Efficacy of furosemide-albumin compared with furosemide in critically ill hypoalbuminemia patients admitted to intensive care unit: a prospective randomized clinical trial.

BACKGROUND: Some physicians co-administer albumin with loop diuretics to overcome diuretic resistance in critically ill hypoalbuminemia patients, though previous studies have reported conflicting results on this matter. OBJECTIVE: The effects of adding albumin to furosemide to enhance its efficacy in critically ill hypoalbuminemia patients are evaluated. METHODS: This was a non-blinded randomized trial. 49 adult critically ill patients with hypoalbuminemia and generalized edema who received randomly furosemide and furosemide/albumin complex were enrolled. The patients' urine was collected at intervals of 2, 4, 6 and 8 h after initiation of the furosemide treatment, and the urine output and urinary excretion of furosemide and sodium were measured. The urinary excretion of furosemide was considered an indicator of drug efficacy. RESULTS: The amount of sodium and furosemide excreted in urine showed no significant differences between the two groups; however, the mean of the urinary excretion of furosemide in the first 2 h after drug infusion was significantly higher (p = 0.03) in the furosemide/albumin group. No significant correlation between APACHE II scores and serum albumin levels and the urinary excretion of furosemide was seen. CONCLUSION: The results indicated that there is not statistically significant differences between groups with furosemide alone and combined with albumin in urinary furosemide excretion. It seems that adding albumin for furosemide pharmacotherapy regime is not recommended as an intervention to increase furosemide efficacy in critically ill hypoalbuminemia patients. TRIAL REGISTRATION: IRCT with the registration number IRCT201412132582N12 in 23 February 2015; https://en.irct.ir/trial/2356 Graphical abstract.

Effects of tolvaptan on urine output in hospitalized heart failure patients with hypoalbuminemia or proteinuria.

Hypoalbuminemia is an independent prognostic factor in hospitalization for heart failure (HHF). Hypoalbuminemia or proteinuria is related to resistance to loop diuretics. Tolvaptan is an oral non-peptide, competitive antagonist of vasopressin receptor-2. It has been used for the treatment of volume overload in HHF patients in several Asian countries. Several studies have demonstrated marked improvement in congestion in HHF patients. However, whether tolvaptan is useful for HHF patients with hypoalbuminemia or proteinuria (both of which are related to resistance to loop diuretics) has not been clarified. We examined the diuretic response to tolvaptan in HHF patients with hypoalbuminemia or proteinuria. We defined hypoalbuminemia as a serum level of albumin < 2.6 g/dl. Fifty-one HHF patients who received additional tolvaptan upon therapies with loop diuretics were divided into the hypoalbuminemia group (n = 24) or control group (n = 27). The changes in urine output per day were not different between the two groups [610 (range 100-1032); 742 (505-1247) ml, P = 0.313]. There was no difference in diuretic responses between patients with and without proteinuria. The serum level of albumin did not correlate with changes in urine output per day after tolvaptan treatment (P = 0.276, r = 0.156). Thus, additional administration of tolvaptan elicited a good diuretic response in HHF patients with hypoalbuminemia or proteinuria. These data suggest that tolvaptan might be beneficial for such HHF patients.

Acid-base disturbances in nephrotic syndrome: analysis using the CO2/HCO3 method (traditional Boston model) and the physicochemical method (Stewart model).

