Early Chronic Kidney Disease Research Articles

Can the implementation of clinical practice guidelines improve clinical competence of physicians and kidney function of patients with type 2 diabetes mellitus?

There are many clinical practice guidelines (CPGs) in Nephrology; however, there is no evidence that their availability has improved the clinical competence of physicians or the outcome of patients with chronic kidney disease (CKD). This study was aimed to evaluate the effect of implementation of CPGs for early CKD on family physicians (FP) clinical competence and subsequently on kidney function preservation of type 2 diabetes mellitus (DM2) patients at a primary healthcare setting. A prospective educative intervention (40-h) based on CPGs for Prevention, Diagnosis and Treatment of Early CKD was applied to FP; a questionnaire to evaluate clinical competence was applied at the beginning and end of the educative intervention (0 and 2 months), and 12 months afterwards. DM2 patients with CKD were evaluated during 1-year of follow-up with estimated glomerular filtration rate (eGFR) and albuminuria. After educative intervention, there was a significant increase in FP clinical competence compared to baseline; although it was reduced after 1 year, it remained higher compared to baseline. One-hundred thirteen patients with early nephropathy (58 stage 1, 55 stage 2) and 28 with overt nephropathy (23 stage 3, 5 stage 4) were studied. At final evaluation, both groups maintained eGFR [(mean change) early 0.20 ± 19 pNS; overt 0.51 ± 13 mL/min pNS], whereas albuminuria/creatinuria (early -67 ± 155 p < 0.0001; overt -301 ± 596 mg/g p < 0.0001), systolic blood pressure (early -10 ± 18 p < 0.05; overt -8 ± 20 mmHg p < 0.05), and total cholesterol (early -11 ± 31 p < 0.05; overt -17 ± 38 mg/dL p < 0.05) decreased. Diastolic blood pressure, waist circumference and LDL-cholesterol were also controlled in early nephropathy patients. CPGs for Prevention, Diagnosis and Treatment of CKD, by means of an educative intervention increases FP clinical competence and improves renal function in DM2 patients with CKD.

Capability of arterial spin labeling and intravoxel incoherent motion diffusion-weighted imaging to detect early kidney injury in chronic kidney disease.

To prospectively investigate the capability of arterial spin labeling (ASL) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for the identification of early kidney injury in chronic kidney disease (CKD) patients with normal estimated glomerular filtration rate (eGFR). Fifty-four CKD patients confirmed by renal biopsy (normal eGFR group [eGFR ≥ 90 mL/min/1.73 m2]: n = 26; abnormal eGFR group [eGFR < 90 mL/min/1.73 m2]: n = 28) and 20 healthy volunteers (HV) were recruited. All subjects were examined by IVIM-DWI and ASL imaging. Renal blood flow (RBF) derived from ASL, true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) derived from IVIM-DWI were measured from the renal cortex. One-way analysis of variance was used to compare MRI parameters among the three groups. The correlation between eGFR and MRI parameters was evaluated by Spearman correlation analysis. Diagnostic performances of MRI parameters for detecting kidney injury were assessed by receiver operating characteristic (ROC) curves. The renal cortical D, D*, f, and RBF values showed statistically significant differences among the three groups. eGFR was positively correlated with MRI parameters (D: r = 0.299, D*: r = 0.569, f: r = 0.733, RBF: r = 0.586). The areas under the curve (AUCs) for discriminating CKD patients from HV were 0.725, 0.752, 0.947, and 0.884 by D, D*, f, and RBF, respectively. D, D*, f, RBF, and eGFR identified CKD patients with normal eGFR with AUCs of 0.735, 0.612, 0.917, 0.827, and 0.733, respectively, and AUC of f value was significantly larger than that of eGFR. IVIM-DWI and ASL were useful for detecting underlying pathologic injury in early CKD patients with normal eGFR. • The renal cortical f and RBF values in the control group were significantly higher than those in the normal eGFR group. • A negative correlation was observed between the renal cortical D, D*, f, and RBF values and SCr and 24 h-UPRO, while eGFR was significantly positively correlated with renal cortical D, D*, f, and RBF values. • The AUC of renal cortical f values was statistically larger than that of eGFR for the discrimination between the CKD with normal eGFR group and the control group.

