Decline In Renal Function Research Articles

Interleukin-2/anti-interleukin-2 immune complex attenuates cold ischemia-reperfusion injury after kidney transplantation by increasing renal regulatory T cells.

Cold ischemia-reperfusion injury (IRI) is an unavoidable complication of kidney transplantation. We investigated the role of regulatory T cells (Treg) in cold IRI and whether the interleukin (IL)-2/anti-IL-2 antibody complex (IL-2C) can ameliorate cold IRI. We developed a cold IRI mouse model using kidney transplantation and analyzed the IL-2C impact on cold IRI in acute, subacute and chronic phases. Treg transfer attenuated cold IRI, while Treg depletion aggravated cold IRI. Next, IL-2C administration prior to IRI mitigated acute renal function decline, renal tissue damage and apoptosis and inhibited infiltration of effector cells into kidneys and pro-inflammatory cytokine expression on day 1 after IRI. On day 7 after IRI, IL-2C promoted renal regeneration and reduced subacute renal damage. Furthermore, on day 28 following IRI, IL-2C inhibited chronic fibrosis. IL-2C decreased reactive oxygen species-mediated injury and improved antioxidant function. When IL-2C was administered following IRI, it also increased renal regeneration with Treg infiltration and suppressed renal fibrosis. In contrast, Treg depletion in the presence of IL-2C eliminated the positive effects of IL-2C on IRI. Tregs protect kidneys from cold IRI and IL-2C inhibited cold IRI by increasing the renal Tregs, suggesting a potential of IL-2C in treating cold IRI. Interleukin (IL)-2/anti-IL-2 antibody complex attenuated acute renal injury, facilitated subacute renal regeneration and suppressed chronic renal fibrosis after cold ischemia-reperfusion injury (IRI) by increasing the renal Tregs. IL-2/anti-IL-2 antibody complex decreased reactive oxygen species-mediated injury and improved antioxidant function. This study suggests the therapeutic potential of the IL-2/anti-IL-2 antibody complex in kidney transplantation-associated cold IR.

Renal function and lipid metabolism in Japanese HIV-1-positive individuals 288 weeks after switching from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate: a single-center, retrospective cohort study

BackgroundContinued use of tenofovir disoproxil fumarate (TDF), an antiretroviral drug, causes renal function decline and tubular damage in individuals with HIV. While tenofovir alafenamide fumarate (TAF) may have less damaging effects, it causes weight gain and abnormal lipid metabolism.MethodsThis single-center, retrospective cohort study used medical records from the National Hospital Organization Sendai Medical Center to investigate renal function of Japanese HIV-1-positive individuals who switched from TDF to antiretroviral therapy including TAF by 2017. The endpoints were: estimated glomerular filtration rate (eGFR), urinary β2 microglobulin (Uβ2MG), weight, and lipid metabolism parameters at 288 weeks after switching. Possible correlation between eGFR and Uβ2MG and factors affecting eGFR decline were examined.ResultsSixty patients switched from TDF to TAF and continued therapy for 288 weeks. eGFR showed a significant decline after 144 weeks, although it was controlled from the time of change until 96 weeks. In the renal impairment group, the decline was suppressed until week 288. Uβ2MG continued to decrease significantly after 48 weeks. However, the suggested correlation between eGFR and Uβ2MG disappeared when patients switched from TDF to TAF. Weight and lipid metabolic parameters increased significantly at 48 weeks and were maintained. Factors associated with decreased eGFR were: history of acquired immune deficiency syndrome (AIDS) and Uβ2MG. However, considering the odds ratio, the switch from TDF to TAF suppressed the eGFR decline in the group with a history of AIDS, and Uβ2MG had no effect on the eGFR decline.ConclusionsSwitching from TDF to TAF for the long term slows eGFR decline, decreases Uβ2MG levels, and reduces worsening of renal function. Weight gain and abnormal lipid metabolism may occur in the short term but are controllable.