BACKGROUND: The Stewart model for analyzing acid-base disturbances emphasizes serum albumin levels, which are ignored in the traditional Boston model. We compared data derived using the Stewart model to those using the Boston model in patients with nephrotic syndrome. METHODS: Twenty-nine patients with nephrotic syndrome and six patients without urinary protein or acid-base disturbances provided blood and urine samples for analysis that included routine biochemical and arterial blood gas tests, plasma renin activity, and aldosterone. The total concentration of non-volatile weak acids (ATOT), apparent strong ion difference (SIDa), effective strong ion difference (SIDe), and strong ion gap (SIG) were calculated according to the formulas of Agrafiotis in the Stewart model. RESULTS: According to the Boston model, 25 of 29 patients (90%) had alkalemia. Eighteen patients had respiratory alkalosis, 11 had metabolic alkalosis, and 4 had both conditions. Only three patients had hyperreninemic hyperaldosteronism. The Stewart model demonstrated respiratory alkalosis based on decreased PaCO2, metabolic alkalosis based on decreased ATOT, and metabolic acidosis based on decreased SIDa. We could diagnose metabolic alkalosis or acidosis with a normal anion gap after comparing delta ATOT [(14.09 - measured ATOT) or (11.77 - 2.64 × Alb (g/dL))] and delta SIDa [(42.7 - measured SIDa) or (42.7 - (Na + K - Cl)]). We could also identify metabolic acidosis with an increased anion gap using SIG > 7.0 (SIG = 0.9463 × corrected anion gap-8.1956). CONCLUSIONS: Patients with nephrotic syndrome had primary respiratory alkalosis, decreased ATOT due to hypoalbuminemia (power to metabolic alkalosis), and decreased levels of SIDa (power to metabolic acidosis). We could detect metabolic acidosis with an increased anion gap by calculating SIG. The Stewart model in combination with the Boston model facilitates the analysis of complex acid-base disturbances in nephrotic syndrome.

Relation between circadian blood pressure rhythm and serum albumin level in non-diabetic patients with proteinuria.

It remains unclear whether the abnormal circadian blood pressure (BP) rhythm in non-diabetic chronic kidney disease (CKD) is related to hypoalbuminemia. We evaluated relationships between circadian BP rhythm and serum albumin concentration (SAC) and also examined autonomic nervous activities. Non-diabetic CKD patients with proteinuria (n = 197; 105 men, 92 women; aged 47.0 ± 13.3 years; estimated glomerular filtration rate ≥30 ml/min) were divided into nephrotic syndrome (NS: n = 46, SAC ≤ 30 g/l), hypoalbuminemia (n = 65, 30 < SAC < 40 g/l) and normoalbuminemia (n = 86, SAC ≥ 40 g/l) groups. Non-proteinuria subjects (n = 97, urinary protein/creatinine ratio < 30 mg/g creatinine) were enrolled as the non-proteinuria group. Ambulatory 24 h BP monitoring was conducted in all subjects. Simultaneously, power spectral analysis of heart rate was performed to evaluate the sympathovagal balance. Waking BP was lower in the hypoalbuminemia and NS groups than the other groups. Sleeping/waking mean BP ratio was not different between non-proteinuria (0.87 ± 0.07) and normoalbuminemia (0.89 ± 0.08) groups, but increased significantly (p < 0.05) in the hypoalbuminemia (0.92 ± 0.08) and NS groups (0.96 ± 0.08). Significant reverse correlations were observed between SAC and sleeping/waking mean BP ratio (r = -0.274, p < 0.001) in all patients. Multivariate regression analysis identified SAC and sympathovagal balance as predictors of increased sleeping/waking BP ratios as the dependent variable. In non-diabetic CKD patients with proteinuria, disturbed circadian BP rhythms were related to SAC and 24 h sympathovagal imbalance.

Co-administration of furosemide with albumin for overcoming diuretic resistance in patients with hypoalbuminemia: a meta-analysis.

PURPOSE: To systematically review clinical studies of co-administration of albumin and loop diuretics in hypoalbuminemic patients as a strategy to overcome diuretic resistance. MATERIALS AND METHODS: Systematic search of electronic databases up to October 2012. We included randomized clinical trials of adults with hypoalbuminemia, comparing co-administration of loop diuretics and albumin versus loop diuretics alone. Quantitative data were synthesized with meta-analytic techniques for clinical, surrogate (urinary volume and urinary sodium excretion) and intermediate (pharmacokinetic and hemodynamic parameters) outcomes. RESULTS: Ten studies were included, of which 8 trials with crossover design were synthesized with meta-analysis. A statistically significant increase in the amount of urine volume (increment of 231 mL [95% confidence interval 135.5-326.5]) and sodium excreted (15.9 mEq [4.9-26.8]) at 8 hours were found in favor of co-administration of albumin and furosemide. These differences were no longer statistically significant at 24 hours. Meta-analyses for intermediate outcomes (ie, furosemide excretion, distribution volume etc.) did not reveal statistically significant differences. CONCLUSIONS: Synthesis of a heterogeneous body of evidence shows transient effects of modest clinical significance for co-administration of albumin with furosemide in hypoalbuminemic patients. Pragmatic, large-scale randomized studies are needed to delineate the role of this strategy.

