Showing papers in "Nephrology in 2019"

Effects of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on fluid distribution: A comparison study with furosemide and tolvaptan.

Abstract: AIM Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an antihyperglycemic drug with diuretic properties. We recently reported that an SGLT2 inhibitor ameliorated extracellular fluid expansion with a transient increase in urinary Na+ excretion. However, the effects of SGLT2 inhibitors on fluid distribution in comparison to conventional diuretics remain unclear. METHODS Forty chronic kidney disease patients with fluid retention (average estimated glomerular filtration rate 29.2 ± 3.2 mL/min per 1.73 m2 ) were divided into the SGLT2 inhibitor dapagliflozin (DAPA), loop diuretic furosemide (FR) and vasopressin V2 receptor antagonist tolvaptan (TLV). The body fluid volume was measured on days 0 and 7 using a bioimpedance analysis device. RESULTS In all three groups, body weight was significantly and similarly decreased, and urine volume numerically increased for 7 days. Bioimpedance analysis showed that the changes in intracellular water were similar, but that there were significant changes in the extracellular water (ECW) (DAPA -8.4 ± 1.7, FR -12.5 ± 1.3, TLV -7.4 ± 1.5%, P = 0.048). As a result, the change in the ratio of ECW to total body water in the DAPA group was significantly smaller than that in the FR group, but numerically larger than that in the TLV group (DAPA -1.5 ± 0.5, FR -3.6 ± 0.5, TLV -0.5 ± 0.4%, P < 0.001). CONCLUSION Sodium-glucose cotransporter 2 inhibitor DAPA predominantly decreased the ECW with a mild increase in urine volume, but the change in the ECW/total body water was smaller than that in patients treated with FR, and larger than that in patients treated with TLV, suggesting that the effects of SGLT2 inhibitors on fluid distribution may differ from those of conventional diuretics.

Periodontal and chronic kidney disease association: A systematic review and meta-analysis.

Abstract: AIM: Chronic kidney disease (CKD) and kidney failure is increasing globally and evidence from observational studies suggest periodontal disease may contribute to kidney functional decline. METHODS: Electronic searches of the PubMed, EMBASE, Web of Science, Scopus and Cochrane Library databases were conducted for the purposes of conducting a systematic review. Hand searching of reference lists was also performed. Meta-analysis of observational studies involving periodontal disease and chronic kidney disease in adults was performed. RESULTS: A total of 17 studies was selected from an initial 4055 abstracts. Pooled estimates indicated the odds of having CKD were 60% higher among patients with periodontitis: pooled OR 1.60 (95% CI 1.44-1.79, I2 35.2%, P = 0.11) compared to those without. Conversely, a similar magnitude but non-significant higher odds of having periodontal disease was found among people with CKD 1.69 (95% CI: 0.84, 3.40, I2 = 89.8%, P < 0.00) versus non-CKD. Meta-regression revealed study quality based on the Newcastle-Ottawa Scale and statistical adjustment for potential confounders explained almost 35% of the heterogeneity in the studies investigating the association between CKD and periodontitis. CONCLUSIONS: Moderate evidence for a positive association between periodontitis and CKD exists. Evidence for the opposite direction is extremely weak based on significant heterogeneity between studies.

LncRNA HOTAIR promotes renal interstitial fibrosis by regulating Notch1 pathway via the modulation of miR‐124

Abstract: AIM To understand the mechanism of long non-coding RNA (LncRNA) HOTAIR on renal interstitial fibrosis (RIF) by regulating Notch1 pathway via the modulation of miR-124. METHODS Unilateral ureteral occlusion (UUO) was used to construct the RIF rat model. HK-2 cells induced by TGF-β1 were used for the in vitro experiment, which were divided into five groups: Vehicle, TGF-β1, si-HOTAIR+TGF-β1, miR-124 inhibitor+TGF-β1, and si-HOTAIR+miR-124 inhibitor+TGF-β1 groups. Quantitative real-time PCR (qRT-PCR) and Western blot were performed to detect the expression of HOTAIR, miR-124, Notch1- and epithelial-to-mesenchymal transition (EMT)-related proteins. RESULTS Significant elevated HOTAIR and reduced miR-124 were presented in UUO rats and TGF-β1-induced HK-2 cells in a time-dependent manner, with the increased Jagged1 (JAG1), Notch1, NICD, α-SMA and FN, as well as the decreased E-cadherin (all P < 0.05). Compared with the TGF-β1 group, cells in the si-HOTAIR+TGF-β1 group were remarkably declined in cell proliferation and the protein expressions of JAG1, Notch1, NICD, α-SMA, and FN, but dramatically higher in E-cadherin expression (all P < 0.05). However, in comparison with the si-HOTAIR+TGF-β1 group, cells in the si-HOTAIR+miR-124 inhibitor+TGF-β1 group were apparently improved in proliferation and the protein expression of JAG1, Notch1, NICD, α-SMA, and FN, but substantially reduced in the level of E-cadherin protein (all P < 0.05). CONCLUSION Silencing lncRNA HOTAIR can up-regulate miR-124 to block Notch1 pathway, and thereby alleviating EMT and RIF, indicating HOTAIR as a potential target for RIF treatment.

