Progressive Decline In Renal Function Research Articles

THE GLA D313Y MUTATION IN FABRY DISEASE: DIAGNOSTIC DILEMMAS AND THERAPEUTIC CONSIDERATIONS

Abstract Fabry disease is a genetic disorder caused by mutations in the GLA gene, which encodes alpha–galactosidase A, leading to enzyme dysfunction and subsequent accumulation of glycosphingolipids. In the classical form, it occurs in childhood or early adolescence with renal, cardiac, and neurological involvement, resulting in a poor prognosis. The GLA D313Y is a missense mutation resulting in a significant reduction of enzyme activity in plasma, while leukocyte enzyme activity remains within normal limits, leading to a "pseudo–deficiency" of enzyme activity with uncertain pathogenicity. In literature, it has been observed that individuals with this mutation may present predominantly with central neurologic manifestations, characterized by multifocal white matter lesions. Historically they do not receive indications for initiating enzyme replacement or molecular chaperone therapies. We present the case of a man affected by arterial hypertension and history of chronic lower limb pain who experienced a lacunar stroke at the age of 35. The GLA D313Y mutation was identified and enzyme activity assay in plasma was within normal limits, precluding the initiation of enzyme replacement therapy. Over the following years, he suffered two additional ischemic strokes, a progressive decline in renal function to stage 3, and acute coronary syndrome. Transthoracic echocardiography revealed hypertrophic non–obstructive cardiomyopathy (SIVd 20 mm) with normal biventricular ejection fraction. Cardiac magnetic resonance showed late gadolinium enhancement of inferior junctional and inferior wall in middle segment (Fig.1). Considering the patient‘s clinical conditions involving multi–organ impairment, an enzymatic activity test was performed on leukocytes, revealing a reduced activity. This prompted the decision to initiate enzyme replacement therapy. This case report supports the hypothesis that the D313Y mutation may be associated with a later presentation and not only neurological involvement. In our experience, it’s mandatory to proceed with the determination of leukocyte enzyme activity in presence of normal enzyme activity in plasma. As an alternative, the detection of glycosphingolipids’ accumulation could be useful, but myocardial and renal biopsy poses a high bleeding risk, especially in anticoagulated or antiaggregated patients. The authors propose considering the initiation of therapy in patients with the D313Y mutation who exhibit significant organ involvement.

Diabetes and Renal Complications: An Overview on Pathophysiology, Biomarkers and Therapeutic Interventions.

Diabetic kidney disease (DKD) is a major microvascular complication of both type 1 and type 2 diabetes. DKD is characterised by injury to both glomerular and tubular compartments, leading to kidney dysfunction over time. It is one of the most common causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Persistent high blood glucose levels can damage the small blood vessels in the kidneys, impairing their ability to filter waste and fluids from the blood effectively. Other factors like high blood pressure (hypertension), genetics, and lifestyle habits can also contribute to the development and progression of DKD. The key features of renal complications of diabetes include morphological and functional alterations to renal glomeruli and tubules leading to mesangial expansion, glomerulosclerosis, homogenous thickening of the glomerular basement membrane (GBM), albuminuria, tubulointerstitial fibrosis and progressive decline in renal function. In advanced stages, DKD may require treatments such as dialysis or kidney transplant to sustain life. Therefore, early detection and proactive management of diabetes and its complications are crucial in preventing DKD and preserving kidney function.

Prevalence of dysmagnesemia among CKD patients in North India

Prevalence of dysmagnesemia among CKD patients in North India

Native T1-mapping as a predictor of progressive renal function decline in chronic kidney disease patients

