Predictors Of Kidney Function Research Articles

Breath Ammonia Is a Useful Biomarker Predicting Kidney Function in Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) is a public health problem and its prevalence has increased worldwide; patients are commonly unaware of the condition. The present study aimed to investigate whether exhaled breath ammonia via vertical-channel organic semiconductor (V-OSC) sensor measurement could be used for rapid CKD screening. We enrolled 121 CKD stage 1–5 patients, including 19 stage 1 patients, 26 stage 2 patients, 38 stage 3 patients, 21 stage 4 patients, and 17 stage 5 patients, from July 2019 to January 2020. Demographic and laboratory data were recorded. The exhaled ammonia was collected and rapidly measured by the V-OSC sensor to correlate with kidney function. Results showed no significant difference in age, sex, body weight, hemoglobin, albumin level, and comorbidities in different CKD stage patients. Correlation analysis demonstrated a good correlation between breath ammonia and blood urea nitrogen levels, serum creatinine levels, and estimated glomerular filtration rate (eGFR). Breath ammonia concentration was significantly elevated with increased CKD stage compared with the previous stage (CKD stage 1/2/3/4/5: 636 ± 94; 1020 ± 120; 1943 ± 326; 4421 ± 1042; 12781 ± 1807 ppb, p < 0.05). The receiver operating characteristic curve analysis showed an area under the curve (AUC) of 0.835 (p < 0.0001) for distinguishing CKD stage 1 from other CKD stages at 974 ppb (sensitivity, 69%; specificity, 95%). The AUC was 0.831 (p < 0.0001) for distinguishing between patients with/without eGFR < 60 mL/min/1.73 m2 (cutoff 1187 ppb: sensitivity, 71%; specificity, 78%). At 886 ppb, the sensitivity increased to 80% but the specificity decreased to 69%. This value is suitable for kidney function screening. Breath ammonia detection with V-OSC is a real time, inexpensive, and easy to administer measurement device for screening CKD with reliable diagnostic accuracy.

PREDICTING KIDNEY FUNCTION AFTER HIGH KDPI KIDNEY TRANSPLANTATION: A COMPARISON OF EXPECTED VS. OBSERVED GLOMERULAR FILTRATION RATE IN A LARGE COHORT OF KDPI &gt;85 KIDNEY TRANSPLANT RECIPIENTS

Purpose: Renal function after transplantation is dependent on a combination of viable donor nephron mass and the adaptation of recipient glomerular filtration. Although previous studies have assessed post-transplant kidney function from living and standard criteria deceased donor kidney transplant recipients, no study has sought to calculate kidney function following high KDPI (KDPI>85) kidney transplantation. Methods: From December 2014 to July 2019, 58 kidney transplants with KDPI>85 were performed at Hartford Hospital. Using the modified Glomerular Filtration Rate Cockcroft and Gault equation (CG-GFR) expected serum creatinine (ExpSCr) at one year was calculated and compared to observed serum creatinine (ObsSCr). Bland-Altman analysis was performed to assess concordance between ExpSCr and ObsSCr. Bias (mean difference between ExpSCr and ObsSCr) and limits of agreement with their 95% confidence intervals were determined.Results: Among 58 high KDPI kidney transplants, the average KDPI was 91±4%. The donor age was 61±6 years, 57% were male with an average BMI of 31.5±8.0 kg/m2. Of the donor cohort, 82% had a history of hypertension, 40% diabetes, 59% died of cardiovascular causes, and 30% donated after cardiac death. Of the recipient cohort, the average age was 63±8 years, 69% were male with a BMI of 29.4±5.1 kg/m2. More than half of the recipients (69%) were male; 45% self-identified as Caucasian, 31% African American, 17% Hispanic and 7% Other; and 50% and 90% had a pre-transplant diagnosis of diabetes and hypertension, respectively. Delayed graft function was observed in 53% of recipients. The 1-year death-censored graft and patient was survival was 95.7% and 91.5% (n=47), respectively. The 6-month and 1-year creatinine for the cohort were 1.86±1.18 (n=49) and 1.68±0.52 mg/dL (n=41), respectively. According to the CG-GFR, the ExpSCr at the first post-transplant year was 1.33±0.47 mg/dL. The average lowest ObsSCr was 1.32±0.47 mg/dL. The bias of expected and ObsSCr and ExpSCr of this cohort of high KDPI kidney transplant recipients was 0.01 mg/dL.Conclusion: Current models for predicting kidney function after living and standard criteria deceased donors accurately predict post-transplant kidney function in high KDPI kidney transplantation. Further research is necessary to identify mitigating risk factors to achieve the optimal donor-recipient match and best possible post-transplant kidney function for high KDPI kidneys.

