Renal Changes Research Articles

Kokusaginine attenuates renal fibrosis by inhibiting the PI3K/AKT signaling pathway

Kokusaginine is an active ingredient alkaloid that has been isolated and extracted from Ruta graveolens L. Some researches have indicated that alkaloids possess anti-inflammatory and antioxidant effects. Nevertheless, the potential nephroprotective effects of kokusaginine on renal fibrosis remain undetermined. This study was conducted to examine the protective effect of kokusaginine on renal fibrosis and to explore the underlying mechanisms using both in vivo and in vitro models. Renal fibrosis was induced in male C57BL/6 J mice by feeding with 0.2% adenine-containing food and UUO surgery. Kokusaginine was administered orally simultaneously after the establishment of renal fibrosis. Renal function was measured by serum levels of creatinine and urea nitrogen. Renal pathological changes were assessed by HE staining and Masson staining. Western blotting was employed to detect the expression levels of fibrosis-related proteins in mice and cells. Additionally, network pharmacology analysis and RNA-seq were utilized to predict the pathways through which kokusaginine could exert its anti-fibrotic effects. The treatment with kokusaginine enhanced renal function, alleviated renal histoarchitectural lesions, and mitigated renal fibrosis in the renal fibrosis models. The network pharmacology and RNA-seq enrichment analysis of the KEGG pathway demonstrated that kokusaginine could exert anti-renal fibrosis activity via the PI3K/AKT signaling pathway. And the results were verified in both in vitro and in vivo experiments. In conclusion, our data implied that kokusaginine inhibited the activation of the PI3K/AKT signaling pathway both in vitro and in vivo, and suppressed the formation of renal fibrosis. Thus, the kokusaginine-mediated PI3K/AKT signaling pathway may represent a novel approach for the treatment of renal fibrosis.

Quantifying Renal Changes: A Study of Area of Bowman's Space Following Prolonged Itopride Hydrochloride Exposure in Albino Rats

Objective: To see the effects of long-term administration of itopride hydrochloride on the histomorphology of kidney of the male Wistar albino rats.Study Design: A Laboratory based experimental study.Place and Duration of Study: The study was conducted at the Department of Anatomy, CMH Multan Institute of Medical Sciences Multan, Pakistan from September 2020 to March 2022.Methods: The study involved two groups: Group A served as the control, and Group B functioned as the experimental group. Each group consisted of 30 adult male albino rats. The animals of group A were administered 2ml/100g of distilled water by oral gavage along with a diet for laboratory rodents daily for 15 days. The animals of group B were given 4.4mg/kg of itopride hydrochloride dissolved in 2ml/100g body weight of distilled water by oral gavage three times a day for 15 days. The kidney was processed for paraffin embedding and stained with Periodic Acid Schiff (PAS). The area of Bowman's space was measured by linear micrometer after calibration with a stage micrometer and image J software. The student's t-test was utilized to assess potential differences between the two groups, with significance set at a p-value of ≤ 0.05.Result: The area of Bowman's space was significantly increased in the experimental group as compared to the control group (p= 0.045).Conclusion: Long-term Itopride Hydrochloride administration appears to influence the area of Bowman's Space in Wistar albino rats. How to cite this: Hashmi A, Syed H, Irfan A, Rabbani A, Mir A, Razzaq M. Quantifying Renal Changes: A Study of Area of Bowman's Space Following Prolonged Itopride Hydrochloride Exposure in Albino Rats. Life and Science. 2024; 5(2): 138-143. doi: http://doi.org/10.37185/LnS.1.1.539

FINERENONE TREATMENT PREVENTS GLOMERULAR DAMAGE AND RENAL INTERSTITIAL INFLAMMATION IN TYPE 1 DIABETIC RATS WITH CHRONIC KIDNEY DISEASE

