Related Kidney Research Articles

Effect of neuromuscular electrical stimulation on renal functions in pregnancy related-acute kidney injury: a randomized controlled trial

Background: Various therapies have been used to restore blood flow and stabilize renal function in patients with pregnancy related acute kidney injury (AKI-P). There are favorable effects of electrical stimulation on muscle metabolism, microcirculation and possibly renal function; therefore, this study suggests for the first time that neuromuscular electrical stimulation (NMES) has a positive effect on renal functions of women with AKI-P.
 Methods: This randomized controlled design study evaluated the effect of NMES on renal blood flow and hemodynamics for women with AKI-P. Patients were randomized into two groups; NMES group (Group ES) versus Control group (Group C). Group ES received routine care and NMES while Group C received routine care only, data was collected from obstetric ICU. Improvement of renal functions was considered the primary outcome and secondary outcome was improvement of hemodynamics.
 Results: NMES application had caused no a statistical significant change in serum creatinine in Group ES than Group C on mid period and last day of the study (230.13 ± 83.69 in Group ES versus 258.3 ± 115.77 in Group C) and (180.21 ± 63.65 in Group ES versus 201.32 ± 84.78 in Group C) (P = 0.285 & P = 0.297) respectively.
 Conclusion: Application of NMES had no effect on their renal functions but there are improvements on hemodynamics.
 Trial registration: The study registered in Clinical-Trials.gov at 8 October 2020 - prospectively registered, http://www. Clinical- Trials.gov.com/ NCT04580329
 Abbreviations: CVP: Central venous pressure; ES: Electrical stimulation; GCS: Glasgow coma scale; HR: Heart rate; MAP: Mean arterial pressure; NMES: Neuromuscular electrical stimulation; AKI-P: Pregnancy related acute kidney injury; RR: Respiratory rate
 Key words: Neuromuscular electrical stimulation; Acute kidney injury; Renal functions
 Citation: Ali ATA, Abdelaal IIM, Obiedallah AMA, Abdelbadie AS. Effect of neuromuscular electrical stimulation on renal functions in pregnancy related acute kidney injury: a randomized controlled trial. Anaesth. pain intensive care 2022;27(1):104−111; DOI: 10.35975/apic.v27i1.2112
 Received: March 10, 2022; Reviewed: November 09, 2022; Accepted: December 17, 2022

Pregnancy Related Acute Kidney Injury: A Multicenter Prospective Observational Study From Bangladesh

Background: Acute kidney injury (AKI) is one of the most challenging and serious complications of pregnancy which imposes a heavy burden of maternal morbidity and mortality if its diagnosis and treatment are delayed. Objective: This prospective study intended to determine the frequency, etiology and outcomes of the patients of pregnancy related acute kidney injury (PRAKI) in different tertiary care hospitals in Bangladesh. Methods: This was a prospective study of patients with pregnancy related complications leading to acute kidney injury admitted in selected departments of different tertiary care hospitals in Bangladesh for a period of one year (October 2018 to September 2019). Patients were included in this study who were healthy previously and developed acute kidney injury (serum creatinine >70.72 mmol/l) due to pregnancy related complications. Recruited patients were monitored after 3 months with a view to exclude chronic kidney disease. Result: A total of 351 patients with pregnancy and puerperium were observed, of these patients studied, 34 (9.2%) had pregnancy-related AKI. In 32 patients who completed the study, the mean age was 27.2±6.2 years. There were more subjects belonging to the rural area (68.8%) and nineteen (59.4%) of patients were below primary level of education. Most of the study subjects from lower socioeconomic status (56.2%). Twenty-one (65.5%) patients were multigravida, and mean parity of the patients included in this study was 1.7±0.8. Nineteen (59.4%) patients did not receive any antenatal care. PRAKI occurred during the post-partum period in 53.2% of the cases, 21.9% in third trimester, and 24.9% in first and 2nd trimester. The most common cause of PRAKI in our study was sepsis, occurring in about 15 patients (46.9%). Most common presentation of PRAKI was oliguria (87.5%) and edema (84.3%). Mean hemoglobin level was 7.8 ±1.7 gm/dl and creatinine level was 573±407 μmol/l. A majority of the patients (81.25%) underwent hemodialysis, while others were treated with conservative management only. At the three-month follow-up, complete resolution of AKI was observed in 62.5% patients, progressed to CKD in 25% whereas mortality occurred in 12.5% patients. In univariate analysis, inappropriate antenatal care (p- 0.0018), low mean platelet count (p-0.00001), higher serum creatinine (p-0.00004), dialysis at presentation (p-0.0154), and septicemia (p-0.0487), have significant effect. Conclusion: Pregnancy related AKI is still a critical situation in developing countries and rare entity in developed countries. Maternal mortality has decreased but sepsis still accounts for majority of cases of PRAKI. Therefore, early diagnosis and treatment is the need of the hour. J Dhaka Med Coll. 2021; 29(1): 76-81