SAT-129 Prenatal Environment, Birth Weight, Predicts Kidney Function in Adolescence and Adult Life

SAT-129 Prenatal Environment, Birth Weight, Predicts Kidney Function in Adolescence and Adult Life

Transtubular potassium gradient predicts kidney function impairment after adrenalectomy in primary aldosteronism.

Background:In primary aldosteronism (PA), kidney function impairment could be concealed by relative hyperfiltration and emerge after adrenalectomy. We hypothesized transtubular gradient potassium gradient (TTKG), a kidney aldosterone bioactivity indicator, could correlate to end organ damage and forecast kidney function impairment after adrenalectomy.Methods:In the present prospective study, we enrolled lateralized PA patients who underwent adrenalectomy and were followed up 12 months after operation in the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry from 2010 to 2018. The clinical outcome was kidney function impairment, defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 at 12 months after adrenalectomy. End organ damage is determined by microalbuminuria and left ventricular mass.Results:In total, 323 patients [mean, 50.8 ± 10.9 years old; female 178 (55.1%)] were enrolled. Comparing pre-operation and post-operation data, systolic blood pressure, serum aldosterone, urinary albumin to creatinine ratio and eGFR decreased. TTKG ⩾ 4.9 correlated with pre-operative urinary albumin to creatinine ratio >50 mg/g [odds ratio (OR) = 2.42; p = 0.034] and left ventricular mass (B = 20.10; p = 0.018). Multivariate logistic regression analysis demonstrated that TTKG ⩾ 4.9 could predict concealed chronic kidney disease (OR = 5.42; p = 0.011) and clinical success (OR = 2.90, p = 0.017) at 12 months after adrenalectomy.Conclusions:TTKG could predict concealed kidney function impairment and cure of hypertension in PA patients after adrenalectomy. TTKG more than 4.9 as an adverse surrogate of aldosterone and hypokalaemia correlated with pre-operative end organ damage in terms of high proteinuria and cardiac hypertrophy.

Everyday Discrimination and Kidney Function Among Older Adults: Evidence From the Health and Retirement Study.

With advancing age, there is an increase in the time of and number of experiences with psychosocial stressors that may lead to the initiation and/or progression of chronic kidney disease (CKD). Our study tests whether one type of experience, everyday discrimination, predicts kidney function among middle and older adults. The data were from 10 973 respondents (ages 52-100) in the 2006/2008 Health and Retirement Study, an ongoing biennial nationally representative survey of older adults in the United States. Estimated glomerular filtration rate (eGFR) derives from the Chronic Kidney Disease Epidemiology Collaboration equation. Our indicator of everyday discrimination is drawn from self-reports from respondents. Ordinary Least Squared regression (OLS) models with robust standard errors are applied to test hypotheses regarding the link between everyday discrimination and kidney function. Everyday discrimination was associated with poorer kidney function among respondents in our study. Respondents with higher everyday discrimination scores had lower eGFR after adjusting for demographic characteristics (B = -1.35, p < .05), and while attenuated, remained significant (B = -0.79, p < .05) after further adjustments for clinical, health behavior, and socioeconomic covariates. Our study suggests everyday discrimination is independently associated with lower eGFR. These findings highlight the importance of psychosocial factors in predicting insufficiency in kidney function among middle-aged and older adults.

Progression of Albuminuria in Sickle Cell Anemia: A Multicenter, Longitudinal Study

