Lower GFR Research Articles

Risks of Polymyxin B Nephrotoxicity and Its Precursors in the Intensive Care Unit: A Retrospective Cohort Study.

Polymyxin group antibiotics constitute a part of our limited arsenal in the treatment of multidrug-resistant gram-negative bacteria. However, their use is limited especially due to nephrotoxicity and other side effects. In this study, we primarily aimed to determine the effect of polymyxin B on the rate of nephrotoxicity in critically ill patients, and secondly to identify the factors that facilitate nephrotoxicity caused by polymyxin B. The study was designed as a retrospective cohort study and conducted by scanning patients aged 18 years or older who had been admitted to our intensive care unit (ICU) in 2022 and treated with polymyxin B for at least 72 hours. Patients without chronic renal failure and acute kidney injury (AKI) before starting polymyxin B therapy were included and AKI was examined after the use of polymyxin B. The patients were then divided into two groups, those with AKI and those without AKI. We tried to find factors that may facilitate AKI by comparing the two groups. Of the patients, 26 were female and 34 were male. In 21 of the patients (35%), renal damage of varying degrees developed; these patients belonged to the nephrotoxicity (NT) group, while the rest belonged to the non-nephrotoxicity (non-NT) group. We found that advanced age (p=0.008), low baseline GFR (p=0.01), baseline creatinine (p=0.006), BMI (p=0.011), concomitant diseases (p<0.001), and days of use of polymyxin B (p=0.006) were statistically different between the two groups. In multivariate analysis of univariate analysis, we found that duration of polymyxin B use, BMI, and advanced age were independent risk factors for AKI development. We found that 21 (35%) of 60 intensive care unit patients who had no previous history of kidney injury developed kidney injury after being treated with polymyxin B. We identified advanced age, high BMI, and duration of polymyxin B use as independent risk factors. Therefore, we recommend close monitoring of renal function and prompt intervention, particularly in patients with risk factors, during polymyxin B use.

Application of GFR estimating equations to children with normal, near-normal, or discordant GFR.

The objective was to determine the extent that eGFR formulas correspond to measured plasma iohexol clearance (iGFR) in children with normal or near normal kidney function, particularly how different eGFR formulas yield discordant results. iGFR from 2 (iGFR-2pt) and 4 (iGFR-4pt) time points along with creatinine and/or cystatin C-based eGFR were measured in children with mild CKD, stages 1-2. eGFR was calculated using 6 equations: 3 under 25 (U25) formulas from the Chronic Kidney Disease in Children (CKiD) study, the full age-combined cystatin C (cysC) and creatinine spectrum (FAS-combined), the European Kidney Function Consortium (EKFC-creatinine) equation, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-epi) cysC-based equation. Twenty-nine children were included, of which 22 had discordant creatinine vs. cystatin C-based eGFR by ≥ 15mL/min/1.73m2. Overall, the FAS-combined had the least bias, while the U25 most accurately identified children with an eGFR < 90 mL/min/1.73m2. When Cr-eGFR was ≥ 15 mL/min higher than CysC-eGFR, the U25 creatinine eGFR was closest to iGFR-4pt. When CysC eGFR was higher, the U25-combined was closest to iGFR-4pt. The formulas that most closely approximated the measured GFR varied depending on the pattern of discordant eGFR results. Based on the results, we recommend using the CKiD U25-combined formula to screen for children with a low GFR. Either the CKiD U25-combined or FAS-combined would be recommended for changes in eGFR longitudinally. However, because all formulas were discordant from the iGFR-4pt in over a third of participants, further refinement of pediatric eGFR formulas is needed at the normal/near-normal range. A higher resolution version of the Graphical abstract is available as Supplementary information.

#4914 LOW LEAN BODY TISSUE IS AN INDEPENDENT RISK FACTOR FOR KIDNEY DISEASE PROGRESSION AND MORTALITY IN PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE

Abstract Background and Aims Lean tissue mass is a marker of good health and is associated with a lower risk of death in patients without chronic kidney disease (CKD). A potentially underestimated risk factor for impaired renal function is low serum albumin concentration. Previous studies have shown that even small decreases in serum albumin concentration levels are strongly associated with cardiovascular disease, heart failure, impaired kidney function, and mortality in vulnerable populations. An association between low lean body tissue with mortality in patients with stage 4 and 5 CKD has recently been demonstrated. The aim of this study was to evaluate the effect of lean body tissue index (LTI) measured by multifrequency bioelectrical impedance analysis (BIA) on kidney disease progression and mortality in a cohort of patients with stage 4 and 5 CKD. Method We performed a retrospective observational cohort study that included patients with stage 4 and 5 CKD who were referred to the Advanced Chronic Kidney Disease outpatient clinic at our centre between January 2014 and December 2020, in whom a baseline measurement of body composition by using BIA was performed in the first 6 months of follow-up. Baseline clinical and laboratory parameters (serum creatinine, glomerular filtration rate, serum albumin, hemoglobin, cholesterol, triglycerides, calcium, phosphorus, PTH and CRP) were defined as those observed at the time of BIA measurement. Low lean tissue was defined as having LTI values below the 10th centile adjusted by age and sex. Renal survival was defined as the absence of need of renal replacement therapy (RRT) at the end of follow-up. Results The study included 145 patients who had a mean age of 72 ± 11.8 years, 69.7% were males, with a mean GFR measured by CKD-EPI of 20.4 ± 4.7 ml/min, mean albumin of 4.1 ± 0.3 g/dl and median urine albumin-creatinine ratio (uACR)of 413 mg/g (IQR 98-1341). The mean body mass index of the population was 30.1 ± 6.1 kg/m2, and BIA showed a mean LTI of 15.4 ± 3.9 kg/m2 and fat tissue index (FTI) of 14.1 ± 6.8 kg/m2. Nineteen patients (13.1%) had low LTI. Patients with low LTI were younger (65.9 ± 12.8 vs 73 ± 11.4 years, p = 0.013) and had higher uACR (1444 [484-1815] vs 318 [68-1188] mg/g, p = 0.002) with no differences in sex, GFR, and other laboratory parameters. After a mean follow-up of 27.7 months (IQR 15.3-45.4), 72 (49.7%) showed CKD progression to RRT and 55 patients (37.9%) died. The Kaplan-Meier survival analysis showed that patients with low LTI had a worse renal survival (log-rank 5.5, p = 0.019) and overall survival (log-rank 7.6, p = 0.006). The multivariate Cox regression analysis showed that low LTI (HR 2.28, 95% CI 1.12-4.62), lower GFR (HR 0.86, 95% CI 0.81-0.92) and higher uACR (HR 1.001, CI 95% 1-1.001) were independent risk factors for CKD progression to ESKD, while low LTI (HR 3.16, 95% CI 1.42-7.05), age (HR 1.09, CI 95% 1.05-1.13) and serum albumin (HR 0.31, CI 95% 0.13-0.77) were the factors that were independently associated with mortality. Conclusion Low lean body tissue index measured by multifrequency bioelectrical impedance analysis is and independent risk factor for CKD progression and mortality in stage 4-5 CKD. Close monitoring of nutritional status by BIA should be followed in these patients to provide timely and adequate nutritional interventions that might help in improving patient outcomes.

#6733 THE PREDICTORS OF CARDIO-RENAL SYNDROME AMONG PATIENTS WITH COVID-19 INFECTION

Abstract Background and Aims Several reports showed that some Covid-19 patients tend to have serious and fatal complications related to the kidney and heart. Rationale and mechanisms inducing this pathogenesis is unclear, but it's more common to happen in patients with hemodynamic instability and refractory severe hypotension related to cytokine storm. It represents an irreversible stage of a sepsis-like illness that induces simultaneous damage to various organs as the myocardium and renal tubules alike the cardio-renal syndrome. The predictors for this injurious effect of COVID-19 on both myocardium and renal tissues might be related to the co-morbidities, late presentation and other factors which need further evaluation.The aim of this article is to study the predictors of cardio-renal syndrome in COVID-19 patients Method Our study is a prospective observational study conducted upon confirmed 160 COVID-19 ICU patients admitted from 15th March till 20th May 2020. All patients were subjected to clinical assessment, full laboratory evaluation including PCR for COVID-19 from nasopharyngeal swab and full radiological evaluation Results As regards the predictors for cardio-renal syndrome [15-17]; Age showed high statistically significance (P &amp;lt;0.0004). Furthermore, serum creatinine and serum K were statistically significant in patients with cardio-renal affection (P= 0.015, 0.021) whereas GFR, D-dimer, need for mechanical ventilation and vasopressors were highly statistically significant with cardio-renal affected patients (P &amp;lt;0.001). Conclusion Cardio-renal syndrome was common in COVID-19 ICU patients. Hypokalemia, lower GFR on admission, mechanical ventilation, vasopressors, age and D-dimer were significant independent predictors for CRS. Moreover,CRS during hospitalization was associated with an increased risk of in-hospital death.