Visnagin Mitigates Glycerol-induced Acute Kidney Injury in Rats through Decreasing Inflammation, Oxidative Stress, and Renal Dysfunction Markers

Abstract: Background: Acute kidney injury (AKI) is a heterogenous condition, characterized by dysregulated kidney function along with reduced glomerular filtration, solute excretion, and urine output. Objectives: This work was focused to investigate the therapeutic roles of visnagin against the glycerol-induced AKI in rats via reducing the inflammation and oxidative stress responses. Materials and Methods: The AKI was induced in the Wistar rats by injecting 50% of glycerol (10 ml/kg). Then AKI rats were treated with 20 and 40 mg/kg of visnagin, respectively for 12 consecutive days. The rats were sacrificed followed at the end of experiments and blood and renal tissue samples were collected. The creatinine, BUN, urea, and LDH was quantified using assay kits. The nitric oxide (NO), MDA, and MPO were analyzed using assay kits. The antioxidants such as GSH, SOD, GSH, GPx, GR, and CAT activities were assessed by the standard methods. The IL-1β, IL-6, TNF-α, TGF-β1, MCP-1, and ICAM-1 levels were measured using assay kits. The histopathological analysis was done on the renal tissues. Results: The 20 and 40 mg/ kg of visnagin treatment reduced the relative kidney weight of AKI rats. The urea, creatinine, BUN, and LDH levels were diminished by the visnagin. The 20 and 40 mg/kg of visnagin treated AKI rats appreciably reduced the MDA, MPO, and NO levels and augmented the GSH, SOD, GPx, GR, and CAT activities in the renal tissues. The IL-6, IL-1β, TNF-α, and TGF-1β levels were reduced by the visnagin treatment. The MCP-1 and ICAM-1 status were also diminished by the visnagin. The findings of the histopathological analysis revealed that visnagin attenuated the glycerolinduced AKI in rats. Conclusion: In conclusion, the outcomes of this study revealed that the visnagin demonstrated nephroprotective effects against glycerol-induced renal damage in rats. The ability of visnagin to ameliorate inflammatory response, oxidative stress, and renal dysfunction make it a potential candidate for treating AKI. Keywords: Glycerol, Renal dysfunction, Creatinine, Inflammation, Visnagin, Rhabdomyolysis.

A Dual-Function Wearable Electrochemical Sensor for Uric Acid and Glucose Sensing in Sweat.

Simultaneous detection of uric acid and glucose using a non-invasive approach can be a promising strategy for related diseases, e.g., diabetes, gout, kidney disease, and cardiovascular disease. In this study, we have proposed a dual-function wearable electrochemical sensor for uric acid and glucose detection in sweat. The sensor with a four-electrode system was prepared by printing the ink on a common rubber glove. CV and chronoamperometry were used to characterize the prepared sensor's electrochemical sensing performance. The sensors exhibited the linear range from 0 to 1.6 mM and 0 to 3.7 mM towards uric acid and glucose electrochemical sensing in phosphate-buffered solution, with the corresponding limit of detection of 3.58 μM and 9.10 μM obtained, respectively. Moreover, the sensors had shown their feasibility of real sample sensing in sweat. The linear detection range for uric acid (0 to 40 μM) and glucose (0 to 1.6 mM) in the sweat can well cover their concentration range in physiological conditions. The prepared dual-function wearable electrochemical sensor features easy preparation, fast detection, high sensitivity, high selectivity, and the practical application potential in uric acid and glucose sensing.

β-Cyclodextrins alter the energy metabolism-related enzyme activities in rats.

