Arif Showkat

Severe hypernatremia correction rate and mortality in hospitalized patients.

Introduction:Hypernatremia is a common problem in hospitalized patients and is associated with high morbidity and mortality. This study was designed to evaluate whether physicians follow the recommended guidelines for the rate of correction of hypernatremia of ≤0.5 mEq/L/hr and to evaluate the effect of the rate of correction of severe hypernatremia on the mortality of hospitalized patients. Methods:A retrospective chart review of 131 consecutively hospitalized patients with severe hypernatremia (serum sodium ≥155 mEq/L) was performed. Primary outcomes were 30-day patient mortality and 72-hour hypernatremia correction. The first 24-hour serum sodium (Na+) correction rate was tested as a categorical variable; slow rate (<0.25 mEq/L/hr) and fast rate (≥0.25 mEq/L/hr). Results:The mean admission serum Na+ level was 159 ± 3 mEq/L. Ninety percent of patients received the recommended <0.5 mEq/L/hr serum Na+ correction rate; however, hypernatremia was corrected only in 27% of patients after 72 hours of treatment. Thirty-day patient mortality rate was 37%. In multivariable analysis, do not resuscitate status [hazards ratio (HR), 3.85; P < 0.0001], slower correction rate of hypernatremia (HR, 2.63; P = 0.02) and high heart rate (>100 beats/min; HR, 1.99; P = 0.03) were the independent predictors of 30-day mortality. Conclusion:In patients with severe hypernatremia, the rate of correction of hypernatremia was slow and resulted in inadequate correction in majority of the patients. Both slow rate of hypernatremia correction during the first 24 hours and do not resuscitate status were found to be significant predictors of 30-day patient mortality.

Assessment of 24,25(OH)2D levels does not support FGF23-mediated catabolism of vitamin D metabolites

Progressive elevations of fibroblastic growth factor 23 [FGF23] in chronic kidney disease may reduce serum 25-hydroxyvitamin D [25(OH)] and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels, via stimulation of 24-hydroxylase (Cyp24A1) mediated catabolism of these vitamin D metabolites. To test this possibility, we measured serum concentrations of 24,25-dihydroxyvitamin D [24,25(OH)2D], a product of Cyp24A1 hydroxylation of 25(OH)D, in the Col4α3 knockout mouse, a model of Alport syndrome-derived chronic kidney disease, and in patients with chronic kidney disease of variable severity. There was an inverse correlation between serum FGF23 and both 25(OH)D and 1,25(OH)2D in the mouse model but no significant relationship was observed in the cross-sectional patient cohort. The FGF23-dependent increase in Cyp24a1 mRNA expression in the mouse kidneys was consistent with the possibility that FGF23 induces vitamin D catabolism. There was, however, a reduction in serum 24,25(OH)2D levels, rather than the expected elevation, in both the mice and patients with chronic kidney disease. Low 25(OH)D and elevated FGF23 and parathyroid hormone levels were correlated with the reduced serum 24,25(OH)2D concentrations of these patients. Thus, we failed to find support for FGF23-mediated catabolism of vitamin D metabolites in chronic kidney disease assessed by 24,25(OH)2D levels.

Activation of FGF-23 Mediated Vitamin D Degradative Pathways by Cholecalciferol

CONTEXT The optimal circulating concentration of 25(OH) vitamin D is controversial. OBJECTIVE The aim was to investigate if FGF-23 and 24,25(OH)2D can guide cholecalciferol replacement. DESIGN Oral cholecalciferol (10,000 IU weekly) administered to subjects with 25(OH)D levels < 20 ηg/mL and eGFR > 60 mL/min/1.73 m(2) (n = 25), chronic kidney disease (CKD) (n = 27), or end stage renal disease (ESRD) (n = 14). SETTING The study was conducted at the Veterans Affairs clinics. MAIN OUTCOME MEASURE Serum FGF-23, PTH, 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, calcium, and phosphorous concentrations, and urinary excretion of calcium and phosphorus at baseline and after 8 weeks of treatment. RESULTS Cholecalciferol treatment increased concentrations of serum 25(OH)D by (19.3 ± 8 ηg/mL, P = .001; 12.2 ± 9 ηg/mL, P = .0001) and 24,25(OH)2D (1.14 ± 0.89 ηg/mL, P = .0024; 1.0 ± 0.72 ηg/mL P = .0002), and reduced serum PTH (-11 ± 21 pg/mL, P = .0292; -42 ± 68 pg/mL, P = .0494) in normal and CKD subjects, respectively. Cholecalciferol increased serum FGF-23 levels only in normal subjects (44 ± 57 ηg/mL, P = .01). Increments in serum 25(OH)D positively correlated with serum FGF-23 and 24,25(OH)2D and negatively correlated with PTH. In ESRD, cholecalciferol administration increased 25(OH)D by (16.6 ± 6.6 ηg/mL P ≤ .05) without changing 24,25(OH)2D, FGF-23 or PTH levels. CONCLUSION Modest elevations of serum 25(OH)D levels after cholecalciferol treatment are sufficient to induce compensatory degradative pathways in patients with sufficient renal reserves, suggesting that optimal circulating 25(OH)D levels are approximately 20 ηg/mL. In addition, catabolism of 25(OH)D may also contribute to the low circulating vitamin D levels in CKD, since elevations of FGF-23 in CKD are associated with increased 24,25(OH)2D after cholecalciferol administration.