Introduction Chronic kidney disease (CKD) is a significant cause of morbidity and mortality in patients with sickle cell anemia (SCA). Albuminuria quantified by urinary albumin-to-creatinine ratio (ACR) is predictive of CKD and end-stage renal disease in other settings (non-SCA). As most sickle cell nephropathy studies are retrospective and cross-sectional, little is known about the natural progression of albuminuria in SCA and its correlation with glomerular filtration rate (GFR) decline and development of CKD. Methods We conducted a prospective, multicenter study (between 2009 and 2017) to investigate the longitudinal progression of sickle cell nephropathy (NCT02239016). Participants with SCA (HbSS or HbSb0 thalassemia) of all ages from 11 centers in the United States and the Caribbean were enrolled and provided urine and blood samples during routine clinic visits at steady-state. Urine ACR, cystatin C-estimated GFR (eGFR), and standard biomarkers of SCA and nephropathy in addition to kidney injury molecule (KIM-1) and N-acetyl-b-D-glucosaminidase (NAG) were followed longitudinally. Participants with albuminuria for ≥ 2 annual measurements were considered to have persistent albuminuria. Results A total of 303 participants with SCA were enrolled and followed for a median of 2 years. Participants were 1.6-64 years old (mean 21 years), and 46% were females. Participants provided annual samples (average 14.5-month interval between sample collections) and contributed to 644 patient-years on the study. 175 participants provided at least three annual samples and were included in a longitudinal analysis. The prevalence of albuminuria (ACR&gt;30mg/g) at baseline was 32% (97/303) of which 26% (80/303) had microalbuminuria (UACR 30-300 mg/g) and 6% (17/303) had macroalbuminuria (UACR&gt;300 mg/g). At study entry, 45% of patients were prescribed hydroxyurea, and 20% received chronic transfusion therapy. In univariate analysis, baseline ACR was significantly associated with older age (P&lt;0.0001), sex (P=0.009), higher systolic and diastolic blood pressure (P&lt;0.0001 and P=0.005), lower hemoglobin (P=0.01) and HbF (P=0.0005), higher bilirubin (P=0.001), and higher NAG (P&lt;0.0001) and KIM-1 (P&lt;0.0001). In a longitudinal multivariate analysis (years 0-3) that included the statistically significant variables from univariate analysis in addition to age-adjusted eGFR, only age (P=0.03), female sex (P=0.009), hemoglobin (P=0.01), bilirubin (P=0.002) and KIM-1 (P&lt;0.0001) were significantly associated with ACR. In participants who had at least 3 annual samples, a baseline ACR ≥100mg/g was predictive of persistent albuminuria (ACR&gt;30mg/g for ≥2 annual measurements): 81% of participants with baseline ACR ≥100 mg/g had persistent albuminuria compared to 19% of participants with baseline ACR&lt;100 mg/g. Participants with persistent albuminuria had significantly higher age, blood pressure, and serum creatinine, but were less likely to be on disease-modifying therapy (hydroxyurea or chronic transfusions), and had significantly lower HbF compared to those with non-persistent albuminuria. eGFR correlated with age (P&lt;0.0001) and persistent albuminuria (P=0.002), but not with baseline ACR. Participants with persistent albuminuria were also more likely to have a rapid decline in eGFR (a decline by &gt;3 ml/min/1.73m2 per year) compared to those with non-persistent albuminuria (48% vs 31%, P=0.03). Conclusion In this longitudinal, prospective, multicenter study of sickle nephropathy, albuminuria was strongly associated with age and progressed over time (figure 1). Despite variability in spot urine ACR measurements, high baseline ACR ( ≥100mg/g) was associated with persistent albuminuria. Patients with persistent albuminuria were more likely to have rapid eGFR decline, a high-risk factor for CKD progression. Use of hydroxyurea and chronic transfusions was associated with less incidence of persistent albuminuria. Our results demonstrate that persistent albuminuria and high ACR at baseline predict kidney function decline in SCA. These findings show the feasibility of determining ACR and monitoring sickle nephropathy at routine clinic visits and have important implications for clinical decision-making and the design of future controlled therapeutic trials. Disclosures Saraf: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding. Quinn:Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Other: Research Support.

Re: Larger Nephron Size, Low Nephron Number, and Nephrosclerosis on Biopsy as Predictors of Kidney Function after Donating a Kidney.

Re: Larger Nephron Size, Low Nephron Number, and Nephrosclerosis on Biopsy as Predictors of Kidney Function after Donating a Kidney.

Rapid Progression of Autosomal Dominant Polycystic Kidney Disease: Urinary Biomarkers as Predictors