#2777 RISK FACTORS ASSOCIATED WITH OUTCOMES IN PATIENTS WITH HENOCH - SCHӧNLEIN PURPURA NEPHRITIS

Abstract Background and Aims Henoch - Schӧnlein purpura (HSP) is an immuno-mediated small-vessel vasculitis that manifests as non—thrombocytopenic purpura, arthritis or arthralgia, abdominal pain and/or kidney involvement. HSP nephritis can presented is micro- or macroscopic hematuria, proteinuria, nephrotic or nephritic syndrome, as well as acute renal failure. The aim of the study is to identify risk factors associated with unfavorable outcomes in patients with HSP nephritis. Method This retrospective study enrolled 68 patients with HSP nephritis. Renal and extra-renal symptoms were analyzed. A diagnosis of HSP nephritis was made when hematuria and/or proteinuria, and/or renal failure was associated with a palpable purpuric eruption or abdominal or joint pains (at least two of these three clinical signs) and predominant mesangial IgA immune deposits, confirmed by renal biopsy. The patients were subdivided into five classes according to the renal manifestation at onset of disease: 1) micro- or macroscopic hematuria; 2) mild proteinuria (&amp;lt;1 g/L) ± hematuria; 3) acute nephritic syndrome, defined as moderate proteinuria, hematuria, increased serum creatinine and/or hypertension; 4) nephrotic syndrome; 5) mixed nephritic-nephrotic syndrome. Results Of 68 patients with HSP nephritis, diagnosed by kidney biopsy, 41 (60,29%) were male and 27 (39,71%) - female. Age of onset was between 18 and 66 years (mean 37,28 ± 9,34). Duration of follow-up was between 2 and 28 years. 29 patients had histories of infection preceding presentation. At onset all patients had palpable purpura and urinary abnormalities (only hematuria - in 16,18%; mild proteinuria ± hematuria – in 44,12%; moderate or severe proteinuria and hematuria – in 39,70%). Arthralgias were present in 49 patients (72,06%), gastrointestinal involvement – in 32 patients (47,05%). Renal function was impaired in 26,47% of patients, and 51,47% were hypertensive. Mesangial hypercellularity lesions were found in most patients (97,06%), endocapillary proliferation – in 20,58%, segmental sclerosis – in 32,35%, tubular atrophy/interstitial fibrosis – in 38,23%. Corticosteroids and cyclophosphamide were prescribed in patients who presented with severe clinical and histological features and/or rapidly progressing renal disease. During follow-up classical extra-renal organ diseases were seen in 55,88% of patients, and hematuria and/or proteinuria – in 77,94%. At final review 26,47% had progression of renal failure. Risk factors for renal failure were moderate or severe proteinuria during follow-up (p&amp;lt;0,001), renal impairment at presentation (p&amp;lt;0,001), hypertension at presentation and during follow up (p&amp;lt;0,05), crescents, interstitial fibrosis and tubular atrophy (p&amp;lt;0,001). No significant difference in renal outcome was observed between patients who had relapses in extra-renal organs versus in those who did not. Conclusion Our results indicated that lower GFR, nephrotic syndrome, nephritic-nephrotic syndrome and crescentic nephritis were risk factors for unfavorable outcomes.

SERUM PARATHORMONE, VITAMIN D AND CARDIOVASCULAR RISK FACTORS

Objective: The aim of this study is to evaluate the associations of serum 25-OHD and PTH concentrations with blood pressure and hypertension mediated target organ damage including left ventricular hypertrophy (LVH) and carotid intima-media thickness (IMT). Design and method: This observational retrospective study included 98 patients admitted at Hypertension Research Center of Federico II University Hospital in Naples without CKD. We collected serum 25-OHD, PTH, creatinine, BMI, lipid profile, blood glucose and office blood pressure. All patients underwent carotid doppler ultrasound and echocardiography. Results: Mean age of the participants was 53±17 years and 69% were men. Pearson's correlation analysis indicated that PTH levels correlated directly with age, diabetes, dyslipidemia, hypertension, fasting glucose, on statin therapy, left ventricular mass and inversely with the GFR, total cholesterol, LDL and vit D level. Vit. D levels correlated inversely with PTH, diabetes and carotid plaque. Multivariate regression models indicated that PTH was significantly associated with higher fasting glucose and with vit D while Vit D was associated with lower GFR and PTH level. Conclusions: In a population at high cardiovascular risk, Vit. D and PTH are not directly associated with hypertension but might influence association with other cardiovascular risk factors and markers.

O041 Recipient outcomes after simultaneous pancreas and kidney transplant delineated by donor EGFR

Abstract Introduction This study aimed to assess if the use of kidneys from donors with a decreased eGFR had an adverse effect on patient and graft survival. Methods 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. Conclusion 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 eGFRs at the time of organ donation.

Nephron-specific deletion of ALMS1 (Alstrom syndrome 1) increases surface NKCC2 expression and NaCl reabsorption in the Thick Ascending Limb

Mutations in the ALMS1 gene in humans cause Alström syndrome, characterized by progressive metabolic alterations that include obesity, hypertension, and chronic kidney disease (CKD). SNPs in the ALMS1 gene in the general population are associated with lower GFR, hypertension and metabolic syndrome. ALMS1 is widely expressed where it localizes to endosomes, centrosomes and the base of cilia. Our lab has previously shown that ALMS1 is expressed in renal tubules of the Thick Ascending Limb (TAL) where NKCC2 is the primary apical NaCl transporter. Whole animal gene deletion of ALMS1 increases blood pressure, and inhibits NKCC2 endocytosis, increasing its surface expression and renal NaCl reabsorption. However, whole animal ALMS1 KO rats or mice develop obesity, affecting the interpretation of organ-specific data. We hypothesized that ALMS1 is a part of protein complex that binds apical NKCC2 in TALs and promotes its endocytosis. To study the role of ALMS1 in the nephron without influence of obesity we generated a loxP flanked exon 7 ALMS1 transgenic mouse line, that we crossed with nephron specific inducible Pax8-rtTA Cre mice (Pax8-ALMS1 KO). 4 weeks after inducing Cre expression with doxycycline (2mg/ml in 2% sucrose), ALMS1 expression in TAL suspensions decreased by 75% (p&lt;0.01). To study the role of ALMS1 in TAL function, we measured surface to total NKCC2 ratio, which was increased by 53±15% in TALs from Pax8-ALMS1 KO compared to control floxed ALMS1 (p&lt;0.01). Recombinant ALMS1 (GST-Carboxyl terminus-ALMS1), or immunoprecipitation of ALMS1, pulled down NKCC2 from WT TAL lysates (n=3), suggesting that the mechanism by which ALMS1 regulates surface NKCC2 involves protein-protein interactions. 4 weeks after inducing Cre expression with doxycycline we measured bumetanide-induced natriuresis (4h) as an index of NKCC2-mediated NaCl absorption. We found that bumetanide induced UNa excretion was higher in Pax8-ALMS1 KO, compared to control (control: 115±19 vs Pax8-ALMS1 KO: 146±30 μmols Na/4h, p&lt;0.05). Since whole animal ALMS1 deletion induced hypertension, we measured systolic blood pressure (SBP) by tail cuff one month after inducible deletion of ALMS1 or in floxed ALMS1 mice treated with doxycycline as controls. Baseline SBP in normal Na diet (0.4%) was similar between strains. However, SBP increased by 12±3 mmHg in Pax8-ALMS1 KO, but not in control floxed ALMS1 littermates after 9 days of high Na diet (WT: 100±10, Pax8-ALMS1 KO: 115±11 mmHg, p&lt;0.05 from baseline, n=4). We conclude that ALMS1, binds NKCC2 to regulate its surface expression. Depletion of ALMS1 in the nephron enhances surface NKCC2, TAL NaCl reabsorption, and induces salt-sensitivity of blood pressure. Our data indicate that regulation of the ALMS1-NKCC2 interaction in the TAL is important for renal NaCl reabsorption and regulation of blood pressure. Funding: NIH R56DK131114, Henry Ford Fund This is the full abstract presented at the American Physiology Summit 2023 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.