Effects of Alterations in Acid-Base Effects on Insulin Signaling.

Insulin tightly regulates glucose levels within a narrow range through its action on muscle, adipose tissue and the liver. The activation of insulin receptors activates multiple intracellular pathways with different functions. Another tightly regulated complex system in the body is acid-base balance. Metabolic acidosis, defined as a blood pH < 7.35 and serum bicarbonate < 22 mmol/L, has clear pathophysiologic consequences including an effect on insulin action. With the ongoing intake of typical acid-producing Western diets and the age-related decline in renal function, there is an increase in acid levels within the range considered to be normal. This modest increase in acidosis is referred to as "acid stress" and it may have some pathophysiological consequences. In this article, we discuss the effects of acid stress on insulin actions in different tissues.

Impact of obesity on renal function in elderly Korean adults: a national population-based cohort study.

Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13-1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84-1.11), 1.10 (0.96-1.27), 1.24 (1.06-1.45), 1.37 (1.12-1.66), and 1.99 (1.42-2.79), respectively (p for trend < 0.001). In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

Advances in understanding of dendritic cell in the pathogenesis of acute kidney injury.

Acute kidney injury (AKI) is characterized by a rapid decline in renal function and is associated with a high morbidity and mortality rate. At present, the underlying mechanisms of AKI remain incompletely understood. Immune disorder is a prominent feature of AKI, and dendritic cells (DCs) play a pivotal role in orchestrating both innate and adaptive immune responses, including the induction of protective proinflammatory and tolerogenic immune reactions. Emerging evidence suggests that DCs play a critical role in the initiation and development of AKI. This paper aimed to conduct a comprehensive review and analysis of the role of DCs in the progression of AKI and elucidate the underlying molecular mechanism. The ultimate objective was to offer valuable insights and guidance for the treatment of AKI.

The predictive value of miR-377 and phospholipase A2 in the early diagnosis of diabetic kidney disease and their relationship with inflammatory factors

ObjectiveThe value of novel biomarkers for DKD has received increasing attention, and there is an urgent need for novel biomarkers with sensitivity, specificity and ability to detect kidney damage.miR-377 regulates many basic biological processes, plays a key role in tumor cell proliferation, migration and inflammation, and can also increase the expression of matrix proteins and fibronectin, leading to renal tubulointerstitial inflammation and renal fibrosis. Lipoprotein-associated phospholipase A2, as an inflammatory marker, is involved in the pathological process of microalbuminuria production and renal function decline, and is a predictive factor of microalbuminuria production and renal function decline, and can be used as an indicator to evaluate the progression of DKD.The aim of this study was to investigate the effects of miR-377 and phospholipase A2 on the development of diabetic kidney disease through regulation of inflammatory factors and the mechanism of action.Methods: 80 diabetic patients were divided into two groups according to urinary albumin-to-creatinine ratio (UACR): diabetic normal proteinuria group (n = 42) and diabetic proteinuria group (n = 38). Forty-three healthy people were selected as the normal control group. The serum levels of TGF-β, IL-6, and IL-18 were measured by ELISA, miR-377 was detected by qPCR, and the serum levels of phospholipase A2 were detected by electrochemiluminescence. Analyze the correlation of study group indicators, ROC curve was used to evaluate the diagnostic efficacy of miR-377 and phospholipase A2 in diabetic kidney disease. Results: The average levels of serum TGF-β, IL-6, IL-18, miR-377 and phospholipase A2 in diabetic proteinuria group were significantly higher than those in normal control group and diabetic proteinuria normal group(P < 0.05). miR-377, phospholipase A2 were significantly correlated with inflammatory factors such as glomerular filtration rate and TGF-β. miR-377 and phospholipase A2 are independent predictors of diabetic kidney disease. The area under the curve of miR-377 and phospholipase A2 in the normal diabetic proteinuria group and the diabetic proteinuria group were 0.731 and 0.744, respectively. Conclusion: miR-377 and phospholipase A2 have good diagnostic efficiency for the early diagnosis of diabetic kidney disease. They can be used as early biomarkers.miR-377 and phospholipase A2 were positively correlated with inflammatory factors and involved in the occurrence and development of diabetic kidney disease.

