Measure Of Kidney Function Research Articles

Kidney Ultrasound Findings in Sickle Cell Anemia According to Kidney Disease and the APOL1 G1/G2 Risk Variants

Sickle cell anemia (SCA) is an inherited red blood cell disorder that leads to kidney disease in up to two-thirds of adults. Ultrasound is a non-invasive modality that can identify pathologic changes in the kidney. Previous studies have demonstrated that SCA patients have larger and more echogenic kidneys compared to non-SCA patients, but the association of abnormal kidney ultrasound findings with kidney function or with the APOL1 G1/G2 kidney risk variants in SCA is not clear.We conducted a retrospective analysis to evaluate the association of kidney ultrasound findings with markers of kidney function and the APOL1 G1/G2 risk variants at our institution. Clinical and laboratory variables were collected closest to the time of the ultrasound. Ultrasounds were independently reviewed by radiologists who were blinded to the measures of kidney function and APOL1 G1/G2 risk status. APOL1 G1 and G2 and α-thalassemia status were determined by PCR. Homozygous or compound heterozygous inheritance of the G1 and/or G2 risk variants was defined as high risk. Echogenicity was classified as normal if the renal cortex was less echogenic than the adjacent liver or spleen, mild if the renal cortex was the same or mildly more echogenic than the adjacent liver or spleen, and markedly increased if the renal cortex echogenicity was obliterating the renal sinus. Normal kidney size ranges were defined as 10-14cm in men and 9-13cm in women. Hemoglobinuria was defined as urinalysis positive for blood by dipstick with < 2 red blood cells per high power field. Comparisons of linear and categorical variables by degree of echogenicity or kidney size were performed using the linear trend test or Cochran's test of linear trend, respectively.Between 2/2002 and 2/2018, 199 SCA patients had an abdominal or retroperitoneal ultrasound performed with assessment of the kidneys. The median age of the cohort was 35 years (interquartile range [IQR], 24-46 years) and 37% were male. Echogenicity of the kidneys was normal in 125 (63%), mildly increased in 43 (22%), and markedly increased in 31 (16%) SCA patients. Incremental kidney echogenicity was associated with older age, increased albuminuria, and lower estimated glomerular filtration rate (eGFR) (P<0.0001; Figure 1). Kidney echogenicity was greater in SCA patients with hemoglobinuria (P=0.03). Co-inheritance of α-thalassemia was associated with reduced kidney echogenicity (P=0.0002) and high risk APOL1 G1/G2 status was associated with increased kidney echogenicity (P=0.03). On logistic regression analysis, abnormal kidney echogenicity was independently associated with older age (10-year increase OR 2.6, P<0.0001), α-thalassemia status (OR 0.3, P<0.0001), and APOL1 G1/G2 risk status (OR 4.9, P=0.007).Kidney size measurements were categorized as small in 20 (10%), normal size in 157 (79%), and large in 22 (11%) of SCA patients. Smaller kidneys were associated with older age (P=0.03), increased albuminuria (P=0.04) and a lower eGFR (P=0.003) (Figure 2). We did not observe significant associations between kidney size and hemoglobinuria, α-thalassemia status, or APOL1 G1/G2 risk variant status.In conclusion, we demonstrate that in SCA patients, increased kidney echogenicity and smaller kidney size are associated with older age, reduced eGFR, and worsening albuminuria. Furthermore, absence of α-thalassemia, and presence of the APOL1 G1/G2 kidney risk variants are associated with the degree of kidney echogenicity. Future studies evaluating the utility of kidney ultrasounds as a clinical tool to monitor kidney disease and its progression in SCA are warranted. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Sex Hormones and Measures of Kidney Function in the Diabetes Prevention Program Outcomes Study.

Despite sex differences in chronic kidney disease (CKD) onset and progression, it is unclear whether endogenous sex hormones are associated with kidney function in persons without CKD. We conducted a secondary analysis of the Diabetes Prevention Program (DPP) and its follow-up observational study, the DPP Outcomes Study, over 11 years. Participants included overweight and glucose-intolerant men (n = 889) and pre- and postmenopausal women (n = 1281) not using exogenous sex hormones and whose urine albumin-to-creatinine ratio (ACR) was <30 mg/g and normal estimated glomerular filtration ratio (eGFR) was ≥60 mL/min/1.73 m2 at randomization. We examined the association between sex hormone levels and incidence of low eGFR and/or ACR ≥30 mg/g on at least one measurement. At randomization, the mean (SD) eGFR was 94 (15) mL/min/1.73 m2; the median ACR (interquartile range) was 4.5 (3.3 to 7.6) mg/g. During follow-up, 187 men (24.6%) and 263 women (24.2%) had incident albuminuria and 136 men (17.9%) and 123 women (11.3%) had incident low eGFR. Among men, higher baseline sex hormone-binding globulin (SHBG) level was associated with reduced low eGFR risk (hazard ratio per SD, 0.80; 95% CI, 0.57 to 0.90) in adjusted analyses. No significant associations were observed among women. There were significant interactions between sex steroid levels and low eGFR by randomization arm. Sex steroids were not associated with development of low eGFR or albuminuria. Among men, higher SHBG level was associated with reduced risk of low eGFR on at least one measurement.

