Progressive Renal Failure Research Articles

Diet and Proteinuria: State of Art.

Proteinuria is a broad term used to describe the pathological presence of proteins, including albumin, globulin, Bence-Jones protein, and mucoprotein in the urine. When persistent, proteinuria is a marker of kidney damage and represents a reliable predictor of the risk of progression of renal failure. Medical nutrition therapy is imperative for patients with proteinuria because it may slow the progression of renal disease. The aim of this review is to explore different nutritional approaches in the management of proteinuria and their influence on pathophysiological processes. As such, protein restriction is the main dietary intervention. Indeed, other management approaches are frequently used to reduce it regarding micro and macronutrients, but also the dietary style. Among these, the nutritional approach represents one of the most used and controversial interventions and the studies rarely take the form of randomized and controlled trials. With this work we aspire to analyze current clinical knowledge of how nutrition could influence proteinuria, potentially representing a useful tool in the management of proteinuric nephropathy.

A case of hepatic and bone marrow sarcoidosis with progressive renal failure: diagnostic and therapeutic challenges.

Sarcoidosis is a systemic granulomatous disease, sometimes characterized by an extrapulmonary localization in 30 - 50% of cases. We describe a 60-year-old Italian man with an unexplained history of fatigue, ascitis and progressive renal function impairment. Diagnosis of hepatic and bone marrow sarcoidosis was established by histology, and fast improvement of renal function was obtained after starting corticosteroid therapy. Atypical presentation and simultaneous involvement of liver, bone marrow and kidneys make diagnosis of extrapulmonary sarcoidosis still a diagnostic challenge. Delayed diagnosis could lead to serious organ damage like a progressive severe kidney failure.

Pregnancy associated atypical hemolytic uremic syndrome presenting with preeclampsia with HELLP syndrome and following treatment with Eculizumab

Abstract Objectives Pregnancy associated atypical hemolytic uremic syndrome (p-aHUS) is a rare condition of thrombotic microangiopathy (TMA) which causes an increase of fetal and maternal morbidity and mortality. It presents typically with a triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia and acute progressive renal failure. Differential diagnoses of HELLP (Hemolysis, Elevated Liver enzymes, and Low Platelets) syndrome, preeclampsia, thrombotic thrombocytopenic purpura (TTP), and disseminated intravascular coagulation (DIC) syndrome must be considered. In the following case report, presented is a 32-year-old, 38 weeks pregnant Caucasian woman admitted to Eberswalde Hospital with signs of preeclampsia and HELLP Syndrome. Caesarean Section was performed due to HELLP syndrome and fetal distress. Acute renal failure occurs shortly after a successful delivery. After a diagnosis of p-aHUS is established, the patient was given Eculizumab, which yielded significant improvements. Case presentation A 32-year-old, 38 week pregnant Caucasian woman was admitted to Eberswalde Hospital with upper right abdominal pain. After a laboratory examination, a diagnosis of HELLP syndrome was established and a Caesarean Section was performed. The follow-up examination revealed deterioration of clinical signs with the patient experiencing dyspnea, oliguria, and oedema, as well as aggravation of laboratory values, ranging from severe thrombocytopenia, hemolytic anemia, liver injury, and acute kidney injury. After excluding other possible causes of TMA, a diagnosis of p-aHUS was established and a treatment with Eculizumab was administered. Clinical and laboratory signs of hemolysis and kidney functions were found to improve gradually after two administrations of Eculizumab. The patient was discharged after 20 days of hospitalization with significantly improved condition and hematological values. Conclusions A successful treatment of p-aHUS requires a comprehensive assessment and a prompt diagnosis, which can be confounded by multiple similar differential diagnoses. Treatment with Eculizumab was found to significantly improve the outcome of the patient, but more studies are required to decide on a standardized regiment for p-aHUS.

Poor Outcomes of Patients With NAFLD and Moderate Renal Dysfunction or Short-Term Dialysis Receiving a Liver Transplant Alone.