Role of Blood Cell Indexes in Progresses to ESRD

AbstractChronic kidney disease (CKD) is a complex health condition characterized by the gradual loss of renal function, often leading to end-stage renal disease (ESRD). It results from a combination of medical, environmental, and genetic factors. Predicting the rate of renal function decline and effectively managing the progression to ESRD is challenging in clinical practice. CKD assessment involves various indicators, including estimated glomerular filtration rate (eGFR), albuminuria levels, serum creatinine, and others. This study aimed to explore the predictive potential of specific blood cell indexes in forecasting further renal function decline and the transition from CKD stage 3–4 to ESRD. We assessed the following blood cell indexes in 377 CKD stage 3–4 patients: absolute neutrophil count (ANC), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), derived NLR (dNLR), mean platelet volume (MPV), aggregate index of systemic inflammation (AISI), and systemic inflammation index (SII). ANC, MPV, NLR, PLR, dNLR, and SII were found to independently predict a rapid decline in eGFR. Notably, NLR and dNLR demonstrated the highest sensitivity and specificity with cut-off values of 3.36 and 2.45, respectively (NLR: 88.6 and 81.7%; dNLR: 85.2 and 75.8%). The corresponding area under the ROC curve values were 0.877 (95% CI 0.837–0.918, p &lt; 0.001) for NLR and 0.849 (95% CI 0.805–0.892, p &lt; 0.001) for dNLR. However, none of the blood cell indexes independently predicted the transition to ESRD. The NLR and the dNLR exhibited the highest predictive capacity towards a rapid decline in renal function in CKD. No blood cell index, however, independently predicted the transition into ERSD.

Sacubitril/valsartan ameliorates tubulointerstitial fibrosis by restoring mitochondrial homeostasis in diabetic kidney disease

BackgroundTubulointerstitial fibrosis plays an important role in the progression of diabetic kidney disease (DKD). Sacubitril/valsartan (Sac/Val) exerts a robust beneficial effect in DKD. However, the potential functional effect of Sac/Val on tubulointerstitial fibrosis in DKD is still largely unclear.MethodsStreptozotocin-induced diabetic mice were given Sac/Val or Val by intragastric administration once a day for 12 weeks. The renal function, the pathological changes of tubule injury and tubulointerstitial fibrosis, as well as mitochondrial morphology of renal tubules in mice, were evaluated. Genome-wide gene expression analysis was performed to identify the potential mechanisms. Meanwhile, human tubular epithelial cells (HK-2) were cultured in high glucose condition containing LBQ657/valsartan (LBQ/Val). Further, mitochondrial functions and Sirt1/PGC1α pathway of tubular epithelial cells were assessed by Western blot, Real-time-PCR, JC-1, MitoSOX or MitoTracker. Finally, the Sirt1 specific inhibitor, EX527, was used to explore the potential effects of Sirt1 signaling in vivo and in vitro.ResultsWe found that Sac/Val significantly ameliorated the decline of renal function and tubulointerstitial fibrosis in DKD mice. The enrichment analysis of gene expression indicated metabolism as an important modulator in DKD mice with Sac/Val administration, in which mitochondrial homeostasis plays a pivotal role. Then, the decreased expression of Tfam and Cox IV;, as well as changes of mitochondrial function and morphology, demonstrated the disruption of mitochondrial homeostasis under DKD conditions. Interestingly, Sac/Val administration was found to restore mitochondrial homeostasis in DKD mice and in vitro model of HK-2 cells. Further, we demonstrated that Sirt1/PGC1α, a crucial pathway in mitochondrial homeostasis, was activated by Sac/Val both in vivo and in vitro. Finally, the beneficial effects of Sac/Val on mitochondrial homeostasis and tubulointerstitial fibrosis was partially abolished in the presence of Sirt1 specific inhibitor.ConclusionsTaken together, we demonstrate that Sac/Val ameliorates tubulointerstitial fibrosis by restoring Sirt1/PGC1α pathway-mediated mitochondrial homeostasis in DKD, providing a theoretical basis for delaying the progression of DKD in clinical practice.

