Lower GFR Research Articles

Differences in the optimization of pharmacological treatment in patients with heart failure and reduced ejection fraction and advanced chronic kidney disease

Abstract Introduction Chronic kidney disease is very prevalent in patients with HF, makes their treatment difficult and worsens their prognosis, especially when it is advanced CKD (glomerular filtration rate <30 mL/min/m2). Renal insufficiency increases the risk of drug intolerance and an increase in serious side effects, which can lead to underuse, with consequent negative effects on patient prognosis. Purpose To analyze in a contemporary registry of HF patients followed in specialized HF units in Spain the achievement of dose targets for the most used drugs in HF with reduced ejection fraction (HFrEF) and the impact of advanced CKD. Methods We analyzed 914 patients with HFrEF consecutively included between 2019 and 2021 in the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology in 45 centers. We evaluated the proportion of patients treated with ACEI, ARA, ARNI, MRA, beta-blockers and SGLT2 inhibitors at the registry inclusion visit, the causes of non-prescription, and the achievement of the maximum dose recommended in the ESC clinical practice guidelines or the maximum tolerated dose in these patients, comparing the GFR groups, greater or less than 30 ml/min/m2. Results Of the 914 patients, 8.9% had a GFR<30 mL/min/m2. Their age was 76.9±9.7 years, 39.7% women, mean LVEF 32.8±9-6%. Patients with GFR<30 received in a significantly lower proportion all HF drugs except diuretics, ARBs and potassium chelators: sacubitril-valsartan 30.5% vs 59.2%; MRAs 31.7 vs 77.8%; SGLT2 inhibitors 34.1 vs 52.9% (p<0.001; Figure 1). The main reason for non-use was intolerance/contraindication for beta-blockers and "other" for the rest of the drugs (Figure 1). The proportion of patients in whom the maximum recommended, or maximum tolerated dose was reached was low in both groups, less than 40-50% for all drugs except MRA. There were no significant differences between the two groups in relation to the degree of renal dysfunction, although there was a tendency for the recommended doses to be obtained more frequently in the group with lower GFR (Figure 2). Conclusions In our contemporary cohort of real-life patients with HFrEF and advanced CKD, the use of recommended drugs for HF was significantly lower than in those patients with better renal function. However, where they were used, maximum recommended or tolerated doses were achieved in a higher proportion of patients. This indicates that with adequate selection it is possible to achieve the objectives proposed by the clinical practice guidelines in this complex group of patients.

Extending the window in clinical decision making: the role for Impella 5.5 in cardiogenic shock

Abstract Background Acute decompensated heart failure (HF) refractory to medical management deteriorates quickly to cardiogenic shock, ultimately requiring mechanical circulatory support (MCS). These devices aim to provide circulatory support as a bridge to advanced therapies. We report patient outcomes with the latest minimally invasive temporary MCS device: Impella 5.5 with SmartAssist. Methods All patients who underwent Impella 5.5 implantation between January 2020 and December 2023 were analyzed. Duration of Impella support and peri-implant parameters were collected from electronic medical records. ANOVA was performed and utilized a p-value of <0.05 as significant for statistical analysis. Results During our review period, a total of 99 patients were supported with Impella 5.5 in the setting of cardiogenic shock. 92 were bridged to heart transplant (BTT), of which 17 also received combined kidney transplantation. Two underwent durable VAD implantation (BTVAD), and 3 had native heart recovery (BTR) and explant. Two patients died, yielding a survival rate of 98%. For BTT group, the median age was 60 years (52-65) at implant and a median BMI of 27 kg/m² (24-31) with a mean support duration of 29 days (SD ±24). Baseline GFR was 49 mL/min/1.73m² (35-65). In the BTVAD group, the median BMI was 43 kg/m² (39-46) with an average duration of support of 22 days (SD ±8) with a GFR of 55 mL/min/1.73m² (38-73). The BTR group had a median BMI of 29 kg/m² (27-30) with an average duration of support of 15 days (SD ±7) and a lower baseline GFR of 36 mL/min/1.73m² (26 – 37) compared to BTT or BTVAD. The two patients that died were supported for an average of 42 days (SD ±9.2) and expired due to non-candidacy in the setting of newly detected prostate cancer in one patient and multi-organ failure in another. All BTVAD and BTT patients did not have a stroke or major vascular complications before terminal therapy. Conclusion Our center highlights the role of early Impella 5.5 placement in the stabilization of patients in cardiogenic shock, thereby providing both patients and providers time for decision-making while optimizing end-organ perfusion beyond the accepted duration of 14 days.Impella Data - Entire CohortImpella Data - Stratified by Outcome

Changes of Procalcitonin Kinetics According to Renal Clearance in Critically Ill Patients with Primary Gram-Negative Bloodstream Infections.