BackgroundTo investigate the potential of Native T1-mapping in predicting the prognosis of patients with chronic kidney disease (CKD).MethodsWe enrolled 119 CKD patients as the study subjects and included 20 healthy volunteers as the control group, with follow-up extending until October 2022. Out of these patients, 63 underwent kidney biopsy measurements, and these patients were categorized into high (25–50%), low (< 25%), and no renal interstitial fibrosis (IF) (0%) groups. The study's endpoint event was the initiation of renal replacement therapy, kidney transplantation, or an increase of over 30% in serum creatinine levels. Cox regression analysis determined factors influencing unfavorable kidney outcomes. We employed Kaplan–Meier analysis to contrast kidney survival rates between the high and low T1 groups. Additionally, receiver-operating characteristic (ROC) curve analysis assessed the predictive accuracy of Native T1-mapping for kidney endpoint events.ResultsT1 values across varying fibrosis degree groups showed statistical significance (F = 4.772, P < 0.05). Multivariate Cox regression pinpointed 24-h urine protein, cystatin C(CysC), hemoglobin(Hb), and T1 as factors tied to the emergence of kidney endpoint events. Kaplan–Meier survival analysis revealed a markedly higher likelihood of kidney endpoint events in the high T1 group compared to the low T1 value group (P < 0.001). The ROC curves for variables (CysC, T1, Hb) tied to kidney endpoint events demonstrated area under the curves(AUCs) of 0.83 (95%CI: 0.75–0.91) for CysC, 0.77 (95%CI: 0.68–0.86) for T1, and 0.73 (95%CI: 0.63–0.83) for Hb. Combining these variables elevated the AUC to 0.88 (95%CI: 0.81–0.94).ConclusionNative T1-mapping holds promise in facilitating more precise and earlier detection of CKD patients most at risk for end-stage renal disease.

Aristolochic acid induces acute kidney injury through ferroptosis.

Aristolochic acid (AA)-induced acute kidney injury (AKI) presents with progressive decline in renal function and rapid progression to end-stage renal disease. Among the multiple mechanisms identified in AKI, ferroptosis has been shown to be involved in various forms of AKI. But few studies have elucidated the role of ferroptosis in AA-induced AKI. In this study, we investigated the role of ferroptosis in AA-induced acute renal tubular injury in vivo and in vitro. Mice with acute aristolochic acid nephropathy showed increased malondialdehyde levels, aggravated lipid peroxidation, decreased superoxide dismutase activity, and glutathione depletion. The expression of glutathione peroxidase 4 was decreased and the expression of acyl-CoA synthetase long-chain family member 4 was increased. Inhibition of ferroptosis by ferrostatin-1 significantly improved the renal function, reduced histopathological lesions, partially alleviated lipid peroxidation, and restored the antioxidant capacity. In vitro studies also revealed that AA significantly reduced cell viability, induced reactive oxygen species production, increased intracellular iron level and decreased ferroptosis-related protein expression. Inhibition of ferroptosis significantly increased cell viability and attenuated AA-induced renal tubular epithelial cell injury. It is suggested that ferroptosis plays an important role in AA-induced acute tubular injury. And inhibition of ferroptosis may exert renoprotective effects possibly by preventing lipid peroxidation, restoring the antioxidant activity or regulating iron metabolism.

Single-access, non-contrast transcatheter aortic valve implantation, the ultimate minimalist approach: a case report

Abstract Background Transcatheter aortic valve implantation (TAVI) is an established treatment for patients with symptomatic severe aortic stenosis. Patients with previous renal transplant are considered as a high-risk cohort who may develop procedural complications related to vascular access and renal impairment post-TAVI. Case summary Herein, we report a case of an 88-year-old male who presented with progressive dyspnoea. His transthoracic echocardiogram revealed severe aortic stenosis with a peak gradient of 75 mmHg and impaired left ventricle systolic function (an estimated ejection fraction of 40%). He had a background of kidney transplant with progressive decline in renal function, requiring the formation of left arm arteriovenous fistula in preparation for future dialysis. He was successfully treated with TAVI using a single vascular access site without administering contrast media. Discussion Single-access, non-contrast TAVI is feasible when treating renal transplant patients with severe aortic stenosis and limited vascular access. The current minimalistic approach should be used only in highly selective patient cases.

Nephrolithiasis Associated with Nephrocalcinosis Is Primarily Composed of Carbonate Apatite.

