Initial outcomes using a novel bedwetting alarm (Gogoband®) that utilizes real time artificial intelligence to wake users prior to wetting.

We evaluated a new bedwetting alarm, GOGOband®® which utilizes real time heart rate variability (HRV) analysis and applied artificial intelligence (AI) to create an alarm that can wake the user prior to wetting. Our aim was to evaluate the efficacy of GOGOband® for users in the first 18-months of use. METHODS: A quality assurance study was conducted on data retrieved from our servers, of initial users of the GOGOband® which includes a heart rate monitor, moisture sensor, bedside PC-tablet, and a parent app. There are three sequential modes beginning with Training, Predictive mode and Weaning mode. Outcomes were reviewed and data analysis was done with SPSS and xlstat. RESULTS: All 54 subjects who used the system from Jan 1, 2020, to June 2021 for more than 30 nights were included in this analysis. The mean age of the subjects is 10.1 ± 3.7 yrs. Subjects wet the bed a median of 7 (IQR6-7) nights per week prior to treatment. Severity and number of accidents per night had no impact on the ability to achieve dryness with GOGOband®. A crosstab analysis was performed which indicated that high compliant users (>80%) can remain dry 93% of the time compared to the whole group 87.7%. Overall ability to achieve 14 dry nights in a row was 66.7% (36/54) with some achieving a median of 16 14-day periods of dryness (IQR 0-35.75). CONCLUSIONS: We found 93% dry night rate in high compliance users in Weaning, this translates to 1.2 wet nights per 30 days. This compares to all users who wet 26.5 nights prior to treatment and 11.3 wet nights per 30 days during Training. The ability to achieve 14 days straight of dry nights was 85%. Our findings indicate that GOGOband® provides a significant benefit to all its users reducing nocturnal enuresis rates.

Defining therapeutic targets for renal fibrosis: Exploiting the biology of pathogenesis.

Renal fibrosis is a failed wound-healing process of the kidney tissue after chronic, sustained injury, which is a common pathway and pathological marker of virtually every type of chronic kidney disease (CKD), regardless of cause. However, there is a lack of effective treatment specifically targeting against renal fibrosis per se to date. The main pathological feature of renal fibrosis is the massive activation and proliferation of renal fibroblasts and the excessive synthesis and secretion of extracellular matrix (ECM) deposited in the renal interstitium, leading to structural damage, impairment of renal function, and eventually end-stage renal disease. In this review, we summarize recent advancements regarding the participation and interaction of many types of kidney residents and infiltrated cells during renal fibrosis, attempt to comprehensively discuss the mechanism of renal fibrosis from the cellular level and conclude by highlighting novel therapeutic targets and approaches for development of new treatments for patients with renal fibrosis.

Kidney Allograft Fibrosis: Diagnostic and Therapeutic Strategies.

Interstitial fibrosis with tubule atrophy (IF/TA) is the response to virtually any sustained kidney injury and correlates inversely with kidney function and allograft survival. IF/TA is driven by various pathways that include hypoxia, renin-angiotensin-aldosterone system, transforming growth factor-ß signaling, cellular rejection, inflammation, and others. In this review, we will focus on key pathways in the progress of renal fibrosis, diagnosis and therapy of allograft fibrosis. This review discusses the role and origin of myofibroblasts as matrix producing cells and therapeutic targets in renal fibrosis with a particular focus on renal allografts. We summarize current trends to use multiomic approaches to identify new biomarkers for IF/TA detection and to predict allograft survival. Furthermore, we review current imaging strategies that might help to identify and follow-up IF/TA complementary or as alternative to invasive biopsies. We further discuss current clinical trials and therapeutic strategies to treat kidney fibrosis.

Implication of cellular senescence in the progression of chronic kidney disease and the treatment potencies.

