Degree Of Renal Dysfunction Research Articles

Close relationship between redox state of human serum albumin and serum cysteine levels in non-diabetic CKD patients with various degrees of renal function.

Human mercaptalbumin (HMA) acts as a covalent-carrier protein for sulfur-containing amino acids, cysteine, and glutathione. In addition, its sulfhydryl residue reacts with peroxyl radicals. In this study, we evaluated the redox state of human serum albumin and its relationship with serum amino thiol levels in non-diabetic chronic kidney disease (CKD) patients with various degrees of renal function. High performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) with selected ion monitoring were used to analyze serum samples collected from 37 non-dialysis patients with primary glomerulonephritis without diabetes mellitus (DM) or other systemic diseases (non-diabetic CKD patients). Total cysteine and homocysteine plasma levels increased with decreasing renal function and showed a significant negative correlation with glomerular filtration rate. The protein-bound ratio of serum cysteine also changed with the degree of renal dysfunction. The HPLC fraction of human mercaptalbumin (HMA) (%) was significantly lower in nondiabetic CKD patients than in healthy subjects. The redox state of human serum albumin (i.e., HMA %) correlated significantly with the total serum cysteine level. The HPLC fraction of HMA (%) closely correlated with the serum cysteine level in non-diabetic CKD patients. An increase in oxidized cysteine with impaired renal function and a reduced plasma redox capacity associated with a decrease in the reduced form of serum albumin (HMA %) may be important risk factors for promoting long-term complications in patients with renal dysfunction.

Peri-operative kidney injury and long-term chronic kidney disease following orthotopic heart transplantation in children.

Significant advances in cardiac intensive care including extracorporeal life support have enabled children with complex congenital heart disease and end-stage heart failure to be supported while awaiting transplantation. With an increasing number of survivors after heart transplantation in children, the complications from long-term immunosuppression, including renal insufficiency, are becoming more apparent. Severe renal dysfunction after heart transplant is defined by a serum creatinine level >2.5 mg/dL (221 μmol/L), and/or need for dialysis or renal transplant. The degree of renal dysfunction is variable and is progressive over time. About 3–10 % of heart transplant recipients will go on to develop severe renal dysfunction within the first 10 years post-transplantation. Multiple risk factors for chronic kidney disease post-transplant have been identified, which include pre-transplant worsening renal function, recipient demographics and morbidity, peri-transplant haemodynamics and long-term exposure to calcineurin inhibitors. Renal insufficiency increases the risk of post-transplant morbidity and mortality. Hence, screening for renal dysfunction pre-, peri- and post-transplantation is important. Early and timely detection of renal insufficiency may help minimize renal insults, and allow prompt implementation of renoprotective strategies. Close monitoring and pre-emptive management of renal dysfunction is an integral aspect of peri-transplant and subsequent post-transplant long-term care.

Prognostic value of regadenoson myocardial single-photon emission computed tomography in patients with different degrees of renal dysfunction

Patients with chronic kidney disease (CKD) have worse cardiovascular outcomes. The prognostic value of the new pharmacological stressor regadenoson (REG) in patients with varying levels of kidney function is not known (REG-SPECT). Furthermore, the impact of varying levels of kidney dysfunction on cardiac outcomes in patients undergoing REG-SPECT has not been defined. Our objective was to evaluate the prognostic value of regadenoson stress imaging in patients with different levels of kidney dysfunction. We followed 1107 consecutive patients who underwent REG-SPECT for a mean duration of 1.8 ± 0.8 years. CKD was defined as estimated glomerular filtration rate (GFR) 60 mL/min/1.73 m(2). Kaplan-Meier survival analysis was performed to evaluate survival, free of major adverse cardiac events (MACE). CKD patients with GFR <60 (47% male, mean age 70 years) had a higher prevalence of cardiac risk factors and a history of coronary artery disease and were on significantly more cardiac medications (P < 0.001) than those with GFR >60. Patients with GFR <60 were significantly more likely to develop adverse cardiac outcomes including congestive heart failure (CHF) (P = 0.02), cardiac death (P < 0.001), all-cause death (P < 0.001), and MACE (P < 0.001) over the period of follow-up. Cardiac death increased with worsening levels of perfusion defects (SSS) across the entire spectrum of renal function (P < 0.001). GFR <60 was an independent predictor of MACE with a hazard ratio (HR) of 1.49 (95% CI: 1.06-2.08). The presence of transient ischaemic dilation (TID) was associated with an HR of 5.06 (95% CI: 1.43-17.90). Renal function is a powerful risk predictor in patients undergoing REG-SPECT. REG-SPECT provides robust prognostication across the entire spectrum of renal function.