The outcomes of patients with moderate renal impairment and the impact of liver disease etiology on renal function recovery after liver transplant alone (LTA) are largely unknown. We explored whether NAFLD patients with pre-LTA moderate renal dysfunction (GFR 25-45ml/min/1.73m2) may be more susceptible to develop post-LTA severe renal dysfunction (GFR<15ml/min/1.73m2) than ALD patients, as well as other overall outcomes. Using the UNOS/OPTN database, we selected patients undergoing liver transplant for NAFLD or ALD (2006-2016), 15,103 of whom received LTA. NAFLD patients with moderate renal dysfunction were more likely to develop subsequent GFR<15ml/min/1.73m2 than ALD patients (11.1% vs. 7.38%, p < 0.001). Patients on short-term dialysis pre-LTA (≤12weeks) were more likely to develop severe renal dysfunction (31.7% vs. 18.1%), especially in NAFLD patients, and were more likely to receive a further kidney transplant (15.3% vs. 3.7%) and had lower survival (48.6% vs. 50.4%) after LTA (p < 0.001 for all). NAFLD was an independent risk factor for post-LTA severe renal dysfunction (HR = 1.2, p = 0.02). NAFLD patients with moderate renal dysfunction and those receiving short-term dialysis prior to LTA are at a higher risk of developing subsequent severe renal dysfunction. Underlying etiology of liver disease may play a role in predicting development and progression of renal failure in patients receiving LTA.

Assessment of C-Reactive Protein, Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Patients at Different Stages of Chronic Kidney Disease

Abstract Background: Low-grade chronic inflammation is an important feature of chronic kidney disease (CKD). Aim: To determine the values of C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with different stages of CKD and to examine how they change depending on the progression of renal damage. Materials and methods: A cross-sectional descriptive comparative study included 157 subjects at different stages of CKD which was assessed based on glomerular filtration rate (GFR) calculated according to the MDRD equation. CRP was analyzed by an immunoturbidimetric method. NLR and PLR were calculated by a mathematical calculation after a blood count was performed. Results: The present study showed an increase in serum creatinine, CRP, and NLR values with progression of renal failure. There was a statistically significant difference in the creatinine and CRP concentrations between groups with different stages of CKD (p &lt;0.001 for all comparisons). A significant positive correlation was found between NLR and CRP, while negative, significant correlations were observed between NLR and eGFR as well as between PLR and eGFR. There was a slight increase in PLR value with the progression of renal impairment, but the correlation between PLR and CRP was not significant. Conclusion: These results suggest that NLR, together with CRP, may serve as an indicator of systemic low-grade inflammation progression in patients with CKD. Larger prospective studies are required to observe the possibility of using NLR as a surrogate marker for CRP in patients with CKD.

Factors of proteolysis in blood and urine as prognostic markers of progression of Alport syndrome in children

BACKGROUND. Alport syndrome is a rare hereditary kidney disease that causes progressive renal failure. There are significant differences in the progression of the disease between patients with Alport syndrome. Identifying patients with a high risk of rapid progression in order to optimally balance benefits and risks for prescribing therapy has become particularly important at this time. In this study, we wanted to assess whether the factors of proteolysis in blood and urine are associated with the nature of the course and to assess their prognostic value for children with Alport syndrome. THE AIM: To determine the level in blood serum and urinary excretion of MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1 and 2, PAI-I, to show the relationship of their changes with the character of the course of Alport syndrome in children as an additional criterion for progression. PATIENTS AND METHODS. The study included 32 children with Alport syndrome. The level of MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1 and 2, PAI-I, in blood serum and urine was determined by ELISA. A decrease in eGFR of ≥ 30 % at 2 years from baseline was chosen to indicate a progressive course of Alport syndrome. RESULTS. 28.1 % of children with Alport syndrome had a progressive course of the dis ease, 71.9 % had a slowly progressive course. The frequency of a decrease in MMP-9 and an increase in TIMP-1 both in blood (88.9 versus 43.5 % and 77.8 versus 21.7 %; p = 0.044 and 0.006, respectively) and in urine (100 versus 47, 8 % and 88.9 versus 30.4 %; 0.012 and 0.005, respectively) were statistically significantly more often detected in children with Alport syndrome with a progressive course of the disease than in a slowly progressive course. CONCLUSION. Type 9 matrix metalloproteinase and type 1 tissue matrix metalloproteinase inhibitor can be considered as risk factors for the progression of Alport syndrome in children.