This study was designed to determine the mineral composition of calculi in nephrocalcinosis with nephrolithiasis, diagnose the underlying disease, and monitor the course of renal function in patients with nephrocalcinosis-nephrolithiasis. Renal calculi extruded in a series of 8 patients with nephrocalcinosis were analysed using Fourier transmission infrared spectrometry. In 4 patients, next-generation sequencing using a nephrocalcinosis-nephrolithiasis panel was performed to determine the nature of the underlying disease. In addition, longitudinal analysis of renal function was performed in all patients. Seven patients revealed carbonate apatite as the sole constituent of renal calculi. One patient showed a mixed composition of dicalcium phosphate dihydrate/carbonate apatite at first analysis yet in subsequent episodes also had calculi composed of pure carbonate apatite. Further molecular analysis displayed distal renal tubular acidosis in 2 of 4 patients who consented to sequencing. No known genetic defect could be found in the other two cases. In line with prior reports, decline of renal function was dependent on underlying disease. Distal renal tubular acidosis revealed a progressive course of renal failure, whereas other causes showed stable renal function in long term analysis. Nephrocalcinosis with nephrolithiasis is a rare condition with heterogeneous aetiology. Yet mineral composition of renal calculi predominantly consisted of pure carbonate apatite. This uniform finding is similar to subcutaneous calcifications of various origins and might propose a general principle of tissue calcification. Progressive decline of renal function was found in distal renal tubular acidosis, whereas other conditions remained stable over time.

Statin therapy for patients with diabetic nephropathy: balance between safety and efficacy of statin treatment for patients with impaired kidney function.

The International Diabetes Federation estimates that by 2035, there will be 592 million people with diabetes worldwide, substantially increasing from the 382 million patients with diabetes recorded in 2013. Diabetes-related nephropathy is a leading cause of end-stage renal disease. Recently, the therapeutic use of statins in patients with chronic kidney disease (CKD) was explored in a series of meta-analyses, which revealed their potential for decreasing mortality and cardiovascular complications in this population, although not in patients undergoing hemodialysis. The current study reviews the current state of knowledge on statin therapy regarding its safety and efficacy concerning renal outcomes in diabetic patients with CKD. The evidence shows that statins may offer a beneficial renoprotective effect in inhibiting the progression of renal function decline. This effect is time-dependent and particularly strong in patients with type 2 diabetes and nephropathy. In addition, whether certain statin types are more beneficial than others in slowing renal function loss and reducing proteinuria remains unclear. Prior research has not examined the impact of high-intensity statin therapy on CKD patient outcomes.

Lessons to be learned from real life data from 98 gout patients using benzbromarone

Aim: This study aims to analyze the efficacy and safety of benzbromarone as uricosuric, in a real-life clinical setting of a retrospective hospital-based gout cohort. Methods: Data from gout patients were retrieved from the digital hospital dossiers. Demographics, clinical variables, and laboratory parameters were collected at baseline and 6 months. Efficacy was measured by reaching a serum uric acid (sUA) target &lt; 0.30 mmol/L at 6 months, and the fractional excretion of uric acid (FeUA) was used as a parameter with a potential predictor value. Results: Data from 98 gout patients were analyzed. Patients were 70 (± 12) years of age, and 90% were male. After 6 months of treatment, 68 out of 98 patients (69%) reached a sUA level &lt; 0.30 mmol/L (5 mg/dL). In patients with a FeUA &lt; 4.5%, so-called low excretors, the FeUA increase was most impressive from 3.2% (± 1.0%) to 12.1% (± 6.9%) after 6 months of benzbromarone treatment (mean increase +8.9% [95% confidence interval (CI): +6.5 to +11.5%], P &lt; 0.001). In non-low excretors, FeUA was on average 7.3% (± 5.1%) and increased to 9.7% (± 6.1%): a mean +2.1% change (95% CI: –2.2 to +6.6%). The increase differed insignificantly in low versus non-low excretors: P &gt; 0.05. Four patients stopped benzbromarone treatment because of a progressive decline in renal function, a condition that was already present before benzbromarone was initiated. Remarkably 38% of patients still using benzbromarone after 3.8 (± 3.4) years of treatment. Conclusions: Using the uricosuric benzbromarone in real-life gout patients proved effectivity in lowering sUA levels within 6 months by increasing FeUA significantly. Particularly low excretors benefit from benzbromarone treatment manipulating this mode of action. Determining FeUA in gout patients may further help to find the patient profile benefiting the most from benzbromarone treatment.