This study aimed to investigate the relationship between procalcitonin (PCT) kinetic and estimated glomerular filtration rates (eGFR) in critically ill patients who had Gram-negative primary bloodstream infection (GN-BSI) and responded to the antimicrobial therapy. This single-centered study was retrospective and observational. Critically ill GN-BSI patients over 18 years old who had clinical and microbiological responses to antibiotic treatment were included in the study. Patients were divided into two groups according to eGFR (eGFR <30 mL/min/1.73m2 and ≥30 mL/min/1.73m2) and compared for PCT kinetic at seven different measurement points as initial, first, third, fifth, seventh, tenth, and fourteenth days. The study included 138 patients. Initial PCT levels were higher in patients with eGFR <30 mL/min/1.73m2 (4.58 [1.36-39.4] ng/mL) than in eGFR ≥30 mL/min/1.73m2 (0.91 [0.32-10.2]) (p<0.001). This elevation was present at all measurement points (p<0.05). The decrease in PCT values by ≥30% (26.0% vs 47.9%; p=0.024) on the third day and ≥50% (69.2% vs 76.6%; p=0.411) on the fifth day was less in the low eGFR (<30 mL/min/1.73m2) group. The effect of low GFR on serum PCT kinetic was present in both fermenter and non-fermenter GN-BSIs but was more prominent in the fermenter group. Serum PCT levels during therapy were higher in patients with low eGFR. Early PCT (<5 days) response was not obtained in non-fermenter GN-BSI patients with low eGFR. Antibiotic revision decisions should be made more carefully in patients with low eGFR due to high initial PCT levels and slow PCT kinetic.

Abstract 38: Loop Diuretic Resistance in a Preclinical Model of Cardiorenal Syndrome 2: Role of Enhanced Distal Convoluted Tubule Sodium Transport

Nearly 60% of heart failure (HF) patients develop a progressive decline in kidney function. Decompensated HF also causes edema, usually treated with loop diuretics, like furosemide, that inhibit the Na-K-2Cl cotransporter NKCC2 in the thick ascending limb (TAL). However, nearly 50% of HF patients do not respond adequately to loop diuretics and become resistant. The mechanisms causing loop diuretic resistance are unclear but may involve TAL-dependent and independent mechanisms. Few have used the mouse as a model of cardiorenal syndrome due to its resistance to renal damage. We hypothesize that mice develop loop diuretic resistance and lower GFR after chronic HF induced by myocardial infarction (MI). MI was induced in C57Bl6J mice through ligation of the left anterior descending coronary artery and compared to a sham surgery group. We assessed heart function by echocardiography and GFR (FITC inulin) in conscious mice. The response to diuretics was studied in metabolic cages. MI mice had a 50% reduction in ejection fraction (EF) one month after MI (MI: 29.94 ± 1.94, Sham: 67.02 ± 1.14%, n= 8, p&lt;0.05). EF was still lower 3 and 6 months after MI. The MI group showed decreased GFR, 6 months after MI (MI: 0.50 ± 0.06, Sham: 0.75±0.05 µl/min, n= 5, p&lt;0.05). Urinary albumin was similar in both groups (n=8). In metabolic cages, a saturating dose of the NKCC2 inhibitor bumetanide (20 mg/Kg), induced diuresis and natriuresis in sham mice (Delta UV: 1.96 ± 0.27 ml/4h, Delta UNa: 117.2 ± 11.02µmols/4h, n= 6) but had an attenuated response in MI mice (Delta UV: 0.88 ± 0.23 ml/4h, Delta UNa: 65.00 ± 4.53 µmols/4h, n= 4, p&lt;0.05 vs sham). To study the distal convoluted tubule (DCT) we measured the response to hydrochlorothiazide (HCTZ). HCTZ (100 mg/Kg) induced a natriuretic response in sham mice (Delta UNa: 75.24±11.18µmols/4h, n= 10) and a higher response in the MI group (Delta UNa: 129.54±11.59µmols/4h, n= 12, p&lt;0.05 vs sham). RNAseq in isolated mTALs from MI and sham mice identified 85 up- and 160 down-regulated genes (n=5, p&lt;0.025). Up-regulated genes involved those in the sphingosine pathway, protein trafficking, PKA signaling (PDE4B, PRKD2) and cell growth/tubule differentiation (FREM2, WFDC1). mRNA expression of TAL NaCl transporters was not affected. We conclude that HF decreases GFR, induces loop diuretic resistance and affects mTAL signaling in mice. Loop diuretic resistance may involve enhanced DCT NaCl reabsorption.