Objective: Finerenone (FIN), a non-steroidal mineralocorticoid receptor antagonist, has shown a protective effect on kidney and cardiovascular damage progression in type 1 diabetic Munich Wistar Frömter rats with established chronic kidney disease (CKD). The gradual decline in kidney function in diabetic CKD is due to a thickening of glomerular and Bowman capsule basement membranes, mesangial matrix expansion, and tubulointerstitial fibrosis. In this study we aimed to characterize whether the renal protection of FIN is related to a decrease in kidney damage through histomorphological changes in diabetic MWF rats. Design and method: Diabetes was induced by a streptozotocin injection (15 mg/Kg, i.p.) together with exposure to a high fat/high sucrose (HF/HS) diet (MWF-D) for 6 weeks. The MWF-D-FIN group was additionally treated with 10 mg/Kg/day of FIN included in the HF/HS diet (n = 6/group). Morphometrical analysis of renal structural changes was performed under hematoxylin and eosin staining, and light microscopy. Matrix metalloproteinases (MMP)-2 and MMP-9 activities were determined by zymography. Results: MWF-D and MWF-D-EP rats exhibited significantly elevated glycemia, water intake, urine volume, glucosuria, and kidney weight compared to control MWF. Histological examination of kidney samples of MWF and MWF-D rats showed hypertrophic glomeruli with an increase of the glomerular tuft and the Bowman's space. These pathological alterations were prevented by FIN treatment. The percentage of glomerulosclerosis was significantly higher in MWF and MWF-D rats and 59% lower in the MWF-D-FIN group (p<0.001) whereas the glomerulosclerosis index was reduced to 33% by FIN (p<0.001). Moreover, MWF-D rats showed an increased interstitial inflammation index compared to MWF rats (p<0.001) which was reduced to 44% (p<0.001) in the MWF-D-FIN group. Since an increase in MMP-2 and MMP-9 activities are associated with fibrosis development, these were determined by zymography in kidney samples of all groups. Both MMP-2 and MMP-9 were significantly higher in MWF-D compared to MWF and decreased by FIN treatment. Conclusions: In conclusion FIN prevents the development of diabetic kidney damage due to a reduction in glomerular alterations and interstitial inflammation associated to an inhibition of MMP-2 and MMP-9 activities.

Effect and mechanism of Yiqing decoction on hyperuricemia rats.

This study aimed to experimentally compare the uric acid-lowering effect and renal protection of Yiqing Fang in a rat model of hyperuricemia. Additionally, we used network pharmacology to predict the potential active components, targets, and pathways of Yiqing Fang. Male SD rats were randomly divided into control, model, Yiqing Fang, allopurinol, and probenecid groups. Serum creatinine (Scr), blood urea nitrogen (BUN), serum uric acid (UA), alanine transaminase (ALT), complete blood count, and urinary NAG enzyme levels were measured. Standard pathology and electron microscopy samples were prepared from the left kidney to observe renal pathological changes, renal fibrosis, and collagen III expression levels. In addition, we employed network pharmacology to investigate the molecular mechanisms and pathways of Yiqing Fang. The Yiqing Fang group showed significantly lower levels of Scr, BUN, UA, ALT, urinary NAG enzyme, complete blood count, and liver function tests compared to the model group (P < 0.05). Furthermore, both the Yiqing Fang and allopurinol groups exhibited significant reductions in renal pathological changes compared to the model group, along with decreased expression of collagen III. Network pharmacology analysis identified a total of 27 specific sites related to hyperuricemia. The main active components were predicted to include quercetin, berberine, beta-sitosterol, epimedin C, and dioscin. The primary target sites were predicted to include TNF, IL-6, IL-17, IL-1B, and VEGFA. Yiqing Fang may exert its effects through regulation of drug response, urate metabolism, purine compound absorption, inflammation response, lipopolysaccharide response, cytokine activity, and antioxidant activity. These effects may be mediated through signaling pathways such as IL-17, HIF-1, and AGE-RAGE. Yiqing Fang offers potential as a treatment for hyperuricemia due to its multiple active components, targeting of various sites, and engagement of multiple pathways.

Dose-Effect Relationship of Kidney Function After SABR for Primary Renal Cell Carcinoma: TROG 15.03 FASTRACK II