Leptin Inhibition Ameliorates Renal Mitochondrial Dysfunction And Associated Renal Injury In Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and polycystic ovaries. Renal injury, increased central adiposity and higher circulating levels of the adipokine leptin are common characteristics of PCOS. Leptin has direct renal fibrotic, hypertrophic, and albuminuric effects and can cause renal mitochondrial dysfunction and oxidative stress leading to chronic kidney disease development. Despite increased circulating leptin level in both lean and obese PCOS women, its role in PCOS-mediated renal damage remains unknown. In a well-characterized mouse model of PCOS, we aimed to test the hypothesis that hyperandrogenemia increases central adiposity leading to hyperleptinemia, which via leptin receptors induces intrarenal mitochondrial oxidative stress and dysfunction causing renal injury. Methods: Three-week-old peripubertal female mice were implanted with Silastic tubes filled with the non-aromatizable androgen dihydrotestosterone (DHT, 8 mg) or vehicle for 12 weeks. Eight weeks post-Silastic tubes implantation, the animals were treated with the leptin receptor antagonist (LepR-Ant) pegylated leptin (2 mg/kg, ip, 3x/week) for 4 weeks. Body weight, fat mass (EchoMRI), kidney weight (gravimetry), plasma leptin (ELISA), the glomerular filtration rate (GFR, transcutaneous fluorescence), as well as the renal injury markers urinary albumin to creatinine ratio (UACR, clinical chemistry analyzer), NGAL, and KIM1 (ELISA) were measured. Freshly isolated kidney mitochondria were used to measure mitochondrial reactive oxygen species (mtROS) by Amplex Red assay. Moreover, mitochondrial complex I and complex II-driven respiration and complex IV activity were assessed using Oroboros Fluorespirometer. Results: DHT significantly (p&lt;0.05) increased body weight (31.6 ± 2.3 vs. 23.6 ± 0.5 g), fat mass (3.5 ± 0.6 vs. 1.9 ± 0.4 g), kidney weight (365.6 ± 13.1 vs. 257.1 ± 3.7 mg), leptin (3.7-fold), UACR (1013.3 ± 56.4 vs. 658.9 ± 103.6 μg albumin/g creatinine), NGAL (6-fold), and KIM1 (3.7-fold). Moreover, PCOS mice had significantly (p&lt;0.05) lower GFR (1067.2 ± 59.9 vs. 1335.6 ± 60.3 uL/min/100g body weight), higher mtROS driven by complexes I (3.8 ± 0.8 vs. 2.0 ± 0.3 % electron leak) and III (8.0 ± 1.8 vs. 3.7 ± 0.9 % electron leak), as well as lower complexes I, II, and IV respiration (43-71%). The LepR-Ant had no effect on kidney weight or GFR; however, it abolished DHT-induced increases in body weight and fat mass. Excitingly, the LepR-Ant inhibited mtROS generation and completely restored complex I and II respiration, which was associated with a significant reduction in the urinary renal injury markers UACR, NGAL, and KIM-1 levels (40-60%, p&lt;0.05). Conclusion and significance: Our findings suggest that leptin via its receptor activation plays a significant role in the renal outcomes in PCOS by inducing mitochondrial dysfunction. Leptin receptor blockade could be a novel therapeutic approach to ameliorate renal injury in PCOS. Supported by NIH grants NIGMS P20GM121334 to KSE, LLYC, and DGR, NIGMS P20GM104357, NHLBI P01HL51971, and American Heart Association Predoctoral Fellowship 903804 (A.M.H.). This is the full abstract presented at the American Physiology Summit 2023 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.

An Improved Method for Estimating Nephron Number and the Association of Resulting Nephron Number Estimates with Chronic Kidney Disease Outcomes.