Hydronephrosis severity as a predictor of postoperative renal function decline following laparoscopic radical nephroureterectomy.

This study aimed to investigate factors, including the degree of hydronephrosis, that may be associated with decreased renal function after radical nephroureterectomy (RNU). This study included 252 patients who underwent laparoscopic RNU with an estimated glomerular filtration rate (eGFR) ≥ 30ml/min/1.73 m2 in three institutions. We assessed the association between hydronephrosis grade and perioperative renal function and performed a stepwise multivariate linear regression analysis to identify factors associated with postoperative eGFR. Patients with preoperative eGFR ≥ 50ml/min/1.73 m2 were divided into a training set and an independent external validation set to develop a predictive model for postoperative renal function. The median preoperative and postoperative eGFR were 61.1 and 46.4ml/min/1.73 m2, respectively. The eGFR preservation rates were 66.9%, 66.6%, 88.1%, and 100.0% in groups without, with mild, moderate, and severe hydronephrosis, respectively, and this difference was statistically significant (p < 0.001). Multivariate analysis revealed that factors predictive of postoperative eGFR included sex, preoperative eGFR, clinical T stage (cT3-4), and the presence of moderate or severe hydronephrosis. Our predictive model, based on these factors, positively correlated with actual postoperative renal function, and the similarity in categories with or without renal function insufficiency between predicted and actual postoperative renal functions was 78% in both training and validation sets. Moderate or severe hydronephrosis is associated with a modest postoperative decline in renal function, while mild hydronephrosis is not. Our predictive model may be useful in predicting postoperative renal function insufficiency and guiding decision-making for perioperative medical treatment.

Intra-abdominal pressure and residual renal function decline in peritoneal dialysis: a threshold-based investigation

Background The potential impact of elevated intra-abdominal pressure (IAP) on residual renal function (RRF) has not been determined. The objective of this study was to investigate the relationship between IAP and the rate of RRF decline in newly initiated peritoneal dialysis (PD) patients, and to identify the optimal IAP threshold value for delaying the deterioration of RRF. Methods A cohort of 62 newly initiated PD patients who completed both 6- and 12-month follow-up evaluations was obtained using the Durand method. A logistic regression model was used to identify variables associated with a rapid decline in RRF. Receiver operating characteristic (ROC) curves were generated to determine the optimal threshold value. Another retrospective cohort analysis was performed to validate the identified critical value. Results For each 1 cmH2O increase in IAP, the risk of a rapid decline in the RRF increased by a factor of 1.679. Subsequent analysis revealed that patients in the high IAP group had more significant decreases in residual renal estimated glomerular filtration rate (eGFR) (Z = −3.694, p < 0.001) and urine volume (Z = −3.121, p < 0.001) than did those in the non-high IAP group. Furthermore, an IAP ≥15.65 cmH2O was a robust discriminator for the prediction of the rate of RRF decline. Conclusion Patients in the high IAP group experienced a more rapid decline in RRF. Additionally, an optimal critical pressure of 15.65 cmH2O was identified for predicting the rate of RRF decline. IAP, as one of the factors contributing to the rapid decline in RRF in the first year of PD, should be given due attention.

Bilateral Renal Ischemia-Reperfusion Model for Acute Kidney Injury in Mice.

