Rapid Kidney Research Articles

TV Watching, but Not Physical Activity, Is Associated With Change in Kidney Function in Older Adults.

Physical activity (PA) may play a role in preserving kidney health. The purpose of this study was to determine if PA and sedentary behavior are associated with incident chronic kidney disease (CKD) and change in kidney function in older adults. The Health, Aging, and Body Composition study is a prospective cohort of 3075 well-functioning older adults. PA and television watching was measured by self-report, and serum cystatin C was used to estimate glomerular filtration rate (eGFR). CKD was defined as an eGFR <60 ml/min/1.73 m(2). Rapid kidney function decline was defined as an annual loss in eGFR of >3 ml/min/1.73 m(2). Discrete survival analysis was used to determine if baseline PA and television watching were related to 10-year cumulative incidence of CKD and rapid decline in kidney function. Individuals who reported watching television >3 hours/day had a higher risk of incident CKD (HR 1.34; 95% CI, 1.09-1.65) and experiencing a rapid decline in kidney function (HR 1.26; 95% CI, 1.05-1.52) compared with individuals who watched television <2 hours/day. PA was not related to either outcome. High levels of television watching are associated with declining kidney function; the mechanisms that underlie this association need further study.

Individualized dosimetry-based activity reduction of 90Y-DOTATOC prevents severe and rapid kidney function deterioration from peptide receptor radionuclide therapy

Assessment of kidney function evolution after (90)Y-DOTATOC peptide receptor radionuclide therapy (PRRT) with capped activity administration based on a 37-Gy threshold of biological effective dose (BED) to the kidney. In a prospective phase II study, patients with metastasized neuroendocrine tumours were evaluated for therapy using 185 MBq (111)In-pentetreotide with amino acid coinfusion. Planar whole-body images were acquired at four time-points after injection and kidney volumes were measured using CT/MRI. BED to the kidneys was estimated using an extended BED formula and biexponential renal clearance. Based on published BED dose-toxicity relationships, we allowed a maximal kidney BED of 37 Gy; if the calculated BED exceeded 37 Gy, treatment activity was reduced accordingly. Kidney function was assessed at baseline and at 18 months, predominantly using (51)Cr-EDTA. The rate of renal function decline was expressed as annual glomerular filtration rate loss (aGFRL). Only 22 of 50 patients reached the 18-months time-point, with most missing patients having died due to disease progression. In the 22 patients who reached 18 months, no rapid kidney function deterioration was observed over the 18 months, aGFRL >33% was not seen, and only three patients showed an increase of one toxicity grade and one patient an increase of two grades. No significant correlations between kidney volume (p = 0.35), baseline GFR (p = 0.18), risk factors for renal function loss (p = 0.74) and aGFRL were observed. Among the 28 patients who did not reach 18 months, one developed grade 4 kidney toxicity at 15 months after PRRT. Prospective dosimetry using a 37 Gy BED as the threshold for kidney toxicity is a good guide for (90)Y-DOTATOC PRRT and is associated with a low risk of rapid renal function deterioration and evolution to severe nephrotoxicity.

Combined application of eGFR and albuminuria for the precise diagnosis of stage 2 and 3a CKD in the elderly

Estimated glomerular filtration rate (eGFR) is the sole diagnostic criterion for stage 3a chronic kidney disease (CKD). Because eGFR decreases with age, its prognostic utility in the elderly is controversial. Albuminuria is an important prognostic factor. To confirm that eGFR use may lead to the overdiagnosis of CKD and to examine the utility of eGFR combined with albuminuria for diagnosing stage 3a CKD in the elderly. This study included 365 elderly patients (age ≥ 65 years) who were diagnosed with stage 2 or 3a CKD. All patients had 3 years of consecutive data at our hospitals from 2000 to 2012. For each eGFR level, patients were divided into normalbuminuria (NOR, urinary albumin excretion rate [UAER] < 30 mg/24 h), microalbuminuria (30 ≥ UAER < 299 mg/24 h), and macroalbuminuria groups (UAER ≥ 300 mg/24 h). Albuminuria was associated with eGFR loss but not baseline eGFR level. When stage 2 NOR was used as a reference, the multivariable adjusted odds ratio (OR) for rapid kidney function decline (RKFD) of stage 3a NOR was 1.329 (95 % confidence interval (CI): 0.334-5.281, P = 0.686). ORs for other groups were significantly higher. In stage 3a NOR, higher ORs for RKFD were associated with younger age groups. Lot of elderly patients with stage 3a CKD and normal albuminuria levels may be over-diagnosed. Albuminuria may be combined with eGFR for improved diagnosis and treatment of stage 3 CKD in the elderly.

