Creatinine Clearance Values Research Articles

P-1556. A Retrospective Evaluation of Methenamine Safety and Efficacy in An Older Population at an Academic Medical Center

Abstract Background Urinary tract infections represent a significant cause of morbidity and mortality in older adults. Limited methods exist to prevent recurrent UTI (rUTI) in this high-risk population. Prophylactic low-dose antibiotics are often considered for this purpose, but can be associated with increased adverse effects and development of resistant pathogens. The urinary antiseptic agent methenamine has re-emerged as an antibiotic-sparing alternative for prevention of rUTI, however its role in therapy for older adults is not well characterized. Methods Retrospective chart review identified patients prescribed methenamine from 2017 to 2023. Excluded were patients on prophylaxis aged < 60 years at the time of initiation, and those with < 3 months duration. Patients who received antibiotics for breakthrough UTI while on methenamine were included. Patient histories were reviewed 1 year prior to methenamine initiation through the end of prophylaxis. Collected were patient demographics, UTI history prior to methenamine, time to recurrence, laboratory values and adverse effects. Results 247 patients were prescribed methenamine during the study period. 55 patients met inclusion criteria. On average, methenamine duration was 8.75 months. 27 patients had creatinine clearance (CLcr) values < 60 mL/min. 29 patients received a concurrent recommendation for ascorbic acid. Use of methenamine provided ≥ 3 months without UTI recurrence in 43 patients (78%) with a wide range of Charlson comorbidity index scores and CLcr values, and 29 patients did not have documented UTI for the duration of methenamine therapy. Seven reports of adverse effects were documented, 3 of which led to discontinuation of therapy. Conclusion In a population ≥60 years of age, methenamine appears to be safe and effective at preventing recurrent UTIs. The number of patients without UTI decreased with time on methenamine, however 55% of patients who remained on prophylaxis at one year had no documented recurrence. Concurrent ascorbic acid therapy was not consistently recommended in this study population, and was not associated with increased methenamine efficacy. Lower CLcr did not appear correlated with lower efficacy or increased adverse effects of methenamine. Disclosures All Authors: No reported disclosures

Epidemiological and Clinical Profile and Pathologies Associated with Chronic Kidney Disease in Internal Medecine Departement at the Abdou Aziz Sy Dabakh Hospital in Tivaouane

Introduction: Chronic kidney disease (CKD) is a major global public health problem. Its prevalence varies according to studies and is influenced by sociodemographic, clinical, and individual factors, the increase of which is correlated with the prevalence of CKD. Material and method: We conducted a retrospective descriptive study in the internal medicine department of the HAAD in Tivaouane. The study period was 3 years, from January 1st, 2019, to December 31st, 2021. The study involved all patients at least 18 years of age followed or hospitalized in the internal medicine department who presented with chronic kidney disease during their follow-up. Results: We Collected Data From 102 Patients Out of a Total of 816 Patients, Representing a Prevalence of 12.5%. The Average Age of Our Patients Was 55.22 Years with ages ranging from 18 to 92 Years. The 60-70 Age Group Was the Most Represented at 28.43% (n=29). The Female Sex Was Predominant with a Sex Ratio of 0.73. Most of Our Patients Were in the Primary Sector and of Low Socioeconomic Status. The clinical manifestations were dominated by clinical anemia (60%), edema of renal origin (33.33%) and altered general condition (72%). The Mean Creatinine Clearance Value According to MDRD Was 51.94 ± 31.25 ml/min/1.73m2 with ranges from of 1.31 to 195.4 ml/min/1.73m2. Most patients were in stage 3 chronic kidney disease (36%), followed by stage 4 (20%). Associated etiologies included benign prostatic hyperplasia (39.22%), diabetes (10.78%), systemic lupus (5.88%) and HIV (5.88%). The prescribed treatment consisted of: diet (56 patients), conservative treatment (64 patients), treatment of hyperkalemia (34 patients). Conclusion: Chronic kidney disease is a frequent complaint in internal medicine departments. It can often complicate certain chronic pathologies.

Estimated glomerular filtration rate versus creatinine clearance to determine anticoagulant dosage after lower-limb orthopedic surgery.