Acute kidney injury (AKI) is defined as a rapid decline in renal function, in which persistent kidney dysfunction gradually progresses to chronic kidney disease (CKD) due to the irreversible loss of nephrons and their maladaptive repair. In recent years, the incidence of AKI has been increasing concerning diverse etiologies, including volume depletion, sepsis, nephrotoxicity, muscle injury, and major trauma, in which ischemia-reperfusion injury (IRI)accounts for most episodes. Development of the IRI model in mice is induced by surgical clamping of the renal pedicles, which provides powerful and controllable tools for preclinical models of AKI. Importantly, the IRI model is deployed at different stages of the AKI development, especially in the processes of AKI to CKD. Despite the IRI model being widely practiced in many laboratories, a series of variables still influence the results of this model. Here, we describe the procedure of IRI model development to provide a repeatable and reliable method for researchers to explore the underlying pathogenesis in the development of AKI and the progression of AKI to CKD.

New-onset metabolic syndrome is associated with accelerated renal function decline partially through elevated uric acid: an epidemiological cohort study.

The burden of metabolic syndrome (MetS) continues to rise globally and is associated with complications of multiple organ systems. We aimed to identify the association between changes in MetS status and accelerated renal function progression through a regional epidemiological survey in China, thus discovering influence factors with treatable potential. This study was a population-based survey conducted in 2008 and 2014, assessing a representative sample of 5,225 individuals from rural areas of China. They were divided into four subgroups according to their MetS status in 2008 and 2014 (Never, Previously abnormal, New-onset, and Consistent). Multivariate logistic regression and stratification analysis evaluated the relationship between clinical factors and renal function decline under different MetS statuses. Smooth curve fitting further addressed the role of serum uric acid, illustrating the vital turning point of uric acid levels in the background of renal function deterioration. Of all groups of MetS states, the new-onset MetS showed the most significant eGFR decline, with a 6.66 ± 8.21 mL/min/1.73 m2 decrease over 6 years. The population with newly-onset MetS showed a considerable risk increase in delta eGFR with a beta coefficient of 1.66 (95%CI=1.09-2.23) after necessary correction. In searching for the drivers, the strength of the association was significantly reduced after additional adjustment for uric acid levels (β=0.91, 95%CI=0.35-1.45). Regarding the turning point, uric acid levels exceeding 426 μmol/L were more significantly associated with the stepped-up deterioration of kidney function for those with new-onset MetS. Metabolic syndrome demonstrated a solid correlation with the progression of renal function, particularly in those with newly-onset MetS status. In addition to the diagnostic components of MetS, hyperuricemia could be used as a marker to identify the high risk of accelerating eGFR decline early. Furthermore, we suggested a potential renal benefit for the newly-onset MetS population when maintaining their serum uric acid level below the criteria for asymptomatic hyperuricemia.

Gender Differences in the Incidence of Nephropathy and Changes in Renal Function in Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Study.

This research aims to examine and scrutinize gender variations in the incidence of diabetic nephropathy (DN) and the trajectory of renal function in type 2 diabetes mellitus (T2DM) patients. We conducted a retrospective cohort study that enrolled 1549 patients diagnosed with T2DM from May 2015 to July 2023. We separately compared the clinical characteristics of male and female participants with and without DN. We utilized the Kaplan-Meier method to examine the cumulative incidence of DN among T2DM patients of varying genders. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using univariable and multivariable Cox proportional hazards regression analysis to evaluate the correlation between various factors and the risk of DN incidence. Multiple linear regression was utilized to investigate the relationship between ΔeGFR% and each factor. Logistic regression with cubic spline function and smooth curve fitting was employed to analyze the nonlinear link between ΔeGFR% and the risk of DN among participants of different genders. The prevalence of DN was higher in female participants (17.31%) than in male participants (12.62%), with a significant cumulative risk ratio (1.33 [1.02-1.73], P = 0.034). Multiple linear regression analysis revealed that creatinine, female gender, blood urea nitrogen, alkaline phosphatase, and total cholesterol had a significant impact on ΔeGFR% in T2DM patients, with standardized β coefficients of -0.325, -0.219, -0.164, -0.084, and 0.071, respectively. The restricted cubic spline analysis demonstrated a strong negative association between ΔeGFR% and the risk of developing DN (P < 0.001). Both male and female patients with T2DM had a higher prevalence of DN over the 5-year follow-up period. However, women had a greater risk of developing DN and a faster decline in renal function compared to men.