Chronic kidney disease (CKD) is an increasing major public health problem worldwide. And CKD shares numerous phenotypic similarities with kidney as well as systemic ageing. Cellular senescence is mainly characterized by a stable cell cycle arrest, senescence-associated secretory phenotype (SASP) and senescent cell anti-apoptotic pathways (SCAPs). Herein, the regulations and the internal mechanisms of cellular senescence will be discussed. Meanwhile, efforts are made to give a comprehensive overview of the recent advances of the implication of cellular senescence in CKD. To date, numerous studies have focused on the effects of ageing risk factors in kidney and thereby trying to interrupt the kidney ageing processes with senolytics. Interestingly, some of them showed enormous clinical application potentials. Therefore, senotherapeutics can be applied as novel potential strategies for the treatment of CKD.

Alarm interventions for nocturnal enuresis in children.

BACKGROUND: Enuresis (bedwetting) affects up to 20% of five-year-olds and can have considerable social, emotional and psychological effects. Treatments include alarms (activated by urination), behavioural interventions and drugs. OBJECTIVES: To assess the effects of enuresis alarms for treating enuresis in children. SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP, and handsearching of journals and conference proceedings (searched 25 June 2018), and reference lists of relevant articles. SELECTION CRITERIA: We included randomised or quasi-randomised trials of enuresis alarms or alarms combined with another intervention for treating nocturnal enuresis in children between 5 and 16 years old. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias and extracted data. MAIN RESULTS: We included 74 trials (5983 children). At treatment completion, alarms may reduce the number of wet nights a week compared to control or no treatment (mean difference (MD) -2.68, 95% confidence interval (CI) -4.59 to -0.78; 4 trials, 127 children; low-quality evidence). Low-quality evidence suggests more children may achieve complete response (14 consecutive dry nights) with alarms compared to control or no treatment (RR 7.23, 95% CI 1.40 to 37.33; 18 trials, 827 children) and that more children may remain dry post-treatment (RR 9.67, 95% CI 4.74 to 19.76; 10 trials, 366 children; low-quality evidence). At treatment completion, we are uncertain whether there is any difference between alarms and placebo drugs in the number of wet nights a week (MD -0.96, 95% CI -2.32 to 0.41; 1 trial, 47 children; very low-quality evidence). Alarms may result in more children achieving complete response than with placebo drugs (RR 1.59, 95% CI 1.16 to 2.17; 2 trials, 181 children; low-quality evidence). No trials comparing alarms to placebo reported the number of children remaining dry post-treatment. Compared with control alarms, code-word alarms probably slightly increase the number of children achieving complete response at treatment completion (RR 1.11, 95% CI 0.97 to 1.27; 1 trial, 353 children; moderate-quality evidence) but there is probably little to no difference in the number of children remaining dry post-treatment (RR 0.91, 95% CI 0.79 to 1.05; moderate-quality evidence). Very low-quality evidence means we are uncertain if there are any differences in effectiveness between the other different types of alarm. At treatment completion, alarms may reduce the number of wet nights a week compared with behavioural interventions (waking, bladder training, dry-bed training, and star chart plus rewards) (MD -0.81, 95% CI -2.01 to 0.38; low-quality evidence) and may increase the number of children achieving complete response (RR 1.77, 95% CI 0.98 to 3.19; low-quality evidence) and may slightly increase the number of children remaining dry post-treatment (RR 1.39, 95% CI 0.81 to 2.41; low-quality evidence). The evidence relating to alarms compared with desmopressin in the number of wet nights a week (MD -0.64, 95% CI -1.77 to 0.49; 4 trials, 285 children) and the number of children achieving complete response at treatment completion (RR 1.12, 95% CI 0.93 to 1.36; 12 trials, 1168 children) is low-quality, spanning possible harms and possible benefits. Alarms probably slightly increase the number of children remaining dry post-treatment compared with desmopressin (RR 1.30, 95% CI 0.92 to 1.84; 5 trials, 565 children; moderate-quality evidence). At treatment completion, we are uncertain if there is any difference between alarms and tricyclics in the number of wet nights a week, the number of children achieving complete response or the number of children remaining dry post-treatment, because the quality of evidence is very low. Due to very low-quality evidence we are uncertain about any differences in effectiveness between alarms and cognitive behavioural therapy, psychotherapy, hypnotherapy and restricted diet. Alarm plus desmopressin may reduce the number of wet nights a week compared with desmopressin monotherapy (MD -0.88, 95% CI -0.38 to -1.38; 2 trials, 156 children; low-quality evidence). Alarm plus desmopressin may increase the number of children achieving complete response (RR 1.32, 95% CI 1.08 to 1.62; 5 trials, 359 children; low-quality evidence) and the number of children remaining dry post-treatment (RR 2.33, 95% CI 1.26 to 4.29; 2 trials, 161 children; low-quality evidence) compared with desmopressin alone. Alarm plus dry-bed training may increase the number of children achieving a complete response compared to dry-bed training alone (RR 3.79, 95% CI 1.85 to 7.77; 1 trial, 80 children; low-quality evidence). It is unclear if there is any difference in the number of children remaining dry post-treatment because of the wide confidence interval (RR 0.56, 95% CI 0.15 to 2.12; low-quality evidence). Due to very low-quality evidence, we are uncertain about any differences in effectiveness between alarm plus bladder training versus bladder training alone. Of the 74 included trials, 17 reported one or more adverse events, nine reported no adverse events and 48 did not mention adverse events. Adverse events attributed to alarms included failure to wake the child, ringing without urination, waking others, causing discomfort, frightening the child and being too difficult to use. Adverse events of comparator interventions included nose bleeds, headaches and abdominal pain. There is probably a slight increase in adverse events between code-word alarm and standard alarm (RR 1.34, 95% CI 0.75 to 2.38; moderate-quality evidence), although we are uncertain because of the wide confidence interval. Alarms probably reduce the number of children experiencing adverse events compared with desmopressin (RR 0.38, 95% CI 0.20 to 0.71; 5 trials, 565 children; moderate-quality evidence). Very low-quality evidence means we cannot be certain whether the adverse event rate for alarms is lower than for other treatments. AUTHORS' CONCLUSIONS: Alarm therapy may be more effective than no treatment in reducing enuresis in children. We are uncertain if alarm therapy is more effective than desmopressin but there is probably a lower risk of adverse events with alarms than with desmopressin. Despite the large number of trials included in this review, further adequately-powered trials with robust randomisation are still needed to determine the full effect of alarm therapy.