Anticoagulation is recommended for thromboprophylaxis after lower-limb orthopedic surgery. The suggested dosage is based on creatinine clearance (CCr) in the labels. However, most facilities only provide estimated glomerular filtration rate (eGFR) as laboratory data. Because the eGFR equation adjusts for a body surface area (BSA) of 1.73 m2, it may overestimate renal function in patients with a small BSA. This retrospective study aimed to determine whether different renal function estimation formulas affect the incidences of venous thromboembolism (VTE) and bleeding when determining anticoagulant dosages. This study included patients who underwent lower-limb orthopedic surgery and received anticoagulants (edoxaban, enoxaparin, and fondaparinux) between 2017 and 2020 at Yaizu City Hospital. Anticoagulant dosing was evaluated using CCr, eGFR, and de-indexed eGFR (without correction for BSA), and the incidences of VTE and bleeding were compared among these formulas. The median values for BSA, CCr, eGFR, and de-indexed eGFR were 1.40 m2, 56.0mL/min, 73.0mL/min/1.73m2, and 60.9mL/min, respectively. There was no significant difference in the VTE incidence among these formulas. However, when dose reduction or contraindication threshold was determined by eGFR vs. CCr, the bleeding incidence was significantly higher in the group that was overdosed by CCr (6.0% vs. 25.7%, p < 0.05). Similarly, using de-indexed eGFR vs. CCr, the bleeding incidence was significantly higher in the group that was overdosed by CCr (7.5% vs. 28.6%, p < 0.05). In orthopedic surgery, anticoagulant dosages should be based on CCr for patients with a small BSA to avoid bleeding risks.

Effectiveness and feasibility of selective intra-arterial low dose of cisplatin infusion and concomitant radiotherapy for patients with advanced laryngeal cancer with impaired renal function: A retrospective cohort study.

Chemoradiation therapy with high-dose cisplatin is the standard regimen against advanced squamous cell carcinoma of the larynx (SCC-L). However, patients with renal dysfunction are ineligible for this regimen. We investigated the effectiveness and feasibility of selective intra-arterial low-dose cisplatin infusion and radiotherapy (modified [m]-RADPLAT) for patients with impaired renal function. We retrospectively reviewed the data of 77 patients with SCC-L who received m-RADPLAT. Fourteen and 63 patients had creatinine clearance (CrCl) values of 30 ≤ CrCl < 60 mL/min and ≥60 mL/min, respectively. The m-RADPLAT regimen led to no significant changes in serum creatinine or CrCl values post-treatment. The 5-year local control, overall survival, and laryngectomy-free survival rates of the CrCl < 60 and ≥60 groups were 90.0% and 90.5%, 100% and 81.8%, and 100% and 79.0%, respectively. Grade 3 or higher toxicity rates were not significantly different between the groups. The m-RADPLAT regimen yielded favorable survival rates and clinical outcomes in patients with impaired renal function.

Evaluation of the Protective Effect of Cystone against Cisplatin Induced Nephrotoxicity in Cancer Patients

Abstract Purpose Cisplatin is a cost effective widely used antineoplastic drug to treat a number of solid tumors. The major dose-limiting toxicity is nephrotoxicity. Cystone is one of drugs that have been tested to reduce the incidence of cisplatin-induced acute kidney injury (CIAKI). This study aimed to investigate the protective effect of Cystone against CIAKI in larger number of patients relative to previously conducted pilot studies . Methods A prospective phase II, open-label randomized controlled study was conducted in patients receiving cisplatin-based chemotherapy in Ain Shams University Hospitals, using cystone tablet (manufactured by the Himalayan Pharmaceutical Company, India) administered as two pills every 8 hours continuously through course of chemotherapy starting from the day before receiving chemotherapy. A total of 99 patients were randomized between the control and cystone arms. The primary endpoint was the incidence of AKI according to Common Terminology Criteria Adverse Events (CTCAE) in each treatment arm. Secondary endpoints include need to dose modification between both arms. Results There was clinical difference in the incidence of CIAKI any grade between the two arms (12% in cystone arm vs 34 % in control arm P = 0.4. Need to dose modification is 10.4% vs 12 % (P = 0.8). There was a statistically significant difference between the two arms as regards the difference between values (mean) of serum creatinine and creatinine clearance values initially and at the end of treatment favoring drop of renal functions in control group (P = 0.000 and 0.003) respectively. Conclusion Our study did not demonstrate clearly a protective role of cystone in decreasing the incidence of CIAKI in patients receiving cisplatin based chemotherapy. However, drop of renal function in control arm with comparison to study arm may give an indication to further study cystone in different doses to assess its protective role against CIAKI.

#1408 Dehydration cannot substitute for any of the triple whammy drugs to cause acute kidney injury