Зв’язок співвідношення альбуміну та креатиніну сечі з різними статево-віковими і клінічними характеристиками в пацієнтів з інфарктом міокарда з елевацією сегмента ST

The work method revealed the clinical course of STEMI depending on the functional state of the kidneys and ACR in the urine. Included were 286 patients with acute coronary syndromes, average age 62.8±9.8 years, after revascularization. Among the examined were 202 (70.6%) men and 84 (29.4%) women. It was established that 158 ​​places were classified as ACR &lt;3, 92 individuals – ACR 3–30 mg/mmol and 36 – ACR &gt;30 mg/mmol. Gender characteristics show that women were significantly more likely to belong to the group of ACR &gt;30 mg/mmol, the distribution into different age gradations according to WHO (2015) showed that at the age of 25–44 all patients belonged to group 1 (ACR &gt;3 mg/mmol ) and group 2 (ACR 3–30 mg/mmol). Among cases aged 75–89, there were significantly more persons with ACR &gt;30 mg/mmol, p1–3=0.003; p2–3=0.01 the value of GFR calculated from the level of cystatin C in plasma according to the CKD-EPI formula Cystatin C shows significantly lower GFR in various categories of ACR based on GFR calculated on the basis of creatinine. With a decrease in GFR, the number of deficiencies that had gradations of ACR 3–30 and ACR &gt;30 significantly increases. The clinical course of STEMI in the treatment of ACR over 30 is characterized by a longer history of hypertension and diabetes, a greater number of patients with diabetes, hereditary history of cardiovascular diseases, diagnosis of atrial fibrillation.

Kidney involvement in ankylosing spondylitis; recent findings

Ankylosing spondylitis is a chronic inflammatory illness that initially involves the spine and sacroiliac joint. It rarely presents with kidney disease. Various biochemical and morphological alterations have been described, consisting of hematuria, proteinuria, and low GFR across immunoglobulin A nephropathy, renal amyloidosis, focal segmental glomerulosclerosis, and chronic interstitial nephritis with different frequencies among populations.

Creatine homeostasis and the kidney: comparison between kidney transplant recipients and healthy controls

Creatine is a natural nitrogenous organic acid that is integral to energy metabolism and crucial for proper cell functioning. The kidneys are involved in the first step of creatine production. With kidney transplantation being the gold-standard treatment for end-stage kidney disease, kidney transplant recipients (KTR) may be at risk of impaired creatine synthesis. We aimed to compare creatine homeostasis between KTR and controls. Plasma and urine concentrations of arginine, glycine, guanidinoacetate, creatine and creatinine were measured in 553 KTR and 168 healthy controls. Creatine intake was assessed using food frequency questionnaires. Iothalamate-measured GFR data were available in subsets of 157 KTR and 167 controls. KTR and controls had comparable body weight, height and creatine intake (all P > 0.05). However, the total creatine pool was 14% lower in KTR as compared to controls (651 ± 178 vs. 753 ± 239 mmol, P < 0.001). The endogenous creatine synthesis rate was 22% lower in KTR as compared to controls (7.8 ± 3.0 vs. 10.0 ± 4.1 mmol per day, P < 0.001). Despite lower GFR, the plasma guanidinoacetate and creatine concentrations were 21% and 41% lower in KTR as compared to controls (both P < 0.001). Urinary excretion of guanidinoacetate and creatine were 66% and 59% lower in KTR as compared to controls (both P < 0.001). In KTR, but not in controls, a higher measured GFR was associated with a higher endogenous creatine synthesis rate (std. beta: 0.21, 95% CI: 0.08; 0.33; P = 0.002), as well as a higher total creatine pool (std. beta: 0.22, 95% CI: 0.11; 0.33; P < 0.001). These associations were fully mediated (93% and 95%; P < 0.001) by urinary guanidinoacetate excretion which is consistent with production of the creatine precursor guanidinoacetate as rate-limiting factor. Our findings highlight that KTR have a disturbed creatine homeostasis as compared to controls. Given the direct relationship of measured GFR with endogenous creatine synthesis rate and the total creatine pool, creatine supplementation might be beneficial in KTR with low kidney function.Trial registration ID: NCT02811835.Trial registration URL: https://clinicaltrials.gov/ct2/show/NCT02811835.

Newly diagnosed heart failure in patients with atrial fibrillation referred for catheter ablation - identifying patients with arrhythmia-induced cardiomyopathy