Association of vascular endothelial growth factor (VEGF) protein levels and gene polymorphism with the risk of chronic kidney disease

ABSTRACT Vascular endothelial growth factor (VEGF) is a heparin-specific growth factor specific for vascular endothelial cells and induces angiogenesis via binding to vascular endothelial growth factor receptor (VEGFR). Chronic kidney disease (CKD), accompanied by microvascular disease, is recognized as an irreversible reduction of renal function. The effects of VEGF on CKD risk were evaluated in this study. 121 CKD patients and 50 healthy volunteers were evaluated in the current study. Data mining using the China Biological Medicine (CBM) and NCBI/PubMed databases, was performed and applicable investigations were pursued. Pooled mean differences (MD) and pooled odds ratios (OR), with corresponding confidence intervals (CIs), were calculated by meta-analysis. The levels of Scr, BUN and VEGF in the CKD group were significantly higher, when compared with the control group (P < 0.01). For the meta-analysis, thirteen articles and our current study were evaluated. VEGF levels was found to be associated with CKD risk (P < 0.00001). In the sub-group meta-analysis, we found that the pooled MD of VEGF levels was related to the early CKD group, although the difference was not notable. However, the meta-analysis itself indicated that the pooled MD of VEGF levels were in accordance with severe CKD group (P < 0.00001). Furthermore, VEGF +936C/T T allele was not associated with CKD risk (P = 0.69). VEGF levels are apparently associated with CKD risk, especially in more severe CKD. Gene polymorphism analysis indicates that the VEGF +936C/T T allele is not associated with CKD risk.

Is Adynamic Bone Always a Disease? Lessons from Patients with Chronic Kidney Disease

Renal osteodystrophy (ROD) is a common complication of end-stage kidney disease that often starts early with loss of kidney function, and it is considered an integral part in management of patients with chronic kidney disease (CKD). Adynamic bone (ADB) is characterized by suppressed bone formation, low cellularity, and thin osteoid seams. There is accumulating evidence supporting increasing prevalence of ADB, particularly in early CKD. Contemporarily, it is not very clear whether it represents a true disease, an adaptive mechanism to prevent bone resorption, or just a transitional stage. Several co-players are incriminated in its pathogenesis, such as age, diabetes mellitus, malnutrition, uremic milieu, and iatrogenic factors. In the present review, we will discuss the up-to-date knowledge of the ADB and focus on its impact on bone health, fracture risk, vascular calcification, and long-term survival. Moreover, we will emphasize the proper preventive and management strategies of ADB that are pivotal issues in managing patients with CKD. It is still unclear whether ADB is always a pathologic condition or whether it can represent an adaptive process to suppress bone resorption and further bone loss. In this article, we tried to discuss this hard topic based on the available limited information in patients with CKD. More studies are needed to be able to clearly address this frequent ROD finding.

Urinary liver-type fatty acid-binding protein in clinically healthy elderly cats: Evaluation of its potential to detect IRIS stage 1 chronic kidney disease and borderline proteinuria.

Urinary liver-type fatty acid-binding protein (uL-FABP) is a promising biomarker to detect early chronic kidney disease (CKD) in cats. Few healthy cats show increased uL-FABP for unknown reasons. The objective of this study was to evaluate uL-FABP in a large healthy elderly cat population comparing cats with and without International Renal Interest Society (IRIS) stage 1 CKD and with and without borderline proteinuria. This was a cross-sectional study. One hundred ninety-six clinically healthy client-owned cats of ≥7 years old were subdivided based on two criteria: (1) having either IRIS stage 1 CKD or no evidence of CKD and (2) having borderline proteinuria or no proteinuria. Urinary L-FABP was measured using a validated commercially available feline L-FABP ELISA. Overall, uL-FABP was detectable in 6/196 (3%) healthy elderly cats. For the first subdivision, nine (5%) cats had IRIS stage 1 CKD, 184 cats had no evidence CKD and three cats were excluded. All cats with IRIS stage 1 CKD had uL-FABP concentrations below the detection limit, whereas 6/184 (3%) cats without IRIS stage 1 CKD had detectable uL-FABP concentrations (median 1.79ng/ml, range 0.79-3.66ng/ml). For the second subdivision, 47 (24%) cats had borderline proteinuria, 147 cats had no proteinuria and two cats were excluded. One of the borderline proteinuric cats had a detectable uL-FABP concentration, whereas the other five cats with detectable uL-FABP concentrations were non-proteinuric. With the current assay, the screening potential of uL-FABP as an early biomarker for feline CKD is limited as uL-FABP was rarely detected in clinically healthy elderly cats independently of the presence of either IRIS stage 1 CKD or borderline proteinuria.

Renoprotective effects of docosahexaenoic acid in cats with early chronic kidney disease due to polycystic kidney disease: a pilot study.