Nephron number currently can be estimated only from glomerular density on a kidney biopsy combined with cortical volume from kidney imaging. Because of measurement biases, refinement of this approach and validation across different patient populations have been needed. The prognostic importance of nephron number also has been unclear. The authors present an improved method of estimating nephron number that corrects for several biases, resulting in a 27% higher nephron number estimate for donor kidneys compared with a prior method. After accounting for comorbidities, the new nephron number estimate does not differ between kidney donors and kidney patients with tumor and shows consistent associations with clinical characteristics across these two populations. The findings also indicate that low nephron number predicts CKD independent of biopsy and clinical characteristics in both populations. Nephron number can be estimated from glomerular density and cortical volume. However, because of measurement biases, this approach needs refinement, comparison between disparate populations, and evaluation as a predictor of CKD outcomes. We studied 3020 living kidney donors and 1354 patients who underwent radical nephrectomy for tumor. We determined cortex volume of the retained kidney from presurgical imaging and glomerular density by morphometric analysis of needle core biopsy of the donated kidney and wedge sections of the removed kidney. Glomerular density was corrected for missing glomerular tufts, absence of the kidney capsule, and then tissue shrinkage on the basis of analysis of 30 autopsy kidneys. We used logistic regression (in donors) and Cox proportional hazard models (in patients with tumor) to assess the risk of CKD outcomes associated with nephron number. Donors had 1.17 million nephrons per kidney; patients with tumor had 0.99 million nephrons per kidney. A lower nephron number was associated with older age, female sex, shorter height, hypertension, family history of ESKD, lower GFR, and proteinuria. After adjusting for these characteristics, nephron number did not differ between donors and patients with tumor. Low nephron number (defined by <5th or <10th percentile by age and sex in a healthy subset) in both populations predicted future risk of CKD outcomes independent of biopsy and clinical characteristics. Compared with an older method for estimating nephron number, a new method that addresses several sources of bias results in nephron number estimates that are 27% higher in donors and 1% higher in patients with tumor and shows consistency between two populations. Low nephron number independently predicts CKD in both populations.

Acute gastroenteritis-related acute kidney injury in a tertiary care center.

Acute gastroenteritis (AGE) can cause acute kidney injury (AKI) via hypoperfusion mechanisms. Early detection of AKI caused by AGE can significantly decrease mortality rates. In Saudi Arabia, studies investigating the association between AGE and AKI are limited; thus, we aimed to fill this knowledge gap. Analyze all cases of AGE reported in tertiary-care hospitals to assess the prevalence of AKI among AGE patients. Retrospective cohort SETTINGS: Single tertiary-care center PATIENTS AND METHODS: The study included patients treated for AGE between October 2017 and October 2022. Stool culture was used to diagnose AGE. Inclusion criteria were infective diarrhea and/ or vomiting, and availability of data (demographics, comorbidities, malignancies, length of hospital stay, vital signs at the time of diagnosis, dehydration, causative agents of diarrhea, hemodialysis status, and laboratory data. Prevalence of AKI among AGE patients and factors associated with development of AKI. 300 patients diagnosed with AGE. Of the 300 patients with AGE, 41 (13.6%) had AKI, those older than 60 years were more likely to develop AKI. The most frequent cause of AGE was Salmonella spp. (n=163, 53.3%), whereas AKI was most common in Clostridium difficile AGE patients (n=21, 51.2%). Furthermore, the most common comorbidity in the present study was malignancy, especially leukemia and lymphoma the risk of AKI was independently associated with mild dehydration, higher serum urea concentrations and low GFR values. Patients hospitalized for diarrheal disease are at an increased risk of developing AKI due to dehydration and comorbid conditions. It is crucial to keep kidney function in mind for AGE patients as this is associated with a high mortality rate and poor prognosis. The main limitation of this study was its retrospective design. Another limitation is that it is limited to a single center. None.

Diminished Auditory Cortex Dynamic Range and its Clinical Correlates in First Episode Psychosis.

There is growing appreciation for the contribution of sensory disruptions to disease morbidity in psychosis. The present study examined auditory cortex (AC) dynamic range: the scaling of neurophysiological responses to stimulus intensity, among individuals with a schizophrenia spectrum illness (FESz) and its relationship to clinical outcomes at disease onset. Magnetoencephalography (MEG) was recorded from 35 FESz and 40 healthy controls (HC) during binaural presentation of tones at three intensities (75 dB, 80 dB, and 85 dB). MRIs were obtained to enhance cortical localization of MEG sensor-level activity. All participants completed the MATRICS cognitive battery (MCCB) and Global Functioning: Role and Social scales (GFR/GFS). Patients were administered the Positive and Negative Syndrome Scale (PANSS). FESz exhibited reduced AC response relative to HC. Enhancement of AC activity to tones of increasing intensity was blunted in FESz relative to HC. Reduced dynamic range (85-75 dB AC response) was associated with lower GFS (r = .58) and GFR (r = .45) scores, worse MCCB performance (r = .45), and increased PANSS Negative symptom subscale scores (r = -.55) among FESz, relationships not observed with AC responses to individual tones. Beyond an impaired AC response to pure tones, FESz exhibit reduced dynamic range relative to HC. This impairment was correlated with markers of disease morbidity including poorer community functioning as well as cognitive and negative symptoms. The relationship with impaired social functioning may reflect the role of AC dynamic range in decoding the emotional content of language and highlights its importance to future therapeutic sensory remediation protocols.