Assessing validity of serum cystatin C for predicting metabolic syndrome.

Serum concentration of cystatin C a marker of glomerular filtration has been associated with Cardiovascular Disease (CVD). The aim of this study was to evaluate cystatin C as a marker of diabetic kidney disease in normoalbuminuric diabetic patients without Chronic Kidney Disease (CKD). The study population consisted of 65 subjects with metabolic syndrome and 32 subjects free of metabolic syndrome (control group). HDL-C, LDL-C, blood urea, triglycerides, glucose, HbA1c, serum cystatin C and serum creatinine were measured in both groups. GFR was calculated in both groups using Cockrofta Gault equation. Metabolic syndrome presented higher cystatin C levels than normal samples (0.98 8 0.26 1.24 8 0.24 p < 0.05). In the binary logistic regression, the presence of diabetes and metabolic syndrome was significantly associated with elevated cystatin C levels. Diabetic patients also presented a slightly greater creatinine (1.11 8 0.09 1.04 0.15 p < 0.05). The results suggest that cystatin C may be a marker for metabolic syndrome and may identify a certain degree of renal dysfunction even when serum creatinine does not exceed normal level.

The impact of chronic kidney disease and short-term treatment with rosiglitazone on plasma cell-free DNA levels.

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease. Circulating free nucleic acids, known as cell-free DNA (cfDNA), have been proposed as a novel biomarker of cardiovascular risk. The impact of renal impairment on cfDNA levels and whether cfDNA is associated with endothelial dysfunction and inflammation in CKD has not been systematically studied. We analysed cfDNA concentrations from patients with varying degrees of CKD. In addition, to determine whether there is a relationship between cfDNA, inflammation, and endothelial dysfunction in CKD, levels of proinflammatory cytokines and von Willebrand Factor (vWF) were measured in patients treated with the peroxisome proliferator-activated receptor gamma agonist rosiglitazone or placebo for 8 weeks. cfDNA levels were not increased with renal impairment or associated with the degree of renal dysfunction (P = 0.5). Treatment with rosiglitazone for 8 weeks, but not placebo, was more likely to lead to a reduction in cfDNA levels (P = 0.046); however, the absolute changes in cfDNA concentrations during treatment were not statistically significant (P > 0.05). cfDNA levels correlated with markers of endothelial dysfunction (hsCRP P = 0.0497) and vWF (P = 0.0005). In conclusion, cell-free DNA levels are not influenced by renal impairment but do reflect endothelial dysfunction in patients with CKD.

Growth retardation in children with chronic renal disease

Despite recent advances in the management of children with chronic renal disease (CRD), growth retardation remains its most visible comorbid condition. Growth retardation has adverse impact on morbidity and mortality rates, quality of life and education, and in adult patients on job family life, and independent leaving accomodation. Pathophysiology of impaired growth in CRD is complex and still not fully understood. The following complications are: anorexia, malnutrition, inflammation, decreased residual renal function, dialysis frequency and adequacy, renal anemia, metabolic acidosis, fluid/electrolyte imbalance, renal osteodistrophy, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) resistance. Malnutrition is most frequent and most important factor contributing to the degree of growth retardation in infancy. The degree of renal dysfunction is the major determinant of variability in growth from third year of age until puberty onset, while in puberty hypergonadotropic hypogonadism has negative effect. The main factors that influence growth after renal transplantation are the age of the recipient and glucocorticoid drugs dosage with negative effect and allograft function with positive effect. In order to improve growth in children with CRD it is necessary to include: diet with optimal caloric intake, correction of fluid/ electrolyte imbalance, correction of acidosis, renal osteodistrophy and anemia. If growth velocity is insufficient to normalize growth, it is necessary to start recombinant human GH (rhGH) therapy at 0.05 mg/kg per day (0.35 mg/kg per week or 28 IU/m2 per week) administered by subcutaneous injection.

