Improvement In Renal Function Research Articles

Bilateral ureteral obstruction caused by a detrusor wall thickness: Case report and review of literature

Benign prostatic enlargement is a common condition in elderly men, caused by a histopathologic disease called benign prostatic hyperplasia. we report a case of a 76-year-old male with a benign prostatic hyperplasia who presented kidney injury due to bilateral hydronephrosis and no amelioration after bladder catheterization. An abdominopelvic computed tomography scan was performed showing bilateral moderate ureterohydronephrosis up to the level of the ureteral orifices within a diffuse thickening of the bladder wall and the endoscopic examination showed trigonal prominence, displacing and deforming the ureteral orifice. Three-months period of ureteral stenting with transurethral resection of prostate leads to significant improvement in renal function. This case underscores the importance of considering detrusor wall thickness as a potential cause of obstructive renal insufficiency, especially in elderly males presenting with chronic retention.

#539 The active ingredient in the Nuphar lutea plant DTBN, ameliorates kidney damage and inflammation in a mouse model of chronic kidney disease (CKD)

Abstract Background and Aims Complications associated with Chronic Kidney Disease (CKD), such as disease progression and anemia, are closely linked to heightened inflammation mediated by the innate immune response. This inflammation can be mitigated through the use of anti-inflammatory agents. 6,6′-dihydroxythiobinupharidine (DTBN), an active compound derived from the aquatic plant Nuphar lutea, demonstrates notable anti-inflammatory properties, primarily by inhibiting NF-κB and LPS-induced cytokine activation. DTBN has shown efficacy in priming neutrophils, enhancing phagocytosis, regulating reactive oxygen species (ROS) production, and modulating NET formation. This study aimed to assess the impact of DTBN on CKD in mice. Method Male C57BL/6J mice, aged 8 weeks, were subjected to an adenine diet known to induce CKD through crystal deposition and tubulointerstitial inflammation. Both control and CKD-induced mice received intraperitoneal injections of DTBN (25 μg QOD) or saline and were euthanized after 8 weeks for evaluation. Results CKD mice treated with DTBN exhibited a significant decrease in serum urea and creatinine levels compared to untreated CKD mice (reduction by 1.4-fold and 1.3-fold, respectively). Histological analysis of kidney tissues revealed a notable reduction in F4/80 positive macrophage infiltration (3.4-fold decrease) and damaged renal areas (three-fold decrease), along with diminished kidney TGF-β levels in DTBN-treated CKD mice. Moreover, the p65 subunit of NF-κB showed a three-fold reduction in CKD mice treated with DTBN compared to untreated CKD mice. Indices of kidney inflammation (IL-1β, IL-6, and P-STAT3) were notably decreased in CKD mice treated with DTBN (reduction by 1.4-fold, 1.6-fold, and 2.9-fold, respectively) compared to untreated CKD mice. Notably, DTBN treatment in control mice did not induce apparent tissue damage; however, it led to reduced weight gain and mild hypoalbuminemia without proteinuria. Conclusion DTBN demonstrated significant improvements in renal function and inflammation indices in CKD mice. Hence, DTBN and substances similar to DTBN could be considered as supplementary treatments for CKD patients.

#1460 Targeting cyst progression: evaluation of anthelmintic and proton pump inhibitor in a rodent PKD model