Renal amyloidosis in dogs: a retrospective study of 91 cases with comparison of the disease between Shar-Pei and non-Shar-Pei dogs.

BACKGROUND: Renal amyloidosis (RA) is a progressive and fatal renal disease. HYPOTHESIS: Clinical and pathologic manifestations of RA differ between Chinese Shar-Pei (CSPs) and non-Shar-Pei (NSPs) dogs. ANIMALS: 91 client-owned dogs. METHODS: Retrospective review of medical records of dogs with a histological diagnosis of RA. Clinical and clinicopathologic data, hospitalization, complications, and outcome were compared between CSPs and NSPs. RESULTS: Comorbid diseases were present in 64% of all dogs. CSPs were significantly younger compared to NSPs (median, 4.8 years; range: 3.6-17 versus median: 9.0 years; range: 2.4-11.1; P < .0001). The frequency of hypoalbuminemia, the most common biochemical abnormality, was higher in NSPs compared to CSPs (100% versus 64.7%, respectively; P < .001). Median serum creatinine concentration at presentation was 5.5 mg/dL, and was 3-fold higher in CSPs compared to NSPs (P = .005). Increased urine protein : creatinine ratio was present in 96% of all dogs. Nephrotic syndrome was present in 10% of NSPs but not in CSPs. Glomerular amyloid deposition, present in both CSPs (78.6%) and NSPs (95.6%) was most commonly diffuse, global, and severe. Renal medullar amyloidosis was more common in CSPs (100%) compared to NSPs (49.0%, P = .002), as was extrarenal amyloid deposition. The median survival time of all dogs was 5 days (range: 0-443 days). Serum creatinine concentration was significantly and negatively associated with survival (P = .025). CONCLUSIONS AND CLINICAL RELEVANCE: The clinical and pathologic manifestations of amyloidosis differ between CSPs and NSPs. The survival time observed herein was unexpectedly low, and argues for early surveillance and management of the underlying predisposing conditions.

Comparison of the diuretic effect of furosemide mixed with human albumin or fresh frozen plasma for patients with hypoalbuminemia in the intensive care unit.

BACKGROUND: Diuretics are commonly used in the intensive care unit (ICU) for patients with fluid over-loading. Hypoalbuminemia is a major cause of diuretic resistance. Albumin mixed with furosemide can promote diuresis and sodium excretion in patients with hypoalbuminemia. The purpose of this study is to compare the diuretic effect of furosemide (FU) mixed with human albumin (HA) or fresh frozen plasma (FFP) in ICU patients with hy-poalbuminemia. METHODS: Patients with fluid overloading and hypoalbuminemia who needed diuretic treatment were enrolled and were divided into 2 groups: the first group having clearance of creatinine (CCr) >20 ml/min, and the second group having CCr < or = 20 ml/min. FU (60 mg) mixed with HA (HA group), 60 mg FU mixed with FFP (FFP group) and water (placebo group) were given intravenously to these patients for 60 minutes in random order on the first, third and fifth day. After drug administration, 8-hour urine was collected, and urine amount and urinary sodium excretion were checked. RESULTS: Both the HA group and the FFP group had significantly higher urinary volume and sodium excretion than the placebo group in the patients with CCr >20 ml/min or CCr < or = 20 ml/min (p < 0.01). In the patients with CCr >20 ml/min, there was no difference in the amount of urine excretion and cumulative urinary sodium excretion between the HA group and FFP group. In the patients with CCr < or =ml;20 ml/min, the HA group had a significantly higher urine output and urinary sodium excretion than the FFP group (p < 0.05). CONCLUSIONS: In ICU patients, 60 mg FU mixed with HA or FFP has a similar diuretic effect in patients with CCr >20 ml/min. FFP is an effective alternative choice for improving diuresis for ICU patients with hypoalbuminemia. In patients with CCr < or = 20 ml/min, albumin mixed with 60 mg FU has a superior diuretic effect compared with FFP mixed with FU.