Background: Markers currently used to predict the likelihood of rapid disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) are expensive and time consuming to assess and often have limited sensitivity. New, easy-to-measure markers are therefore needed that alone or in combination with conventional risk markers can predict the rate of disease progression. In the present study, we investigated the ability of tubular damage and inflammation markers to predict kidney function decline. Methods: At baseline, albumin, immunoglobulin G, kidney injury molecule 1, β2 microglobulin (β2MG), heart-type fatty acid-binding protein, neutrophil gelatinase-associated lipocalin, and monocyte chemotactic protein-1 ­(MCP-1) were measured in 24-h urine samples of patients participating in a study investigating the therapeutic efficacy of lanreotide in ADPKD. Individual change in estimated glomerular filtration rate (eGFR) during follow-up was calculated using mixed-model analysis taking into account 13 ­eGFRs (chronic kidney disease EPIdemiology) per patient. Logistic regression analysis was used to select urinary biomarkers that had the best association with rapidly progressive disease. The predictive value of these selected urinary biomarkers was compared to other risk scores using C-statistics. Results: Included were 302 patients of whom 53.3% were female, with an average age of 48 ± 7 years, eGFR of 52 ± 12 mL/min/1.73 m², and a height-adjusted total kidney volume (htTKV) of 1,082 (736–1,669) mL/m. At baseline, all urinary damage and inflammation markers were associated with baseline eGFR, also after adjustment for age, sex and baseline htTKV. For longitudinal analyses only patients randomized to standard care were considered (n = 152). A stepwise backward analysis revealed that β2MG and MCP-1 showed the strongest association with rapidly progressive disease. A urinary biomarker score was created by summing the ranking of tertiles of β2MG and MCP-1 excretion. The predictive value of this urinary biomarker score was higher compared to that of the Mayo htTKV classification (area under the curve [AUC] 0.73 [0.64–0.82] vs. 0.61 [0.51–0.71], p = 0.04) and comparable to that of the predicting renal outcomes in ­ADPKD score (AUC 0.73 [0.64–0.82] vs. 0.65 [0.55–0.75], p = 0.18). In a second independent cohort with better kidney function, similar results were found for the urinary biomarker score. Conclusion: Measurement of urinary β2MG and MCP-1 excretion allows selection of ADPKD patients with rapidly progressive disease, with a predictive value comparable to or even higher than that of TKV or PKD mutation. Easy and inexpensive to measure urinary markers therefore hold promise to help predict prognosis in ADPKD.

Association between urinary biomarkers and disease progression in adults with autosomal dominant polycystic kidney disease.

BackgroundHeight-adjusted total kidney volume (htTKV) is considered as the best predictor of kidney function in patients with autosomal dominant polycystic kidney disease (ADPKD), but its limited predictive capacity stresses the need to find new biomarkers of ADPKD progression. The aim of this study was to investigate urinary biomarkers of ADPKD progression.Methods This observational study included ADPKD patients, and two comparator groups of ischaemic and non-ischaemic kidney injury: benign nephroangiosclerosis patients and non-ischaemic chronic kidney disease (CKD) patients. Proteinuria, htTKV and urinary levels of molecules are associated with ischaemia and/or tubular injury. The slope of estimated glomerular filtration rate (eGFR) was used as a dependent variable in univariate and multivariate models of kidney function decline.ResultsThe study included 130 patients with ADPKD, 55 with nephroangiosclerosis and 40 with non-ischaemic CKD. All patients had increased urinary concentrations of biomarkers associated with tubular lesions (liver fatty acid-binding protein, kidney injury molecule-1, β2-microglobulin) and molecules overexpressed under ischaemic conditions [hypoxia-inducible factor-1α, vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1)]. These biomarkers correlated positively with htTKV and negatively with the eGFR slope. htTKV was the single best predictor of the eGFR slope variability in univariate analyses. However, a multivariate model including urinary levels of β2-microglobulin, MCP-1 and VEGF improved the capacity to predict the decline of eGFR in ADPKD patients compared with htTKV alone.ConclusionsThe urinary levels of molecules associated with either renal ischaemia (VEGF and MCP-1) or tubular damage (β2-microglobulin) are associated with renal function deterioration in ADPKD patients, and are, therefore, candidates as biomarkers of ADPKD progression.

Automation of the kidney function prediction and classification through ultrasound-based kidney imaging using deep learning

Prediction of kidney function and chronic kidney disease (CKD) through kidney ultrasound imaging has long been considered desirable in clinical practice because of its safety, convenience, and affordability. However, this highly desirable approach is beyond the capability of human vision. We developed a deep learning approach for automatically determining the estimated glomerular filtration rate (eGFR) and CKD status. We exploited the transfer learning technique, integrating the powerful ResNet model pretrained on an ImageNet dataset in our neural network architecture, to predict kidney function based on 4,505 kidney ultrasound images labeled using eGFRs derived from serum creatinine concentrations. To further extract the information from ultrasound images, we leveraged kidney length annotations to remove the peripheral region of the kidneys and applied various data augmentation schemes to produce additional data with variations. Bootstrap aggregation was also applied to avoid overfitting and improve the model’s generalization. Moreover, the kidney function features obtained by our deep neural network were used to identify the CKD status defined by an eGFR of <60 ml/min/1.73 m2. A Pearson correlation coefficient of 0.741 indicated the strong relationship between artificial intelligence (AI)- and creatinine-based GFR estimations. Overall CKD status classification accuracy of our model was 85.6% —higher than that of experienced nephrologists (60.3%–80.1%). Our model is the first fundamental step toward realizing the potential of transforming kidney ultrasound imaging into an effective, real-time, distant screening tool. AI-GFR estimation offers the possibility of noninvasive assessment of kidney function, a key goal of AI-powered functional automation in clinical practice.

