Does Hypertension Affect the Recovery of Renal Functions after Reversal of Unilateral Ureteric Obstruction?

Research has demonstrated that hypertension can lead to an exaggeration in the renal functional and histological changes caused by ureteral obstruction. These changes were particularly observed shortly after the release of a relatively brief period of unilateral ureteral obstruction (UUO). However, the long-term impact of hypertension on the recovery of renal functions has not been investigated beyond the immediate period after UUO reversal. In order to investigate this effect, a group of spontaneously hypertensive rats (G-SHR, n = 11) and a group of normotensive Wistar Kyoto rats (G-NTR, n = 11) were subjected to a 48 h reversible left UUO. The impact of UUO was then examined 45 days after the reversal of obstruction. The glomerular filtration rate, renal blood flow, and the fractional excretion of sodium in the post-obstructed left kidney (POK) showed similarities to the non-obstructed right kidney (NOK) in both groups. However, the changes in the albumin creatinine ratio, renal injury markers, pro-apoptotic markers, and histological changes in the G-SHR were much more pronounced compared to the G-NTR. We conclude that hypertension continues to have a significant impact on various aspects of renal injury and function, even several weeks after UUO reversal.

The Effect of Hypertension on the Recovery of Renal Dysfunction following Reversal of Unilateral Ureteral Obstruction in the Rat.

Both ureteral obstruction (UO) and hypertension are common conditions that affect kidney functions. Hypertension and chronic kidney disease are closely associated with an overlapping and intermingled cause-and-effect relationship. The effect of hypertension on the renal dysfunction following reversible UO has not been studied previously. To study this effect, spontaneously hypertensive (G-HT, n = 10) and normotensive Wistar (G-NT, n = 10) rats underwent 48-h reversible left unilateral UO (UUO), and the effect of UUO was studied 96 h following UUO reversal. The glomerular filtration rate, renal blood flow, and renal tubular functions such as the fractional excretion of sodium in the post-obstructed left kidney (POK) in both groups were significantly altered compared with the non-obstructed right kidney (NOK). However, the alterations in the G-HT were significantly more exaggerated when compared with the G-NT. Similar findings were observed with the histological features, gene expression of kidney injury markers, pro-inflammatory, pro-fibrotic and pro-apoptotic cytokines, and pro-collagen, as well as tissue levels of apoptotic markers. We conclude that hypertension has significantly exaggerated the alterations in renal functions and other parameters of renal injury associated with UUO.

Hepato-renal toxicities associated with heavy metal contamination of water sources among residents of an oil contaminated area in Nigeria.

OBJECTIVES: This study was conducted to estimate the heavy metal (HM) content of water sources from oil contaminated area, HM and hepato-renal functions of residents and to determine association between consumption of crude oil contaminated water and development of multiple organ toxicities. METHODS: Heavy metals (Pb, Cd, As, Hg) content of 20 surface water sources (SWS) and 20 underground water sources (UWS) from crude oil contaminated area and 40 water sources (20 SWS and 20 UWS) from uncontaminated area (controls) were estimated using AAS. The HM, indices of liver function (aspartate and alanine aminotransferases (AST and ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total protein (TP), albumin, total and conjugated bilirubin (TB and CB)) and renal functions (urea, creatinine, sodium, chloride, potassium, bicarbonate and kidney injury molecule-1 (KIM-1)) were determined in 120 residents each from contaminated and control areas using enzyme-colorimetry and ELISA methods. RESULTS: The HM levels of all water sources studied were above WHO standards. Water sources from contaminated area had higher HM levels compared to control. HM contents of SWS from contaminated area and control were higher than UWS from both areas. Residents of contaminated area had higher levels of HM, urea, bicarbonate, chloride, sodium, KIM-1, ALP, GGT, AST, ALT, TB and CB and lower TP and albumin compared to residents of control area. CONCLUSION: Water contamination with crude oil is associated with elevated HM content with perturbations in HM, liver and renal functions of consumers which may suggest an increased risk of hepato-renal toxicities.

Despite initial recovery of GFR, long-term renal functions deteriorate following short periods of unilateral ureteral obstruction.