Risk Factors for Recurrent Acute Kidney Injury in a Large Population-Based Cohort

Acute kidney injury (AKI) has numerous sequelae. Repeated episodes of AKI may be an important determinant of adverse outcomes, including chronic kidney disease and death. In a population-based cohort study, we sought to determine the incidence of and predictors for recurrent AKI. Retrospective cohort study. 38,659 hospitalized members of Kaiser Permanente Northern California who experienced an episode of AKI from 2006 to2013. Demographic, clinical, and laboratory data, including baseline kidney function, proteinuria, hemoglobin level, comorbid conditions, and severity of AKI. Incidence and predictors of recurrent AKI. Multivariable Cox proportional hazard regression. 11,048 (28.6%) experienced a second hospitalization complicated by AKI during follow-up (11.2 episodes/100 person-years), with the second episode of AKI occurring a median of 0.6 (interquartile range, 0.2-1.9) years after the first hospitalization. In multivariable analyses, older age, black race, and Hispanic ethnicity were associated with recurrent AKI, along with lower estimated glomerular filtration rate, proteinuria, and anemia. Concomitant conditions, including heart failure, acute coronary syndrome, diabetes, and chronic liver disease, were also multivariable predictors of recurrent AKI. Those who had higher acuity of illness during the initial hospitalization were more likely to have recurrent AKI, but greater AKI severity of the index episode was not independently associated with increased risk for recurrent AKI. In multivariable analysis of matched patients, recurrent AKI was associated with an increased rate of death (HR, 1.66; 95% CI, 1.57-1.77). Analyses were based on clinically available data, rather than protocol-driven timed measurements of kidney function. Recurrent AKI is a common occurrence after a hospitalization complicated by AKI. Based on routinely available patient characteristics, our findings could facilitate identification of the subgroup of patients with AKI who may benefit from more intensive follow-up to potentially avoid recurrent AKI episodes.

Design and methodology of the screening for CKD among older patients across Europe (SCOPE) study: a multicenter cohort observational study

BackgroundDecline of renal function is common in older persons and the prevalence of chronic kidney disease (CKD) is rising with ageing. CKD affects different outcomes relevant to older persons, additionally to morbidity and mortality which makes CKD a relevant health burden in this population. Still, accurate laboratory measurement of kidney function is under debate, since current creatinine-based equations have a certain degree of inaccuracy when used in the older population. The aims of the study are as follows: to assess kidney function in a cohort of 75+ older persons using existing methodologies for CKD screening; to investigate existing and innovative biomarkers of CKD in this cohort, and to align laboratory and biomarker results with medical and functional data obtained from this cohort. The study was registered at ClinicalTrials.gov, identifier NCT02691546, February 25th 2016.Methods/designAn observational, multinational, multicenter, prospective cohort study in community dwelling persons aged 75 years and over, visiting the outpatient clinics of participating institutions. The study will enroll 2450 participants and is carried out in Austria, Germany, Israel, Italy, the Netherlands, Poland and Spain. Participants will undergo clinical and laboratory evaluations at baseline and after 12 and 24 months- follow-up. Clinical evaluation also includes a comprehensive geriatric assessment (CGA). Local laboratory will be used for ‘basic’ parameters (including serum creatinine and albumin-to-creatinine ratio), whereas biomarker assessment will be conducted centrally. An intermediate telephone follow-up will be carried out at 6 and 18 months.DiscussionCombining the use of CGA and the investigation of novel and existing independent biomarkers within the SCOPE study will help to provide evidence in the development of European guidelines and recommendations in the screening and management of CKD in older people.Trial registrationThis study was registered prospectively on the 25th February 2016 at clinicaltrials.gov (NCT02691546).

