Related Kidney Research Articles

Association between relative fat mass and kidney stones in American adults

Our study aimed to investigate the association between RFM and kidney stones, focusing specifically on the mediating role of high-density lipoprotein cholesterol (HDL-C). We performed a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) covering the years 2007 to 2018. Our analytical approach included multivariate logistic regression modeling, subgroup analysis, generalized additive modeling (GAM), smoothed curve fitting, and receiver operating characteristic (ROC) curve, as well as mediation analysis to assess the association between RFM and kidney stones. Finally, we categorized RFM into normal and elevated groups to conduct a sensitivity analysis. This study involved 29,712 participants, with a kidney stone prevalence of 9.88%. We discovered a positive association between RFM and kidney stones (OR = 1.41 per SD increment, 95% CI: 1.24, 1.60). Subgroup analysis revealed a consistent positive association across all subgroups, with a notably higher likelihood of developing kidney stones in young adulthood (P for interaction < 0.05). The smooth curve fitting shows that RFM is nonlinearly and positively correlated with the prevalence of kidney stones. Additionally, HDL-C was found to be negatively associated with kidney stones. Importantly, HDL-C demonstrated a significant mediating effect, with a mediation ratio of 13.52%. ROC analysis indicated that RFM (AUC = 0.616) provided better diagnostic accuracy than traditional measures such as BMI (AUC = 0.565) and WC (AUC = 0.599). Furthermore, the sensitivity analysis further supports the robustness of our findings. RFM is nonlinearly and positively correlated with the prevalence of kidney stones, with HDL cholesterol playing a significant mediating role in this relationship. However, further studies are needed to confirm these associations and explore potential mechanisms.

Ameliorative effect of rutecarpine supplementation against cisplatin-induced nephrotoxicity in rats via inhibition of monocyte chemoattractant protein-1, intercellular adhesion molecule-1, high-mobility group box 1, and nuclear factor kappa B.

Cisplatin, the pioneering heavy metal compound, stands out as a potent drug for the treatment of various solid tumors. However, its clinical utility is hampered by notable toxicity and adverse effects, particularly nephrotoxicity. The potency of rutecarpine, a phytochemical, in mitigating cisplatin-induced nephrotoxicity was assessed in the present study. In this experimental setup, healthy male Wistar rats were grouped into four and Group I rats served as the control group, receiving only vehicle control. Group II rats were subjected to cisplatin treatment alone, administered intraperitoneally at a dosage of 7mg/kg body weight on the 19th, 20th, and 21st days. Group III and IV rats were orally administered with rutecarpine at doses of 10 and 20mg/kg body weight, respectively, starting from Day 1 and continuing daily for 21 days. Additionally, they were injected intraperitoneally with cisplatin at the same dosage and schedule as Group II. Relative kidney weight and renal biochemical markers blood urea nitrogen, lactate dehydrogenase, serum urea, and creatinine were measured to assess rutecarpine inhibitory potency against cisplatin toxicity. Markers of oxidative damage and antioxidants levels were quantified in the ruteacarpine- and cisplatin-treated rats. The study investigated the anti-inflammatory property of rutecarpine in cisplatin-induced nephrotoxicity by analyzing inflammatory cytokines. Renal tissue levels of monocyte chemoattractant protein-1, intercellular adhesion molecule-1, high-mobility group box 1, and nuclear factor kappa B, key markers of nephrotoxicity, were quantified to assess rutecarpine's potential to mitigate cisplatin-triggered damage. Histopathological examinations were performed to confirm the impact of rutecarpine against cisplatin-induced nephrotoxicity. Treatment with rutecarpine notably reduced renal biochemical markers, prevented renal edema, and attenuated oxidative stress-induced damage in cisplatin-treated rats. Both inflammatory and nephrotoxicity markers showed significant decreases in rats treated with rutecarpine along with cisplatin. Histological analysis affirmed that rutecarpine pretreatment effectively prevented cisplatin-induced nephrotoxicity. The study findings demonstrate that rutecarpine ameliorates cisplatin-triggered nephrotoxicity through its antioxidant and anti-inflammatory properties, suggesting that rutecarpine supplementation alongside cisplatin treatment could potentially reduce nephrotoxicity in cancer patients.

Kidney volume and function of low-birth-weight children at 5years: impact of singleton and twin birth.