Chronic Kidney Disease and Diabetes Mellitus Predict Resistance to Vitamin D Replacement Therapy

Background:25-Hydroxyvitamin D [25(OH)D] is a marker of nutritional status; however, chronic kidney disease (CKD) results in alterations in vitamin D metabolism, including the loss of vitamin D-binding proteins and alterations in CYP27B1 and CYP24 enzymes that metabolize 25(OH)D. This study was designed to determine the predictors of responsiveness to correction of vitamin D deficiency with oral vitamin D2 (ergocalciferol) in adults. Methods:A retrospective study of 183 veterans with 25(OH)D level <30 ng/mL, who were treated with 50,000 IU per week of vitamin D2, was performed. Logistic regression models were developed to determine the factors predicting the response to treatment, defined as either the change in serum 25(OH)D level/1000 IU of vitamin D2 or the number of vitamin D2 doses (50,000 IU per dose) administered. Results:The mean age of the patients was 63 ± 12 years. About 87% were men and 51% diabetic, and 29% had an estimated glomerular filtration rate of <60 mL/min/1.73 m2. The average number of vitamin D2 doses was 10.91 ± 5.95; the average increase in 25(OH)D level was 18 ± 10.80 ng/mL. 25(OH)D levels remained <30 ng/mL in 61 patients after treatment. A low estimated glomerular filtration rate and the presence of diabetes mellitus were significant independent predictors for inadequate response to vitamin D2 treatment in logistic regression models. Patients with CKD required greater amounts of vitamin D2 to achieve similar increases in 25(OH)D levels, versus non-CKD patients. Conclusions:The presence of CKD and diabetes mellitus is associated with resistance to correction of 25(OH)D deficiency with vitamin D2 therapy. The underlying mechanism needs to be evaluated in prospective studies.

Endovascular stent migration to the right ventricle causing myocardial injury

Central stenosis of the subclavian and internal jugular veins is common in end stage renal disease. Treatment of these stenoses is difficult as these veins respond poorly to angioplasty alone and often require metallic stents to ensure patency. These stents are not without complications. Reports of stent fracture, thrombosis and vessel rupture abound in the literature. Stent migration can occur when used in large central veins leading to severe consequences such as pulmonary infarction, tricuspid regurgitation and right sided heart failure. In this report, we report a case of a subclavian vein stent which migrated into the right heart and caused subendocardial injury. As the use of vascular stents is becoming a common treatment option for central venous stenosis, the occurrences of serious complications associated with the stents are likely to rise.

Effect of α-Lipoic Acid on Oxidative Stress in End-Stage Renal Disease Patients Receiving Intravenous Iron

Oxidative stress is associated with increased risk of cardiovascular disease in end-stage renal disease (ESRD) patients. Intravenous (IV) iron has been shown to increase oxidative stress. The aim of the study was to evaluate changes in oxidative stress markers following administration of IV sodium ferric gluconate (SFG) to ESRD patients with and without administration of the antioxidant, α-lipoic acid. This is an open-label, crossover study. 125 mg of IV SFG was administered during control (C) and intervention (I) visits. During the I visit, 600 mg of α-lipoic acid was given orally prior to IV SFG. Blood samples were collected at defined time periods for F2-isoprostane (FIP), lipid hydroperoxide (LHP), malondialdehyde (MDA), and iron indices. We recruited ten African-American ESRD subjects: 50% male; mean age 45 ± 9 years; mean hemoglobin 13 ± 1 g/dL; ferritin 449 ± 145 ng/mL; transferrin saturation 27 ± 4%. There were no significant differences in iron indices between the two visits after IV SFG. MDA, FIP, and LHP increased significantly for both C and I visits with a greater increase in the I group. Administration of IV SFG results in an acute rise in oxidative stress in ESRD patients. In contrast to previous studies, administration of α-lipoic acid was associated with a greater increase in oxidative stress.