Abstract Background and Aims Polymedication in patients with chronic diseases, such as hypertension, can lead to undesired drug interactions. The combination of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) with diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) can cause triple whammy (TW)-induced acute kidney injury (TW-AKI). Up to 9% of hypertensive patients used NSAIDs in combination with ACEIs / ARBs and diuretics. AKI has a mortality rate of 40% and TW increases the risk of AKI by 30% compared to the combination of only two drugs. In addition, TW-AKI is associated with other risk factors such as dehydration, which may exacerbate the injury. Consequently, the aim of our study was to determine whether dehydration combined with two of the TW drugs could induce AKI in an in vivo experimental model. Method Three months old male Spontaneously Hypertensive Rats (SHR) were divided into four experimental groups: control group (CT); TW group (TW), which received four days of double therapy with trandolapril and furosemide, followed by a triple therapy for two days with trandolapril, furosemide and ibuprofen; trandolapril and ibuprofen group (T+I), which received four days of trandolapril followed by two days of trandolapril and ibuprofen; furosemide and ibuprofen group (F+I), which received four days of furosemide followed by two days of furosemide and ibuprofen; and trandolapril and furosemide group (T+F), which received six days of trandolapril and furosemide. All groups were subjected to a 60-70% water restriction of basal intake (i.e. 15 mL/day) to generate mild dehydration. Blood and urine samples were collected at baseline (B), day 4 and day 6. Blood pressure was measured at baseline and day 4. Renal function was assessed by plasma creatinine, plasma urea and creatinine clearance, and hydration status was determined by plasma osmolarity and water balance (i.e. water intake minus urine flow). Results Under basal conditions, all rats were hypertensive. The combination of trandolapril and furosemide significantly reduced the mean blood pressure on day 4 (p = 0.0066), while trandolapril or furosemide alone did not achieve these decreases. After four days of water restriction to 15 mL/day, all groups showed mild dehydration with a decrease in water balance and an increase in plasma osmolarity by. Plasma creatinine and plasma urea values were only increased on day 6 in the TW group (p = 0.0009 and p = 0.02, respectively). Creatinine clearance was also clearly reduced in the TW group (p = 0.0004). F+I and T+F groups showed slight decreases in creatinine clearance at day 6, as well as slight increases in plasma urea. However, these changes were not as pronounced as those observed in the TW group. Conclusion In our in vivo model of TW-AKI, mild dehydration cannot replace any of the TW drugs, although it appears that combination of F+I and T+F in dehydrated rats slightly alter plasma urea and creatinine clearance values at day 6, suggesting that this condition maintained over time might lead to the development of AKI. Funding This research was funded by grants from Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación (PI21/01226 and PI21/00548 co-funded by the European Union; and RICORS2040, RD21/0005/0004, co-funded by the European Union—NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR)) and from Consejería de Educación, Junta de Castilla y León (IES160P20), co-funded by FEDER funds. Noelia Diaz-Morales is recipient of a Juan de la Cierva-Formación postdoctoral contract (FJC2020-043205-I) funded by MCIN/AEI/10.13039/501100011033 and the European Union “NextGenerationEU/PRTR”. Eva M. Baranda-Alonso is recipient of a predoctoral fellowship from the Junta de Castilla y Leon (Spain) and the European Social Fund from the European Commission.

Comparative analysis of two-hour creatinine clearance and the C-G formula for renal function assessment in critically ill patients

Objective and rationaleTo investigate if the 2-h creatinine clearance (Ccr2) provides a more precise and timely assessment of renal function in critically ill patients compared to the Cockcroft-Gault formula (CrC-G). Materials and methodsThis cohort study incorporated 74 patients who were hospitalized for more than 48 h in the Intensive Care Unit over 6 months. A 24-h urine collection protocol was observed, and concurrently, 316 2-h urine specimens were obtained. Then calculated and analyzed the correlation and consistency between Ccr2, CrC-G, and 24-h creatinine clearance (Ccr24) values. The rates of change in Ccr2(ΔCcr2) and CrC-G(ΔCrC-G) were compared over two consecutive samples. ResultsThe R-values of Ccr2 and Ccr24 in the early, middle and late 24 h were 0.640, 0.886 and 0.854 (P < 0.001), with biases of −2.1, 1.7, and 6.3 ml/min/1.73 m2, respectively. Meanwhile, the R-values for CrC-G and Ccr24 at these time points were 0.618, 0.822, and 0.828(P < 0.001), with biases of −14.0, −5.2, and −1.8 ml/min/1.73 m2, respectively. For patients with Ccr24≥60 ml/min/1.73 m2, the R-value of Ccr2 and Ccr24 during the middle 2 h was 0.852(P < 0.001), while the R-values for CrC-G and Ccr24 were 0.763(P < 0.001), with biases of −2.3 ml/min/1.73 m2 and -14.2 ml/min/1.73 m2 respectively. For the group with Ccr24 ≥ 120 ml/min/1.73 m2 (n = 72), both Ccr2 and Ccr24 displayed a statistically significant elevation compared to CrC-G (P < 0.001), yet no significant difference was observed between Ccr2 and Ccr24 (P = 0.289). Out of 50 patients, 46(92 %) experienced a ΔCcr2≥20 % at least once, compared to 20(40 %) with a ΔCrC-G≥20 %(P < 0.001). 25(50 %) with a ΔCcr2≥50 %, compared to 3(6 %) with a ΔCrC-G≥50 %(P < 0.001). ConclusionCcr2 demonstrates a more accurate and more timely indicator of renal function in critically ill patients than CrC-G.