Incident Type 2 Diabetes Among Individuals With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Few studies have examined incident type 2 diabetes mellitus (T2DM) in chronic kidney disease (CKD). Our objective was to examine rates of and risk factors for T2DM in CKD, using several alternative measures of glycemic control. Prospective cohort study. 1,713 participants with reduced glomerular filtration rates and without diabetes at baseline, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Measures of kidney function and damage, fasting blood glucose, hemoglobin A1c (HbA1c), HOMA-IR (homeostatic model assessment of insulin resistance), demographics, family history of diabetes mellitus (DM), smoking status, medication use, systolic blood pressure, triglyceride level, high-density lipoprotein cholesterol level, body mass index, and physical activity. Incident T2DM (defined as fasting blood glucose≥ 126mg/dL or prescription of insulin or oral hypoglycemic agents). Concordance between fasting blood glucose and HbA1c levels was assessed using κ. Cause-specific hazards modeling, treating death and end-stage kidney disease as competing events, was used to predict incident T2DM. Overall T2DM incidence rate was 17.81 cases/1,000 person-years. Concordance between fasting blood glucose and HbA1c levels was low (κ for categorical versions of fasting blood glucose and HbA1c= 13%). Unadjusted associations of measures of kidney function and damage with incident T2DM were nonsignificant (P≥ 0.4). In multivariable models, T2DM was significantly associated with fasting blood glucose level (P= 0.002) and family history of DM (P= 0.03). The adjusted association of HOMA-IR with T2DM was comparable to that of fasting blood glucose level; the association of HbA1c level was nonsignificant (P≥ 0.1). Harrell's C for the models ranged from 0.62 to 0.68. Limited number of outcome events; predictors limited to measures taken at baseline. The T2DM incidence rate among individuals with CKD is markedly higher than in the general population, supporting the need for greater vigilance in this population. Measures of glycemic control and family history of DM were independently associated with incident T2DM.

Advanced Heart Failure Therapies and Cardiorenal Syndrome.

Heart failure (HF) is extremely prevalent and for those with end-stage (stage D) disease, 1-year survival is only 25-50%. Several studies have captured the mortality impact of kidney disease on patients with HF, and measures of kidney function are a component of many HF risk stratification scores. The management of advanced HF complicated by cardiorenal syndrome (CRS) is challenging, and irreversible kidney failure often limits patient candidacy for advanced HF therapies, such as transplant or left ventricular assist device therapy. Thus, prompt institution of aggressive therapy is warranted in stage D HF patients with CRS to prevent irreversible kidney failure. In this chapter, we discuss the assessment and management of patients with CRS with end-stage HF. In addition to discussing medical therapy aimed at decongestion and increased cardiac inotropy, we provide a summary of temporary circulatory support devices that can be considered for those whom hospice is not desired. In all circumstances, a close collaboration between the advanced HF specialist and nephrologist is needed to achieve the best patient outcomes.

Renal Function and exposure to Bisphenol A and phthalates in children with Chronic Kidney Disease

Rationale and objectiveExposure to Bisphenol A (BPA) and phthalates is ubiquitous among adults and children in the United States. Among children and adolescents, those with chronic kidney disease (CKD) are potentially at greater risk of adverse effects from BPA and phthalate exposure. The objective of this study was to evaluate BPA and phthalate exposure among children with CKD and evaluate associations with three measures of kidney function. Study designCross sectional study. Setting, participants, and measurementsThe CKD population was represented by the Chronic Kidney Disease in Children (CKiD) Study, a multicenter, prospective cohort study of children with impaired kidney function in the US. The main outcome was assessment of the relationship between chemical exposures and clinical laboratory findings at enrollment into CKiD. Data collected at baseline from participants 1 to 17 years old (N = 538) were analyzed. Urinary BPA and phthalate levels were evaluated at this time point. Data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative pediatric population, were used for comparison to the CKiD cohort. ResultsUrinary BPA and phthalate levels in the CKiD population were consistently lower than levels detected in healthy children. Additionally, BPA was not significantly associated with blood pressure, proteinuria, or estimated glomerular filtration rate (eGFR). Within the CKiD population, for select individual and combined phthalates, there was an inverse relationship with the urinary protein:creatinine ratio (LMW phthalates, − 9.53% change; 95% CI: − 14.21, − 4.21; p = 0.001), and in most cases, a positive relationship with eGFR (LMW phthalates, a 3.46 unit increase in eGFR, 95% CI: 1.85, 5.07; p < 0.001). LimitationsLack of longitudinal data, limited assessment of diet and nutritional status. ConclusionIn the study cohort, children with CKD did not have increased exposure to BPA and phthalates. Longitudinal studies with repeated measures are likely to be more informative about the possible health effects of prolonged exposure to BPA and phthalates in pediatric patients with CKD.