Role of Sodium-Glucose Co-Transporter 2 Inhibitors in Chronic Kidney Disease, Congestive Heart Failure and Stroke-A Review and Clinical Guide for Healthcare Professionals.

Diabetic kidney disease (DKD) causes a progressive decline in renal function, leading to end-stage kidney disease (ESKD), and increases the likelihood of cardiovascular events and mortality. The recent introduction of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor has been a game changer in managing chronic kidney disease (CKD) and congestive heart failure (CHF). These agents not only slow down the progression of kidney disease but also have cardioprotective benefits, including for patients with congestive heart failure and atherosclerotic cardiovascular disease. Some evidence suggests that they can decrease the risk of stroke as well. This review aims to provide a comprehensive overview of the role of SGLT-2 inhibitors in CKD and CHF and their efficacy in stroke prevention. This review includes a comparison with glucagon-like peptide-1 (GLP-1) agonist and finerenone; focuses on safety data, the potential benefits beyond glycemic control, and a review of significant trials; and provides guidance in clinical practice.

Niclosamide from an anthelmintic drug to a promising adjuvant therapy for diabetic kidney disease: randomized clinical trial

BackgroundDiabetic kidney disease (DKD) is a serious complication that begins with albuminuria and often leads to a rapid progressive decline in renal function. Niclosamide is a potent inhibitor of the Wnt/β-catenin pathway, which controls the expression of multiple genes of the renin–angiotensin–aldosterone system (RAAS), which in turn is influences the progression of DKD. This study was conducted to evaluate the effect of niclosamide as adjuvant therapy on DKD.MethodsOut of 127 patients screened for eligibility, 60 patients completed the study. After randomization, 30 patients in the niclosamide arm received ramipril plus niclosamide, and 30 patients in the control arm received ramipril only for 6 months. The primary outcomes were the changes in urinary albumin to creatinine ratio (UACR), serum creatinine, and estimated glomerular filtration rate (eGFR). The secondary outcomes were measurements of urinary matrix metalloproteinase-7 (MMP-7), 8-hydroxy-2ʹ-deoxyguanosine (8-OHdG), and podocalyxin (PCX). Comparisons between the two arms were done using student t-test. Correlation analysis was done using Pearson correlation.ResultsNiclosamide decreased UACR by 24% (95% CI − 30 to − 18.3%) while there was a rise in UACR in the control arm by 11% (95% CI 4 to 18.2%) after 6 months (P < 0.001). Moreover, a significant reduction in MMP-7 and PCX was noticed in the niclosamide arm. Regression analysis revealed a strong association between MMP-7, which is a noninvasive biomarker predicting the activity of the Wnt/β-catenin signaling, and UACR. A 1 mg/dL decline in MMP-7 level was associated with a 25 mg/g lowering in UACR (B = 24.95, P < 0.001).ConclusionThe addition of niclosamide to patients with diabetic kidney disease receiving an angiotensin-converting enzyme inhibitor significantly reduces albumin excretion. Further larger-scale trials are needed to confirm our results.Trial registration: The study was prospectively registered on clinicaltrial.gov on March 23, 2020, with identification code NCT04317430.

Discovering crystals; ancillary adventures in light chain tubulopathy

Light chain associated proximal tubulopathy is a rare form of Monoclonal Gammopathy-related kidney disease. Common causes include myeloma, monoclonal gammopathy of renal significance and B-cell lymphomas.1,2 Accumulation of intracytoplasmic crystalline inclusions, composed of abnormal monoclonal light chains, cause chronic damage to proximal tubules. These light chains are resistant to enzymatic breakdown.2,3 We present a case of a 61-year-old man with progressive decline in renal function without proteinuria.