Lipids containing n-3 fatty acids have been reported to have protective effects on renal function, with docosahexaenoic acid (DHA) expected to be particularly effective. However, no reports have demonstrated the renoprotective effects of DHA-enriched lipids in cats with chronic kidney disease (CKD). Therefore, the aim of this pilot study was to examine the renoprotective effects of DHA-enriched fish oil in cats. Five healthy cats and five cats with early non-azotaemic CKD due to autosomal dominant polycystic kidney disease (PKD) were orally administered DHA-enriched fish oil in liquid form (250 or 500 mg/kg body weight [BW] and 250 mg/kg BW of DHA, respectively) for 28 days. Inappropriately dilute urine and markedly increased urinary N-acetyl-d-glucosamine (NAG) index were detected in cats with PKD before DHA-enriched fish oil administration. Changes in the fatty acid composition ratio in the blood of all 10 cats were assessed after orally administering 250 mg/kg of DHA. Post-administration, no adverse clinical effects were observed, and blood and urine tests were within the reference intervals in healthy cats. Cats with PKD showed significantly decreased serum symmetric dimethylarginine (SDMA), urine protein:creatinine ratio (UPC) and urinary NAG index at post-administration. Furthermore, oral administration of DHA-enriched fish oils significantly decreased the blood concentration ratio of arachidonic acid (AA) in cats with PKD post-administration. Furthermore, the concentration ratio of DHA in the blood significantly increased in both healthy cats and cats with PKD, and the DHA:AA ratio also increased. Oral administration of DHA-enriched fish oils for 28 days significantly decreased blood AA levels and significantly increased DHA concentration and DHA:AA ratios in cats with PKD, and improved the SDMA, UPC and urinary NAG index, suggesting its potential for renoprotective effects in cats with early non-azotaemic CKD due to PKD.

Calcitriol levels and the stage of chronic kidney disease in children

Background Kidney damage in chronic kidney disease (CKD) disrupts the 1?-hydroxylase enzyme, preventing the conversion of vitamin D into the active form of calcitriol. To our knowledge, no previous studies have assessed calcitriol levels in children with CKD. Decreased vitamin D levels may occur at an early stage of the disease, so it is important to evaluate calcitriol levels in children with early stage CKD.&#x0D; Objective To assess calcitriol levels in children with CKD according to disease stage and other characteristics.&#x0D; Methods This cross-sectional study was conducted on 43 pediatric CKD patients at Dr. M Djamil Hospital, Padang, Indonesia. We recorded patient characteristics and performed laboratory tests, including routine hematology, blood urea nitrogen (BUN), creatinine, uric acid, electrolytes, calcium, and calcitriol levels. Based on estimated glomerular filtration rate (GFR), patients were grouped into either early-stage (stages I and II), or advanced-stage (stages III to V) CKD. Univariate and multivariate analyses were conducted to determine the association between calcitriol levels with disease stage and other characteristics.&#x0D; Results The overall mean calcitriol level of our subjects was 108.77 (SD 10.79) pmol/L. Mean levels at each CKD stage from I to V were 164.28 (SD 160.90), 94.14 (SD 50.63), 72.16 (SD 13.18), 62.92 (SD 4.87), and 67.51 (SD 4.87) pmol/L, respectively. Calcitriol levels did not differ significantly by CKD stage (P=0.114) when each stage from I to V was considered separately. There was no significant difference in calcitriol levels by growth characteristics (P=0.944), etiology (P=0.311), or anemic status (P=0.104). However, low calcitriol levels were found in all subjects with advanced stage CKD, compared to 63.6% subjects with early stage CKD (P=0.004). Mean calcitriol levels were significantly lower in CKD stage IV (P=0.049) and stage V (P=0.027) compared to stage I.&#x0D; Conclusions The decrease in calcitriol level occurs at an early stage in CKD. Calcitriol levels are significantly lower in advanced stage than in early stage CKD.

Urinary Protein Profiling for Potential Biomarkers of Chronic Kidney Disease: A Pilot Study.

