Background: Estimating the glomerular filtration rate (eGFR) when the creatinine (Cr) is rapidly changing, as in acute kidney injury (AKI), has been a challenge. The Kinetic Estimated Glomerular Filtration Rate (KeGFR) formula by S. Chen estimates the GFR in the acute state by factoring the time interval between rising Cr values and the volume of distribution (V_D). It provides the clinician with an eGFR value for each non-steady state Cr value. We applied the KeGFR formula to detect AKI in an adult non-ICU inpatient setting. We then compared KeGFR with the current standard Acute Kidney Injury Network (AKIN criteria) and Risk Injury Failure Loss End-Stage Kidney Disease (RIFLE criteria) and new criteria (Waikar-Bonventre, Delta check) for AKI detection. Methods: A total of 250 consecutive adult patients admitted to the Medical wards were screened. Patient episodes with a change in Cr of > 4.3% (Biological Variation) were included in the study (n = 80). The KeGFR equation was applied to this cohort after calculating the V_D individually after estimating the initial GFR by using MDRD equation. A fall in KeGFR of 25% or more was considered as AKI. The AKIN, Waikar-Bonventre, RIFLE, and Delta Check criteria were also applied to this cohort and compared with the KeGFR criterion. Clinical adjudication was performed when there was discordance between AKI episodes detected by AKIN and KeGFR criteria. Results: There were 50 episodes of AKI by AKIN classification and 31 episodes by KeGFR criterion. All but 1 (30) episode detected by KeGFR criterion fulfilled the AKI definition by AKIN. AKIN diagnosed an additional 20 episodes. However, all of these had an elevated Cr level on admission; thus, requiring the incorporation of baseline Cr by AKIN which is not part of the KeGFR formula. Five of these 20 patients were deemed as not having AKI by clinical adjudication. All patients with in-hospital AKI and ongoing AKI were detected by both the criteria. The KeGFR criteria detected almost all (24/25) episodes of AKI identified by the Waikar-Bonventre method. The latter method detected 77% (24/31) of the AKI episodes identified by KeGFR. Conclusion: The KeGFR equation can be readily applied to estimate GFR in the non-steady state. A KeGFR-based criterion successfully detected ongoing and in-hospital AKI in this study. Community acquired AKI that did not progress after admission was not detected by the KeGFR criterion.

Tissue microarrays (TMAs) enable high-throughput molecular profiling of multiple tissue samples by immunohistochemistry. Our arrays comprise 10 × 12 sections of 1 mm cores obtained from fixed formalin, paraffin-embedded myocardium. Each heart is represented by two separate core samples. We developed four TMAs containing cardiac samples from patients undergoing heart transplantation; in addition to samples from several non-failing (unused donor) hearts, which served as healthy controls. To validate the TMAs for quantitative protein expression, we undertook a pilot study to measure the protein expression of four-and-a-half LIM protein-2 (FHL2) in hypertrophic and dilated cardiomyopathy relative to non-failing hearts. The LIM domain is a cysteine-histidine rich, zinc-coordinating domain, consisting of two tandemly repeated zinc fingers. Many LIM domain proteins were initially identified as cytoskeletonassociated proteins but are now known to influence gene expression by interacting with transcription factors such as members of the cyclic-AMP-response-element binding protein family. We studied FHL2 as it is preferentially expressed in high levels in the adult heart and is seen in both healthy and diseased states. The antibody was raised in rabbits against synthetic peptides of the FHL2 gene sequence to produce affinity-purified polyclonal FHL2 antibodies. We confirmed changes in FHL2 expression using Western blotting of SDS-PAGE gels. This pilot study demonstrated that FHL2 largely localises at the intercalated discs in cardiomyocytes. Preliminary evidence suggests there is a significant decrease in expression of FHL2 in hypertrophic cardiomyopathy and a trend towards decreased expression in idiopathic dilated cardiomyopathy. http://dx.Background: Cardio-renal syndrome (CRS) in heart failure (HF) is associated with increased mortality, morbidity and cost of care. Fibrosis plays an important role in disease progression in HF in patient with CRS. We examined the effect of the anti-fibrotic agent, tranilast on ameliorating these processes.Methods: 5/6 nephrectomy (STNx) was induced in Sprague Dawley (SD) rats, then randomised to tranilast (300 mg/kg/day, p.o.) or vehicle for 12 weeks, then echocardiogram was performed. Myocardial tissues were harvested for histological analysis.Results: Tranilast reduced blood pressure, increased GFR improved diastolic cardiac function and reduced collagen I and III deposition in the heart post-STNx (Table).Conclusion: Tranilast reduced cardiac fibrosis and improved diastolic cardiac function, renal function and blood pressure in STNx rats. These findings support the use of direct antifibrotic strategies in CRS to improve cardiac structure and function.