Evaluation of a creatinine clearance correction equation based on body fat mass in older Japanese patients with diabetes.

The estimation of creatinine clearance (CCr) in older adult patients with diabetes is subject to deviations from the results of actual measurements because of changes in body composition. In the present study, we aimed to create a correction for the equation used for the estimation of CCr in older adult Asian patients with diabetes using body composition parameters. We enrolled 50 older Japanese patients with diabetes in whom the measured values of CCr were compared with values estimated using the Cockcroft-Gault equation. The relationships between the error in the estimated CCr and body composition parameters were investigated, and the Cockcroft-Gault equation was corrected using the appropriate parameters. To evaluate the generalizability of the corrected equation, the utility of the Cockcroft-Gault equation, which was corrected on the basis of body composition measured using a household body composition meter, was also investigated. Body fat mass (BFM) was closely correlated with the error in the estimated CCr. The BFM-corrected Cockcroft-Gault equation was more accurate than the original equation. Similarly, the error became smaller using BFM measured with a household body composition meter. The BFM-corrected Cockcroft-Gault equation may provide an accurate method of estimating CCr that can be used in general practice.

Fabrication and Characterization of Chitosan-Polyvinyl Pyrolidone K-30 for Creatinine Transport Membranes

The investigation of membrane-based hemodialysis is an interesting study due to its efficacy in eliminating metabolic waste compounds, such as creatinine, from the body. However, not all membrane types exhibit optimal transport capabilities, necessitating modifications. In this study, we conducted modifications on chitosan (CS) membranes by incorporating polyvinyl pyrrolidone K-30 (PVP K-30) and assessing their physicochemical characteristics. The modified membrane underwent characterization and subsequent evaluation of its transport capabilities. The primary objective of this research is to design a membrane composed of chitosan and PVP K-30 with enhanced creatinine transport capabilities. The study commenced with the fabrication of CS membranes combined with CS-PVP, involving six variations of CS and PVP K-30 with volume ratios of 5:0, 4:1, 3:2, 1:1, 2:3, and 4:1. The resulting solution was then printed into a flat sheet membrane. All completed membranes underwent comprehensive characterization, including tests for functional groups using Fourier Transform Infrared (FTIR), membrane weight and thickness, porosity, water absorption, swelling, hydrophilicity, pH resistance, and biodegradation. In the final phase, the membrane was utilized in the creatinine transport process. FTIR analysis of the CS-PVP K-30 membrane revealed O-H and N-H group spectra at wave numbers 3363.06 cm-1 and 1587.17 cm-1, indicating hydrogen bonding between the two polymers. Characterization tests demonstrated that the CS-PVP membrane exhibited increased porosity, water absorption, swelling, and hydrophilicity. In the creatinine transport test, the CS-PVP membrane demonstrated enhanced creatinine transport ability compared to the CS membrane. The highest clearance value for creatinine was observed in the CS-PVP5 membrane, with an increase in the amount of PVP K-30 correlating with an elevated creatinine clearance value. The creatinine clearance values for the CS membrane, CS-PVP1, CS-PVP2, CS-PVP3, CS-PVP4, and CS-PVP5 were 0.30, 0.36, 0.37, 0.39, 0.42, and 0.46 mg/dL, respectively.

The model of functional disorders in rats with kidney nephrectomy ¾ in comparison with a high-salt diet