Role of Soluble Endothelial Cell–Selective Adhesion Molecule Biomarker in Albuminuria and Kidney Function Changes in Patients With Coronary Artery Disease

Endothelial dysfunction is a possible mechanism to explain the association between atherosclerosis and kidney disease. This study evaluated circulating soluble endothelial cell-selective adhesion molecule (sESAM), a marker of endothelial dysfunction, as a risk factor for kidney function decline and albuminuria. In the Heart and Soul Study, we measured sESAM from baseline serum samples and defined elevated levels of sESAM by the highest quartile (quartile 4 [Q4]: >65.4 ng/mL). We evaluated the associations of high sESAM with baseline estimated glomerular filtration rate (eGFR) and ratio of urine albumin to creatinine (ACR), and with longitudinal changes in eGFR and ACR. Among 990 participants with sESAM measurements, median sESAM was 54.5 ng/mL (interquartile range, 45.3-65.8). After multivariable adjustment, elevated levels of sESAM were strongly and independently associated with baseline reduced eGFR <60 mL/min per 1.73 m(2) (odds ratio [OR], 11.44; P<0.0001) and ACR ≥30 mg/g (OR, 5.23; P<0.0001). Associations of sESAM (Q4 versus quartile 1 [Q1]) with change in ACR (β=54.47; P<0.0001) were also significant after full adjustment. The association with change in eGFR (1.56%; P=0.0049) was not statistically significant after application of the Bonferroni correction for multiple markers. In unadjusted models, sESAM was associated with rapid kidney function loss, defined as 3% annual eGFR decline (OR, 2.28; P=0.0003), although this was attenuated by adjustment (OR, 2.11; P=0.0095). sESAM is associated with albuminuria and reduced kidney function in both cross-sectional and longitudinal analyses. These findings implicate endothelial dysfunction as a potential contributor to the elevated kidney disease risk in persons with cardiovascular disease.

Quiz Page August 2013: Kidney Failure in a Transplant From an Identical Twin

Quiz Page August 2013: Kidney Failure in a Transplant From an Identical Twin

Development of a New Thiol Site-Specific Prosthetic Group and Its Conjugation with [Cys40]-exendin-4 for in Vivo Targeting of Insulinomas

A new tracer, N-5-[(18)F]fluoropentylmaleimide ([(18)F]FPenM), for site-specific labeling of free thiol group in proteins and peptides was developed. The tracer was synthesized in three steps ((18)F displacement of the aliphatic tosylate, di-Boc removal by TFA to expose free amine, and incorporation of the free amine into a maleimide). The radiosynthesis was completed in 110 min with 11-17% radiochemical yield (uncorrected), and specific activity of 20-49 GBq/μmol. [(18)F]FPenM showed comparable labeling efficiency with N-[2-(4-[(18)F]fluorobenzamido)ethyl]maleimide ([(18)F]FBEM). Its application was demonstrated by conjugation with glucagon-like peptide type 1 (GLP-1) analogue [cys(40)]-exendin-4. The cell uptake, binding affinity, imaging properties, biodistribution, and metabolic stability of the radiolabeled [(18)F]FPenM-[cys(40)]-exendin-4 were studied using INS-1 tumor cells and INS-1 xenograft model. Positron emission tomography (PET) results showed that the new thiol-specific tracer, [(18)F]FPenM-[cys(40)]-exendin-4, had high tumor uptake (20.32 ± 4.36%ID/g at 60 min postinjection) and rapid liver and kidney clearance, which was comparable to the imaging results with [(18)F]FBEM-[cys(40)]-exendin-4 reported by our group.

