Kidney injury molecule-1 correlates with kidney function in renal allograft recipients

IntroductionKIM-1 (kidney injury molecule-1) is responsible for the clearance of debris from damaged renal tubules. KIM-1 can be expressed and excreted in urine within 12 hours after the initial ischemic insult and before regeneration of the epithelium, persisting over time thereafter. Urinary KIM-1 has been reported to be a noninvasive, rapid, sensitive, and reproducible biomarker of experimental nephrotoxic and ischemic acute kidney injury. Renal KIM-1 expression is significantly increased in human kidney tissue among patients with a wide range of kidney diseases, including various types of glomerulonephritis, chronic allograft nephropathy, acute rejection, hypertension, and Wegener's granulomatosis. Both renal and urinary KIM-1 correlate with kidney damage and negatively with renal function, but not with proteinuria. The aim of this study was to assess whether urinary KIM-1 correlated with kidney function in kidney allograft recipients.MethodsSerum NGAL, creatinine and estimated glomerular filtration rate (eGFR) were evaluated in 170 kidney allograft recipients on therapy with a calcineurin inhibitor plus mycophenolate mofetil or azathioprine and prednisone as well as in healthy volunteers. KIM-1 was estimated in urine using a commercially available kit.ResultsKidney transplant recipients showed significantly higher KIM-1 values than the control group. Normotensive kidney allograft recipients displayed significantly lower NGAL results than hypertensive subjects. Urinary KIM-1 was significantly higher among diabetic than nondiabetic subjects, whereas creatinine did not differ significantly between them. Upon univariate analysis urinary KIM-1 strongly correlated with serum creatinine (r = .64) and eGFR (r = ?.71), and only weakly with other parameters. Upon multiple regression analysis, the best predictor of urinary KIM-1 was eGFR (beta ?0.61), which explained 61% of KIM-1 concentrations.ConclusionEven a successful kidney transplantation is associated with kidney injury as reflected by elevated urinary KIM-1 and lower eGFR. Therefore, KIM-1 needs to be investigated as a potential early marker for impaired renal function/kidney injury, especially in patients with other risk factors for damage such as hypertension or diabetes.     

Prevalence of chronic kidney disease in orthotopic heart transplant recipients and kidney allograft recipients using the new Chronic Kidney Disease Epidemiology Collaboration formula

Chronic kidney disease (CKD) is an important long-term complication of all forms of nonrenal organ transplantation. The aim of this study was to assess the prevalence of kidney dysfunction among heart (n = 163) and kidney allograft recipients (n = 169) using the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, which includes age, gender, and comorbidities. The mean serum creatinine values in these populations were 1.58 ± 0.75 mg/dL and 1.36 ± 0.56 mg/dL, respectively. In heart allograft recipients mean estimated glomerular filtration rate (eGFR) by (MDRD) was 57.14 ± 26.17 mL/min, and by CKD-EPI formula was 57.44 ± 26.76 mL/min whereas in kidney allograft recipients it was 63.91 ± 25.43 mL/min and 65.20 ± 25.60 mL/min, respectively. According to the MDRD formula, stage 2 CKD was noted in 35 patients; stage 3 CKD in 79 patients, and stage 4 in 23 patients. According to the CKD-EPI formula stage 2 CKD was displayed by 35 patients; stage 3 CKD in 78 patients, and stage 4 in 23 patients. Clinically significant CKD (GFR < 60 mL/min) was observed in 62% of patients. According to the MDRD normal kidney function was present in 22 and according to the CKD-EPI formula in 27 patients. According to the MDRD formula stage 2 CKD was found in 59 kidney allograft recipients; stage 3 in 58 patients; and stage 4 in 16 patients. According to the CKD-EPI formula, stage 2 CKD was noted in 63 patients; stage 3 in 58 patients; and stage 4 in 15 patients. Clinically significant CKD was observed in 44% of patients. Using MDRD or CKD-EPI normal kidney function was found in 36 and 33 patient, respectively.CKD prevalence is extremely high among heart and kidney transplant recipients. Evaluation of renal function is important to select the appropriate strategy to reduce the cardiovascular risk.     

Predictors of growth and body composition in HIV‐infected children beginning or changing antiretroviral therapy

Objectives

The aim of the study was to describe growth and body composition changes in HIV‐positive children after they had initiated or changed antiretroviral therapy (ART) and to correlate these with viral, immune and treatment parameters.

Methods

Ninety‐seven prepubertal HIV‐positive children were observed over 48 weeks upon beginning or changing ART. Anthropometry and bioelectrical impedance analysis results were compared with results from the National Health and Nutrition Examination Survey 1999–2002 (NHANES) to generate z‐scores and with results for HIV‐exposed, uninfected children from the Women and Infants Transmission Study (WITS). Multivariate analysis was used to evaluate associations between growth and body composition and disease parameters.