Spectrum of chronic kidney disease in China: A national study based on hospitalized patients from 2010 to 2015

Abstract: Aim To investigate the spectrum of chronic kidney disease (CKD) in China. Methods We used a large national in-patient database covering 878 class three hospitals and involving 64.7 million adult patients in China from 2010 to 2015. The class 3 hospital in China is ranked as the top tier of medical system in China with at least 500 beds and the accreditation from health authorities. The specific causes of CKD were extracted from the International Classification of Diseases-10 codes of discharge diagnoses. Results A total of 4.5% of hospitalized patients (1.8 million) were identified as CKD, with an increased percentage from 2010 (3.7%) to 2015 (4.7%). Increasing trends of diabetic kidney disease and hypertensive nephropathy were observed from 2010 to 2015 (19.5% vs 24.3% and 11.5% vs 15.9%, respectively), especially for urban residents from north China. The proportion of obstructive nephropathy also increased gradually (10.3% in 2010 vs 15.6% in 2015) and constituted another important cause of CKD for patients, especially for those from south China and rural residents. Conclusion The spectrum of CKD is changing in China, with variations over time and geographic regions, which has implication regarding developing the prevention strategy of CKD.

Is immunoglobulin A nephropathy different in different ethnic populations

Abstract: Immunoglobulin A nephropathy (IgAN) is one of the commonest global patterns of primary glomerulonephritis and remains a leading cause of chronic kidney disease and end-stage renal disease. The sole diagnostic criterion of IgAN remains the presence of dominant mesangial immunoglobulin A deposits on kidney biopsy. Beyond this defining feature, there is significant heterogeneity in the epidemiology, clinical presentation, renal progression and long-term outcomes of IgAN in different ethnic populations. Mirroring this heterogeneity in clinical phenotypes, there is also marked ethnic variation in the extent of histopathological lesions observed on kidney biopsy, which may partly explain the well-documented differences in response to immunomodulatory agents reported in different regions of the world. In parallel, disparities have been identified in genetic association studies and key pathogenic pathways in different ethnic populations. Understanding the basis for these differences in IgAN has important implications for both clinical care and future research. In this review, we will examine the impact of ethnicity on the epidemiology, clinical presentation and outcomes, pathogenesis and genetic associations in IgAN.

Biomarkers for acute kidney injury in decompensated cirrhosis: A prospective study.

Abstract: Aim Acute kidney injury (AKI) is a frequent complication in cirrhotic patients. As serum creatinine is a poor marker of renal function in this population, we aimed to study the utility of several biomarkers in this context. Methods A prospective study was conducted in hospitalized patients with decompensated cirrhosis. Serum creatinine (SCr), Cystatin C (CystC), NGAL and urinary NGAL, KIM-1, protein, albumin and sodium were measured on three separate occasions. Renal resistive index (RRI) was obtained. We analyzed the value of these biomarkers to determine the presence of AKI, its aetiology [prerenal, acute tubular necrosis (ATN), or hepatorenal (HRS)], its severity and a composite clinical outcome at 30 days (death, dialysis and intensive care admission). Results We included 105 patients, of which 55 had AKI. SCr, CystC, NGAL (plasma and urinary), urinary sodium and RRI at inclusion were independently associated with the presence of AKI. SCr, CystC and plasma NGAL were able to predict the subsequent development of AKI. Pre-renal state showed lower levels of SCr, NGAL (plasma and urinary) and RRI. ATN patients had high levels of NGAL (plasma and urinary) as well as urinary protein and sodium. HRS patients presented an intermediate pattern. All biomarkers paralleled the severity of AKI. SCr, CystC and plasma NGAL predicted the development of the composite clinical outcome with the same performance as the MELD score. Conclusions In patients with decompensated cirrhosis, early measurement of renal biomarkers provides valuable information on AKI aetiology. It could also improve AKI diagnosis and prognosis.

Cost-utility analysis of the National Health Screening Program for chronic kidney disease in Korea.

Abstract: Aim Although a National Health Screening Program (NHSP) for chronic kidney disease (CKD) has been implemented in Korea since 2002, its cost-effectiveness has never been determined. This study aimed to estimate the cost-utility of NHSP for CKD in Korea. Methods A Markov decision analytic model was constructed to compare CKD screening strategies of the NHSP with no screening. We developed a model that simulated disease progression in a cohort aged 20-120 years or death from the societal perspective. Results Biannual screening starting at age 40 for CKD by proteinuria (dipstick) and estimated glomerular filtration ratio had an ICUR of $66 874/QALY relative to no screening. The targeted screening strategy had an ICUR of $37 812/QALY and $40 787/QALY for persons with diabetes and hypertension, respectively. ICURs improved with lower cost strategies. The most influential parameter that might make screening more cost-effective was the effectiveness of treatment on CKD to decrease disease progression and mortality. Conclusions The Korean NHSP for CKD is more cost-effective for patients with diabetes or hypertension than the general population, consistent with prior studies. Although it is too early to conclude the cost-effectiveness of the Korean NHSP for CKD, this study provides evidence that is useful in evaluating the cost-effectiveness of CKD interventions.

