Plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) in dogs with acute kidney injury or chronic kidney disease.

BACKGROUND Neutrophil gelatinase-associated lipocalin (NGAL) is a protein that is used in human medicine as a real-time indicator of acute kidney injury (AKI). HYPOTHESIS Dogs with AKI have significantly higher plasma NGAL concentration and urine NGAL-to-creatinine ratio (UNCR) compared with healthy dogs and dogs with chronic kidney disease (CKD). ANIMALS 18 healthy control dogs, 17 dogs with CKD, and 48 dogs with AKI. METHODS Over a period of 1 year, all dogs with renal azotemia were prospectively included. Urine and plasma samples were collected during the first 24 hours after presentation or after development of renal azotemia. Plasma and urine NGAL concentrations were measured with a commercially available canine NGAL Elisa Kit (Bioporto® Diagnostic) and UNCR was calculated. A single-injection plasma inulin clearance was performed in the healthy dogs. RESULTS Median (range) NGAL plasma concentration in healthy dogs, dogs with CKD, and AKI were 10.7 ng/mL (2.5-21.2), 22.0 ng/mL (7.7-62.3), and 48.3 ng/mL (5.7-469.0), respectively. UNCR was 2 × 10(-8) (0-46), 1,424 × 10(-8) (385-18,347), and 2,366 × 10(-8) (36-994,669), respectively. Dogs with renal azotemia had significantly higher NGAL concentrations and UNCR than did healthy dogs (P < .0001 for both). Plasma NGAL concentration was significantly higher in dogs with AKI compared with dogs with CKD (P = .027). CONCLUSIONS AND CLINICAL IMPORTANCE Plasma NGAL could be helpful to differentiate AKI from CKD in dogs with renal azotemia.

Kidney disease in antiretroviral-naïve HIV-positive adults with high CD4 counts: prevalence and predictors of kidney disease at enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES HIV infection has been associated with an increased risk of chronic kidney disease (CKD). Little is known about the prevalence of CKD in individuals with high CD4 cell counts prior to initiation of antiretroviral therapy (ART). We sought to address this knowledge gap. METHODS We describe the prevalence of CKD among 4637 ART-naïve adults (mean age 36.8 years) with CD4 cell counts > 500 cells/μL at enrolment in the Strategic Timing of AntiRetroviral Treatment (START) study. CKD was defined by estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) and/or dipstick urine protein ≥ 1+. Logistic regression was used to identify baseline characteristics associated with CKD. RESULTS Among 286 [6.2%; 95% confidence interval (CI) 5.5%, 6.9%] participants with CKD, the majority had isolated proteinuria. A total of 268 participants had urine protein ≥ 1+, including 41 with urine protein ≥ 2+. Only 22 participants (0.5%) had an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) , including four who also had proteinuria. Baseline characteristics independently associated with CKD included diabetes [adjusted odds ratio (aOR) 1.73; 95% CI 1.05, 2.85], hypertension (aOR 1.82; 95% CI 1.38, 2.38), and race/ethnicity (aOR 0.59; 95% CI 0.37, 0.93 for Hispanic vs. white). CONCLUSIONS We observed a low prevalence of CKD associated with traditional CKD risk factors among ART-naïve clinical trial participants with CD4 cell counts > 500 cells/μL.

Copeptin Is Associated with Kidney Length, Renal Function, and Prevalence of Simple Cysts in a Population-Based Study.

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=-2.1; 95% confidence interval [95% CI], -3.3 to -0.8; P=0.002) and kidney length (β=-1.2; 95% CI, -1.9 to -0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts.

Determinants of renal tissue oxygenation as measured with BOLD-MRI in chronic kidney disease and hypertension in humans.