Results

All baseline lean and fat mass measures were below those of controls from NHANES. Weight, height and fat free mass (FFM) index (FFM/height²) z‐scores increased over time (P=0.004, 0.037 and 0.027, respectively) and the waist:height ratio z‐score decreased (P=0.045), but body mass index and per cent body fat z‐scores did not change. Measures did not increase more than in uninfected WITS controls. In multivariate analysis, baseline height, mid‐thigh circumference and FFM z‐scores related to CD4 percentage (P=0.029, P=0.008 and 0.020, respectively) and change in FFM and FFM index z‐scores to CD4 percentage increase (P=0.010 and 0.011, respectively). Compared with WITS controls, baseline differences in height and mid‐thigh muscle circumference were also associated with CD4 percentage. Case–control differences in change in both subscapular skinfold (SSF) thickness and the SSF:triceps skinfold ratio were inversely associated with viral suppression. No measures related to ART class(es) at baseline or over time.

Conclusions

In these HIV‐positive children, beginning or changing ART was associated with improved growth and lean body mass (LBM), as indicated by FFM index. Height and LBM related to CD4 percentage at baseline and over time. Altered fat distribution and greater central adiposity were associated with detectable virus but not ART class(es) received.     

Analysis of serious non‐AIDS events among HIV‐infected adults at Latin American sites

Objective

Acquired immune deficiency appears to be associated with serious non‐AIDS (SNA)‐defining conditions such as cardiovascular disease, liver and renal insufficiency and non‐AIDS‐related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort.

Materials and methods

Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV‐associated factors on non‐AIDS‐defining conditions.

Results

Among 6007 patients in follow‐up, 130 had an SNA event (0.86 events/100 person‐years of follow‐up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non‐AIDS‐defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T‐cell count prior to index date (P=0.0056, with an average difference of more than 100 cells/μL) and area under the CD4 cell curve in the year previous to index date (P=0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors.

Conclusions

The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.     

Elevated resistin is related to inflammation and residual renal function in haemodialysed patients

AIM: Resistin is an adipocytokine that recently generated much interest. Because of the fact that inflammation, endothelial cell damage or injury is invariably associated with such clinical conditions as thrombosis, atherosclerosis and their major clinical consequences, that is, cardiovascular disease and resistin play a role in linking inflammation and cardiovascular disease, the aim of the study was to assess resistin in correlation with markers of inflammation, endothelial cell injury and residual renal function in haemodialysed (HD) patients. METHODS: We assessed resistin, markers of coagulation: thrombin-antithrombin complexes (TAT), prothrombin fragments 1+2; fibrinolysis: tPA, plasminogen activator inhibitor type 1, plasmin-antiplasmin complexes (PAP); endothelial function/injury: von Willebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM); inflammation: high sensitivity C-reactive protein (hsCRP), tumour necrosis factor alpha and interleukin-6 (IL-6). RESULTS: Healthy volunteers and HD patients did not differ significantly regarding age, leucocyte count, serum iron, aspartate and alanine aminotransferases activities, calcium, cholesterol, tPA concentration. Triglycerides, CRP (assessed by high sensitivity method), phosphate, urea, creatinine, IL-6, tumour necrosis factor alpha, vWF, prothrombin fragments 1+2, TAT, PAP, thrombomodulin, ICAM, plasminogen activator inhibitor type 1 and resistin, were elevated in HD patients when compared with the control group. Serum albumin, total protein, haemoglobin and haematocrit were significantly lower in HD patients when compared with the control group. In HD patients with hsCRP 0e; 6 mg/L, resistin, IL-6, vWF and F1+2 were significantly higher, whereas tPA was significantly lower than in patients with hsCRP<6 mg/L. Moreover, HD patients with residual renal function have significantly lower resistin when compared with patients without it. Resistin was significantly higher in diabetics. In HD patients, resistin correlated significantly, in univariate analysis, with calcium, phosphate, PTH, TIBC, vWF residual renal function, urea, hsCRP, IL-6 and tended to correlate with tPA and ferritin. In the healthy volunteers, resistin was related to IL-6 and hsCRP. In multiple regression analysis, resistin was independently related to hsCRP, IL-6, residual renal function in HD patients. CONCLUSION: Elevated resistin related to markers of inflammation may represent a novel link between inflammation and adipocytokines in HD patients. Impaired renal function and inflammation are responsible for elevated resistin in HD patients.     

Assessment of kidney function in diabetic patients. Is there a role for new biomarkers NGAL,cystatin C and KIM-1?

PurposeAssessment of kidney injury early detection in diabetic patients has great importance for therapy and prognosis. The aim of this study was to assess whether neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, and kidney injury molecule-1 (KIM-1) could represent sensitive markers of kidney function/injury in patients with coronary heart disease and diabetes.Materials and MethodsThe study comprised 121 consecutive patients with diabetes referred for coronary angiography due to coronary heart disease and a reference group consisting of 64 patients without diabetes.ResultsCystatin C, serum and urinary NGAL values were significantly higher in diabetics than in non-diabetics. There was no significant difference in KIM-1 levels in both groups. Serum NGAL in diabetic group was associated with serum creatinine, fibrinogen, urinary NGAL, cystatin C and inversely related to kidney function assessed with 4 equations. After analysing levels of studied biomarkers in both groups, no significant difference in patients with estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73m² was found. The analysis of patients with eGFR over 60 ml/min/1.73m² showed significant differences in cystatin C and urinary NGAL levels. The area under the curve for serum NGAL, urinary NGAL and cystatin C was 0.60 (95% CI, 0.51 to 0.69), 0.59 (95% CI, 0.5 to 0.68), 0.62 (95% CI, 0.54 to 0.71), respectively, good cut-off values of studied biomarkers to detect diabetes were not found.ConclusionNGAL, cystatin C and KIM-1 are not more useful than eGFR in the assessment of kidney function in diabetic patients with coronary heart disease.     