BackgroundStereotactic ablative body radiotherapy (SABR) is a novel option to treat primary renal cell carcinoma (RCC). However, a high radiation dose may be received by the treated kidney, which may affect its function post-treatment. This study investigates the dose-effect relationship of kidney SABR with posttreatment renal function. MethodsThis was a prespecified secondary endpoint of the multicenter FASTRACK II clinical trial (NCT02613819). Patients received either 26 Gy in a single fraction (SF) for tumors with a maximal diameter of 4 cm or less, or 42 Gy in three fractions (multi-fraction (MF)) for larger tumors. To determine renal function change, 99mTc-DMSA SPECT/CT scans were acquired, and the glomerular filtration rate (GFR) was estimated at baseline, 12-, and 24-months post-treatment. Imaging datasets were rigidly registered to the planning CT where kidneys were segmented to calculate dose-response curves. ResultsFrom 71 enrolled patients, data from 36 (51%) and 26 (37%) patients were included in this study based on availability of post-treatment data at 12- and 24-months, respectively. The ipsilateral kidney GFR decreased from baseline by 42% and 39% in the SF cohort, and by 45% and 62% in the MF cohort, at 12- and 24-months respectively (p-values < 0.03). The loss in renal function was 3.6±0.8% and 4.5±1.0% in the SF cohort, and 1.7±0.1% and 1.7±0.2% in the MF cohort, at 12- and 24-months respectively. The major loss in renal function occurred in high-dose regions, where dose-response curves converged to a plateau. ConclusionsFor the first time in a multicenter study, the dose-effect relationship at 12- and 24-months post-SABR treatment for primary RCC was quantified. Kidney function reduces linearly with dose up to 100 Gy BED3.

Evaluating the Safety of Herbal Medicine on Renal Function: A Comprehensive Analysis from Six Randomized Controlled Trials Conducted with Four Formulations from Traditional Korean Medicine.

The growing popularity of herbal medicine raises concerns about potential nephrotoxicity risks, while limited evidence hinders a comprehensive impact assessment. This study aims to investigate the overall risk features of herbal medicine on kidney injury. We conducted a retrospective analysis on renal function changes, including blood urea nitrogen (BUN), serum creatinine, and estimated glomerular filtration rate (eGFR), through data from six randomized controlled trials (RCTs) in South Korea. A total of 407 participants (142 males, 265 females) received either one of four different herbal medicines (240 participants) or a placebo (167 participants). When comparing changes in eGFR regarding the mean, 90th-percentile value, and 20% reduction after treatment, there was no significant difference between the herbal-treated and placebo groups. This study provided a helpful reference for examining the safety issues of herbal remedies, especially regarding kidney function.

Is 3D Volumetric Evaluation Consistent with Postoperative Renal Parenchymal Preservation in Open and Robot-Assisted Laparoscopic Partial Nephrectomy?

Introduction: To evaluate by using 3D renal volumetric assessment and compare renal parenchymal preservation between patient who underwent open partial nephrectomy (OPN) and robot assisted laparoscopic partial nephrectomy (RALPN). Methods: We retrospectively reviewed the records of the patients to evaluate the effect of OPN (23 patients) or RALPN (19 patients) partial nephrectomy on renal parenchymal preservation. The CT or MRI were examined using 3D-Slicer image processing software. The tumor volume and preoperative and postoperative non-tumor bearing parenchymal volumes were evaluated with the segmentation. The preoperative and postoperative parenchymal volumes, serum creatinine levels, and estimated glomerular filtration rates (eGFRs) were compared between the surgical techniques. Results: The data of 42 patients were included in the final analysis. The patient and tumor characteristics were similar between the two groups. Postoperative renal parenchymal volumetric changes were seen similar between groups. Although the serum creatinine levels and eGFRs did not change postoperatively in the RALPN group (P = .145 and P = .085, respectively), creatinine increased while eGFR decreased in the OPN group (P = .003 and P = .002, respectively). Conclusions: Our analysis showed that RALPN could be considered similar to OPN in terms of parenchymal volume preservation, but the rate of parenchymal volume preservation was not associated with the change in functional parameters. These results should be supported by further research.

Activation of the IL-6/STAT3 pathway contributes to the pathogenesis of membranous nephropathy and is a target for Mahuang Fuzi and Shenzhuo Decoction (MFSD) to repair podocyte damage