Many studies have demonstrated the association between low birth weight (LBW) and chronic kidney disease, estimated glomerular filtration rate (eGFR) and kidney volume (KV). However, studies on twins and those investigating numerous perinatal factors beyond LBW, and their associations with various kidney parameters are scarce. A two-center cross-sectional study on five-year-old LBW children was conducted between 2021 and 2023. 110 children were enrolled (8 LBW, 58 very LBW (VLBW), 44 extremely LBW (ELBW)); 56 were twins. We examined associations between birth weight (BW), various prenatal, perinatal and postnatal factors, and eGFR, KV, tubular abnormalities and kidney ultrasound abnormalities, both in singletons and twins. In children with ELBW, eGFR correlated with BW (r = 0.55, P = 0.0018), while in those with BW ≥ 1000g, eGFR remained constant. Other factors associated with decreased eGFR were hypertensive disorder of pregnancy (93.86 vs. 87.26ml/min/1.73m2, P = 0.0285) in singletons, decreased growth velocity (β = 0.83, P = 0.0277) in twins, and lower total KV (tKV) and relative KV (rKV) in both singletons (r = 0.60, P < 0.0001 for tKV and r = 0.45, P = 0.0010 for rKV) and twins (β = 0.34, P < 0.0001 for tKV and β = 0.23, P = 0.0002 for rKV). Based on the multivariable models excluding KV, BW and gestational age were associated with eGFR in singletons, while male gender, BW, growth velocity, and coffee drinking during pregnancy were associated with eGFR in twins. However, in models that included KV, BW, gestational age and growth velocity were no longer significant. Total KV was associated with BW (r = 0.39, P = 0.0050 for singletons; β = 2.85, P < 0.0001 for twins), body mass index (r = 0.34, P = 0.0145 for singletons; β = 8.44, P < 0.0001 for twins), and growth velocity (β = 1.43, P = 0.0078). Twins born small for gestational age had lower tKV (70.88 vs 89.20ml, P < 0.0001). Relative KV showed similar associations. Relative kidney volumes were significantly lower for both kidneys compared to the reference population (55.02 vs 65.42ml/m2, P < 0.0001 for right kidney and 61.12 vs 66.25ml/m2, P = 0.0015 for left kidney); however, only 8.6% of children had rKV below 10th percentile. Many factors affect eGFR and KV, some of them differ between twins and singletons. Based on multivariable models, eGFR seems to be better predicted by KV than by BW and gestational age in LBW children. Relative kidney volumes were significantly lower in our cohort compared to the reference population, but only 8.6% of rKV were below 10th percentile.

A low-dose pemetrexed-cisplatin combination regimen induces significant nephrotoxicity in mice

BackgroundPemetrexed is combined with cisplatin to treat cancer. Whether pemetrexed-cisplatin combination chemotherapy exacerbates cisplatin nephrotoxicity is unclear. Here, we investigated kidney injury in mice administered a non-lethal low-dose regimen of pemetrexed or cisplatin alone and compared it with a pemetrexed-cisplatin combination.MethodsMice were randomly divided into four groups and administered intraperitoneally the experimental drugs solubilized in captisol (sulfobutylether β-cyclodextrin). Group 1 received captisol, Group 2 pemetrexed (10 mg/kg), Group 3 cisplatin (1 mg/kg), and Group 4 pemetrexed (10 mg/kg) plus cisplatin (1 mg/kg). The mice were treated every other day for two weeks, three times per week. Glomerular filtration rate (GFR) was determined on the third day after the last treatment, followed by a necropsy.ResultsWhereas the relative kidney weight was comparable in the control vs. pemetrexed or cisplatin alone group, it was significantly increased in the combination group. Mice treated with cisplatin and pemetrexed-cisplatin combination exhibited reduced GFR. The pemetrexed-cisplatin combination caused significant increases in the plasma or urinary levels of kidney injury biomarkers, renal lipid peroxidation, and nitrosative stress compared with pemetrexed or cisplatin alone. Histopathology revealed that pemetrexed or cisplatin alone had minimal effects on the kidneys. By contrast, the pemetrexed-cisplatin combination caused tubular degeneration, dilatation, and granular casts. Live-cell imaging showed that the pemetrexed-cisplatin combination caused more severe apoptosis of primary renal epithelial cells than individual concentrations.ConclusionsThese findings suggest that combining pemetrexed and cisplatin causes oxidative kidney damage at individual doses that do not cause significant nephrotoxicity. Hence, the renal function of patients undergoing treatment with the pemetrexed-cisplatin combination needs extensive monitoring.