Abstract Background and Aims In polycystic kidney disease (PKD) cyst formation and growth leads to progressive kidney damage. Recognizing the need for effective cyst-inhibitory drugs, we previously performed high-content screening of approved, repurposable drugs in a zebrafish model and identified several compounds with cyst-inhibitory activity and low toxicity. Here, we further tested two of the identified compounds, an anthelmintic agent and proton pump inhibitor, in a rodent model of PKD (PCK rat) for their cyst inhibitory and GFR-preserving capacity in mammals. Method The identified compounds were administered to 3-week-old male and female PCK rats for a total of 10 weeks to evaluate early drug effects on kidney function. Untreated PCK rats fed a normal ROD16 diet served as controls. After 5 weeks of treatment, total kidney and cystic volume and number of cysts were assessed in vivo by ultrasound. Following 10 weeks of treatment, kidney function was assessed by transcutaneous measurement of FITC-Sinistrin. After perfusion fixation in the same week, the kidneys, liver, heart, and pancreas were harvested for subsequent histological and molecular biological analyses. Results In male rats, 5-week proton pump inhibitor treatment was associated with a 50% reduction in the number of cysts (p < 0.05) and a nominal 22% reduction of fractional cystic kidney volume (CKV). Females showed a 16% reduction in cyst count and a modest reduction in fractional CKV. Treatment with the anthelmintic tended to reduce fractional CKV and cyst count in female animals whereas fractional cyst volume in males increased. After 10 weeks of treatment, a trend towards better preservation of GFR was observed for both therapies. Conclusion In conclusion, our study demonstrates a potential therapeutic benefit of a proton pump inhibitor and an anthelmintic agent in attenuating the progression of polycystic kidney disease (PKD) in a PCK rat model. The observed reductions in fractional cystic kidney volume and cyst count, coupled with marginal improvements in renal function, document a potential therapeutic effect of these compounds. Our preliminary findings justify further exploration of novel treatment modalities targeting cyst progression and renal dysfunction in this challenging clinical condition.

#1165 Targeted-release budesonide can preserve the glomerular filtration rate in patients diagnosed with IgA nephropathy after 3 months of administration.

Abstract Background and Aims The four-hit hypothesis constitutes the main immunological sequence of the IgA nephropathy (IgAN) pathogenesis. However, the activation of intestinal-renal axis is considered the initial step during IgA nephropathy (IgAN) pathogenesis. Aim of this prospective pilot study is to evaluate parameters which influence early response to targeted release budesonide. Method Adult IgAN patients, diagnosed the last 10 years, maintaining eGFR >30 ml/min/1.73m2 and Uprotein >750 mg/24 hr, despite standard supportive treatment, commenced on budesonide 16 mg/d, and followed for 3 months. Renal biopsies were re-evaluated and scored according to Oxford classification, parameters of renal function recorded at time of diagnosis (T-d),at the beginning of treatment (T0), and 3 months later (T3). Results Fifteen IgAN patients, M/F:12/3, Mean age: 52 (34-74) years from two different departments fulfilled the criteria and they have already started on budesonide treatment, 51.6 ± 45 months following diagnosis. eGFR had declined from T-d to T0, 57.43 ± 10.58 to 49.23 ± 13.63 ml/min/1.73 m2, p = 0.03, and Uprot was stable 3.33 ± 1.16 to Uprot = 2.98 ± 1.19 gr/24 hrs, p = NS. During the 3 first months of budesonide (T3), eGFR showed slight improvement, eGFR = 54.38 ± 13.67 while Uprot remained stable 3.17 ± 1,04 gr/24 hrs. Improvement in renal function was not associated with any of histologic findings, but was remarkably more evident within patients with <4 years of diagnosis, eGFR from 62 ± 5.2 to 73 ± 2.4, compared to change in the eGFR from 23 ± 5.6 ml/min/1.73 m2 to 25 ± 3.6 ml/min/1.73 m2. Conclusion Our preliminary findings suggest that, independent of renal histology, budesonide treatment showed a trend in improving renal function, mainly in patients with relatively short time from diagnosis. So, budesonide can

#2699 Rare glomerular microangiopathy: clinicopathological characteristics and prognosis