BackgroundPrimary membranous nephropathy (PMN) is an autoimmune glomerular disease. IL-6 is a potential therapeutic target for PMN. Previous clinical studies have demonstrated the effectiveness of Mahuang Fuzi and Shenzhuo Decoction (MFSD) in treating membranous nephropathy. However, the mechanism of action of MFSD remains unclear. MethodsSerum IL-6 levels were measured in patients with PMN and healthy subjects. The passive Heymann nephritis (PHN) rat model was established, and high and low doses of MFSD were used for intervention to observe the repair effect of MFSD on renal pathological changes and podocyte injury. RNA-seq was used to screen the possible targets of MFSD, and the effect of MFSD targeting IL-6/STAT3 was further verified by combining the experimental results. Finally, the efficacy of tocilizumab in PHN rats was observed. ResultsSerum IL-6 levels were significantly higher in PMN patients than in healthy subjects. These levels significantly decreased in patients in remission after MFSD treatment. MFSD treatment improved laboratory indicators in PHN rats, as well as glomerular filtration barrier damage and podocyte marker protein expression. Renal transcriptome changes showed that MFSD-targeted differential genes were enriched in JAK/STAT and cytokine-related pathways. MFSD inhibits the IL6/STAT3 pathway in podocytes. Additionally, MFSD significantly reduced serum levels of IL-6 and other cytokines in PHN rats. However, treatment of PHN with tocilizumab did not achieve the expected effect. ConclusionThe IL-6/STAT3 signaling pathway is activated in podocytes of experimental membranous nephropathy. MFSD alleviates podocyte damage by inhibiting the IL-6/STAT3 pathway.

The pattern of renal artery Doppler indices in patients with sickle cell disease

Aim: To evaluate the pattern of renal artery Doppler indices in patients with sickle cell disease who do not have laboratory evidence of renal impairment. Material and methods: A case-control study was carried out after enrolling 50 patients with sickle cell disease (HbSS phenotype) (sickle cell disease group) and 50 con- trol subjects (control group). All the participants underwent ultrasound and color Doppler examination, and the pulsatility index and resistive index values of the main renal artery, segmental artery, and interlobar artery in both kidneys were recorded and compared. Results: The Doppler measurements of the main renal artery, segmental artery, and interlobar artery were compared between the control and sickle cell disease groups. It was found that both pulsatility index and resistive index were significantly higher in the sickle cell disease group, as compared to the control group, for the main renal artery, segmental artery, and interlobar artery (p &lt;0.0001, p &lt;0.0001, and p &lt;0.0001, respectively). The optimal cut-off points for mean pulsatility index and resistive index, as measured by the Youden index, were found to be &gt;1.08 (72% sensitivity and 88% specificity) and &gt;0.635 (66% sensitivity and 98% specificity), respectively. Conclusions: Resistive index and pulsatility index values in renal Doppler sonography can serve as early radiologic predictors of renal vascular changes in sickle cell disease patients who do not have laboratory evidence of renal impairment.

Co-exposure of arsenic and polystyrene-nanoplastics induced kidney injury by disrupting mitochondrial homeostasis and mtROS-mediated ferritinophagy and ferroptosis

Arsenic (As) and polystyrene nanoplastics (PSNPs) co-exposure induced biotoxicity and ecological risks have attracted wide attention. However, the combined effects of As and PSNPs on the kidney and their underlying mechanisms of toxicities remain to be explored. Here, we investigated the effects of As and PSNPs co-exposure on structure and function in mice kidney, and further explored the possible mechanisms. In this study, we identified that co-exposure to As and PSNPs exhibited conspicuous renal structural damage and pathological changes, accompanied by renal tissue fibrosis (increased protein expression of Collagen I and α-SMA and deposition of collagen fibers), whereas alone exposure to As or PSNPs does not exhibit nephrotoxicity. Subsequently, our results further showed that combined action of As and PSNPs induced mitochondrial oxidative damage and impaired mitochondrial dynamic balance. Furthermore, co-treatment with As and PSNPs activated NCOA4-mediated ferritinophagy and ferroptosis in mice kidney and TCMK-1 cells, which was confirmed by the changes in the expression of ferritinophagy and ferroptosis related indicators (NCOA4, LC3, ATG5, ATG7, FTH1, FTL, GPX4, SLC7A11, FSP1, ACSL4 and PTGS2). Meaningfully, pretreatment with the mtROS-targeted scavenger Mito-TEMPO significantly attenuated As and PSNPs co-exposure induced mitochondrial damage, ferritinophagy and ferroptosis. In conclusion, these findings demonstrated that mtROS-dependent ferritinophagy and ferroptosis are important factors in As and PSNPs co-exposure induced kidney injury and fibrosis. This study provides a new insight into the study of combined toxicity of nanoplastics and heavy metal pollutants.