Progression of chronic kidney disease in a multi‐ethnic community cohort of patients with diabetes mellitus

Ethnicity is a risk factor for the prevalence of severe chronic kidney disease among patients with diabetes. We studied the effect of ethnicity on progression of chronic kidney disease in people with diabetes managed in community settings. A 5-year retrospective, community-based cohort study of 3855 people with diabetes mellitus of white, black or South Asian ethnicity with an estimated glomerular filtration rate of < 60 ml min⁻¹ 1.73 m⁻² was undertaken. From 135 general practices in east London, all cases with at least 3 years clinical data were included. Using repeated-measures analysis, the annual decline in estimated glomerular filtration rate was calculated. Comparisons between the rate of decline in the three main ethnic groups, with and without proteinuria at baseline, were made. The annual adjusted decline in estimated glomerular filtration rate for this cohort was 0.85 ml min⁻¹ 1.73 m⁻². The rate of chronic kidney disease progression was significantly greater in South Asian groups (-1.01 ml min⁻¹ 1.73 m⁻²) compared with white groups (-0.70 ml min⁻¹ 1.73 m⁻²) (P = 0.001). For those with proteinuria at baseline, the annual decline was greater at 2.05 ml min⁻¹ 1.73 m⁻², with both South Asian and black groups having a significantly faster rate of decline than white groups. For patients with diabetes and chronic kidney disease managed in primary care, the annual decline of renal function is less than previously thought and approximates the age-related annual decline of 1 ml min⁻¹ 1.73 m⁻². Patients with proteinuria and those of South Asian and Black ethnicity need additional monitoring as they are at greater risk of rapid chronic kidney disease progression.

Association of Obesity and Kidney Function Decline among Non-Diabetic Adults with eGFR > 60 ml/min/1.73m2: Results from the Multi-Ethnic Study of Atherosclerosis (MESA).

Obesity is associated with higher end-stage renal disease incidence, but associations with earlier forms of kidney disease remain incompletely characterized. We studied the association of body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) with rapid kidney function decline and incident chronic kidney disease in 4573 non-diabetic adults with eGFR ≥ 60 ml/min/1.73m2 at baseline from longitudinal Multi-Ethnic Study of Atherosclerosis cohort. Kidney function was estimated by creatinine and cystatin C. Multivariate analysis was adjusted for age, race, baseline eGFR, and hypertension. Mean age was 60 years old, BMI 28 kg/m2, baseline eGFRCr 82 and eGFRCys 95 ml/min/1.73m2. Over 5 years of follow up, 25% experienced rapid decline in renal function by eGFRCr and 22% by eGFRCys. Incident chronic kidney disease (CKD) developed in 3.3% by eGFRCys, 11% by eGFRCr, and 2.4% by both makers. Compared to persons with BMI < 25, overweight (BMI 25 - 30) persons had the lowest risk of rapid decline by eGFRCr (0.84, 0.71 - 0.99). In contrast, higher BMI categories were associated with stepwise higher odds of rapid decline by eGFRCys, but remained significant only when BMI ≥ 35 kg/m2 (1.87, 1.41 - 2.48). Associations of BMI with incident CKD were insignificant after adjustment. Large WC and WHR were associated with increased risk of rapid decline only by eGFRCys, and of incident CKD only when defined by both filtration markers. Obesity may be a risk factor for kidney function decline, but associations vary by filtration marker used.

Association of Arterial Rigidity with Incident Kidney Disease and Kidney Function Decline

The association of large arterial rigidity and kidney function decline in longitudinal analyses is not well established. This study evaluated the association of aortic pulse wave velocity (aPWV) and pulse pressure (PP) with rapid kidney function decline and incident CKD in the Health, Aging and Body Composition study. Participants were 2129 older adults with a baseline measurement of aPWV, PP, and cystatin C and at least one additional measurement of cystatin C, either at year 3 or year 10. Outcomes were rapid kidney function decline (estimated GFRcysC loss of >3 ml/min per 1.73 m(2) per year) and incident CKD (eGFRcysC < 60 ml/min per 1.73 m(2) in participants with baseline estimated GFR > 60 ml/min per 1.73 m(2)). Multivariate regression models were used to evaluate association of aPWV and PP with each outcome. Mean (SD) baseline estimated GFRcysC was 79±29 ml/min per 1.73 m(2). Median follow-up duration was 8.9 years. In multivariable analyses, aPWV was not associated with rapid decline (odds ratio [OR], 95% confidence interval [CI] 1.16, 0.89-1.52) but was associated with incident CKD (incident rate ratio [IRR], 95% CI, 1.39, 1.09-1.77) and PP was associated with both rapid decline (OR, 95% CI 1.10, 1.04-1.16) and incident CKD (IRR, 95% CI, 1.06, 1.01-1.11). Large arterial stiffness assessed by aPWV and pulsatility assessed by PP were associated with incident CKD among older adults. Pulsatility assessed by PP was associated with rapid kidney function decline and incident CKD. Future research should determine whether interventions targeting arterial rigidity will prevent CKD development and progression.