Abstract Background and Aims Different from the typical histologic changes of thrombotic microangiopathy (TMA), we identified a group of patients whose pathology with glomerular involvement without blood vessel lesions, which was rare and known as glomerular microangiopathy (GMA). Method In Peking Union Medical College Hospital, a total of 33 patients were diagnosed as GMA with proliferation and swelling of glomerular endothelial cells, fragmented red blood cells, fibrin or platelet thrombi in the capillary lumen, thickening of the basement membrane, stenosis or occlusion of capillary lumen, but no abnormalities in the endothelium of renal small vessels. The pathology and clinical data were from the medical records and analyzed. Results The patients were 66.7% male with a mean of 45 years (14 to 74 years). The primary diseases were Castleman's disease (CD, 30.3%), POEMS syndrome (21.2%), cancer patients receiving agents targeting vascular endothelial growth factor (21.2%), and others. All the patients showed various degrees of proteinuria, with an average 24-hour urinary protein of 2.66 g/d, hematuria (63.6%), and acute kidney injury (AKI, 39.4%). The median serum creatinine (SCr) was 142 (107.5, 169) μmol/L. The AKI patients had lower Alb (P < 0.0001), PLT (P = 0.0192), higher high-sensitivity C-reactive protein (hs-CRP) (P = 0.0199), and reduction of IgA (P = 0.0021). There is no significant difference in SCr and proteinuria among patients with different etiologies. The CD patients exhibited higher hs-CRP and D-Dimer. Treatment included targeting therapy of underlying hematological disorders, glucocorticoid combination with or without immunosuppressant, and supportive treatment. After treatment, we observed proteinuria remission (66.7%), partial improvement (27.3%), or complete recovery (45.5%) of renal function. Conclusion In Castleman's disease, POEMS syndrome, and patients receiving agents targeting VEGF, initial attention to GMA might improve the prognosis and shed light on the study of the mechanisms.

Ketonuria as an Indicator of Improvement of Renal Function in Patients with Type 2 Diabetes Receiving SGLT2 Inhibitor Treatment.

We investigated the potential association between ketonuria during treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors and its renoprotective effect in patients with type 2 diabetes. We included 192 patients who had received SGLT2 inhibitors for more than 6 months. After propensity score matching, 52 patients each were allocated into groups with or without ketonuria, respectively. The estimated glomerular filtration rate exhibited a significant improvement only in subjects with ketonuria (without ketonuria: mean difference, -0.02 mL/min/1.73 m2 [95% confidence interval (CI), -3.87 to 3.83 mL/min/1.73 m2] vs. with ketonuria: mean difference, 6.81 mL/min/1.73 m2 [95% CI, 3.16 to 10.46 mL/min/1.73 m2]; P<0.001). Improvement in estimated glomerular filtration rate at 6 months was associated with female sex and lower baseline body weight, blood pressure, and triglyceride levels in patients with ketonuria. In conclusion, the presence of ketonuria was associated with the renoprotective effect of SGLT2 inhibitors, and female sex and the absence of metabolic syndrome components may serve as additional indicators of these medications' substantial renoprotective effects in individuals with ketonuria.

Immunosuppressant Agents as Add-On Therapy Failed to Improve the Outcome of Immunoglobulin A Nephropathy with Crescent Score C1.

Background The renoprotective benefits of adding immunosuppressant therapy to corticosteroid (CS) treatment for immunoglobulin A nephropathy (IgAN) patients with less than 25% crescent formation (C1) remains uncertain, warranting further research. Methods A retrospective study was conducted on IgAN patients with crescent C1 lesions confirmed by renal biopsy at Xinqiao Hospital between May 1, 2017, and May 1, 2020. Patients were stratified into either the CS treatment group or the CS combined with an additional immunosuppressant therapy group. Follow-up assessments were conducted within 24 months. Propensity score analysis was used to match patients receiving CS and CS+immunosuppressant drug treatment in a 1:1 ratio. Primary outcomes included changes in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Subgroup analyses were performed to evaluate the benefits of different populations. Composite endpoint outcomes comprised a 30% eGFR decrease, end-stage kidney disease (ESKD) necessitating dialysis or transplant, or kidney disease-related mortality. Adverse events were also compared between the two groups. Results: 296 IgAN patients with C1 lesions were included in the analysis. Baseline characteristics indicated that IgAN patients in the CS+immunosuppressant group exhibited poorer renal function and higher UACR levels. Propensity score analysis effectively minimized the influence of baseline clinical characteristics, including age, serum creatinine, initial eGFR, UACR, and 24-hour proteinuria. Both treatment groups demonstrated continuous eGFR improvement and significant UACR reduction during follow-up, especially at 6 months. However, no significant differences in eGFR and UACR reduction rates were observed between the two groups throughout the entire follow-up period, both before and after matching. Subgroup analysis revealed improved eGFR in both treatment groups, notably among patients with an initial eGFR below 90 ml/min/1.73 m2. Conversely, IgAN patients with C1 lesions and a cellular crescent ratio exceeding 50% treated with CS and immunosuppressant therapy experienced a significant improvement in renal function and a decline in urinary protein creatinine ratio. Composite endpoint outcomes did not significantly differ between the two groups, while the incidence of adverse events was comparable. Conclusion Our findings suggest that the addition of immunosuppressant therapy to corticosteroid monotherapy did not confer significant therapeutic advantages in patients with C1 lesions compared to CS monotherapy, although some specific patient populations appeared to derive modest benefits from this combined approach.