Although widely used in medicine, separation technology, and other fields, the effects of cyclodextrins on the activities of phosphoryl transfer enzymes have not been previously evaluated. In vivo studies evaluated the function of cyclodextrins as active compounds. Despite the use of cyclodextrins as active compounds, the effects of cyclodextrins on hepatic and renal tissues remain to be fully elucidated. The primary objective of this study was to evaluate the effects of β- cyclodextrins, methyl-β-cyclodextrin (M-β- cyclodextrins), and (2-hydroxypropyl)-β-cyclodextrin (HP-β-cyclodextrins) on enzyme activities regulating the maintenance of energy homeostasis in the kidney and liver tissues in relation to toxicity. Serum levels of liver and kidney markers were measured, and oxidative stress parameters were assessed. After 60-day treatments, we observed that the administration of β-cyclodextrins and M-β-cyclodextrins inhibited the hepatic activity of pyruvate kinase, an irreversible enzyme within the glycolytic pathway. Additionally, administration of HP-β-cyclodextrins inhibited creatine kinase activity and increased the total sulfhydryl content in kidneys. Here, we demonstrated for the first time that β-cyclodextrins, M-β-cyclodextrins, and HP-β-cyclodextrins cause bioenergetic dysfunction in renal and hepatic tissues. These findings suggest that understanding the balance between cyclodextrins' efficacy and adverse effects is essential for better accepting their use in medicine.

Ferritin and procalcitonin in COVID-19 associated acute kidney injury – gender disparities, but similar outcomes

Abstract Background: Acute kidney injury is a severe complication of COVID-19. Both COVID-19 and related acute kidney injury are reported in the literature to be more prevalent and more severe in males. Methods: We performed a retrospective analysis of the COVID-19 associated acute kidney injury cases in order to search for differences between genders regarding patients’ and renal outcome. Results: 250 patients with acute kidney injury were included in the study: 93 women (37.20%), 157 men (62.80%). There were no differences between sexes regarding age. Diabetes mellitus was significantly more present in women. Peak ferritin and procalcitonin levels were significantly higher in men, but other severity markers for COVID-19 did not differ between genders. There were no differences between sexes regarding history of chronic kidney disease, timing of acute kidney injury, need for dialysis or recovery of renal function. ICU admission and in-hospital mortality were similar between men and women. Conclusions: In our study, COVID-19 related-AKI was more prevalent in men than in women, but the patients’ and renal outcome were similar. Significantly higher ferritin and procalcitonin serum levels registered in male patients when compared to women may have additional explanations beside more severe SARS-CoV-2 infection in males.

The effects of tarantula cubensis extract on renal ischemia reperfusion injury in rats.

Renal ischemia-reperfusion (IR) related acute kidney injury (AKI) is an important health problem and has not yet been fully treated. Tarantula cubensis extract (TCE) is a homeopathic drug that has antiinflammatory and antioxidant effects. This study aimed to investigate the effects of TCE on renal ischemia-reperfusion injury in rats. This study was carried out on 48 Spraque-Dawley male rats, which were divided into six groups. The first, second, and third groups were control, sham, and IR groups, respectively. Group four received IR and 0.2 mL of 96% ethanol. Group five and six received ischemia and reperfusion and TCE 0.01 and 0.1 mg per rat (which correspond to approximately 0.04 mg/kg, and 0.4 mg/kg), respectively. Tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), total antioxidant status (TAS), and total oxidant status (TOS) levels in renal tissue were measured by enzyme-linked immunosorbent assay (ELISA). Oxidative stress index (OSI) was obtained by proportioning TAS and TOS. Superoxide dismutase (SOD), myeloperoxidase (MPO) activities, and malondialdehyde (MDA) levels were determined by manual spectrophotometric methods. The histopathological changes were evaluated via hematoxylineosin and immunohistochemical staining. In IR group, renal tissue TNF-α and IL-1β levels were significantly higher than control group (p < 0.0001 for both), and low(p < 0.0001 for both) and high dose (p < 0.0001 for both) TCE administration decreased these markers. Low and high doses of TCE decreased OSI values compared with IR group (p = 0.04 and p = 0.001 respectively). Although TCE decreased MDA levels, it was not statistically significant. MPO levels significantly decreased. In addition, TCE has been found to prevent hemorrhage, cast formation, and dilatation caused by IR in renal tissues stained with hematoxylin-eosin. And also, the most intense nuclear factor kappa B (NFκB) and caspase-3 immunopositivity found in IR group was decreased in both of the TCE groups. Although TCE showed a protective effect by inhibiting inflammation against IR damage in renal tissues, there was no clear effect on oxidative stress. Larger and more detailed studies are needed to clarify the issue.