Following the release of short periods of unilateral ureteral obstruction (UUO), glomerular filtration rate (GFR) recovers by time. However, research in experimental animal models has demonstrated the presence of an ongoing element of renal interstitial fibrosis a few weeks following UUO reversal. Interstitial fibrosis can cause deterioration in GFR, and it is not known whether it leads to an ongoing slow deterioration in other renal functions despite the apparent initial recovery postreversal. To investigate this, rats underwent a 72-h reversible UUO. Renal functions of nonobstructed and previously obstructed kidneys were measured 1, 4, and 18 mo postreversal. GFR in nonobstructed and previously obstructed kidneys was similar up to 18 mo postreversal. However, there was ongoing tubulointerstitial fibrosis, and the degree of tubular atrophy and dilatation deteriorated by time. This was associated with an increase in urinary albumin leakage and alterations in renal injury markers, proinflammatory and profibrotic cytokines, and p53 from 4 mo onward despite the recovery in GFR. In conclusion, several aspects of renal functions continue to deteriorate following reversal of relatively short periods of UUO despite the initial recovery in GFR. This might stimulate further research in this area and might have clinical implications in terms of determining the best time for intervention following acute ureteral obstruction and long-term monitoring of these individuals.

Renal profile of chronic hepatitis C patients with sofosbuvir-based therapy.

PURPOSE: The impact of SOF-based therapy on renal functions is quite controversial in clinical practice. Therefore, we aimed to evaluate the serial changes of renal indices during SOF-based therapy in CHC patients with normal kidney function or mild renal impairment. METHODS: We retrospectively reviewed all CHC patients who received different SOF-based regimens from January 2015 until December 2017, and presented with a baseline eGFR ≥ 30 ml/min/1.73m2. Patients who didn't achieve SVR, with missing creatinine or eGFR data, and patients with eGFR less than 30 ml/min/1.73m2 at baseline were excluded. eGFR was calculated for each time of evaluation using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. RESULTS: A total of 1004 patients were finally included. The mean serum creatinine and eGFR levels varied between 0.84 mg/dl and 106.53 ml/min/1.73m2 for baseline and 0.87 mg/dl and 104.24 ml/min/1.73m2 for SVR12, respectively. The maximum increase of creatinine was 3.69 mg/dl and the maximum decrease of eGFR level was 83.30 ml/min/1.73m2 during treatment. Moreover, 74.4% of treated patients stayed in the same eGFR category, 14.3% progressed to a higher eGFR category, and 11.3% had an improvement eGFR category at EOT and continued to SVR12. Age > 65 years, baseline eGFR, and ribavirin-containing regimens were independent risk factors of eGFR decline during and after SOF-based treatment. CONCLUSION: SOF-based therapies seem to be safe in CHC patients with baseline normal or slightly impaired renal function.

Glomerular filtration rate: when to measure and in which patients?

Of the glomerular, tubular and endocrine functions of the kidney, nephrologists have mostly focused their attention on the glomerular functions-albuminuria and glomerular filtration rate (GFR)-to grade the severity of chronic kidney disease (CKD). Although both albuminuria and GFR are associated with renal and cardiovascular morbidity and mortality, the utility of measured GFR (mGFR) has been questioned. GFR when measured adequately is the most precise measure of glomerular function and can be useful to individualize therapy among patients with CKD. In situations where estimated GFR is known to provide imprecise estimates of glomerular function, for example, sarcopenia and advanced cirrhosis, the measurement of GFR may be especially important. We discuss several clinical situations where mGFR can potentially influence the quality of life or complications of therapy because of interventions based on imperfect knowledge of GFR. We reason that although large databases may not detect the benefits of mGFR at the population level, precision medicine requires that therapy be individualized based on the best estimate of GFR that can be obtained particularly when the risk of harm is increased. The recent standardization of mGFRs is a step in the right direction and may help in treating the individual patient with CKD with a lower risk of complications and a better quality of life. We call for research in these subgroups of patients where it is clinically felt that mGFR is useful for clinical decision-making.

Neurological manifestations and neuroimaging presentations in patients with severe preeclampsia: predisposing factors and clinical implications.