Sustained improvement in renal function with palopegteriparatide in adults with chronic hypoparathyroidism: 2-year results from the phase 3 PaTHway trial

Sustained improvement in renal function with palopegteriparatide in adults with chronic hypoparathyroidism: 2-year results from the phase 3 PaTHway trial

Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patient with chronic hepatitis B.

Our study evaluated the outcomes of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB). We assessed viral and biochemical responses as well as changes in the estimated glomerular filtration rate (eGFR) and bone mineral density (BMD). This retrospective multicenter study included CHB patients who achieved virologic response (VR) (HBV DNA<20IU/mL) while on TDF and were subsequently switched to TAF between April 2018 and October 2021. This study included 309 patients with a median age of 59years, and 42.1% were male. The mean duration of TDF and TAF administration were 54.0 and 37.5months, respectively. All patients maintained VR after switching to TAF. Alanine aminotransferase (ALT) normalization rate significantly increased 6months after switching (74.8%-83.5%; P=0.008). Adjusted eGFR significantly improved at 6months (+5.55±10.52mL/min/1.73m2; P<0.001) and 12months (+6.02±10.70mL/min/1.73m2; P<0.001) after switching. In the subgroup of patients with renal impairment (eGFR<60mL/min/1.73m2), significant improvement in renal function was observed at 6months (+0.6±10.5mL/min/1.73m2; P<0.001) and 12months (+1.0±10.7mL/min/1.73m2; P<0.001) after switching to TAF. In patients with osteoporosis (n=182), switching to TAF resulted in significant improvement in spine and hip BMD at 12months, with increases of 9.7% (95% CI: 7.0-12.5) and 9.4% (95% CI: 7.0-11.8), respectively. In this real-world study, switching to TAF was effective and safe in patients, with notable improvements in ALT levels, renal function, and BMD.

Megalin-targeted acetylcysteine polymeric prodrug ameliorates ischemia-reperfusion-induced acute kidney injury

Acute kidney injury (AKI), a condition associated with reactive oxygen species (ROS), causes high mortality in clinics annually. Active targeted antioxidative therapy is emerging as a novel strategy for AKI treatment. In this study, we developed a polymeric prodrug that targets the highly expressed Megalin receptor on proximal tubule cells, enabling direct delivery of N-Acetylcysteine (NAC) for the treatment of ischemia reperfusion injury (IRI)-induced AKI. We conjugated NAC with low molecular weight chitosan (LMWC), a biocompatible and biodegradable polymer consisting of glucosamine and N-acetylglucosamine, to enhance its internalization by tubular epithelial cells. Moreover, we further conjugated triphenylphosphonium (TPP), a lipophilic cation with a delocalized positive charge, to low molecular weight chitosan-NAC in order to enhance the distribution of NAC in mitochondria. Our study confirmed that triphenylphosphonium-low molecular weight chitosan-NAC (TLN) exhibits remarkable therapeutic effects on IRI-AKI mice. This was evidenced by improvements in renal function, reduction in oxidative stress, mitigation of pathological progress, and decreased levels of kidney injury molecule-1. These findings suggested that the polymeric prodrug TLN holds promising potential for IRI-AKI treatment.

