Effects of Qidan Tangshen Granule on diabetic kidney disease in patients with type 2 diabetes.

BACKGROUND: This study aimed to conduct a prospective, randomized, controlled clinical trial using, Qidan Tangshen Granule, a traditional Chinese medicine (TCM), as an antioxidant, to treat diabetic kidney disease (DKD) patients. METHODS: A total of 355 patients were enrolled, and after exclusions, 219 patients were divided into an intervention group (n = 109) receiving Qidan Tangshen Granule treatment and a control group (n = 110) receiving conventional treatment. Demographic and physiological parameters were evaluated at baseline and 3 months and 12 months of follow-up. The levels of serum oxidants including 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 3-nitrotyrosine (3-NT), and the enzymic anti-oxidant, superoxide dismutase (SOD), were evaluated using enzyme-linked immunosorbent assays. RESULTS: Qidan Tangshen Granule treatment significantly reduced hemoglobin A1c (HbA1c) and albumin-to-creatinine ratio (UACR) levels, improved renal function, and exerted antioxidative effects in DKD patients. Compared to the control group, the intervention group showed increased levels of SOD and decreased levels of 8-OHdG and 3-NT, indicating reduced oxidative stress. Furthermore, the intervention group demonstrated a significant decrease in HbA1c and UACR levels and an improvement in glomerular filtration rate compared to the control group. CONCLUSIONS: Qidan Tangshen Granule may be a potential therapeutic option for the treatment of DKD, offering improved clinical outcomes for patients.

Tangshen formula protects against podocyte apoptosis via enhancing the TFEB-mediated autophagy-lysosome pathway in diabetic nephropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease and currently there are no specific and effective drugs for its treatment. Podocyte injury is a detrimental feature and the major cause of albuminuria in DN. We previously reported Tangshen Formula (TSF), a Chinese herbal medicine, has shown therapeutic effects on DN. However, the underlying mechanisms remain obscure. AIM OF THE STUDY: This study aimed to explore the protective effect of TSF on podocyte apoptosis in DN and elucidate the potential mechanism. MATERIALS AND METHODS: The effects of TSF were assessed in a murine model using male KKAy diabetic mice, as well as in advanced glycation end products-stimulated primary mice podocytes. Transcription factor EB (TFEB) knockdown primary podocytes were employed for mechanistic studies. In vivo and in vitro studies were performed and results assessed using transmission electron microscopy, immunofluorescence staining, and western blotting. RESULTS: TSF treatment alleviated podocyte apoptosis and structural impairment, decreased albuminuria, and mitigated renal dysfunction in KKAy mice. Notably, TSF extracted twice showed a more significant reduction in proteinuria than TSF extracted three times. Accumulation of autophagic biomarkers p62 and LC3, and aberrant autophagic flux in podocytes of DN mice were significantly altered by TSF therapy. Consistent with the in vivo results, TSF prevented the apoptosis of primary podocytes exposed to AGEs and activated autophagy. However, the anti-apoptosis capacity of TSF was countered by the autophagy-lysosome inhibitor chloroquine. We found that TSF increased the nuclear translocation of TFEB in diabetic podocytes, and thus upregulated transcription of its several autophagic target genes. Pharmacological activation of TFEB by TSF accelerated the conversion of autophagosome to autolysosome and lysosomal biogenesis, further augmented autophagic flux. Conversely, TFEB knockdown negated the favorable effects of TSF on autophagy in AGEs-stimulated primary podocytes. CONCLUSIONS: These findings indicate TSF appears to attenuate podocyte apoptosis and promote autophagy in DN via the TFEB-mediated autophagy-lysosome system. Thus, TSF may be a therapeutic candidate for DN.

Associations Between Individual and Combined Metal Exposures in Whole Blood and Kidney Function in U.S. Adults Aged 40 Years and Older.

The effects of metal exposure on kidney function have been reported in previous literature. There is limited and inconsistent information on the associations between individual and combined exposures to metals and kidney function among the middle-aged and older population. The aim of this study was to clarify the associations of exposure to individual metals with kidney function while accounting for potential coexposure to metal mixtures and to evaluate the joint and interactive associations of blood metals with kidney function. A total of 1669 adults aged 40 years and older were enrolled in the present cross-sectional study using the 2015-2016 National Health and Nutrition Examination Survey (NHANES). Single-metal and multimetal multivariable logistic regression models, quantile G-computation, and Bayesian kernel machine regression models (BKMR) were fitted to explore the individual and joint associations of whole blood metals [lead (Pb), cadmium (Cd), mercury (Hg), cobalt (Co), manganese (Mn), and selenium (Se)] with the odds of decreased estimated glomerular filtration rate (eGFR) and albuminuria. A decreased eGFR was defined as an eGFR ≤ 60 mL/min per 1.73 m2, and albuminuria was categorized as a urinary albumin-creatinine ratio (UACR) of ≥ 30.0 mg/g. The results from quantile G-computation and BKMR indicated positive associations between exposure to the metal mixture and the prevalence of decreased eGFR and albuminuria (all P values < 0.05). These positive associations were mainly driven by blood Co, Cd, and Pb. Furthermore, blood Mn was identified as an influential element contributing to an inverse correlation with kidney dysfunction within metal mixtures. Increasing blood Se levels were negatively associated with the prevalence of decreased eGFR and positively associated with albuminuria. In addition, a potential pairwise interaction between Mn-Co on decreased eGFR was identified by BKMR analysis. Findings from our study suggested a positive association between exposure to the whole blood metal mixture and decreased kidney function, with blood Co, Pb, and Cd being the main contributors to this association, while Mn demonstrated an inverse relationship with renal dysfunction. However, as our study was cross-sectional in nature, further prospective studies are warranted to better understand the individual and combined effects of metals on kidney function.