Long-term lithium therapy and risk of chronic kidney disease, hyperparathyroidism and hypercalcemia: a cohort study

BackgroundLithium is well recognized as the first-line maintenance treatment for bipolar disorder (BD). However, besides therapeutic benefits attributed to lithium therapy, the associated side effects including endocrinological and renal disorders constitute important parameters in prescribing patterns and patient adherence. The objectives of this study is to (i) determine whether long-term lithium therapy is associated with a decrease in renal function, hyperparathyroidism and hypercalcemia and (ii) identify risk factors for lithium-induced chronic kidney disease (CKD).MethodsWe conducted a single-centered cohort study of adult patients (≥ 18 years) treated with lithium, who were enrolled at Rennes University Hospital in France between January 1, 2018 and June 1, 2020. Required data were collected from the patient’s medical records: demographics characteristics (age, sex, body mass index), biologic parameters (GFR, lithium blood level, PTH and calcium), medical comorbidities (hypertension and diabetes), lithium treatment duration and dosage, and length of hospitalization.ResultsA total of 248 patients were included (mean age: 60.2 ± 16.5 years). Duration of lithium treatment correlated with (i) deterioration of renal function estimated at − 2.9 mL/min/year (p < 0.0001) and (ii) the development of hyperparathyroidism (p < 0.01) and hypercalcemia (p < 0.01). We also noted that patients with lithium blood level > 0.8 mEq/mL had significantly lower GFR than patients with lithium blood level < 0.8 mEq/mL (61.8 mL/min versus 77.6 mL/min, respectively, p = 0.0134). Neither diabetes mellitus nor hypertension was associated with more rapid deterioration of renal function.ConclusionThis study suggests that the duration of lithium treatment contribute to the deterioration of renal function, raising the question of reducing dosages in patients with a GFR < 60 mL/min. Overdoses has been identified as a risk factor for CKD, emphasizing the importance of regular re-evaluation of the lithium dose regimen. Also, long-term lithium therapy was associated with hyperparathyroidism and hypercalcemia. Particular vigilance is required on these points in order to limit the occurrence of endocrinological and renal lithium adverse effects.

GFR estimated with creatinine rather than cystatin C is more reflective of the true risk of adverse outcomes with low GFR in kidney transplant recipients.

Serum cystatin C-based estimated glomerular filtration rate (eGFRcys) generally associates with clinical outcomes better than serum creatinine-based eGFR (eGFRcr) despite similar precision in estimating measured GFR (mGFR). We sought to determine whether the risk of adverse outcomes with eGFRcr or eGFRcys was via GFR alone or also via non-GFR determinants among kidney transplant recipients. Consecutive adult kidney transplant recipients underwent a standardized GFR assessment during a routine follow-up clinic visit between 2011 and 2013. Patients were followed for graft failure or the composite outcome of cardiovascular (CV) events or mortality through 2020. The risk of these events by baseline mGFR, eGFRcr and eGFRcys was assessed unadjusted, adjusted for mGFR and adjusted for CV risk factors. There were 1135 recipients with a mean baseline mGFR of 55.6, eGFRcr of 54.8 and eGFRcys of 46.8ml/min/1.73m2 and a median follow-up of 6years. Each 10ml/min/1.73m2 decrease in mGFR, eGFRcr or eGFRcys associated with graft failure [hazard ratio (HR) 1.79, 1.68 and 2.07, respectively; P<.001 for all) and CV events or mortality outcome (HR 1.28, 1.19 and 1.43, respectively; P<.001 for all). After adjusting for mGFR, eGFRcys associated with graft failure (HR 1.57, P<.001) and CV events or mortality (HR 1.49, P<.001), but eGFRcr did not associate with either. After further adjusting for CV risk factors, risk of these outcomes with lower eGFRcys was attenuated. eGFRcr better represents the true relationship between GFR and outcomes after kidney transplantation because it has less non-GFR residual association. Cystatin C is better interpreted as a nonspecific prognostic biomarker than is eGFR in the kidney transplant setting.

Impact of diabetes and hypertension for the development of cardiovascular diseases: a systematic review

This study aimed to systematically evaluate the evidence respecting the association of risk factors for the development of cardiovascular disease (CVD) among patients with diabetes and hypertension (HTN). Articles were searched from 2015 to 2022 through PubMed, MEDLINE, and Embase. The inclusion criteria included risk factors such as hemoglobin A1c (HbA1c), blood pressure measurement, body mass index, determining the glomerular filtration rate(GER), and blood lipid profile in patients with HTN and diabetes. The quality of the study was assessed by assessment Newcastle-Ottawa scale (NOS). After thorough research, only seven out of 170 articles were selected. The systolic blood pressure (SBP) and GER were calculated. All studies&amp;apos; quality was good under the NOS criteria. Generally, high HbA1c: 138 mmHg, high or low GFR: &amp;gt;60 ml/minute/1.75 m2), and increasing SBP (SBP from 120 to 139 to &amp;ge;140 mmHg) are great risk factors for CVD among diabetes and HTN patients. No data on blood lipid profile and body mass index was available among the selected studies. It was concluded that relatively well-controlled HTN and diabetes might reduce the risk factors for the development of CVD.