Associations of Urinary Levels of Kidney Injury Molecule 1 (KIM-1) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) With Kidney Function Decline in the Multi-Ethnic Study of Atherosclerosis (MESA)

Whether elevations in levels of urinary biomarkers of tubular injury (urine neutrophil gelatinase-associated lipocalin [NGAL] and kidney injury molecule 1 [KIM-1]) are associated with future risk of kidney disease has not been investigated. 1:1 nested case-control study. 686 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). NGAL and KIM-1 were measured at baseline, expressed as log-transformed continuous variables, and categorized into deciles. Kidney function was estimated by cystatin C level using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Incident CKD stage 3 was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) and an eGFR decrease >1 mL/min/1.73 m(2) per year, and rapid kidney function decrease was defined as decrease ≥3 mL/min/1.73 m(2) per year. Cases were defined as persons with eGFR >60 mL/min/1.73 m(2) who subsequently developed incident CKD stage 3 and/or had rapid kidney function decrease by the MESA year-5 visit. Controls were matched for age, sex, race, diabetes, and baseline eGFR. We adjusted for age, hypertension, and presence of albuminuria (albumin-creatinine ratio ≥30 mg/g). Of 343 cases, 145 had incident CKD stage 3, 141 had rapid kidney function decrease, and 57 had both. Mean eGFR for controls was 81 ± 10 mL/min/1.73 m(2) at baseline and 80 ± 10 mL/min/1.73 m(2) at follow-up compared with 82 ± 13 and 58 ± 10 mL/min/1.73 m(2) for cases. Each doubling of KIM-1 level (in picograms per milliliter) was associated with an OR of 1.15 (95% CI, 1.02-1.29) for incident CKD stage 3 and/or rapid kidney function decrease. Compared with the lowest 90%, the highest decile of KIM-1 level was associated with an OR of 2.02 (95% CI, 1.15-3.56) for the outcome; these associations were independent of albuminuria. NGAL levels (in nanograms per milliliter) were not associated with incident CKD stage 3 and/or rapid kidney function decrease (OR, 1.04; 95% CI, 0.99-1.10). Results were similar when KIM-1 and NGAL levels were standardized for urine creatinine. The case-control design limits the ability to account for persons who died or were not available for follow-up. Urinary KIM-1 level is associated with future risk of kidney disease independent of albuminuria. Urinary biomarkers of tubular injury are a promising tool for identifying persons at risk of CKD.

Subclinical Cardiac Abnormalities and Kidney Function Decline

Clinical heart failure (HF) is associated with CKD and faster rates of kidney function decline. Whether subclinical abnormalities of cardiac structure are associated with faster kidney function decline is not known. The association between cardiac concentricity and kidney function decline was evaluated. This is a longitudinal study of 3866 individuals from the Multi-Ethnic Study of Atherosclerosis (2000-2007) who were free of clinical cardiovascular disease, with an estimated GFR (eGFR) ≥60 ml/min per 1.73 m(2) at baseline and 5 years of follow-up. Concentricity, a measurement of abnormal cardiac size, was assessed by magnetic resonance imaging and evaluated as a continuous measurement and in quartiles. GFR was estimated by creatinine (eGFRcr) and cystatin C (eGFRcys). The association of concentricity with annual eGFR decline, incident CKD, and rapid kidney function decline (>5% per year) was investigated using linear mixed models as well as Poisson and logistic regression, respectively. Analyses adjusted for demographics, BP, diabetes, and inflammatory markers. Median decline was -0.8 (interquartile range, -3.1, -0.5) by eGFRcr. Compared with the lowest quartile of concentricity, persons in the highest quartile had an additional 21% (9%-32%) decline in mean eGFRcr in fully adjusted models. Concentricity was also associated with incident CKD and with rapid kidney function decline after adjustment. Subclinical abnormalities in cardiac structure are associated with longitudinal kidney function decline independent of diabetes and hypertension. Future studies should examine mechanisms to explain these associations.