Elevated Serum Levels Of Von Willebrand Factor (vWF) Predict For Early Death and Shorter Survival In Patients With Primary Systemic Light Chain (AL) Amyloidosis Independently Of Cardiac Biomarkers

Organ dysfunction in systemic light chain (AL) amyloidosis is caused by the deposition of amyloid fibrils composed of immunoglobulin light chains in tissue microcirculation. vWF is mainly produced, stored and secreted by endothelial cells (ECs) and it is critical for thrombus formation. The secretion of vWF by ECs is triggered by several conditions and it has been proposed that changes in the levels of circulating vWF may reflect a state of “stimulation” of the endothelium. Cardiac involvement is the main determinant of prognosis in AL amyloidosis, but the role of endothelium in this disease has not been extensively studied and no marker of endothelial dysfunction has been evaluated, as yet. Thus, we studied the prognostic role of vWF in patients with AL amyloidosis who were treated with novel agents.The vWF antigen (vWFag) levels were measured using a latex particle-enhanced immunoturbidimetric assay (HemosIL vWF antigen) with an automated coagulometer (ACL Top 3G, Instrumentation Laboratory, Lexington, MA, USA). The inter- and intra-assay CVs were 2% and 3% at a concentration of 123.5 U/dL, respectively, and the lower limit of detection was 2.2 U/dL.The analysis included 81 consecutive patients with newly diagnosed AL amyloidosis who were treated in a single center (Department of Clinical Therapeutics, University of Athens, Greece) from 2005 to 2012. Median age of the patients was 68 years (range 42-82 years) and the median number of involved organs was 2; heart was involved in 62%, kidneys in 74%, peripheral nerve in 24%, liver in 9% and soft tissue in 21% of patients. Median NTproBNP level was 2,318 pg/mL (range 33-75,000 pg/mL); 36% had NTproBNP levels ≥4,000 pg/mL and 28%, 38% and 34% of patients had Mayo stage -1, -2 and -3, respectively. Primary therapy based on bortezomib was given in 52% of patients, on lenalidomide in 44%, while 4% received MDex. Median survival of the cohort was 47 months; 3- and 6-month mortality was 12% and 20%, respectively.The median serum level of vWFag in patients with AL amyloidosis was 181 (range 20-557) U/dL and was significantly higher than that measured in healthy controls (median: 84 U/dL, range 48-124; p <0.001). There was no significant association of vWFag levels with renal, cardiac, nerve or liver involvement. There was no significant correlation of vWFag levels with the levels of NTproBNP (or BNP) or Mayo stage and there was no significant correlation with the degree of renal dysfunction, serum albumin levels or proteinuria. Levels of involved free light chains did not have any correlation with vWFag levels either.We then examined the prognostic significance of vWFag and we found that levels of vWFag within the top quartile (≥230 U/dL) were associated with a very poor outcome (median survival 4 months vs. 47 months, p=0.001). Because the most important predictor of early death in patients with AL amyloidosis is cardiac involvement, we performed a multivariate analysis which included NTproBNP levels: vWFag levels ≥230 U/dL were independently associated with survival (HR: 2.64, 95% CI 1.2-5.8, p=0.01), along with NTproBNP levels ≥4,000 pg/ml (HR: 4.17, 95% CI 1.98- 8.8, p<0.001). Because the survival curves indicated that patients with vWFag ≥230 U/dL had a significant probability of early death, we performed an analysis to identify whether vWFag is a significant predictor of early death, adjusting for the levels of NTproBNP ≥4000 pg/mL. Thus, in multivariate analysis, vWFag ≥230 U/dL was independent predictor of death within 6 months from initiation of therapy (HR: 15, 95% CI 2.6-84, p=0.002) together with NTproBNP ≥4,000 pg/mL (HR: 16.8, 95% CI 3- 94, p=0.001). A combination of the two risk factors was able to identify patients at a very high risk of early death: 75% of patients with both risk factors present died within 3 months from initiation of therapy (figure).In conclusion, vWFag levels are elevated in patients with AL amyloidosis but are not correlated with other features of the disease, such as pattern of organ involvement and cardiac biomarkers. For the first time, we found that high levels of vWFag are associated with a high risk of early death and shorter survival in patients with AL amyloidosis, independently of cardiac biomarkers. In addition, wWFag levels improve the prognostic ability of cardiac biomarkers in patients with AL amyloidosis. Our data also justify the investigation of the role of endothelial dysfunction in AL amyloidosis. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Characteristic kidney pathology, gene abnormality and treatments in LCAT deficiency

Lecithin:cholesterol acyltransferase (LCAT) is a key enzyme involved in reverse cholesterol transport from the peripheral tissues to the liver. LCAT deficiency, in which this enzyme is congenitally absent, is a genetic disease that impairs the esterification of free cholesterol in the plasma, leading to accumulation of phospholipids, including lecithin, in the organs of the body; the clinical manifestations include corneal opacities, normochromic anemia, renal disorder, etc. The prognosis is determined by the degree of renal dysfunction, and renal biopsy specimens reveal characteristic light- and electron-microscopic findings. The disease, transmitted by autosomal recessive inheritance, is extremely rare. There have only been 88 gene mutations of the LCAT gene reported around the world, and 13 of them are from Japan. One of the characteristics of LCAT deficiency is the strong correlations among the patterns, extent and phenotypes of these gene mutations.