BACKGROUND AND PURPOSE: Neurological manifestations and neuroimaging abnormalities are common in patients with severe preeclampsia; however, the differences between these abnormal features occurring during early- and late-onset severe preeclampsia are unclear, and the factors associated with abnormal imaging changes in patients with neurological manifestations have not yet been fully elucidated. MATERIALS AND METHODS: A retrospective study was conducted on 172 patients with severe preeclampsia from January 2017 to June 2018 in the Department of Neurology and Obstetrics, Shengjing Hospital of China Medical University. The neurological manifestations, clinical parameters, laboratory, and neuroimaging findings were analyzed. RESULTS: Early- and late-onset preeclampsia were diagnosed in 83 and 89 patients, respectively. Headache and dizziness were more common in patients with early-onset preeclampsia than in patients with late-onset preeclampsia (p = 0.013, p = 0.004, respectively). Serum uric acid, creatinine, and urea nitrogen were significantly elevated in the patients with early-onset preeclampsia (p < 0.001, p = 0.004, and p = 0.005, respectively). Neuroimaging was performed in 81 patients, of which 57 were positive. Findings indicating cerebral edema were the most common neuroimaging abnormality. Gestational weeks (p = 0.014), headache (p < 0.001), and blood urea nitrogen level (p = 0.027) may be associated with positive imaging findings. By multiple logistic regression, headache (OR = 10.2, 95% CI, 2.4-42.7; p = 0.002) proved to be an independent factor associated with neuroimaging abnormality. CONCLUSIONS: Neurological symptoms such as headache and dizziness were more common in patients with early-onset preeclampsia. Renal dysfunction may also associate with early-onset severe preeclampsia. Cerebral edema was the most common neuroimaging abnormality, and headache might be independently associated with abnormal imagine changes.

Alda-1, an aldehyde dehydrogenase-2 agonist, causes deterioration in renal functions following ischemia-reperfusion injury due to crystalline nephropathy.

Renal ischemia-reperfusion injury (IRI) induces the production of aldehydes which are detoxified by aldehyde dehydrogenases (ALDHs). Alda-1 is a selective ALDH2 agonist and its protective effect was demonstrated in several conditions. The effect of Alda-1 on the kidney or on renal IRI was not investigated. We investigated the effect of Alda-1 on the renal dysfunction following IRI. Wistar rats underwent left IRI for 40 min. Group-Alda (n = 11) received Alda-1 starting 24 h before IRI and continued for 7 days thereafter when renal functions were measured. Group-Vx (n = 11) underwent similar protocol but received the dissolvent. Alda-1 did not affect renal blood flow or glomerular filtration rate in the left ischemic kidney in Group-Alda compared to Group-Vx (3.05 ± 0.50 vs. 3.53 ± 0.70, and 0.40 ± 0.06 vs. 0.51 ± 0.08, respectively, p > .05 for both). However, left renal fractional sodium excretion was higher in Group-Alda (2.80 ± 0.43 vs. 1.37 ± 0.36, p = .02). Alda-1 also adversely affected the gene expressions of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin (217 ± 38 vs. 99 ± 13 and 49 ± 13 vs. 20 ± 5, respectively, p < .05 for both) and the alterations in tumor necrosis factor-α, transforming growth factor-ß1, plasminogen activator inhibitor-1, fibronectin 1 and p53 (4.4 ± 0.9 vs. 2.1 ± 0.3, 1.5 ± 0.1 vs. 1.1 ± 0.1, 30.0 ± 2.7 vs. 11.7 ± 2.3, 3.6 ± 0.4 vs. 2.1 ± 0.2 and 1.3 ± 0.1 vs. 0.9 ± 0.07, respectively, p ≤ .05 for all). This was associated with intratubular crystal deposition suggestive of crystalline nephropathy. Alda-1 exacerbated the IRI-induced renal tubular dysfunction and alterations in markers of acute kidney injury, biomarkers of inflammation, fibrosis and apoptosis and this was associated with intratubular crystal deposition suggestive of crystalline nephropathy.

The effects of blood transfusion on renal functions in orthopaedic surgery.