Inflammation and Coagulation Markers and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis (MESA)

The strength and direction of the associations between inflammation and coagulation biomarkers with kidney disease onset and progression remain unclear, especially in a population-based setting. Prospective observational study. 4,966 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with a cystatin C-based estimate of glomerular filtration rate (eGFR(cys)) >60 mL/min/1.73 m(2) and at least one follow-up measurement of kidney function. All participants were free of cardiovascular disease at entry. We evaluated the associations of C-reactive protein (CRP), interleukin 6 (IL-6), fibrinogen, factor VIII, and d-dimer levels with kidney function decrease. Kidney function decrease was assessed primarily by repeated measurements of eGFR(cys) over 5 years. Rapid decrease in kidney function was defined as eGFR decrease >3 mL/min/1.73 m(2) per year. Incident low eGFR was defined as the onset of eGFR(cys) <60 mL/min/1.73 m(2) at any follow-up examination and eGFR(cys) decrease ≥1 mL/min/1.73 m(2) per year. Mean age was 60 years, 39% were white, 52% were women, and 11% had diabetes. Mean eGFR(cys) was 96 mL/min/1.73 m(2) and 7% had albuminuria. Median follow-up was 4.77 years. Higher factor VIII levels (per 1 standard deviation [SD] of biomarker) had the strongest association with kidney function decrease (β = -0.25; 95% CI, -0.38 to -0.12; P < 0.001), followed by IL-6 (β = -0.16; 95% CI, -0.29 to -0.03; P = 0.01), CRP (β = -0.09; 95% CI, -0.22 to 0.03; P = 0.1), and fibrinogen levels (β = -0.09; 95% CI, -0.22 to 0.04; P = 0.2). Each 1-SD higher concentration of IL-6 (OR, 1.15; 95% CI, 1.07-1.23), factor VIII (OR, 1.11; 95% CI, 1.03-1.18), and CRP (OR, 1.09; 95% CI, 1.02-1.16) at baseline was associated significantly with rapid kidney function decrease. Only IL-6 level was associated significantly with incident low eGFR (OR, 1.09; 95% CI, 1.00-1.19). Observational study design and absence of measured GFR. Inflammation and coagulation biomarkers are associated with decreasing kidney function in ambulatory adults without established cardiovascular disease or chronic kidney disease.

Involvement of the endothelin and nitric oxide systems in the pathogenesis of renal ischemic damage in an experimental diabetic model

AimsIschemic acute kidney injury (iAKI) in experimental diabetes mellitus (DM) is associated with a rapid kidney dysfunction more than in non-diabetic rats. We hypothesize that this vulnerability is due to excessive endothelin-1 (ET-1) expression along with dysregulation of nitric oxide synthase (NOS) isoforms. The aim of the present study was to assess the impact of ischemia on renal function in diabetic rats as compared with non-diabetic rats, and to investigate the involvement of ET-1 and NO systems in the susceptibility of diabetic kidney to ischemic damage. Main methodsDM was induced by Streptozotocin. iAKI was induced by clamping of left renal artery for 30min. Right intact kidney served as control. 48h following ischemia, clearance protocols were applied to assess glomerular filtration rate (GFR), urinary flow (V) and sodium excretion (UNaV) in both kidneys. The renal effects of ABT-627, ETA antagonist; A192621.1, ETB antagonist; L-NAME, NOS non-selective inhibitor; 1400W, inducible NOS (iNOS) inhibitor; and NPLA, neuronal NOS (nNOS) inhibitor, were assessed following ischemic renal injury in diabetic rats. Key findingsInduction of iAKI in diabetic and non-diabetic rats caused significant reductions in GFR, V, and UNaV, which were greater in diabetic than non-diabetic rats. While, treatment with ABT-627 decreased V and UNaV, and increased GFR, A192621.1 decreased all these parameters. L-NAME, 1400W, and NPLA improved GFR in the ischemic diabetic kidney. SignificanceExcessive vasoconstrictive effects of ET-1 via ETA and upregulation of iNOS, are partly responsible for the impaired recovery of renal function following ischemia in diabetic rats.