Renal volume reconstruction using free-hand ultrasound scans

Kidney volume is a predictor of kidney function or the number of surviving nephrons; as such, it is a valuable biomarker in tracking the onset and progression of chronic kidney disease (CKD). Existing techniques to measure renal volumes [CT, MRI, three-dimensional (3D) ultrasound] are limited by high cost, long scan times, and low portability. To overcome these limitations, we propose a real-time, low-cost solution for estimating renal volumes using free-hand ultrasound scans. The method involves an Intel RealSense D415 camera mounted on a conventional one-dimensional ultrasound probe; RGB-D SLAM is used to localize the probe in free space. The acquired two-dimensional images are manually segmented by trained clinicians and combined with their corresponding poses to form a 3D volume. The method was tested on ex vivo sheep kidneys embedded in gelatin phantoms. Three different scanning protocols were tested: transverse linear scan (TL), transverse fan scan (TF), and longitudinal fan scan (LF). Ultrasound measured renal volumes were compared to those obtained using the water displacement (WD) method; TL = 66.2 ml, LF = 58.3 ml, TF = 53.3 ml, and WD = 66.6 ml. Further investigation includes automating kidney segmentation, accounting for patient motion, and in vivo validation.

Larger nephron size, low nephron number, and nephrosclerosis on biopsy as predictors of kidney function after donating a kidney.

It is unclear whether structural findings in the kidneys of living kidney donors predict postdonation kidney function. We studied living kidney donors who had a kidney biopsy during donation. Nephron size was measured by glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area. Age-specific thresholds were defined for low nephron number (calculated from CT and biopsy measures) and nephrosclerosis (global glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis). These structural measures were assessed as predictors of postdonation measured GFR, 24-hour urine albumin, and hypertension. Analyses were adjusted for baseline age, gender, body mass index, systolic and diastolic blood pressure, hypertension, measured GFR, urine albumin, living related donor status, and time since donation. Of 2673 donors, 1334 returned for a follow-up visit at a median 4.4months after donation, with measured GFR <60mL/min/1.73m2 in 34%, urine albumin >5mg/24h in 13%, and hypertension in 5.3%. Larger glomerular volume and interstitial fibrosis/tubular atrophy predicted follow-up measured GFR <60mL/min/1.73m2 . Larger cortex volume per glomerulus and low nephron number predicted follow-up urine albumin >5mg/24h. Arteriosclerosis predicted hypertension. Microstructural findings predict GFR <60mL/min/1.73m2 , modest increases in urine albumin, and hypertension shortly after kidney donation.

Plasma endostatin predicts kidney outcomes in patients with type 2 diabetes

Novel biomarkers are needed to predict kidney function decline in patients with type 2 diabetes, especially those with preserved glomerular filtration rate (GFR). There are limited data on the association of markers of endothelial dysfunction with longitudinal GFR decline. We used banked specimens from a nested case-control study in the Action to Control Cardiovascular Disease (ACCORD) trial (n=187 cases: 187 controls) and from a diverse contemporary cohort of type 2 diabetic patients from the Mount Sinai BioMe Biobank (n=871) to assess the association of plasma endostatin and kidney outcomes. We measured plasma endostatin at enrollment and examined its association with a composite kidney outcome of sustained 40% decline in estimated GFR or end-stage renal disease. Baseline plasma endostatin levels were higher in participants with the composite outcome. Each log2 increment in plasma endostatin was associated with approximately 2.5-fold higher risk of the kidney outcome (adjusted odds ratio [OR] 2.5; 95% confidence interval [CI] 1.5-4.3 in ACCORD and adjusted hazard ratio [HR] 2.6; 95% CI 1.8-3.8 in BioMe). Participants in the highest vs. lowest quartile of plasma endostatin had approximately four-fold higher risk for the kidney outcome (adjusted OR 3.6; 95% CI 1.8-7.3 in ACCORD and adjusted HR 4.4; 95% CI 2.3-8.5 in BioMe). The AUC for the kidney outcome improved from 0.74 to 0.77 in BioMe with the addition of endostatin to a base clinical model. Plasma endostatin was strongly associated with kidney outcomes in type 2 diabetics with preserved eGFR and improved risk discrimination over traditional predictors.