Frequency of adverse perinatal outcomes in patients with pregnancy related acute renal (kidney) injury in a tertiary care hospital

Background &amp; Objective: Pregnancy related acute kidney injury (Pr-AKI) is coupled with adverse feto-maternal outcomes. Adverse perinatal outcome comprising of still births, intrauterine growth retardation, neonatal deaths are indicators of severity of underlying obstetrical conditions ending on Pr-AKI. These perinatal outcomes can also serve as potential predictors for long term outcomes of Pr-AKI. Our study aimed to determine frequencies of adverse perinatal outcomes and to evaluate adverse perinatal outcome as predictor for persistent renal injury in patients with pregnancy induced acute renal injury (Pr-AKI). Method: A descriptive case series including 100 women with Pr-AKI, was conducted in a tertiary care hospital of Peshawar from 1st August 2021 to 31st July 2022. Included patients were followed for three months period, from their date of delivery. Adverse perinatal outcome included stillbirths, and early neonatal deaths. Results: The mean age of study sample was 29.20±6.40. The pre dominant etiology for Pr-AKI was primary postpartum hemorrhage, occurring in 52% women. Still births were seen in 48% cases, while early neonatal deaths were seen in 7% cases. Adverse perinatal outcome had statistically significant association with persistent renal failure (p-0.01). Other factors having statistically significant association with persistent renal injury (PRF) were multiparity and cesarean births. (p&lt;0.05) Association of adverse perinatal outcome with persistent renal injury persisted on multivariate logistic regression. a OR 6.14; CI 1.15-32.29, p-0.033. Conclusion: Almost half of the cases with Pr-AKI have still births. Still birth in patients with Pr-AKI is associated with persistent renal injury at 12 weeks follow up period. doi: https://doi.org/10.12669/pjms.40.10.9228 How to cite this: Mohammad N, Qazi Q, Liaqat N. Frequency of adverse perinatal outcomes in patients with pregnancy related acute renal (kidney) injury in a tertiary care hospital. Pak J Med Sci. 2024;40(10):2267-2270. doi: https://doi.org/10.12669/pjms.40.10.9228 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

9210 Nephron specific ATP6AP2 knockout reduces renal fat accumulation in mice consuming high fat diet

Abstract Disclosure: S.A. Culver: None. J. Balugo: None. M. Jansen: None. T. Harris: None. H.M. Siragy: None. Diet induced obesity causes increased renal fat accumulation in both humans and mice which contributes to obesity related kidney injury. We have previously shown that mice with nephron specific ATP6AP2 knockout (KO) consuming high fat diet (HFD) are resistant to weight gain due to increased urinary excretion of glucose, albumin, and fatty acids. Magnetic resonance imaging (MRI) is a useful imaging modality for quantifying organ fat content in live animals though there are few reports of its use quantifying fat in murine kidney. We hypothesized that nephron specific ATP6AP2 knockout inhibits renal fat accumulation with HFD and that we would be able to detect this using MRI. Eight-week-old male wild type (WT) or inducible nephron specific ATP6AP2 KO mice underwent either induction with oral doxycycline or received sucrose water as controls before being placed on either normal diet (ND) (12% fat) or HFD (45% fat) for 3 months. Mice were then imaged using a 9.4 Tesla Bruker BioSpin MRI to determine both liver and kidney cortex fat content. The mean weight of WT HFD mice was 36.03 g compared to 29.03 g in WT ND controls. ND fed and HFD fed KO mice weighed 22.74 g and 23.03 g respectively. MRI showed significant 67% (p&amp;lt;0.05) increase in liver fat content in WT HFD compared to WT ND fed controls, confirming the ability of our MRI technique to detect expected differences in organ fat content. In renal cortex, MRI detected a 54% (p&amp;lt;0.05) increase in lipid content for WT HFD mice compared to WT ND controls. Nephron specific ATP6AP2 KO on HFD demonstrated reduced renal cortical lipid content by 36% (p&amp;lt;0.05) compared to WT HFD controls. These results indicate that ATP6AP2 KO is associated with reduced renal fat accumulation that is measurable with in vivo MRI. MRI therefore represents a valuable tool for studying renal sequelae of obesity in live murine models. Future investigation should examine whether ATP6AP2 KO prevents renal lipotoxicity and kidney injury in the setting of obesity. Presentation: 6/3/2024

