Hala M. Alshayeb

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.

CKD–Mineral and Bone Disorder Management in Kidney Transplant Recipients

Kidney transplantation, the most effective treatment for the metabolic abnormalities of chronic kidney disease (CKD), only partially corrects CKD-mineral and bone disorders. Posttransplantation bone disease, one of the major complications of kidney transplantation, is characterized by accelerated loss of bone mineral density and increased risk of fractures and osteonecrosis. The pathogenesis of posttransplantation bone disease is multifactorial and includes the persistent manifestations of pretransplantation CKD-mineral and bone disorder, peritransplantation changes in the fibroblast growth factor 23-parathyroid hormone-vitamin D axis, metabolic perturbations such as persistent hypophosphatemia and hypercalcemia, and the effects of immunosuppressive therapies. Posttransplantation fractures occur more commonly at peripheral than central sites. Although there is significant loss of bone density after transplantation, the evidence linking posttransplantation bone loss and subsequent fracture risk is circumstantial. Presently, there are no prospective clinical trials that define the optimal therapy for posttransplantation bone disease. Combined pharmacologic therapy that targets multiple components of the disordered pathways has been used. Although bisphosphonate or calcitriol therapy can preserve bone mineral density after transplantation, there is no evidence that these agents decrease fracture risk. Moreover, bisphosphonates pose potential risks for adynamic bone disease.

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.

Non Hodgkin's lymphoma associated membranoproliferative glomerulonephritis: rare case of long term remission with chemotherapy: a case report

IntroductionAlthough membranoproliferative glomerulonephritis has been reported to occur in association with non-Hodgkins lymphoma, information concerning the long term effects of treatment of non-Hodgkins lymphoma on the associated membranoproliferative glomerulonephritis is limited.Case presentationThe current report describes a patient who presented with the abrupt onset of hypertension, mixed nephritic/nephrotic syndrome and acute renal failure. Kidney biopsy was consistent with membranoproliferative glomerulonephritis, type 1. Bone marrow biopsy performed in the evaluation of periaortic lymphadenopathy, hepatosplenomegaly, and thrombocytopenia confirmed the diagnosis of low grade B-cell non-Hodgkins lymphoma. The patients renal function improved and proteinuria resolved after initial treatment of non-Hodgkins lymphoma with chemotherapy. During eleven years of follow up, membranoproliferative glomerulonephritis has remained in remission, as confirmed by repeatedly negative urinalyses, normal blood pressure and absence of clinical signs and symptoms suggestive of nephritic/nephrotic syndrome.ConclusionMembranoproliferative glomerulonephritis has been known to be associated with both chronic lymphocytic leukemia and non-Hodgkins lymphoma, particularly with B cell lymphocytic type non-Hodgkins lymphoma. There is limited information available concerning the effects of treatment of non-Hodgkins lymphoma on the progression of non-Hodgkins lymphoma associated membranoproliferative glomerulonephritis. In the few reported cases we found, long term follow up after initial resolution of the membranoproliferative glomerulonephritis was lacking. This report presented a rare case of non-Hodgkins lymphoma associated membranoproliferative glomerulonephritis, that continued to be in remission during eleven years of follow up after initial chemotherapy treatment of lymphoma.

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.

Treatment of Proliferative and Membranous Lupus Nephritis: Review of Key Clinical Trials

Abstract:Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE), which is associated with significant morbidity and mortality. Renal involvement in SLE is heterogeneous; therefore, the treatment of LN is determined by the pathological type of LN and ranges from nonspecific measures such as maintenance of adequate blood pressure control and blockade of renin-angiotensin-aldosterone system to the use of immunosuppressive medications. Cyclophosphamide in combination with prednisone has been the standard of care for the treatment of proliferative forms of LN. However, the high rates of progression to end-stage renal disease coupled with adverse side effects from cyclophosphamide and prednisone administration have lead to an intensive search for more effective and less toxic therapies for LN. The authors review available treatment options for proliferative and membranous LN and summarize the results of recently published clinical trials that add new perspectives to the management of kidney disease in SLE.

Management of Transplantation Renal Bone Disease: Interplay of Bone Mineral Density and Decisions Regarding Bisphosphonate Use

Despite improvement in some chronic kidney disease (CKD) metabolic derangements of bone and mineral metabolism after kidney transplantation, bone disease remains a significant problem. Kidney transplant recipients are at increased risk of bone mineral density (BMD) loss, fractures, and osteonecrosis, all of which are associated with substantial morbidity [1–11]. The pathogenesis of post-transplant bone disease is multifactorial [12–32], including but not limited to interactions of the complex abnormalities in pre-transplant mineral homeostasis [12] and renal osteodystrophy [24, 25], the degree of persistently impaired kidney function, peri-transplant alternations in calciotropic and phosphotropic regulatory hormonal pathways [26], and the potential deleterious skeletal effects of immunosuppressive therapy [27–32].

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.