Does bicarbonate prevent contrast-induced nephropathy in cardiovascular patients undergoing contrast imaging?: Table 1:

A best evidence topic in cardiovascular surgery was written according to a structured protocol. The question addressed was whether administering sodium bicarbonate (NaHCO3) prevents contrast-induced nephropathy (CIN) in cardiovascular patients undergoing contrast imaging. In total, 266 papers were found using the reported search, 16 of which represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. CIN is thought to occur as a result of ischaemic or oxidative injury to the kidney. It is postulated that NaHCO3attenuates this renal damage by alkanizing renal tubular fluid thus reducing the generation of contrast-induced free radicals, which damage the kidney. Of the 16 trials, 15 recruited patients with various degrees of renal dysfunction at baseline. The benefit of using NaHCO3 was demonstrated at all stages of chronic kidney disease. Apart from four studies, 12 studies used low toxicity, low-osmolar contrast. Merten et al. published the first trial of NaHCO3 vs (saline) NaCl in preventing CIN, demonstrated a significantly lower rate in the NaHCO3 group and advocated its widespread use. Subsequent trials using the same regimen have collaborated these results. However, more recently, Gomes et al. concluded that NaHCO3 is not superior to saline-based hydration. Similarly, Brar et al. randomized 323 patients with moderate-to-severe renal insufficiency to receive either an NaHCO3 or an NaCl infusion and observed no difference in CIN rates. Two studies investigated the effects of rapid urine alkanization with bolus injections of NaHCO3 prior to contrast and found significant reductions in CIN rates compared with NaCl-treated groups. One study observed that NaCl is superior to NaHCO3, while all other studies showed a beneficial effect or no difference between NaCl- and NaHCO3-based hydration. The most recent meta-analysis by Jang et al. incorporated 3609 patients across 19 trials and concluded that NaHCO3-based hydration regimens are superior to NaCl-based ones. Based on this review, the authors recommend NaHCO3 alongside an NaCl hydration regimen. The exact regimen will depend on the context within which contrast is being administered and needs further evaluation.

Warfarin treatment, kidney dysfunction and outcome in acute myocardial infarction patients with a history of atrial fibrillation

Recent studies suggest that warfarin increases the risk of ischemic stroke and mortality in people with end-stage renal disease and atrial fibrillation (AF). It is unknown at which degree of renal dysfunction the risk outweights the benefit. Cross-sectional study with prospective follow-up in the SWEDEHEART registry. Inclusion criteria were consecutive survivors of MI with history of AF and known serum creatinine (n=24317). Patients were classified into 5 renal disease stages according to their estimated glomerular filtration rate (eGFR). Primary outcome was a composite of death, readmission due to MI, ischemic stroke and bleeding within 1 year. Secondary outcomes were each event separately. Multivariate adjustment included age, sex, comorbidities, presentation, hospital course and discharge medication. A total of 5292 (21,7%) patients received warfarin at discharge. Warfarin treatment was significantly associated with lower risk for both the primary (HR and 95% CI 0.76 [0.72-0.81]) and secondary outcomes (Death, 0.67 [0.61, 0.73]; MI readmission 0.88 [0.81, 0.96]; Ischaemic stroke 0.58 [0.48, 0.71]) without increasing the risk of bleeding (1.04 [0.88, 1.23]). As many as 53,5% of patients had moderate to several renal disease (eGFR<60 ml/min/1.73 m2). For each renal disease strata, warfarin treatment was associated with a decreased risk of overall events as well as of death MI readmission or stroke alone. Bleeding events were neither increased nor reached statistical significance across differing degrees of renal dysfunction. View this table: Table 1. Fully adjusted Cox regression models showing hazards associated with warfarin use in individuals with differing renal function compared to equivalent individuals not receiving warfarin Warfarin treatment associated with a decreased 1-year risk of a composite event of death, readmission for MI, stroke and bleeding in MI patients with a history of AF. This was also true in individuals with mild, moderate and severe renal disease.