Physiological determinants of residual cerebral arterial pulsatility on best medical treatment after TIA or minor stroke

Cerebral arterial pulsatility is strongly associated with cerebral small vessel disease and lacunar stroke yet its dependence on central versus local haemodynamic processes is unclear. In a population-based study of patients on best medical managment, 4–6 weeks after a TIA or non-disabling stroke, arterial stiffness and aortic systolic, diastolic and pulse pressures were measured (Sphygmocor). Middle cerebral artery peak and trough flow velocities and Gosling’s pulsatility index were measured by transcranial ultrasound. In 981 participants, aortic and cerebral pulsatility rose strongly with age in both sexes, but aortic diastolic pressure fell more with age in men whilst cerebral trough velocity fell more in women. There was no significant association between aortic systolic or diastolic blood pressure with cerebral peak or trough flow velocity but aortic pulse pressure explained 37% of the variance in cerebral arterial pulsatility, before adjustment, whilst 49% of the variance was explained by aortic pulse pressure, arterial stiffness, age, gender and cardiovascular risk factors. Furthermore, arterial stiffness partially mediated the relationship between aortic and cerebral pulsatility. Overall, absolute aortic pressures and cerebral blood flow velocity were poorly correlated but aortic and cerebral pulsatility were strongly related, suggesting a key role for transmission of aortic pulsatility to the brain.     

An australian audit of vaccination status in children and adolescents with inflammatory bowel disease

Background

Pre-existing polyps, especially large polyps, are known to be the major source for colorectal cancer, but there is limited available information about factors that are associated with polyp size and polyp growth. We aim to determine factors associated with polyp size in different age groups.

Methods

Colonoscopy data were prospectively collected from 67 adult gastrointestinal practice sites in the United States between 2002 and 2007 using a computer-generated endoscopic report form. Data were transmitted to and stored in a central data repository, where all asymptomatic white (n = 78352) and black (n = 4289) patients who had a polyp finding on screening colonoscopy were identified. Univariate and multivariate analysis of age, gender, performance site, race, polyp location, number of polyps, and family history as risk factors associated with the size of the largest polyp detected at colonoscopy.

Results

In both genders, size of the largest polyp increased progressively with age in all age groups (P < .0001). In subjects ≥ 80 years the relative risk was 1.55 (95% CI, 1.35-1.79) compared to subjects in the youngest age group. With the exception of family history, all study variables were significantly associated with polyp size (P < .0001), with multiple polyps (≥ 2 versus 1) having the strongest risk: 3.41 (95% CI, 3.29-3.54).

Conclusions

In both genders there is a significant increase in polyp size detected during screening colonoscopy with increasing age. Important additional risk factors associated with increasing polyp size are gender, race, polyp location, and number of polyps, with polyp multiplicity being the strongest risk factor. Previous family history of bowel cancer was not a risk factor.     

Anemia Is a Predictor of Outcome in Heart Transplant Recipients

Background

Cardiovascular disease and kidney disease share similar characteristics. It has been recently recognized that many patients with cardiovascular disease have anemia, which often is associated with kidney dysfunction. Even the term “cardiorenal anemia syndrome” was endorsed to stress the dangerous association.

Objective

To assess the prevalence of anemia in relation to chronic kidney disease in 160 patients after orthotopic heart transplantation.

Results

According to the World Health Organization definition of anemia (hemoglobin concentration <13 g/dL in males and <12 g/dL in females), 41% of our patients had anemia. Patients with anemia exhibited a significantly lower mean (SD) glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease formula vs the Cockcroft-Gault formula: 44.46 (26.84) mL/min vs 62.70 (24.15) mL/min and 48.93 (27.80) mL/min vs 72.11 (29.76) mL/min, respectively (P < .001). In addition, they demonstrated lower creatinine clearance, red blood cell count, hemoglobin concentration, and ejection fraction and significantly higher creatinine and N-terminal probrain natriuretic peptide concentrations. Presence of anemia was associated with time since transplantation, GFR, creatinine clearance, N-terminal probrain natriuretic peptide and cholesterol concentrations, and ejection fraction. At multiple regression analysis, the only predictor of anemia was kidney function (GFR or creatinine clearance), which accounts for 22% of the variation. Type of immunosuppression regimen (calcineurin inhibitors vs mammalian target of rapamycin) did not seem to affect prevalence of anemia in the study population.

Conclusions

The prevalence of anemia is relatively high in heart allograft recipients and is not adequately treated. In patients with cardiovascular disease, GFR should be estimated because renal dysfunction and subsequent anemia are important risk factors for cardiovascular morbidity and mortality. Chronic heart failure is also more common in patients with anemia.