The Influence of Peritoneal Dialysis Catheter Tip Design on Technique Survival: A Retrospective Observational Study.

The clinical practice guidelines for peritoneal access state that no particular peritoneal dialysis catheter (PDC) type has been proven superior to another. We present our experience with the use of different PDC tip designs. The study is a retrospective, real-world, observational, outcome analysis correlating the PDC tip design (straight vs. coiled-tip) and technique survival. The primary outcome was technique survival, and the secondary outcome included catheter migration and infectious complications. A total of 50 PDC (28 coiled-tip and 22 straight-tip) were implanted between March 2017 and April 2019 by using a guided percutaneous approach. The 1-month and 1-year technique survival in the coiled-tip PDC was 96.4% and 92.8%, respectively. Of the two coiled-tip catheters lost, one was a consequence of the patient having undergone live related kidney transplantation. The corresponding 1-month and 1-year technique survival with straight-tip PDC was 86.4% and 77.3%, respectively. When compared to straight-tip PDC, the use of coiled-tip PDC was associated with fewer early migration (3.6% vs. 31.8%; odds ratio (OR): 12.6; 95% confidence interval (CI): 1.41-112.39; P = 0.02) and a trend toward favorable 1-year technique survival (P = 0.07; numbers needed to treat = 11). Therapy-related complications noted in the study included peri-catheter leak and PD peritonitis. The PD peritonitis rate in the coiled-tip and straight-tip group was 0.14 and 0.11 events per patient year, respectively. The use of coiled-tip PDC, when placed using a guided percutaneous approach, reduces early catheter migration and shows a trend toward favorable long-term technique survival.

Sonographic Evaluation of the Morphology of Kidneys Among Apparently Healthy Children in Northwest Ethiopia, 2021: The Normal Limits and Percentile Curves

Establishing a customized reference chart and curve of renal size for a specific population of the same sociodemographic characteristics enables a better interpretation of sonographic assessments. To evaluate the morphology of kidneys using ultrasound and establish the normal limits and percentile curves among apparently healthy children in northwest Ethiopia, 2021. A hospital-based cross-sectional study design. The study was conducted in Debre Markos comprehensive specialized hospital, Finote Selam general hospital, and Bichena primary hospitals. The study participants were 403 apparently healthy school-age children, from December 2019 to June 2020. Data were collected using a structured questionnaire, physical examination, and ultrasound. We used EPI-Data Version 3.1 for data entry. Height and body surface area-related kidney length and volume curves and tables were generated after lambda-mu-sigma (LMS) quantile regression with a Box-Cox Transformation to Normality using the vector generalized additive model (VGAM) method and generalized additive model for location, scale and shape (GAMLSS) (R, VGAM, and GAMLSS package). The height and body surface area of children was the best predictor of the sonographic dimensions of the kidneys. Reference intervals were established using height and body surface area specific for clinically practical dimensions of the kidney (length and volume). Calibration of measuring tools in the hospitals was not conducted frequently; community fatigue due to presence of many research projects in the selected hospitals was observed. According to this study, the children are considered to have normal sonographic dimensions if ultrasound values lie between the 2.5th and 97.5th percentile based on their respective height and body surface area.

Diosmin Mitigates Gentamicin-Induced Nephrotoxicity in Rats: Insights on miR-21 and -155 Expression, Nrf2/HO-1 and p38-MAPK/NF-κB Pathways.