Kidney toxicology of a novel compound Lithium Bis(trifluoromethanesulfonyl)imide (LiTFSI, ie. HQ-115) used in energy applications: An epigenetic perspective

Exposure to emerging energy-based environmental contaminants such as lithium bis(trifluoromethanesulfonyl)imide (LiTFSI, trade name HQ-115), poses a significant threat to human health, yet its impact on kidney function and epigenetic regulation remains poorly understood. Here, we investigated the effects of LiTFSI exposure on kidney-related biochemical indicators, renal injuries, and epigenetic alterations in male CD-1 mice under both 14-day and 30-day exposure durations. Our study revealed that LiTFSI exposure led to changes in kidney-related markers, notably affecting serum bicarbonate levels, while relative kidney weight remained unaffected. Histological analysis revealed tubule dilation, inflammation, and loss of kidney structure in LiTFSI-exposed mice, alongside dysregulated expression of genes associated with inflammation, renal function, and uric acid metabolism. Epigenetic analysis further identified widespread DNA methylation changes in the two exposure regimes. Functional analysis revealed that differentially methylated regions are implicated in cell apoptosis and cancer-related pathways and are enriched with development-related transcription factor binding motifs, suggesting a potential mechanism of action underlying exposure induced kidney damage. These findings underscore the intricate interplay between environmental exposures, epigenetic modulation, and kidney health, emphasizing the need for additional research to unravel precise mechanisms and develop targeted interventions to mitigate the adverse effects of LiTFSI and exposure of similar clean energy compounds on human health.

Paving the way ahead: protocol optimization of mouse models in crush syndrome related acute kidney injury research.

Crush syndrome (CS) is the leading cause of death after earthquakes, second only to direct trauma. Acute kidney injury (AKI) is the most severe complication of CS. Research based on the CS-AKI mouse model and kidney function assessment by glomerular filtration rate (GFR) helps to elucidate the pathogenesis of CS-AKI, which contributes to effective treatment measures. Mice were modeled by the multi-channel small animal crushing platform. We set up different CS-AKI modeling parameters by applying different crushing weights (0.5 kg, 1.0 kg, 1.5kg), crushing durations (6 h, 12 h, 16h), and decompression durations (6 h, 12 h, 24h). The GFR, serum creatinine (SCr), blood urea nitrogen (BUN), kidney tissue Kim-1 mRNA and Ngal mRNA expression levels, and HE staining were examined to evaluate the results of different protocols. The results showed that with the crushing weight increased, the kidney function assessment's gold standard GFR significantly decreased, and the levels of SCr and BUN increased. Meanwhile, the longer crushing durations found a higher extension of inflammatory cell infiltration in the kidney. The degree of kidney injury continued to worsen with the duration of decompression, indicating severe damage after reperfusion, which was associated with tubular injury and a sustained elevation of the inflammatory state. We successfully constructed CS-AKI mouse models with different severities under the above parameters. Applying 1.5kg for 16h and then decompressing for 24h induced severe AKI. These findings provide clues for further exploration of the mechanism and treatment of traumatic AKI.

New perspectives of drug related kidney diseases and disorders.

The aim of this review is to provide a discussion of new perspectives for up-to-date definitions, a contemporary classification system, and the potential role of stress and damage biomarkers in the context of drug related kidney diseases and disorders. Acute kidney disease (AKD) is a term recently introduced in the literature describing an abnormality in kidney structure and function that lasts for less than 3 months. Drugs in the context of AKD is described as a new perspective; referred to as drug induced AKD. A framework that includes drugs into the 2X2 classification schema for acute kidney injury (AKI) is provided. Finally, stress and damage biomarkers are examined to assess risk of drug associated AKI (D-AKI), differentiate which drugs cause AKI, differentiate drugs from other etiologies and assess the prognosis of D-AKI. Consistent definitions should be adopted with consideration to drug related diseases and disorders. Drug management can be guided using novel biomarkers to isolate a possible drug cause in the presence of more than one nephrotoxin or a nondrug cause, assisting with the diagnosis of pseudo-AKI, and deciding the likelihood AKI recovery. Furthermore, stress and damage kidney biomarkers provide the opportunity to detect subclinical AKI for early intervention in patients at high-risk for severe AKI.