Mutational analysis of phospholipase C epsilon 1 gene in Egyptian children with steroid-resistant nephrotic syndrome

BackgroundSteroid-resistant nephrotic syndrome (SRNS) is characterized by unresponsiveness of nephrotic range proteinuria to standard steroid therapy, and is the main cause of childhood renal failure. The identification of more than 53 monogenic causes of SRNS has led researchers to focus on the genetic mutations related to the molecular mechanisms of the disease. Mutations in the PLCE1 gene, which encodes phospholipase C epsilon 1 (PLCε1), have been described in patients with early-onset SRNS characterized by progressive renal failure. In this study we screened for PLCE1 mutations in Egyptian children with SRNS. This is a descriptive case series study aiming to screen for PLCE1 gene mutations by direct sequencing of five exons—9, 12, 15, 19, 27—in 20 Egyptian children with SRNS who entered the Nephrology Unit, Faculty of Medicine, Ain-Shams University from November 2015 to December 2017. The variants detected were submitted to in silico analysis.ResultsWe screened for mutations in five selected exons of PLCE1 gene. We identified seven variants in the five selected exons with homozygous and heterozygous inheritance pattern, two are intronic variants, two are silent variants, and three are missense variants. We identified four novel variants two are silent with no clinical significance and two are missense with uncertain clinical significance and pathogenic in-silico predictions; one p.Arg1230His in exon 12, the other is p.Glu1393Lys in exon 15.ConclusionsWe identified four novel mutations, findings which added to the registered SNP spectrum of the PLCE1 gene. These results widen the spectrum of PLCE1 gene mutations and support the importance of genetic testing in different populations of SRNS patients, therefore, to assess the vulnerability of Egyptian children to SRNS candidate genes, further studies needed on a larger number of cases which undoubtedly provide new insights into the pathogenic mechanisms of SRNS and might help in control of the patient. Additionally, the use of computational scoring and modeling tools may assist in the evaluation of the way in which the SNPs affect protein functionality.

Bilateral nephrectomy for severe nephrotic syndrome in systemic AA amyloidosis

Systemic amyloid A (AA) amyloidosis is an uncommon complication of Crohns disease. The natural history is of nephrotic syndrome and progressive renal failure

PSAT010 Severe Cholestatic Jaundice (Stauffer Syndrome) as a Rare Paraneoplastic Manifestation in Adrenocortical Carcinoma