How renal toxins respond to renal function deterioration and oral toxic adsorbent in pH-controlled releasing capsule.

The number of patients with chronic kidney disease (CKD) is increasing. Oral toxin adsorbents may provide some value. Several uremic toxins, including indoxyl sulfate (IS), p-cresol (PCS), acrolein, per- and poly-fluoroalkyl substances (PFAS), and inflammation markers (interleukin 6 [IL-6] and tumor necrosis factor [TNF]-alpha) have been shown to be related to CKD progression. A total of 81 patients taking oral activated charcoal toxin adsorbents (AC-134), which were embedded in capsules that dissolved in the terminal ileum, three times a day for 1 month, were recruited. The renal function, hemoglobulin (Hb), inflammation markers, three PFAS (PFOA, PFOS, and PFNA), and acrolein were quantified. Compared with the baseline, an improved glomerular filtration rate (GFR) and significantly lower acrolein were noted. Furthermore, the CKD stage 4 and 5 group had significantly higher concentrations of IS, PCS, IL-6, and TNF but lower levels of Hb and PFAS compared with the CKD Stage 3 group at baseline and after the intervention. Hb was increased only in the CKD Stage 3 group after the trial (p = .032). Acrolein did not differ between the different CKD stage groups. Patients with improved GFR (responders) (about 77%) and nonresponders had similar baseline GFR. Responders had higher acrolein and PFOA levels throughout the study and a more significant reduction in acrolein, indicating a better digestion function. Responders had higher acrolein and PFOA levels throughout the study and a more significant reduction in acrolein, while PFOA increased in responders. Both the higher PFOA and lower acrolein may be related to improved eGFR (and possibly to improvements in proteinuria, which we did not measure. Proteinuria is associated with PFAS loss in the urine), AC-134 showed the potential to improve the GFR and decrease acrolein, which might better indicate renal function change. Future studies are needed with longer follow-ups.

Severe Acute Pancreatitis Complicated by Acute Pulmonary Embolism: a case report

Acute pancreatitis is a painful condition in which the pancreas becomes inflamed and edematous usually for a short period of time. Pulmonary embolism due to severe acute pancreatitis is a rare but serious condition. A 68-year-old patient got admitted in gastroenterology department of a tertiary care hospital of Dhaka, Bangladesh with chief complaints of severe abdominal pain for 5 hours and several episodes of vomiting for same duration. After admission relative investigation and examination were done. His USG revealed swollen oedematous pancreas with peripancreatic fluid collection, bilateral renal parenchyma changes with cortical cyst. Patient’s Glasgow Imrie score was 3, Numeric pain score (NRS) was 4, Urine output was normal. The patient was categorized into severe acute pancreatitis. The patient was treated with antimicrobials, proton pump inhibitors, analgesic, and fluid resuscitation. But patient’s medical condition deteriorated and oxygen demand increased. Due to susceptibility of pulmonary embolism and worsening of patient’s condition a thrombolysis was done. Severe acute pancreatitis complicating with pulmonary embolism is a fatal condition.1 Early diagnosis and treatment are fundamental for treating this dreadful condition. When Patient with acute pancreatitis exhibits dyspnoea, leg oedema and thromboembolic events, pulmonary embolism should be suspected. Following early diagnosis, thrombolysis is necessary to combat this situation. Bangladesh Crit Care J March 2024; 12 (1): 50-54

Evaluation of hepatic and renal functional changes in patients undergoing laparoscopic cholecystectomy

Background: In this era of laparoscopic surgery, with the use of carbon dioxide insufflation in creating pneumoperitoneum for ease of trocar insertion and visualization of anatomy, it comes certain systemic changes in the patient due to the compression effect of the gas as well as resorption of it through peritoneum. Aims and Objectives: The aim of the study was to assess baseline standards of hepatic and renal functional status in pre-operative patients in comparison with post-operative patients undergoing laparoscopic cholecystectomy (LC). Materials and Methods: Cases were chosen among the persons who presented with chronic calculus cholecystitis to the surgical out-patient department of Ramakrishna Mission Seva Pratishthan, Vivekananda Institute of Medical Sciences, Kolkata. Pre-operative liver function tests (LFT) and renal function tests (RFT) values were recorded. Again, LFT and RFT values were evaluated on post-operative day 1 (POD1) and POD12. Results: Serum conjugated and unconjugated bilirubin, aspartate amino transaminase, alanine amino transaminase, urea, estimated glomerular filtration rate values increases immediate postoperatively on POD1 but returns to normal pre-operative levels on POD 12. Serum alkaline phosphatase, albumin, and creatinine values decrease on POD1 and return to normal pre-operative values in POD 12. Conclusion: Hepatic and renal function changes in the immediate post-operative period of 24 h following LC. This change is transient and returns to normal levels within POD 12.