OBJECTIVE: The effects of perioperative blood transfusion on renal functions have been studied in various studies. In this study, we investigated the effects of blood transfusion on postoperative kidney functions in patients who underwent orthopaedic surgeries. METHOD: Total 136 patients who were operated for several orthopedic pathologies between June 2013 and December 2014 were evaluated. The patients were divided into two groups according to the amounts of blood transfusion. Ninety five patients (69.8%) who were transfused less than 3 units were included in Group 1 and 41 patients (30.2%) who received 3 and more units of blood were included in Group 2. RESULTS: There were no statistical difference between the two groups in terms of preoperative gender, hypertension, diabetes mellitus, chronical renal failure and smoking habbits (P > 0.05). No statistical differences between the groups were seen in terms of postoperative hospital stay, pulmonary and other complications as well as mortality (P > 0.05). When the two groups were compared for blood parameters showing postoperative renal and other system functions, no statistical differences were detected (P > 0.05). CONCLUSION: Blood transfusion does not have negative effects on postoperative BUN and creatinine levels in patients operated for orthopaedic pathologies.

Diabetes mellitus with normal renal function is associated with anaemia.

BACKGROUND: Anaemia is a common complication of diabetes mellitus (DM), usually related to renal failure. There is scarce information as to the levels of haemoglobin (Hb) and the rate of anaemia in diabetic patients with normal renal function. We, therefore, evaluated haemoglobin levels and the rate of anaemia in diabetic subjects with normal renal functions [estimated glomerular filtration rate (eGFR) > 60 mL/min]. METHODS: The charts of 9250 subjects who attended the Institute of Periodic Medical Examinations at the Chaim Sheba Medical Center for a routine yearly check-up were reviewed. Four hundred and forty-five subjects with type 2 DM and normal renal function were indentified and compared with those without DM who were routinely examined at the same time. Subjects' electronic records were used to build a biochemical and clinical database. RESULTS: Mean haemoglobin levels were lower in subjects with DM than in those without (14.2 vs. 14.7 g/dL, respectively; p < 0.001). Anaemia was observed in 48 (10.8%) subjects in the diabetic group and in only 12 (2.7%) in the nondiabetic group (p < 0.001). Multivariate analysis revealed that age, gender, history of gastrointestinal disease, use of beta blockers, renal function and DM were independent determinants of haemoglobin levels. After adjustment for age, gender, history of gastrointestinal tract diseases and renal function, DM remained a significant determinant of anaemia with an odds ratio of 2.15 (confidence interval: 1.07-4.31). CONCLUSIONS: Anaemia is more common in diabetic patients even when eGFR > 60 mL/min.

Effects of percutaneous cryoablation for renal tumor on overall and split renal function.

PURPOSE: To evaluate retrospectively the influence of percutaneous cryoablation for small renal tumors on total and affected kidney function and risk factors associated with worsening function of the affected kidney. MATERIALS AND METHODS: Between April 2016 and March 2022, 27 patients who underwent cryoablation for small renal tumors at our institution participated in this study, which investigated time-dependent changes in postoperative renal function. We evaluated estimated glomerular filtration rates (eGFRs) and split renal function revealed by scintigraphy using 99 m technetium-mercaptoacetyltriglycine (99mTc-MAG3) before cryoablation and at 1 week, 1 month, and 6 months after cryoablation. Numerous variables were analyzed to assess risk factors for worsening renal function. RESULTS: Baseline eGFR (mean ± standard deviation) was 56.5 ± 23.7 mL/min/1.73 m2 (mean ± SD; range, 20.5-112.5). Mean eGFRs at 1 week, 1 month, and 6 months after cryoablation were 57.4 ± 24.5 (19.1-114.9), 57.1 ± 25.1 (21.5-114.9), and 53.8 ± 23.9 mL/min/1.73 m2 (20.0-107.5), respectively. Changes were statistically insignificant (p = 1.0000, = 0.6749, and = 0.0761, respectively). Regarding split renal function, mean baseline contribution of the affected kidney determined by 99mTc-MAG3 was 49.7% ± 6.0% (38.8-63.3%); these rates at 1 week, 1 month, and 6 months after cryoablation were 43.7% ± 8.8 (29.1-70.6%), 46.2% ± 7.7% (32.6-70.3%), and 46.0% ± 8.5% (32.5-67.6%), respectively. Differences from baseline were significant for all periods (p < 0001, < 0001, = 0.0001, respectively). Serum C reactive protein and lactate dehydrogenase at 1 day following cryoablation, tumor's nearness to the collecting system or sinus, and volume of ablated normal renal parenchyma were significantly correlated with decreased contributions of the affected kidney by > 10% after cryoablation. CONCLUSION: Unlike total renal function, affected kidney function could worsen after cryoablation.