Antidiabetic Therapy in Patients Related to CKD (Chronic Kidney Disease)

Patients with type 2 diabetes mellitus (T2DM) are more likely to have chronic kidney disease (CKD) in stages 3-5 (glomerular filtration rate [GFR] 60 mL/min) by roughly 25–30%. Despite the limits of most oral anti-diabetic medications in people with CKD, incretin-based treatments are being utilized more frequently to treat type 2 diabetes. This study examines the impact of CKD on the pharmacokinetics of glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, as well as the efficacy/safety profile of these medications when used in patients with T2DM and CKD. Sitagliptin, Vildagliptin, Saxagliptin, and Alogliptin are the most common DPP-4 inhibitors that are primarily excreted by the kidneys. This led to recommendations for appropriate dose reductions based on the severity of CKD after pharmacokinetic studies revealed that total exposure to the medication is increased in proportion to the fall in GFR. Clinical investigations found that patients with CKD had a high effectiveness and safety profile under these circumstances. Lintagliptin, on the other hand, is primarily excreted through the hepatobiliary system. No dose adjustment of lintagliptin is necessary in the setting of CKD because a pharmacokinetic investigation revealed that lower GFR had a negligible impact on total exposure. Patients with CKD have less experience using GLP-1 receptor agonists. Exenatide should not be administered to patients with severe CKD because it is excreted through renal processes. Due to the limited experience with CKD patients, ligarglutide should be administered with caution even if the kidneys do not remove it from the body. For lixisenatide, exenatide long-acting release (LAR), and other once-weekly GLP-1 receptor agonists now under development, only scant pharmacokinetic data are also available. GLP-1 receptor agonists have been implicated in several case reports of acute renal failure, which was most likely brought on by dehydration brought on by gastrointestinal side effects. Nevertheless, improving GLP-1 may also have advantageous renal effects that could help lower the incidence of diabetic nephropathy. In conclusion, the physician has new chances due to the DPP-4 inhibitors' broad and encouraging experience in CKD patients, whereas the limited experience with GLP-1 receptor agonists in this population calls for greater caution.

ECG for Detection of Left Ventricular Hypertrophy in patients with Chronic Kidney Disease

Background: Left ventricular hypertrophy is the most common cardiac event associated with chronic kidney disease. Aim: To detect LVH by electrocardiography in patients with CKD. Study design: Observational study. Methodology: It was an observational study with total of 62 CKD patients enrolled through convenience sampling. Their blood 3ml was drawn aseptically for estimation of serum creatinine. All enrolled subjects underwent electrocardiographic examination. Patients with low GFR (&lt;60ml/min/1.73m2) and high serum creatinine concentration (&gt;1.5mg/dl) were included. Data was evaluated by using SPSS vr 24. The results were presented as counts, means and standard deviation as appropriate. Results: Left ventricular hypertrophy was present in 50% of enrolled patients as depicted by ECG recording. The calculated sensitivity and specificity of ECG for LVH were 75% and 100% respectively. Almost 38.7% patients were 56-65 years of age. There were 33.9% patients in the age of 35-45 years and 27.4% was in the age of 46-55 years. The median (IQR) age was 54.50 (41.75-60) years. In our study population, median (IQR) of height was 152cm (150-156). The mean weight was 65.85 kg with standard deviation of 8.42 kg i.e., 65.85 ±8.42kg. Mean body mass index was 27.85. Practical Implication: Current project helped health providers to diagnose cardiac event at an early stage among patients of kidney fail¬ure on ECG findings thus the adverse outcomes could be prevented or delayed. Conclusion: ECG abnormalities are common in hospitalized CKD patients in local population. All hospitalized CKD patients should undergo ECG to screen for cardiovascular disease. It was thus concluded that ECG can be used as a sensitive diagnostic tool in combination with different ECG indices to detect LVH. Key words: Electrocardiography, Chronic Kidney Disease, Left Ventricular Hypertrophy and Sokolow-Lyon Voltage Index

742 PROGNOSTIC IMPACT OF HIGH BLEEDING RISK IN PATIENTS WITH CALCIFIED CORONARY ARTERY DISEASE UNDERGOING ROTATIONAL ATHERECTOMY PCI

Abstract Background Percutaneous coronary interventions (PCI) in calcified coronary artery lesions is associated with higher rate of cardiovascular adverse events and mortality. The aim of our study was to evaluate the prognostic impact of High Bleeding Risk (HBR) condition, as defined by the Academic Research Consortium (ARC) HBR criteria, on clinical outcomes in patients with complex calcified coronary artery disease undergoing PCI after lesion preparation using Rotational Atherectomy (RA). Methods In this observational retrospective study, all patients with calcified coronary artery disease undergoing RA-assisted PCI between 2011 and 2021 were included. According to ARC-HBR criteria, patients were considered at HBR if at least one major criterion or two minor criteria were met. The primary endpoint was the occurrence of major adverse cardiac and cerebrovascular events (MACCE) at 4 years defined as the composite of cardiovascular death, myocardial infarction, stroke and target vessel revascularization (TVR). Secondary endpoints were cardiovascular death, bleeding events and TVR. Results The final population consisted of 343 patients. Median follow-up was 39 months. Among patients, 198 (57,7%) met the HBR criteria while 145 (42,7%) did not. Patients with HBR criteria were older [78.21 vs 71.68; p &amp;lt; 0.001], with lower GFR (ml/min/1.73m2) [53.67 vs 77.51; p &amp;lt; 0.001] and lower hemoglobin levels [Hb: g/dl; 11.93 vs 13.74; p &amp;lt; 0.001] compare with patients without HBR. The rate of MACCE was significantly higher in patients at HBR compare with patients not at HBR (HR 1.86 [1.08-3.26]; p = 0.026) mainly driven by an increased risk of cardiovascular death. No significant differences were found concerning the rates of TVR (HR 0.48 [0.21-1.04]; p = 0.057), stroke (HR=7.7 [0.98-61.09], p=0.05) and MI (HR 2.2[0.58-8.35], p=0.241) between the two groups. Bleedings were more frequent in patients at HBR (HR 12.31 [2.93-51.64]; p &amp;lt; 0.001) compared to patients without HBR. Conclusion In patients with calcified coronary artery disease PCI, despite the use of dedicated tools for optimal lesion preparation such as RA, those at HBR still present higher risk of MACCE and cardiovascular death. Conversely, rates of TVR and MI were comparable, suggesting frailty and comorbidities as primary causes of worse outcomes in patients at HBR. Figure Legend: Panel A: the rate of MACCE was significantly higher in patients at HBR compare with patients not at HBR (HR 1.86 [1.08-3.26]; p = 0.026),) mainly driven by an increased risk of cardiovascular death (Panel B). Panel C: the rates of TVR were not significant different between the two groups (HR 0.48 [0.21-1.04]; p = 0.057). Panel D: Bleedings were more frequent in patients at HBR (HR 12.31 [2.93-51.64]; p &amp;lt; 0.001) compared to patients without HBR.