Abstract Introduction Adrenocortical Carcinoma (ACC) is a rare and often aggressive malignancy arising from the adrenal cortex. Rarely, ACC can be associated with a paraneoplastic syndrome, such as tumor-associated hypoglycemia due to insulin-like growth factor-2 secretion, hyperreninemic hyperaldosteronism, erythropoietin-associated polycythemia, and leukocytosis due to chemokine release from the tumor. Stauffer syndrome is a paraneoplastic syndrome characterized by reversible cholestasis in the absence of liver metastases, most frequently described in the context of renal cell carcinoma. Our case is the first reported association between Stauffer syndrome and ACC. Clinical Case A 38-year-old man presented with nausea, vomiting, painless jaundice, pruritus, and weight loss. Laboratory evaluation revealed an elevated total bilirubin of 8.7 mg/dL (N&amp;lt;1.3), the INR was elevated secondary to the cholestasis from vitamin K insufficiency. Computed tomography (CT) scan revealed a 20.4 cm, heterogeneous left adrenal mass with central necrosis concerning for ACC. There was no evidence of liver metastases. Additional laboratory workup showed elevated DHEA-sulfate of 1764.2 ug/dL (N&amp;lt;568.9), ACTH of 18 pg/mL (N&amp;lt;7-63), cortisol of 18.30 mcg/dL (N&amp;lt;19.50), androstenedione of 247 ng/dL (N&amp;lt;150), estradiol of 123 pg/mL (N&amp;lt;41), testosterone of 237 ng/dL (N&amp;lt;871), aldosterone of 11 ng/dL (N&amp;lt;=21), and plasma renin activity of 14 ng/mL/hr (N&amp;lt;4.3). Plasma metanephrines and catecholamines were normal. The patient's condition deteriorated rapidly with progressive renal failure and uremia requiring intensive care unit admission for continuous renal replacement therapy and critical care optimization preoperatively. The patient's total bilirubin increased to 34.5 mg/dL, which prompted liver biopsy. This revealed no evidence of cirrhosis or hepatic metastasis. Therefore, severe cholestasis was attributed to Stauffer syndrome, a paraneoplastic cholestatic jaundice from the underlying adrenal mass. The patient underwent exploratory laparotomy with left adrenalectomy, left nephrectomy, left ureterolysis, and wedge liver biopsy. Histopathology showed a necrotic ACC with tumor invasion into the adrenal capsule, no lymphovascular invasion, margins uninvolved, and Ki-67 index of 40%. Kidney parenchyma exhibited diffuse pigment casts. The liver specimen contained diffuse bile deposits and minimal chronic inflammation in the portal tracts, consistent with Stauffer syndrome. Postoperatively, the patient had rapid improvement in his renal function, and bilirubin level normalized after several weeks. Mitotane therapy was deferred until the complete recovery of the liver function. Conclusion Our case highlights a unique presentation of paraneoplastic hepatic dysfunction with jaundice associated with newly diagnosed ACC. Although Stauffer syndrome is one of the most characteristic paraneoplastic syndromes associated with renal cell carcinoma and other malignancies, paraneoplastic hepatic dysfunction associated with ACC has not been previously reported. The patient had rapid improvement of hyperbilirubinemia after surgical resection of the tumor. Stauffer syndrome should be considered in patients with ACC with liver dysfunction and jaundice without evidence of liver metastases. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Ovarian Hyperstimulation Syndrome (OHS): A Rare Cause of Acute Renal Failure: A Case Report

We report in this work, the evolution and management of a case of ovarian hyperstimulation syndrome (OHS) complicated by severe acute renal failure (ARI). A young 31-year-old patient pregnant with twins after 17 weeks of amenorrhea was admitted to nephrology department for rapidly progressive acute renal failure (AKI) (creatinine increases in 48 hours from 28mg/l to 55mg/l) and was complicated by major hydro-electrolyte disorders and multi-organ failure. Her past medical history revealed an ovulation induction before her last pregnancy and a spontaneous abortion seven years ago before her hospitalization which occurred in the 2nd trimester of her 1st twin pregnancy obtained by medically assisted reproduction. Despite optimal care, the patient improves her renal function and her multiorgan failure after abortion in gynecological intensive care. Because of worldwide increase of infertility cases and the use of new ovulation induction techniques with these risks of serious complications, we report this interesting clinical case of OHS.

Diclofenac Induced Rapidly Progressive Renal Failure in Elderly Patient – A Case Report

Diclofenac Induced Rapidly Progressive Renal Failure in Elderly Patient – A Case Report

Bone marrow stromal cell antigen-1 (CD157) regulated by sphingosine kinase 2 mediates kidney fibrosis.