Herbal Components for the Treatment of Various Kidney Disorders

Abstract:: Acute kidney injury is described as a loss of renal excretory function that occurs suddenly. AKI is one of several ailments grouped together as acute kidney diseases and disorders (AKD), in which progressive degradation of kidney function or persistent renal dysfunction is associated with irreversible loss of kidney cells and nephrons, potentially leading to chronic kidney disease (CKD). The prevalence and incidence of KDs are assessed in light of population disparities in the prevalence of risk factors such as diabetes, hypertension, and obesity. However, the presence of these associated illnesses does not fully explain the increased rate of progression of chronic renal disease in high-risk patients (CKD). The development of renal disease is accompanied by a decline in renal function, which eventually leads to renal failure. The current status of diagnostic testing does not allow for accurate early disease diagnosis, prognosis, or therapy efficacy monitoring. Despite significant advances in care and understanding of the causes of acute renal failure (ARF), many aspects of ARF remain controversial, confusing, and uncertain. Accurate information on the disease's prevalence, genesis, and clinical manifestations is required to successfully advocate for enough funding and resources to manage the disease. Herbal components for the treatment of a variety of kidney disorders, and the page includes a list of plants that are good for kidney treatment. This review focuses on several herbal products used to treat renal problems. It is clear from this study that medicinal plants play an important role in the fight against many different diseases. Several different plants and plant extracts have been shown to have beneficial effects in treating renal disease. These medications have great promise for use in treating kidney damage because of their nephroprotective, cytoprotective, immunomodulatory, antioxidant, anti-inflammatory, and reducing effects on oxidative stress, renal hypertension, and blood toxins such as urea, creatinine, and others. Therefore, India's traditional medicine offers a wide variety of medications that can be utilized in renal illnesses due to their effectiveness in both treating the ailment and restoring normal kidney function. Therefore, it is suggested that additional research be conducted to learn many aspects and mechanisms of medications.

Cumulative blood pressure load and hypertensive nephropathy in Han Chinese hypertensive patients.

The study aims to assess the relationship between cumulative blood pressure load (cBPL) and the risk of renal function decline in hypertensive patients and determine the blood pressure (BP) threshold required to prevent hypertensive nephropathy. A single-center prospective cohort study was conducted on hypertensive patients. The cBPL was defined as the proportion of area beyond variable BP cutoffs under ambulatory BP monitoring. Renal events were defined as>25% (minor) or>50% (major) decline of baseline estimated glomerular filtration rate (eGFR). Cox regression analysis was conducted between cBPL, other ambulatory BP parameters, and renal events. The results revealed a total of 436 Han Chinese hypertensive patients were eligible for enrollment. During an average follow-up period of 5.1±3.3 years, a decline of>25% and>50% in eGFR was observed in 77 and eight participants, respectively. Cox regression analysis revealed that cSBPL140 (hazard ratio [HR], 1.102; 95% confidence interval [CI], 1.017-1.193; p=.017), cSBPL130 (HR, 1.076; 95% CI, 1.019-1.137; p=.008), and cSBPL120 (HR, 1.054; 95% CI, 1.010-1.099; p=.015) were independently associated with minor renal events. Similarly, cSBPL140 (HR, 1.228; 95% CI, 1.037-1.455; p=.017), cSBPL130 (HR, 1.189; 95% CI, 1.045-1.354; p=.009), and cSBPL120 (HR, 1.155; 95% CI, 1.039-1.285; p=.008) were independently associated with major renal events. In conclusion, cBPL is associated with renal function decline in hypertensive patients. Minimizing cBPL120 may decrease the risk of hypertensive nephropathy.