Gentamicin (GNT) is the most frequently used aminoglycoside. However, its therapeutic efficacy is limited due to nephrotoxicity. Thus, the potential anticipatory effect of Diosmin (DIOS) against GNT-prompted kidney damage in rats together with the putative nephroprotective pathways were scrutinized. Four groups of rats were used: (1) control; (2) GNT only; (3) GNT plus DIOS; and (4) DIOS only. Nephrotoxicity was elucidated, and the microRNA-21 (miR-21) and microRNA-155 (miR-155) expression and Nrf2/HO-1 and p38-MAPK/NF-κB pathways were assessed. GNT provoked an upsurge in the relative kidney weight and serum level of urea, creatinine, and KIM-1. The MDA level was markedly boosted, with a decline in the level of TAC, SOD, HO-1, and Nrf2 expression in the renal tissue. Additionally, GNT exhibited a notable amplification in TNF-α, IL-1β, NF-κB p65, and p38-MAPK kidney levels. Moreover, caspase-3 and BAX expression were elevated, whereas the Bcl-2 level was reduced. Furthermore, GNT resulted in the down-regulation of miR-21 expression along with an up-regulation of the miR-155 expression. Histological examination revealed inflammation, degradation, and necrosis. GNT-provoked pathological abnormalities were reversed by DIOS treatment, which restored normal kidney architecture. Hence, regulating miR-21 and -155 expression and modulating Nrf2/HO-1 and p38-MAPK/NF-κB pathways could take a vital part in mediating the reno-protective effect of DIOS.

Unrelated versus related living-donor kidney transplantation is associated with higher acute rejection rate but similar graft survival Running title: Outcomes in living-donor kidney transplantation

Kidney transplantation (KT) from living donors has been shown to have multiple benefits compared with that from deceased donors. We sought to compare significant graft outcomes, namely acute rejection (AR), graft function, and survival, between transplant recipients who received a kidney from a living-related donor (LRD) and from a living unrelated donor (LURD). Our cohort comprised 198 donor and recipient pairs undergoing living-donor KT at our center over 10 years. LRD recipients were compared with LURD recipients according to demographic and clinical characteristics, transplant variables (including immunosuppression), graft function, survival, and AR rate. The estimated glomerular filtration rate (eGFR) was similar in both groups over the follow-up time, of 60-65 mL/min (p&lt;0.05 over a 10-year period). Censored graft survival was similar between LRD and LURD recipients (96.9% vs. 98.0% at 5 years and 87.8% vs. 79.4% at 10 years, respectively; p=0.837). LURD recipients had a higher incidence of AR, although LURD recipient status was not an independent risk factor for AR. Multivariate analysis showed that human leukocyte antigen (HLA) -DR mismatch (MM) was an independent predictor of AR (hazard ratio [HR] 2.256, p&lt;0.05). HLA-A and HLA-B MM did not affect the AR HR between the groups. Graft function and censored-death survival rates were similar between the LURD and LRD KT recipients. HLA-DR MM was an independent risk factor for AR.

Glucosamine inhibits extracellular matrix accumulation in experimental diabetic nephropathy.

Glucosamine, the intermediate metabolite of the hexosamine biosynthesis pathway (HBP), is widely used as a supplementary drug in patients with osteoarthritis. However, its consequences in such patients concomitantly suffering from diabetic nephropathy is unknown. The aim of the study was to investigate the effect of exogenous administration of glucosamine in the diabetic kidney. A mouse model of streptozotocin-induced diabetic nephropathy in vivo and cultured endothelial cells in vitro were used in the study. The mice were treated with glucosamine for 6 months. Renal function was evaluated by metabolic cage, and histology of the kidney was estimated by periodic acid-schiff (PAS) staining. The expression of related genes was assessed by real-time PCR, immunofluorescence staining, immunoblotting and ELISA. There was no significant difference in urinary albumin secretion, relative kidney weight, or creatinine clearance between the groups treated with glucosamine and controls. Assessment of the kidney demonstrated reduction in mesangial expansion and fibronectin expression in the diabetic glomeruli treated with glucosamine. Glucosamine treatment significantly decreased α-smooth muscle actin (α-SMA) protein expression in both diabetic and control kidneys, whereas the expression of other fibrosis-related genes and inflammatory factors was unaltered. Moreover, α-SMA colocalized with the endothelial marker CD31 in the diabetic and control kidneys, and glucosamine reduced α-SMA+ ECs in the diabetic glomeruli. In addition, glucosamine suppressed α-SMA expression in endothelial cells treated with or without high glucose. In summary, this is the first report to show that glucosamine reduces mesangial expansion and inhibits endothelial-mesenchymal transition in diabetic nephropathy. The underlying mechanisms need to be further investigated.

Efficacy of multiple Biomarkers: NGAL, KIM1, Cystatin C and IL18 in predicting pregnancy related acute kidney injury.