Systemic immune-inflammation index could estimate the cross-sectional high activity and the poor outcomes in immunosuppressive drug-naïve patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Abstract: OBJECTIVES We investigated whether systemic immune-inflammation index (SII) at diagnosis can estimate the cross-sectional high activity and predict the poor outcomes in immunosuppressive drug-naive patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) METHODS We retrospectively reviewed the medical records of 163 patients with AAV and obtained clinical and laboratory data We calculated Birmingham vasculitis activity score (BVAS) as well as five-factor score (FFS) (2009) at diagnosis SII at diagnosis was calculated by the equation of (SII at diagnosis = platelet count × neutrophil count/lymphocyte count at diagnosis) Severe AAV was defined as BVAS at diagnosis ≥16 The odds ratio was assessed using the multivariable logistic regression analysis and cumulative survival rates were compared by the Kaplan-Meier survival analysis RESULTS The median age at diagnosis was 580 years old and 51 patients were men The median BVAS was 120 Fifty-seven patients had severe AAV The median SII at diagnosis was 13496 In the multivariable analysis, only SII exhibited a significant odds ratio for the cross-sectional severe AAV (P = 0043) We obtained the cut-off of SII at diagnosis for severe AAV as 157356 Patients with SII at diagnosis ≥157356 exhibited a significantly high relative risk of the cross-sectional severe AAV compared to those without (relative risk 4625) Furthermore, patients with SII at diagnosis ≥157356 exhibited significantly the lower cumulative relapse free and renal survivals than those without CONCLUSION Systemic immune-inflammation index at diagnosis could estimate the cross-section severe AAV and predict the poor outcomes in AAV patients

Allocation of deceased donor kidneys: A review of international practices.

Abstract: The demand for kidney transplantation continues to exceed the availability of deceased donor kidneys. Balancing the overarching principles of the optimal use of (utility) and equal access to (equity) this scarce resource requires a sophisticated allocation system. This review will examine how various factors are addressed in allocation systems around the world to strike a balance between utility and equity.

Mild cognitive impairment in older adults with pre-dialysis patients with chronic kidney disease: Prevalence and association with physical function.

Abstract: Aim Chronic kidney disease (CKD) is a risk factor for declining cognitive and physical function. However, the prevalence of mild cognitive impairment (MCI) and its relationship with physical function is not clear. Therefore, our aim was to evaluate the prevalence of MCI and the relationship between MCI and physical function among older adults with pre-dialysis CKD. Methods We conducted a cross-sectional study of 120 patients, aged ≥ 65 years (mean age, 77.3 years), with pre-dialysis CKD but without probable dementia (Mini Mental State Examination < 24). MCI was evaluated using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). For analysis, patients were classified into two cognitive function groups: normal (MoCA-J ≥26) and MCI (MoCA-J <26). Physical, clinical, and biochemical parameters were compared between the groups. Logistic and linear regression analyses were used to evaluate the specific association between cognitive and physical function. Results Seventy-five patients (62.5%) patients belonged to the MCI group. Significant differences between the two groups were identified for gait speed, balance, age, and haemoglobin concentration. After adjustment for covariates, only gait speed was significantly associated with MCI (odds ratio, 0.06; 95% confidence interval, 0.009-0,411). Conclusion The prevalence of MCI among older adults with pre-dialysis CKD was as high as 62.5%. The association between MCI and reduced gait speed supports the possible interaction between physical and cognitive functions and the need for early screening.

Quantifying cognitive dysfunction across the spectrum of end-stage kidney disease: A systematic review and meta-analysis.

Abstract: Cognitive dysfunction is reportedly highly prevalent among chronic kidney disease (CKD) patients. A variety of screening tools and neuropsychiatric batteries are used to quantify the magnitude and nature of this dysfunction. Our objective is to summarize the neurocognitive testing used, and determine what degree cognitive dysfunction is reported in CKD patients. All study designs published in English that contained participants who were either pre-dialysis patients, haemodialysis (HD) or peritoneal dialysis (PD) patients or renal transplant recipients were considered. Reported comparative non-CKD control data was also collected. All study designs were included. The search period encompassed articles from 1980 to May 2018. This review is registered with PROSPERO (CRD42018096568). Of the 1711 articles screened, 148 articles were relevant and used in the meta-analysis. Commonly used assessments were The Mini-Mental State Examination (MMSE), The Modified Mini-Mental State Examination, the Trails Making Tests (TMT) forms A and B and components of the Wechsler Adult Intelligence Scale: Digit Span and Digit Symbol. Means for all assessments were adjusted using a random effects model to account for the differences in variance. Adjusted mean MMSE scores were significantly lower for both pre-dialysis (26.08, n = 17 073) and HD (26.31, n = 3314) patients when compared to non-CKD controls (28.21, n = 5226). PD (58.01 s, n = 859) and HD (56.04 s, n = 2344) patients also took significantly longer to complete the Trails Making Task A than non-CKD controls (37.62 s, n = 4809). Patients with CKD, especially pre-dialysis and those requiring dialysis, are likely to exhibit impairments in cognition that can be identified with specific screening neuropsychological assessments.

Investigating barriers to immunosuppressant medication adherence in renal transplant patients.

Abstract: Immunosuppressant medication non-adherence can result in allograft rejection and loss. The aim of this study was to investigate the prevalence of non-adherence and barriers to adherence with immunosuppressant medications, in an adult renal transplant cohort. Kidney transplant recipients completed a self-report survey consisting of five validated questionnaires (Basel Assessment of Adherence Immunosuppression Scale (BAASIS), Beliefs about Medicines Questionnaire, Immunosuppressant Therapy Barrier Scale, Brief-Illness Perception Questionnaire, and Multidimensional Health Locus of Control Scale), and provided sociodemographic information. Adherence was categorised according to BAASIS, with adherence barriers compared between the groups. 161 patients in total completed the survey. Eighty-six participants (55%) were categorised as non-adherent, with 45% delaying doses, and 25% skipping doses. Non-adherent patients were more likely to forget doses (p=0.005), and more likely to skip doses when their daily routine changed (p Over half the patients self-reported non-adherence. The main modifiable barriers leading to non-adherence were forgetfulness and skipped doses. Personalised interventions focused on habit forming may improve adherence in this population.

