How useful is exercise and dietary counseling after liver transplantation?
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Biomedical subjects
Publications and source records attributed to Hassan N Ibrahim.
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BACKGROUND: Identifying urinary biomarkers associated with acute rejection (AR) of kidney allografts could improve recipient care by allowing AR to be diagnosed noninvasively and treated earlier. We attempted to identify novel biomarkers associated with AR by analyzing urinary proteins by using matrix-associated laser desorption ionization time-of-flight mass spectroscopy (MALDI-TOF MS). METHODS: Using MALDI-TOF MS, we analyzed urine samples from 30 renal allograft recipients with biopsy-proven AR, 15 allograft recipients without AR, preoperative samples from 29 kidney donors, and 10 subjects with proteinuric native kidney disease. RESULTS: In samples obtained at the time of AR, we identified a protein peak at 11.7 kd that correlated strongly with AR. In regard to its predictive power for AR, this protein peak showed sensitivity of 83.3%, specificity of 80%, positive predictive value of 89%, and negative predictive value of 70.6%, suggesting that this protein is highly associated with AR. We identified this peak as being beta2-microglobulin. This was validated by using enzyme-linked immunosorbent assay, which documented the presence of high urinary beta2-microglobulin levels in subjects with AR. CONCLUSION: Beta2-microglobulin could be a strong biomarker for AR if used in conjunction with other biomarkers, producing an AR-specific urinary protein signature. This possibility must be confirmed in a larger cohort of kidney transplant recipients.
Protein profile analysis is increasingly used for identification of disease biomarkers. The approaches vary from surface-enhanced laser desorption/ionization to protein arrays. Newer platforms are constantly being developed. Almost all are based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and are often coupled with sophisticated software tools. Protein profiling has been applied to a variety of samples including plasma, urine, cerebrospinal fluid, saliva and solid tissue. This article focuses on those instances where it is possible to obtain sequential samples from the same individual. In the authors use of a profile method, many protein changes with highly significant correlations to disease have been found. The main challenge lies in the validation of the marker to demonstrate its adequacy for use in the clinical setting. The latter requires a methodology that is robust and amenable to high-throughput. One problem is that interindividual variability among the healthy population can mask major changes that occur on an intraindividual basis. Often, a large change for an individual may remain within the range of healthy individuals. Thus, one strategy to optimize biomarker discovery is to examine serial samples from a given individual, where a disease biomarker is established by comparison with the individual's own baseline sample. The focus of this review is to illustrate the principle and value of serial protein profiling using a rapid protein extraction method.
BACKGROUND: Transplantation before the initiation of dialysis is associated with prolonged allograft survival. It is unclear if this benefit is attributable to greater residual renal function or to avoidance of dialysis exposure. The authors performed an analysis to determine whether higher renal function at transplant was associated with increased patient and graft survival rates. METHODS: The authors identified individuals who between 1994 and June 2000 were >or= 18 years and had undergone a living donor renal transplant (Tx) as initial form of renal replacement therapy. Pre-Tx and 6-month estimated glomerular filtration rates (eGFR) were calculated using the 4-variable Modification of Diet in Renal Disease formula. Survival was compared in those with a pre-Tx eGFR >or=15mL/min to those with an eGFR less than 15 mL/min, after adjusting for demographic variables, co-morbidities, and transplant characteristics. Survival rate then was adjusted for calculated propensity scores. RESULTS: A total of 4,046 patients were included. Mean pre-Tx eGFR was 9.9 mL/min (0.9 to 57.1 mL/min). There was no difference in graft survival rates by strata of eGFR in any of the tested models, even after correcting for propensity score (hazard ratio, 0.95; 95% confidence interval, 0.69 to 1.30). There was no correlation between pre-Tx eGFR and 6-month post-Tx eGFR (r(2) =-0.005). CONCLUSION: Recipients of preemptive transplants fare equally, regardless of the eGFR at which they receive their transplant. There was no relationship between pre-Tx eGFR and 6-month eGFR, suggesting that post-Tx renal function is independent of the level of pre-Tx renal function. These data suggest that preemptive kidney transplantation should be delayed as long as possible, provided the patient does not have uremic symptoms, and dialysis can be safely avoided.
