Retinal abnormalities characteristic of inherited renal disease.

Many inherited renal diseases have retinal features that are helpful diagnostically. These include coloboma, drusen, atrophy and pigmentation (retinitis pigmentosa), hamartoma, vascular anomalies, and crystals. Retinal abnormalities occur because the kidney and retina share developmental pathways and structural features including basement membrane collagen IV protomer composition and their vascularity, and because both the kidney and retina are functionally dependent on ciliated cells. Diagnosis of inherited renal disease is important because of the risks of further renal and systemic complications, the implications for other family members, the predictability of the clinical course, and the possibility of treatment. Furthermore, retinal abnormalities may help explain the pathogenesis of the renal disease, and can sometimes be used to monitor its course.

Challenging the glucose challenge test.

BACKGROUND: To reduce the number of patients needing oral glucose tolerance test (OGTT), screening options have been considered, balancing patient comfort, cost and risk of missed diagnosis. Australian Diabetes in Pregnancy Society (ADIPS) recommends glucose challenge test (GCT) as screening for gestational diabetes mellitus (GDM), while others suggest fasting plasma glucose (FPG). International Association of Diabetes and Pregnancy Study Group (IADPSG) recently recommended new diagnostic criteria for GDM using one-step OGTT. AIM: (i) To determine how many GDM patients would be missed with GCT/OGTT or FPG/OGTT compared to OGTT alone. (ii) To assess GCT in screening for GDM using new IADPSG criteria. METHODS: Austin Pathology database was searched from 2005 to 2007; 8486 episodes of GCT and OGTT were found. Test characteristics were determined for: (i) Simulated GCT/OGTT, where the 60-min OGTT value was regarded as equivalent to 60-min GCT value; (ii) Simulated FPG/OGTT, investigating the utility of different FPG values to indicate need for OGTT. RESULTS: Oral glucose tolerance test (one-step procedure): Of 5473 patients who had OGTT alone, 14% had GDM (ADIPS criteria). Actual GCT/OGTT: Of 2407 GCT, 17.3% were abnormal, with 75% having normal follow-up OGTT. Simulated studies: In the simulated GCT/OGTT, using ADIPS criteria, GCT had a sensitivity of 87%, specificity of 74% and would miss 13% of cases. Although simulated FG/OGTT had similar sensitivity of 82% for FPG ≥4.4 mmol/L, specificity was 42%. Using IADPSG criteria, 19% were diagnosed with GDM, screening GCT had a sensitivity of 83%, specificity of 75% and would miss 17% of cases. CONCLUSION: Oral glucose tolerance test alone is the best procedure without prior preliminary testing.

Serial increased cardiac troponin T predicts mortality in asymptomatic patients treated with chronic haemodialysis.

BACKGROUND: A single detectable cardiac troponin predicts mortality in patients treated with dialysis. There are limited data on changes in troponin concentration over time and the clinical implications of serial troponin measurement. METHODS: Serial cardiac troponin T (cTnT) was assayed five times over 12 months in a prospective cohort study of patients with end-stage kidney disease treated with haemodialysis. A concentration of cTnT > or = 0.04 microg/L was considered increased. Mortality and cardiovascular events were analysed by survival analysis, according to the serial troponin results. RESULTS: From 100 patients who provided a baseline sample for cTnT, 81 completed five serial measurements. The analysis of patients who completed serial cTnT measurements demonstrated that 28 patients (35%) had normal cTnT concentrations in all five samples, 20 patients (24%) had between one and four increased cTnT measurements and 33 patients (41%) had increased concentrations of cTnT in all five samples. The 1.7-y patient survival was 100%, 90% and 78% for patients with zero, one to four, or five out of five concentrations of cTnT increased, respectively (P = 0.037), and the corresponding cardiovascular event-free survival was 100%, 91% and 78%, respectively (P = 0.027). CONCLUSIONS: Serial measurements of cTnT concentration were frequently increased in patients receiving haemodialysis. The number of abnormal measurements over time predicted mortality and cardiovascular adverse events.