Abstract Introduction Atrial tachyarrhythmias are primary drivers in the development of arrhythmia-induced cardiomyopathy (AiCM). The restoration of sinus rhythm in patients with an AF (atrial fibrillation) based AiCM results in enhancement of left ventricular ejection fraction (LV-EF). This study aims to assess the prevalence of undiagnosed and unexplained heart failure among patients with AF referred for catheter ablation and seeks to phenotype these patients. Methods Our registry, a prospective, observational clinical cohort that recruits patients with heart rhythm disorders at a large tertiary-care center since March 2021 was interrogated for AF patients. These patients underwent screening for heart failure based on clinical, laboratory, and imaging characteristics. Undiagnosed heart failure at baseline, lack of heart failure medication and absence of known structural heart disease were considered suspicious for AiCM. Results A total of 1225 patients were analyzed. 35.2% were female, median age 67 (IQR 59;75) years, median LV-EF 55.0 (IQR 50;60) % and median N-terminal pro B-type natriuretic peptide (NT-proBNP) 686 (IQR 210;1630) mg/dl. NYHA class I was reported in 28.3% cases, NYHA class II in 32.2%, NYHA class III in 20.2% and NYHA class IV in 2%. At baseline, 263 patients (17.6%) had an LV-EF &amp;lt; 50% of those 110/263 (42%) with suspected AiCM. Patients with suspected AiCM were 67 (IQR 58;76) years old, 40.9% were female, median LV-EF was 41.0 (IQR 35;41) % and NT-proBNP at admission was 1681 (IQR 775;2352) mg/dl. Patients with suspected AiCM had a significantly reduced TAPSE (19 vs. 22 mm; p&amp;lt;0.001), showed generic characteristics of heart failure (NTproBNP: p&amp;lt;0.001, NYHA class: p=0.049), while EHRA score was significantly lower (p=0.006). In contrast, patients with known cardiomyopathy of non-AiCM origin at baseline and EF &amp;lt; 50% (n=153) had significantly higher LAVI (44.8 vs. 38.8 ml/m2; p=0.002), were predominantly male (76.5 vs. 59.1 %; p=0.004) and had lower GFR (60.2 vs. 68.5 ml/min; p=0.002) compared to AiCM patients. Among 29/110 suspected AiCM patients with available TTE at follow-up (within 12 months post-catheter ablation), 26/29 exhibited an improved LV-EF (40% at baseline vs. 54% at FU; p&amp;lt;0.001). 3/3 patients without LV-EF improvement exhibited arrhythmia recurrence. Conclusion Primary AiCM was suspected in 42% of all AF patients with reduced LV function referred for catheter ablation. These patients exhibited a different phenotype compared to the remaining cohort. After catheter ablation, ejection fraction improved in 90% of AiCM patients. These findings call for structured HF screening in clinical routine in AF patients. In the future, validated scores are required to enable early rhythm control for these patients.Proportion of patients with HFrEFCourse of EF after catheter ablation

#546 Decline of kidney function before and after start of peritoneal dialysis (PD)

Abstract Background and Aims Residual kidney function (RKF) is a key component for PD adequacy and associated with improved volume status, nutrition and quality of life as well as with increased survival. The aim of the present study was to compare decline of kidney function before and after start of PD. Method We studied patients starting PD (during 2000-2019) in an ongoing prospective study of patients starting dialysis. Study inclusion in almost all PD patients coincided with PD catheter insertion. Patients were included in the present analysis if they had at least one urinary collection before, and one after PD initiation (a), PD initiation less than six months after study inclusion (b) and &amp;gt; 6 months PD treatment (c). P-creatinine to calculate eGFR was retrospectively collected for 12 months before start of PD. During a large part of the study period, it was a clinical routine to collect 24-hour urine collections regularly in CKD5 patients, and these data were retrieved when available. After start of PD, regular 24-hour urine collections were part of the clinical routine to follow up and were retrieved for up to 12 months after PD start. eGFR was measured using the CKD-epi 2021 equation and GFR was calculated as the average of urinary creatinine and urea clearance corrected for BSA. The decline of eGFR before start of PD, the decline of GFR from 24-hour urine collections and the decline of GFR after start of PD were compared to each other. Results We studied 138 patients starting PD. The mean age was 55 ± SD13 years, and there were 80 males and 58 females. The mean blood pressure was 153 ± SD21/89 ± SD11 mmHg and BMI was 25 ± SD4 kg/m2. The etiologies of end stage kidney disease were nephrosclerosis 17%, diabetic nephropathy 22%, glomerulonephritis 25%, polycystic kidney disease 14% and other 22%. The GFR at PD start was 8.5 ± SD 2.3 mL/min/1,73 m² and eGFR was 5.8 ± SD 1.9 mL/min/1,73 m². The results show a significantly slower kidney function decline rate after start of PD, with an average of −0.59 mL/min/1,73 m²/month before PD initiation compared to −0.34 mL/min/1,73 m²/month after. Conclusion Decline of GFR was slower after start of PD suggesting that earlier initiation of dialysis may be beneficial for the preservation of RKF. Notably, there was a marked attenuation after 3 months of dialysis. Furthermore, the decline rate of GFR before PD start was similar using eGFR or GFR from 24-h urine collection, though for eGFR at somewhat lower levels. However, there were pronounced differences between those two methods in individual patients demonstrating that eGFR is unreliable with very low GFR. Further study will be performed to analyze what factors that are associated with better preservation of RKF.