Dextran-Conjugated Vascular Endothelial Growth Factor Receptor Antibody for In Vivo Melanoma Xenografted Mouse Imaging

Intact immunoglobulin G antibody has a relatively large molecule size of approximately 150 kDa that remains in the bloodstream for many weeks, which is a considerable disadvantage when it is used to carry radioactive materials for imaging. To lower background activity and increase the contrast of images, we investigated antivascular endothelial growth factor (VEGF) receptor 2 antibody (DC101) conjugated dextran for VEGF receptor 2 imaging in tumor xenografted mice. DTPA-conjugated aminodextran was synthesized, reacted with sulfo-LC-SPDP, and then reacted with DC101. The binding affinity of DTPA-dextran-DC101 to Flk-1 was measured. The gamma imaging and biodistributions of (99m)Tc-DTPA-dextran-DC101, (99m)Tc-DTPA-DC101, and (125)I-DC101 were studied in B16F10 melanoma xenografted mice. The dissociation values for DC101, DTPA-DC101, and DTPA-dextran-DC101 were 22.48, 3.05, and 14.74 pM, respectively. In gamma images, (99m)Tc-DTPA-dextran-DC101 showed weak liver uptake and rapid kidney elimination. In biodistribution results, the liver uptake of (99m)Tc-DTPA-dextran-DC101 was similar with that of (99m)Tc-DTPA-DC101 at each time point. However, the blood activity of (99m)Tc-DTPA-dextran-DC101 has shown significant differences, compared with (99m)Tc-DTPA-DC101 at all time points. The tumor accumulation of dextran-conjugated antibody was increased with time, whereas that of dextran nonconjugated antibody decreased. In particular, the pattern of tumor uptake of (99m)Tc-DTPA-dextran-DC101 was similar to that of (125)I-DC101, so this was thought to reflect the kinetics of DC101, unlike the nonconjugated form. The results of this study suggested that introduction of dextran moiety to make (99m)Tc-radiolabeled DC101 imaging agent could provide better images with the impaired background and the steady increasing binding to the receptor. However, further studies are necessary to improve clinical pharmacokinetics, such as enhancement of tumor uptake and impaired renal uptake.

Rapid Anuric Acute Kidney Injury After the Administration of IV Anti-D in a Teenager

Abstract 4691 Introduction:A 16 year old male developed dark brown urine and prolonged anuric renal failure requiring hemodialysis after receiving IV anti-D. He was diagnosed with idiopathic thrombocytopenia purpura (ITP) after presenting with diffuse petechiae and a platelet count of 7000/μl, about a week after onset of viral prodrome that had resolved 2 days before. The white cell count, hemoglobin, PT, PTT, INR, and direct Coomb's screen (IgG and complement) values were normal/negative at initial presentation, as were plasma chemistries, including LDH and uric acid levels. Except for small ketones and small heme reactions, the initial urinalysis was also unremarkable. Following IV anti-D, the patient developed intravascular coagulation concurrent with hemolysis and renal failure. Method:In this case report we describe a teenager who presented with ITP and rapidly developed severe anuric acute kidney injury (AKI) associated with mild intravascular hemolysis and coagulopathy. We review previous reports of IV Anti-D associated AKI, in order to identify common risk factors that may be used as a pre-treatment screen. Result:Anuric renal failure following IV anti-D has previously been reported and is a profoundly rare complication associated with a high risk of death. There is no reliable screening test, as this case illustrates. The clinical and laboratory course in this teenager, as well as from other reported cases, lead us to speculate that while hemolysis following IV-anti D infusion is necessary for the development of acute renal failure, it is insufficient unless there is a concurrent or antecedent intravascular coagulopathy. We suggest that the D-dimers assay should be formally evaluated as a screen prior to IV anti-D therapy to identify those individuals at risk for this life-threatening adverse reaction. Conclusion:IV anti-D is a good option for the treatment of ITP but the risks should be seriously considered prior to administration. A preliminary workup should be initiated prior to therapy. Other forms of treatment may be necessary in patients with evidence of renal insufficiency, hemolysis, recent EBV infection, known positive C-antigen or evidence of coagulopathy. We are planning a prospective study to evaluate the usefulness of obtaining a D-dimer in ITP patients prior to treatment. This will elicit information that is currently unavailable regarding the frequency of positive D-Dimers in patients with ITP prior to treatment. Disclosures:No relevant conflicts of interest to declare.