The impact of pulmonary hypertension on the risk of early graft dysfunction in related kidney transplantation

Introduction. Pulmonary hypertension is a common complication among patients with end-stage renal disease and has a significant impact on the outcome of kidney transplantation, including during kidney transplantation from a living related donor.Objective. To study the prevalence of pulmonary hypertension among patients with end-stage renal disease and to determine its impact on the development of early renal graft dysfunction.Material and methods. The study was based on the analysis of treatment results in 650 patients who underwent kidney transplantation from a living related donor. Depending on the graft function, 2 groups of patients were identified: group I consisting of patients with early renal graft dysfunction (n=82); group II (n=79) that included the patients with a primary graft function who were selected by demographic and clinical laboratory data statistically comparable to patients of group I (p&gt;0.5). This allowed us to equalize the chances of achieving the study endpoint (early graft dysfunction). Transthoracic echocardiography was performed in all patients, with the calculation of the mean pulmonary artery pressure. The relative risk of early renal graft dysfunction was calculated depending on the presence of pulmonary hypertension and its severity.Results. Among group I patients, pulmonary hypertension was detected in 97.56% of cases (mean pulmonary artery pressure 48.26±18.63 mmHg), versus 86.08% in patients with a primary graft function (mean pulmonary artery pressure 31.92±16.11 mmHg) (p&lt;0.001). The presence of mild pulmonary hypertension increased the relative risk of early graft dysfunction by 2.58 times (95% CI [0.698-9.547]; p=0.174), moderate by 3.18 times (95% CI [0.860-11.764]; p=0.064), severe by 5.91 times (95% CI [1.644-21.241]; p&lt;0.001) compared with patients without pulmonary hypertension.Conclusions. When performing kidney transplantation from a living donor, the presence of severe pulmonary hypertension in the recipient is associated with an increased risk of early graft dysfunction. This suggests that pulmonary hypertension may be one of the modifiable risk factors for this complication.

HLA tailored immunosuppression in living related pediatric kidney transplants in a low-income country. Cost and survival benefits

HLA tailored immunosuppression in living related pediatric kidney transplants in a low-income country. Cost and survival benefits

222.1: Nocardiosis in living related donor kidney transplant recipients: A study from a low income country.

222.1: Nocardiosis in living related donor kidney transplant recipients: A study from a low income country.

P.311: Outcomes of living related kidney donors in a tertiary care liver and kidney transplant facility of a developing country.

P.311: Outcomes of living related kidney donors in a tertiary care liver and kidney transplant facility of a developing country.

Highly selective optical and naked-eye recognition of L-cystine through spectroscopy and development of cellulose paper nano biosensor test strips for the early diagnosis of cystinuria

Accurate sensing of small biomolecules from complex biofluid media remains a challenge due to adverse interaction of metallic salts and other biofluid components. L-cystine is the most important biomarker for the disease cystinuria. Recognition of L-cystine in urine is thus fundamental for the timely detection of cystinuria and related chronic kidney disease (CKD). Poor solubility of L-cystine offer limits to design suitable sensors. Herein, we report the synthesis of thioglycolated-β-CD (TG-β-CD) anchored silver nanoparticles (AgNP) as a potential receptor (TG-β-CD⊃AgNP) for the effective optical recognition and quantification of L-cystine through UV–Vis and SERS (surface enhanced Raman spectroscopy) spectroscopic fingerprinting and suitable colourimetric naked-eye detection of L-cystine by indicator displacement assay. Methyl orange (Met-O) indicator was precomplexed with the receptor to generate the probe solution (Met-O@TG-β-CD⊃AgNP). Indicator has been exchanged from Met-O@TG-β-CD⊃AgNP by the addition of L-cystine, with an instantaneous visible colour change from yellow to red. The method is tolerable to other interfering abundant ions and biomolecules. Based on the innovative sensing assay a cellulose paper-dye test strip is developed for point-of-care detection and quantification of the biomarker. Structures of TG-β-CD, TG-β-CD⊃AgNP and Met-O@TG-β-CD⊃AgNP were elucidated by UV–Vis, FT-IR, PXRD, 1H NMR, etc. spectroscopy. Scanning electron microscopy (SEM) was used to examine the morphology of TG-β-CD, AgNP and TG-β-CD⊃AgNP. The chemical changes during the assay were evaluated by conductance, UV–Vis and SERS. The competitive displacement of the indicator and UV turn-on at ppm level analyte concentration made the process compatible for day-to-day point-of-care units.