Impact of catheterized ductal closure on renal and cerebral oximetry in premature neonates.

Percutaneous catheter-based closure is increasingly utilized in premature newborns. While near-infrared spectroscopy (NIRS) has been examined for assessment of interventional closure in surgical ligation, its application in percutaneous transcatheter closure remains unexplored. This study aims to assess cerebral and renal hemodynamic changes using NIRS during percutaneous closure compared to surgical closure in preterm infants. A prospective observational study enrolled preterm infants born at 32 weeks of gestation or less and diagnosed with hsPDA between January 2020 and December 2022. These infants received either surgical or catheter-based closure of the PDA. Cerebral and renal oxygen saturation was monitored using the INVOS 5100 device from 12 h before the intervention until 24 h after. Linear mixed-effects models were used to analyze time-dependent variables. Twenty-two patients were enrolled, with catheter-based closure performed in 16 cases and conventional surgery in 6 cases. Following ductal closure, a significant increase in renal and cerebral oximetry was observed alongside a decrease in renal and cerebral tissue oxygen extraction. These changes were particularly pronounced in the renal territory. No differences were detected between catheterization and surgical closure. Conclusion: An improvement in cerebral and renal oximetry following hsPDA closure was observed. However, we did not identify differences in this pattern based on the type of interventional procedure for PDA, whether surgery or catheterization. What is Known: •The presence of a significant ductus is common in premature patients. Studies have shown that it affects cerebral and renal hemodynamics negatively, leading to decreased oximetry values in these areas. It has been reported that closure of the ductus, either pharmacologically or surgically, results in improved oximetry values. What is New: •This study assess the impact of percutaneous closure of ductus, revealing increased oximetry values in cerebral and renal territories without significant differences compared to surgical ligation. Notably, renal oximetry values showed a greater increase, underscoring the importance of multi-location monitoring.

JMJD3 activation contributes to renal protection and regeneration following acute kidney injury in mice.

We have recently demonstrated that Jumonji domain-containing protein D3 (JMJD3), a histone demethylase of histone H3 on lysine 27 (H3K27me3), is protective against renal fibrosis, but its role in acute kidney injury (AKI) remains unexplored. Here, we report that JMJD3 activity is required for renal protection and regeneration in murine models of AKI induced by ischemia/reperfusion (I/R) and folic acid (FA). Injury to the kidney upregulated JMJD3 expression and induced expression of H3K27me3, which was coincident with renal dysfunction, renal tubular cell injury/apoptosis, and proliferation. Blocking JMJD3 activity by GSKJ4 led to worsening renal dysfunction and pathological changes by aggravating tubular epithelial cell injury and apoptosis in both murine models of AKI. JMJD3 inhibition by GSKJ4 also reduced renal tubular cell proliferation and suppressed expression of cyclin E and phosphorylation of CDK2, but increased p21 expression in the injured kidney. Furthermore, inactivation of JMJD3 enhanced I/R- or FA-induced expression of TGF-β1, vimentin, and Snail, phosphorylation of Smad3, STAT3, and NF-κB, and increased renal infiltration by F4/80 (+) macrophages. Finally, GSKJ4 treatment caused further downregulation of Klotho, BMP-7, Smad7, and E-cadherin, all of which are associated with renal protection and have anti-fibrotic effects. Therefore, these data provide strong evidence that JMJD3 activation contributes to renal tubular epithelial cell survival and regeneration after AKI.

Assessing renal tissue temperature changes and perfusion effects during laser activation in an in vivo porcine model.