[The effect of a medicinal plant preparation on the frequency of episodes of exacerbation of recurrent cystitis and metabolic parameters in patients with type 2 diabetes mellitus taking glyphlosins].

BACKGROUND: The problem of recurrent urinary tract infections (UTI) in patients with type 2 diabetes mellitus (DM 2) is relevant, especially when there is a combination of predisposing factors, such as female gender, history of UTI episodes, and therapy with sodium glucose cotransporter type 2 (SGLT-2) inhibitors, and the choice of effective and safe means could cause some difficulties, including ina terms of the burden of antibiotic resistance. AIM: To evaluate the effectiveness and safety of the phytoproduct Canephron® N for the prevention of exacerbations of recurrent cystitis and the effect on metabolic parameters in patients with type 2 diabetes taking SGLT-2 inhibitors. MATERIALS AND METHODS: Prospective, randomized, open, parallel group study in 60 women. The main group took the drug Canephron® N for 3 months. The main parameters for evaluating were the frequency of recurrence of cystitis, level of albuminuria and LDL-cholesterol peroxidation product - malondialdehyde. RESULTS: Within 3 months of taking Canephron® N, exacerbations of chronic cystitis were diagnosed 2 times less often, a decrease in albuminuria was found in the form of an increase in the proportion of patients with an optimal level of albuminuria by 20%, a 50% reduction in the frequency of the initial increase in albuminuria, and the absence of moderate albuminuria in all patients at the end of course of therapy. A decrease in the level of MDA by 1.4 times was noted (p=0.019). CONCLUSION: Thus, the herbal drug Canephron® N can be used for accompanying therapy and prophylactic treatment in patients with recurrent cystitis on the background of DM 2, taking SGLT-2 inhibitors. The course of therapy should last at least 3 months.

The drivers of non-adherence to albuminuria testing guidelines and the clinical and economic impact of not identifying chronic kidney disease.

BACKGROUND: Regular monitoring is required to ensure that patients who have, or are at risk of, chronic kidney disease (CKD) receive appropriate management. Guidelines recommend regular testing of estimated glomerular filtration rate (GFR) and albuminuria. However, evidence suggests that albuminuria testing rates, specifically urine albumin-to-creatinine ratio (UACR), are suboptimal. AIM: To assess published evidence relating to the drivers of non-adherence to albuminuria testing guidelines and the impact of not identifying CKD across the course of progression. MATERIALS AND METHODS: A systematic review of five bibliographic databases was conducted, supplemented by hand searches of relevant conference abstracts. RESULTS: One study was identified that reported drivers of non-adherence to albuminuria testing guidelines. The largest barrier was the perception that testing does not impact patient management. Thirteen studies were identified that evaluated the impact of not identifying CKD patients. All included studies analyzed the effect of not identifying worsening CKD severity leading to late referral (LR). 12/13 studies reported only on clinical impact, and 1/13 reported on clinical and economic impact. LR led to higher costs and worse outcomes than early referral, including higher rates of mortality and worsened kidney replacement therapy preparation. CONCLUSION: This systematic review demonstrates a gap in evidence exploring the drivers of non-adherence to albuminuria testing guidelines and the impact of not identifying patients in the early stages of CKD. Guideline-recommended testing allows timely identification, referral, and treatment for patients with, or at risk of, CKD, providing the best chance of avoiding the worsened outcomes identified in this review.

Integrated multi-omics and bioinformatic methods to reveal the mechanisms of sinomenine against diabetic nephropathy.