Predicting Renal Function Outcomes After Partial and Radical Nephrectomy

BackgroundPartial nephrectomy (PN) is generally favored for cT1 tumors over radical nephrectomy (RN) when technically feasible. However, it can be unclear whether the additional risks of PN are worth the magnitude of renal function benefit. ObjectiveTo develop preoperative tools to predict long-term estimated glomerular filtration rate (eGFR) beyond 30d following PN and RN, separately. Design, setting, and participantsIn this retrospective cohort study, patients who underwent RN or PN for a single nonmetastatic renal tumor between 1997 and 2014 at our institution were identified. Exclusion criteria were venous tumor thrombus and preoperative eGFR <15ml/min/1.73m2. InterventionRN and PN. Outcome measurements and statistical analysisHierarchical generalized linear mixed-effect models with backward selection of candidate preoperative features were used to predict long-term eGFR following RN and PN, separately. Predictive ability was summarized using marginal RGLMM2, which ranges from 0 to 1, with higher values indicating increased predictive ability. Results and limitationsThe analysis included 1152 patients (13 206 eGFR observations) who underwent RN and 1920 patients (18 652 eGFR observations) who underwent PN, with mean preoperative eGFRs of 66ml/min/1.73m2 (standard deviation [SD]=18) and 72ml/min/1.73m2 (SD=20), respectively. The model to predict eGFR after RN included age, diabetes, preoperative eGFR, preoperative proteinuria, tumor size, time from surgery, and an interaction between time from surgery and age (marginal RGLMM2=0.41). The model to predict eGFR after PN included age, presence of a solitary kidney, diabetes, hypertension, preoperative eGFR, preoperative proteinuria, surgical approach, time from surgery, and interaction terms between time from surgery and age, diabetes, preoperative eGFR, and preoperative proteinuria (marginal RGLMM2). Limitations include the lack of data on renal tumor complexity and the single-center design; generalizability needs to be confirmed in external cohorts. ConclusionsWe developed preoperative tools to predict renal function outcomes following RN and PN. Pending validation, these tools should be helpful for patient counseling and clinical decision-making. Patient summaryWe developed models to predict kidney function outcomes after partial and radical nephrectomy based on preoperative features. This should help clinicians during patient counseling and decision-making in the management of kidney tumors.

Association of different glucose traits with kidney function decline risk in a Chinese community-based population without chronic kidney disease.

BackgroundChronic kidney disease (CKD) has become a major issue worldwide and hyperglycemia is known as an important risk factor responsible for CKD progression. Few studies have investigated whether fasting plasma glucose (FPG) could predict kidney function decline (KFD) risk better than postprandial plasma glucose, and vice versa. In this study, we investigated the roles of FPG and 2-hour plasma glucose (2 h-PG) in predicting KFD risk in a Chinese community-based population without baseline deterioration of kidney functions.MethodsSubjects with normal kidney function from an atherosclerosis cohort in Beijing, China were followed up for 2.3 years. The outcome was KFD (a drop in glomerular filtration rate category accompanied by 25% or greater decline of estimated glomerular filtration rate from the baseline or a sustained decline of more than 5 mL/min/1.73 m2/year rate).ResultsA total of 3,738 subjects were included of which, 7.7% of the subjects suffered from KFD. After covariates adjustments, both FPG (OR =1.23, P<0.001) and 2 h-PG (OR =1.07, P<0.001) were associated with KFD. Furthermore, FPG was independent of 2 h-PG to predict KFD (OR =1.26, P<0.001). Subgroup analyses and interaction tests including diabetes mellitus, after adjusting all covariates, revealed no significant heterogeneity among analyzed subgroups. We also found subjects with FPG level of 6.1–7.0 mmol/L and >7.0 mmol/L had 1.83 times and 2.51 times KFD risk respectively, compared to subjects with FPG level <5.6 mmol/L.ConclusionFPG was superior to 2 h-PG in predicting KFD in a Chinese community-based population without CKD. FPG screening may be an important measure for CKD primary prevention even in subjects with impaired fasting glucose.

Relationship of fibroblast growth factor 21 with kidney function and albuminuria: multi-ethnic study of atherosclerosis.