Effects of probiotic supplements on the progression of chronic kidney disease: A meta-analysis.

Abstract: Background Chronic kidney disease (CKD) is a worldwide public health problem. Although accumulated data suggested that probiotic supplements played roles in CKD, the results remained controversial. Here, we performed a meta-analysis to assess the effects of probiotic supplements on the CKD progression. Methods A systematic search was conducted through the PubMed, Embase and Cochrane databases until September 2018. Randomized controlled trials with control receiving placebo, evaluating the effects of probiotic supplements on CKD were included. Results A total of 10 randomized controlled trials in 8 countries were selected. In the meta-analysis, urea level was significantly reduced in probiotics-administrated non-dialysis patients (mean differences (MD) = -30.01; 95% confidence interval (CI) = [-56.78, -3.25]; P = 0.03) while no significant change was found in the dialysis patients receiving probiotics (MD = 0.1; 95% CI = [-9.28, 9.48]; P = 0.98). Probiotic supplements also exhibited no effect on uric acid (MD = -0.43; 95% CI = [-1.19, 0.33]; P = 0.27), C-reactive protein (MD = -0.48; 95% CI = [-1.29, 0.33]; P = 0.24), creatinine (MD = -0.18; 95% CI = [-0.82, 0.47]; P = 0.59), and estimated glomerular filtration rate (MD = 2.10; 95% CI = [-1.31, 5.52]; P = 0.23) of CKD patients. Conclusion Our results highlighted that probiotic supplements exerted a statistically significant effect on urea levels in non-dialysis CKD population, while no evidence suggested that probiotics possessed meaningful impacts on the reduction of uric acid, C-reactive protein, creatinine and estimated glomerular filtration rate preservation of CKD population.

Validation of acute kidney injury according to the modified KDIGO criteria in infants after cardiac surgery for congenital heart disease.

Abstract: AIM We aimed to validate the incidence of, risk factors for, and postoperative outcomes of acute kidney injury (AKI) according to the modified Kidney Disease Improving Global Outcomes (m-KDIGO) criteria and compare this criteria with both the paediatric Risk, Injury, Failure, Loss, End-stage disease (pRIFLE) and Acute Kidney Injury Network (AKIN) criteria in infants after cardiac surgery. METHODS We retrospectively enrolled 145 consecutive infants who underwent open-heart surgery at Kagoshima University Hospital. RESULTS Acute kidney injury was present in 55 (37.9%), 111 (75.9%), and 95 (65.5%) patients according to the m-KDIGO, pRIFLE, and AKIN criteria, respectively. Among these, 71.9% of patients pRIFLE Risk patients and 60.5% of AKIN 1 patients were categorized in the 'no-AKI' group according to the m-KDIGO criteria. Low body weight (m-KDIGO odds ratio [OR], 0.73; P = 0.015; pRIFLE OR, 0.66; P = 0.001; AKIN OR 0.69, P = 0.002) and prolonged cross-clamp time (m-KDIGO OR, 1.02;

5-Aminolevulinic acid exerts renoprotective effect via Nrf2 activation in murine rhabdomyolysis-induced acute kidney injury.

Abstract: Aim Acute kidney injury (AKI) is associated with chronic kidney disease, as well as high mortality, but effective treatments for AKI are still lacking. A recent study reported the prevention of renal injury, such as ischemia-reperfusion injury, by 5-aminolevulinic acid (ALA), which induces an antioxidant effect. The current study aimed to investigate the effect of ALA in a rhabdomyolysis-induced mouse model of AKI created by intramuscular injection of 50% glycerol. Methods Rhabdomyolysis-induced AKI was induced by an intramuscular injection of glycerol (5 mL/kg body weight) into mice. Administration of ALA (30 mg/kg, by gavage) was started from 48 h before or 24 h after glycerol injection. The mice were sacrificed at 72 h after glycerol injection. The roles of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), which is one of the Nrf2-related antioxidants, were further investigated through in vivo and in vitro methods. Results 5-aminolevulinic acid markedly reduced renal dysfunction and tubular damage in mice with rhabdomyolysis-induced AKI. ALA administration decreased oxidative stress, macrophage infiltration, and inflammatory cytokines and apoptosis. The expression of Nrf2 was upregulated by ALA administration. However, administration of Zinc protoporphyrin-9 (ZnPPIX) to inhibit HO-1 activity did not abolish these improvements by ALA. The expression of Nrf2-associated antioxidant factors other than HO-1 was also increased. Conclusion These findings indicate that ALA exerts its antioxidant activity via Nrf2-associated antioxidant factors to provide a renoprotective effect against rhabdomyolysis-induced AKI.

Effect of long non-coding RNA growth arrest-specific 5 on apoptosis in renal ischaemia/reperfusion injury.