OBJECTIVES: Diabetic Nephropathy (DN) is a serious complication of diabetes, the diagnosis and treatment of DN is still limited. Sinomenine (SIN) is an active extract of herbal medicine and has been applied into the therapy of DN. METHODS: In the part of bioinformatic analyses, network pharmacology and molecular docking analyses were conducted to predict the important pathway of SIN treatment for DN. In-vivo study, DN rats were randomized to be treated with vehicle or SIN (20 mg/kg or 40 mg/kg) daily by gavage for 8 weeks. Then, the pharmacological effect of SIN on DN and the potential mechanisms were also evaluated by 24 h albuminuria, histopathological examination, transcriptomics, and metabolomics. RESULTS: Firstly, network pharmacology and molecular docking were performed to show that SIN might improve DN via AGEs/RAGE, IL-17, JAK, TNF pathways. Urine biochemical parameters showed that SIN treatment could significantly reduce 24 h albuminuria of DN rats. Transcriptomics analysis found SIN could affect DN progression via inflammation and EMT pathways. Metabolic pathway analysis found SIN would mainly involve in arginine biosynthesis, linoleic acid metabolism, arachidonic acid metabolism, and glycerophospholipid metabolism to affect DN development. CONCLUSIONS: We confirmed that SIN could inhibit the progression of DN via affecting multiple genes and metabolites related pathways.

Add-on Rehmannia-6-Based Chinese Medicine in Type 2 Diabetes and CKD: A Multicenter Randomized Controlled Trial.

BACKGROUND: Diabetes is the leading cause of CKD and kidney failure. We assessed the real-world effectiveness of Rehmannia-6-based Chinese medicine treatment, the most used Chinese medicine formulation, on the change in eGFR and albuminuria in patients with diabetes and CKD with severely increased albuminuria. METHODS: In this randomized, assessor-blind, standard care-controlled, parallel, multicenter trial, 148 adult patients from outpatient clinics with type 2 diabetes, an eGFR of 30-90 ml/min per 1.73 m 2 , and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g were randomized 1:1 to a 48-week add-on protocolized Chinese medicine treatment program (using Rehmannia-6-based formulations in the granule form taken orally) or standard care alone. Primary outcomes were the slope of change in eGFR and UACR between baseline and end point (48 weeks after randomization) in the intention-to-treat population. Secondary outcomes included safety and the change in biochemistry, biomarkers, and concomitant drug use. RESULTS: The mean age, eGFR, and UACR were 65 years, 56.7 ml/min per 1.73 m 2 , and 753 mg/g, respectively. Ninety-five percent ( n =141) of end point primary outcome measures were retrievable. For eGFR, the estimated slope of change was -2.0 (95% confidence interval [CI], -0.1 to -3.9) and -4.7 (95% CI, -2.9 to -6.5) ml/min per 1.73 m 2 in participants treated with add-on Chinese medicine or standard care alone, resulting in a 2.7 ml/min per 1.73 m 2 per year (95% CI, 0.1 to 5.3; P = 0.04) less decline with Chinese medicine. For UACR, the estimated proportion in the slope of change was 0.88 (95% CI, 0.75 to 1.02) and 0.99 (95% CI, 0.85 to 1.14) in participants treated with add-on Chinese medicine or standard care alone, respectively. The intergroup proportional difference (0.89, 11% slower increment in add-on Chinese medicine, 95% CI, 0.72 to 1.10; P = 0.28) did not reach statistical significance. Eighty-five adverse events were recorded from 50 participants (add-on Chinese medicine versus control: 22 [31%] versus 28 [36%]). CONCLUSIONS: Rehmannia-6-based Chinese medicine treatment stabilized eGFR on top of standard care alone after 48 weeks in patients with type 2 diabetes, stage 2-3 CKD, and severely increased albuminuria. CLINICAL TRIAL REGISTRY: Semi-individualized Chinese Medicine Treatment as an Adjuvant Management for Diabetic Nephropathy (SCHEMATIC), NCT02488252 .

Emerging Therapies and Advances in Sickle Cell Disease with a Focus on Renal Manifestations.

The underlying mechanisms of disease in sickle cell disease (SCD) contribute to a multifaceted nephropathy, commonly manifested as albuminuria. In severe SCD genotypes ( e.g. , Hemoglobin SS [HbSS]), albuminuria and CKD are major predictors of mortality in this population. Therefore, the monitoring and management of renal function is an intrinsic part of comprehensive care in SCD. Management of nephropathy in SCD can be accomplished with SCD-directed therapies and/or CKD-directed therapies. In the past 5 years, novel disease-modifying and palliative therapies have been approved in SCD to target aspects of the disease, such as anemia, inflammation, and vasculopathy. Along with conventional hydroxyurea and chronic transfusion, l -glutamine, crizanlizumab, and voxelotor have all been shown to mitigate some adverse effect of SCD, and their effect on nephropathy is being investigated. CKD-directed therapies such as renin-angiotensin-aldosterone system blockers have long been used in SCD nephropathy; however, more complete long-term studies on benefits are needed. Given the effect of renal disease on survival, further assessment of the mechanisms and efficacy of these SCD-directed or CKD-directed therapeutic agents is essential.

Klotho Supplementation Reverses Renal Dysfunction and Interstitial Fibrosis in Remnant Kidney.