Proteinuria is a risk factor for chronic kidney disease (CKD) progression and associated complications. However, there is insufficient information on individual protein components in urine and the severity of CKD. We aimed to investigate urinary proteomics and its association with proteinuria and kidney function in early-stage CKD and in healthy individuals. A 24 h urine sample of 42 individuals (21-CKD and 21-healthy individuals) was used for mass spectrometry-based proteomics analysis. An exponentially modified protein abundance index (emPAI) was calculated for each protein. Data were analyzed by Mascot software using the SwissProt database and bioinformatics tools. Overall, 298 unique proteins were identified in the cohort; of them, 250 proteins belong to the control group with median (IQR) emPAI 39.1 (19−53) and 142 proteins belong to the CKD group with median (IQR) emPAI 67.8 (49−117). The level of 24 h proteinuria positively correlated with emPAI (r = 0.390, p = 0.011). The emPAI of some urinary proteomics had close positive (ALBU, ZA2G, IGKC) and negative (OSTP, CD59, UROM, KNG1, RNAS1, CD44, AMBP) correlations (r < 0.419, p < 0.001) with 24 h proteinuria levels. Additionally, a few proteins (VTDB, AACT, A1AG2, VTNC, and CD44) significantly correlated with kidney function. In this proteomics study, several urinary proteins correlated with proteinuria and kidney function. Pathway analysis identified subpathways potentially related to early proteinuric CKD, allowing the design of prospective studies that explore their response to therapy and their relationship to long-term outcomes.

Quality of life in older adults with chronic kidney disease and transient changes in renal function: Findings from the Oxford Renal cohort.

BackgroundQuality of life (QoL) is an important measure of disease burden and general health perception. The relationship between early chronic kidney disease (CKD) and QoL remains poorly understood. The Oxford Renal Study (OxRen) cohort comprises 1063 adults aged ≥60 years from UK primary care practices screened for early CKD, grouped according to existing or screen-detected CKD diagnoses, or biochemistry results indicative of reduced renal function (referred to as transient estimated glomerular filtration rate (eGFR) reduction).ObjectivesThis study aimed to compare QoL in participants known to have CKD at recruitment to those identified as having CKD through a screening programme.MethodsHealth profile data and multi-attribute utility scores were reported for two generic questionnaires: 5-level EuroQol-5 Dimension (EQ-5D-5L) and ICEpop CAPability measure for Adults (ICECAP-A). QoL was compared between patients with existing and screen-detected CKD; those with transient eGFR reduction served as the reference group in univariable and multivariable linear regression.ResultsMean and standard deviation utility scores were not significantly different between the subgroups for EQ-5D-5L (screen-detected:0.785±0.156, n = 480, transient:0.779±0.157, n = 261, existing CKD:0.763±0.171, n = 322, p = 0.216) or ICECAP-A (screen-detected:0.909±0.094, transient:0.904±0.110, existing CKD:0.894±0.115, p = 0.200). Age, smoking status, and number of comorbidities were identified as independent predictors of QoL in this cohort.ConclusionQoL of participants with existing CKD diagnoses was not significantly different from those with screen-detected CKD or transient eGFR reduction and was similar to UK mean scores for the same age, suggesting that patient burden of early CKD is minor. Moreover, CKD-related comorbidities contribute more significantly to disease burden in earlier stages of CKD than renal function per se. Larger prospective studies are required to define the relationship between QoL and CKD progression more precisely. These data also confirm the essentially asymptomatic nature of CKD, implying that routine screening or case finding are required to diagnose it.

The Beneficial Effects of Bariatric-Surgery-Induced Weight Loss on Renal Function.

Obesity represents an independent risk factor for the development of chronic kidney disease (CKD), leading to specific histopathological alterations, known as obesity-related glomerulopathy. Bariatric surgery is the most effective means of inducing and maintaining sustained weight loss. Furthermore, in the context of bariatric-surgery-induced weight loss, a reduction in the proinflammatory state and an improvement in the adipokine profile occur, which may also contribute to the improvement of renal function following bariatric surgery. However, the assessment of renal function in the context of obesity and following marked weight loss is difficult, since the formulas adopted to estimate glomerular function use biomarkers whose production is dependent on muscle mass (creatinine) or adipose tissue mass and inflammation (cystatin-c). Thus, following bariatric surgery, the extent to which reductions in plasma concentrations reflect the actual improvement in renal function is not clear. Despite this limitation, the available literature suggests that in patients with hyperfiltration at baseline, GFR is reduced following bariatric surgery, whereas GFR is increased in patients with decreased GFR at baseline. These findings are also confirmed in the few studies that have used measured rather than estimated GFR. Albuminuria is also decreased following bariatric surgery. Moreover, bariatric surgery seems superior in achieving the remission of albuminuria and early CKD than the best medical treatment. In this article, we discuss the pathophysiology of renal complications in obesity, review the mechanisms through which weight loss induces improvements in renal function, and provide an overview of the renal outcomes following bariatric surgery.