Galectins as potential pharmacological targets in renal injuries of diverse etiology.

Galectins are carbohydrate-binding proteins, and their importance in renal diseases of diverse etiology has been documented. Amongst different galectins, the role of galectin-3 in the pathophysiology of renal diseases has been well documented. There is an increase in galectin-3 in the circulation as well as on the kidneys in chronic kidney disease patients. The increase in galectin-3 is negatively correlated with a decrease in renal function and overall survival rate. The preclinical studies also correlate the increase in galectin-3 levels with renal dysfunction. Accordingly, scientists have exploited galectin-3 as a potential pharmacological target to improve renal functions in different preclinical models of renal injury. Apart from galectin-3, there have been few studies documenting the role of galectin-1, 8, and 9 in renal diseases. The role of galectin-1 is not clearly identified, and there have been conflicting reports regarding its role in renal diseases. Galectin-8 and 9 impart renoprotective effects as per clinical and preclinical studies, respectively. The present review discusses the role of different galectins in renal diseases of diverse etiology.

The Use of Genomics to Drive Kidney Disease Drug Discovery and Development.

As opposed to diseases such as cancer, autoimmune disease, and diabetes, identifying drugs to treat CKD has proven significantly more challenging. Over the past 2 decades, new potential therapeutic targets have been identified as genetically altered proteins involved in rare monogenetic kidney diseases. Other possible target genes have been implicated through common genetic polymorphisms associated with CKD in the general population. Significant challenges remain before translating these genetic insights into clinical therapies for CKD. This paper will discuss how genetic variants may be leveraged to develop drugs and will especially focus on those genes associated with CKD to exemplify the value and challenges in including genetic information in the drug development pipeline.