Several biomarkers like NGAL, KIM-1, IL-18, and Cystatin C has been previously reported as reliable marker to predict AKI. However, their predictive accuracy varies widely. We aim to observe the efficacy of multiple markers, NGAL, KIM-1, Cystatin C and IL-18, in obstetric population who are at risk of developing AKI. This prospective study was carried out between June 2021 to March 2022 at Department of Obstetrics & Gynecology Unit II, Ruth Pfau KM Civil Hospital and Sindh Institute of Urology & Transplant (SIUT), Karachi Pakistan. On women brought to OBGYN-ER with the diagnosis of hemorrhage (antepartum and postpartum), hypertension (pre-eclampsia and eclampsia) and sepsis. The urine samples and 3cc blood was collected at the time of admission, blood sample processed for biochemistry at time of admission and repeat blood samples for serum creatinine at 24 and 48 hours. Urine was stored at -80ºC and later evaluated for NGAL, KIM-1, Cystatin C and IL-18. Serum Cystatin C was also processed for the time zero sample. The biomarkers were tested using ELISA assays. A total of 149 women were included in the study, 83% of these women were non-booked. Twenty-six (17%) women developed AKI. Serum Cystatin C, urinary Cystatin C and urinary NGAL were found significantly raised in women who developed AKI. While KIM-1 and IL-18 were not raised to statistical significance in this population. However, urinary KIM-1 along with urinary Cystatin C were significantly raised in women with positive quick sequential organ failure assessment (qSOFA). This study validates the use of serum and urinary Cystatin C and urinary NGAL as highly predictable biomarkers for the development of AKI and nullifies urinary IL-18 and KIM-1 in this regard.

Varicella zoster virus and cytomegalovirus co-infection in a live related kidney transplant recipient: a case report

Amit Bari, Nura Afza Salma Begum, Farnaz Nobi, Mamunur Rashid, Mohammad Shakib Uz-Zaman Arefin, Shoeb Nomany, Harun Ur Rashid, Abu Sayed, Sabbirul Islam. Korean J Transplant 2022;36:244. https://doi.org/10.4285/ATW2022.F-3847

Toxicological Outcome of Combined Exposure to Potassium Dichromate and Levonorgestrel in the Kidney of Female Rats

Co-exposure to chromate (VI) compound and oral contraceptives is common in our environment especially among women working in chromate-related industries. Exposure to either chromate (VI) or oral contraceptives is linked with the etiology of several diseases including cancers and renal injury. However, there is paucity of information on the toxic effect of combined co-exposure to both compounds. The present study examines the toxicity of combined exposure to potassium dichromate (PDC) and an oral contraceptive, levonorgestrel in the kidney of female rats. Control animals were fed distilled water, while experimental rats were injected 12 mg/kg body weight of PDC once a week for six weeks and oral daily exposure to 15µg/kg body weight of levonorgestrel either alone or in combination. Absolute and relative kidney weight, renal function, oxidative stress and pathological lesion were assessed in plasma and kidney of control and experimental rats. The PDC and levonorgestrel significantly (p&lt;0.05) increased plasma urea creatinine and malondialdehyde levels in treated-rats, while renal superoxide dismutase and glutathione-S-transferase activities were reduced by both compounds. Moreover, histopathological lesions including necrotizing nephritis was observed in the kidney of PDC-treated rats, while tubular epithelial degeneration and necrosis was observed in levonorgestrel-treated rats. Combined exposure to both compounds aggravated the increase in urea, creatinine and renal damage. Additionally, the antioxidant enzymes were further repressed in the co-treatment group. The study suggests that combined exposure to potassium dichromate and levonorgestrel worsened nephrotoxicity in rats by increasing oxidative stress.

Empagliflozin Is Not Renoprotective in Non-Diabetic Rat Models of Chronic Kidney Disease.