#2287 Impact of renal reserve before donation in post-transplant renal function of donors and recipients

Abstract Background and Aims The influence of Renal Reserve (RR), i.e. its presence or absence, in post-transplant renal function both in living kidney donors and recipients is unknown. The presence of RR in donors may be beneficial in terms of better renal function both for the donor and recipient after transplantation. In the other hand, the absence of RR in donors might indicate a lower renal endowment and so predispose to lower GFR post-transplantation in donors and recipients. However, little evidence is available in this field. Method In a previous study (ERA Abstract 2023, #3737) we described in a group of 52 potential living kidney donors, the presence (24-46%), absence (13-25%) or use (15-29%) of RR before donation. The latter was defined as the lack of increase in GFR after stimulation in patients with basal GFR &amp;gt; 100 mL/min. GFR was measured before and after transplantation by the clearance of iohexol with dried blood spots. Presence of RR was defined as an increase &amp;gt;10% of basal GFR after IV amino acid infusion. GFR was unadjusted to body surface area (BSA). In this follow-up study we investigated the impact of the presence, absence or use of RR before donation in GFR 12 months after transplantation, both in donors and recipients. Results Of the 52 pairs of donors and recipients, renal transplantation was performed in 21 who also had 12 months of follow-up. Before transplantation 9 donors had RR, 4 did not and 8 had RR in use. Pre-transplant GFR was 95 ± 15 ml/min, 89 ± 6 ml/min and 127 ± 16 ml/min in donors with RR, without RR and with RR in use, respectively. At 12 months after kidney donation, GFR was higher in donors who had RR in use before donation: 79 ± 12 ml/min, compared with those with RR: 65 ± 9 ml/min (p = 0.048) and those without RR 59 ± 10 (p = 0.03). In recipients, GFR was comparable between those who had a donor with RR or RR in use: 72 ± 19 ml/min vs 68 ± 12 ml/min (p = ns), whereas both groups had higher GFR than those recipients whose donors had no RR before donation 53 ± 5 ml/min, although of borderline signification (p = 0.07). Non parametric tests were used. No major complications after transplantations such as rejections or surgical complications, etc, that could alter GFR were observed. Conclusion The presence or use of RR may determine a better renal function 12 months after donation both for donors and recipients. This is a preliminary study and we acknowledge that the low number of cases is a limitation and so, these results require further studies.

Glomerular Hemodynamics During Recovery from Renal Ischemia-Reperfusion Injury Addressed with Micropuncture in Rats

Objective: To establish the physical basis for low GFR in ischemic renal injury (IR) and determine whether abnormalities in GFR determinants persist after renal recovery. Method: IR was generated in male and female Wistar Froemter rats by clamping both renal pedicles for 60 minutes. Controls had same surgery without pedicle clamp. Glomerular hemodynamics were assessed by renal micropuncture (MP) after 1 day, 1 week, or 4 weeks. Single nephron GFR (SNGFR) was paired with tubular stop-flow (PSF) and free-flow pressure (PFF) in each nephron. Afferent Starling pressure (EFPa) is PSF-PFF. Glomerular capillary pressure (PGC) was computed from PSF, PFF and plasma oncotic pressure. ANOVA factors included IR, sex, time point and date of experiment (nested). Inter-nephron heterogeneity was extracted from normalized root-square difference between each data point and the mean for that animal. (total n=349 nephrons, 47 rats). Results: [Formula: see text] Summary and conclusion: The physical cause of low GFR in IR was low EFPa, which resulted from low PGC with normal PFF in all animals except 1. The injured kidney manifest elevated inter-nephron variability for all variables. Mean values for SNGFR and intra-renal pressures returned to normal in the “recovered” kidney, but variability between nephrons did not return to normal. Female rats had lower baseline SNGFR and PGC than males but the hemodynamic patterns during IR and renal recovery were not differentiable by sex (excluding one female outlier with high PFF). Despite “normal” GFR and PGC, the “recovered” kidney is not a “normal” kidney. NIH NIDDK R01 132690. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Central Body Fat Distribution and Kidney Function after Living Kidney Donation.

In most screening guidelines, high body mass index (BMI) is considered a contraindication for kidney donation. New insights suggest that central body fat distribution might provide greater power in assessing kidney risk. This study aimed to determine whether BMI and central body fat distribution measures are associated with long-term kidney function after donor nephrectomy. We hypothesized that higher BMI, waist circumference (WC), and waist-to-height ratio (WHtR) were associated with lower kidney function long term after donation. The study population consisted of living kidney donors. BMI, WC, and WHtR were measured during donor screening. The outcome postdonation kidney function was assessed using measured GFR (mGFR) (mGFR, 125 I-iothalamate infusion) at 3 months ( n =1042), 5 years ( n =556), and 10 years ( n =210) of follow-up. Primary multivariable linear regression analyses were performed with BMI and WC and secondary analyses with WHtR. Linear mixed models were performed to investigate change in postdonation eGFR. The donor age was 52±11 years, and 48% were male. The mean BMI was 26.1±3.6 kg/m 2 , and WC was 91±11 cm. Higher predonation BMI was associated with lower mGFR throughout follow-up: -1.35 (95% confidence interval [CI], -1.95 to -0.80), -1.55 (95% CI, -2.50 to -0.65), and -2.35 (95% CI, -4.10 to -0.60) ml/min per m 2 per 5 kg/m 2 higher BMI at 3 months, 5, and 10 years after donation, respectively, adjusted for sex, age, and predonation GFR. For WC, differences in mGFR were -1.30 (95% CI, -1.70 to -0.90), -1.50 (95% CI, -2.20 to -0.80), and -1.70 (95% CI, -3.00 to -0.50) ml/min per m 2 per 10 cm higher WC at 3 months, 5, and 10 years after donation, respectively. In male donors, BMI and WC were significantly associated with a negative postdonation change in eGFR. Higher BMI and WC were independently associated with lower GFR (long term) after living kidney donation.