Proteomic analysis of laser captured tubular tissues reveals complement activation and mitochondrial dysfunction in autoimmune related kidney diseases

Autoimmune related kidney diseases (ARKDs), including minimal change nephropathy (MCN), membranous nephropathy (MN), IgA nephropathy (IgAN), and lupus nephritis (LN), significantly affect renal function. These diseases are characterized by the formation of local immune complexes and the subsequent activation of the complement system, leading to kidney damage and proteinuria. Despite the known patterns of glomerular injury, the specific molecular mechanisms that contribute to renal tubular damage across ARKDs remain underexplored. Laser capture microdissection and liquid chromatography–tandem mass spectrometry (LC–MS/MS) were used to conduct a comparative proteomic analysis of renal tubular tissues from formalin-fixed paraffin-embedded samples. The cohort comprised of 10 normal controls (NC), 5 MCN, 4 MN, 17 IgAN, and 21 LN patients. Clinical parameters and histopathological assessments were integrated with proteomic findings to comprehensively investigate underlying pathogenic processes. Clinical evaluation indicated significant glomerular damage, as reflected by elevated urinary protein levels and reduced plasma albumin levels in patients with ARKD. Histological analyses confirmed varying degrees of tubular damage and deposition of immune complexes. Proteomic analyses identified significant changes in protein expression, particularly in complement components (C3, C4A, C4B, C8G, CFB, and SERPINA1) and mitochondrial proteins (ATP5F1E and ATP5PD), highlighting the common alterations in the complement system and mitochondrial proteins across ARKDs. These alterations suggest a novel complement–mitochondrial–epithelial–mesenchymal transition (EMT) pathway axis that contributes to tubular damage in ARKDs. Notably, significant alterations in CFB in tubular ARKD patients were revealed, implicating it as a therapeutic target. This study underscores the importance of complement activation and mitochondrial dysfunction in the pathogenesis of ARKDs, and proposes CFB as a potential therapeutic target to inhibit complement activation and mitigate tubular damage. Future research should validate the complement-mitochondrial-EMT pathway axis and explore the effects and mechanisms of CFB inhibitors in alleviating ARKD progression.

Piezo ion channels: long-sought-after mechanosensors mediating hypertension and hypertensive nephropathy.

Recent advances in mechanobiology and the discovery of mechanosensitive ion channels have opened a new era of research on hypertension and related diseases. Piezo1 and Piezo2, first reported in 2010, are regarded as bona fide mechanochannels that mediate various biological and pathophysiological phenomena in multiple tissues and organs. For example, Piezo channels have pivotal roles in blood pressure control, triggering shear stress-induced nitric oxide synthesis and vasodilation, regulating baroreflex in the carotid sinus and aorta, and releasing renin from renal juxtaglomerular cells. Herein, we provide an overview of recent literature on the roles of Piezo channels in the pathogenesis of hypertension and related kidney damage, including our experimental data on the involvement of Piezo1 in podocyte injury and that of Piezo2 in renin expression and renal fibrosis in animal models of hypertensive nephropathy. The mechanosensitive ion channels Piezo1 and Piezo2 play various roles in the pathogenesis of systemic hypertension by acting on vascular endothelial cells, baroreceptors in the carotid artery and aorta, and the juxtaglomerular apparatus. Piezo channels also contribute to hypertensive nephropathy by acting on mesangial cells, podocytes, and perivascular mesenchymal cells.

Factors Responsible for Nonselection of Donors in Living Related Kidney Transplantation.