BACKGROUND. Modeling of chronic kidney disease using nephrectomy of 5/6 kidney parenchyma is actively used in experimental nephrology. However, the remaining 17 % of the organ parenchyma is associated with severe renal fibrosis in humans. A high-salt diet has traditionally been considered as a systemic hemodynamic model for the development of chronic kidney disease.THE AIM: to compare the functional disorders that occur in rats with nephrectomy of ¾ of the kidneys and when using only a high-salt diet.MATERIAL AND METHODS. The study was performed on 30 male Wistar rats. The animals were randomly divided into 3 equal groups: control (falsely operated, L), high-salt diet (falsely operated, LVD), nephrectomy ¾ renal parenchyma (NE). The rats received a balanced laboratory feed daily, differing only in the content of sodium chloride (NaCl). In the L and NE groups, rats received a feed containing 0.34 % NaCl, and in the VD group – 4 % NaCl. The duration of follow-up was 16 weeks. Systolic blood pressure (SBP) was measured on the tail by the cuff method. The serum and urine concentrations of creatinine, urea, potassium, sodium, chlorine, as well as the degree of proteinuria and albuminuria were determined.RESULTS. During the observation, the SBP in group L did not change. In the LVD group, SBP increased from 120 [120; 125] mmHg to 130.0 [125.0; 140.0] mmHg, p=0.011. In the NE group, SBP also increased from 120 [120; 125] mmHg to 135.0 [132.5; 137.5] mmHg, p=0.011. In the LVD group, there was an increase in serum creatinine concentration compared to the control to 52.5 [50.0; 56.0] mmol/l, p=0.0001; urea to 6.0 [5.6; 6.6] mmol/l, p=0.0001; potassium to 5.6 [5.3; 5.8] mmol/l, p=0.0001; chlorine up to 87.5 [86.6; 87.9] mmol/l, p= 0.0001. At the same time, creatinine clearance decreased from 187.5 [160.0; 205.0] ml/min in the L group to 92.0 [81.2; 99.0] ml/min, p=0.0003 in the LVD group and to 83.9 [65.7; 85.9] ml/min p=0.0001 in the NE group. The value of albuminuria before the end of the experiment was statistically significantly higher compared to the control in both the LVD group of 12.12 [6.36;18.41] mg/g creatinine, p= 0.0001, and in the NE group of 72.5 [61.6; 92.9] mg/g creatinine, p= 0.0001. When conducting a nonparametric correlation analysis (all three observation groups were combined), a statistically significant relationship was noted between the level of SBP after 1 month from the start of the experiment and the amount of albuminuria at its completion (Rs=0.583 p=0.001). A statistically significant relationship between the value of SBP and creatinine clearance was revealed before the end of the experiment (Rs=-0.700 p=0.005). Also, before the end of the experiment, a statistically significant relationship between albuminuria and creatinine clearance was revealed (Rs=-0.671 p=0.006).CONCLUSION. The NE model of the renal parenchyma is expected to be accompanied by the development of less severe functional changes compared to NE 5/6 of the renal parenchyma. In this regard, we assume that its use may be useful in studying the effectiveness of nephroprotective measures at the initial stages of CKD development. The negative effects of a high-salt diet are comparable in a number of indicators to nephrectomy of the renal parenchyma. Traditionally, an increase in salt intake is associated with an increase in blood pressure, which could result in an increase in albuminuria. However, we could not identify any relationships between albuminuria and the value of SAD. We assume that the model of a high-salt diet can be considered as a variant of a local, rather than a systemic hemodynamic model of the development of chronic kidney disease. In the future, we will present the results of nephrobiopsy in the experimental groups described above.

Facile modification of polyvinylidene fluoride membrane for enhancing dialysis performance: sulfonation, adding polyethylene glycol and tuning coagulation bath temperature

Modifications were successfully carried out on the polyvinylidene fluoride (PVDF) flat sheet membrane, involving the sulfonation and adding polyethylene glycol (PEG), along with variations in the coagulation bath temperature (CBT). The primary objective of these modifications was to examine their impact on the physicochemical characteristics of the membrane and its permeability to a creatinine solution. The findings revealed that the sulfonated PVDF/PEG membrane, printed at a temperature of 30 °C, displayed substantial increases in porosity, hydrophilicity, water uptake and swelling degree. It is important to note that modifications to the PVDF membrane led to a reduction in thermal stability and an increase in creatinine transport efficiency. For the unmodified PVDF membranes, the clearance values for creatinine in phosphate buffer and phosphate buffer saline media were 0.43 (Transport = 28.65%) and 0.42 mg/dL (Transport = 28.05%), respectively. Conversely, the highest creatinine clearance values were achieved by the SPP30 membrane (sulfonated PVDF/PEG-CBT 30 °C), measuring 0.64 mg/dL (Transport = 42.81%) for creatinine and 0.60 mg/dL for urea (Transport = 39.66%). These results indicate that the sulfonated PVDF/PEG membrane exhibits strong potential for use in hemodialysis applications.

Effect of perceived and objectively-assessed frailty on outcomes in edoxaban-treated patients with atrial fibrillation: data from the ETNA-AF-Europe 4-year follow-up