Abstract: Aim Long non-coding RNA (lncRNAs) have been shown to play a critical role in a variety of pathophysiological processes, such as cell proliferation, apoptosis and migration. However, there were few studies addressing the function of lncRNAs in renal ischaemia/reperfusion (I/R) injury. Apoptosis is an important pathogenesis during I/R injury. Here, we identified the effect of hypoxia-responsive lncRNA growth arrest-specific 5 (GAS5) on apoptosis in renal I/R injury. Methods Ischaemia/reperfusion injury in mice or hypoxia/re-oxygenation (H/R) in human proximal renal tubular epithelial cells (HK-2) was practiced to induce apoptosis. The kidneys and blood were collected at 24 h after reperfusion. The GAS5 messenger RNA (mRNA) expression and apoptosis-related gene mRNA and protein levels, including p53, cellular inhibitor of apoptosis protein 2 (cIAP2) and thrombospondin-1 (TSP-1), were analysed. GAS5 small-interfering RNA was transfected with H/R induced cells. Over-expression of GAS5 was performed by plasmid transfection. Results Apoptotic cells significantly increased in I/R-injured kidneys. GAS5 could be up-regulated in kidneys at 24 h after reperfusion and 3 h after re-oxygenation, combined with increased expression of its downstream apoptosis-related proteins p53 and cIAP2. GAS5 small-interfering RNA treatment down-regulated the mRNA and protein levels of p53 and TSP-1, and attenuated apoptosis induced by H/R in HK-2 cells. Conversely, over-expression of GAS5 up-regulated the mRNA and protein levels of p53 and TSP-1, and promoted apoptosis in HK-2 cells. Conclusion Long non-coding RNA GAS5 induced by I/R injury could promote apoptosis in kidney. TSP-1 might be one of the downstream effectors of GAS5, which will be explored in the future.

Compensatory renal hypertrophy following nephrectomy: When and how?

Abstract: Following surgical removal of one kidney, the other enlarges and increases its function. The mechanism for the sensing of this change and the growth is incompletely understood but begins within days and compensatory renal hypertrophy (CRH) is the dominant contributor to the growth. In many individuals undergoing nephrectomy for cancer or kidney donation this produces a substantial and helpful increase in renal function. Two main mechanisms have been proposed, one in which increased activity by the remaining kidney leads to hypertrophy, the second in which there is release of a kidney specific factor in response to a unilateral nephrectomy that initiates CRH. Whilst multiple growth factors and pathways such as the mTORC pathway have been implicated in experimental studies, their roles and the precise mechanism of CRH are not defined. Unrestrained hypoxia inducible factor activation in renal cancer promotes growth and may play an important role in driving CRH.

Chronic kidney disease progression in kidney transplant recipients: A focus on traditional risk factors.

Abstract: Kidney transplant recipients are a subset of patients with chronic kidney disease (CKD) that remain at high risk for progression to dialysis and mortality. Recent advances in immunosuppression have only partially improved long-term graft and patient survival. Discovery of new immunosuppressive regimens is a slow and resource-intensive process. Hence, recognition and management of modifiable allogeneic and non-allogeneic risk factors for progression to CKD among kidney transplant recipients is of major interest for improving long-term outcomes. Graft survival is mainly determined by the quality of the allograft and by the patient's alloimmune response, which is influenced by human leukocyte antigen matching and the presence of donor-specific antibodies. Alloimmune responses manifest as acute and chronic forms of cell- and antibody-mediated rejection, which can be worsened by patient non-adherence or under-immunosuppression. However, donor and patient ages, glomerular disease recurrence, time on dialysis, pre-existing cardiovascular burden, medication side-effects and traditional risk factors, such as hypertension, proteinuria, anaemia, dyslipidaemia, diabetes and bone mineral disorder, which can ultimately lead to severe endothelial derangement, also contribute to graft loss and mortality. These traditional risk factors, common to pre-dialysis patients, often are considered of secondary importance when compared to alloimmunity and immunosuppression concerns. In this review article, we focus on the epidemiological, pathophysiological and therapeutic features of non-allogeneic traditional risk factors for CKD. We also discuss the benefit of adopting a multidisciplinary approach to pursue the same therapeutic targets recommended for pre-dialysis patients.

Big Data in Nephrology: Are We Ready for the Change?

Abstract: Chronic kidney disease (CKD) is a major public health issue worldwide. However, the status of kidney health care needs to be strengthened globally and research evidence in nephrology is relatively limited. The unmet needs in nephrology leave ample space for imagination regarding leveraging big data and artificial intelligence (AI). Big data has potential to drive medical innovation, reduce medical costs and improve health care quality. Compared with other specialties such as cardiology, the scopes of utilizing big data in nephrology need to be enhanced. We reviewed the studies on the application of big data in nephrology, such as disease surveillance, risk prediction and clinical decision support systems (CDSS), and proposed several potential directions of utilizing big data and AI. The efforts including building a CKD surveillance system and collaborative network, implementing a real-world cohort in a cost-effective manner, strengthening the application and transformation of AI and CDSS, and stimulating the activeness of medical imaging in nephrology, could be considered. In the era of big data, a nephrologist would be stronger and smarter if he or she could get intelligent assistance from knowledge or big data-driven CDSS.

Daclatasvir and reduced-dose sofosbuvir: An effective and pangenotypic treatment for hepatitis C in patients with estimated glomerular filtration rate <30 mL/min.