INTRODUCTION: While recent investigations show that klotho exerts renoprotective actions, it has not been fully addressed whether klotho protein supplementation reverses renal damage. METHODS: The impacts of subcutaneous klotho supplementation on rats with subtotal nephrectomy were examined. Animals were divided into 3 groups: group 1 (short remnant [SR]): remnant kidney for 4 weeks, group 2 (long remnant [LR]): remnant kidney for 12 weeks, and group 3 (klotho supplementation [KL]): klotho protein (20 µg/kg/day) supplementation on the remnant kidney. Blood pressure, blood and urine compositions with conventional methods such as enzyme-linked immunosorbent assay and radioimmunoassay, kidney histology, and renal expressions of various genes were analyzed. In vitro studies were also performed to support in vivo findings. RESULTS: Klotho protein supplementation decreased albuminuria (-43%), systolic blood pressure (-16%), fibroblast growth factor (FGF) 23 (-51%) and serum phosphate levels (-19%), renal angiotensin II concentration (-43%), fibrosis index (-70%), renal expressions of collagen I (-55%), and transforming growth factor ß (-59%) (p < 0.05 for all). Klotho supplementation enhanced fractional excretion of phosphate (+45%), glomerular filtration rate (+76%), renal expressions of klotho (+148%), superoxide dismutase (+124%), and bone morphogenetic protein (BMP) 7 (+174%) (p < 0.05 for all). CONCLUSION: Our data indicated that klotho protein supplementation inactivated renal renin-angiotensin system, reducing blood pressure and albuminuria in remnant kidney. Furthermore, exogenous klotho protein supplementation elevated endogenous klotho expression to increase phosphate excretion with resultant reductions in FGF23 and serum phosphate. Finally, klotho supplementation reversed renal dysfunction and fibrosis in association with improved BMP7 in remnant kidney.

Combined detection of urinary biomarkers noninvasively predicts extent of renal injury in patients with early diabetic kidney disease with kidney qi deficiency syndrome: A retrospective investigation.

Incipient diagnosis and noninvasive forecasts using urinary biomarkers are important for preventing diabetic kidney disease (DKD) progression, but they are also controversial. Previous studies have shown a potential relationship between urinary tubular biomarkers (UTBs) and traditional Chinese medicine (TCM) syndrome in patients with DKD. Thus, we further evaluated the clinical significance of combined detection of urinary biomarkers in noninvasively predicting the extent of renal damage in patients with early DKD with kidney qi deficiency syndrome, and preliminarily explored the potential biological link between UTBs and TCM syndrome in DKD. We categorized 92 patients with Type 2 diabetes mellitus into three groups as follows: 20 patients with normoalbuminuria, 50 patients with microalbuminuria, and 22 patients with macroalbuminuria. We found that, in all groups, 24 hr urinary albumin (24hUAlb) and urinary albumin-to-creatinine ratio (UACR) showed stepwise and significant increases. Urinary cystatin C (UCysC), urinary N-acetyl-ß-d-glucosaminidase (UNAG), and urinary retinol-binding protein (URBP) synchronously increased gradually, consistent with the degree of albuminuria in all groups. Moreover, 24hUAlb and UACR were positively correlated with UCysC, UNAG, and URBP, respectively. In 72 patients with Type 2 DKD with albuminuria, a positive correlation was observed between UNAG and URBP, UCysC was also positively correlated with UNAG and URBP, respectively. Additionally, TCM syndrome distributional characteristics in all patients were consistent with clinical manifestations of kidney qi deficiency syndrome. Therefore, the combined detection of UCysC, UNAG, URBP, and UAlb may be used as a practical clinical technique to noninvasively forecast the extent of renal injury in patients with early Type 2 DKD with kidney qi deficiency syndrome. UTBs may be one of the biological bases of the specific TCM syndromes in DKD.

Plasma levels of carboxylic acids are markers of early kidney dysfunction in young people with type 1 diabetes.