Chronic kidney disease is a progressive disease that may lead to end-stage renal disease. Interstitial fibrosis develops as the disease progresses. Therapies that focus on fibrosis to delay or reverse progressive renal failure are limited. We and others showed that sphingosine kinase 2-deficient mice (Sphk2–/–) develop less fibrosis in mouse models of kidney fibrosis. Sphingosine kinase2 (SphK2), one of two sphingosine kinases that produce sphingosine 1-phosphate (S1P), is primarily located in the nucleus. S1P produced by SphK2 inhibits histone deacetylase (HDAC) and changes histone acetylation status, which can lead to altered target gene expression. We hypothesized that Sphk2 epigenetically regulates downstream genes to induce fibrosis, and we performed a comprehensive analysis using the combination of RNA-seq and ChIP-seq. Bst1/CD157 was identified as a gene that is regulated by SphK2 through a change in histone acetylation level, and Bst1–/– mice were found to develop less renal fibrosis after unilateral ischemia-reperfusion injury, a mouse model of kidney fibrosis. Although Bst1 is a cell-surface molecule that has a wide variety of functions through its varied enzymatic activities and downstream intracellular signaling pathways, no studies on the role of Bst1 in kidney diseases have been reported previously. In the current study, we demonstrated that Bst1 is a gene that is regulated by SphK2 through epigenetic change and is critical in kidney fibrosis.

Microbiome in Chronic Kidney Disease.

The gut microbiome is a complex collection of microorganisms with discrete characteristics and activities. Its important role is not restricted to food digestion and metabolism, but extends to the evolution, activation and function of the immune system. Several factors, such as mode of birth, diet, medication, ageing and chronic inflammation, can modify the intestinal microbiota. Chronic kidney disease (CKD) seems to have a direct and unique effect, as increased urea levels result in alteration of the gut microbiome, leading to overproduction of its metabolites. Therefore, potentially noxious microbial uremic toxins, which have predominantly renal clearance, including p-cresyl sulfate, indoxyl sulfate and N-oxide of trimethylamine [Trimethylamine-N-Oxide (TMAO)], accumulate in human’s body, and are responsible not only for the clinical implications of CKD, but also for the progression of renal failure itself. Certain changes in gut microbiome are observed in patients with end stage renal disease (ESRD), either when undergoing hemodialysis or after kidney transplantation. The purpose of this review is to summarize the changes of gut microbiome and the protein bound uremic toxins which are observed in CKD and in different kidney replacement strategies. In addition, we attempt to review the connection between microbiome, clinical implications and immune response in CKD.

Liposomal drug delivery systems for the treatment of leishmaniasis.

Human le ishmaniasis is a vector-borne, neglected infectious disease that is widely distributed in America, Africa, Europe, and Asia. Current therapy is based on old and toxic drugs, including antimonials, aminoglycosides, and amphotericin. As a neglected disease, investment in the development of new therapeutic molecules is scarce. Considering these aspects, the optimization of treatment through novel delivery systems for current therapeutic agents is an attractive alternative. The encapsulation into liposomes of drugs used in treating leishmaniasis increases the concentration of these molecules in macrophages, which may not only increase the chance of cure but also expand their therapeutic spectrum to include resistant Leishmania, as well as reducing toxicity since the drug is less exposed to healthy cells. The classical example is the liposomal formulation of amphotericin B, a well-established therapeutic option that uses liposomes to decrease the progression of renal failure in patients. However, loading other leishmanicidal drugs into liposomes, such as pentavalent antimonials, presents an opportunity for innovative and cheaper therapeutic options for the treatment of human leishmaniasis. This review aims to discuss liposomes as a drug delivery system for leishmanicidal drugs.

Usage of Biological Therapy in Rheumatoid Arthritis Patients with Chronic Renal Failure: A Retrospective Study from a Single Center

Kronik böbrek hastalığı (KBH) olan romatoid artrit (RA) hastalarında, potansiyel toksisiteleri nedeniyle hastalığı modifiye edici antiromatizmal ilaçların (DMARD) çoğunu ve steroid olmayan antiinflamatuar ilaçları (NSAİİ) kullanmak uygun değildir. Biyolojik DMARD'lar RA hastaları için oldukça etkili bir tedavi seçeneği olsa da böbrek fonksiyonları üzerindeki etkisi ve güvenilirliği tam olarak belirlenememiştir. KBH’si olan RA’lı hastalarda biyolojik tedavilerin kullanımına ilişkin veriler kısıtlıdır. 2011-2018 yılları arasında RA tanısı ile takip ettiğimiz, biyolojik ajan kullanan ve düzenli vizitleri bulunan 700 hasta arasından tahmini glomerüler filtrasyon hızı (eGFR) üç aydan uzun süredir

Association of the estimated glomerular filtration rate (eGFR) and/or proteinuria to predict the risk of initiation of dialysis in people with and without diabetes.