Anemia in chronic kidney disease

Anemia is one of the earliest and most frequent complications of chronic kidney disease (CKD). Anemia is associated with poor quality of life, increased cardiovascular morbidities and mortalities, and accelerated progression of renal function decline. Although the pathogenesis of anemia in CKD is multifactorial, absolute or relative erythropoietin (EPO) deficiency is central to it. Iron deficiency is the second most important cause of anemia. EPO-stimulating agents and iron replacement had been central in the management of anemia of CKD. Newer information regarding the role of hypoxia-inducible factor (HIF) mediating EPO release has the potential to change the current management paradigm. Orally administered HIF inhibitors are shown to be safer and have similar efficacy compared to ESAs, and may become the mainstay of treatment of CKD anemia.

Autosomal Dominant Polycystic Kidney Disease: Role of Imaging in Diagnosis and Management.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disorder with progressive renal function decline, and disease severity is determined based on the type of genetic mutation. The diagnosis is usually established at imaging, primarily at US, and is based on age-dependent criteria and the number of visible cysts. ADPKD is classified into class 1 (typical) and class 2 (atypical) according to the Mayo Clinic Imaging Classification (MCIC) system. Height-adjusted total kidney volume (TKV) has emerged as a predictor of future renal function decline and renal failure in ADPKD, and several methods can be used for estimation. MCIC class 1 ADPKD is further subdivided into five types based on height-adjusted TKV (A, B, C, D, and E). Patients with a larger height-adjusted TKV (ie, MCIC 1C-E) are at high risk for progression to end-stage renal disease and will potentially benefit from vasopressin receptor antagonists, which have been shown to reduce the rate of cyst growth and slow renal function decline. Other renal complications primarily relate to hemorrhage within cysts or cyst infections. Subtraction images are key for assessment of complex cysts when malignancy is suspected, as the presence of protein and blood can limit the assessment for an enhancing component. The radiologist has a central role in establishing a diagnosis, excluding mimics, identifying complications, assessing severity, and predicting future renal failure. Interventional radiologists play a therapeutic role in management of complications by cyst drainage, sclerotherapy, or embolization. © RSNA, 2022 Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

De novo collapsing glomerulopathy after kidney transplantation: Description of two cases.

Among different forms of de novo focal segmental glomerulosclerosis (FSGS), which can develop after kidney transplantation (KTx), collapsing glomerulopathy (CG) is the least frequent variant, but it is associated with the most severe form of nephrotic syndrome, histological findings of important vascular damage, and a 50% risk of graft loss. Here, we report two cases of de novo post-transplant CG. A 64-year-old White man developed proteinuria and worsening of renal function 5 years after KTx. Before the KTx, the patient was affected by an uncontrolled resistant hypertension, despite multiple antihypertensive therapies. Blood levels of calcineurin inhibitors (CNIs) were stable, with intermittent peaks. Kidney biopsy showed the presence of CG. After introduction of angiotensin receptor blockers (ARBs), urinary protein excretion progressively decreased in 6 months, but subsequent follow-up confirmed a progressive renal function decline. A 61-year-old White man developed CG 22 years after KTx. In his medical history, he was hospitalized twice to manage uncontrolled hypertensive crises. In the past, basal serum cyclosporin A levels were often detected above the therapeutic range. Low doses of intravenous methylprednisolone were administered due to the histological inflammatory signs shown on renal biopsy, followed by a rituximab infusion as a rescue therapy, but no clinical improvement was seen. These two cases of de novo post-transplant CG were supposed to be mainly caused by the synergic effect of metabolic factors and CNI nephrotoxicity. Identifying the etiological factors potentially responsible for de novo CG development is essential for an early therapeutic intervention and the hope of better graft and overall survival.

Clinical Utility of the OmniGraf Biomarker Panel in the Care of Kidney Transplant Recipients (CLARITY): Protocol for a Prospective, Multisite Observational Study