Abstract: AIM Sofosbuvir is a key agent for HCV treatment. It is not recommended for patients with chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) <30 mL/min. We report real-life experience of treating a cohort of CKD patients with eGFR <30 mL/min using daclatasvir and half-daily dose of sofosbuvir. METHODS Adults patients who (i) had eGFR<30 mL/min and detectable HCV RNA and (ii) were treated with interferon and ribavirin free, DAA based regimens were included. All patients were treated with daily doses of daclatasvir 60 mg and sofosbuvir 200 mg. The planned duration of treatment was 12 weeks, except for 24 weeks in those with either clinical evidence of cirrhosis or on immunosuppressive drugs. The end-points of the study were: (i) 12 weeks of follow-up after treatment completion, (ii) treatment discontinuation, or (iii) death or loss to follow-up. RESULTS Thirty-six (88%) among 41 included patients (median [range] age: 48 [19-75] years; 25 [61%] male; genotype 1/3/4 were 17/ 22/2; cirrhosis 5) completed the treatment, two discontinued and three died during treatment. On an intention-to-treat basis, HCV RNA were undetectable at 4 weeks of treatment, treatment completion and after 12 weeks of follow-up in 40/41 (97.6%), 37/41 (90.2%) and 37/41 (90.2%), respectively. None of the patients had a relapse. CONCLUSIONS Daclatasvir and half-daily dose of sofosbuvir was effective against genotype 1 and 3 HCV infection in patients with eGFR <30 mL/min. This combination could be a pangenotypic treatment option for such patients.

KHA-CARI Guideline recommendations for renal biopsy.

Abstract: Department of Renal and General Medicine, Eastern Health Clinical School, Monash University Melbourne, Melbourne, Victoria, Australia Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia Royal Women's Hospital, Melbourne, Victoria, Australia Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, New South Wales, Australia Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Victoria, Australia Renal Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia Department of Nephrology, Monash Health, Melbourne, Victoria, Australia Counties Manukau Health, Auckland, New Zealand Department of Nephrology, Liverpool Hospital, Liverpool, New South Wales, Australia

Development of a new mortality scoring system for acute kidney injury with continuous renal replacement therapy.

Abstract: Aim On the basis of the worst outcomes of patients undergoing continuous renal replacement therapy (CRRT) in intensive care unit, previously developed mortality prediction model, Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) needs to be modified. Methods A total of 828 patients who underwent CRRT were recruited. Mortality prediction model was developed for the prediction of death within 7 days after starting the CRRT. Based on regression analysis, modified scores were assigned to each variable which were originally used in the APACHE II and SOFA scoring models. Additionally, a new abbreviated Mortality Scoring system for AKI with CRRT (MOSAIC) was developed after stepwise selection analysis. Results We used all the variables included in the APACHE II and SOFA scoring models. The prediction powers indicated by C-statistics were 0.686 and 0.683 for 7-day mortality by the APACHE II and SOFA systems, respectively. After modification of these models, the prediction powers increased up to 0.752 for the APACHE II and 0.724 for the SOFA systems. Using multivariate analysis, seven significant variables were selected in the MOSAIC model wherein its C-statistic value was 0.772. These models also showed good performance with 0.720, 0.734 and 0.773 of C-statistics in the modified APACHE II, modified SOFA and MOSAIC scoring models in the external validation cohort (n = 497). Conclusion The modified APACHE II/SOFA and newly developed MOSAIC models could be more useful tool for predicting mortality for patients receiving CRRT.

Heart rate variability as a predictor of rapid renal function deterioration in chronic kidney disease patients.

Abstract: AIM Autonomic dysfunction contributes to cardiovascular morbidity/mortality and can be evaluated with heart rate variability (HRV). This study is to evaluate the prognostic significance of HRV on renal function in non-dialysis chronic kidney disease (CKD) patients. METHODS We enrolled 326 non-dialysis CKD patients in this prospective observational study. The median follow-up period was 2.02 years. Five-minutes of electrocardiography recordings obtained at enrolment were reprocessed to assess HRV. Five frequency-domain measures and one time-domain measures were obtained. Rapid CKD progression was defined as annual estimated glomerular filtration rate (eGFR) loss over 30% per year or eGFR decline rate over 3 mL/min per 1.73 m2 per year. The prevalence of abnormal HRV, associated factors of HRV and impact of HRV on the risk of CKD progression were analyzed. RESULTS The abnormality of HRV increased along with the severity of CKD. In patients with stage 5 CKD, the proportion of abnormal ln(low frequency power) (LF), ln(high frequency power) (HF), lnLF/HF were 69.5, 52.8 and 50%, respectively. Associated factors of HRV included advanced CKD, diabetes mellitus, serum albumin, severe proteinuria, Beck Anxiety Inventory score, erythropoietin use, renin-angiotensin system inhibitors and heart failure. Multivariate logistic regression model analysis revealed lower lnLF/HF, hypertension and severe proteinuria were the risk factors of rapid CKD progression. CONCLUSION The prevalence of autonomic dysfunction measured by HRV among each stage CKD patients is different. Most patients in advanced CKD stage have reduced values of HRV parameters. The estimation of lnLF/HF also provided prognostic information on CKD progression in addition to classical risk factors.

Comparison between incremental and thrice-weekly haemodialysis: Systematic review and meta-analysis.

Abstract: AIM Incremental haemodialysis (HD) regimen has recently gained attention. However, its efficacy and safety, compared with conventional thrice-weekly HD, are controversial and previous research results are not convincing. We sought to conduct a meta-analysis to evaluate the benefits and limitations of incremental HD regimen in patients with end-stage renal disease. METHODS We searched PubMed, Embase, and the Cochrane Central Register databases for controlled trials published until January 2017. Outcomes of interest included baseline patient characteristics, mortality risk, renal function, urine volume, laboratory values, and hospitalization rate. RESULTS Overall, 16 studies (n = 252 330), including 15 observational studies and 1 cross-sectional study, were included. Incremental HD reduced mortality risk, compared with conventional HD (risk ratio [RR], 0.797; 95% confidence interval [CI], 0.731-0.870; P < 0.001; I2 = 0%). Renal function (standardized mean difference [SMD] = 0.677, 95% CI: 0.035 to 1.318, P = 0.039; I2 = 92.7%) and urine volume (weighted mean difference [WMD] = 333.37, 95% CI: 86.81 to 579.93, P = 0.008; I2 = 92.7%) were also better preserved in patients on incremental HD. Other clinical outcomes, including serum levels of calcium, phosphate, albumin, haemoglobin, and hospitalization rate, were similar between groups. CONCLUSION An incremental therapeutic approach as a beginning haemodialysis regimen is associated with lower mortality and better preservation of greater residual renal function.