Does Age Influence the Functional Recovery after Infant Pyeloplasty?

ABSTRACT Purpose: The purpose was to study the correlation between age at surgery and functional recovery after infant pyeloplasty. Materials and Methods: All infants who underwent pyeloplasty were analyzed retrospectively in this multicenter study. Anteroposterior diameter (APD) &gt;2 cm, split renal function (SRF) &lt;40%, and Society of Fetal Urology (SFU) grade 3–4 were surgical indications. Based on the age at pyeloplasty, they were divided into Group 1 (1–3 months) and Group 2 (4–12 months). APD and SRF were compared before and after surgery in both groups. The fractional recoverable function (post-SRF-pre-SRF)/(50-pre-SRF) ×100 was correlated with age. Results: Fifty-one infants underwent pyeloplasty (mean age: 1.6 months – Group 1 and 7.2 months – Group 2). The mean APD decreased from 3 cm to 1.2 cm in Group 1 while 2.8 cm to 2 cm in Group 2 (P = 0.001). The mean SRF increased from 32.28% to 42.81% in Group 1 while 31%–34.18% in Group 2. SRF recovery was significantly higher in Group 1 compared to Group 2 (P = 0.001). Regression analysis showed a weak negative correlation (r = −0.2792) between age at surgery and renal function improvement. Conclusion: Functional recovery after pyeloplasty is better when done earlier (1–3 months), as this gives the growing kidney the best opportunity to recover.

Renal artery occlusion in a young woman - a tale of mysterious thrombosis.

Renal artery thrombosis is rare and limited reports exist in the young population. The most common aetiology is thromboembolic disease or abdominal trauma in this population and isolated occurrences are extremely rare. We present the case of an 18-year-old woman with spontaneous unilateral renal artery thrombosis and infarction for whom reperfusion was achieved through endovascular intervention. The aetiology of her thrombosis remains unclear and is under investigation with differential diagnoses being fibromuscular dysplasia, large and medium vessel vasculitis, and thromboembolic causes. To demonstrate the value in attempting salvage of an ischaemic kidney in a young patient with an unexplained spontaneous renal thrombosis. JM is an 18-year-old woman who presented to a large regional tertiary hospital with 3days of right flank pain. She had no infective symptoms and no urinary or bowel changes before admission. She was not pregnant, and her only medication was the oral contraceptive pill commenced 3months prior. A CT angiogram demonstrated right renal artery thrombosis with renal infarction. The kidney was deemed potentially salvageable, and ultrasound defined adequate vessel calibre to access for thrombectomy in the context of a negative coagulopathy screen. The patient underwent thrombolysis, thrombectomy and balloon angioplasty. Intraoperatively, a thin segment of distal stenosis was identified, and angiogram reperfusion was achieved with subsequent improvement in renal function. Renal artery thrombosis in young people is extremely rare and presents a diagnostic and management challenge requiring input from multiple teams including nephrology, rheumatology, paediatrics and vascular surgery. Systemic coagulopathy and vasculitis are differentials against anatomical aetiologies such as fibromuscular dysplasia. Our case adds to the limited literature regarding this in the young population. Renal artery thrombosis with occlusion in young people is very rare and is most often associated with a systemic coagulopathic disorder, such as antiphospholipid syndrome or structural pathology of the renal vasculature such as fibromuscular dysplasia. The work-up of a young female presenting with renal artery thrombosis without any previous medical history screens for a wide range of pathological processes.

Angiotensin Receptor-Neprilysin Inhibitor Suppresses Renin-Angiotensin-Aldosterone System Activation After Cardiac Surgery Using Cardiopulmonary Bypass.