Head-to-Head Comparison of Oxidative Stress Biomarkers for All-Cause Mortality in Hemodialysis Patients.

Oxidative stress (OS) presents even in the early chronic kidney disease (CKD) stage and is exacerbated in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis (MHD). There is still a debate over the association between oxidative stress and mortality. Our study aims to compare head-to-head the prognostic value of different oxidative markers for all-cause mortality in hemodialysis (HD) patients. We thus enrolled 347 patients on HD in this prospective study. Four OS biomarkers were measured (carbonyl proteins, myeloperoxidase (MPO), advanced oxidation protein products (AOPPs), and oxidized low-density lipoprotein (ox-LDL)). During the 60-month follow-up period, 9 patients have been lost to follow-up and 168 (48.4%) patients died. Concerning the oxidative stress (ox-stress) byproducts, carbonyl proteins were lower in survivors (105.40 ng/mL (IQR 81.30–147.85) versus 129.65 ng/mL (IQR 93.20–180.33); p < 0.001), with similar results for male patients (103.70 ng/mL (IQR 76.90–153.33) versus 134.55 ng/mL (IQR 93.95–178.68); p = 0.0014). However, there are no significant differences in MPO, AOPP, and ox-LDL between the two groups. Kaplan–Meier survival analysis indicated that patients in the higher carbonyl proteins concentration (>117.85 ng/mL group) had a significantly lower survival rate (log-rank test, p < 0.001). Univariate Cox regression analysis showed a positive correlation between carbonyl proteins and all-cause mortality in the higher and lower halves. Even after adjustment for conventional risk factors, it remained a statistically significant predictor of an increased risk of death in MHD. Univariate Cox regression analysis of MPO showed that continuous MPO and Log MPO were significantly associated with all-cause mortality, except for binary MPO (divided according to the median of MPO). Multivariate Cox analysis for MPO showed that the mortality prediction remains significant after adjusting for multiple factors. In conclusion, not all ox-stress biomarkers predict all-cause mortality in HD patients to a similar extent. In the present study, carbonyl proteins and MPO are independent predictors of all-cause mortality in HD patients, whereas AOPPs and oxLDL are clearly not associated with all-cause mortality in HD patients.

Effect of Early Introduction of Calcium Carbonate on Fibroblast Growth Factor 23 (FGF23) Levels in Children with Normophosphatemic Early Chronic Kidney Disease (CKD)

Effect of Early Introduction of Calcium Carbonate on Fibroblast Growth Factor 23 (FGF23) Levels in Children with Normophosphatemic Early Chronic Kidney Disease (CKD)

Urinary sodium excretion is low prior to acute kidney injury in patients in the intensive care unit.

The incidence of acute kidney injury (AKI) is high in intensive care units (ICUs), and a better understanding of AKI is needed. Early chronic kidney disease is associated with urinary concentration inability and AKI recovery with increased urinary solutes in humans. Whether the inability of the kidneys to concentrate urine and excrete solutes at appropriate levels could occur prior to the diagnosis of AKI is still uncertain, and the associated mechanisms have not been studied. In this single-center prospective observational study, high AKI risk in ICU patients was followed up for 7 days or until ICU discharge. They were grouped as "AKI" or "No AKI" according to their AKI status throughout admission. We collected daily urine samples to measure solute concentrations and osmolality. Data were analyzed 1 day before AKI, or from the first to the fifth day of admission in the "No AKI" group. We used logistic regression models to evaluate the influence of the variables on future AKI diagnosis. The expression of kidney transporters in urine was evaluated by Western blotting. We identified 29 patients as "No AKI" and 23 patients as "AKI," the latter being mostly low severity AKI. Urinary sodium excretion was lower in "AKI" patients prior to AKI diagnosis, particularly in septic patients. The expression of Na+/H+ exchanger (NHE3), a urinary sodium transporter, was higher in "AKI"patients. Urinary sodium excretion is low before an AKI episode in ICU patients, and high expressions of proximal tubule sodium transporters might contribute to this.

Influence of positive and negative affect on self-management among patients with early chronic kidney disease during the COVID-19 pandemic: The mediating and suppressing effect of ego depletion.