Inonotus obliquus (Chaga) against HFD/STZ-induced glucolipid metabolism disorders and abnormal renal functions by regulating NOS-cGMP-PDE5 signaling pathway.

Our prior investigations have established that Inonotus obliquus (Chaga) possesses hypoglycemic effects. Persistent hyperglycemia is known to precipitate renal function abnormalities. The functionality of the kidneys is intricately linked to the levels of cyclic guanosine-3',5'-monophosphate (cGMP), which are influenced by the activities of nitric oxide synthase (NOS) and phosphodiesterase (PDE). Enhanced cGMP levels can be achieved either through the upregulation of NOS activity or the downregulation of PDE activity. The objective of the current study is to elucidate the effects of Chaga on disorders of glucolipid metabolism and renal abnormalities in rats with type 2 diabetes mellitus (T2DM), while concurrently examining the NOS-cGMP-PDE5 signaling pathway. A model of T2DM was developed in rats using a high-fat diet (HFD) combined with streptozotocin (STZ) administration, followed by treatment with Chaga extracts at doses of 50 and 100 mg·kg-1 for eight weeks. The findings revealed that Chaga not only mitigated metabolic dysfunctions, evidenced by improvements in fasting blood glucose, total cholesterol, triglycerides, and insulin resistance, but also ameliorated renal function markers, including serum creatinine, urine creatinine (UCr), blood urea nitrogen, 24-h urinary protein, and estimated creatinine clearance. Additionally, enhancements in glomerular volume, GBM thickness, podocyte foot process width (FPW), and the mRNA and protein expressions of podocyte markers, such as nephrin and wilms tumor-1, were observed. Chaga was found to elevate cGMP levels in both serum and kidney tissues by increasing mRNA and protein expressions of renal endothelial NOS and neural NOS, while simultaneously reducing the expressions of renal inducible NOS and PDE5. In summary, Chaga counteracts HFD/STZ-induced glucolipid metabolism and renal function disturbances by modulating the NOS-cGMP-PDE5 signaling pathway. This research supports the potential application of Chaga in the clinical prevention and treatment of T2DM and diabetic nephropathy (DN), with cGMP serving as a potential therapeutic target.

Efficacy of Endopyelotomy for Secondary Pelvi-Ureteric Junction (PUJ) Obstruction in Terms of Improvement in Renal Function.

Objective The objective of this study is to measure renal function improvement after endopyelotomy for secondary pelvi-ureteric junction (PUJ) obstruction using technetium-99m diethylene-triamine-pentaacetate (DTPA) renal scintigraphy. Material and methods This descriptive study was carried out at the Department of Urology, Institute of Kidney Diseases, Peshawar, Pakistan from June 1, 2021, to May 31, 2023. The study included 118 secondary PUJ blockage patients who underwent endopyelotomy. Patient demographics, clinical history, and preoperative imaging findings were obtained. DTPA renal scintigraphy assessed renal function improvement postoperatively at intervals to determine the efficacy of endopyelotomy. Results The majority of the patients included in the study were male (n=65, 55.1%). The average age of the patients was 45.2 years, with the majority falling within the age range of 46-60 years (n=42, 35.6%). All patients had ultrasonography and computed tomography imaging done, and preoperative renal functions were obtained. Comorbidities included hypertension in 32 (27.12%) and diabetes in 18 (15.25%). DTPA renal scintigraphy showed improved renal function in 81.35% of patients at three months, 88.13% at six months, and 83.05% at 12 months; 15.3% of patients needed further treatments, and 5.1% had PUJ blockage recurrence. Conclusion This study offers significant insights into the results and complexities of endopyelotomy in patients suffering from PUJ blockage. The findings indicate that the technique efficiently enhances kidney function and alleviates symptoms in most patients. However, the study also emphasizes the need to monitor patients undergoing this procedure.