Metabolic Reprogramming in Autosomal Dominant Polycystic Kidney Disease: Evidence and Therapeutic Potential.

Autosomal dominant polycystic kidney disease is characterized by progressive development and enlargement of kidney cysts, leading to ESKD. Because the kidneys are under high metabolic demand, it is not surprising that mounting evidence suggests that a metabolic defect exists in in vitro and animal models of autosomal dominant polycystic kidney disease, which likely contributes to cystic epithelial proliferation and subsequent cyst growth. Alterations include defective glucose metabolism (reprogramming to favor aerobic glycolysis), dysregulated lipid and amino acid metabolism, impaired autophagy, and mitochondrial dysfunction. Limited evidence supports that cellular kidney metabolism is also dysregulated in humans with autosomal dominant polycystic kidney disease. There are notable overlapping features and pathways among metabolism, obesity, and/or autosomal dominant polycystic kidney disease. Both dietary and pharmacologic-based strategies targeting metabolic abnormalities are being considered as therapies to slow autosomal dominant polycystic kidney disease progression and are attractive, particularly given the slowly progressive nature of the disease. Dietary strategies include daily caloric restriction, intermittent fasting, time-restricted feeding, a ketogenic diet, and 2-deoxy-glucose as well as alterations to nutrient availability. Pharmacologic-based strategies include AMP-activated kinase activators, sodium glucose cotransporter-2 inhibitors, niacinamide, and thiazolidenediones. The results from initial clinical trials targeting metabolism are upcoming and anxiously awaited within the scientific and polycystic kidney disease communities. There continues to be a need for additional mechanistic studies to better understand the role of dysregulated metabolism in autosomal dominant polycystic kidney disease and for subsequent translation to clinical trials. Beyond single-intervention trials focused on metabolic reprograming in autosomal dominant polycystic kidney disease, great potential also exists by combining metabolic-focused therapeutic approaches with compounds targeting other signaling cascades altered in autosomal dominant polycystic kidney disease, such as tolvaptan.

[Bardoxolone: a new potential therapeutic agent in the treatment of autosomal dominant polycystic kidney disease?]

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of chronic renal failure. The natural history of ADPKD is characterized by development of multiple bilateral renal cysts that progressively destroy the architecture of the parenchyma and lead to an enlargement in the total kidney volume (TKV) and to the decline of the renal function. Cyst growth activates the immune system response causing interstitial inflammation and fibrosis that contribute to disease progression. In recent years, the therapeutic toolkit available to the nephrologist in the treatment of ADPKD has been enriched with new tools, and in this context bardoxolone is classified as a potential therapeutic agent. It is a semisynthetic derivative of triterpenoids, a family of compounds widely used in traditional Asian medicine for their multiple effects. Bardoxolone exerts antioxidant activity by promoting the activation of Nrf2 (Nuclear factor erythroid2-derivative - 2) and the downregulation of the proinflammatory NF-kB (Nuclear factor kappa-light-chain-enhancer of activated B cells) signaling. Several pieces of evidence support the use of bardoxolone in the treatment of chronic kidney disease (CKD) documenting an effect on the increase of glomerular filtration rate (GFR). However, its use is limited to patients at risk of heart failure. The FALCON study will clarify the efficacy and safety of bardoxolone in the treatment of ADPKD.

BMP1 inhibitor UK383,367 attenuates renal fibrosis and inflammation in CKD.