Knee extensor muscle strength and index of renal function associated with an exercise capacity of 5 metabolic equivalents in male chronic heart failure patients with chronic kidney disease

The goal of the present study was to determine knee extensor muscle strength (KEMS) and degree of renal dysfunction associated with an exercise capacity of ≥5 metabolic equivalents (METs) in male chronic heart failure (CHF) patients with chronic kidney disease (CKD). In this cross-sectional study of 75 male CHF patients with CKD (65.3±11.6years), we measured clinical characteristics, peak [Formula: see text], estimated glomerular filtration rate (eGFR), and KEMS. Patients were divided into two groups by exercise capacity: ≥5 METs group (n=41) and <5 METs group (n=34). Cutoff values for KEMS and eGFR resulting in an exercise capacity of ≥5 METs were selected with ROC curves. Patients were divided into four groups according to cutoff values, and numbers of patients attaining an exercise capacity of ≥5 METs were compared between groups. Age was significantly higher although eGFR, Hb, and KEMS were lower in the <5 METs versus ≥5 METs group (P<0.001). Multiple logistic regression analysis revealed a positive significant relation between KEMS and eGFR and exercise capacity of ≥5 METs. Exercise capacity of ≥5 METs was associated with KEMS of approximately 1.69Nm/kg and an eGFR of 45.7mL/min/1.73m(2). The number of patients attaining an exercise capacity of ≥5 METs in the patients who did not reach both cutoff values was significantly lower than that in any other patients (P<0.001). KEMS and eGFR may be useful indices for predicting attainment of exercise capacity of ≥5 METs in male CHF patients with CKD.

Evaluation of digoxin concentration after loading dose in patients with renal dysfunction.

Loading dose recommendations for digoxin are based on the volume of distribution, which is proportional to lean body weight, whereas maintenance dose recommendations depend on renal function. The volume of distribution of this drug is demonstrably reduced in severe renal dysfunction, but the threshold at which a reduction in loading dose is warranted remains unknown. To describe the practice of digoxin loading at The Ottawa Hospital and to determine the proportion of patients, categorized by degree of renal function, who experienced digoxin toxicity after a loading dose. Data were collected retrospectively from charts of patients who had received a digoxin loading dose between May 2008 and January 2012, with a blood sample drawn for determination of digoxin concentration 6 to 24 h later. Patients were categorized into 4 groups according to creatinine clearance. The mean loading dose of digoxin (± standard deviation) was 9.8 ± 4.1 μg/kg among patients with creatinine clearance below 15 mL/min, 14.4 ± 5.4 μg/kg for those with creatinine clearance between 15 and 29 mL/min, 16.0 ± 5.6 μg/kg for those with creatinine clearance between 30 and 59 mL/min, and 14.0 ± 3.7 μg/kg for those with creatinine clearance 60 mL/min or above. Degree of renal dysfunction, particularly creatinine clearance below 60 mL/min, predicted the likelihood of experiencing a toxic serum concentration of digoxin after the loading dose, after adjustment for dose and weight (odds ratio 2.60, 95% confidence interval 1.55-4.39). Patients with creatinine clearance below 60 mL/min were more likely than those with creatinine clearance of 60 mL/min or greater to experience toxic serum digoxin concentrations with current loading dose strategies. It is recommended that loading doses be reduced (to 6-10 μg/kg) for these patients. Prospective trials are required to determine the clinical implications of these findings and to determine if greater reductions in loading dose are required for patients with severe renal dysfunction (i.e., creatinine clearance below 30 mL/min).