Effect of Tyrosine Kinase Inhibitor Therapy on Estimated Glomerular Filtration Rate in Patients with Chronic Myeloid Leukemia

IntroductionThe advent of tyrosine kinase inhibitors (TKIs) was revolutionary in the management of chronic myeloid leukemia (CML). Although TKIs were generally considered to be safe, they can be associated with renal injury. We evaluated the effect of TKIs on renal functions in a cohort of patients with long-term follow-up. Material and MethodsWe retrospectively examined patients with chronic phase CML treated with TKIs. We analyzed the estimated glomerular filtration rate (eGFR) of patients from the initiation of TKI to the last follow-up. eGFR values of CML patients were compared to those of patients with stage 1 or 2 chronic kidney disease (CKD). ResultsA total of 195 patients with CML and 138 patients with CKD were examined. eGFR decline was 1.556 ml/min/1.73m2/year for patients with CML (P = .221). Patients receiving second-generation TKIs (2GTKI) were estimated to have 0.583 ml/min/1.73m2 higher eGFR value than that of the imatinib group, but it was not significant (P = .871). eGFR of patients who had used bosutinib had a downward trend. Duration of TKI therapy, age, and hypertension were found to be significant factors in eGFR decline for CML patients. Lower baseline GFR was associated with an increased risk of CKD development. ConclusionImatinib could result in a decline in eGFR which was clinically similar to early-stage CKD patients. We did not observe significant kidney function deterioration in patients receiving 2GTKIs including dasatinib and nilotinib. We recommend close renal function monitoring in patients receiving imatinib, especially for elderly patients with lower baseline eGFR and hypertension.

Epidemiological profile of type 2 diabetic patients followed at a secondary care referral center: Data from a Moroccan cohort study

BackgroundType 2 diabetes is a major public health problem responsible for several macro and microvascular complications, including diabetic nephropathy. The main objective of this study was to describe the epidemiological profile of type 2 diabetic patients at admission to a reference center for chronic diseases and to explore associated factors with a glomerular filtration rate decline (GFR). MethodsThis retrospective cohort study aims to examine the epidemiological characteristics of patients with type 2 diabetes who had at least one consultation between November 2005 and December 2020. ResultsThe study included 19,953 patients, of whom 67.8 % were women, with an average age of 58.2 ± 12.2 years. The majority (64.7 %) had a diabetes duration of less than 5 years. On admission, 37.6 % of patients had high blood pressure, 41.8 % were overweight, while 31.5 % were obese. Nearly 9 % of patients had at least one complication on admission: 2.6 % had heart disease, 2 % had nephropathy, 1.8 % had retinopathy, 0.7 % had neuropathy and 0.5 % had a diabetic foot. The study found that 76.8 % of patients had poorly controlled diabetes, and 30.1 % had a GFR 〈 60 ml/min/1.73 m². Women, patients over 65 years, those with a diabetes duration 〉 30 months, hypertensive patients, those with at least one complication on admission, patients with overweight or obesity, and those with positive albuminuria had significantly lower GFR (p < 0.001). ConclusionOur study showed that most patients were initially diagnosed with Type 2 diabetes in primary healthcare and had a very high risk of complications. Primary care health centers may not have sufficient human and material resources to effectively screen for and monitor these complications. Therefore, it is crucial to strengthen secondary care referral centers to ensure comprehensive and optimal management of diabetes patients, including diabetic control and early detection and management of its complications.

Identification of Some Specific Hematological Indicators as Bladder Cancer Risk Factors

Background: Our study’s objectives were measuring the levels of blood glucose BG, blood pressure BP, glomerular filtration rate GFR, body mass index BMI and creatinine in the blood of patients with bladder cancer in order to control the development of a relationship between those hematological parameters in the case of bladder cancer BC.&#x0D; Methods and Results: Blood samples were collected during the application of this work on 155 participants diagnosed with BC were admitted to medical –Baghdad city and Al-Kindey teaching hospital. All the participants were with the age ranged (25-70 years).There are many people who have been excluded because of their young age under 20 years old and those who have any type of common cancer, which was outlined as any malignant neoplasm, including those with hematological or lymphoid origin and other tissues associated with them. All the participants wearing light clothing and no shoes in order to measure their height and weight. BP was recorded using a standard mercury sphygmomanometer after an average of 2 readings taken with a 10 min interval. Creatinine and GFR and DM also were measured meanwhile.&#x0D; It was noticed through the results that there is a high percentage of patients who are of advanced ages about 67(43.2%) with age ≥65 years, and those with high weights BMI ≥ 30 were 64(41.3%). After conducting pathological analyzes of blood samples, it was found that patients were having high levels of sugar, especially those with long duration of diabetics type 2, as well as high blood pressure, creatinine levels, and low GFR levels, and it was clear that males outperformed females in the height of all measurements, which is the dominant characteristic in this research.&#x0D;

Increasing rates of referrals for investigation of primary aldosteronism at a tertiary centre.