Is There Any Effect of Retrograde Intrarenal Stone Surgery on Renal Functions in Childhood?

Purpose In this study, we aimed to demonstrate whether retrograde intrarenal stone surgery (RIRS) performed due to renal stones during the childhood period has any detrimental impact on renal functions. Materials and methods We retrospectively analyzed 121 patients aged 2 to 16 years who underwent RIRS for renal stones between March 2018 and February 2023. Data were available for 41 patients. The estimated glomerular filtration rate (eGFR) was computed using the modification of diet in renal disease (MDRD) formula on the day preceding the surgery and the third month after the surgery. We employed the National Kidney Foundation's chronic kidney disease (CKD) classification to categorize the glomerular filtration rate (GFR) into five groups. Preoperative and postoperative eGFR values of pediatric patients were compared by analyzing changes in CKD groups. Results Of the patients included in the study, 21 (51.2%) were male, while 20 (48.8%) were female children. No significant difference was found between the preoperative median eGFR and the postoperative median eGFR values (p=0.958). In the 3rd month after surgery, it was observed that 5 (12.1%) patients showed an improvement in their CKD stage, while deterioration was noted in 1 (2.4%) patient. Although a negative correlation was observed between the median eGFR change and both the operation time and the stone volume in Pearson correlation analysis, it was determined that this change did not create a significant difference (p=0.213 and p=0.295, respectively). Conclusion Stone surgery conducted with RIRS appears to yield positive outcomes on kidney function in the pediatric population. Nevertheless, being particularly attentive to patients with prolonged operation times and larger stone volumes is essential.

Emergency medicine pharmacotherapy compromises accuracy of plasma creatinine determination by enzyme-based methods: real-world clinical evidence and implications for clinical practice.

Background: Assessment of kidney function in emergency settings is essential across all medical subspecialties. Daily assessment of patient creatinine results from emergency medical services showed that some deviated from expected values, implying drug-related interference. Methods: Real-time clinical evaluation of an enzyme method (Roche CREP2) in comparison with the Jaffé gen. 2 method (Roche CREJ2) was performed. During the period of December 2022 and January 2023, we analyzed 8,498 patient samples, where 5,524 were heavily medicated STAT patient specimens, 500 were pediatric specimens, and 2,474 were from a distant general population in a different region using the same methods. Results: In 109 out of 5,524 hospital specimens (1.97%, p < 0.001), the CREP2 value was apparently (25% or more) lower than CREJ2. Suspect interfering medication was found in a sample of 43 out of 46 reviewed patients where medication data were available. This phenomenon was not observed in the general population. Conclusion: In a polymedicated urgent care hospital population, a creatinine enzyme method produces unreliable results, apparently due to multiple drug-related interferences.

Therapeutic potential and protection enhancement of mesenchymal stem cell against cisplatin-induced nephrotoxicity using hyaluronic acid-chitosan nanoparticles as an adjuvant.

A newly synthesized nanoplatform of hyaluronic acid and chitosan nanoparticles (HA/CNPs) was applied to improve the therapeutic efficacy and protection of bone marrow mesenchymal stem cells (BM-MSCs) against cisplatin (CDDP)-induced nephrotoxicity in rats. CDDP administration causes significant increases in levels of serum creatinine (SCr), urea, and KIM-1 coupled with significant albumin level falls, as indicative of acute renal dysfunction. Moreover, the level of the antioxidant enzyme (GSH) was significantly decreased, while the levels of lipid peroxidation (MDA) and inflammatory (IL-6) and apoptotic (caspase-3) markers were significantly increased, indicating a decline in the kidney's antioxidant defense and increased inflammation. In contrast, when rats were pre-treated with either MSCs or MSCs-HA/CNPs before receiving CDDP, the levels of SCr, urea, KIM-1, MDA, IL-6, and caspase-3 were significantly decreased with simultaneous significant rises in GSH and albumin, impelling a great improvement in the antioxidant and anti-inflammatory defenses of the kidney as well as its functions. Intriguingly, MSCs-HA/CNPs were more effective against caspase-3 than MSCs alone, revealing the high anti-apoptotic capability of HA/CNPs. This finding suggests that HA/CNPs could effectively protect MSCs from oxidative stress and apoptosis and thus increase their stability and longevity.