Fibroblast growth factor 21 (FGF21) may play a role in the development of chronic kidney disease (CKD). We therefore investigated the relationship of plasma FGF21 levels with kidney function and albuminuria in the Multi-Ethnic Study of Atherosclerosis (MESA). The analysis included 5724 MESA participants ages 45-84 years between 2000 and 2002, free of clinically apparent cardiovascular disease (CVD). Participants were followed up in person at four additional clinic visits over 10 years. Plasma FGF21 levels were measured at baseline examination by enzyme-linked immunosorbent assay. Kidney function was assessed by estimated glomerular filtration rate (eGFR). Outcomes were urinary albumin:creatinine ratio (UACR) progression, incident CKD by eGFR (reaching eGFR <60 mL/min/1.73m2 with eGFR loss rate ≥1 mL/min/1.73m2 per year) and rapid kidney function decline (eGFR decline >5%/year). At baseline, higher FGF21 levels, assessed as both continuous and categorical quartile variables, were significantly associated with lower eGFR and higher UACR, after adjusting for demographic, socioeconomic and other confounding factors [adjusted mean differences of -2.63 mL/min/1.73m2 in eGFR and 0.134 in log normally transformed UACR (mg/g) for the highest FGF21 quartile compared with the lowest quartile, all P < 0.001]. However, in longitudinal analyses, baseline FGF21 levels did not predict incident CKD by eGFR, rapid kidney function decline or UACR progression. No significant interaction with sex and race/ethnicity was found (all P > 0.05). Our study does not support a role of FGF21 as a biomarker for predicting kidney function decline or albuminuria in adults free of clinically apparent CVD at baseline.

Mild Albuminuria Is a Risk Factor for Faster GFR Decline in the Nondiabetic Population

IntroductionA minimal increase in the albumin-to-creatinine ratio (ACR) predicts cardiovascular disease and mortality, but whether it predicts kidney function loss in nondiabetic persons is unclear. We investigated the association between ACR in the optimal or high-normal range and the rate of glomerular filtration rate (GFR) decline in a cohort from the general population without diabetes, cardiovascular, or chronic kidney disease.MethodsIn the Renal Iohexol Clearance Survey, we measured GFR using iohexol clearance in 1567 middle-aged nondiabetic individuals with an ACR <3.40 mg/mmol (30.0 mg/g) at baseline. The ACR was measured in unfrozen morning urine samples collected on 3 days before the GFR measurements. A total of 1278 (81%) participants had follow-up with GFR measurements after a median of 5.6 years.ResultsThe median ACR at baseline was 0.22 mg/mmol (interquartile range: 0.10−0.51 mg/mmol), the mean ± SD GFR was 104.0 ± 20.1 ml/min, and the mean ± SD GFR decline rate was −0.95 ± 2.23 ml/min per year. Higher baseline ACR levels were associated with a steeper GFR decline in adjusted linear mixed models. Study participants with ACR levels of 0.11 to 0.45 and 0.46 ± 3.40 mg/mmol had a 0.25 ml/min per year (95% confidence interval [95% CI]: −0.03 to 0.53) and 0.31 ml/min per year (95% CI: 0.02−0.60) steeper rate of decline than those with ACR ≤0.10 mg/mmol in multivariable-adjusted analyses. Among study participants with an ACR of <1.13 mg/mmol (defined as the optimal range), those with an ACR of 0.11 to 1.12 mg/mmol (n = 812) had a 0.28 ml/min per year (95% CI: 0.04−0.52) steeper rate of GFR decline than those with an ACR of ≤0.10 mg/mmol (n = 655).ConclusionA mildly increased ACR is an independent risk factor for faster GFR decline in nondiabetic individuals.

Kidney Biomarkers and Decline in eGFR in Patients with Type 2 Diabetes.

Biomarkers may improve identification of individuals at risk of eGFR decline who may benefit from intervention or dialysis planning. However, available biomarkers remain incompletely validated for risk stratification and prediction modeling. We examined serum cystatin C, urinary kidney injury molecule-1 (uKIM-1), and urinary neutrophil gelatinase-associated lipocalin (UNGAL) in 5367 individuals with type 2 diabetes mellitus and recent acute coronary syndromes enrolled in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial. Baseline concentrations and 6-month changes in biomarkers were also evaluated. Cox proportional regression was used to assess associations with a 50% decrease in eGFR, stage 5 CKD (eGFR<15 ml/min per 1.73 m2), or dialysis. eGFR decline occurred in 98 patients (1.8%) over a median of 1.5 years. All biomarkers individually were associated with higher risk of eGFR decline (P<0.001). However, when adjusting for baseline eGFR, proteinuria, and clinical factors, only baseline cystatin C (adjusted hazard ratio per 1 SD change, 1.66; 95% confidence interval, 1.41 to 1.96; P<0.001) and 6-month change in urinary neutrophil gelatinase-associated lipocalin (adjusted hazard ratio per 1 SD change, 1.07; 95% confidence interval, 1.02 to 1.12; P=0.004) independently associated with CKD progression. A base model for predicting kidney function decline with nine standard risk factors had strong discriminative ability (C-statistic 0.93). The addition of baseline cystatin C improved discrimination (C-statistic 0.94), but it failed to reclassify risk categories of individuals with and without eGFR decline. The addition of cystatin C or biomarkers of tubular injury did not meaningfully improve the prediction of eGFR decline beyond common clinical factors and routine laboratory data in a large cohort of patients with type 2 diabetes and recent acute coronary syndrome. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_01_16_CJASNPodcast_18_3_G.mp3.