BackgroundSelf-management in patients with early chronic kidney disease (CKD) can effectively delay damage to renal function. However, with the continuous spread of COVID-19, patients cannot receive timely treatment, which can lead to different affects, resulting in ego depletion and serious challenges to self-management. This study aimed to investigate the mediating and suppressing roles of ego depletion on the relationship between positive and negative affect and self-management among patients with early CKD during the COVID-19 pandemic in China.MethodsA total of 383 patients with early CKD from three tertiary hospitals were enrolled by convenience sampling in our cross-sectional study from September 2021 to March 2022. Participants completed the Sociodemographic Questionnaire, Positive Affect and Negative Affect Scale, Self-Regulating Fatigue Scale and Chronic Kidney Disease Self-Management Instrument. A structural equation model was conducted to test the mediating and suppressing effects of ego depletion on the relationship between positive and negative affect and self-management.ResultsThe average score of the participants' self-management was 84.54 (SD: 19.72), and nearly 60% of them were at low and moderate levels. The mediating effect of positive affect on self-management through ego depletion was significant (β = 0.248, 95% CI: 0.170 to 0.376), accounting for 53.22% of the total effect. The suppressing effect of negative affect on self-management through ego depletion was significant (β = −0.191, 95% CI: −0.310 to −0.118), and the absolute value of the ratio of the suppressing effect to the direct effect was 66.55%.ConclusionsEgo depletion partially mediated the relationship between positive affect and self-management while suppressing the relationship between negative affect and self-management among patients with early CKD during the COVID-19 pandemic. The reduction of patients' ego depletion must be taken as the intervention target to improve self-management and delay the progression of CKD.

The Influence of the Severity of Early Chronic Kidney Disease on Oxidative Stress in Patients with and without Type 2 Diabetes Mellitus.

Early Chronic Kidney Disease (CKD) is a condition that tends to progress to End-Stage Kidney Disease (ESKD). Early diagnosis of kidney disease in the early stages can reduce complications. Alterations in renal function represent a complication of diabetes mellitus (DM). The mechanisms underlying the progression of CKD in diabetes could be associated with oxidative and inflammatory processes. This study aimed to evaluate the state of inflammation and oxidative stress (OS) on the progression of CKD in the early stages in patients with and without type 2 diabetes mellitus (T2DM). An analytical cross-sectional study was carried out in patients with CKD in early stages (1, 2, 3) with and without T2DM. The ELISA method determined the expression of pro-inflammatory cytokines IL-6 and TNF-α as well as lipoperoxides (LPO), nitric oxide (NO), and superoxide dismutase activity (SOD). Colorimetric methods determined glutathione peroxidase (GPx) and total antioxidant capacity (TAC). Patients with CKD and T2DM had significantly decreased antioxidant defenses for SOD (p < 0.01), GPx (p < 0.01), and TAC (p < 0.01) compared to patients without T2DM. Consequently, patients with T2DM had higher concentrations of oxidant markers, NO (p < 0.01), inflammation markers, IL-6 (p < 0.01), and TNF-α than patients without T2DM. CKD stages were not related to oxidative, antioxidant, and inflammatory marker outcomes in T2DM patients. Patients without T2DM presented an increase in SOD (p = 0.04) and a decrease in NO (p < 0.01) when the stage of CKD increased. In conclusion, patients with T2DM present higher levels of oxidative and inflammatory markers accompanied by a decrease in antioxidant defense. However, these oxidative status markers were associated with CKD stage progression in patients without T2DM. Thus, NO and SOD markers could help detect the early stages of CKD in patients who have not yet developed metabolic comorbidities such as T2DM.

The controversy of klotho as a potential biomarker in chronic kidney disease.

Klotho is an identified longevity gene with beneficial pleiotropic effects on the kidney. Evidence shows that a decline in serum Klotho level occurs in early chronic kidney disease (CKD) and continues as CKD progresses. Klotho deficiency is associated with poor clinical outcomes and CKD mineral bone disorders (CKD-MBD). Klotho has been postulated as a candidate biomarker in the evaluation of CKD. However, the evidence for the clinical significance of the relationship between Klotho and kidney function, CKD stage, adverse kidney and/or non-kidney outcomes, and CKD-MBD remains inconsistent and in some areas, contradictory. Therefore, there is uncertainty as to whether Klotho is a potential biomarker in CKD; a general consensus regarding the clinical significance of Klotho in CKD has not been reached, and there is limited evidence synthesis in this area. To address this, we have systematically assessed the areas of controversy, focusing on the inconsistencies in the evidence base. We used a PICOM strategy to search for relevant studies and the Newcastle–Ottawa Scale scoring to evaluate included publications. We reviewed the inconsistent clinical findings based on the relationship of Klotho with CKD stage, kidney and/or non-kidney adverse outcomes, and CKD-MBD in human studies. Subsequently, we assessed the underlying sources of the controversies and highlighted future directions to resolve these inconsistencies and clarify whether Klotho has a role as a biomarker in clinical practice in CKD.