Death with a functioning allograft has become the leading category of graft loss in kidney transplant recipients at all time points. Previous analyses have demonstrated that causes of death in kidney transplant recipients are predominated by comorbidities strongly associated with immunosuppressant medications. Adverse drug events (ADEs) have been strongly associated with nonadherence, health care utilization, and graft loss; clinicians face a difficult decision on whether making immunosuppressant adjustments in the face of ADEs will improve symptomology or simply increase the risk of acute rejection. Clinicians also face a treatment quandary in 50% of kidney transplant recipients with stage 3 or worse chronic kidney disease at 1 year post transplantation, as progressive decline in renal function has been strongly associated with inferior allograft survival. The primary objective of the CLinical Utility of the omnigrAf biomarkeR Panel In The Care of kidneY Transplant Recipients (CLARITY) trial is to evaluate change in renal function over time in kidney transplant recipients who are undergoing OmniGraf monitoring in conjunction with monitoring of their medication-related symptom burden (MRSB). A secondary objective of this study is to identify the impact of OmniGraf use in conjunction with patient-reported MRSB as part of clinical care on patients' self-efficacy and quality of life. CLARITY is a 3-year prospective, multisite, observational study of 2000 participants with a matched control, measuring the impact of real-time patients' MRSB and the OmniGraf biomarker panel on change in renal function over time. Secondary outcome measures include the Patient-Reported Outcomes Measurement Information System (PROMIS) Self-Efficacy for Managing Chronic Conditions-Managing Medications and Treatment-Short Form 4a; the PROMIS-29 Profile (version 2.1); the PROMIS Depression Scale, hospitalizations-subcategorized for hospitalizations owing to infections; treated rejections, MRSB, and proportion of participants with overall graft survival at year 3 post transplantation; graft loss or death during the 3-year study follow-up period; and change in provider satisfaction. The primary outcome measure of the study will be a comparison of the slope change in estimated glomerular filtration rate from baseline to the end of follow-up between study participants and a matched control group. Secondary outcome measures include changes over time in PROMIS Self-Efficacy for Managing Chronic Conditions-Managing Medications and Treatment-Short Form 4a, the PROMIS-29 Profile (version 2.1), and PROMIS Depression Scale in the study group, as well as a comparison of hospitalizations and causes, rejections, and graft and patient survival compared between participants and a matched cohort. The anticipated first enrollment in the study is October 2022 with data analysis and publication expected in October 2027. Through this report, we describe the study design, methods, and outcome measures that will be utilized in the ongoing CLARITY trial. ClinicalTrials.gov NCT05482100; https://clinicaltrials.gov/ct2/show/NCT05482100. PRR1-10.2196/41020.

Kidney injury in patients who have contracted coronavirus disease: status of the problem today

As of January 2021, 87.6 million cases of COVID-19 have been registered in the world, of which 1.9 million cases have resulted in death. In Ukraine, at the end of 2020, the number of cases of the disease was 1,099,493, of which 19,505 resulted in death. The progressive course of COVID-19 can induce severe damage to the lungs, kidneys, heart and other organs and systems with the formation of acute respiratory distress syndrome and multiple organ failure syndrome. Kidney damage in the case of COVID-19 is still considered to be mainly secondary and associated with hypoxia, ischemia, disseminated intravascular coagulation in the case of severe and extremely severe disease. However, it is worth noting that kidney damage also occurs against the background of the massive use of medications that are sufficiently nephrotoxic.The purpose of this work is to review scientific results, which contain information about the current state of the problem of kidney damage in patients who have contracted the coronavirus disease.Patients with chronic kidney disease have an increased risk of infection with COVID-19, its severe course and mortality. Endothelial dysfunction, microangiopathy, coagulation disorders, and imbalance of the renin-angiotensin-aldosterone system are key links to kidney damage in the case of such concomitant pathology. An increase in the level of serum creatinine and blood urea nitrogen, the appearance and increase in the level of hematuria and proteinuria - these changes require careful study.Conclusions. 1. To date, scientific data on the mechanisms of kidney damage in patients with COVID-19 have been expanded. This makes it possible to develop methods of timely drug exposure to prevent the progression of renal function decline. 2. The incidence of acute kidney injury and mortality in COVID-19 patients with CKD is significantly higher than without CKD. 3. After recovery from COVID-19, patients with CKD should have dispensary observation and treatment.