Chronic Kidney Disease Is Associated With Greater Bone Marrow Adiposity

Bone marrow adiposity is associated with aging, osteoporosis, and reduced hematopoiesis, as well as anorexia nervosa, but little is known about the underlying mechanisms that affect marrow adiposity. Chronic kidney disease (CKD) may influence bone marrow adipose tissue (BMAT), possibly through loss of lean mass or higher circulating levels of sclerostin. To test these hypotheses, we investigated the cross-sectional association between estimated glomerular filtration rate (eGFR) as a measure of kidney function and 1 H-MRS-based measurement of vertebral BMAT (L1 to L4) in 475 older adults from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study. Mean BMAT was compared in those with eGFR >60 (n = 297) versus those with eGFR 45 to 60 (n = 120) or eGFR <45 (n = 58) using linear regression models. Participants had a mean age of 81.5 (SD 4.1) years, mean eGFR of 64.3 (SD 16.1) mL/min/1.734 cm2 , mean BMAT of 54.5% (SD 8.5); 48.2% were women. In unadjusted and adjusted models (age, visit window, gender, diabetes and visceral adipose tissue), BMAT was higher in those with eGFR <45 (adjusted mean 58.5%; 95% CI, 56.2 to 60.7) compared with those with eGFR >60 (adjusted mean 53.8%; 95% CI, 52.8 to 54.8) (p = 0.0002). BMAT did not differ in those with eGFR 45 to 60 (adjusted mean 54.3%; 95% CI, 52.8 to 55.9) compared with those with eGFR >60 (p = 0.58). In a subgroup of participants with serum sclerostin available (n = 253), additional adjustment for sclerostin attenuated the difference in adjusted mean vertebral BMAT between those with eGFR <45 versus >60 from 3.7% (p = 0.04) to 2.4% (p = 0.20). CKD stage 3b or worse was associated with greater bone marrow adiposity; this association may be partially mediated by sclerostin. © 2018 American Society for Bone and Mineral Research.

Associations between longitudinal serum perfluoroalkyl substance (PFAS) levels and measures of thyroid hormone, kidney function, and body mass index in the Fernald Community Cohort

Perfluoroalkyl substances (PFAS) are a diverse class of manufactured compounds used in a wide range of industrial processes and consumer products and have been detected in human serum worldwide. Previous cross-sectional and cohort studies in humans have suggested exposure to PFAS is associated with a wide array of chronic diseases, including endocrine disruption, developmental health effects, cancer and metabolic changes. We examined the associations between a panel of eight PFAS and indicators of thyroid disruption, kidney function, and body mass index (BMI), all of which were measured at repeated time points (1990–2008) over the course of the study. Participants (N = 210) were selected from the Fernald Community Cohort based on household water supply from a PFAS-contaminated aquifer. In adjusted repeated measures models, we observed several notable associations between serum PFAS and thyroid hormones as well as kidney function as measured by estimated glomerular filtration rate (eGFR). An interquartile (IQR) increase in serum PFOS was associated with a 9.75% (95% CI = 1.72, 18.4) increase in thyroid stimulating hormone. An IQR increase in serum PFNA, PFHxS, and PFDeA was associated with a −1.61% (95% CI = −3.53, −0.59), −2.06% (95% CI = −3.53, −0.59), and −2.20% (95% CI = −4.25, −0.14) change in eGFR, respectively. On the other hand, an IQR increase in serum Me-PFOSA was associated with a 1.53% (95% CI = 0.34, 2.73) increase in eGFR. No significant associations with BMI and serum PFAS were noted. Our findings are in agreement with previous reports that serum PFAS are associated with altered kidney and thyroid function.