Experimentally renal tissue hypoxia appears to play an important role in the pathogenesis of chronic kidney disease (CKD) and arterial hypertension (AHT). In this study we measured renal tissue oxygenation and its determinants in humans using blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) under standardized hydration conditions. Four coronal slices were selected, and a multi gradient echo sequence was used to acquire T2* weighted images. The mean cortical and medullary R2* values ( = 1/T2*) were calculated before and after administration of IV furosemide, a low R2* indicating a high tissue oxygenation. We studied 195 subjects (95 CKD, 58 treated AHT, and 42 healthy controls). Mean cortical R2 and medullary R2* were not significantly different between the groups at baseline. In stimulated conditions (furosemide injection), the decrease in R2* was significantly blunted in patients with CKD and AHT. In multivariate linear regression analyses, neither cortical nor medullary R2* were associated with eGFR or blood pressure, but cortical R2* correlated positively with male gender, blood glucose and uric acid levels. In conclusion, our data show that kidney oxygenation is tightly regulated in CKD and hypertensive patients at rest. However, the metabolic response to acute changes in sodium transport is altered in CKD and in AHT, despite preserved renal function in the latter group. This suggests the presence of early renal metabolic alterations in hypertension. The correlations between cortical R2* values, male gender, glycemia and uric acid levels suggest that these factors interfere with the regulation of renal tissue oxygenation.

Proliferative kidney disease in brown trout – infection level, pathology and mortality under field conditions

Proliferative kidney disease (PKD) is an emerging disease threatening wild salmonid populations. In temperature-controlled aquaria, PKD can cause mortality rates of up to 85% in rainbow trout. So far, no data about PKD-related mortality in wild brown trout Salmo trutta fario are available. The aim of this study was to investigate mortality rates and pathology in brown trout kept in a cage within a natural river habitat known to harbor Tetracapsuloides bryosalmonae. Young-of-the-year (YOY) brown trout, free of T. bryosalmonae, were exposed in the River Wutach, in the northeast of Switzerland, during 3 summer months. Samples of wild brown trout caught by electrofishing near the cage location were examined in parallel. The incidence of PKD in cage-exposed animals (69%) was not significantly different to the disease prevalence of wild fish (82 and 80% in the upstream and downstream locations, respectively). The mortality in cageexposed animals, however, was as low as 15%. At the termination of the exposure experiment, surviving fish showed histological lesions typical for PKD regression, suggesting that many YOY brown trout survive the initial infection. Our results at the River Wutach suggest that PKD in brown trout does not always result in high mortality under natural conditions.

Effect of Chronic Kidney Disease in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents: A Patient-Level Pooled Analysis of Randomized Controlled Trials.

OBJECTIVES This study sought to evaluate: 1) the effect of impaired renal function on long-term clinical outcomes in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES); and 2) the safety and efficacy of new-generation compared with early-generation DES in women with chronic kidney disease (CKD). BACKGROUND The prevalence and effect of CKD in women undergoing PCI with DES is unclear. METHODS We pooled patient-level data for women enrolled in 26 randomized trials. The study population was categorized by creatinine clearance (CrCl) <45 ml/min, 45 to 59 ml/min, and ≥60 ml/min. The primary endpoint was the 3-year rate of major adverse cardiovascular events (MACE). Participants for whom baseline creatinine was missing were excluded from the analysis. RESULTS Of 4,217 women included in the pooled cohort treated with DES and for whom serum creatinine was available, 603 (14%) had a CrCl <45 ml/min, 811 (19%) had a CrCl 45 to 59 ml/min, and 2,803 (66%) had a CrCl ≥60 ml/min. A significant stepwise gradient in risk for MACE was observed with worsening renal function (26.6% vs. 15.8% vs. 12.9%; p < 0.01). Following multivariable adjustment, CrCl <45 ml/min was independently associated with a higher risk of MACE (adjusted hazard ratio: 1.56; 95% confidence interval: 1.23 to 1.98) and all-cause mortality (adjusted hazard ratio: 2.67; 95% confidence interval: 1.85 to 3.85). Compared with older-generation DES, the use of newer-generation DES was associated with a reduction in the risk of cardiac death, myocardial infarction, or stent thrombosis in women with CKD. The effect of new-generation DES on outcomes was uniform, between women with or without CKD, without evidence of interaction. CONCLUSIONS Among women undergoing PCI with DES, CKD is a common comorbidity associated with a strong and independent risk for MACE that is durable over 3 years. The benefits of newer-generation DES are uniform in women with or without CKD.