Living donor kidney transplant is the preferred method of renal transplant in Pakistan as deceased donor transplant has not yet been estab-lished. However, many patients who are dialysis-dependent, particularly younger patients, lack suitable living related donors. We aimed to determine factors contributing to nonselection of donors for living related renal transplant in Pakistan. For this cross-sectional study, we included patients seen at the Sindh Institute of Urology & Transplantation Karachi, Pakistan) from March to November 2019. Potential donors were adult family members who accompanied patients with end-stage kidney disease to the clinic. Demographic and clinical information were recorded on predesigned proforma. After workup and baseline investigations had been completed, potential living related donors were selected. Factors leading to nonselection of donors were noted for those who did not qualify for donation. We used SPSS version 20 for analysis. During the study period, 253 potential donors (151 males, 102 females) with mean age of 35.68 ± 6.14 years were found to be ineligible for kidney donation. ABO incompatibility was the most common factor leading to nonselection (n = 101; 39.92%), followed by diabetes mellitus (n = 71; 28.06%), hypertension (n= 50; 19.76%), renal disease (n = 15; 5.92%), liver disease (n = 8; 3.16%), crossmatch positive (n = 5; 1.97%), and ischemic heart disease (n = 3; 1.18%). No differences were shown between potential male and female donors regarding factors leading to nonselection; diabetes was significantly more prevalent among those <40 years of age (P = .025). ABO incompatibility, diabetes mellitus, and hypertension were the most common factors leading to nonselection of potential donors in living related kidney transplant. More efforts are needed to expand the donor pool by considering second- or third-degree relatives to tackle the scarcity of organs for transplantation.

Safety outcomes of remdesivir for treatment of COVID-19 hospitalised patients in Indonesia

Background: Remdesivir has been granted emergency use authorisation for hospitalised COVID-19 patients. However, the available evidence in Indonesia is limited to related liver and kidney injuries. Objective: This study aims to assess the safety of remdesivir based on liver and kidney function and its association with comorbidity and disease severity. Method: This retrospective study evaluated remdesivir's efficacy in hospitalised COVID-19 patients of varying severity by collecting baseline and follow-up data on aspartate aminotransferase (AST), alanine aminotransferase (ALT), Glomerular filtration rate (GFR) and Blood urea nitrogen (BUN). Result: In this study, 189 patients with elevated transaminase enzyme levels were given hepatoprotection therapy. Patients who did not receive the treatment experienced a significant rise in ALT levels (p &lt; 0.001), while BUN levels increased significantly (p = 0.001) but within the normal range. There was no worsening of GFR value (p &lt; 0.001), and no significant association was found between AST and ALT levels with comorbidity and disease severity (p &lt; 0.001; OR 50.202). Conclusion: Remdesivir demonstrated good tolerability despite increased ALT and BUN without correlating to comorbidity or disease severity in COVID-19.

#363 Altered filtration of middle-sized molecules is related to cardiovascular disease-related proteins

Abstract Background and Aims Cardiovascular (CV) complications, driven by complex vascular-metabolic interactions, are the leading cause of frailty in chronic kidney disease (CKD) complications. Advancing knowledge on cardio-renal interactions is a key to preventive and treatment strategies. Still, the cost-effective tools and biomarkers for early detection of altered glomerular filtration that subsequently leads to accelerated cardiovascular aging and, thus, higher CV mortality are lacking. Our objective was to investigate how molecules of varying masses, specifically cystatin C and creatinine, are filtered in kidney in relation to variations of plasma protein levels that might accelerate vascular changes, ultimately leading to early vascular aging and chronic kidney disease (CKD). Method From the Malmo Diet Cancer cohort, 4426 out of the 5061 participants had cardiovascular and renal biomarkers measured (mean age of 57 ± 6 years). These biomarkers included factors related to tissue growth and repair (EGFR), matrix metalloproteinases (MMP-12), proinflammatory cytokines (TNF-R1, TNF-R2, CXCL13, CXCL5), markers of vascular repair (SCF), homeostatic cytokines (CCL19), anti-apoptotic proteins (REG-4), adipokines (FABP4, LEP), as well as other cardiovascular proteins (NT-pro-BNP, MB) and indicators of kidney function. These 13 proteins were analyzed using multiplex proximity extension assay (Olink Cardiovascular II and Oncology panels), and have molecular masses either like creatinine (0.113 kDa) or cystatin C (13.3 kDa). These proteins were previously shown to be associated with measured glomerular filtration rate (mGFR) by Christensson A et al. (Proteomics Clin App, 2018). Kidney function was estimated by using cystatin C (CAPA, CKD-EPIcys) and creatinine (Lund-Malmo revised, CKD-EPIcr) equations. The filtration ratio was presented as CAPA/LMrev and CKD-EPIcys/CKD-EPIcr. The subgroups of this ratio were &amp;lt;0.70. Results Mean kidney function was as follows: 65 (±15)/ 69 (±16)/ 78 (±13) and 76 (±14) mL/min/1.73 m2 (CAPA/ CKD-EPIcys/ LMrev and CKD-EPIcr, respectively). The CAPA/LMrev filtration ratio was 0.84 (±0.18), whereas CKD-EPIcys/cr was 0.91 (±0.19). The filtration ratio negatively correlated with TNF-R1, TNF-R2, SCF, MMP-12, FABP4, LEP, NT-pro-BNP, CCL19, CXCL5, CXCL13 and REG-4; positively to EGFR and MB (all p &amp;lt; 0.001). In the whole cohort, participants with filtration ratio below 0.7 had significantly higher levels of TNF-R1, TNF-R2, MMP12, FABP4, LEP, NT-pro-BNP, CCL19, REG-4, and CXCL13, but similar levels of EGFR. CXCL5 and SCF levels were higher at &amp;lt;0.70 compared to 0.84-0.99 and &amp;gt;1.0 (Fig. 1). Interestingly, in women, MB was highest at &amp;lt;0.70; SCF level was higher at &amp;lt;0.70 compared to 0.84-0.99 and &amp;gt;1.00; EGFR level was highest at 0.70-0.84 compared to 0.84-0.99. In men, higher FABP4, LEP, CCL19, and MB were observed at &amp;lt;0.70 compared to 0.84-0.99 and &amp;gt;1.00. Conclusion Altered glomerular filtration for middle-sized molecules is related to the accumulation of plasma proteins that have similar molecular mass to creatinine and cystatin C and have sex-specific patterns. The proteins studied have been previously shown to contribute to vascular aging, cardiac damage and remodeling, and chronic kidney disease, and thus enlighten complex mechanisms behind cardio-renal interactions.