BACKGROUND: We compared plasma metabolites of amino acid oxidation and the tricarboxylic acid (TCA) cycle in youth with and without type 1 diabetes mellitus (T1DM) and related the metabolites to glomerular filtration rate (GFR), renal plasma flow (RPF), and albuminuria. Metabolites associated with impaired kidney function may warrant future study as potential biomarkers or even future interventions to improve kidney bioenergetics. METHODS: Metabolomic profiling of fasting plasma samples using a targeted panel of 644 metabolites and an untargeted panel of 19,777 metabolites was performed in 50 youth with T1DM ≤ 10 years and 20 controls. GFR and RPF were ascertained by iohexol and p-aminohippurate clearance, and albuminuria calculated as urine albumin to creatinine ratio. Sparse partial least squares discriminant analysis and moderated t tests were used to identify metabolites associated with GFR and RPF. RESULTS: Adolescents with and without T1DM were similar in age (16.1 ± 3.0 vs. 16.1 ± 2.9 years) and BMI (23.4 ± 5.1 vs. 22.7 ± 3.7 kg/m2), but those with T1DM had higher GFR (189 ± 40 vs. 136 ± 22 ml/min) and RPF (820 ± 125 vs. 615 ± 65 ml/min). Metabolites of amino acid oxidation and the TCA cycle were significantly lower in adolescents with T1DM vs. controls, and the measured metabolites were able to discriminate diabetes status with an AUC of 0.82 (95% CI: 0.71, 0.93) and error rate of 0.21. Lower glycine (r:-0.33, q = 0.01), histidine (r:-0.45, q < 0.001), methionine (r: -0.29, q = 0.02), phenylalanine (r: -0.29, q = 0.01), serine (r: -0.42, q < 0.001), threonine (r: -0.28, q = 0.02), citrate (r: -0.35, q = 0.003), fumarate (r: -0.24, q = 0.04), and malate (r: -0.29, q = 0.02) correlated with higher GFR. Lower glycine (r: -0.28, q = 0.04), phenylalanine (r:-0.3, q = 0.03), fumarate (r: -0.29, q = 0.04), and malate (r: -0.5, q < 0.001) correlated with higher RPF. Lower histidine (r: -0.28, q = 0.02) was correlated with higher mean ACR. CONCLUSIONS: In conclusion, adolescents with relatively short T1DM duration exhibited lower plasma levels of carboxylic acids that associated with hyperfiltration and hyperperfusion. TRIAL REGISTRATION: ClinicalTrials.gov NCT03618420 and NCT03584217 A higher resolution version of the Graphical abstract is available as Supplementary information.

Association of habitual coffee consumption and kidney function: A prospective analysis in the Rotterdam Study.

BACKGROUND & AIMS: Population-based studies have suggested a protective effect of coffee against development of chronic kidney disease (CKD), possibly through coffee's anti-inflammatory and antioxidant compounds. Studies on coffee and kidney function decline in the general population are scarce. We studied associations of habitual coffee consumption with repeated assessments of estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR). METHODS: We used data from 7,914 participants of the population-based Rotterdam Study. Baseline coffee consumption data (cups/day) were obtained from home interviews and validated food frequency questionnaires (1997-2008). Repeated assessments of eGFR (ml/min per 1.73 m2, 1997-2014) were calculated according to the creatinine-based CKD Epidemiology Collaboration equation of 2012. Repeated assessments of urinary albumin and creatinine were used to estimate ACR (mg/g, 2006-2014). Data were analyzed by applying linear mixed models, adjusted for sociodemographic, lifestyle and dietary factors, and cardiovascular disease risk factors. Predefined subgroup analyses were performed stratified by CKD risk factors. RESULTS: Participants' mean (SD) baseline age was 66 (10) years, 57% were women and median [IQR] coffee consumption was 3.0 [2.0, 5.0] cups/day. Those drinking more coffee were more likely to smoke, and to have type 2 diabetes (T2D) and obesity. Mean eGFR was 79 (15) ml/min per 1.73 m2. In the total study population, coffee was not associated with longitudinal eGFR during a median of 5.4 years of follow-up (ß = 0.04 ml/min per 1.73 m2 per one cup/day [95% CI: -0.10,0.18]). However, among those aged >70 years, one additional coffee cup/day was associated with on average 0.84 (0.51,1.18) ml/min per 1.73 m2 higher longitudinal eGFR. Among obese participants this estimate was 0.32 (0.01,0.63). A protective trend was also observed among former smokers (0.17 [-0.03,0.39]) and those with T2D (0.42 [-0.05,0.88]). Coffee was not associated with longitudinal ACR (0.01 mg/ml [-0.01,0.02]). CONCLUSION: While coffee was not associated with eGFR and ACR in the total population, more coffee consumption was associated with higher longitudinal eGFR among those at higher risk for CKD, i.e., among those aged 70+ and obese participants. These findings require confirmation in other prospective cohort studies.

Association of single and joint metals with albuminuria and estimated glomerular filtration longitudinal change in middle-aged adults from Spain: The Aragon workers health study.

The nephrotoxicity of low-chronic metal exposures is unclear, especially considering several metals simultaneously. We assessed the individual and joint association of metals with longitudinal change in renal endpoints in Aragon Workers Health Study participants with available measures of essential (cobalt [Co], copper [Cu], molybdenum [Mo] and zinc [Zn]) and non-essential (As, barium [Ba], Cd, chromium [Cr], antimony [Sb], titanium [Ti], uranium [U], vanadium [V] and tungsten [W]) urine metals and albumin-to-creatinine ratio (ACR) (N = 707) and estimated glomerular filtration rate (eGFR) (N = 1493) change. Median levels were 0.24, 7.0, 18.6, 295, 3.1, 1.9, 0.28, 1.16, 9.7, 0.66, 0.22 µg/g for Co, Cu, Mo, Zn, As, Ba, Cd, Cr, Sb, Ti, V and W, respectively, and 52.5 and 27.2 ng/g for Sb and U, respectively. In single metal analysis, higher As, Cr and W concentrations were associated with increasing ACR annual change. Higher Zn, As and Cr concentrations were associated with decreasing eGFR annual change. The shape of the longitudinal dose-responses, however, was compatible with a nephrotoxic role for all metals, both in ACR and eGFR models. In joint metal analysis, both higher mixtures of Cu-Zn-As-Ba-Ti-U-V-W and Co-Cd-Cr-Sb-V-W showed associations with increasing ACR and decreasing eGFR annual change. As and Cr were main drivers of the ACR change joint metal association. For the eGFR change joint metal association, while Zn and Cr were main drivers, other metals also contributed substantially. We identified potential interactions for As, Zn and W by other metals with ACR change, but not with eGFR change. Our findings support that Zn, As, Cr and W and suggestively other metals, are nephrotoxic at relatively low exposure levels. Metal exposure reduction and mitigation interventions may improve prevention and decrease the burden of renal disease in the population.