Renal fibrosis is a key pathological phenomenon of chronic kidney disease (CKD) contributing to the progressive loss of renal function. UK383,367 is a procollagen C proteinase inhibitor that has been selected as a candidate for dermal antiscarring agents, whereas its role in renal fibrosis is unclear. In the present study, UK383,367 was applied to a CKD mouse model of unilateral ureteral obstruction (UUO) and cell lines of renal tubular epithelial cells (mouse proximal tubular cells) and renal fibroblast cells (NRK-49F cells) challenged by transforming growth factor-ß1. In vivo, bone morphogenetic protein 1, the target of UK383,367, was significantly enhanced in UUO mouse kidneys and renal biopsies from patients with CKD. Strikingly, UK383,367 administration ameliorated tubulointerstitial fibrosis as shown by Masson's trichrome staining in line with the blocked expression of collagen type I/III, fibronectin, and α-smooth muscle actin in the kidneys from UUO mice. Similarly, the enhanced inflammatory factors in obstructed kidneys were also blunted. In vitro, UK383,367 pretreatment inhibited the induction of collagen type I/III, fibronectin, and α-smooth muscle actin in both mouse proximal tubular cells and NRK-49F cells treated with transforming growth factor-ß1. Taken together, these findings indicate that the bone morphogenetic protein 1 inhibitor UK383,367 could serve as a potential drug in antagonizing CKD renal fibrosis by acting on the maturation and deposition of collagen and the subsequent profibrotic response and inflammation.

Targeting STAT3 signaling in kidney disease.

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is a multifaceted transduction system that regulates cellular responses to incoming signaling ligands. STAT3 is a central member of the JAK/STAT signaling cascade and has long been recognized for its increased transcriptional activity in cancers and autoimmune disorders but has only recently been in the spotlight for its role in the progression of kidney disease. Although genetic knockout and manipulation studies have demonstrated the salutary benefits of inhibiting STAT3 activity in several kidney disease models, pharmacological inhibition has yet to make it to the clinical forefront. In recent years, significant effort has been aimed at suppressing STAT3 activation for treatment of cancers, which has led to the development of a wide variety of STAT3 inhibitors, but only a handful have been tested in kidney disease models. Here, we review the detrimental role of dysregulated STAT3 activation in a variety of kidney diseases and the current progress in the treatment of kidney diseases with pharmacological inhibition of STAT3 activity.

CRRL269.

RATIONALE: Acute kidney injury (AKI) has a high prevalence and mortality in critically ill patients. It is also a powerful risk factor for heart failure incidence driven by hemodynamic changes and neurohormonal activation. However, no drugs have been approved by the Food and Drug Administration. Endogenous pGC-A (particulate guanylyl cyclase A receptor) activators were reported to preserve renal function and improve mortality in AKI patients, although hypotension accompanied by pGC-A activators have limited their therapeutic potential. OBJECTIVE: We investigated the therapeutic potential of a nonhypotensive pGC-A activator/designer natriuretic peptide, CRRL269, in a short-term, large animal model of ischemia-induced AKI and also investigated the potential of uCNP (urinary C-type natriuretic peptide) as a biomarker for AKI. METHODS AND RESULTS: We first showed that CRRL269 stimulated cGMP generation, suppressed plasma angiotensin II, and reduced cardiac filling pressures without lowering blood pressure in the AKI canine model. We also demonstrated that CRRL269 preserved glomerular filtration rate, increased renal blood flow, and promoted diuresis and natriuresis. Further, CRRL269 reduced kidney injury and apoptosis as evidenced by ex vivo histology and tissue apoptosis analysis. We also showed, compared with native pGC-A activators, that CRRL269 is a more potent inhibitor of apoptosis in renal cells and induced less decreases in intracellular Ca2+ concentration in vascular smooth muscle cells. The renal antiapoptotic effects were at least mediated by cGMP/PKG pathway. Further, CRRL269 inhibited proapoptotic genes expression using a polymerase chain reaction gene array. Additionally, we demonstrated that AKI increased uCNP levels. CONCLUSIONS: Our study supports developing CRRL269 as a novel renocardiac protective agent for AKI treatment.

Beta2-adrenergic receptor in kidney biology: A current prospective.