#1640 Alternative complement pathway disorders in the transplant setting—experience from a large volume center

Abstract Background and Aims Complement alternative pathway disorders, atypical hemolytic-uremic syndrome (aHUS) and C3 glomerulopathy (C3G), are rare diseases with a high rate of recurrence after kidney transplantation. Due to limited availability of testing, patients may go undiagnosed, indicating testing during pretransplant evaluation. Posttransplant thrombotic microangiopathy (TMA) is a rare complication of transplantation. A large number of post transplant TMAs is regarded as secondary, either to immunosuppressive drugs or transplant itself. In select cases, complement alternative pathway disorders analysis is warranted. Method We retrospectively reviewed all patients in whom complement system diagnostic work-up was performed in the transplant setting in our center, from 2017 to 2022. Complement system analysis in isolated histological TMA of the allograft, without extrarenal manifestations and with known cause of native kidneys ESRD, was not performed routinely. Patients in whom alternative pathway disorders were confirmed were compared with those with no abnormalities detected by complement system analysis. Results 12 patients were identified, 75% male, median age 39.5 years (IQR 28-60.25). 8 patients were evaluated before transplantation. 4 of the 8 patients were referred for transplantation with diagnosed aHUS. Genetic testing was used for recurrence risk stratification. In living donor transplantations 2 donors were tested as well. One patient was referred from a neighboring resource poor country and was not on eculizumab therapy. He was homozygous for a high risk causative mutation. He was declined for living related donor kidney transplant, due to risk to the donor and unavailability of eculizumab. Compassionate use request was initiated. One patient was referred as possible C3G and repeat complement analysis revealed elevated C3Nef. Out of 3 patients, previously diagnosed as CKD of unknown origin or immune complex-mediated membranoproliferative glomerulonephritis, 2 were diagnosed during pretransplant evaluation: one as C3G and the other as aHUS. 4 patients were evaluated posttransplant. One analysis was performed due to recurrent C3G of the allograft, with confirmed competent dysregulation. 2 analyses were in liver transplant recipients, both with systemic TMA. Severe overactivation with consumption of complement was proven in one and treated with eculizumab. The characteristics of patients with diagnosed disorders of the complement system and those without are shown in Table 1. Conclusion Transplant physicians should keep a high volume of suspicion for complement dysregulation disorders, both during the pretransplant work-up and when evaluating TMA and recurrent GN posttransplant. Special caution should be advised when a patient is referred as chronic GN, MPGN or unknown cause ESKD at a young age.