Hyperuricemia is associated with acute kidney injury and all-cause mortality in hospitalized patients.

Abstract: AIM Hyperuricemia is a risk factor for high morbidity and mortality in several diseases. However, the relationship between uric acid (UA) and the risk of acute kidney injury (AKI) and mortality remain unresolved in hospitalized patients. METHODS Data from 18 444 hospitalized patients were retrospectively reviewed. The odds ratio (OR) for AKI and the hazard ratio (HR) for all-cause mortality were calculated based on the UA quartiles after adjustment for multiple variables. All analyses were performed after stratification by sex. RESULTS The fourth quartile group (male, UA > 6.7 mg/dL; female, UA > 5.4 mg/dL) showed a higher risk of AKI compared with the first quartile group (male, UA < 4.5 mg/dL; female, UA < 3.6 mg/dL), with the following OR: 3.2 (2.55-4.10) in males (P < 0.001); and 3.1 (2.40-4.19) in females (P < 0.001). There were more patients who did not recover from AKI in the fourth quartile compared with the first quartile, with the following OR: 2.0 (1.32-3.04) in males (P = 0.001) and 2.4 (1.43-3.96) in females (P = 0.001). The fourth quartile group had a higher risk of all-cause mortality compared with the first quartile group, with the following HR: 1.4 (1.20-1.58) in males (P < 0.001) and 1.2 (1.03-1.46) in females (P = 0.019). The in-hospital mortality risk was also higher in the fourth quartile compared with the first quartile, which was significant only in males (OR, 2.1 (1.33-3.31) (P = 0.002)). CONCLUSION Hyperuricemia increases the risks of AKI and all-cause mortality in hospitalized patients.

Deleterious effect of anti-angiotensin II type 1 receptor antibodies detected pretransplant on kidney graft outcomes is both proper and synergistic with donor-specific anti-HLA antibodies.

Abstract: AIM Both donor-specific antibodies (DSA) and anti-angiotensin II type 1 receptor antibodies (AT1R-abs) have been associated with poor graft outcomes after kidney transplantation (KT). We aimed to understand the impact of pretransplant AT1R-abs with or without concomitant DSA on KT outcomes. METHODS Seventy-six patients transplanted in 2009 were studied. DSA (MFI > 1000) and/or AT1R-abs (>10UI) were detected by solid-phase assays in pre-KT sera. Multivariable Cox regression models were used to determine independent predictors of outcomes: acute rejection (AR) and graft failure. RESULTS At transplant, 48 patients were AT1R-abs (-)/DSA (-), 12 AT1R-abs (+)/DSA (-), 9 AT1R-abs (-)/DSA (+) and 7 AT1R-abs (+)/DSA (+). Incidence of acute rejection at 1-year increased from 6% in AT1R-abs (-)/DSA (-), to 35% in AT1R-abs (+)/DSA (-), 47% in AT1R-abs (-)/DSA (+) and 43% in AT1R-abs (+)/DSA (+) (P < 0.001). No difference in DSA strength and C1q-binding ability was observed between AT1R-abs (-) /DSA (+) and AT1R-abs (+)/DSA (+) patients. Graft survival at 6-years was the lowest in AT1R-abs (+)/DSA (+) (57%), followed by AT1R-abs (+)/DSA (-) (67%), and higher in AT1R-abs (-)/DSA (-) (94%) and AT1R-abs (-)/DSA (+) (89%) patients (P = 0.012). AT1R-abs (+)/DSA (-) (HR = 6.41, 95% CI: 1.43-28.68; P = 0.015) and AT1R-abs (+)/DSA (+) (HR = 7.75, 95% CI: 1.56-38.46; P = 0.012) were independent predictors of graft failure. CONCLUSION Acute rejection incidence and graft failure were associated with both DSA and AT1R-abs. These results demonstrate a proper negative effect of AT1R-abs on graft outcomes, besides a synergistic one with DSA. Pretransplant AT1R-abs should be acknowledged to better stratify patients' immunological risk.

Methylglyoxal as a prognostic factor in patients with chronic kidney disease

Abstract: Aim Advanced glycation end products and their precursors cause vascular damage through oxidative stress. We investigated the hypothesis that methylglyoxal (MG), 3-deoxyglucosone (3-DG) and pentosidine influence outcomes of chronic kidney disease (CKD) patients. Methods We conducted a 3 years prospective observational study involving 150 outpatients at CKD stages 3-5. At enrolment, MG, 3-DG and pentosidine plasma concentrations were measured; patients were divided into tertiles according to the concentration of each substance. The primary endpoint was death, a cardiovascular event or end-stage renal disease. Survival analysis was performed using the Cox regression model. Results The patients' mean age was 62 ± 12 years, 97 were men, and 20 had diabetic nephropathy. The mean estimated glomerular filtration rate was 25.0 ± 12.1 mL/min per 1.73 m2 , which negatively correlated with MG but not with 3-DG and pentosidine. Forty-eight patients reached the primary endpoint. Compared with the lowest MG tertile, the hazard ratio for the primary endpoint was 7.57 (95% confidence interval (CI): 1.71-33.54) in the middle tertile and 27.00 (CI: 6.46-112.82) in the highest tertile. When adjusted for characteristics at baseline, the corresponding hazard ratio decreased to 2.09 (CI: 0.37-11.96) and 6.13 (CI: 0.97-38.82), but MG tertile remained an independent risk factor for the primary endpoint. However, 3-DG and pentosidine were not related to the primary outcome. Conclusion Methylglyoxal has a close clinical association with CKD. Higher MG concentrations may contribute renal function deterioration in CKD. In CKD patients, MG concentration might be useful when determining the prognosis.