Determining the optimal method for proteinuria detection in chronic spinal cord injury

Study design:A retrospective analysis.Objectives:The objective of this study is to determine whether dipstick protein analysis (DSP) or random urine protein:creatinine ratios (UPC) are accurate in predicting clinical proteinuria in the chronic spinal cord injury (SCI) population.Methods:A retrospective analysis was performed in 219 veterans with SCI, comparing DSP and 24-h urine protein excretion. Sensitivity, specificity, predictive values (PV) and receiver–operator characteristic (ROC) curves of DSP in predicting clinical proteinuria were calculated with and without correction for specific gravity (SG). A prospective study was also performed in 62 SCI patients, comparing the UPC and 24-h urines. Sensitivity, specificity, PV and ROC curves of UPC in predicting clinical proteinuria were calculated.Results:Any level of positive DSP had high specificity, but low sensitivity, for detecting the presence of clinical proteinuria. ROC curves of DSP for identifying clinical proteinuria yielded area under the curve of 0.749 (95% confidence interval 0.699–0.794), and adjustment for SG did not significantly improve accuracy. A UPC of <0.3 was sensitive with a high negative PV for ruling out clinical proteinuria, whereas a ratio >0.8 was specific with a high positive PV. A UPC between 0.3–0.8 had an intermediate sensitivity and specificity.Conclusion:Urine collections of 24-h are still needed in the chronic SCI population for accurate detection of clinically significant proteinuria. DSP may not reliably detect low-grade clinical proteinuria, whereas a UPC below 0.3 may be used to rule out clinical range proteinuria.

C20209T prothrombin gene mutation associated deep venous thrombosis in a hemodialysis patient

Venous thromboembolism (VTE) represents the formation of a blood clot in one of the deep veins of human body. The significant morbidity and mortality rates associated with VTE have spurred increasing investigations seeking to identify causative factors for this complex condition. While the most frequent causes of an inherited hypercoagulable state are the Factor V Leiden mutation and the prothrombin gene mutation, polymerase chain reaction (PCR) analysis has helped to identify other rare causes of inherited VTE. We report a case of a recurrent deep venous thrombosis in an end-stage renal disease patient. All laboratory tests for hypercoagulable states were normal. However, PCR analysis detected a rare polymorphism of prothrombin gene mutation at position C20209T, instead of G20210A. The patient was treated successfully with a high dose of warfarin to maintain adequate anti-coagulation during the 2-year follow-up.

A case of renal infarction associated with elevated factor VIII level.

Elevated factor VIII level has recently been shown to be associated with increased risk of thrombosis. We report here a case of renal infarction in association with elevated factor VIII level. The patient presented with a three-day history of flank pain. Laboratory studies on presentation showed an elevated serum creatinine concentration and microscopic hematuria. He was found to have bilateral pulmonary emboli and left common femoral vein thrombosis; imaging studies showed evidence of renal arterial thrombosis with infarction. Hypercoagulability assessment showed an elevated factor VIII level. He was treated with heparin and warfarin with significant improvement in his renal function. Consideration should be given to measurement of factor VIII level as a part of the workup of unexplained thrombo-embolic events.

Spontaneous massive bilateral peri-renal hemorrhage as a complication of ANCA-negative granulomatous vasculitis.

Spontaneous retroperitoneal hemorrhage (SRH) is a rare, life-threatening clinical entity most commonly associated with renal cell cancers. Systemic vasculitis has also been described as a rare cause of SRH. The current report describes a patient with acute kidney failure complicated by massive SRH, which occurred in the setting of anti-neutrophil cytoplasmic antibody (ANCA)-negative systemic necrotizing angiocentric granulomatous vasculitis involving multiple organs with minimal constitutional symptoms and no respiratory tract involvement.