Microangiopathy associated with poor outcome of immunoglobulin A nephropathy: a cohort study and meta-analysis

ABSTRACT Background Microangiopathy (MA) lesions are not rare in immunoglobulin A nephropathy (IgAN) and have been suggested to have a potential role in increasing risk in renal function decline. However, this suggestion has not been universally accepted. We aimed to investigate its role in our cohort and in multiple studies through a systematic meta-analysis. Methods This cohort study included 450 IgAN patients, confirmed by renal biopsy, at Tongji Hospital, China, from January 2012 to December 2016. Clinical data were collected and analysed. We systematically searched PubMed and Web of Science for studies investigating the association between MA lesions and IgAN. Results In our cohort, IgAN patients with MA were significantly older and had higher blood pressure, more proteinuria, worse kidney function and increased uric acid levels compared with patients without MA. When comparing pathological features with the non-MA group, the MA group exhibited more global glomerulosclerosis and interstitial fibrosis/tubular atrophy. MA lesions were independently associated with a composite kidney outcome in IgAN patients {adjusted hazard ratio 2.115 [95% confidence interval (CI) 1.035–4.320], P = .040}. Furthermore, this relationship was validated in a meta-analysis involving 2098 individuals from five independent cohorts. The combined data showed a 187% adjusted risk of poor renal outcome in IgAN patients with MA compared with patients without MA [adjusted risk ratio 2.87 (95% CI 2.05–4.02; I2 = 53%). Conclusion MA lesions could serve as a valuable predictor for disease progression in patients with IgAN, extending beyond the widely recognized Oxford MEST-C score.

Renal Function Evolution and Hypoaldosteronism Risk After Unilateral Adrenalectomy for Primary Aldosteronism.

Few studies demonstrated a percentage decrease in the estimated glomerular filtration rate (eGFR) at a single time and the rate of hypoaldosteronism after adrenalectomy for primary aldosteronism (PA). Our aim was to investigate the evolution of renal function and the hypoaldosteronism risk after adrenalectomy for PA. Aldosterone, renin, eGFR, and electrolyte levels were determined before and at 1 week, 1, 3 and 6 months after unilateral adrenalectomy in 94 PA patients (40 men and 54 women). The main outcome was the postoperative eGFR decline using analysis of covariance with the preoperative eGFR as a covariate. eGFR decreased during first postoperative week compared to 3 months before surgery. During the first 6 months, eGFR remained stable at similar levels to the first week after surgery. Age (p=0.001), aldosterone levels (p=0.021) and eGFR 3 months before surgery (p+<+0.0001) had a significant correlation with eGFR during first postoperative week. High aldosterone levels at diagnosis were correlated with decline in renal function in the univariate model (p=0.033). In the multivariate analysis, aldosterone levels at diagnosis had a tendency to be an independent predictor of renal function after surgery (p=0.059). Postoperative biochemical hypoaldosteronism was diagnosed in 48% of the cases after adrenalectomy, but prolonged hyperkalemia occurred in only 4 cases (4.5%). Our findings showed a decrease of eGFR after unilateral adrenalectomy for PA. Additionally, aldosterone levels at diagnosis correlated with postoperative renal function. Postoperative biochemical hypoaldosteronism occurred in almost half of the patients, but prolonged hyperkalemia with fludrocortisone replacement was less frequent.

Tubular Endogenous Erythropoietin Protects Renal Function against Ischemic Reperfusion Injury.