Review of the Role of Enteral Factor in the Development of Secondary Hyperoxaluria

Objectives: Discuss the role of the enteric factor in the hyperoxaluria development.&#x0D; Methods: Using the Internet and written materials, the relevant factors of enteral factor; hyperoxaluria; oxalotrophia; Oxalobacter formigenes; kidney stones, and with 36 references, were comprehensively analyzed and studied.&#x0D; Results: Under the condition of excessive intake of oxalate and its precursors, increased intestinal absorption of oxalate and imbalance of intestinal flora, resulting in increased urine oxalate and calcium oxalate crystal, which lead to hematuria, proteinuria, recurrent kidney stones and nephrocalcinosis.&#x0D; Discussion: Hyperoxaluria is a disease caused by metabolism disorder of oxalic acid and intestinal factors have significant influence on its progression. This disease can occur under the condition of excessive intake of oxalate and its precursors, increased intestinal absorption of oxalate and imbalance of intestinal flora, resulting in increased urine oxalate and calcium oxalate crystal, which lead to hematuria, proteinuria, recurrent kidney stones and nephrocalcinosis. Some patients may further progress to the AKI and CKD. With progressive decline in renal function, oxalate is reduced and deposits in the body can affect other tissues and organs. And adjustment of enteral factors is helpful for the treatment of hyperoxaluria.&#x0D; In this article we discuss the role of the enteric factor in the hyperoxaluria development. Hyperoxaluria is a metabolic disease characterized by excessive urinary oxalic acid excretion and calcium oxalate crystal deposition, whose intestinal factors affecting its onset includes the increased intake of oxalic acid and its precursors, the increased intestinal absorption of oxalate and the imbalance of intestinal flora, etc. Severe hyperoxaluria can lead to kidney stones. At present, the influence of intestinal factors on hyperoxaluria has become a research focus, this paper will give a comprehensive description of its related research.

Chronic Kidney Disease: Challenges in Translational Medicine.

Chronic kidney disease (CKD) has long been recognized as a state of progressive decline in renal function. Morbidity and mortality are well correlated to the stage of renal function decline. Approximately one million deaths are estimated to be related to CKD worldwide. They are mostly associated with cardiovascular disease as a result of concurrent hypertension, accelerated atherosclerosis, and volume overload. Even with the best current treatment, disease progression is the general rule with a small fraction who reach CKD stage 5 requiring kidney transplantation or dialysis. Transplant patients show substantial reductions in mortality and cardiovascular events, as well as improvements in quality of life. However, the capacity of health systems to deliver kidney transplantation varies worldwide with worse indicators in low-income countries. Consequently, exploring novel and better therapeutic options for CKD is mandatory. Cell-based therapy is a promising strategy for treating CKD in preclinical models, and several clinical trials involving kidney disease exhibit a favorable safety profile. This chapter aims to provide an overview of CKD and the recent results of clinical trials of cell therapy in kidney diseases.

Swimming exercise activates peroxisome proliferator-activated receptor-alpha and mitigates age-related renal fibrosis in rats.

Aging results in progressive decline of renal function as well as histological alterations including glomerulosclerosis and interstitial fibrosis. The objective of current study was to test the benefits of moderate swimming exercise in aged rats on renal function and structure and investigate its molecular mechanisms. Aged rats of 21-months old were given moderate swimming exercise for 12weeks. Swimming exercise in aged rats led to reduced plasma levels of creatinine and blood urea nitrogen. Periodic acid-Schiff staining results revealed reduced renal injury scores in aged rats after swimming exercise. Swimming exercise in aged rats mitigated renal fibrosis and downregulated the mRNA expression of Acta2, Fn, Col1a, Col4a, and Tgfb1 in kidneys. Swimming exercise in aged rats attenuated lipid accumulation and reduced levels of triglyceride in kidneys. Swimming exercise in aged rats abated oxidative stress, evidenced by reduced MDA levels and increased MnSOD activities in kidneys. Swimming exercise in aged rats inhibited NF-κB activities and reduced renal expression of pro-inflammatory cytokines including MCP-1, IL-1β and IL-6. Mechanistically, swimming exercise restored mRNA and protein expression of PPAR-α in kidney of aged rats. Furthermore, swimming exercise in aged rats increased expression of PPAR-α-targeting microRNAs including miR-21 and miR-34a. Collectively, swimming exercise activated PPAR-α, which partly explained the benefits of moderate swimming exercise in aging kidneys.