To describe the frequency and characteristics of patients referred for specialist investigation of primary aldosteronism (PA) in the lower North Island over a 5-year period, and the outcomes of those who received treatment. Patients who underwent confirmatory testing or treatment for PA at Wellington Regional Hospital were retrospectively identified and data were collected from electronic clinical records. There has been a five-fold increase in both referrals and confirmatory testing for PA in 2021 compared to 2015. Compared to patients without PA, those eventually diagnosed with PA had a higher ARR, serum sodium, antihypertensive requirement and cardiovascular disease prevalence, as well as lower serum renin, potassium and GFR (all p <0.05), but similar blood pressure. Complete or partial clinical success was achieved in 96% of surgically treated patients compared with 70% of medically treated patients. Thirty-nine percent of patients experienced minor adverse effects with spironolactone and only one significant adverse event was experienced perioperatively. The rate of referrals and confirmatory testing for PA are increasing in our region. Adrenalectomy and mineralocorticoid antagonist therapy are both safe and effective treatments, although minor adverse effects were common with spironolactone.

Plasma levels of amyloid beta 1-40 are associated with ultrasonographic morphological characteristics related with carotid plaque vulnerability in individuals without cardiovascular disease

Abstract Background Amyloid-beta (1-40) (Αb40), a proinflammatory and pro-atherosclerotic peptide, is associated with concurrent subclinical atherosclerotic cardiovascular disease (ASCVD) and with major adverse cardiac events in both primary and secondary prevention settings conferring additive and reclassification value over traditional risk factors and risk scores. This evidence supports the hypothesis that Ab40 could be a biomarker of ASCVD. However, mechanistic data on the association of Αb40 with in vivo morphological characteristics of atherosclerosis related with plaque vulnerability are not available. Purpose To examine the association of Ab40 levels with characteristics of the carotid artery wall in the general population. Methods In the settings of the Athens Vascular registry, subjects without clinically overt ASCVD were consecutively recruited (n=301). Subclinical carotid atherosclerosis was assessed by ultrasonography and the images were subsequently analyzed using a dedicated software (AMS v3.03). The sum and maximal area of atherosclerotic plaques (PLQ) and the minimum echogenicity using grey scale median (GSM) of intima-media thickness (IMT, IMT_GSM) and atherosclerotic plaques (PLQ_GSM) were used as the main endpoints of the analysis. Αb40 was measured in plasma samples. Results Subjects with Ab40 levels in the highest tertile had higher prevalence of male sex, presence of carotid plaque atherosclerosis, higher sum and maximal PLQ are and lower GFR HDL-C levels and lower PLQ_GSM (p&amp;lt;0.05 for all). Ab40 in the highest vs. lower tertile was associated with higher sum and maximal plaque area (b-coefficient= 22.9 95% CI: 0.72, 45.1, p=0.43 and b-coefficient= 10.5 95% CI: 1.77, 19.3, p=0.019, for sum and maximal plaque area, respectively) after adjustment for traditional cardiovascular risk factors and GFR (core model). Moreover, Ab40 in the highest tertile was associated with decreased GSM of both IMT and PLQ in the carotid arteries (b-coefficient= -6.0 95% CI: -9.6, -2.36, p=0.001, for IMT and b-coefficient= -8.66 95% CI: -16.5, -0.79, p=0.31, for PLQ) after adjustment for the core model. Conclusion In individuals without clinically overt ASCVD, higher levels of Ab40 are associated with the larger atherosclerotic burden and with ultrasonographic characteristics related to higher plaque vulnerability. These findings suggest a mechanistic background for the established association of Ab40 with major adverse cardiovascular events.