To determine the associations between combined urinary protein (UP) and a reduced estimated glomerular filtration rate (eGFR) and the risk of starting dialysis with or without diabetes mellitus (DM). A nationwide database with claims data on 335,778 people with and without DM aged 19-72 years in Japan was used to elucidate the impact of the severities of UP and eGFR on starting dialysis. Initiation of dialysis was determined from claims using ICD-10 codes and medical procedures. Using multivariate Cox modeling, we investigated the severities of UP and eGFR to predict the initiation of dialysis with and without DM. Both eGFR < 60 and UP(+) were independent predictors for starting dialysis with and without DM, and their values exhibited a synergistic risk of dialysis. eGFR < 60 presented a nearly twofold risk for starting dialysis compared to UP(+) regardless of DM. Risk of starting dialysis was increased with UP(+) and eGFR ≥ 60 accompanied by DM although this association was not observed without DM. Those who had UP(-) and eGFR < 60 had a high risk of starting dialysis regardless of DM. Compared with DM(-)UP(-)eGFR ≥ 60, HRs for starting dialysis for DM(+)UP(+)eGFR ≥ 60, DM(+)UP(-)eGFR < 60 and DM(+)UP(+)eGFR < 60 significantly increased 17.7 (10.6-29.7), 25.5 (13.8-47.1) and 358.1 (239.1-536.5) times, respectively. eGFR < 60 and UP(+) together presented an extremely high risk of dialysis especially with DM. UP( +) increased the risk of starting dialysis regardless of the eGFR with DM. Both patient education and a treatment strategy by physicians might be helpful to avoid the progression of renal failure.

Ингибиторы НГЛТ-2 при хронической болезни почек: современное состояние проблемы

All patients with chronic kidney disease (CKD) require treatment to reduce the risk of cardiovascular events and to prevent progression of renal failure. ACE inhibitors and angiotensin receptor blockers are widely used for cardio- and nephroprotection in patients with CKD. Sodium glucose cotransporter type 2 (SGLT-2) inhibitors show significant prospects for reducing morbidity and mortality in this population. SGLT-2 inhibitors have been developed for treatment of patients with type 2 diabetes mellitus. However, evidence from multiple randomized clinical trials suggested that these drugs have cardio- and nephroprotective effects in patients with and without diabetes. Despite a wealth of data, SGLT-2 inhibitors remain underused by nephrologists or cardiologists. This is not surprising since new therapies traditionally take decades from research to clinical implementation due to many barriers, including lack of knowledge, concern about drug side effects, lack of decision support, cost, and clinical inertia. The review article presents data from scientific studies on the renoprotective effect of SGLT-2 inhibitors and the mechanisms of this activity in CKD patients.

Determinants of microalbuminuria among type 2 diabetes mellitus patients in Kuala Selangor district: A cross-sectional study.

Microalbuminuria presents significant health risks for the progression of endstage renal-failure (ESRF) among type 2 diabetes mellitus (T2DM) patients. This study aims to determine the proportion and associated factors of microalbuminuria among T2DM patients in Kuala Selangor district, Malaysia. A retrospective cross-sectional study was conducted from December 2020 to February 2021 using secondary data from the National Diabetic Registry (NDR), Malaysia, and reviewed patients' diabetic records for the year 2020. All T2DM patients aged >18 years who were registered with the NDR in 2020 and fulfilled the inclusion and exclusion criteria were included in the study. Descriptive statistics and multiple logistic regression analysis were performed. Data were analysed using SPSS version 26.0. A total of 343 samples were included in this study for the determination of the proportion of microalbuminuria and its associated factors. Of 343 respondents, 34.4% had microalbuminuria. HbAlc >7.0% (AdjOR 2.19, 95% CI: 1.35, 3.55, p=0.001), HDL <1.04 mmol/L (AdjOR 2.44, 95% CI: 1.323, 4.52, p=0.004), dyslipidaemia (AdjOR 1.90, 95% CI: 1.03, 3.48, p=0.039), and peripheral neuropathy (AdjOR 3.01, 95% CI: 1.02, 8.93, p=0.047) were significantly associated with microalbuminuria. Conclusion: Microalbuminuria is a modifiable risk factor in preventing the progression of ESRF among T2DM patients. Therefore, identification of factors associated with microalbuminuria among this high-risk group is important to facilitate early screening and prompt treatment to prevent progression of diabetic kidney disease to ESRF.