Aortic-to-brachial stiffness gradient and kidney function in type 2 diabetes.

A reversed aortic-to-brachial stiffness gradient (ab-SG), defined as aortic pulse wave velocity (aPWV) greater than brachial PWV (bPWV), was recently shown to predict mortality independent of aPWV in dialysis patients. Patients with type 2 diabetes mellitus (T2DM) have increased risk of renal damage and exhibit haemodynamic abnormalities at rest and during exercise that may alter the ab-SG. This study aimed to examine ab-SG in patients with T2DM by comparison with nondiabetic controls during rest and exercise, and to determine associations between ab-SG, aPWV, and kidney function. Study participants were 60 patients with T2DM and 60 age and sex-matched nondiabetic controls (58 ± 8 years, 55% male both). ab-SG was defined as the quotient of bPWV (carotid-to-radial) and aPWV (carotid-to-femoral) recorded via applanation tonometry. Kidney function was assessed using estimated glomerular filtration rate (eGFR). The exercise substudy was undertaken in 21 patients with T2DM and 21 matched nondiabetic controls during semirecumbent exercise. ab-SG was significantly lower in patients with T2DM (0.99 ± 0.2 vs. 1.2 ± 0.3, P < 0.001) and aPWV, but not bPWV, was significantly higher (P < 0.001 and P = 0.25). A total of 58% of patients with T2DM vs. 27% of nondiabetic controls (χ = 11.0, P < 0.001) had a reversed ab-SG (aPWV ≥ bPWV). ab-SG predicted eGFR independent of age, sex, T2DM status, and cardiovascular risk factors (β = 13.2, P = 0.024), whereas aPWV did not (β = -0.88, P = 0.30). Exercise ab-SG was significantly lower in patients with T2DM (0.97 ± 0.2 vs. 1.2 ± 0.2, P < 0.001), but did not predict eGFR. Patients with T2DM have a reversed ab-SG during rest and exercise. Resting ab-SG predicts kidney function independent of aPWV, implying a reversed ab-SG may have a pathophysiological function.

Carotid Intima-Media Thickness and Incident ESRD: The Atherosclerosis Risk in Communities (ARIC) Study.

Carotid intima-media thickness has been reported to predict kidney function decline. However, whether carotid intima-media thickness is associated with a hard kidney end point, ESRD, has not been investigated. We studied 13,197 Atherosclerosis Risk in Communities participants at visit 1 (1987-1989) without history of cardiovascular disease, including coronary heart disease, stroke, and heart failure, at baseline and assessed whether carotid intima-media thickness measured by B-mode ultrasound is associated with ESRD risk using Cox proportional hazards models. Regarding carotid intima-media thickness parameters, we investigated the mean and maximum values of overall and segment-specific (common, bifurcation, and internal carotid arteries) measurements. Mean age was 54.0 (SD=5.7) years old, and there were 3373 (25.6%) blacks and 7370 (55.8%) women. During a median follow-up of 22.7 years, 433 participants developed ESRD (1.4/1000 person-years). After adjusting for shared risk factors for atherosclerosis and kidney disease, including baseline kidney function, carotid intima-media thickness was significantly associated with ESRD risk (hazard ratio [HR] between quartiles 4 and 1, 1.46; 95% confidence interval [95% CI], 1.02 to 2.08 for overall mean intima-media thickness and HR between quartiles 4 and 1, 1.75; 95% CI, 1.24 to 2.48 for overall maximum intima-media thickness). The associations were largely consistent in demographic and clinical subgroups. When we explored segment-specific intima-media thicknesses, the associations with ESRD were most robust for bifurcation carotid (e.g., adjusted HR between quartiles 4 and 1 of mean intima-media thickness, 1.49; 95% CI, 1.04 to 2.13 for bifurcation; adjusted HR between quartiles 4 and 1 of mean intima-media thickness, 1.36; 95% CI, 0.94 to 1.97 for common; and adjusted HR between quartiles 4 and 1 of mean intima-media thickness, 0.93; 95% CI, 0.67 to 1.29 for internal). Carotid intima-media thickness was independently associated with incident ESRD in the general population, suggesting the shared etiology of atherosclerosis and ESRD.