Standardizing health outcomes for chronic kidney disease. Adaptation of the international consortium for health outcomes measurement standard set to the Spanish setting.

BACKGROUND AND OBJECTIVES: We aim to adapt the International Consortium for Health Outcomes Measurements standard set for chronic kidney disease (CKD) patients to the Spanish setting and supplement it with those variables agreed upon through initiatives proposed by the Spanish Society of Nephrologists (S.E.N.). MATERIAL AND METHODS: The working group defined a first standard set of variables based on a literature review. The S.E.N. members then assessed the suitability of each variable for inclusion (Consensus≥75%). A second draft of the standard set was generated and evaluated by the Patient advocacy group Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón (ALCER). Lastly, the working group established the final standard set of variables (Consensus≥75%). RESULTS: The standard set targets patients with very high-risk CKD (G3a/A3 and G3b/A2-G5) in pre-end-stage kidney disease (pre-ESKD), hemodialysis (HD), peritoneal dialysis (PD), kidney transplantation (KT) or conservative care (CC). The essential follow-up variables agreed for all patients (All) were patient survival, hospitalizations, cardiovascular events, smoking status, health-related quality of life, pain, fatigue, physical function, daily activities, depression, renal function and hemoglobin. Additionally, it was agreed to collect PD survival (in PD patients), peritonitis (PD), infection/bacteremia (PD, HD, KT), vascular access type (HD), vascular access survival (HD), acute rejection (KT), post-transplant cancer (KT), albuminuria (KT) and kidney allograft survival (KT). The optional variables agreed were phosphorus (All), potassium (All), diabetes control (All with diabetes), and albuminuria (pre-ESKD). CONCLUSIONS: This standard set may constitute a highly efficient tool allowing the evaluation of patient outcomes and helping to define strategies to enhance CKD patients' quality of care in the Spanish healthcare system.

Nontraditional Risk Factors for Progression Through Chronic Kidney Disease Risk Categories: The Coronary Artery Risk Development in Young Adults Study.

BACKGROUND: There may be nontraditional pathways of chronic kidney disease (CKD) progression that are complementary to classical pathways. Therefore, we aimed to examine nontraditional risk factors for incident CKD and its progression. METHODS: We used the generally healthy population (n = 4382) starting at age 27-41 years in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, which is an observational longitudinal study. Nontraditional risk factors included forced vital capacity, inflammation, serum urate, and serum carotenoids. CKD risk category was classified using the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) measured in 1995-1996 and repeated every 5 years for 20 years: No CKD, low risk, moderate risk, high risk, and very high risk. RESULTS: At baseline, 84.8% had no CKD (eGFR ≥60 mL/min/1.73 m2 and UACR <10 mg/g), 10.3% were in the low risk (eGFR ≥60 and UACR 10-29), and 4.9% had CKD (eGFR <60 and/or UACR ≥ 30). Nontraditional risk factors were significantly associated with the progression of CKD to higher categories. Hazard ratios per standard deviation of the predictor for incident CKD and its progression from the No CKD and low and moderate risk into CKD were inverse for forced vital capacity and serum carotenoids and positive for serum urate, GlycA, and C-reactive protein, the first 3 even after adjustment for conventional risk factors. CONCLUSION: Several nontraditional markers were significantly associated with an increased risk of progression to higher CKD categories in generally healthy young to middle-aged adults.

Modulation effects of Etlingera elatior ethanol extract as anti-inflammatory on chronic kidney disease in mice with hypertension and diabetes.