High fluid temperatures have been seen in both in vitro and in vivo studies with laser lithotripsy, yet the thermal distribution within the renal parenchyma has not been well characterized. Additionally, the heat-sink effect of vascular perfusion remains uncertain. Our objectives were twofold: first, to measure renal tissue temperatures in response to laser activation in a calyx, and second, to assess the effect of vascular perfusion on renal tissue temperatures. Ureteroscopy was performed in three porcine subjects with a prototype ureteroscope containing a temperature sensor at its tip. A needle with four thermocouples was introduced percutaneously into a kidney with ultrasound guidance to allow temperature measurement in the renal medulla and cortex. Three trials of laser activation (40W) for 60s were conducted with an irrigation rate of 8ml/min at room temperature in each subject. After euthanasia, three trials were repeated without vascular perfusion in each subject. Substantial temperature elevation was observed in the renal medulla with thermal dose in two of nine trials exceeding threshold for tissue injury. The temperature decay time (t½) of the non-perfused trials was longer than in the perfused trials. The ratio of t½ between them was greater in the cortex than the medulla. High-power laser settings (40W) can induce potentially injurious temperatures in the in vivo porcine kidney, particularly in the medullary region adjacent to the collecting system. Additionally, the influence of vascular perfusion in mitigating thermal risk in this susceptible area appears to be limited.

A Study Assessing the Role of Renal Grayscale Ultrasonography and Flowmetry in Correlation With Renal Function Tests Across Various Renal Diseases.

Background Renal insufficiency, a critical concern in native and transplant kidneys, necessitates effective screening modalities for evaluation and management. Grayscale sonography has been a cornerstone in renal diagnostics, providing basic anatomical insights such as renal length, cortical thickness, and collecting system dilatation. Despite technological advancements, its impact on the differential diagnosis or management of renal disease remains limited, often showing normal findings in the presence of severe renal dysfunction. On the other hand, Doppler sonography, particularly the Doppler resistive index (RI), has shown potential in enhancing the assessment of renal dysfunction by quantifying alterations in renal blood flow and correlating with various renal pathologies and prognoses. Thus, this study aims to assess and compare the sensitivity of transabdominal and Doppler sonography as a diagnostic modality to evaluate medical renal diseases with altered renal function tests (RFTs). Methodology Participants included patients visiting the ultrasonography (USG)room at our hospital for USG of the kidneys, ureters, and bladder (USG KUB) and USG of the whole abdomen(USG W/A) with altered RFTs. Each underwent renal grayscale USG and RImeasurement, alongside standard RFTs, aiming to investigate the relationship between USG and RI findings and RFT outcomes to assess their predictive accuracy for renal function. Renal grayscale USG assessed parameters including renal dimensions, echogenicity, corticomedullary differentiation, and RI. Data management and charting were conducted with Microsoft Excel 2021 and Microsoft Word 2021. IBM SPSS Statistics for Windows, Version 24 (IBM Corp.,Armonk, NY) was utilized for data analysis. The analysis of variance (ANOVA) test examined relationships between renal parameters and RI across diagnostic groups. Furthermore, the chi-square test evaluated associations of renal ultrasound findings with RFTs and their significance. Results The study analyzed 93 patients with altered RFTs. Chronic kidney disease (CKD) affected 68 patients, primarily males in their fifth and sixth decades, showing reduced renal dimensions, increased cortical echogenicity, and elevated Doppler RI mean (RIm) with 83% sensitivity. Acute kidney injury (AKI) was found in 12 patients, mainly in their fourth decade, displaying increased renal parameters and elevated RIm with 75% sensitivity. Glomerular diseases, including nephrotic syndrome (NS) and nephritic syndrome (NeS), occurred in 9 patients, predominantly males in their fourth decade, with heightened renal cortical echogenicity and elevated RIm with 55.5% sensitivity. Lupus nephritis (LN) was detected in 4 female patients, despite normal renal parameters, showing elevated serum creatinine levels. Conclusions Doppler assessment of renal vascular waveforms effectively identifies chronic renal changes, aiding in the diagnosis of altered RFTs and guiding prognosis. While it detects typical changes like decreased size and parenchymal atrophy, it may not be as indicative of diabetic nephropathy. Key ultrasound indicators such as changes in echotexture and size, along with associated findings like ascites and effusions, help recognize altered renal function and minimize unnecessary interventions.

