Vinod Bansal

Treatment of lupus nephritis: A meta-analysis of clinical trials

The best therapeutic choice in lupus nephritis remains shrouded in a body of controversial literature. The purpose of this review was to assess and compare by meta-analysis the efficacy of therapeutic agents used in the treatment of lupus nephritis using outcomes of end-stage renal disease (ESRD) and total mortality. An exhaustive search was performed using MEDLINE (1970 to 1995) and manual search of bibliographic notations and nonindexed sources. Twenty prospective controlled trials with treatment allocation by random assignment or consecutive enrollment were identified using diagnostic evidence of systemic lupus erythematosus based on American Rheumatism Association (ARA) criteria and clinical/biopsy evidence of lupus nephritis. One trial was excluded, resulting in 19 trials (n = 440) using treatment groups of oral prednisone alone, azathioprine with and without concomitant prednisone, oral cyclophosphamide with prednisone, azathioprine and oral cyclophosphamide with prednisone, and intravenous cyclophosphamide with prednisone. Crude risk data was pooled. An adjusted pooled risk was calculated using the random effects model of DerSimonian and Laird. Two measures of clinical effectiveness were used to compare treatments: absolute risk differences and number needed to treat. Analysis was completed between treatment groups as follows: oral prednisone compared with all immunosuppressive agents with prednisone and all treatment groups compared with one another. When compared with oral prednisone alone, immunosuppressive agents used in conjunction with oral prednisone were found to be statistically more effective for both total mortality and ESRD (absolute risk differences, 13.2% and 12.9%, respectively). When treatment groups were compared, intravenous cyclophosphamide in conjunction with oral prednisone was found to be statistically more effective than oral prednisone alone for both total mortality and ESRD (absolute risk differences, 19.9% and 16.2%, respectively). The simultaneous use of azathioprine and oral cyclophosphamide concomitant with oral prednisone was found to be 16.9% more effective than oral prednisone alone in reducing incidence of ESRD. No difference was seen in total mortality and data represented only two studies (n = 30). No immunosuppressive agent was found to be statistically more effective than another for either total mortality or ESRD. Future prospective studies are needed to control for numerous variables and renal function changes to provide more definitive answers.

Hypercalcemia Associated with Silicone-Induced Granulomas

HYPERCALCEMIA occurs in a variety of chronic granulomatous diseases, such as sarcoidosis,1 2 3 4 tuberculosis,5 , 6 and berylliosis.7 Except in sarcoidosis, the mechanism for the hypercalcemia obse...

In vivo effects of acute changes in osmolality and sodium concentration on myocardial contractility

Effects of acute changes in osmolality and sodium concentration (Na) on myocardial contractility (MC) were examined in anesthetized dogs. Using a carotid to left anterior descending bypass, 4 cc of NaCl and/or dextrose of varying osmolality as injected and the percentage of change in MC measured. At Na = O mEq/L, a positive inotropic response occurred, which varied inversely as osmolality increased from 300 (MC = 100 +/- 23%) to 700 mOsm/L (MC = 39 +/- 10%, p less than 0.01). Similar ranges of positive responses of lesser magnitude were noted at Na = 75 mEq/L. At Na = 150, 190, or 350 mEq/L, similar increments in osmolality caused an increasingly negative inotropic response. An inverse relationship between Na and MC was noted with osmolality held constant. Injections of the nonionic contrast agent, P297, in 5% dextrose or 0.9% NaCl, resulted in 28 +/- 3% or -17 +/- 4% (p less than 0.01) change in MC, respectively. Sodium concentration and osmolality have independent effects on MC. Hyperosmolality/hypernatremia causes a negative inotropic response while hyponatremia causes a positive one.

Erythropoietin-Induced Thrombosis as a Result of Increased Inflammation and Thrombin Activatable Fibrinolytic Inhibitor:

Chronic inflammation is a major cause of morbidity and mortality in end-stage renal disease. The associated anemia in these patients due to renal cortical atrophy and erythropoietin deficiency is treated with recombinant erythropoietin. Recent reports suggest a growing incidence of symptomatic venous thrombosis in cancer patients treated with recombinant erythropoietin. Several investigators have reported on different mechanisms of thrombosis in these patients. We hypothesize that thrombosis in patients with end-stage renal disease due to increased expression of C-reactive protein (CRP) as a result of chronic inflammation promotes the release of thrombin activatable fibrinolytic inhibitor causing fibrinolytic deficit and eventually thrombosis. Furthermore, because endothelial nitric oxide is responsible for the maintenance of the normal vascular function, the decreased levels of nitric oxide in chronic inflammation cause endothelial damage and result in thrombosis. To test this hypothesis, blood samples were collected from 106 patients (49 male and 57 female, aged 59.8±15.7 years) with end-stage renal disease undergoing hemodialysis and treated with recombinant erythropoietin at a mean dose of 201.8 U/kg/week. Blood samples were drawn in 5-mL tubes containing 3.2% sodium citrate just before the hemodialysis procedure. These blood samples were immediately centrifuged to obtain platelet-poor plasma, which was aliquoted and frozen at -70°C until further analysis. Erytropoietin antibodies were measured using an anti-EPO enzyme-linked immunosorbent assay (ELISA) method developed in our laboratory. Nitric oxide was measured using a NO analyzer (Sievers 280I, Ionics, Boulder, CO). Plasma CRP levels were measured with a highly sensitive ELISA method IMUNOCLONE CRP ELISA (American Diagnostica, Greenwich, CT). TAFI antigen levels in plasma were analyzed with an IMUCLONE TAFI ELISA kit (American Diagnostica, Greenwich, CT). TAFI functional activity was assayed with an ACTICHROME TAFI activity kit. The measured levels of nitric oxide, CRP, TAFI antigen, and TAFI functional were 37.36±36.8 (normal value, 37.49±18.96; range, 19.3-102 μM), 12.27±10.6 (normal value, < 1 μg/mL), 146.9±28.4% NHP (normal, 100% NHP), and 102.55±37% NHP (normal range, 22.3-165.7; mean, 89.5% NHP), respectively. The erythropoietin antibody was detected in 9.4% of the patient group. While 20% of the erythropoietin antibody-positive and 27.1% of the erythropoietin antibody-negative patients experienced chest pain, thrombotic events developed in 9.4% of the erythropoietin antibody-negative patients. These data provide the rationale for a novel mechanism of thrombosis through increased activity of CRP, nitric oxide, and TAFI, leading to fibrinolytic deficit and thrombosis in patients treated with erythropoietin.

Intractable hypoglycemia in a patient with renal failure.

A patient with chronic renal failure developed intractable hypoglycemia after 2 1/2 years of dialysis. Metabolic studies did not suggest that malnutrition, substrate limitation, hormone deficiency, or insulin excess were responsible for the low blood glucose level. Impaired gluconeogenesis may have been an important factor, but studies in this patient suggest that enhanced glucose utilization may also play a role in the pathogenesis of hypoglycemia in renal failure.

Correlations of Na+-Li+ exchange activity with Na+ and Li+ binding and phospholipid composition in erythrocyte membranes of white hypertensive and normotensive individuals: a nuclear magnetic resonance investigation.

Enhanced Na+-Li+ exchange activity has been reported in red blood cells (RBCs) of white patients with essential hypertension compared with RBCs of normotensive individuals. To understand the factors responsible for this finding, we applied novel and conventional spectroscopic and kinetic methods to blood samples from 10 hypertensive and 10 normotensive individuals. We measured the kinetic parameters (V std, V max, and K m) for RBC Na+-Li+ exchange by atomic absorption spectrophotometry and used 23Na and 7Li nuclear magnetic resonance relaxation methods to measure Na+ and Li+ binding to RBC membranes as well as 31P nuclear magnetic resonance spectroscopy to measure membrane phospholipid compositions. We found significant differences between the two groups for the affinity of Na+ for the RBC membrane (0.202 +/- 0.054 mmol/L-1 for hypertensive patients versus 0.296 +/- 0.071 mmol/L-1 for normotensive subjects, P<.005). The kinetic parameters of RBC Na+-Li+ exchange (V std, V max, and K m) were 0.32 +/- 0.09 and 0.66 +/- 0.17 mmol Li+/L cell.h and 160 +/- 62 mmol/L, respectively, for hypertensive patients versus 0.21 +/- 0.06 and 0.32 +/- 0.14 mmol Li+/L cell.h and 86 +/- 69 mmol/L for normotensive subjects (P<.05). The fractions of phosphatidylserine and phosphatidylethanolamine were 0.153 +/- 0.009 and 0.294 +/- 0.016 for hypertensive patients versus 0.138 +/- 0.013 and 0.325 +/- 0.018 for normotensive subjects (P<.05). The Na+ binding constants were negatively correlated with the Km values for both the hypertensive (r=-.61, P=.01) and normotensive (r=-.43, P=.04) groups. Changes in lipid-protein interactions in the RBC membranes of hypertensive patients appear to be responsible for weaker Na+ binding to the membrane and for the faster rates of RBC Na+-Li+ exchange.