The Effect of Treatment With Aminoguanidine, an Advanced Glycation End Product Inhibitor, on Streptozotocin-Induced Diabetic Rats and Its Effects on Physiological and Renal Functions.

BACKGROUND/AIM: Diabetes is a multifactorial syndrome that affects the functioning of the renin-angiotensin system (RAS). The role of advanced glycation end products (AGEs) in diabetes is well known. In the present study, we hypothesized that the prevention of AGE accumulation or abrogation of AGE synthesis using an AGE inhibitor, aminoguanidine (AG), in streptozotocin (STZ)-induced diabetic animal models would affect the progression of diabetes and its related complications. We determined the effects of aminoguanidine (AG), an AGE inhibitor, in STZ-induced diabetic rats by determining various indices of RAS and renal functions. Additionally, we also investigated the effect of the drug, AG, on various hemodynamic and physiological functions in the body of the animals. METHODS: Male Sprague Dawley rats weighing 200-250 g were assigned to four groups (n = 4-6): Vehicle, Vehicle+AG, STZ-induced, and STZ-induced+AG rats. Type 1 diabetes was induced by a single intraperitoneal (IP) injection of streptozotocin (55 mg/kg) dissolved in sodium citrate buffer. The control groups (Vehicle) were injected with buffer. The blood glucose levels were measured after 48 hours, and animals with blood glucose levels > 300 mg/dL were included in the study. Blood glucose levels in the vehicle rats were also determined to ensure non-diabetic conditions. After confirmation, AG was administrated at a dose of 1 g/L in drinking water for two weeks. Urine was collected to measure the glomerular filtration rate (GFR), and the immune reactivity for AT1 and AT2 proteins was analyzed by immunoblotting. Data were expressed as mean ± standard error of the mean (SEM), and a p-value < 0.05 was considered statistically significant. RESULTS: Diabetic rats had a significant drop in body weight, accompanied by increased food and water consumption. The diabetic rats exhibited significantly increased urine flow and GFR. These phenotypes were significantly or considerately reversed by AG treatment in the STZ+AG-treated diabetic rats. Aminoguanidine prevented the increase in blood sugar levels compared to STZ-induced diabetic rats alone (295.9 ± 50.69 versus 462.3 ± 18.6 mg/dL (p < 0.05)). However, it did not affect the glomerular filtration rate (GFR) and glomerular damage, as assessed by the renal histopathological studies. The STZ-induced diabetic rats had an increased sodium excretion (3.24 ± 0.40 mmol) and significantly increased expression of the AT2 receptor and that of the AT1 receptor, which was slightly reversed by the treatment with AG. Treatment with AG decreased sodium excretion (2.12 ± 0.63, as compared to the diabetic rats). These rats also had modestly decreased expression of the AT2 receptor (0.99 ± 0.07 versus 1.12 ± 0.08, as compared to the STZ-induced diabetic rats), while the AT1 receptors showed a slight increase in the STZ+AG-treated rats compared to the STZ-induced diabetic rats (1.1 ± 0.19 versus 1.08 ± 0.12). CONCLUSION: This study highlights the action of the drug AG in not exacerbating any damage in diabetic rats. Employing AG as a pharmacological intervention to prevent an increase in blood sugar adds a new dimension to controlling increased blood sugar and preventing diabetic complications. The employability and pharmacological intervention of the drug AG, in diabetes, therefore, need a renewed and further investigation.

Renally Inappropriate Medications in the Old Population: Prevalence, Risk Factors, Adverse Outcomes, and Potential Interventions.

Like most organs, the renal system decreases in function as we age. In the elderly, chronic kidney disease is common. When patients with chronic kidney disease take nephrotoxic medications, they are more likely to suffer adverse drug reactions, be hospitalized, and spend an extended period in the hospital. Calculating the renal clearance of a drug dose based on its glomerular filtration rate, or creatinine clearance, is necessary. Multiple tools are available for identifying renally inappropriate medications (RIMs). RIM prescriptions can be influenced by various factors, which vary according to the study. A higher number of medications means a higher likelihood of using RIMs. Numerous studies have investigated RIMs. The most contraindicated drug in renal insufficiency patients was a non-steroidal anti-inflammatory medication. A variety of interventions have been used to reduce RIM prescriptions to varying degrees of success.