Beta2-adrenergic receptor (ß2 -AR) is a G-protein-coupled adrenergic receptor family member, whose clinical significance has been extensively investigated in lung, cardiovascular and muscular diseases, but its role in kidney biology remains understudied. In this review, we discuss some of the recent studies, where the effect of agonist/antagonist-mediated activation/inhibition of ß2 -AR on disease pathogenesis process was studied, and highlighted the role of ß2 -AR in kidney biology. The expression of ß2 -AR has been noted in many kidney subunits including proximal tubules, glomeruli and podocytes. In vivo studies have shown that in cultured proximal tubules ß2 -AR is involved in Na-ATPase activity and transcellular Na-transport through protein kinase-C activation; whereas in cultured podocytes, it was associated with depolarization of the membrane. The animal studies further revealed that ß2 -AR activation by short-acting ß2 agonists attenuated monocyte activation, pro-inflammatory and pro-fibrotic responses through ß-arrestin2 dependent NF-kB inactivation in diabetic kidney disease; in contrast, activation by long-acting ß2 agonists restored mitochondrial and renal function in the acute kidney injury mice models through PGC-1α dependent mitochondrial biogenesis. In conclusion, the activation of ß2 -AR may present a rapidly developing therapeutic target for renal diseases.

Effect of Alprostadil on the Prevention of Contrast-Induced Nephropathy: A Meta-Analysis of 36 Randomized Controlled Trials.

Contrast-induced nephropathy (CIN) is the third leading cause of acquired acute renal injury in hospitalized patients. Alprostadil plays a role in the maintenance and redistribution of intrarenal blood flow and the excretion of electrolytes and water. However, the effectiveness of alprostadil in preventing CIN remains controversial. Thirty-six articles with a total of 5495 patients were included in this study. Both groups (experimental group and control group) received standard hydration therapy. In the experimental group, patients received different doses of alprostadil. Serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), cystatin C, creatinine clearance rate (CCr), and ß2-microglobulin (ß2-MG) were measured at 24, 48, and 72 hours after contrast media injection. The incidence of CIN in the experimental group was significantly lower than that in the control group (6.56% vs 16.74%). The level of SCr, cystatin C, BUN, and ß2-MG in the experimental group was lower than those in the control group; CCr and eGFR in the experimental group were higher than those in the control group. This study demonstrated that alprostadil may reduce the incidence of CIN in patients undergoing coronary angiogram and/or percutaneous coronary intervention.

[Cardiorenal syndrome]. / Das kardiorenale Syndrom.

Patients in the intensive care unit often suffer from cardiorenal syndrome, which can have an important influence on the patient's outcome. The heart and kidney influence each other via organ crosstalk. We screened and evaluated current publications on cardiorenal syndromes and their therapy. A key role in the management of cardiorenal syndromes is renal decongestion via loop diuretics.

Long-Term Mortality and Bone Safety in Patients with End-Stage Renal Disease Receiving Lanthanum Carbonate.

BACKGROUND/AIMS: This post-marketing observational study assessed the long-term safety of lanthanum carbonate (LaC) in US patients with end-stage renal disease (NCT00567723). METHODS: Patients (≥18 years old) undergoing dialysis, who had Medicare as their primary healthcare payer, and records in the United States Renal Data System were followed-up for 5 years. Patients who had received LaC for at least 12 consecutive weeks formed the exposed cohort. During the same time period, patients who had undergone dialysis for at least 12 consecutive weeks and had been treated with any other phosphate binder formed the primary comparator cohort. A historical cohort was also evaluated. Primary outcomes were all-cause mortality, and time to and incidence of first bone-fracture event requiring hospitalization. Secondary outcomes were time to first occurrence of and incidence of specific gastrointestinal (GI) disease, liver disease, malignancy, and major infectious episode requiring hospitalization. -Results: 2,026 and 8,094 patients were included in the exposed and primary comparator cohorts, respectively. A Cox proportional hazards model showed that patients receiving LaC were not at increased risk of all-cause mortality (adjusted hazard ratio 0.94; 95% CI 0.88-1.01; p = 0.078), bone fractures (0.86; 0.71-1.05; p = 0.130), specific GI disease (0.86; 0.76-0.97; p = 0.015), liver disease (0.88; 0.70-1.09; p = 0.236), malignancy (0.85; 0.54-1.34; p = 0.496), or major infectious episodes (0.87; 0.80-0.94; p < 0.001) requiring hospitalization compared with primary comparator patients. CONCLUSIONS: LaC was not associated with increased risk of mortality, bone fractures, or any secondary outcome.