Hepatocyte Nuclear Factor 1α Proinflammatory Effect Linked to the Overexpression of Liver Nuclear Factor-κB in Experimental Model of Chronic Kidney Disease.

Chronic kidney disease (CKD) is associated with low-grade inflammation that activates nuclear factor–κB (NF–κB), which upregulates the expression of numerous NF–κB responsive genes, including the genes encoding IL-6, ICAM-1, VCAM-1, and MCP-1. Herein, we found the coordinated overexpression of genes encoding RelA/p65 (a subunit of NF–κB) and HNF1α in the livers of chronic renal failure (CRF) rats—an experimental model of CKD. The coordinated overexpression of RelA/p65 and HNF1α was associated with a significant increase in IL-6, ICAM-1, VCAM-1, and MCP-1 gene expressions. A positive correlation between liver RelA/p65 mRNA levels and a serum concentration of creatinine and BUN suggest that RelA/p65 gene transcription is tightly related to the progression of renal failure. The knockdown of HNF1α in the HepG2 cell line by siRNA led to a decrease in Rel A/p65 mRNA levels. This was associated with a decrease in IL-6, ICAM-1, VCAM-1, and MCP-1 gene expressions. The simultaneous repression of HNF-1α and RelA/p65 by clofibrate is tightly associated with the downregulation of IL-6, ICAM-1, VCAM-1, and MCP-1 gene expression. In conclusion, our findings suggest that NF–κB could be a downstream component of the HNF1α-initiated signaling pathway in the livers of CRF rats.

Associations between ATG16L1 gene polymorphism and antineutrophil cytoplasmic antibody-associated vasculitis in the Chinese Guangxi population: A case-control study.

BackgroundAntineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is an autoimmune disease often accompanied by rapidly progressive renal failure, and the genetic background is still unknown. Our study was performed to test whether autophagy‐related 16 like 1 (ATG16L1) rs4663402 and rs4663396 single nucleotide polymorphisms (SNPs) were associated with AAV in the Chinese Guangxi population.MethodsOne hundred seventy seven unrelated AAV patients and 216 healthy controls were included in this case–control study. Multiplex polymerase chain reaction combined with high‐throughput sequencing was used for typing, and SNPStats and SHEsis were used for association analysis, pairwise linkage disequilibrium, and haplotype analysis.Resultsrs4663402 and rs4663396 were in Hardy–Weinberg equilibrium in AAV and control groups. The frequencies of rs4663402 AA, AT, and TT genotypes were 82.5%, 16.9%, and 0.6%, respectively, in patients with AAV, and 83.5%, 16.2%, and 0.5%, respectively, in controls. The frequencies of rs4663396 CC, CT, and TT genotypes were 63.8%, 33.9%, and 2.3%, respectively, in patients with AAV, and 69.2%, 26.6%, and 4.2%, respectively, in controls. Haplotype analysis revealed two SNPs in a single haplotype block (D′ = 1.0). Our logistic regression adjusted for sex and age showed no association between rs4663402 and rs4663396 and the risk for AAV in genetic models (p > 0.05). However, ATG16L1 rs4663396 CC and CT + TT genotypes exhibited statistically significant differences in the incidence of arthralgia (p = 0.03).ConclusionsOur results indicated that ATG16L1 rs4663402 and rs4663396 polymorphisms were not associated with AAV in the Chinese Guangxi population. ATG16L1 rs4663396 CT + TT genotype may be associated with arthralgia.