Many large-scale studies show that exogenous erythropoietin, erythropoiesis-stimulating agents, lack any renoprotective effects. We investigated the effects of endogenous erythropoietin on renal function in kidney ischemic reperfusion injury (IRI) using the prolyl hydroxylase domain (PHD) inhibitor, Roxadustat (ROX). Four h of hypoxia (7% O2) and 4 h treatment by ROX prior to IRI did not improve renal function. In contrast, 24-72 h pretreatment by ROX significantly improved the decline of renal function caused by IRI. Hypoxia and 4 h ROX increased interstitial cells-derived Epo production by 75- and 6-fold, respectively, before IRI, and worked similarly to exogenous Epo. ROX treatment for 24-72 h increased Epo production during IRI by 9-fold. Immunohistochemistry revealed that 24 h ROX treatment induced Epo production in proximal and distal tubules and worked similarly to endogenous Epo. Our data show that tubular endogenous Epo production induced by 24-72 h ROX treatment results in renoprotection but peritubular exogenous Epo production by interstitial cells induced by hypoxia and 4 h ROX treatment did not. Stimulation of tubular, but not peritubular, Epo production may link to renoprotection.

Is eGFR Slope a Novel Predictor of Chronic Complications of Type 2 Diabetes Mellitus? A Systematic Review and Meta-Analysis.

Diabetic kidney disease affects approximately 40% of patients with type 2 diabetes mellitus (T2DM) and is associated with an increased risk of end-stage kidney disease (ESKD) and cardiovascular (CV) events, as well as increased mortality. Among the indicators of decline in renal function, the eGFR slope is acquiring an increasing clinical interest. The aim of this study was to evaluate, through a systematic review of the literature and meta-analysis of the collected data, the association between the decline of the eGFR slope, chronic complications, and mortality of T2DM patients, in order to understand whether or not the eGFR slope can be defined as a predictive indicator of complications in T2DM. The review and meta-analysis were conducted according to PRISMA guidelines considering published studies on patients with T2DM. A scientific literature search was carried out on PubMed from January 2003 to April 2023 with subsequent selection of scientific papers according to the inclusion criteria. Fifteen studies were selected for meta-analysis. Risk analysis as hazard ratio (HR) indicated a significant association between all events considered (all-cause mortality, CV events, ESKD, and microvascular events) for patients with steeper eGFR slope decline than subjects with stable eGFR. Calculated HRs (with 95% CI) were as follows: for all-cause mortality, 2.31 (1.70-3.15); for CV events, 1.73 (1.43-2.08); for ESKD, 1.54 (1.45-1.64); and for microvascular events, 2.07 (1.57-2.73). Overall HR was 1.82 (1.72-1.92). An association between rapid eGFR decline and chronic diabetes complications was demonstrated, suggesting that eGFR slope variability significantly impacts the course of T2DM and that eGFR slope should be considered as a predictor for chronic complications in patients with T2DM. According to the obtained results, the therapeutic management of the patient with diabetes should not focus exclusively on glycaemic control, and particular attention should be paid to preserve renal function.

Natural History and Management of Ultrasound-detected Small Renal Angiomyolipoma.

Recent advances in imaging methods increased the incidental detection of small renal angiomyolipoma (AML). However, guidelines for managing small AML are lacking, and decisions about imaging frequency and timing of intervention are made on an individual basis. This study aims to investigate the clinical behavior of small sporadic AML and propose an optimal follow-up strategy. The study is a retrospective analysis of 168 individuals who had hyperechoic lesions, suggestive of AML detected during abdominal ultrasound as a part of their health checkup. The clinical information of the individuals, including tumor characteristics and renal function, was reviewed. Statistical analysis was performed to identify factors associated with tumor growth and renal function. Most AMLs were small (≤20 mm) and did not exhibit malignant characteristics. The tumors showed a slow growth rate, with a mean growth rate of 0.24 mm/year. Only a small proportion of cases (1.2%) required intervention due to significant enlargement. Factors such as tumor size and gender were not significantly associated with tumor growth rate or renal function. However, younger patients showed a higher tumor growth rate and a more pronounced decline in renal function. Small sporadic AMLs have a slow growth rate and little risk of malignancy. Neither tumor size nor gender was predictive factors for tumor growth or renal function. Nevertheless, close monitoring of tumor growth and renal function is advised, particularly in younger patients. This study highlights the need for further research and guidelines to establish an optimal surveillance protocol for small AMLs.