Abstract 14106: Predicting Persistently Elevated Pulmonary Artery Diastolic Pressure Despite Adequate Diuresis

Introduction: Patients with chronic HF can be challenging to manage via ambulatory hemodynamic monitoring due to persistent elevations in pulmonary artery diastolic pressure (PADP) despite appropriate diuresis. Knowing what factors predict persistently elevated PADP on CardioMEMS can help guide patient selection and management. Hypothesis: We propose that underlying heart failure phenotypes exist that are less likely to respond to hemodynamic guided management. Methods: This was a single-center, retrospective analysis of Scripps Clinic patients who underwent CardioMEMS implantation from June 2015 to September 2022. A total of 115 patients were included and divided into two cohorts based off their average PADP calculated using their last 4 transmissions. The normal PADP cohort included patients with an average PADP ≤ 20 mmHg while the persistently elevated PADP cohort included patients with a PADP &gt; 20 mmHg. Results: Of the 115 patients analyzed, 62 patients were in the normal PADP cohort while 53 patients were in the persistently elevated PADP cohort. There was no significant difference between baseline demographic data, except for renal function, as shown in Table 1. There was a significant difference between the two groups when comparing pulmonary pressures and PVR via right heart catheterization prior to CardioMEMS implantation, but not when comparing pulmonary artery pressure obtained via echocardiogram (Table 1). The persistently elevated PADP cohort had a significantly lower GFR and were on higher doses of loop diuretics than the normal PADP cohort. Conclusions: Our analysis shows that renal function, baseline invasive hemodynamic data consistent with pulmonary vascular remodeling and decreased cardiac index can help predict patients with persistent elevations in their PADP on ambulatory hemodynamic monitoring and highlights the importance of early HF management before vascular remodeling complicates hemodynamic guided management.

A study on thyroid function assessment in patients with chronic kidney disease: An investigative analysis

Background: Chronic Kidney Disease (CKD) and thyroid dysfunction often coexist, and understanding their relationship is crucial for diagnosis and management. Aims and Objectives: This study aimed to explore the prevalence, clinical significance, and implications of thyroid function abnormalities in CKD patients, providing valuable insights for improving patient care and outcomes. Methods: This observational cross-sectional study included 46 CKD patients undergoing conservative management at Aditya Hospitals and Diagnostics, Dibrugarh, from July 2021 to July 2022. Participants met predefined inclusion criteria and provided informed consent. Exclusion criteria encompassed active treatment with dialysis or kidney transplantation, nephrotic-range proteinuria, hypoalbuminemia, acute illness, diabetes mellitus, recent surgery, trauma, burns, liver diseases, and medications affecting thyroid function. Results: The study involved 31 male (67.39%) and 15 female (32.60%) CKD patients aged 19 to 69 years. CKD symptoms' duration ranged from 4 to 30 months (mean 9.8 months). Serum T3 levels ranged from 0.2 to 2.0 ng/ml (mean 0.67 ng/ml), T4 levels from 0.9 to 8.5 μg/dl (mean 5.7 μg/dl), and TSH levels from 0.6 to 38 μIU/ml (mean 6.5 μIU/ml). Hypothyroidism symptoms were observed in 31 patients (67%). Low T3 syndrome was found in 27 patients, low T4 syndrome in 11 patients, and hypothyroidism in 3 patients. Conclusion: The study revealed that the incidence of low T3 syndrome increased with age and CKD severity. Patients with lower GFR exhibited decreased serum T3 levels. Interestingly, in patients with low T3 syndrome, TSH values remained within the normal range and did not correlate with GFR. The findings suggest that low T3 levels in CKD may play a protective role in protein conservation. This investigation sheds light on the complex relationship between thyroid function and CKD, emphasizing the need for regular thyroid assessments in CKD patients for better management and improved clinical outcomes. Early identification and appropriate intervention for thyroid abnormalities in CKD may contribute to optimizing patient care and overall well-being.

1221 Recipient Outcomes After Simultaneous Pancreas and Kidney Transplant Delineated by Donor eGFR

Abstract Aim This study aimed to assess if the use of kidneys with a decreased eGFR had an adverse effect on patient and graft survival. Method Data on all UK SPKT’s from 2001-2021 were obtained from the NHSBT UK Transplant Registry (n = 2,631). Cases with missing information were removed, leaving a final cohort of 1,819 (69.1%). eGFR was calculated using the CKD-EPI equation. Pancreas Graft (PGS), Kidney Graft (KGS) and patient survival analyses were conducted using Kaplan-Meier plots and Cox-regression models. Results 71% (n = 1,292) of grafts were from donors with an eGFR&amp;gt;90 and 29%(n = 530) were from donors with an eGFR&amp;lt;90. Donors with an eGFR&amp;lt;90 were statistically significantly more likely to be older (p&amp;lt;0.0001), a DBD donor (p = 0.0086**) and have a higher BMI(p&amp;lt;0.0001). Recipients who received a graft from a donor with an eGFR&amp;lt;90 were well matched with those who received a graft from a donor with an eGFR&amp;gt;90. Univariate analysis showed a statistically significant decreased KGS(p = 0.007**) when the donor had an eGFR&amp;lt;90. This trend was not seen when comparing patient or pancreas survival. Conclusions We accept a lower GFR could be indicative of either an AKI or a sign of early chronic kidney disease. In this current data analysis, we have been unable to successfully distinguish between the two however we have shown poorer KGS in those with a lower eGFR (&amp;lt;90). This had no impact on pancreas or patient survival. Further analysis is needed to explain the precise reasons for the lower eGFR’s at the time of organ donation.