 1998, a survey was performed in 790 subjects living in control and cadmium polluted areas. 497 subjects was followed up in 2006. 373-407 subjects with normal renal function were included in this analysis. The cadmium in blood (BCd) and urine (UCd) were detected using flame atomic absorption spectrometry. The differences in BCd, UCd, UBMG, UNAG and UALB between 1998 and 2006 were analyzed. Logistic regression model was used to identify the potential predicting factors for renal function at follow-up. Nomogams were developed based on those predictive factors. Bootstrap self-sampling, calibration curves and Receiver Operating Characteristic curves (ROC) were performed to quantify our modeling strategy. Results: The BCd levels were significant decreased (differences: 3.42 - 3.45 μg/L) and renal biomarker were increased at the follow-up compared to those at baseline. UCd levels were also decreased (0.20 - 0.52 μg/g creatinine), but no significant differences were found. Significant increases were observed in urinary β2Microglobulin (UBMG), urinary Nacetyl-β d-glucosaminidase (UNAG) and urinary albumin (UALB) in 2006. Baseline age, gender, BCd and UNAG or UBMG or UALB were used to construct the nomogam. The internal validation showed the C-index was 0.70-0.74 in predicting renal dysfunction. The area under the curve of the nomogram was 0.70 - 0.74. Decision curve analysis verified the predictive value of nomogram. Conclusion: Nomogram may be a potential risk assessment tool for predicting the progress of renal function in a cadmium-exposed population with normal baseline kidney function. Funding Statement: This study was funded by National Natural Science foundation of China (No. 81773460, 81102148) and the European Union (Sixth Framework Programme; PHIME; FOOD-CT-2006-016253). Declaration of Interests: The authors stated: None. Ethics Approval Statement: The study was approved by Institutional Review Board of Fudan University (Shanghai, China). During the study, Declaration of Helsinki was followed. Informed consent was obtained from each participant.

Evaluation and Treatment of Severe Rhabdomyolysis in a Patient with Legionnaires' Disease

A 53-year-old man with alcoholism and a three-day history of diarrhea and abdominal pain was hospitalized with mild acute kidney injury (AKI) and rhabdomyolysis after a fall where he was down for a short duration. Subsequent testing revealed patchy right lower lobe infiltrates on chest X-ray and a positive urinary Legionella antigen test. Creatinine phosphokinase (CPK) peaked at 85,780 U/L (normal 0-250) on hospital day two and remained markedly elevated for five days despite aggressive intravenous (IV) hydration and appropriate antibiotic treatment. When the patient defervesced and showed clinical signs of resolution of pneumonia, the CPK level declined rapidly, and renal function returned to baseline. Rhabdomyolysis with AKI is a rare but serious complication of Legionella pneumonia, with most patients requiring dialysis. Our patient’s complete recovery without renal replacement therapy can probably be attributed to his normal baseline renal function, timely diagnosis of his Legionella-associated rhabdomyolysis, and prompt treatment with aggressive IV hydration and appropriate antibiotics. Legionella infection should be considered in acutely ill patients with rhabdomyolysis of unclear etiology.

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Indeed, the benefit of performing nephron sparing surgery off-clamp remains controversial. The present findings are meaningful to the extent that, at least in the short term, the off-clamp approach does not appear to result in vastly superior renal functional preservation in most patients; surgeons who perform RAPN on-clamp clearly need not avoid doing so in reaction to this study. However, the findings should be considered in the context of the abovementioned limitations including a relatively short follow-up period and the enrollment of patients with normal baseline renal function. Furthermore, if warm ischemia times are minimized to the extent reported herein, the choice between on-clamp and off-clamp in terms of functional preservation may ultimately prove to be inconsequential. The path is clear for future prospective trials to further examine this potentially underutilized technique in patients more susceptible to renal functional loss.

A Nomogram to Predict Significant Estimated Glomerular Filtration Rate Reduction After Robotic Partial Nephrectomy

BackgroundDecreased functional outcome after partial nephrectomy is associated with overall mortality. ObjectiveTo create a model that predicts ≥25% reduction from baseline estimated glomerular filtration rate (eGFR) in patients undergoing robot-assisted partial nephrectomy (RAPN) and to investigate the role of acute kidney injury (AKI) in this patient population. Design, setting, and participantsA total of 999 patients were identified from a multi-institutional database. Renal function was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for chronic kidney disease (CKD). AKI was defined as >25% reduction in eGFR from pre-RAPN period to discharge. Outcome measurements and statistical analysisA nomogram to predict significant eGFR reduction (≥25% from baseline) in the time-frame between 3 and 15mo after RAPN was built based on the coefficients of Cox survival function that ultimately included age, sex, Charlson comorbidity index, baseline eGFR, RENAL nephrometry score, AKI in patients with normal baseline renal function, and AKI on CKD. Such landmark analysis was chosen in order to account for eGFR fluctuations occurring within the first 3mo of RAPN. The proportional hazard assumption was evaluated through the Schönfeld test. Internal validation was performed using the leave-one-out cross validation. Calibration was graphically investigated. The decision curve analysis (DCA) was used to evaluate the net clinical benefit. Results and limitationsMedian (interquartile range [IQR]) age at surgery was 61yr (51, 68). Overall, 146 patients experienced significant eGFR reduction; median follow-up for survivors was 12.4mo. The 15-mo probability of significant eGFR reduction was 19%. All variables fitted into the model, including AKI in patients with normal renal function (hazard ratio [HR]: 4.51; 95% confidence interval [CI]: 3.12, 6.60; p<0.001) and AKI on CKD (HR: 4.90; 95% CI: 2.17, 11.1; p<0.001), emerged as predictors of significant eGFR reduction (all p≤0.048) and were considered to build a nomogram. The internally validated c index was 73%. The model demonstrated excellent calibration and a net benefit at the DCA with probabilities ≥4%. ConclusionsWe developed a nomogram that accurately predicts significant eGFR reduction after RAPN. This model may serve as a tool for early identification of patients at high risk for significant renal function decline after surgery. Patient summaryWe have developed a model for the prediction of renal function loss after partial nephrectomy for renal cancer.