B-type natriuretic peptides strongly predict mortality in patients who are treated with long-term dialysis.

BACKGROUND AND OBJECTIVES: Left ventricular abnormalities contribute to cardiovascular disease in patients with chronic kidney disease and may be detected by measurement of B-type natriuretic peptide in serum. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a prospective cohort study of predialysis patients, patients who were on dialysis, and kidney transplant recipients, serum was collected and assayed for both B-type natriuretic peptide and its N-terminal fragment. Median levels were compared using nonparametric tests, and predictors of B-type natriuretic peptide were determined by linear regression. Survival analysis and Cox regression were performed to examine the association of levels of B-type natriuretic peptide with cardiovascular events and death. RESULTS: Levels of B-type natriuretic peptide were highest in patients who were on dialysis. Patients who were receiving dialysis and had known cardiovascular disease, were not on the waiting list for kidney transplantation, or had left ventricular systolic dysfunction on echocardiography had significantly higher levels of B-type natriuretic peptide than patients without these characteristics. Glomerular filtration rate was an important predictor of B-type natriuretic peptide levels for patients who were not on dialysis (predialysis and renal transplant recipients). Left ventricular systolic dysfunction predicted B-type natriuretic peptide levels in patients who were on dialysis. Both forms of B-type natriuretic peptide were associated with a two- to three-fold increased risk for death in patients who were on dialysis. CONCLUSIONS: Levels of B-type natriuretic peptide are greatest in patients who are on dialysis and have cardiovascular comorbidities and are strong predictors of death.

N-Acetylcysteine does not artifactually lower plasma creatinine concentration.

BACKGROUND: All randomized controlled trials of N-acetylcysteine (NAC) in contrast media-induced nephropathy used creatinine as a marker of renal function. However, it has been suggested that NAC may lower plasma creatinine levels independent of any effects on glomerular filtration rate (GFR). METHODS: At a tertiary hospital 110 cardiac surgical patients were randomly allocated to peri-operative infusion of NAC (300 mg/kg over 24 h, N = 30) or placebo (N = 80). We compared the plasma concentrations of creatinine, cystatin C and urea, the plasma creatinine/plasma cystatin C ratio and the estimated GFR at baseline and at 24 and 72 h after commencement of the infusion. We measured urinary creatinine concentration at 24 h. RESULTS: At baseline, the plasma creatinine/plasma cystatin C ratio did not differ between the NAC and placebo group (0.90 versus 0.92; P = 0.94). There was no significant difference in the plasma creatinine/plasma cystatin C ratio for the NAC and placebo group either during or after NAC infusion at 24 h (1.03 versus 1.00; P = 0.78) and 72 h (0.94 versus 0.89; P = 0.09). Those allocated to NAC showed no difference in urinary creatinine excretion when compared to placebo (P = 0.24). CONCLUSIONS: The results of our study do not demonstrate that NAC artifactually lowers creatinine measured using the Jaffé method. (ClinicalTrials.gov, NCT00332631, NCT00334191).

Cardiac troponin levels in asymptomatic patients on the renal transplant waiting list.

AIMS: Cardiac troponin levels predict mortality and cardiovascular events in asymptomatic patients receiving dialysis and may be a useful clinical tool to stratify high-risk asymptomatic individuals. METHODS: The present study examined levels of troponins I (cTnI) and T (cTnT) in patients with chronic renal impairment, patients receiving dialysis and renal transplant recipients. Patients receiving dialysis on the renal transplant waiting list were compared with those excluded from the list based on medical criteria. Median levels were compared using the Kruskal-Wallis test and proportions compared by chi-squared. RESULTS: Median troponin levels were higher in patients on dialysis than transplant recipients. Comparing patients receiving dialysis not listed compared with those listed for renal transplant, median cTnI levels were significantly higher (0.03 versus 0.02 microg/L, P < 0.01) whereas median cTnT levels were not. Patients listed for transplantation were younger, had less clinical cardiovascular disease and lower C-reactive protein than those awaiting renal transplantation. The proportion of patients with elevated cTnT was not substantially different between patients awaiting renal transplantation (38%) and those excluded (52%). Levels of cTnI and cTnT were inversely related to renal function in predialysis and transplant patients, but were not related to time on dialysis for those receiving dialysis therapy. CONCLUSION: As patients awaiting renal transplantation are clinically screened for cardiovascular disease but have frequently elevated cardiac troponin levels, troponin may be a useful clinical tool to identify high-risk asymptomatic patients on dialysis prior to renal transplantation. The influence of renal function on the interpretation of cardiac troponin and risk prediction requires further evaluation.