Dipstick Proteinuria as a Screening Strategy to Identify Rapid Renal Decline

Rapid kidney function decline (RKFD) predicts cardiovascular morbidity and mortality, but serial assessment of estimated GFR (eGFR) is not cost-effective for the general population. Here, we evaluated the predictive value of albuminuria and three thresholds of dipstick proteinuria to identify RKFD in 2,574 participants in a community-based prospective cohort study with a median of 7 years follow-up. Median change in eGFR was -0.78 ml/min per 1.73 m(2) per year; with 8.5% experiencing RKFD, defined as a >5% annual eGFR decline from baseline. Of those with RKFD, 65% advanced to a new CKD stage compared with 19% of those without RKFD. Dipstick protein ≥ 1 g/L was a stronger predictor of RKFD than albuminuria. Overall, 2.5% screened positive for dipstick protein ≥ 1 g/L at baseline; one of every 2.6 patients would have RKFD if all were followed with serial eGFR measurement. Overall, the screening strategy correctly identified progression status for 90.8% of patients, mislabeled 1.5% as RKFD, and missed 7.7% with eventual RKFD. Among those with risk factors (cardiovascular disease, age >60, diabetes, or hypertension), the probability of identifying RKFD from serial eGFR measurements increased from 13 to 44% after incorporating dipstick protein (≥ 1 g/L threshold). In summary, inexpensive screening with urine dipstick should allow primary care physicians to follow fewer patients with serial eGFR assessment but still identify those with rapid decline of kidney function.

Quantitative Whole Body Biodistribution of Fluorescent-Labeled Agents by Non-Invasive Tomographic Imaging

When small molecules or proteins are injected into live animals, their physical and chemical properties will significantly affect pharmacokinetics, tissue penetration, and the ultimate routes of metabolism and clearance. Fluorescence molecular tomography (FMT) offers the ability to non-invasively image and quantify temporal changes in fluorescence throughout the major organ systems of living animals, in a manner analogous to traditional approaches with radiolabeled agents. This approach is best used with biotherapeutics (therapeutic antibodies, or other large proteins) or large-scaffold drug-delivery vectors, that are minimally affected by low-level fluorophore conjugation. Application to small molecule drugs should take into account the significant impact of fluorophore labeling on size and physicochemical properties, however, the presents studies show that this technique is readily applied to small molecule agents developed for far-red (FR) or near infrared (NIR) imaging. Quantification by non-invasive FMT correlated well with both fluorescence from tissue homogenates as well as with planar (2D) fluorescence reflectance imaging of excised intact organs (r2 = 0.996 and 0.969, respectively). Dynamic FMT imaging (multiple times from 0 to 24 h) performed in live mice after the injection of four different FR/NIR-labeled agents, including immunoglobulin, 20–50 nm nanoparticles, a large vascular imaging agent, and a small molecule integrin antagonist, showed clear differences in the percentage of injected dose per gram of tissue (%ID/g) in liver, kidney, and bladder signal. Nanoparticles and IgG1 favored liver over kidney signal, the small molecule integrin-binding agent favored rapid kidney and bladder clearance, and the vascular agent, showed both liver and kidney clearance. Further assessment of the volume of distribution of these agents by fluorescent volume added information regarding their biodistribution and highlighted the relatively poor extravasation into tissue by IgG1. These studies demonstrate the ability of quantitative FMT imaging of FR/NIR agents to non-invasively visualize and quantify the biodistribution of different agents over time.