Gliflozins (sodium-glucose transporter-2 inhibitors) exhibited renoprotective effects not only in diabetic but also in non-diabetic patients with chronic kidney disease (CKD). Controversial results were reported in experimental non-diabetic models of CKD. Therefore, we examined empagliflozin effects in three CKD models, namely, in fawn-hooded hypertensive (FHH) rats, uninephrectomized salt-loaded (UNX + HS) rats, and in rats with Goldblatt hypertension (two-kidney, one-clip 2K1C) that were either untreated or treated with empagliflozin (10 mg/kg/day) for eight weeks. Plethysmography blood pressure (BP) was recorded weekly, and renal parameters (proteinuria, plasma urea, creatinine clearance, and sodium excretion) were analyzed three times during the experiment. At the end of the study, blood pressure was also measured directly. Markers of oxidative stress (TBARS) and inflammation (MCP-1) were analyzed in kidney and plasma, respectively. Body weight and visceral adiposity were reduced by empagliflozin in FHH rats, without a significant effect on BP. Experimentally induced CKD (UNX + HS and 2K1C) was associated with a substantial increase in BP and relative heart and kidney weights. Empagliflozin influenced neither visceral adiposity nor BP in these two models. Although empagliflozin increased sodium excretion, suggesting effective SGLT-2 inhibition, it did not affect diuresis in any experimental model. Unexpectedly, empagliflozin did not provide renoprotection because proteinuria, plasma urea, and plasma creatinine were not lowered by empagliflozin treatment in all three CKD models. In line with these results, empagliflozin treatment did not decrease TBARS or MCP-1 levels in either model. In conclusion, empagliflozin did not provide the expected beneficial effects on kidney function in experimental models of CKD.

Mortality and its associated factors in transfused patients at a tertiary hospital in Uganda.

Blood transfusion is life-saving but sometimes also associated with morbidity and mortality. There is limited data on mortality in patients transfused with whole blood in sub-Saharan Africa. We described the 30-day all-cause mortality and its associated factors in patients transfused with whole blood to inform appropriate clinical intervention and research priorities to mitigate potential risks. A retrospective study was performed on purposively sampled patients transfused with whole blood at the Uganda Cancer Institute (UCI) and Mulago hospital in the year 2018. Two thousand twelve patients with a median (IQR) age of 39 (28-54) years were enrolled over a four month period. There were 1,107 (55%) females. Isolated HIV related anaemia (228, 11.3%), gynaecological cancers (208, 10.3%), unexplained anaemia (186, 9.2%), gastrointestinal cancers (148, 7.4%), and kidney disease (141, 7.0%) were the commonest diagnoses. Most patients were transfused with only one unit of blood (n = 1232, 61.2%). The 30 day all-cause mortality rate was 25.2%. Factors associated with mortality were isolated HIV related anaemia (HR 3.2, 95% CI, 2.3-4.4), liver disease (HR 3.0, 95% CI, 2.0-4.5), kidney disease (HR 2.2, 95% CI, 1.5-3.3; p<0.01), cardiovascular disease (HR 2.9, 95% CI, 1.6-5.4; p<0.01), respiratory disease (HR 3.0, 95% CI 1.8-4.9; p<0.01), diabetes mellitus (HR 4.1, 95% CI, 2.3-7.4; p<0.01) and sepsis (HR 6.2, 95% CI 3.7-10.4; p<0.01). Transfusion with additional blood was associated with survival (HR 0.8, 95% CI 0.7-0.9, p<0.01). In conclusion, the 30-day all-cause mortality was higher than in the general inpatients. Factors associated with mortality were isolated HIV related anaemia, kidney disease, liver disease, respiratory disease, cardiovascular disease, diabetes mellitus and sepsis. Transfusion with additional blood was associated with survival. These findings require further prospective evaluation.

Nephroprotective and Antioxidant Effects of Flavonoid-Rich Extract of Thymelaea microphylla Coss. et Dur Aerial Part

Thymelaea microphylla Coss. et Dur (T. microphylla), a medicinal herb that grows in arid and desert pastures, has been traditionally utilized by Moroccans to treat many diseases, including kidney failure. This study aims to evaluate the nephroprotective effect against gentamicin-induced nephrotoxicity (GM), and thus the antioxidant activity of an aqueous extract rich in flavonoids from the aerial part of T. microphylla (APTM). The antioxidant activity of APTM was assessed using the 2-2-diphenyl-1-picrylhydrazyl (DPPH) scavenging test and the β-carotene bleaching assay. The nephroprotective effect of this extract was evaluated in two doses of 200 and 400 mg/kg in GM-exposed male rats. Acute toxicity of the APTM was tested out on Swiss albino mice using 2000 mg/kg as the dose limit. The findings showed that the aqueous extract of APTM is abundant in total polyphenols and flavonoids and has significant antioxidant properties against DPPH radicals and β-carotene oxidation. According to the acute toxicity research findings, the administered doses of the APTM extract do not cause toxicity and death. A significant increase in the serum concentrations of creatinine, urea, uric acid, sodium, chloride, calcium, gamma-glutamyl transpeptidase (gamma-GT), and alkaline phosphatase, as well as an increase in urinary volume, water consumption, and relative kidney weight, were all caused by the administration of GM to rats. In addition, a significant reduction in urinary concentrations of creatinine, uric acid, urea, and albumin, and thus the clearance of creatinine and weight gain were observed in rats injected with GM. Also, the administration of GM dramatically raised the malondialdehyde level in the kidneys. Likewise, rats that had been poisoned with GM had histological kidney abnormalities. However, the daily treatment of APTM aqueous extract to rats given GM injections dramatically improved the biochemical and histological parameters affected by GM administration in rats. Finally, APTM extract enhanced GM’s biochemical and histological indicators of nephrotoxicity, supporting its use as an ethnomedicinal.