404 RENAL DYSFUNCTION IS COMMON IN HBV POSITIVE PATIENTS: A SINGLE CENTRE EXPERIENCE

Background and Aims: A close relationship exists between HBV infection and renal dysfunction. This study was undertaken to evaluate the degree of renal dysfunction in HBV positive patients in a university hospital in Mumbai and factors predicting it. Methods: We retrospectively analyzed 663 HBV positive patients presenting to our clinic from January 2010-June 2012 for renal dysfunction (estimated Glomerular Filtration rate (eGFR) by MDRD formula). Excluding 13 patients on maintenance hemodialysis and 66 with missing data, 584 patients (467 males; median age 43, range 9–80 years) were included. Results: Of 584 patients, 24 had acute hepatitis, 209 non-cirrhotic Chronic Hepatitis B (CHB), 214 were inactive carriers, 108 had CHB with cirrhosis, 22 were in immunotolerant phase, 6 had acuteon-chronic liver failure, 1 patient post liver transplant. Majority of patients were HBeAg negative (74.82%). 141 patients (24.1%) had comorbidities (diabetes mellitus and/or systemic hypertension). Serum creatinine was elevated (>1.5mg/ml) in 20 patients (2.7%) while eGFR (MDRD) was below normal ( 90ml/min/1.72m, 293 patients. Based on HBV disease status, renal function was different: In acute group (acute hepatitis, immunotolerant), 26.53% patients had mild renal dysfunction (eGFR 60–90ml/min/1.72m) versus chronic disease group (inactive carrier status, CHB, cirrhosis, others) with 44.49% (p =0.008). In multivariate analysis, age, gender, hypertension and chronic disease stage had significant association with reduced eGFR. 1 year follow-up eGFR values were available for 321 patients, of which 79 (25%) showed worsening of renal function by >20% while 58 patients (15%) showed >20% improvement. Within the cirrhotic population, Diabetes was significantly more prevalent than in other populations (33% of patients). 62/108 (57%) of cirrhotic patients had reduced renal function. Conclusion: HBV infection is associated with significant degree of reduced renal function, reaching up to 50% in the chronic population of our clinic. Comorbidities (25%) or antiviral treatment might further increase renal risk, therefore regular monitoring of renal function is recommended. MDRD formula was shown to be more sensitive than serum creatinine for renal function evaluation.

405 HARPE STUDY: PREVALENCE OF RENAL ABNORMALITIES IN CHRONIC HBV INFECTION

Background and Aims: A close relationship exists between HBV infection and renal dysfunction. This study was undertaken to evaluate the degree of renal dysfunction in HBV positive patients in a university hospital in Mumbai and factors predicting it. Methods: We retrospectively analyzed 663 HBV positive patients presenting to our clinic from January 2010-June 2012 for renal dysfunction (estimated Glomerular Filtration rate (eGFR) by MDRD formula). Excluding 13 patients on maintenance hemodialysis and 66 with missing data, 584 patients (467 males; median age 43, range 9–80 years) were included. Results: Of 584 patients, 24 had acute hepatitis, 209 non-cirrhotic Chronic Hepatitis B (CHB), 214 were inactive carriers, 108 had CHB with cirrhosis, 22 were in immunotolerant phase, 6 had acuteon-chronic liver failure, 1 patient post liver transplant. Majority of patients were HBeAg negative (74.82%). 141 patients (24.1%) had comorbidities (diabetes mellitus and/or systemic hypertension). Serum creatinine was elevated (>1.5mg/ml) in 20 patients (2.7%) while eGFR (MDRD) was below normal ( 90ml/min/1.72m, 293 patients. Based on HBV disease status, renal function was different: In acute group (acute hepatitis, immunotolerant), 26.53% patients had mild renal dysfunction (eGFR 60–90ml/min/1.72m) versus chronic disease group (inactive carrier status, CHB, cirrhosis, others) with 44.49% (p =0.008). In multivariate analysis, age, gender, hypertension and chronic disease stage had significant association with reduced eGFR. 1 year follow-up eGFR values were available for 321 patients, of which 79 (25%) showed worsening of renal function by >20% while 58 patients (15%) showed >20% improvement. Within the cirrhotic population, Diabetes was significantly more prevalent than in other populations (33% of patients). 62/108 (57%) of cirrhotic patients had reduced renal function. Conclusion: HBV infection is associated with significant degree of reduced renal function, reaching up to 50% in the chronic population of our clinic. Comorbidities (25%) or antiviral treatment might further increase renal risk, therefore regular monitoring of renal function is recommended. MDRD formula was shown to be more sensitive than serum creatinine for renal function evaluation.

Acute kidney injury in the pregnant patient

Acute kidney injury (AKI) is costly and is associated with increased mortality and morbidity. An understanding of the renal physiologic changes that occur during pregnancy is essential for proper evaluation, diagnosis, and management of AKI. As in the general population, AKI can occur from prerenal, intrinsic, and post-renal causes. Major causes of pre-renal azotemia include hyperemesis gravidarum and uterine hemorrhage in the setting of placental abruption. Intrinsic etiologies include infections from acute pyelonephritis and septic abortion, bilateral cortical necrosis, and acute tubular necrosis. Particular attention should be paid to specific conditions that lead to AKI during the second and third trimesters, such as preeclampsia, HELLP syndrome, acute fatty liver of pregnancy, and TTP-HUS. For each of these disorders, delivery of the fetus is the recommended therapeutic option, with additional therapies indicated for each specific disease entity. An understanding of the various etiologies of AKI in the pregnant patient is key to the appropriate clinical management, prevention of adverse maternal outcomes, and safe delivery of the fetus. In pregnant women with pre-existing kidney disease, the degree of renal dysfunction is the major determining factor of pregnancy outcomes, which may further be complicated by a prior history of hypertension.