Use of Calcium Channel Blockers is Associated with Mortality in Patients with Chronic Kidney Disease.

BACKGROUND/AIMS The use of antihypertensive medicines has been shown to reduce proteinuria, morbidity, and mortality in patients with chronic kidney disease (CKD). A specific recommendation for a class of antihypertensive drugs is not available in this population, despite the pharmacodynamic differences. We have therefore analysed the association between antihypertensive medicines and survival of patients with chronic kidney disease. METHODS Out of 2687 consecutive patients undergoing kidney biopsy a cohort of 606 subjects with retrievable medical therapy was included into the analysis. Kidney function was assessed by glomerular filtration rate (GFR) estimation at the time point of kidney biopsy. Main outcome variable was death. RESULTS Overall 114 (18.7%) patients died. In univariate regression analysis the use of alpha-blockers and calcium channel antagonists, progression of disease, diabetes mellitus (DM) type 1 and 2, arterial hypertension, coronary heart disease, peripheral vascular disease, male sex and age were associated with mortality (all p<0.05). In a multivariate Cox regression model the use of calcium channel blockers (HR 1.89), age (HR 1.04), DM type 1 (HR 8.43) and DM type 2 (HR 2.17) and chronic obstructive pulmonary disease (HR 1.66) were associated with mortality (all p < 0.05). CONCLUSION The use of calcium channel blockers but not of other antihypertensive medicines is associated with mortality in primarily GN patients with CKD.

Effects of overweight and obesity on economic outcomes among U.S. adults with kidney disease

Background. Kidney disease is a growing public health phenomenon in the U.S. and in the world. Downstream interventions, dialysis and renal transplants covered by Medicare's renal disease entitlement policy in those who are 65 years and over have been expensive treatments that have been not foolproof. The shortage of kidney donors in the U.S. has grown in the last two decades. Therefore study of upstream events in kidney disease development and progression is justified to prevent the rising prevalence of kidney disease. Previous studies have documented the biological route by which obesity can progress and accelerate kidney disease, but health services literature on quantifying the effects of overweight and obesity on economic outcomes in the context of renal disease were lacking. Objectives . The specific aims of this study were (1) to determine the likelihood of overweight and obesity in renal disease and in three specific adult renal disease sub-populations, hypertensive, diabetic and both hypertensive and diabetic (2) to determine the incremental health service use and spending in overweight and obese renal disease populations and (3) to determine who financed the cost of healthcare for renal disease in overweight and obese adult populations less than 65 years of age. Methods. This study was a retrospective cross-sectional study of renal disease cases pooled for years 2002 to 2009 from the Medical Expenditure Panel Survey. The likelihood of overweight and obesity was estimated using chi-square test. Negative binomial regression and generalized gamma model with log link were used to estimate healthcare utilization and healthcare expenditures for six health event categories. Payments by self/family, public and private insurance were described for overweight and obese kidney disease sub-populations. Results. The likelihood of overweight and obesity was 0.29 and 0.46 among renal disease and obesity was common in hypertensive and diabetic renal disease population. Among obese renal disease population, negative binomial regression estimates of healthcare utilization per person per year as compared to normal weight renal disease persons were significant for office-based provider visits and agency home health visits respectively (p=0.001; p=0.005). Among overweight kidney disease population health service use was significant for inpatient hospital discharges (p=0.027). Over years 2002 to 2009, overweight and obese renal disease sub-populations had 53% and 63% higher inpatient facility and doctor expenditures as compared to normal weight renal disease population and these result were statistically significant (p=0.007; p=0.026). Overweigh renal disease population had significant total expenses per person per year for office-based and outpatient associated care. Overweight and obese renal disease persons paid less from out-of-pocket overall compared to normal weight renal disease population. Medicare and Medicaid had the highest mean annual payments for obese renal disease persons, while mean annual payments per year were highest for private insurance among normal weight renal disease population. Conclusion. Overweight and obesity were common in those with acute and chronic kidney disease and resulted in higher healthcare spending and increased utilization of office-based providers, hospital inpatient department and agency home healthcare. Healthcare for overweight and obese renal disease persons younger than 65 years of age was financed more by private and public insurance and less by out of pocket payments. With the increasing epidemic of obesity in the U.S. and the aging of the baby boomer population, the findings of the present study have implications for public health and for greater dissemination of healthcare resources to prevent, manage and delay the onset of overweight and obesity that can progress and accelerate the course of the kidney disease.^