Impact of contrast-enhanced versus non-contrast computed tomography on acute kidney injury in acute necrotizing pancreatitis: A randomized controlled trial.

BACKGROUND: The data evaluating contrast-induced-acute kidney injury (AKI) in patients with acute pancreatitis is scarce. This study aimed to compare the frequency of AKI in patients with acute necrotizing pancreatitis undergoing non-contrast computed tomography (NCCT) with those undergoing contrast-enhanced computed tomography (CECT) during hospitalization. METHODS: This prospective randomized controlled trial (CTRI/2019/12/022206) screened consecutive patients with acute pancreatitis for eligibility and randomly allocated patients with acute necrotizing pancreatitis (based on CECT in the first week of illness) and normal renal functions to receive either NCCT or CECT during hospitalization. The incidence of development of new AKI and clinical outcomes was compared between the two groups. Post-hoc analysis was done to adjust for disease severity. RESULTS: As many as 105 patients completed the study as per protocol (NCCT = 45 and CECT = 60). AKI occurred in 36 (34.3%) patients, nine (20%) in the NCCT and 27 (45%) in the CECT group. Contrast induced-AKI occurred in 11 (18.3%) patients, while 25 had AKI secondary to acute pancreatitis. The relative risk (RR) of AKI in the CECT group was 2.25 (95% CI 1.17-4.30, p = .0142). The frequency of intensive care unit (ICU) admission (RR = 2.1, 95% CI 1.34-3.27, p = .0001) and need for drainage of collections (RR = 1.39, 95% CI 1.1-1.7, p = .005) was significantly higher and the length of hospitalization (p = .001) and ICU admission (p = 0.001) were significantly longer in the CECT group. However, when adjusted for the severity of acute pancreatitis, there was no difference in AKI and clinical outcomes between the NCCT and CECT groups. The duration of AKI was significantly longer and the need for dialysis was significantly higher in patients who had AKI secondary to acute pancreatitis compared to those with contrast induced-AKI (p = .003). CONCLUSION: CECT is not significantly associated with AKI in acute necrotizing pancreatitis.

Role of Salvia officinalis Silver Nanoparticles in Attenuation Renal Damage in Rabbits Exposed to Methotrexate.

Nanomaterials are now considered in an extensive range of applications in various fields such as biotechnology and biomedicine. The present study aimed to investigate the protective role of Salvia officinalis Silver Nanoparticles (SOSNPs) as an anti-oxidant on nephrotic damage induced by methotrexate (MTX) in adult rabbits. Green silver nanoparticles were synthesized using alcoholic extract of Salvia officinalis (S. Officinalis) leaves and were characterized by UV-spectrophotometry and scanning electron microscope. The mixing of the plant extract of S. Officinalis with silver nitrate solution leads to the change of the reaction mixture color to yellowish within 1 h and dark brown after 8 h. For studying the protective role of SOSNPs, a total of 28 adult Wistar albino rabbits were divided into four groups and treated intramuscularly (twice per week) for 45 days as follows: T1: S. Officinalis (150 mg/kg B.W), T2: SOSNPs (150 mg/kg B.W); T3: MTX (0.25 mg/kg B.W) and SOSNPs (150 mg/kg B.W); T4: MTX (0.25 mg/kg B.W). Blood was collected at 0, 15, 30, and 45 days using retro-orbital sinus and cardiac puncture technique, and the serum factors including malondialdehyde (MDA), glutathione (GSH) in serum, creatinine, as well as blood urea nitrogen and uric acid concentrations were measured at the next step. The results indicated that MTX (T4) caused a case of oxidative stress by a significant decrease in GSH and MDA as well as an increase in serum creatinine, urea, and uric acid concentrations. On the other hand, the protective roles of S. Officinalis and SOSNPs given concurrently with MTX were clarified in T2 and T3 groups, where there was the alleviation of renal damage through the correction of the previously mentioned parameters as well as the correction of anti-oxidant status. Finally, the present study documented the anti-oxidant activity and renal protective effects of SOSNPs against the damaging effects of MTX in rabbits.