Assessment of renal dysfunction using urinary markers in canine babesiosis caused by Babesia rossi

Renal damage is deemed a common, yet poorly documented, complication in canine babesiosis. Serum urea and creatinine are insensitive and non-specific markers of early renal dysfunction and their measurements are influenced by hemolysis caused by babesiosis. Therefore, the aim of this study was to use urinary markers to assess the localization and degree of renal dysfunction in dogs with Babesia rossi infection. Urinary immunoglobulin G (uIgG) and urinary C-reactive protein (uCRP) were measured as markers for glomerular dysfunction, while urinary retinol-binding protein (uRBP) was used as a marker for tubular dysfunction. Eighteen dogs presenting with uncomplicated babesiosis were included and compared with eight clinically healthy dogs. Previously validated commercial ELISA kits were used for the measurement of uIgG, uCRP, and uRBP. Results were related to urinary creatinine concentrations (c). Dogs with babesiosis had significantly higher concentrations of all three measured urinary markers compared to healthy dogs. Except for urinary protein/c ratio (UPC), routine urinary and serum markers for renal function (urine specific gravity (USG), serum urea and creatinine (sCr)) were not significantly different between dogs with babesiosis and healthy dogs. All three urinary markers were positively correlated with each other and with UPC. The data supports the presence of both glomerular and tubular dysfunction in dogs suffering from uncomplicated B. rossi infection. Urinary markers were superior to USG, serum urea and creatinine concentrations for the early detection of renal dysfunction in dogs with babesiosis.

Diffusion-weighted MRI in assessment of renal dysfunction

Background:Diffusion-weighted magnetic resonance imaging (DW-MRI) in renal diseases is an evolving field and its potential is yet to be fully realized.Purpose:To study the relationship between apparent diffusion coefficient (ADC) values of renal parenchyma and serum markers of renal function and stage of chronic kidney disease (CKD).Materials and Methods:A retrospective review was performed of all adult patients who underwent DW-MRI (at b-values of 0 and 500 s/mm2) for renal lesions from January 2009 to September 2010 and revealed 88 patients, of which 22 patients had renal dysfunction and 66 had normal renal function. Of these 22, 15 patients were known cases of CKD and were staged depending on disease severity. ADC values were determined for renal parenchyma and compared. Receiver operating characteristic (ROC) curves were drawn to establish cut-off ADC values. Pearson's correlation coefficient (R) was calculated between ADC and renal function parameters.Results:ADC values in patients with renal dysfunction were significantly lower than in patients with normal renal function (2.1133 ± 0.2851 vs. 2.3198 ± 0.1246 (×10-3 mm2/s)). ADC values lower than 2.0354 (×10-3 mm2/s) were seen only with renal dysfunction and higher than 2.4516 (×10-3 mm2 /s) were seen only with normal function. There was significant inverse correlation between ADC and serum creatinine (R = -0.530), blood urea (R= -0.502), and significant linear correlation (R = 0.784) with estimated glomerular filtration rate (eGFR). ADC values showed a statistically significant decreasing trend with increasing stage of CKD.Conclusion:ADC values may serve as an additional marker for the presence and degree of renal dysfunction.