Hemodialysis prognostic nutrition index as a predictor for morbidity and mortality in hemodialysis patients and its correlation to adequacy of dialysis

OBJECTIVE Prospectively examine the use of a hemodialysis prognostic nutrition index (HD-PNI) as a predictor for morbidity and mortality in hemodialysis patients and its correlation to adequacy of dialysis. DESIGN Prospective randomized collaborative study group. SETTING There were 211 chronic hemodialysis centers; 202 from 43 United States, 9 from Canada. PATIENTS There were 1527 hemodialysis patients undergoing treatment a minimum of 3 months and at least 18 years of age. Sample mirrored United States Renal Data System data for age, sex, race, and etiology of renal failure. INTERVENTIONS None; routinely collected demographic, biochemical, and clinical data for 8-month baseline and 3-month predictive phases. METHODS HD-PNI calculated from baseline data as linear mathematical equation using level of serum albumin, level of serum creatinine, and number of days and times hospitalized; HD-PNI risk defined as >/=0.8. Adequacy of dialysis calculated as urea reduction ratio (URR) from baseline data; adequacy risk defined as URR of </=65%. MAIN OUTCOME MEASURES Number of times and days hospitalized, mortality. RESULTS For this research, 1167 patients completed the study (76%) with 360 (24%) dropped due to death, incomplete data, transfer, or change in modality. Patients completing study with HD-PNI risk (n = 208, 18%) compared with patients who had no HD-PNI risk (n = 959, 82%) were hospitalized more often (57.2% v 28.5%, P <. 01), hospitalized with infection more often (14.6% v 4.6%, P <.01), and had greater mortality (7.7% v 2.5%, P <.01). Stratification of HD-PNI risk by URR of >/=65% did not significantly improve prediction. CONCLUSIONS Use of HD-PNI is an effective screening tool to identify hemodialysis patients at risk for morbidity and mortality. No correlation was found between URR and HD-PNI.

Medical Nutrition Therapy in Adults with Chronic Kidney Disease: Integrating Evidence and Consensus into Practice for the Generalist Registered Dietitian Nutritionist

Chronic kidney disease is classified in stages 1 to 5 by the National Kidney Foundations Kidney Disease Outcomes Quality Initiative depending on the level of renal function by glomerular filtration rate and, more recently, using further categorization depending on the level of glomerular filtration rate and albuminuria by the Kidney Disease Improving Global Outcomes initiative. Registered dietitian nutritionists can be reimbursed for medical nutrition therapy in chronic kidney disease stages 3 to 4 for specific clients under Center for Medicare and Medicaid Services coverage. This predialysis medical nutrition therapy counseling has been shown to both potentially delay progression to stage 5 (renal replacement therapy) and decrease first-year mortality after initiation of hemodialysis. The Joint Standards Task Force of the American Dietetic Association (now the Academy of Nutrition and Dietetics), the Renal Nutrition Dietetic Practice Group, and the National Kidney Foundation Council on Renal Nutrition collaboratively published 2009 Standards of Practice and Standards of Professional Performance for generalist, specialty, and advanced practice registered dietitian nutritionists in nephrology care. The purpose of this article is to provide an update on current recommendations for screening, diagnosis, and treatment of adults with chronic kidney disease for application in clinical practice for the generalist registered dietitian nutritionist using the evidence-based library of the Academy of Nutrition and Dietetics, published clinical practice guidelines (ie, National Kidney Foundation Council on Renal Nutrition, Renal Nutrition Dietetic Practice Group, Kidney Disease Outcomes Quality Initiative, and Kidney Disease Improving Global Outcomes), the Nutrition Care Process model, and peer-reviewed literature.