Sacubitril/valsartan, being both a neprilysin inhibitor and angiotensin receptor blocker, exhibits a renin-angiotensin-aldosterone system (RAAS) inhibitory effect. However, no study has investigated the administration of sacubitril/valsartan in patients early after surgery using cardiopulmonary bypass.Methods and Results: This was a prospective observational study of 63 patients who underwent open heart surgery and were treated with sacubitril/valsartan. No serious adverse events occurred. Among the 63 patients, sacubitril/valsartan was discontinued in 13 due to hypotension (n=10), renal dysfunction (n=2), and dizziness (n=1). Atrial natriuretic peptide concentrations increased significantly from Day 3 of treatment (P=0.0142 vs. Postoperative Day 1) and remained high thereafter. In contrast, plasma renin activity was significantly suppressed from Day 3 onwards (P=0.00206 vs. Postoperative Day 1). A decrease in creatinine concentrations and an increase in the estimated glomerular filtration rate were observed on Day 3; this improvement in renal function was not observed in the historical control group, in which patients did not receive sacubitril/valsartan. New postoperative atrial fibrillation was less frequent in the study group compared with the historical control (12.7% vs. 38.0%; P=0.0034). Sacubitril/valsartan administration was safe immediately after open heart surgery in patients without postoperative hypotension. It enhanced serum atrial natriuretic peptide concentrations and suppressed RAAS activation.

Role of inferior vena cava assessment in volume management in acute kidney injury patients

BackgroundIntravascular volume assessment is critical to guiding volume management in patients with acute kidney injury (AKI). This study aimed to compare the impact of using inferior vena cava (IVC) diameter and collapsibility index (IVC-CI) measurements versus clinical assessment on the management of volume status and improvement of renal function in patients with AKI.MethodsThis prospective comparative study included 88 patients with AKI or AKI on top of chronic kidney disease (CKD) who were randomly allocated into two groups: In group 1, volume status was managed according to IVC assessment, while in group 2, volume status was managed according to clinical assessment. In addition, group 1 patients were assessed clinically and compared with IVC measurements in the same group.ResultsThere was moderate agreement between the IVC and clinical methods in diagnosing 86.4% of patients (P < 0.001) within group 1. The percentage of patients with edema increased post-treatment in group 2. There was no statistically significant difference between the two groups regarding renal recovery and survival.ConclusionBedside ultrasonographic IVC assessment is a non-invasive method that can facilitate volume management in AKI patients, helping to administer fluids more wisely without unintended excess fluid administration.

Telmisartan ameliorates nephropathy and restores the hippo pathway in rats with metabolic syndrome

The main objective of this study was to determine if the telmisartan-ameliorative effects of metabolic syndrome (MetS)-evoked nephropathy are attributed to the Hippo pathway. A secondary objective was to investigate the potential of vitamin D3 to enhance telmisartan-favourable effects. A diet composed of 24% fat and 3% salt, along with drinking water containing 10% fructose, was administered for 12 weeks to induce MetS. MetS-rats were given telmisartan (5 mg/kg/day), vitamin D3 (10 μg/kg/day) or both by gavage, starting in the sixth week of experimental diet administration. Assessments performed at closure included renal function, histological examination, catalase, malondialdehyde (MDA), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphatase and tensin homolog (PTEN), and transforming growth factor-β (TGF-β). Matrix metalloproteinase-9 (MMP-9) immunostaining was conducted. The expression of the Hippo pathway components, as well as that of angiotensin II type 1 and type 2 (AT1 and AT2), receptors was evaluated. Telmisartan attenuated MetS-evoked nephropathy, as demonstrated by improvement of renal function and histological features, enhancement of catalase, reduction of MDA, inflammation (NF-κB, IL-6), and renal fibrosis (increased PPAR-γ and PTEN and reduced MMP-9 and TGF-β). Telmisartan downregulated AT1-receptor, upregulated AT2-receptor and restored the Hippo pathway. Vitamin D3 replicated most of the telmisartan-elicited effects and enhanced the antifibrotic actions of telmisartan. The alleviative effects of telmisartan on MetS-evoked nephropathy may be related to the restoration of the Hippo pathway. The combination of vitamin D3 and telmisartan exerted more favourable effects on metabolic and nephropathic biomarkers compared with either one administered alone.