Synthesis and characterization of a novel retinylamine analog inhibitor of constitutively active rhodopsin mutants found in patients with autosomal dominant retinitis pigmentosa

Two different mutations of the active-site Lys-296 in rhodopsin, K296E and K296M, have been found to cause autosomal dominant retinitis pigmentosa (ADRP). In vitro studies have shown that both mutations result in constitutive activation of the protein, suggesting that the activated state of the receptor may be responsible for retinal degeneration in patients with these mutations. Previous work has highlighted the potential of retinylamine analogs as active-site directed inactivators of constitutively active mutants of rhodopsin with the idea that these or related compounds might be used therapeutically for cases of ADRP involving mutations of the active-site Lys. Unfortunately, however, amine derivatives of 11-cis-retinal, although highly effective against a K296G mutant of rhodopsin, were without affect on the two naturally occurring ADRP mutants, presumably because of the greater steric bulk of Glu and Met side chains in comparison to Gly. For this reason we synthesized a retinylamine analog one carbon shorter than the parent 11-cis-retinal and show that this compound is indeed an effective inhibitor of both the K296E and K296M mutants. The 11-cis C19 retinylamine analog 1 inhibits constitutive activation of transducin by these mutants and their constitutive phosphorylation by rhodopsin kinase, and it does so in the presence of continuous illumination from room lights.

Is routine hospital episode data sufficient for identifying individuals with chronic kidney disease? : A comparison study with laboratory data

© The Author(s) 2014. Acknowledgements We thank the Information Services Division, Scotland, who provided the SMR01 data, and NHS Grampian, who provided the biochemistry data. We also thank the University of Aberdeen’s Data Management Team. Funding This work was supported by the Chief Scientists Office for Scotland (grant no. CZH/4/656).

Bone fragility as a possible complication of chronic kidney disease in early stages

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

New opportunities in treating kidney disease [microform] : hearing before the Subcommittee on Investigations and Oversight of the Committee on Science and Technology, U.S. House of Representatives, Ninety-seventh Congress, second session, October 12, 1982.

"No. 153."

Effect of pravastatin on cardiovascular events in people with chronic kidney disease

Background - Limited data describe the cardiovascular benefit of HMG-CoA reductase inhibitors (statins) in people with moderate chronic kidney disease (CKD). The objective of this analysis was to determine whether pravastatin reduced the incidence of cardiovascular events in people with or at high risk for coronary disease and with concomitant moderate CKD. Methods and Results - We analyzed data from the Pravastatin Pooling Project (PPP), a subject-level database combining results from 3 randomized trials of pravastatin ( 40 mg daily) versus placebo. Of 19 700 subjects, 4491 ( 22.8%) had moderate CKD, defined by an estimated glomerular filtration rate of 30 to 59.99 mL/min per 1.73 m(2) body surface area. The primary outcome was time to myocardial infarction, coronary death, or percutaneous/surgical coronary revascularization. Moderate CKD was independently associated with an increased risk of the primary outcome ( adjusted HR 1.26, 95% CI 1.07 to 1.49) compared with those with normal renal function. Among the 4491 subjects with moderate CKD, pravastatin significantly reduced the incidence of the primary outcome ( HR 0.77, 95% CI 0.68 to 0.86), similar to the effect of pravastatin on the primary outcome in subjects with normal kidney function ( HR 0.78, 95% CI 0.65 to 0.94). Pravastatin also appeared to reduce the total mortality rate in those with moderate CKD ( adjusted HR 0.86, 95% CI 0.74 to 1.00, P = 0.045). Conclusions - Pravastatin reduces cardiovascular event rates in people with or at risk for coronary disease and concomitant moderate CKD, many of whom have serum creatinine levels within the normal range. Given the high risk associated with CKD, the absolute benefit that resulted from use of pravastatin was greater than in those with normal renal function.