Association of rs7903146 polymorphism in the TCF7L2 gene with diabetic nephropathy and decreased estimated GFR in an Arab population in southwest Iran

Background: Transcription factor 7-like 2 (TCF7L2) acts as a downstream effector in the Wnt signaling pathway. It plays important roles in the proliferation and differentiation of islet betacell, insulin secretion and kidney development. Objectives: This study aimed to demonstrate whether rs7903146 variant is associated with diabetic nephropathy (DN) and measures of kidney function in a diabetic and healthy Arab population in southwest of Iran. Patients and Methods: This study is comprised of 132 diabetic subjects (T2DM) and 66 healthy participants. The diabetic subgroups were composed of patients with DN (n=56) and early onset of diabetes (n=71). The rs7903146 polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in all the participants. Blood glucose, HbA1c, blood urea nitrogen (BUN), creatinine and urinary albumin were evaluated by a biochemistry analyzer and enzyme-linked immunosorbent assay (ELISA) was employed for cystatin C measurement. Results: The frequency of genotypes was significantly different between all the diabetic cases and control subjects (P<0.05). The TT variant odds ratio (OR) versus CT/CC genotypes for diabetes was 2.47 (95% CI 1.11-5.48). An association was observed between TT homozygous and DN (OR for TT 2.78, 1.13-6.84). Early onset diabetic patients showed stronger association (OR: 4.64, 1.64-13.14, P=0.003). The TT genotype was also found to be a risk variant for decreased estimated glomerular filtration rate (eGFR)(Cys-Cr) below 60 mL/min/1.73 m2 (OR: 3.36, 1.4-8.1, P=0.005). Conclusions: The results confirmed that the TCF7L2 gene rs7903146 variants are significantly associated with T2DM in Arab population of Iran. The TT genotype of this SNP is also predisposed to the risk of developing DN especially in subjects with early onset diabetes. Patients with TT genotype were also at risk of decreased GFR.

Serum Calcification Propensity and Fetuin-A: Biomarkers of Cardiovascular Disease in Kidney Transplant Recipients

Background: “T50,” shortened transformation time from primary to secondary calciprotein particles may reflect deranged mineral metabolism predisposing to vascular calcification and cardiovascular disease (CVD). The glycoprotein fetuin-A is a major T50 determinant. Methods: The Folic Acid For Vascular Outcome Prevention In Transplantation (FAVORIT) cohort is a completed, large, multiethnic controlled clinical trial cohort of chronic, stable kidney transplant recipients (KTRs). We conducted a longitudinal case-cohort analysis using a randomly selected subcohort of patients, and all individual cases who developed CVD. Serum T50 and fetuin-A were determined in this total of n = 685 FAVORIT trial participants at randomization. Results: During a median surveillance of 2.18-years, 311 incident or recurrent CVD events occurred. Shorter T50 (minutes) or reduced fetuin-A concentrations (g/L) were associated with CVD after adjustment for treatment assignment, systolic blood pressure, age, sex, race, preexisting CVD and diabetes, smoking, body mass index, total cholesterol/HDL cholesterol, kidney allograft vintage and type, calcineurin inhibitor, or lipid-lowering drug use, estimated glomerular filtration rate, and urinary albumin/creatinine: tertile 1 (lowest) to tertile 3 (highest) comparisons, T50, (hazard ratio [HR] 1.86; 95% CI 1.20–2.89); fetuin-A, (HR 2.25; 95% CI 1.38–3.69). Elevated high sensitivity c-reactive protein (hsCRP) was an effect modifier of both these associations. Conclusions: Shortened T50, as well as reduced fetuin-A levels, ostensible promoters of vascular calcification, remained associated with greater risk for CVD outcomes, after adjustment for major CVD risk factors, measures of kidney function and damage, and KTR clinical characteristics and demographics, in a large, multiethnic cohort of long-term KTRs. Increased hsCRP was an effect modifier of these CVD risk associations.

A Systematic Review of Renal Health in Healthy Individuals Associated with Protein Intake above the US Recommended Daily Allowance in Randomized Controlled Trials and Observational Studies.

A systematic review was used to identify randomized controlled trials (RCTs) and observational epidemiologic studies (OBSs) that examined protein intake consistent with either the US RDA (0.8 g/kg or 10–15% of energy) or a higher protein intake (≥20% but <35% of energy or ≥10% higher than a comparison intake) and reported measures of kidney function. Studies (n = 26) of healthy, free-living adults (>18 y old) with or without metabolic disease risk factors were included. Studies of subjects with overt disease, such as chronic kidney, end-stage renal disease, cancer, or organ transplant, were excluded. The most commonly reported variable was glomerular filtration rate (GFR), with 13 RCTs comparing GFRs obtained with normal and higher protein intakes. Most (n = 8), but not all (n = 5), RCTs reported significantly higher GFRs in response to increased protein intake, and all rates were consistent with normal kidney function in healthy adults. The evidence from the current review is limited and inconsistent with regard to the role of protein intake and the risk of kidney stones. Increased protein intake had little or no effect on blood markers of kidney function. Evidence reported here suggests that protein intake above the US RDA has no adverse effect on blood pressure. All included studies were of moderate to high risk of bias and, with the exception of 2 included cohorts, were limited in duration (i.e. <6 mo). Data in the current review are insufficient to determine if increased protein intake from a particular source, i.e., plant or animal, influences kidney health outcomes. These data further indicate that, at least in the short term, higher protein intake within the range of recommended intakes for protein is consistent with normal kidney function in healthy individuals.