Exercise promotes irisin expression to ameliorate renal injury in type 2 diabetic rats

To investigate the role of irisin in exercise-induced improvement of renal function in type 2 diabetic rats. Forty male SD rats aged 4-6 weeks were randomized into normal control group, type 2 diabetes mellitus model group, diabetic exercise (DE) group and diabetic irisin (DI) group (n=8). The rats in DE group were trained with treadmill running for 8 weeks, and those in DI group were given scheduled irisin injections for 8 weeks. After the treatments, blood biochemical parameters of the rats were examined, and renal histopathology was observed with HE, Masson and PAS staining. Western blotting was used to detect the protein expression levels in the rats'kidneys. The diabetic rats showed significantly increased levels of fasting insulin, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen with lowered serum irisin level (all P < 0.05). Compared with those in DM group, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen levels were decreased and serum irisin levels were increased in both DE and DI groups (all P < 0.05). The rats in DM group showed obvious structural disorders and collagen fiber deposition in the kidneys, which were significantly improved in DE group and DI group. Both regular exercises and irisin injections significantly ameliorated the reduction of FNDC5, LC3-II/I, Atg7, Beclin-1, p-AMPK, AMPK and SIRT1 protein expressions and lowered of p62 protein expression in the kidneys of the diabetic rats (all P < 0.05). Both exercise and exogenous irisin treatment improve nephropathy in type 2 diabetic rats possibly due to irisin-mediated activation of the AMPK/SIRT1 pathway in the kidneys to promote renal autophagy.

Shen Shuai II recipe improves renal hypoxia to attenuate renal injury in 5/6 renal ablation/infarction rats and effect evaluation using blood oxygenation level-dependent functional magnetic resonance imaging

Background: Renal hypoxia plays a key role in the progression of chronic kidney disease (CKD). Shen Shuai II Recipe (SSR) has shown good results in the treatment of CKD as a common herbal formula. This study aimed to explore the effect of SSR on renal hypoxia and injury in CKD rats. Methods: Twenty-five Wistar rats underwent 5/6 renal ablation/infarction (A/I) surgery were randomly divided into three groups: 5/6 (A/I), 5/6 (A/I) + losartan (LOS), and 5/6 (A/I) + SSR groups. Another eight normal rats were used as the Sham group. After 8-week corresponding interventions, blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) was performed to evaluate renal oxygenation in all rats, and biochemical indicators were used to measure kidney and liver function, hemoglobin, and proteinuria. The expression of fibrosis and hypoxia-related proteins was analyzed using immunoblotting examination. Results: Renal oxygenation, evaluated by BOLD-fMRI as cortical and medullary T2* values (COT2* and MET2*), was decreased in 5/6 (A/I) rats, but increased after SSR treatment. SSR also downregulated the expression of hypoxia-inducible factor-1α (HIF-1α) in 5/6 (A/I) kidneys. With the improvement of renal hypoxia, renal function and fibrosis were improved in 5/6 (A/I) rats, accompanied by reduced proteinuria. Furthermore, the COT2* and MET2* were significantly positively correlated with the levels of creatinine clearance rate (Ccr) and hemoglobin, but negatively associated with the levels of serum creatinine (SCr), blood urea nitrogen (BUN), serum cystatin C (CysC), serum uric acid (UA), 24-h urinary protein (24-h Upr), and urinary albumin:creatinine ratio (UACR). Conclusion: The degree of renal oxygenation reduction is correlated with the severity of renal injury in CKD. SSR can improve renal hypoxia to attenuate renal injury in 5/6 (A/I) rats of CKD.

Differentiation Syndrome Presenting as Acute Kidney Injury in a Patient of Acute Promyelocytic Leukemia on All-trans Retinoic Acid and Arsenic Trioxide Regimen: A Case Report