Demographic and clinical profile of black patients with chronic kidney disease attending a tertiary hospital in Johannesburg, South Africa.

BackgroundThe prevalence of chronic kidney disease (CKD) is increasing worldwide; black patients have an increased risk of developing CKD and end stage kidney disease (ESKD) at significantly higher rates than other races.MethodsA cross sectional study was carried out on black patients with CKD attending the kidney outpatient clinic at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in South Africa, between September 2019 to March 2020. Demographic and clinical data were extracted from the ongoing kidney outpatient clinic records and interviews, and were filled in a questionnaire. Patients provided blood and urine for laboratory investigations as standard of care, and data were descriptively and inferentially entered into REDcap and analysed using STATA version 17. Multivariable logistic regression analysis was used to identify demographic and clinical variables associated with advanced CKD.ResultsA total of 312 black patients with CKD were enrolled in the study with a median age of 58 (IQR 46–67) years; 58% patients had advanced CKD, 31.5% of whom had grossly increased proteinuria, 96.7% had hypertension, 38.7% had diabetes mellitus and 38.1% had both hypertension and diabetes mellitus. In patients with advanced CKD, the median age was 61 (IQR 51–69) years, eGFR 33 (30–39) mL/min/1.73 m2, serum bicarbonate 22 (IQR 20–24), haemoglobin 12.9 (IQR 11.5–14.0) g/dl and serum uric acid 0.43 (IQR 0.37–0.53). The prevalence of metabolic acidosis was 62.4%, anemia 46.4% and gout 30.9% among those with advanced CKD, while the prevalence of metabolic acidosis and anaemia was 46.6% and 25.9% respectively in those with early CKD. Variables with higher odds for advanced CKD after multivariable logistic regression analysis were hypertension (OR 3.3, 95% CI 1.2–9.2, P = 0.020), diabetes mellitus (OR 1.8, 95% CI 1.1–3.3, P = 0.024), severe proteinuria (OR 3.5, 95% CI 1.9–6.5, P = 0.001), angina (OR 2.5, 95% CI 1.2–5.1, P = 0.008), anaemia (OR 2.9, 95% CI 1.7–4.9, P = 0.001), hyperuricemia (OR 2.4, 95% CI 1.4–4.1, P = 0.001), and metabolic acidosis (OR 2.0, 95% CI 1.2–3.1, P = 0.005). Other associations with advanced CKD were loss of spouse (widow/widower) (OR 3.2, 95% CI 1.4–7.4, P = 0.006), low transferrin (OR 2.4, 95% CI 1.1–5.1, P = 0.028), hyperkalemia (OR 5.4, 95% CI 1.2–24.1, P = 0.029), use of allopurinol (OR 2.4, 95% CI 1.4–4.3, P = 0.005) and doxazosin (OR 1.9, 95% CI 1.2–3.1, P = 0.006).ConclusionHypertension and diabetes mellitus were strongly associated with advanced CKD, suggesting a need for primary and secondary population-based prevention measures. Metabolic acidosis, anemia with low transferrin levels, hyperuricemia and hyperkalemia were highly prevalent in our patients, including those with early CKD, and they were strongly associated with advanced CKD, requiring clinicians and dietitians to be proactive in supporting the needs of CKD patients in meeting their daily dietary requirements towards preventing and slowing the progression of CKD.

Nomogram model for predicting early onset of chronic kidney disease using color Doppler region of interest technique.