New insights into the role and mechanism of Wnt/ß-catenin signalling in kidney fibrosis.

Wnt/ß-catenin is an evolutionarily conserved, developmental signalling pathway that regulates embryogenesis, injury repair and pathogenesis of human diseases. Dysregulated activation of Wnt/ß-catenin is associated with the development and progression of renal fibrotic lesions after injury. Wnt are induced and ß-catenin is activated in various models of experimental chronic kidney disease (CKD) and in human nephropathies. Recent findings indicate that pro(renin) receptor is an amplifier of Wnt/ß-catenin by acting as a downstream target and an obligatory component for its signal transduction. Genetic blockade of Wnt secretion in a cell type-specific manner uncovers renal tubular epithelium as the major source of Wnt ligands in CKD. Wnt/ß-catenin controls the expression of a wide variety of downstream mediators implicated in kidney fibrosis, such as fibronectin, Snail1, matrix metalloproteinase-7, hepatocyte growth factor and various components of the renin-angiotensin system. Targeted inhibition of Wnt/ß-catenin is able to ameliorate kidney fibrotic lesions in pre-clinical settings. In this review, we summarize recent advances in our understanding of the regulation, signal transduction, role and mechanisms of Wnt/ß-catenin signalling in the pathogenesis of kidney fibrosis. We also discuss the therapeutic potential of targeting this pathway for the treatment of fibrotic CKD.

[Correlation between TGF-B gene promoter-509C/T polymorphism and IgA nephropathy in core families in Guangxi Zhuang Autonomous Region and the therapeutic effect of dendrobium].

OBJECTIVE: To investigate the correlation between transformation growth factor (TGF- B) polymorphisms and IgA nephropathy and the therapeutic effect of dendrobium on IgA nephropathy. METHODS: Polymerase chain reaction- restriction fragment length polymorphism (PCR- RFLP) and direct sequencing were used for analysis of 118 patients with IgA nephropathy from core families in Guangxi Zhuang Autonomous Region. The imbalanced transfer of TGF iso1-509 C/T in the affected offsprings was observed by transfer imbalance test and HRR analysis. The TGF-B genotype of the patients and the core family members were detected. The therapeutic effects of Dendrobium candidum combined with hormone and ACEI/ARB treatments were evaluated by observing the patient's urine protein (24 hUpr), serum albumin (ALB), creatinine (Scr) and urea nitrogen (BUN) levels. RESULTS: In the 118 patients with IgA nephropathy, we identified TGF-B 1 promoter -509C/T genotype CC in 32 (27.1%) cases, CT in 58 (49.2%) cases, and TT in 28 (23.7%) cases. In the core family of the patients, CC genotype was found in 33 (28.0%) cases, CT in 55 (46.6%) cases, and TT in 30 (28.0%) cases. The treatments significantly lowered 24 hUpr, Scr, and BUN levels (P > 0.05) in patients with CC genotype, significantly lowered 24 hUpr and BUN levels in patients with CT genotype (P < 0.05), and significantly lowered 24 hUpr and BUN level and increased (P < 0.05) ALB level (P < 0.01) in patients with TT genotype. CONCLUSIONS: There is no significant correlation between TGF-B promoter - 509C/T polymorphism and IgA nephropathy. The patients with CC genotype are sensitive to the treatments with hormone and ACEI/ ARB and show a stronger response to combined treatments with dendrobium.