Nephroprotective Effects of Polyherbal Formulation on Gentamicin-induced Toxicity in Wistar Rats

Effect of a polyherbal formulation (polyherbal alcoholic extract; PAE) prepared from Withania somnifera (root), Aegle marmelos (leaves), Tribulus terrestris (fruit) was studied on gentamicin-induced nephrotoxicity. Thirty Wistar rats were equally divided into five groups; group I (control), group II (gentamicin alone), group III (prophylactic), group IV (curative) and group V (formulation alone). Gentamicin caused signs of depression, dullness, polyurea, restlessness, reduced body weight, and reduced water and feed intake. These toxicity signs were recovered in the PAE pre-treated prophylactic group; however, in the PAE-treated therapeutic group, some mild toxicity signs were noticed and subsided gradually. Gentamicin increased relative kidney weight but in groups III and IV animals, no significant effect was observed. The Hb, PCV, TEC, TLC and MCV of group II animals revealed a significant decrease, whereas; BUN, creatinine, AST, ALT, ALP, total protein, albumin and globulin were significantly increased. The PAE treatment caused significant recovery in these hematobiochemical parameters in groups III and IV. Gentamicin caused histopathological alterations in kidney represented by focal renal degenerative and necrotic changes, with intratubular hyaline cast. In PAE-treated groups III and IV, minimal histopathological alterations were seen. In conclusion, PAE showed significant protective and moderate therapeutic potential against gentamicin-induced nephrotoxicity in Wistar rats.

Feto-maternal outcome of pregnancy related acute kidney injury in a North Indian population.

Acute kidney injury (AKI) is a serious complication in pregnancy, resulting in significant maternal and fetal morbidity/mortality. The aim of this study was to evaluate the magnitude of pregnancy-related AKI (PRAKI) in a North Indian population, and its contributing factors. This prospective study was carried out at the department of obstetrics and gynecology in collaboration with the nephrology unit and internal medicine department at King George Medical University from June 2019 to October 2020. After informed consent and ethical clearance, a total of 150 PRAKI women were enrolled, and 98 women were subjected to renal replacement therapy as per Kidney Disease Improving Global Outcomes 2012 guideline and were followed for 3 months for renal and fetomaternal outcome. There was a high incidence (1.02%) of AKI during pregnancy and puerperium. Majority (57.3%) of the women were aged 26-30 years, and 93.3% had institutional deliveries. About 49% of the women suffering from PRAKI were multipara, and most were identified in the postpartum period (82%). Hypertensive disorder of pregnancy (48%), puerperal sepsis (45%), and hemorrhage (34%) were the associated causes for PRAKI. Stillbirth/intrauterine death (IUD) was higher in Stage II (53.8%) and Stage III AKI (37.7%) (none in Stage I AKI). The majority of the neonates were born with a birth weight of ≤2500 g irrespective of the stages of AKI. Preterm deliveries were significantly higher in Stage II AKI (53.8%) than in Stage I (33.3%) and Stage III (20.0%). Thirty-seven cases of PRAKI were managed conservatively, while 98 required dialysis. Complete recovery occurred in 27.3% and partial renal recovery in 31.3%. However, 3.3% progressed to chronic kidney disease, 34% expired, and 4% were lost to follow-up. High maternal mortality of 30.1% was observed in those dialyzed. AKI is associated with fetal growth restriction and preterm deliveries. Stillbirth/IUD is higher in Stage II and Stage III AKI.