Abstract Background Frailty is common in patients with atrial fibrillation (AF). However, different definitions of frailty are used, and these may variably overlap with frailty perception among physicians. Long-term data on outcomes based on perceived versus objective frailty in patients with AF treated with a non-vitamin K antagonist oral anticoagulant are lacking. Purpose To assess the effect of perceived versus objective frailty on outcome events in patients with AF treated with edoxaban during the 4-year follow-up of the ETNA-AF-Europe registry (NCT02944019). Methods ETNA-AF-Europe is a multinational, multicentre, post-authorisation, observational study conducted in patients with AF receiving edoxaban. In this sub-analysis, patients were evaluated in terms of perceived or objective frailty status (yes or no categories). Perceived frailty was based on investigators’ own clinical binary judgement in each patient. Objective frailty was determined using a Modified Frailty Index, a simplified adaptation of the Rockwood’s Frailty Index. Patient demographics and characteristics were collected at baseline. The efficacy and safety outcomes are reported here comparing frailty status (yes versus no) among perceived or objectively classified patients. Results Among the 13,164 patients with 4 years of follow-up, the prevalence of perceived and objective frailty was 10.7% and 4.1%, respectively. Compared with the objectively frail group, those perceived as frail were older, with a lower proportion of males, had lower body weight and creatinine clearance values, yet lower CHA2DS2-VASC and modified HAS-BLED scores (Table 1). Further, patients with objective frailty tended to have more comorbidities (e.g., diabetes, heart failure, hypertension; Table 1). Those deemed frail were more likely to receive the reduced 30 mg edoxaban dose versus non-frail patients (p&amp;lt;0.001 for both groups), and non-recommended dosing regimens (60 or 30 mg) were more often prescribed in frail versus non-frail patients (p&amp;lt;0.0001 for all comparisons; Table 1). Patients perceived as frail had a significantly higher risk of all evaluated outcomes compared with non-frail patients (p-value range: &amp;lt;0.0001 – 0.0459; Figure 1). Similar data were seen for objectively frail patients, with the exception of no significant differences in the risk of intracranial haemorrhage (ICH, p=0.0918) or haemorrhagic stroke (p=0.1619; Figure 1). Conclusions Frailty was associated with an inappropriate dosing of edoxaban and an increased incidence of outcome events, quantitatively similar in the perceived and objective frailty groups. After 4 years of therapy, even if ICH risk was increased in frail subjects, its cumulative incidence was low.

Study of Sequence of Histopathological Changes in Hyperglycaemia-Induced Experimental Diabetic Nephropathy in Wistar Rat Model

The sequence of histopathological changes in hyperglycaemia-induced nephrotoxicity as well as alteration in renal parameters is still not well established in diabetic models. Hyperglycaemic ambience has been shown to generate oxidative stress which becomes a trigger for further degenerative changes that occur in the microenvironment of the kidney. This study was therefore intended to investigate histopathological alterations in vascular, glomerular and tubulointerstitial compartments of the renal tissues, and the corresponding changes in values of oxidative stress markers, creatinine clearance, proteinuria and serum creatinine concentration in a duration of three, seven and twelve weeks of sustained hyperglycaemia in diabetic. The experiment included four groups of adult Wistar rat, Group A (Normal Control, treated with normal saline), Groups B, C and D were induced with diabetes (treated with 65mg/kg body weight of streptozotocin) and allowed for 3 weeks 7 weeks and 12 weeks respectively. At termination, Oxidative stress markers were analyzed using Oxidative stress marker kits. A 24 hours urine collection was obtained from metabolic cages few hours before sacrifice and used for renal analysis and histopathological examination was done using a light microscope. Results reveals that oxidative stress was climaxed at 7th week and was maintained at a constant level while histopathological changes in glomerulus first presented on the 3rd week accompanied by vascular changes. Tubulointerstitial changes were noticed on the 7th week. On the 12th week renal parameters were significantly altered when compared to the animals sacrificed on 3th and 7th week. In conclusion, the sequence in diabetic–induced renal dysfunction begins with changes in vascular and glomerular compartment followed by distortion in tubulointerstitial compartment. An alteration in renal parameters presents lastly and correlates with the histopathological changes. These findings can be adopted in clinical management and treatment of diabetes-induced kidney dysfunction. J. Bio-Sci. 31(1): 29-37, 2023

Renal impairment as a risk factor for trifluridine/tipiracil-induced adverse events in metastatic colorectal cancer patients from the REGOTAS study

Renal impairment may be associated with an increased risk of hematologic events (AEs) in patients undergoing treatment with trifluridine/tipiracil (FTD/TPI). This study aimed to investigate the specific types of AEs linked to renal impairment in patients with metastatic colorectal cancer (mCRC) receiving FTD/TPI, using real-world data. Among the patients included in the REGOTAS study (a retrospective study of FTD/TPI versus regorafenib), those treated with FTD/TPI were evaluated. Creatinine clearance values of < 30, 30–60, 60–90, and > 90 mL/min were defined as severe, moderate, mild renal impairment, and normal renal function, respectively. Renal impairment was analyzed as a risk factor for grade 3 or higher AEs using a logistic regression model. Overall survival (OS) and progression-free survival (PFS) based on renal impairment were evaluated. A total of 309 patients were included in the analysis, with 124, 130, and 55 patients divided into the normal, mild, and moderate-to-severe groups, respectively. The risk of grade 3 or higher neutropenia was significantly higher in the moderate-to-severe group (odds ratio 3.47; 95% confidence interval 1.45–8.30; P = 0.005), but there was no significant increase in the risk of non-hematologic AEs in any of the groups. The OS and PFS of patients in the mild and moderate-to-severe groups were comparable to those in the normal group. Patients with mCRC and moderate/severe renal impairment receiving FTD/TPI therapy may develop severe neutropenia; however, FTD/TPI remains a viable treatment option due to its clinical benefit.