Longitudinal Association of Depressive Symptoms with Rapid Kidney Function Decline and Adverse Clinical Renal Disease Outcomes

Depression is a risk indicator for adverse outcomes in dialysis patients, but its prognostic impact in individuals who are not yet on dialysis is unknown. This study examines whether depressive symptoms are longitudinally associated with renal function decline, new-onset chronic kidney disease (CKD), ESRD, or hospitalization with acute kidney injury (AKI). Depressive symptoms were measured in a longitudinal cohort study with the 10-item Centers for Epidemiologic Studies Depression scale using a previously validated cut-off value (≥8). CKD at study entry and during follow-up was defined as an estimated GFR (eGFR) < 60 ml/min per m(2). Outcomes were rapid decline in eGFR (>3 ml/min per m(2) per year), new-onset CKD, ESRD (U.S. Renal Data System-based), and AKI (based on adjudicated medical record review). The median follow-up duration was 10.5 years. Depressed participants (21.2%) showed a higher prevalence of CKD at baseline compared with nondepressed participants in multivariable analysis. Depression was associated with a subsequent risk of rapid decline in eGFR, incident ESRD, and AKI, but not incident CKD in unadjusted models. In multivariable analyses, only associations of depressive symptoms with AKI remained significant. Elevated depressive symptoms are associated with subsequent adverse renal disease outcomes. The depression-related elevated risk of AKI was independent of traditional renal disease risk factors and may in part be explained by the predictive value of depression for acute coronary syndromes and heart failure hospitalizations that can be complicated by AKI.

Association of Dietary Patterns With Albuminuria and Kidney Function Decline in Older White Women: A Subgroup Analysis From the Nurses' Health Study

Dietary patterns have been linked to such chronic diseases as cardiovascular disease, but sparse data currently are available for associations between dietary patterns and microalbuminuria or kidney function decline. Subgroup analysis from a prospective observational cohort study. Female participants in the Nurses' Health Study who had dietary pattern data from food frequency questionnaires returned in 1984, 1986, 1990, 1994, and 1998 and urinary albumin-creatinine ratios from 2000 (n = 3,121); estimated glomerular filtration rate (eGFR) change between 1989 and 2000 was available for 3,071. Prudent (higher intake of fruits, vegetables, legumes, fish, poultry, and whole grains), Western (higher intake of red and processed meats, saturated fats, and sweets), and Dietary Approach to Stop Hypertension (DASH)-style dietary patterns (also greater intake of vegetables, fruits, and whole grains). Microalbuminuria (albumin-creatinine ratio, 25-354 μg/mg) in 2000 and change in kidney function using eGFR between 1989 and 2000. After multivariable adjustment, the highest quartile of Western pattern score compared with the lowest quartile was associated directly with microalbuminuria (OR, 2.17; 95% CI, 1.18-3.66; P for trend = 0.01) and rapid eGFR decline ≥3 mL/min/1.73 m(2)/y (OR, 1.77; 95% CI, 1.03-3.03). Women in the top quartile of the DASH score had decreased risk of rapid eGFR decline (OR, 0.55; 95% CI, 0.38-0.80), but no association with microalbuminuria. These associations did not vary by diabetes status. The prudent dietary pattern was not associated with microalbuminuria or eGFR decline. Study cohort included primarily older white women and generalizability of results would benefit from validation in nonwhites and men. A Western dietary pattern is associated with a significantly increased odds of microalbuminuria and rapid kidney function decrease, whereas a DASH-style dietary pattern may be protective against rapid eGFR decline.

Central Blood Pressure and Chronic Kidney Disease Progression

Hypertension, diabetes, and proteinuria are well-recognized risk factors for progressive kidney function loss. However, despite excellent antihypertensive and antidiabetic drug therapies, which also often lower urinary protein excretion, there remains a significant reservoir of patients with chronic kidney disease who are at high risk for progression to end-stage kidney disease. This has led to the search for less traditional cardiovascular risk factors that will help stratify patients at risk for more rapid kidney disease progression. Among these are noninvasive estimates of vascular structure and function. Arterial stiffness, manifested by the pulse wave velocity in the aorta, has been established in a number of studies as a significant risk factor for kidney disease progression and cardiovascular endpoints. Much less well studied in chronic kidney disease are measures of central arterial pressures. In this paper we cover the physiology behind the generation of the central pulse wave contour and the studies available using these approaches and conclude with some speculations on the rationale for why measurements of central pressure may be informative for the study of chronic kidney disease progression.