The risk factors of chronic kidney disease were analyzed by using the region of interest quantitative technology of color Doppler combined with QLab software, and a Nomogram was established to conduct an individualized assessment of patients with chronic kidney disease. A total of 500 patients with chronic kidney disease diagnosed in our hospital from June 2019 to March 2021 were selected as the chronic kidney disease group, and 300 healthy patients during the same period were selected as the control group. Univariate analysis was performed on the test indexes and the vascularity index, flow index, and vascularization flow index measured by the color doppler region of interest quantitative technique. The above meaningful indicators were included in the Logistics regression analysis to obtain the independent risk factors of early chronic kidney disease. The independent risk factors were imported into R software to draw a Nomogram model for predicting early chronic kidney disease and evaluate the model. Single factor analysis results suggest age, hypertension, diabetes, hyperlipidemia, disease of heart head blood-vessel, body mass index, vascularity index, flow index, and vascularization flow index, fasting blood sugar, triglyceride, total cholesterol, urea nitrogen, creatinine, uric acid, glomerular filtration rate differences statistically significant (P < 0.05). Logistics regression analysis showed that hypertension, diabetes, flow index, and vascularization flow index, urea nitrogen, and albumin were independent risk factors for the early occurrence of chronic kidney disease. The C-index of this Nomogram using independent risk factors is 0.896 (95%CI 0.862-0.930), which indicates that the Nomogram has good discriminant power. The receiver operating curve of the histograph was area under the curve (AUC) 0.884 (95%CI 0.860-0.908). The receiver operator characteristic curve (ROC) of urea nitrogen, albumin, flow index, and vascularization flow index were evaluated. The results indicated that the best cutoff value of urea nitrogen was 5.9mmol/L, flow index was 14.67, vascularization flow index was 4.6, and albumin was 40.26g/L. In the prediction of chronic kidney disease I-II stage, the quantitative technique of color Doppler region of interest has certain diagnostic value. The model established in this study has good discriminative power and can be applied to clinical practice, giving certain indicative significance.

Nomogram-Based Chronic Kidney Disease Prediction Model for Type 1 Diabetes Mellitus Patients Using Routine Pathological Data.

Type 1 diabetes mellitus (T1DM) patients are a significant threat to chronic kidney disease (CKD) development during their life. However, there is always a high chance of delay in CKD detection because CKD can be asymptomatic, and T1DM patients bypass traditional CKD tests during their routine checkups. This study aims to develop and validate a prediction model and nomogram of CKD in T1DM patients using readily available routine checkup data for early CKD detection. This research utilized 1375 T1DM patients’ sixteen years of longitudinal data from multi-center Epidemiology of Diabetes Interventions and Complications (EDIC) clinical trials conducted at 28 sites in the USA and Canada and considered 17 routinely available features. Three feature ranking algorithms, extreme gradient boosting (XGB), random forest (RF), and extremely randomized trees classifier (ERT), were applied to create three feature ranking lists, and logistic regression analyses were performed to develop CKD prediction models using these ranked feature lists to identify the best performing top-ranked features combination. Finally, the most significant features were selected to develop a multivariate logistic regression-based CKD prediction model for T1DM patients. This model was evaluated using sensitivity, specificity, accuracy, precision, and F1 score on train and test data. A nomogram of the final model was further generated for easy application in clinical practices. Hypertension, duration of diabetes, drinking habit, triglycerides, ACE inhibitors, low-density lipoprotein (LDL) cholesterol, age, and smoking habit were the top-8 features ranked by the XGB model and identified as the most important features for predicting CKD in T1DM patients. These eight features were selected to develop the final prediction model using multivariate logistic regression, which showed 90.04% and 88.59% accuracy in internal and test data validation. The proposed model showed excellent performance and can be used for CKD identification in T1DM patients during routine checkups.

Effects of dietary phosphorus concentration and phosphate salt form on renal tubule function in unilateral nephrectomized rats.

Background: Excessive consumption of phosphorus (P) impairs renal tubule function; however, the effects of different dietary phosphate salts on chronic kidney disease (CKD) are unclear. Aim: To examine the effects of potassium dihydrogen phosphate (KH2PO4) and potassium tripolyphosphate (K5P3O10) and P concentration on renal function in a rat model of early CKD. Methods: Male sham-operated Sprague-Dawley rats were fed a diet containing KH2PO4 with a normal P level. Kidney injury was induced by unilateral nephrectomy (UNx), and the rats were divided into four groups fed dietary KH2PO4 or K5P3O10 with a normal (UNx-NKH, UNx-NKP) or high (UNx-HKH, UNx-HKP) P concentration, respectively, for 21 days. Results: UNx-NKH rats showed significantly lower creatinine clearance (CCr) and higher albumin (ALB) compared with those of sham rats, confirming UNx-induced kidney injury. The urinary levels of liver-type fatty acid-binding protein (L-FABP) and ALB were significantly higher in UNx-HKP rats than in UNx-HKH rats. However, other markers of renal tubule function, such as CCr, serum creatinine (CRE), calcium (Ca), and hormones, only differed among groups according to the P concentration and not the dietary phosphate salt form. Histological examination showed higher incidence and severity of tubulointerstitial lesions, tubule regeneration, tubule dilation, and calcification in the high-phosphorus than in the normal-phosphorus UNx groups. These changes were more severe in the UNx-HKP group compared with the UNx-HKH group. Conclusion: This study highlights the importance of controlling dietary P intake in terms of both concentration and source to prevent the progression of CKD.