Estimating Glomerular Filtration Rate Calculated by Serum Creatinine Lacks Precision and Accuracy in Adults with Type 2 Diabetes with Preserved Renal Function

We evaluated the performance of creatinine-based estimating equations for glomerular filtration rate (GFR) in adults with type 2 diabetes without nephropathy compared to measured GFR by gold-standard inulin clearance methods. mGFR was performed 4 times over the course of a 1 month treatment period in the context of a small randomized placebo-controlled trial measuring the intrarenal hemodynamics function responses to the dipeptidyl peptidase 4 inhibitor sitagliptin. Thirty-two adults with type 2 diabetes (randomized 1:1 to placebo or sitagliptin) completed the trial, and all participants underwent mGFR by inulin clearance and GFR estimated by serum creatinine using the MDRD (eGFRMDRD) and CKD-EPI (eGFRCKD-EPI). Performance of eGFR equations was evaluated using measurements of bias (mean difference), precision (standard deviations [SD]), and inaccuracy (defined as the proportion of eGFR that differed by &amp;gt;20% of mGFR). The effects of treatment and time on bias were evaluated using linear mixed effects models. Mean±SD age, diabetes duration, HbA1c, and BMI was 60±8 years, 9±7 years, 7.2±0.8%, and 31.0±6.2 kg/m2, respectively, and 12(38%) participants were female. At baseline, mean mGFR was 113±24, mean eGFRMDRD was 93±12, and mean eGFRCKD-EPI was 94±9, all in mL/min/1.73m2. When all 128 observations (32 participants measured 4 times) were evaluated, both equations substantially underestimated mGFR. For the eGFRMDRD, mean bias was -21.5 mL/min/1.73m2, precision was 22.7 mL/min/1.73m2, and 46% of observations differed by more than 20%. Results were similar for eGFRCKD-EPI. No time or treatment effects on bias were observed. In adults with type 2 diabetes, eGFR equations underestimated mGFR, lacked precision and accuracy, and had lower performance at higher ranges of mGFR. More accurate measures of kidney function may improve clinical decision-making in adults with type 2 diabetes. Disclosure J.A. Lovshin: Other Relationship; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi, Merck Sharp &amp; Dohme Corp.. Other Relationship; Self; Novo Nordisk Inc.. L. Lovblom: None. P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. Y. Lytvyn: None. H. Rajasekeran: None. D. Scarr: None. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc. D. Cherney: Consultant; Self; AbbVie Inc.. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company. Consultant; Self; Sanofi. Other Relationship; Self; Merck &amp; Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Self; Janssen Pharmaceuticals, Inc..

Calcineurin Inhibitor and Nonsteroidal Anti‐inflammatory Drug Interaction: Implications of Changes in Renal Function Associated With Concurrent Use

Evidence for a drug interaction between calcineurin inhibitors (CNIs) and nonsteroidal anti-inflammatory drugs (NSAIDs) is meager, and the magnitude of risk for adverse renal effects associated with this interaction is unclear. To explicate these uncertainties, sequential measures of kidney function were evaluated in hospitalized adult solid organ or allogeneic hematopoietic stem cell transplant recipients who received maintenance CNI therapy and concurrent treatment with an oral or parenteral NSAID. A comparator group of closely matched transplant recipients on CNI therapy who did not receive NSAID treatment during hospitalization was similarly evaluated. Among inpatients on CNIs, treatment-emergent acute kidney injury occurred in 5 of 41 (12.2%) patients exposed to concurrent NSAIDs and in 7 of 126 (5.6%) of matched patients who were not exposed to NSAIDs (relative risk ratio 2.20, 95% confidence interval 0.74 to 6.54). During hospitalization, an increase in serum creatinine above baseline occurred in 80.5% of patients on CNI therapy who were exposed to NSAIDs as compared with 56.3% of patients on CNIs who were not exposed (P = .001). NSAID administration was an independent predictor for a rapid increase in serum creatinine (P = .026). The event rate for worsened renal function was highest among patients exposed to parenteral ketorolac. Because the likelihood of developing treatment-related worsening of renal function is increased with combined use of CNIs and NSAIDs, concurrent use of these medications is inadvisable. Patients and clinicians should be counseled accordingly.