Fibroblast growth factor 23 as a predictor of left atrial appendage thrombosis in patients with nonvalvular atrial fibrillation and various risk of stroke

Aim. To study the role of fibroblast growth factor 23 (FGF-23) as a predictor of left atrial appendage (LAA) thrombosisin patients (pts) with non-valvular atrial fibrillation (AF) and different risk levels of thromboembolic complications (TEC) according to the CHA2DS2-VASc score.Methods. The study included 250 pts with non-valvular AF hospitalized for radiofrequency ablation, divided into 2 groups: group (gr.) 1 - with 0-1 points (n=79) and gr.2 - with ≥2 points on the CHA2DS2-VASc scale (n=171). According to the results of transesophageal echocardiography, pts of each group were divided into subgroups depending on the presence of LAA thrombosis, which was found in 19 pts of gr.1 and 72 of gr.2. Patients underwent transthoracic echocardiography, determination of blood biomarkers: NT-proBNP (pg/ml), GDF-15 (pg/ml), FGF-23 (pmol/l), highly sensitive C-reactive protein (mg/l), cystatin C (mg/l).Results. Pts with LAA thrombosis in both groups had in common: a longer history of arterial hypertension, a greater proportion of coronary artery disease and persistent AF, lower GFR, higher values of atrial volume indices, left ventricle myocardial mass, systolic pressure in the pulmonary artery, median NT-proBNP, FGF-23 and GDF-15. Logistic regression analysis performed separately in the groups revealed the same independent predictors of LAA thrombosis in both groups: LA volume index (LAVI) and the level of FGF-23 in the blood. At the same time, the threshold value of FGF-23, separating pts by the presence of LAA thrombosis, was higher in gr.1 (≥0.85 and ≥0.5 pmol/l, respectively), and the area under the AUC curve for FGF-23 in gr.1 was greater: 0.964 vs 0.865 in gr.2 (p=0.026).Conclusion. The serum level of FGF-23, along with the LAVI, is an independent predictor of LAA thrombosis in pts with AF and various risk of TEC according to CHA2DS2-VASc; the threshold level of FGF-23 for pts at low risk of TEC is significantly higher than for high risk pts, and allows more accurate prediction of the presence of LAA thrombosis.

Urine protein electrophoresis as a prognostic factor in childhood nephrotic syndrome relapse – An observational study in govt. medical college, Mulankunnathukavu, Thrissur

Childhood nephrotic syndrome (NS) is a chronic illness characterized by relapses and remissions. In many there will be disability, caused by the disease and from the treatment in the form of immunosuppression or end stage renal disease. Progression to renal failure will require anticipation for dialysis and/or renal transplant. A noninvasive biomarker such as urine protein profile that accurately predicts responsiveness to steroid therapy would be valuable in predicting the course of nephrotic syndrome. Our study tries to correlate between the selectivity of proteinuria and the outcome of relapses and thus prognosticate the course of the disease. Few similar studies have been done in India.Our study is a cross-sectional hospital based study, comprised of a population of 43 children with nephrotic syndrome relapse, between 1 and 14 years of age. Blood and urine samples were collected, to look for selective or nonselective proteinuria using the Agarose gel electrophoresis (Age) method. The treatment for relapse was started with steroid and, outcome was then related to the selectivity of proteinuria.Majority of our patients had non selective proteinuria (NSP) 60.5%, the rest had selective proteinuria (SP) 39.5%.There was a significant relation between nonselective proteinuria and- 1: Hypertension (p =0.049); 2: Low GFR p&amp;#60;0.001(p =0.0005); 3: Steroid dependent nephrotic syndrome. (p =0.0199).Non selective proteinuria was more in children, above the age of 6 years (p=0.001).The nonselective proteinuria group took more time for remission pointing to the lesser degree of steroid sensitivity.Non selective proteinuria can be used as a biomarker to predict the course in childhood nephrotic syndrome. The higher prevalence of non-selective proteinuria could be due to severe forms of nephrotic syndrome in our study. Selective proteinuria had a better outcome.