Evaluation of factors predicting the benefit from systemic oncological treatment for severely ill hospitalized patients: a retrospective study

BackgroundPatients with cancer in the disease’s end-stage with poor performance represent a challenging clinical scenario, as they have high chance of a fatal outcome due to clinical conditions, oncological emergencies, and/or metastatic disease. This study examines the factors predicting the potential benefit of “urgent” chemotherapy during hospitalization in this setting, thus addressing a research gap.MethodsThis retrospective observational study was conducted in the largest cancer center in the outskirts of São Paulo. It identified factors predicting the benefit from antineoplastic treatment in severe in-hospital patients admitted during 2019–2020, considering post-chemotherapy survival time as the main dependent variable. Data were retrieved from medical records. All patients aged ≥ 18 years, with an ECOG-PS score ≥ 2, and undergoing non-elective systemic cancer treatment were included.ResultsThis study evaluated 204 records, of which 89 were included in the final analysis. A statistically significant association with the worse outcome (death within 30 days of chemotherapy) was found with higher ECOG performance status; chemotherapy dose reduction; lower values of serum albumin, hemoglobin, and creatinine clearance; and higher values of leukocytes, neutrophils, direct bilirubin, urea, and C-reactive protein. In the multivariate analysis, only albumin remained statistically associated with the outcome (hazard ratio = 0.35; confidence interval: 0.14, 0.90; p = 0.034).ConclusionsSerum albumin and other clinical and laboratory variables might be associated with early post-treatment deaths in patients with cancer. The study data might help guide the decision to administer systemic treatment in this scenario and manage critically ill patients. This study adds to our knowledge of the factors predicting the objective benefits from “heroic” or “urgent” chemotherapy for hospitalized and severely ill patients with cancer.

Association Between Biomarkers of Kidney Disorders and Atrial Fibrillation: A Literature Review

Kidney diseases and atrial fibrillation often occur together. Renal impairment increases the risk of developing incident atrial fibrillation (AF) and is linked to it in a bidirectional manner, making it a prothrombotic and pro-hemorrhagic condition. In Japanese patients with nonvalvular AF, lower creatinine clearance values were associated with thromboembolism, all-cause death, and cardiovascular death, but not with major haemorrhage. Older individuals with elevated serum levels of cystatin C had a significantly higher prevalence of AF. Moderate to severe chronic kidney disease individuals with increased levels of fibroblast growth factor-23 were independently associated with prevalent and incident AF. A higher baseline glomerular filtration rate was associated with an increased risk of AF. Elevated levels of insulin-like growth factor binding protein-7 were also observed in AF patients, while reduced circulating tissue inhibitor of metalloproteinase 2 levels were also associated with an increased risk of AF. Patients with AF had higher levels of non-esterified fatty acids and liver type fatty acid binding protein. Interleukin-18 levels in blood plasma were also found to be higher in AF patients. Furthermore, higher baseline urea/blood urea nitrogen levels were significantly associated with the incidence of AF in women and kidney disease in both men and women.

Prevention of contrast induced-acute kidney injury using coenzyme Q10 in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

We assessed the potential effect of CoQ10 administration for the prevention of contrast induced-acute kidney injury (CI-AKI) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). One hundred fifty STEMI patients who were candidates for primary PCI, along with intravenous saline hydration, randomly received a placebo or CoQ10. CoQ10 was administrated orally, 400 mg before the procedure and 200 mg twice daily after the procedure for three consecutive days. Serum creatinine concentration and corresponding creatinine clearance (estimated by the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation) were measured at baseline and 24, 48, and 72 h after primary PCI. Furthermore, the serum level of superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA) was measured before and 72 h after primary PCI. The mean serum creatinine concentration before contrast administration was similar in the two groups (0.98 ± 0.08 versus 0.99 ± 0.09mg/dL). While in both study groups, compared to baseline, the mean serum creatinine concentration increased at 48 and 72 h after contrast exposure, the CoQ10 group showed a lower serum creatinine concentration than the placebo group (P-value = 0.017 and 0.004, respectively). However, comparing the mean values of creatinine clearance between the groups at the study time points did not demonstrate a statistically significant difference. CI-AKI, defined as a > 25% or 0.5 mg/dL increase in baseline serum creatinine concentration, occurred in 8.00% of the cases in the CoQ10 group versus 20.00% in the placebo group (P-value = 0.034). Furthermore, at 72 h, the CoQ10-treated group exhibited higher serum levels of SOD and TAC and a lower MDA level than the placebo-treated group. Our research's findings proposed CoQ10 supplementation as an adjuvant to saline hydration as a preventive approach against CI-AKI. The trial was registered at Iranian Registry of Clinical Trials ( https://www.irct.ir/trial/60435 , identifier code: IRCT20120215009014N414). Registration date: 2021-12-29.