PURPOSE OF REVIEW: Interruption of the renin-angiotensin-aldosterone system, chiefly with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, has yielded beneficial results in retarding injury and progression in numerous intrinsic renal diseases. The renoprotection offered by these agents is incomplete and far from optimal. Studying mediators of progression other than angiotensin II is therefore extremely important. The emerging role of aldosterone in progression of renal disease and the utility of its antagonism is discussed here. RECENT FINDINGS: The experimental evidence linking aldosterone to renal disease is discussed. The exciting results from clinical studies employing mineralocorticoid receptor blockers are also described. SUMMARY: Aldosterone antagonism offers additional antiproteinuric benefits to those achieved with angiotensin-converting enzyme inhibition. Long-term trials addressing effectiveness and safety, especially in regards to hyperkalemia, are greatly needed.
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The remnant kidney model of progressive renal disease is marked by arterial hypertension, especially when produced by nephrectomy and partial infarction. Hyperaldosteronism sustains much of the hypertension, but the stimuli to the increased aldosterone levels are uncertain. It is hypothesized that the hyperaldosteronism attending this model stems from the combination of fixed dietary potassium load in the face of reduced filtration on the one hand, and persistent renin secretion from the scarred remnant kidney on the other. This hypothesis predicted that dietary potassium restriction would lower aldosterone and BP in this model. To test this prediction, two groups of rats with a remnant kidney were studied. Group 1 consumed 0.4 +/- 0.06 mEq (mean +/- SD) of potassium chloride daily, and group 2 ate 4.8 +/- 1.0 mEq daily. Two sham-operated groups with intact kidneys also were studied. Group 3 consumed 1.7 +/- 0.2 mEq daily and group 4 ate 15.2 +/- 1.4 mEq daily. These levels of intake were designed to provide at least as much potassium per liter of GFR in the sham groups as in the remnant kidney rats. Systolic BP (SBP), 24-h protein excretion, plasma aldosterone levels, 24-h urinary aldosterone excretion, and plasma renin activity (PRA) were determined in all groups at 2 wk. At 4 wk, after SBP and protein excretion measurements, remnant kidneys were perfusion-fixed for morphometric analysis. SBP was normal in both sham-operated groups and was not different between the groups (113 +/- 13 versus 117 +/- 2 mmHg, group 3 versus group 4). In the remnant animals, SBP at 2 wk followed potassium intake: Group 1 had a lower SBP than group 2 (140 +/- 26 versus 170 +/- 34 mmHg, P = 0.005). The same SBP pattern persisted at 4 wk (153 +/- 25 versus 197 +/- 27 mmHg, group 1 versus group 2, P = 0.0006). However, 24-h urinary protein excretion was not different between the two groups with remnant kidneys at either 2 or 4 wk. Both plasma and 24-h urinary aldosterone excretion at 2 wk followed potassium intake (120 +/- 124 versus 580 +/- 442 pg/ml for plasma aldosterone, group 1 versus group 2, P = 0.03, and 2.6 +/- 1.8 versus 23.2 +/-9.8 ng/d for urinary aldosterone, group 1 versus group 2, P = 0.0001). PRA, however, followed a reverse pattern in which dietary potassium restriction resulted in higher levels (16 +/- 6 versus 6 +/- 3 ng angiotensin I/ml per h, group 1 versus group 2, P = 0.01). A similar pattern for PRA and aldosterone excretion was also observed in the sham groups, in which lower potassium intake also resulted in a significantly higher PRA and lower aldosterone excretion. The constancy of BP in the sham groups likely reflects their lack of nephron reduction and greater sodium excretory capacity. Morphometric analysis in remnant animals revealed no significant difference between the two dietary groups in the prevalence of glomerular sclerosis, glomerular volume, or interstitial volume. It is concluded that dietary potassium is a potent determinant of hypertension in the remnant kidney model probably through the actions of aldosterone and that the high aldosterone secretion in this model is a function of the dietary potassium load. In this model, reduction in nephron number is also critical in promoting hypertension in conjunction with hyperaldosteronism.
Spontaneous hemorrhage in the kidney, also known as Wunderlich Syndrome is a rare clinical problem and it's occurrence raises clinical suspicion of the presence of an underlying malignancy. Herein we present two cases that presented with severe spontaneous subcapsular hemorrhage, where no underlying structural abnormality was identified, despite a careful search. The common feature in these two cases was the presence of an underlying chronic kidney disease, a known cause of coagulopathy, but a previously unrecognized association with Wunderlich syndrome. The literature on spontaneous kidney hemorrhage in the modern imaging era is also reviewed.