Introduction: Acute promyelocytic leukemia (APL), classified as Subtype M3 of acute myeloid leukemia, is known for its relatively favorable prognosis, primarily due to the high effectiveness of all-trans retinoic acid (ATRA) in treating the maturation block. However, it is essential to be aware of potential complications such as ATRA syndrome, which can affect 5%–25% of patients and manifest with symptoms such as fever, interstitial pulmonary infiltration, pleural/pericardial effusion, and acute renal failure. Methods: We present the case of a 47-year-old female with a history of hypertension, who experienced rash, fever, and reduced urine output during the induction phase with ATRA. Her serum creatinine levels exhibited a rapid increase from 2.63 mg/dL on October 07, 2022, to 7 mg/dL on October 18, 2022, despite having normal-sized kidneys and normal corticomedullary differentiation. A renal biopsy conducted on October 20, 2022, revealed features consistent with active tubulointerstitial nephritis, with direct immunofluorescence showing no significant glomerular immune deposits. A total of 17 hemodialysis sessions were performed. Results: A subsequent bone marrow examination conducted on October 26, 2022, demonstrated a hypercellular aspirate with normal morphology. However, due to the persistence of renal failure, a repeat biopsy was performed, revealing severe acute tubular injury. Pulse steroids were initiated, and ATRA was discontinued, resulting in an improvement in renal function. Conclusion: This case highlights an instance of acute, early, and severe differentiation syndrome (DS) occurring after induction therapy in a patient with APL. The DS in this case was particularly severe, leading to renal failure necessitating hemodialysis. The prompt initiation of pulse steroids and discontinuation of ATRA proved to be effective in managing this complication. Clinicians should remain vigilant for DS and its potential complications, including acute kidney injury and acute tubulointerstitial nephritis, when treating patients with APL.

Thrombotic Microangiopathy in Solid Organ Transplantation

Thrombotic Microangiopathy (TMA) is a syndrome characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. The presence of schistocytes on peripheral smear, a negative Coombs test, elevated lactate dehydrogenase, increased reticulocyte count and low haptoglobin are often the clues for MAHA. The microvascular process often targets vasculature in kidneys, brain, gastrointestinal system, heart, and skin. A timely diagnosis and treatment are often crucial to prevent severe end organ damage and death. TMA is classified into primary and secondary forms. Primary TMA includes TTP and complement mediated or atypical hemolytic uremic syndrome (aHUS), often related to a mutation or deficiency and clinically expressed in the setting of a precipitant condition. Secondary TMA is a manifestation of underlying disorder and can occur in clinical scenarios associated with autoimmune disease, malignancy, infections, SOT (Solid Organ Transplant), pregnancy, HSCT (Hematopoietic Stem Cell Transplantation), medications, or methylmalonic acidemia. Transplant associated TMA (TA-TMA) can be complement mediated or aHUS and could be related to the ischemic reperfusion injury, induction regimen, calcineurin inhibitor (CNI) use, mammalian target of rapamycin (MTOR) inhibitor use, or could be infection related. Cost, access, and turnaround time are often the limitations for certain TTP and complement specific testing. Treatment should not be delayed while waiting for such tests. Treatment must be individualized based on the underlying cause of TMA. Terminal complement blockade utilizing monoclonal antibodies directed against C5 complement is the treatment for complement mediated TMA. C5 inhibitors have also been used successfully in treatment of secondary HUS cases where, unlike aHUS, defects in complement cannot be demonstrated. Such treatment has demonstrated improvement in renal function, MAHA and platelet counts.

Polyarteritis Nodosa Confined to the Kidneys in a Patient with Proteinuria and Mild Renal Impairment

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis predominantly involving medium- or small-sized arteries, typically of the kidneys and other internal organs. Given the rarity of PAN and the variable clinical presentation, diagnosis is challenging and, to date, no definitive diagnostic marker has been identified. A patient diagnosed with immunoglobulin A nephropathy was observed to exhibit deterioration in renal function. To determine whether new structural abnormalities had developed, computed tomography scans of the kidneys, ureters, and bladder were obtained. Both kidneys exhibited multiple cortical defects, and a renal angiogram was performed to determine the cause. Angiography revealed partial obliteration of the left distal renal artery branches and multifocal extensive infarctions in both kidneys, and the patient was diagnosed with renal-limited PAN. Following steroid monotherapy, an improvement in renal function was observed. We believe that this case report may be helpful to physicians who assess and treat patients with suspected renal-limited PAN.