Clinical significance of serum urea-to-creatinine ratio in patients undergoing peritoneal dialysis.

We aimed to determine the correlation between the serum urea-to-creatinine ratio and residual kidney function (RKF) in patients undergoing peritoneal dialysis (PD), as well as its predictive value for PD-related outcomes. This study included a cross-sectional study to assess the correlation between serum urea-to-creatinine ratio and RKF in 50 patients on PD and a retrospective cohort study to assess the association between serum urea-to-creatinine ratio and PD-related outcomes in 122 patients who initiated PD. Serum urea-to-creatinine ratios had significant positive correlations with renal Kt/V and creatinine clearance values (r = 0.60, p < 0.001 and r = 0.61, p < 0.001, respectively). Additionally, serum urea-to-creatinine ratio was significantly associated with a lower risk of transfer to hemodialysis or PD/hemodialysis hybrid therapy (hazard ratio: 0.84, 95% confidence interval: 0.75-0.95). The serum urea-to-creatinine ratio can be an indicator of RKF and a prognostic factor in patients undergoing PD.

The effect of glycine on oxidative stress, inflammation and renin-angiotensin system in kidneys and aorta of cyclosporine-administered rats

Cyclosporine A (CsA) is an immunosuppressive drug, used in organ transplantations. Oxidative stress, inflammation and renin-angiotensin system (RAS) activation play an important role in CsA-toxicity. Glycine (Gly) has antioxidant and anti-inflammatory effects. In this study, Gly was investigated for its protective role against CsA-induced toxicity. CsA (20 mg/kg/day; subcutaneously) was administered to rats along with Gly injection (250 or 1000 mg/kg; intraperitoneally) for 21 days. Renal function markers [serum urea and creatinine and urinary protein and kidney injury molecule levels and creatinine clearance values] together with histopathological examinations were performed. Oxidative stress (reactive oxygen species, thiobarbutiric acid reactive substances, advanced oxidation products of protein, glutathione, ferric reducing anti-oxidant power and 4-hydroxynonenal levels), and inflammation (myeloperoxidase activity) were determined in kidney tissue. The RAS system [angiotensin II (Ang II) levels, and mRNA expressions of angiotensin converting enzyme (ACE), angiotensin II type-I receptor (AT1R)] and NADPH-oxidase 4 (NOX4) were measured in kidney and aorta. CsA caused significant disturbances in renal function markers, increases in oxidative stress and inflammation parameters and renal damage. Serum angiotensin II levels and mRNA expressions of ACE, AT1R and NOX4 elevated in the aorta and kidney of CsA-rats. Gly, especially its high-dose, alleviated renal function markers, oxidative stress, inflammation and renal damage in CsA-rats. Moreover, serum Ang II levels and mRNA expressions of ACE, AT1R and NOX4 decreased significantly in aorta and kidney in CsA-rats due to Gly treatment. Our results indicate that Gly may be useful for the prevention of CsA-induced renal and vascular toxicity.

STUDY OF DOSAGE ADJUSTMENT OF ORAL ANTIDIABETIC DRUG IN TYPE II DIABETES MELLITUS PATIENTS WITH DISORDERS KIDNEY FUNCTION AT DR. SOEKARDJO TASIKMALAYA HOSPITAL

Diabetic nephropathy is one of the complications in DM that can end up becoming DM kidney failure. Nephropathy complications, if not handled properly, will lead to terminal chronic kidney disease. One of the factors that trigger complications of diabetic nephropathy in DM patients is the long-term use of oral anti-diabetic drugs. Therefore, proper dosage adjustment of these antidiabetic drugs, which are excreted through the kidneys, is required. The purpose of this study was to determine whether the dose received by type II DM patients with impaired renal function in the hospital was appropriate or not. This research will be carried out quantitatively and retrospectively by collecting patient medical record data at the hospital, and then the data obtained will be analyzed descriptively by calculating the creatinine clearance using the Cockcroft &amp; Gault formula and comparing it with the literature dose based on the value of creatinine clearance. The sampling technique used was purposive sampling using the inclusion and exclusion criteria determined by the researcher. The inclusion criteria are data on type II diabetes mellitus patients with impaired kidney function at dr. Soekardjo Tasikmalaya Hospital in October–December 2020 who were treated with oral anti-diabetic drugs. The exclusion criteria were type II DM patients with impaired renal function who were treated with insulin, type I DM patients, and type II DM patients with impaired renal function who were treated with oral antidiabetic with incomplete laboratory data. Based on research that has been conducted on 35 samples, as many as 25 people, or 71.43 percent of patients, received therapeutic doses that were not in accordance with their kidney conditions. Meanwhile, 10 people, or 28,57% of patients, received a therapeutic dose according to their kidney condition.