Protective effect of the BET protein inhibitor JQ1 in cisplatin-induced nephrotoxicity.

As a potent chemotherapy drug, cisplatin is also notorious for its side-effects including nephrotoxicity in kidneys, presenting a pressing need to identify renoprotective agents. Cisplatin nephrotoxicity involves epigenetic regulations, including changes in histone acetylation. Bromodomain and extraterminal (BET) proteins are "readers" of the epigenetic code of histone acetylation. Here, we investigated the potential renoprotective effects of JQ1, a small molecule inhibitor of BET proteins. We show that JQ1 significantly ameliorated cisplatin-induced nephrotoxicity in mice as indicated by the measurements of kidney function, histopathology, and renal tubular apoptosis. JQ1 also partially prevented the body weight loss during cisplatin treatment in mice. Consistently, JQ1 inhibited cisplatin-induced apoptosis in renal proximal tubular cells. Mechanistically, JQ1 suppressed cisplatin-induced phosphorylation or activation of p53 and Chk2, key events in DNA damage response. JQ1 also attenuated cisplatin-induced MAP kinase (p38, ERK1/2, and JNK) activation. In addition, JQ1 enhanced the expression of antioxidant genes including nuclear factor erythroid 2-related factor 2 and heme oxygenase-1, while diminishing the expression of the nitrosative protein inducible nitric oxide synthase. JQ1 did not suppress cisplatin-induced apoptosis in A549 nonsmall cell lung cancer cells and AGS gastric cancer cells. These results suggest that JQ1 may protect against cisplatin nephrotoxicity by suppressing DNA damage response, p53, MAP kinases, and oxidative/nitrosative stress pathways.

Chronic kidney disease and peripheral nerve function in the Health, Aging and Body Composition Study.

Chronic kidney disease (CKD) is associated with poor mobility. Peripheral nerve function alterations play a significant role in low mobility. We tested the hypothesis that early CKD is associated with altered sensory, motor and autonomic nerve function. Participants in the Health, Aging and Body Composition cohort who had kidney function measures in Year 3 (1999-2000) and nerve function measurements at Year 4 (2000-01) were analyzed (n = 2290). Sensory (vibration threshold, monofilament insensitivity to light and standard touch), motor [compound motor action potentials (CMAPs), nerve conduction velocities (NCVs)] and autonomic (heart rate response and recovery after a 400-m walk test) nerve function as well as participant characteristics were compared across cystatin C- and creatinine-based estimated glomerular filtration rate categorized as ≤60 (CKD) or >60 mL/min/1.73 m2 (non-CKD). The association between CKD and nerve function was examined with logistic regression adjusted for covariates. Participants with CKD (n = 476) were older (77 ± 3 versus 75 ± 3 years; P < 0.05) and had a higher prevalence of diabetes (20.6% versus 13.1%; P < 0.001). CKD was associated with higher odds for vibration detection threshold {odds ratio [OR] 1.7 [95% confidence interval (CI) 1.1-2.7]} and light touch insensitivity [OR 1.4 (95% CI 1.1-1.7)]. CMAPs and NCVs were not significantly different between CKD and non-CKD patients. In adjusted analyses, participants with CKD had higher odds of an abnormal heart rate response [OR 1.6 (95% CI 1.1-2.2)] and poor heart rate recovery [OR 1.5 (95% CI 1.1-2.0)]. CKD is associated with changes in sensory and autonomic nerve function, even after adjustment for demographics and comorbidities, including diabetes. Longitudinal studies in CKD are needed to determine the contribution of nerve impairments to clinically important outcomes.

Zinc-alpha 2-glycoprotein serum level in Egyptian females with preeclampsia and eclampsia

Objective: The aim of this study was to measure serum zinc-α2-glycoprotein (ZAG) in pregnant Egyptian females with preeclampsia and eclampsia and to correlate its levels to biochemical measures of kidney function, lipid and glucose metabolism.Study Design: It was a retrospective study.Patients and Methods: This study measured ZAG levels by enzyme linked immunosorbent assay (ELISA) in pregnant females with preeclampsia (PE) (no. = 40) and eclampsia (no.=20) and were compared to healthy gestational age-matched subjects (no.=20). In addition, the association of ZAG with kidney function, lipid and glucose metabolism was studied.Results: Significant difference was detected on comparing the different groups regarding ZAG levels (p = 0.001). Furthermore, ZAG was positively correlated to systolic blood pressure, urinary protein, fasting insulin and HOMA-IR.After adjusting for other parameters,the association between ZAG and SBP, urinary protein, serum insulin and HOMA-IR remained significant by multivariate linear regression analysis.Conclusion: The study noted that maternal ZAG serum levels are significantly increased in PE

Point-of-care creatinine testing for kidney function measurement prior to contrast-enhanced diagnostic imaging: evaluation of the performance of three systems for clinical utility.