Immune Response to Hepatitis B Vaccine in Patients with Chronic Kidney Disease

Despite the use of hepatitis B virus (HBV) vaccines and preventive mDespite the use of hepatitis B virus (HBV) vaccines and preventive measures, infection with HBV remains a major global health problem. Patients with chronic kidney disease (CKD) are at an increased risk of acquiring HBV infections from shared dialysis equipment, increased exposure to blood products, and immunodeficiency associated with CKD [1][2]. In addition, they may be more likely to develop chronic infections on exposure to HBV [1][2], and HBV infection among CKD patients is associated with high rates of morbidity and mortality [3][4]. Vaccination s important both for preventing susceptible patients from acquiring HBV and for reducing the pool of HBVinfected patients. HBV infection remains a concern in dialysis populations, because the vaccination programs have been less successful in these populations than in the general population. The causes of poor seroconversion in CKD patients include malnutrition, uremia, and immunosuppression due to renal failure [5]. In the current issue of Hepatitis Monthly, Behnam Hashemi et al. [6] compared the seroconversion rates of patients with different stages of CKD who received the HBV vaccine. The overall seroconversion rate was found to be 78%. This result was comparable with those of studies in patients with end stage renal disease (ESRD) (seroconversion rates, 60–90.5%) [7]. The HBV vaccination is less effective in patients with ESRD than in those without CKD [7]. The seroconversion rate among individuals without CKD was over 90% whereas that among patients with ESRD was only 50–60% [8]. In addition, compared to patients without CKD, ESRD patients frequently showed lower seroconversion rates, lower peak antibody titers, and a more rapid decline of antibody levels [9]. Behnam Hashemi et al. showed that there was significant correlation between hepatitis B surface (HBs) antibody titer and the glomerular filtration rate (GFR) (P = 0.001). However, there was no evident correlation between the seroconversion rate and severity of renal dysfunction. They showed that HBV vaccination in the early stages of CKD did not result in significantly higher seroconversion rates than those achieved on HBV vaccination in the late stages of CKD. Another stu showed that there was no association between the response rate and degree of renal dysfunction in individuals with mild to moderate CKD [10]. However, several studies showed that ESRD patients who were vaccinated before they required dialysis showed higher seroconversion rates and antibody titers than those who were undergoing dialysis when they received vaccination, suggesting a correlation betweenimmune response and degree of renal dysfunction [5][7][11]. It is very important that HBV vaccination be carried out in the early stage of CKD, since seroconversion is correlated with the amount of GFR [5]. DaRoza et al. in a large cohort study showed that patients with higher GFR levels showed a better immune response to the HBV vaccine [5]. These diverse findings may be partly attributable to different inclusion criteria; for example, the ESRD patients included in the study by DaRoza et al. [5] had a poorer GFR than that of the patients in the study by McNulty et al [10]. Nonetheless, the strategies recommended for improving seroconversion rates among ESRD patients include vaccination in the early stages of CKD [12]. Furthermore, elderly patients with ESRD seemed to have a lower rate of seroconversion than that in the younger patients [10][11][12][13]. Behnam Hashemi et al., showed a significant negative correlation between old age (> 60 years) with seroconversion rate. Advanced age, male gender, diabetes CKD patients, and previous blood transfusions are associated with poor seroconversion rates [7][8][9][10][11][12][13][14]. Advanced age gatively affected the seroconversion rate regardless of the patient’s status [5][7][15]. In conclusion, HBV vaccination is necessary in CKD patients, because they are at a high-risk of developing HBV infections. Despite these controversial findings, many clinicians recommend that patients with CKD receive vaccination as soon as chronic progressive renal failure is diagnosed, and if possible, before dialysis is required.

A pilot study to investigate the potential of mass spectrometry profiling in the discovery of novel serum markers in chronic renal disease

There has been significant criticism of how technologies such as SELDI have been used in biomarker discovery and how the data have been analysed. We initiated a proof-of-principle pilot study using SELDI with stringent pre-analytic and analytical procedures with robust statistical analysis, to determine whether, under such conditions, using different degrees of renal dysfunction as a model, useful data could be obtained. SELDI-TOF-MS profiling with stringent quality control measures was used to examine the proteomic profile of serum from healthy controls (n=30), patients with end-stage renal failure being treated by dialysis (n=30) and renal transplant patients (n=50) with varying degrees of graft stability. Principal component analysis of the data suggests that the continuum from normality to end-stage renal failure through 'stable' and 'unstable' transplant may be detected by SELDI profiling. Serum β2 microglobulin was identified as a major component and this was validated using immunonephelometry. This pilot study suggests that stringently controlled SELDI analysis is able to detect proteins which may be useful in the stratification of patients post-renal transplant. Further studies using a larger cohort of patients with chronic allograft dysfunction, defined by protocol biopsies, are indicated.

Commentary to ‘Persistent renin-angiotensin system activation after anti-reflux surgery and its management’

The authors present compelling work on a controversial topic: the pathogenesis of renal damage in patients with VUR. The authors propose that renal scarring in patients with VUR is mediated through RAS activation. They report a temporary decline in plasma renin activity following reflux surgery with further improvement in renal function which was maintained with the addition of an ACE-I. The authors recommend ACE-I ‘soon’ after surgery to prevent further renal injury but only have data for patients on medical therapy in the late postoperative period. Should one be surprised that following ACE-I administration an improvement in several renal parameters was seen knowing the renal protective effects of ACE-I in patients with renal dysfunction? Given the high preponderance of boys in the study group and the degree of renal dysfunction found during