Potential deaths averted and serious adverse events incurred from adoption of the SPRINT (systolic blood pressure intervention trial) intensive blood pressure regimen in the United States: Projections from NHANES (National Health and Nutrition Examination Survey)

Background —The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated a 27% reduction in all-cause mortality with a systolic blood-pressure (SBP) goal of Methods —SPRINT eligibility criteria were applied to the 1999-2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥ 50 years, SBP of 130-180 mmHg (depending on the number of antihypertensive medications being taken), and high CVD risk. Exclusion criteria were diabetes, history of stroke, >1 gram of proteinuria, heart failure, estimated glomerular filtration rate 2 , or dialysis. Annual mortality rates were calculated by dividing the Kaplan-Meier 5-year mortality by 5. Hazard ratios for all-cause mortality and heart failure and absolute risks for SAEs in SPRINT were used to estimate the number of potential deaths and heart failure cases prevented and SAEs incurred with intensive SBP treatment. Results —The mean age was 68.6 years and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95%CI 1.91%-2.48%) and intensive SBP treatment was projected to prevent about 107,500 deaths per year (95%CI 93,300-121,200) and give rise to 56,100 (95%CI 50,800-61,400) episodes of hypotension, 34,400 (95%CI 31,200-37,600) episodes of syncope, 43,400 (95%CI 39,400-47,500) serious electrolyte disorders, and 88,700 (95%CI 80,400-97,000) cases of acute kidney injury per year. The analysis of extremes approach indicated that the range of estimated lower and upper bound number of deaths prevented per year with intensive SBP control was 34,600 to 179,600. Intensive SBP control was projected to prevent 46,100 (95%CI 41,800-50,400) cases of heart failure annually. Conclusions —If fully implemented in eligible U.S. adults, intensive SBP treatment could prevent about 107,500 deaths per year. A consequence of this treatment strategy, however, could be an increase in SAEs.Background: SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal of <120 versus <140 mm Hg among US adults at high cardiovascular disease risk but without diabetes mellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults. Methods: SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to 180 mm Hg (depending on the number of antihypertensive medications being taken), and high cardiovascular disease risk. Exclusion criteria were diabetes mellitus, history of stroke, >1 g proteinuria, heart failure, estimated glomerular filtration rate <20 mL·min−1·1.73 m−2, or dialysis. Annual mortality rates were calculated by dividing the Kaplan-Meier 5-year mortality by 5. Hazard ratios for all-cause mortality and heart failure and absolute risks for serious adverse events in SPRINT were used to estimate the number of potential deaths and heart failure cases prevented and serious adverse events incurred with intensive SBP treatment. Results: The mean age was 68.6 years, and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95% confidence interval [CI], 1.91–2.48), and intensive SBP treatment was projected to prevent ≈107 500 deaths per year (95% CI, 93 300–121 200) and give rise to 56 100 (95% CI, 50 800–61 400) episodes of hypotension, 34 400 (95% CI, 31 200–37 600) episodes of syncope, 43 400 (95% CI, 39 400–47 500) serious electrolyte disorders, and 88 700 (95% CI, 80 400–97 000) cases of acute kidney injury per year. The analysis-of-extremes approach indicated that the range of estimated lower- and upper-bound number of deaths prevented per year with intensive SBP control was 34 600 to 179 600. Intensive SBP control was projected to prevent 46 100 (95% CI, 41 800–50 400) cases of heart failure annually. Conclusions: If fully implemented in eligible US adults, intensive SBP treatment could prevent ≈107 500 deaths per year. A consequence of this treatment strategy, however, could be an increase in serious adverse events.

Strategies to promote adherence to nutritional advice in patients with chronic kidney disease: a narrative review and commentary

Chronic kidney disease (CKD) requires extensive changes to food and lifestyle. Poor adherence to diet, medications, and treatments has been estimated to vary between 20% and 70%, which in turn can contribute to increased mortality and morbidity. Delivering effective nutritional advice in patients with CKD coordinates multiple diet components including calories, protein, sodium, potassium, calcium, phosphorus, and fluid. Dietary intake studies have shown difficulty in adhering to the scope and complexity of the CKD diet parameters. No single educational or clinical strategy has been shown to be consistently effective across CKD populations. Highest adherence has been observed when both diet and education efforts are individualized to each patient and adapted over time to changing lifestyle and CKD variables. This narrative review and commentary summarizes nutrition education literature and published strategies for providing nutritional advice in CKD. A cohort of practical and effective strategies for increasing dietary adherence to nutritional advice are provided that include communicating with “talking control” principles, integrating patient-owned technology, acknowledging the typical food pattern may be snacking rather than formal meals, focusing on a single goal rather than multiple goals, creating active learning and coping strategies (frozen sandwiches, visual hands-on activities, planting herb gardens), and involving the total patient food environment.