The incidence of diabetes increased significantly around the world in accordance with lifestyle and change in eating behaviour. Streptozotocin-Nicotinamide (STZ-NA) is capable of inducing Diabetes Mellitus type 2 in experimental animals for insulin resistance. In this research, we inspect the therapeutic potential of Etlingera elatior ethanol extract (EEEE) on diabetes associated with diabetic nephropathy and hypertension complications in mice models. Diabetes and hypertension are induced in mice using STZ 45 mg/kgBB and NA 110 mg/kgBB, followed by unilateral ureter ligation (UUO) for 4 weeks after a week of STZ-NA induction. The EEEE solution was given in the last 4 weeks with doses of 200, 400, 600, and 800 mg/kgBB. The results of this study prove the effect of vanillic acid on improving systolic blood pressure, plasma creatinine, plasma glucose, albuminuria and reducing the inflammatory marker high sensitivity C-reactive protein (hs-CRP). Histopathology of kidney is under investigation for being part of diabetes hypertension pathology. Treatment using EEEE 600 and 800 mg/kgBB for 4 weeks in experimental mice results in the decrease of plasma glucose, systolic blood pressure, plasma creatinine, albuminuria, and hs-CRP, including the restoration of kidney histology significantly compared to 200 and 400 mg/kgBB doses. This result concludes that EEEE offers modulation effects on diabetes hypertension control by reducing blood glucose rate, blood pressure rate, kidney defect, and inflammation markers.

Traditional Chinese medicine body constitution predicts new-onset diabetic albuminuria in patients with type 2 diabetes: Taichung diabetic body constitution prospective cohort study.

This prospective cohort study explored whether body constitution (BC) independently predicts new-onset albuminuria in persons with type 2 diabetes mellitus (T2DM) enrolled in the diabetes care management program (DCMP) of a medical center, providing evidence of integrating traditional Chinese medicine into DCMP for improving care quality. Persons with T2DM (n = 426) originally without albuminuria enrolled in DCMP were recruited in 2010 and were then followed up to 2015 for detecting new-onset albuminuria. The participants received urinalysis and blood test annually. Albuminuria was determined by an elevated urinary albumin/creatinine ratio (≥ 30 µg/mg), and poor glucose control was defined as Glycosylated hemoglobin above or equal to 7%. BC type (Yin deficiency, Yang deficiency, and phlegm stasis) was assessed using a well-validated body constitution questionnaire at baseline. Risk factors for albuminuria (sociodemographic factors, diabetes history, lifestyle behaviors, lipid profile, blood pressure, and kidney function) were also recorded. Hazard ratios (HR) of albuminuria for BC were estimated using multivariate Cox proportional hazards model. During the 4-year follow-up period, albuminuria occurred in 30.5% of participants (n = 130). The HR indicated that Yin deficiency was significantly associated with an increased risk of new-onset albuminuria in persons with T2DM and good glucose control after adjustment for other risk factors (HR = 2.09; 95% confidence interval = 1.05-4.17, P = .04), but not in those with poor glucose control. In persons with T2DM and poor glucose control, phlegm stasis was also significantly associated with a higher risk of albuminuria (2.26; 1.03-4.94, P = .04) after multivariate adjustment, but not in those with good glucose control. In addition to already-known risk factors, BC is an independent and significant factor associated with new-onset albuminuria in persons with T2DM. Our results imply Yin deficiency and phlegm stasis interacting with glucose control status may affect new-onset albuminuria in persons with T2DM.

Effect of the administration of different forms of vitamin D on central blood pressure and aortic stiffness, and its implication in the reduction of albuminuria in chronic kidney disease. / Efecto de la administración de diferentes formas de vitamina D en la presión arterial y rigidez aórticas, y su implicación en la reducción de la albuminuria en la enfermedad renal crónica.