Acute kidney injury (AKI) can occur rarely in patients exposed to iodinated contrast and result in contrast-induced AKI (CI-AKI). A key risk factor is the presence of preexisting chronic kidney disease (CKD); therefore, it is important to assess patient risk and obtain kidney function measurement prior to administration. Point-of-care (PoC) testing provides an alternative strategy but there remains uncertainty, with respect to diagnostic accuracy and clinical utility. A device study compared three PoC analysers (Nova StatSensor, Abbott i-STAT and Radiometer ABL800 FLEX) with a reference laboratory standard (Roche Cobas 8000 series, enzymatic creatinine). Three hundred adult patients attending a UK hospital phlebotomy department were recruited to have additional blood samples for analysis on the PoC devices. The ABL800 FLEX had the strongest concordance with laboratory measured serum creatinine (mean bias=-0.86, 95% limits of agreement=-9.6 to 7.9) followed by the i-STAT (average bias=3.88, 95% limits of agreement=-8.8 to 16.6) and StatSensor (average bias=3.56, 95% limits of agreement=-27.7 to 34.8). In risk classification, the ABL800 FLEX and i-STAT identified all patients with an eGFR≤30, whereas the StatSensor resulted in a small number of missed high-risk cases (n=4/13) and also operated outside of the established performance goals. The screening of patients at risk of CI-AKI may be feasible with PoC technology. However, in this study, it was identified that the analyser concordance with the laboratory reference varies. It is proposed that further research exploring PoC implementation in imaging department pathways is needed.

Recent advances of metabolomics techniques for diagnosis and treatment of kidney disease

Kidney disease(KD) is a major challenge for global public healthcare systems. Traditional biomarkers (such as serum creatinine and urea) for measuring kidney function are not sufficient sensitivity and specificity. They are not only affected by many factors, but also were only increase significantly in severe KD. Therefore, more sensitive biomarkers for evaluation of KD is essential. Metabolomics is a promising tool that identify non-targeted, global small-molecule metabolite profiles of complex samples, such as biofluids and tissues extract. The application of metabolomics in KD studies has developed rapidly in the past years. Many benefits have been shown from the use of metabolomics in identifying biomarkers for KD. In particular, metabolomic approaches have the potential to diagnose KD with a higher accuracy than traditional diagnostic methods. Metabolomics in KD research has been expanded from experimental study into clinical applications.(Chin J Lab Med, 2018, 41: 246-250) Key words: Kidney disease; Biomarker; Metabonome/metabolome; Metabonomics/metabolomics

Proximal Tubular Secretory Clearance: A Neglected Partner of Kidney Function.

The secretion of small molecules by the proximal tubules of the kidneys represents a vital homeostatic function for rapidly clearing endogenous solutes and medications from the circulation. After filtration at the glomerulus, renal blood flow is directed through a network of peritubular capillaries, where transporters of the proximal tubules actively secrete putative uremic toxins and hundreds of commonly prescribed drugs into the urine, including protein-bound substances that cannot readily cross the glomerular basement membrane. Despite its central physiologic importance, tubular secretory clearance is rarely measured or even estimated in clinical or research settings. Major barriers to estimating tubular solute clearance include uncertainty regarding optimal endogenous secretory markers and a lack of standardized laboratory assays. The creation of new methods to measure tubular secretion could catalyze advances in kidney disease research and clinical care. Differences in secretory clearance relative to the GFR could help distinguish among the causes of CKD, particularly for disorders that primarily affect the tubulointerstitium. As the primary mechanism by which the kidneys excrete medications, tubular secretory clearance offers promise for improving kidney medication dosing, which is currently exclusively on the basis of filtration. The differing metabolic profiles of retained solutes eliminated by secretion versus glomerular filtration suggest that secretory clearance could uniquely inform uremic toxicity, refine existing measures of residual kidney function, and improve prediction of cardiovascular and kidney disease outcomes. Interdisciplinary research across clinical, translational, and laboratory medicine is needed to bring this often neglected kidney function into the limelight.