Cardiovascular biomarkers in CKD: pathophysiology and implications for clinical management of cardiac disease.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with all forms of chronic kidney disease (CKD). The underlying pathological state is caused by a complex interplay of traditional and nontraditional risk factors that results in atherosclerosis, arteriosclerosis, and altered cardiac morphological characteristics. This multifactorial disease introduces new challenges in predicting and treating patients with CVD sufficiently early in the course of CKD to positively alter patient outcome. Asymptomatic individuals with progressive CVD are a group of patients that deserve focused attention because early detection and intervention may provide the best opportunity for improved outcome. However, identifying CVD in asymptomatic patients with CKD or end-stage renal disease remains a significant hurdle in the management of these patients. Recently, a number of cardiovascular biomarkers were identified as predictors of patient outcome in individuals with CVD and, with additional research, may be used to guide the early diagnosis of and therapy for CVD in patients with CKD. This review examines the pathophysiological characteristics and potential clinical role of these novel cardiovascular biomarkers in risk stratification, risk monitoring, and selection of preventive therapies for patients with CKD.

Capillary electrophoresis of hemoglobin.

Capillary electrophoresis (CE) has been used in a variety of in-house capillary isoelectric focusing (CIEF) and capillary zone electrophoresis (CZE) assays for the detection of hemoglobin (Hb) variants and the quantitation of HbA2 and HbF. A commercial kit has also been produced for the analysis of hemoglobin variants and thalassemia screening. Though CE methods have been shown to be able to detect many variants, final identification of the variant needs specialized testing such as DNA technology. Over the past 2 years, many instruments that had been used for these hemoglobin variant screening and thalassemia assays have been withdrawn from sale. Although CE HbA1c analysis is available, it cannot compete in turnaround time or cost with automated HPLC commercial instruments that give accurate HbA1c results in 3 or 4 minutes. Hence we do not anticipate a bright future for the analysis of hemoglobin by CE.

Cystatin C for estimation of glomerular filtration rate in patients with spinal cord injury.

BACKGROUND: Serum creatinine is not a satisfactory marker of glomerular filtration rate (GFR) in patients with spinal cord injury (SCI) who have varying degrees of muscle atrophy. In contrast to serum creatinine, serum cystatin C, a 13-kDa protein, is not affected by muscle mass and is therefore potentially a useful marker of GFR in patients with SCI. In addition, cystatin C is not dependent on sex or age and is not secreted by the renal tubule. AIM: We assessed serum cystatin C as a surrogate marker of GFR in SCI patients. METHODS: Cystatin C was analysed using a particle-enhanced immunonephelometric assay (Dade Behring) in serum samples sent for routine measurement of creatinine (64 patients) and creatinine clearance (27 patients) from patients in the Spinal Unit of the Austin Health. We compared these results with serum cystatin C of 57 non-SCI patients who had had a creatinine clearance measurement during the study period. RESULTS: In patients with SCI, the reciprocal of cystatin C had a stronger correlation (r = 0.48, P<0.01) with creatinine clearance than the reciprocal of serum creatinine (r = 0.25, P<0.19). Further, the value of serum creatinine was much lower for a given creatinine clearance in SCI patients than in non-SCI patients; the serum cystatin C concentrations were equivalent. CONCLUSION: The serum cystatin C is a convenient and more reliable surrogate marker of GFR than serum creatinine and will enable early detection of renal impairment. We need to confirm this finding with a larger study, including comparison with an accepted gold standard for GFR.