BACKGROUND AND OBJECTIVES: Vitamin D(vitD) participates in phospho-calcium metabolism and exerts multiple pleiotropic effects. There is tissue 1-α (OH)ase that converts 25-OH cholecalciferol (25 (OH) D) in calcitriol that exerts autocrine and paracrine effects. 25 (OH)D deficiency could limit these tissue effects of vitD. The administration of nutritional vitD and the activator of the vitD receptor, paricalcitol, may promote beneficial effects on vascular and renal function. The objective of this work was to study in subjects with chronic kidney disease (CKD) the effect that the administration of different forms of vitD has on arterial function and albuminuria, and the possible relationship between the modifications of these variables. PATIENTS AND METHODS: We studied in 97 patients with CKD stages 3-4 the effect of the administration of cholecalciferol (group 2; n: 35) and paricalcitol (n: 31; group 3) on parameters derived from brachial blood pressure, aortic blood pressure and on aortic stiffness studied using carotid-femoral pulse velocity (Vpc-f), and on albuminuria. A group of patients with stages 3-4 CKD who did not receive vitD therapy served as a control group (n: 31; group 1). All parameters were studied at baseline and after the follow-up period which was 7 ± 2 months. RESULTS: In the baseline phase, no differences were observed between the groups in brachial systolic blood pressure (bSBP), central systolic blood pressure (SBP), brachial pulse pressure (bPP), and central pulse pressure (pCP) or in aortic stiffness that was increased in all groups with a baseline Vpc-f value of 10.5 (9.2-12.1) m/sec. The baseline albuminuria value in the grouped patients was 229 (43-876) mg / g (median (interquartile range)), with no differences between the groups. Serum calcium and phosphorus increased significantly in those treated with cholecal-ciferol (native vitD) and paricalcitol (active vitD). Parathormone (PTH) values decreased in those treated with paricalcitol.bPP and cPP decreased in all groups treated with native and active vitD. No significant changes in bPP and cPP were observed in the control group. Vpc-f did not change significantly in any of the groups, although the variation was quantitatively greater in group 3 (11.2±2 vs. 10.7±1.6 (P=.06)). No differences were observed in the changes in Vpc-f between the groups when adjusted to the baseline values of estimated glomerular filtration rate (eGFR), albuminuria, PTH, vitD, brachial and central blood pressure parameters, and their changes with treatment.Those who received treatment with native and active vitD presented a significant decrease in albuminuria of 17% (group 2) and 21% (group 3) compared to a 16% increase in the untreated group (group 1) (P=.01). A decrease in albuminuria ≥30% was observed more frequently in the groups treated with some form of vitD (group 2: 23%; group 3: 45%) than in the control group (13%) (P=.03). The decrease in albuminuria observed in the groups treated with any of the forms of vitD did not vary when the baseline values of the biochemical parameters of phosphorus-calcium metabolism, those of arterial function (PPb, PPc, Vpc-f) or its modifications were introduced as covariates. There was no significant correlation between changes in Vpc-f and albuminuria. In logistic regression, changes in arterial function parameters were also not explanatory for the ≥30% decrease in albuminuria. CONCLUSIONS: In patients with CKD stages 3-4, treated with RAS blockers and with residual albuminuria, the administration of or paricalcitol reduces brachial and aortic pulse pressures, and albuminuria. The decrease in albuminuria does not seem to be mediated, at least not decisively, by changes in central hemodynamics or aortic stiffness.

Phosphate restriction using a processed clay mineral reduces vascular pathologies and microalbuminuria in rats with chronic renal failure.

BACKGROUND: The progression of chronic kidney disease (CKD) is associated with an increasing risk of cardiovascular morbidity and mortality due to elevated serum phosphate levels. Besides low phosphate diets and hemodialysis, oral phosphate binders are prescribed to treat hyperphosphatemia in CKD patients. This study reports on a processed clay mineral as a novel and efficient phosphate sorbent with comparable efficacy of a clinically approved phosphate binder. METHODS: 5/6 nephrectomized rats, which develop chronic renal failure (CRF), received a high phosphate and calcium diet supplemented with either a processed Montmorillonite-Illite clay mineral (pClM) or lanthanum carbonate (LaC) for 12 weeks. Levels of plasma uremic toxins, glomerular filtration rates and microalbuminuria were determined and the histomorphology of blood vessels and smooth muscle cells was analyzed. RESULTS: 5/6 nephrectomy induced an increase in plasma uremic toxins levels and progressive proteinuria. Treatment of CRF rats with pClM decreased observed vascular pathologies such as vascular fibrosis, especially in coronary vessels. The transition of vascular smooth muscle cells from a contractile to a secretory phenotype was delayed. Moreover, pClM administration resulted in decreased blood creatinine and urea levels, and increased glomerular filtration rates, reduced microalbuminuria and eventually the mortality rate in CRF rats. CONCLUSION: Our study reveals pClM as a potent phosphate binding agent with beneficial impacts on pathophysiological processes in an animal model of CKD. pClM effectively attenuates the progression of vascular damage and loss of renal function which are the most severe consequences of chronic renal failure.

Is screening for chronic kidney disease in patients with diabetes mellitus being properly conducted in primary care?

INTRODUCTION: Screening patients with diabetes mellitus (DM) for chronic kidney disease (CKD) enables early diagnosis and helps to establish adequate treatment and avoid possible damages to health associated with disease progression. This study aimed to verify whether screening for CKD has been properly conducted in populations with diabetes mellitus seen at primary care clinics. METHODS: This descriptive study included 265 individuals with DM seen at Basic Healthcare Clinics in Divinópolis, MG, Brazil. Clinical and laboratory data were collected from the Integrated Health System. Frequency of testing and kidney function evaluations performed within the last 12 months were calculated along with the proportion of patients with increased urinary albumin excretion (UAE) and decreased glomerular filtration rate (GFR) to determine the proportion of patient with kidney involvement. RESULTS: We found that 41.2% of the patients had kidney involvement and that 61.2% of the individuals with kidney involvement were on nephroprotective medication. Of the 21.9% tested for isolated albuminuria, 46.5% had increased UAE. The albumin-to-creatinine ratio (ACR) was measured in 12.1% of the patients, with 43.8% having an increased ACR. We found that 89.0% of the patients had their serum creatinine levels measured, and that 33.1% had a decreased GFR. CONCLUSION: CKD screening was more frequently performed via the GFR than UAE, a parameter analyzed only in a small proportion of patients. Therefore, CKD screening for patients with diabetes is not being performed properly in primary care.