Introduction to renal pathology

In recent decades, nephropathology has developed worldwide as asubspeciality of pathology, which requires special methodological and technical equipment to process the material and specific clinical and pathological expertise to interpret the findings. These special requirements mean that nephropathology is not available at all pathology institutes, but is carried out on alarge scale in afew highly specialised centres. The history of nephropathology, or in anarrower sense the specialised histopathological examination of kidney biopsies, began in 1958 with the first use or performance of akidney biopsy [1]. It thus replaced the practice of urinalysis, which had been common since the Middle Ages, as adiagnostic tool for kidney diseases. Specialised techniques such as immunofluorescence or immunohistology but also electron microscopy are required to assess specific renal changes, for which the examination of renal biopsies is one of the few remaining routine applications today. In Germany and German-speaking countries, the discipline developed thanks to the work of outstanding people in the field of pathology who were primarily involved in this discipline and had the necessary technical and human resources in their laboratories to ensure that these biopsies could be analysed.

Significance of the total renal chronicity score in predicting renal outcome in PLA2R-associated membranous nephropathy.

Phospholipase A2 receptor (PLA2R)-associated membranous nephropathy accounts for the majority of membranous nephropathy; however, few studies have determined the prognostic impact and clinicalapplication of renal pathologic change on this disease. A retrospective cohort study of 262 patients with PLA2R-associated membranous nephropathy was conducted. The total renal chronicity score calculatedaccording to the degree ofglomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriosclerosis was applied to evaluate renal chronicity. Baseline bias was adjusted by inverse probability weight whenassessing the prognostic impact of chronicity, and multiple parameters were used to evaluatethe application valueof renalchronicity. During a median follow-up of 24.5 months, renal outcome (kidney function deteriorationand/or end-stage kidney disease) was observed in 22 (8.40%) patients. Not only did a higher total renal chronicity score independently predict renal outcome [odds ratio (OR): 1.562, 95% confidence interval (CI) 1.073-2.273, P = 0.020], but non-minimal chronicity was also an independent risk factor for renal outcome (OR: 3.170, 95% CI 1.040-9.659, P = 0.042). Moreover, the membranous nephropathy risk classification in the Kidney Disease: Improving Global Outcomes (KDIGO) guideline integrated with non-minimal chronicity showed improvements in categorical net reclassification (0.174, 95% CI 0.012-0.335, P = 0.035), continuous net reclassification (0.462, 95% CI 0.087-0.838, P = 0.016), and integrated discrimination (0.019, 95% CI 0.003-0.035, P = 0.020) compared to the original classification. Renal chronicity is closely associated withrenal outcomes in PLA2R-associated membranous nephropathy, and combiningthe KDIGO risk classification with chronicity scoresmay provide amore accurate prognostic prediction.

Comparative analysis of four nutritional scores in predicting adverse outcomes in biopsy-confirmed diabetic kidney Disease.

Malnutrition is associated with adverse outcomes in patients with diabetic kidney disease (DKD). However, it is uncertain which nutritional assessment tools are most effective in predicting the adverse outcomes of DKD. This retrospective study was conducted at a single center and included 367 patients diagnosed with DKD based on biopsy results between August 2009 and December 2018. Four nutritional assessment indices, namely the Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Triglycerides (TG) × Total Cholesterol (TC) × Body Weight (BW) Index (TCBI), and Controlling Nutritional Status (CONUT) score, were selected and calculated. We aimed to assess the association between these nutritional scores and adverse outcomes, including progression to end-stage kidney disease (ESKD), cardiovascular diseases events (CVD), and all-cause mortality. Univariate and multivariate Cox regression analyses, Kaplan-Meier analysis, along with Restricted cubic spline analysis were used to examine the relationship between nutritional scores and adverse outcomes. Furthermore, the area under the curve (AUC) was calculated using time-dependent receiver operating characteristics to determine the predictive value of the four nutritional scores alone and some combinations. Lastly, ordered logistic regression analysis was conducted to explore the correlation between the four nutritional scores and different renal histologic changes. The incidence of ESKD, CVD, and all-cause mortality was significantly higher in patients with DKD who had a lower PNI, lower GNRI, and higher CONUT score. Additionally, The TCBI performed the worst in terms of grading and risk assessment. The PNI offer the highest predictive value for adverse outcomes and a stronger correlation with renal histologic changes compared to other nutritional scores. Patients diagnosed with DKD who have a worse nutritional status are more likely to experience higher rates of adverse outcomes. The PNI might offer more valuable predictive values and a stronger correlation with different renal histologic changes compared to other nutritional scores.