Association between end-stage diabetic nephropathy and MTHFR (C677T and A1298C) gene polymorphisms.

Abstract: AIM Methylenetetrahydrofolate reductase (MTHFR) is a regulatory enzyme of homocysteine metabolism. The C677T and A1298C polymorphism of the MTHFR gene has been reported to be associated with elevated plasma homocysteine in patients with Diabetic nephropathy. This study aimed to investigate the influence of the C677T and A1298C polymorphisms on the progression chronic kidney disease in diabetic nephropathy of south Indian population. METHODS We genotyped 145 DN cases and 100 controls for the C677T and A1298C polymorphisms using PCR-RFLP based protocols, and all diabetic nephropathy cases divided into two groups based on CKD stages: 60 DN cases were early stage (CKD1 to CKD3) and 85 DN cases were advanced stage (CKD4 and CKD5). Association χ2 and univariate analysis were performed. RESULTS The C677T (OR = 4.2; 95% CI = 2.31-7.64 and P = 0.001) and A1298C (OR = 2.8; 95% CI = 1.05-7.57 and P = 0.033) polymorphism was shown that the significant association between the cases and control. Furthermore, the MTHFR gene polymorphism C677T (OR = 2.48; 95% CI = 1.25-4.9 and P = 0.008) was observed that the significant contribution of the progression of CKD in DN. CONCLUSION These findings suggest that the C677T and A1298C polymorphism of MTHFR gene was associated with diabetic nephropathy in a south Indian population. Furthermore, the present study provides evidence that the C677T polymorphism was associated with CKD progression in DN.

Access to waitlisting for deceased donor kidney transplantation in Australia.

Abstract: Aim A detailed analysis of waitlisting for deceased donor kidney transplantation in Australia has not previously been reported We aimed to determine if patient characteristics associated with waitlisting identify areas of potential inequality in access to transplantation in Australia Methods A competing risk time-to-event model was used to determine predictors of waitlisting for all adult incident renal replacement therapy patients in Australia between 2006 and 2015 Secondary analysis was performed to determine predictors of overall access to transplantation (using a combined outcome of waitlisting and living donor transplantation) Results The cohort consisted of 21 231 patients with a median age of 63 years Overall, 4361 (205%) were waitlisted and 1239 (58%) received a living donor transplant without being previously waitlisted Primary analysis revealed that medical comorbidities, older age, smoking status and body mass index were all significant predictors of waitlisting and that and there was variation in waitlisting practice across states Despite adjustment for the above factors, demographic characteristics, including Indigenous ethnicity (subdistribution hazard ratios (SHR) 046 (95% confidence interval (CI) 038-055)), female gender (SHR 085 (95% CI 080, 091)) and residence in a regional area (SHR 088 (95% CI 081-095)) were also associated with a lower likelihood of waitlisting Secondary analysis showed younger age and higher socio-economic advantage were additional predictors of overall access to transplantation, driven by higher rates of living donor transplantation Conclusion Demographic as well as clinical characteristics are associated with reduced likelihood of waitlisting for kidney transplantation in Australia Further analysis and auditing should be considered to determine if this reflects other unmeasured factors or highlights a need to address inequality

Kinetic estimated glomerular filtration rate as a predictor of successful continuous renal replacement therapy discontinuation.

Abstract: Aim No standardized criteria for continuous renal replacement therapy (CRRT) discontinuation have been established. Kinetic estimated glomerular filtration rate (eGFR) is a newly developed estimation method based on dynamic changes of serum creatinine expected to reflect the true GFR. This study aimed to evaluate the predictive role of kinetic eGFR for CRRT discontinuation. Methods A retrospective single-centre cohort study was conducted. Acute kidney injury (AKI) patients who received CRRT between May 2015 and April 2016 were enrolled. Successful CRRT discontinuation was defined as neither resuming CRRT for the next 48 h nor receiving intermittent haemodialysis 7 days from the CRRT discontinuation. Clinical factors associated with CRRT discontinuation were evaluated by receiver operating characteristic (ROC) curve analysis. Results Of 52 AKI patients treated with CRRT, 38 could discontinue CRRT while 14 could not. Urine volume, regular and kinetic eGFR of days 0 (day of CRRT discontinuation) and 1 were all good predictive parameters (area under the ROC curve (AUC) > 0.7). Kinetic eGFR of day 1 showed the AUC of 0.87 [95% confidence interval 0.73-0.94]). Combining kinetic eGFR of day 1 and urine volume of day 0 gave a high AUC of 0.93 [95% confidence interval 0.82-0.97]. The combination was significantly greater than urine volume of day 0 (P = 0.008). Conclusion Kinetic eGFR combined with urine volume was a better predictor for CRRT discontinuation. Evaluation of kinetic eGFR utility in other clinical settings will be necessary.